Butyltin exposure causes a rapid decrease in cyclic AMP levels in human lymphocytes.

PubMed

Whalen, M M; Loganathan, B G

2001-03-15

Natural killer (NK) cells are a subset of lymphocytes that are capable of killing tumor cells, virally infected cells, and antibody-coated cells. Butyltins (BTs) are used in a variety of consumer products and industrial applications. Tributyltin (TBT) is found in dairy products, meat, and fish. Dibutyltin (DBT) is found in plastic products, beverages stored in PVC pipes during manufacturing, and poultry products. BTs appear to increase the risk of cancer and viral infections in exposed individuals. This increased risk may be due in part to the inhibitory effect of these compounds on the cytotoxic function of NK cells. A 24-h exposure of NK cells to 200 nM TBT or 1.5 microM DBT decreased the cytotoxic function of NK cells by greater than 90%. Higher concentrations of TBT and DBT decreased the cytotoxic function of NK cells (by greater than 90%) after only a 1-h exposure. A 24-h exposure to either TBT or DBT decreased intracellular ATP levels by about 30%. However, as much as a 1-h exposure to either 300 nM TBT or 10 microM DBT caused no significant decrease in ATP levels. Thus, a decrease in ATP levels is a longer-term consequence of BT exposure. Intracellular levels of cAMP are decreased by as much as 80% within 5 min of exposure to either TBT or DBT. This rapid decline in cAMP levels in NK cells may be a consequence of BT exposure that is related to the rapid decrease in the cytotoxic function of NK cells. Copyright 2001 Academic Press.

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.

Chronic treatment with caffeine and its withdrawal modify the antidepressant-like activity of selective serotonin reuptake inhibitors in the forced swim and tail suspension tests in mice. Effects on Comt, Slc6a15 and Adora1 gene expression.

PubMed

Szopa, Aleksandra; Doboszewska, Urszula; Herbet, Mariola; Wośko, Sylwia; Wyska, Elżbieta; Świąder, Katarzyna; Serefko, Anna; Korga, Agnieszka; Wlaź, Aleksandra; Wróbel, Andrzej; Ostrowska, Marta; Terlecka, Joanna; Kanadys, Adam; Poleszak, Ewa; Dudka, Jarosław; Wlaź, Piotr

2017-12-15

Recent preclinical and clinical data suggest that low dose of caffeine enhances the effects of common antidepressants. Here we investigated the effects of chronic administration of caffeine (5mg/kg, twice daily for 14days) and its withdrawal on day 15th on the activity of per se ineffective doses of fluoxetine (5mg/kg) and escitalopram (2mg/kg) given on day 15th. We found decreased immobility time in the forced swim and tail suspension tests in mice in which caffeine was administered simultaneously with antidepressants on day 15th following a 14-day caffeine treatment and no alterations in the spontaneous locomotor activity. A decrease in the level of escitalopram and an increase in the level of caffeine in serum were observed after concomitant administration of these compounds, while the joint administration of caffeine and fluoxetine was not associated with changes in their levels in serum or brain. Caffeine withdrawal caused a decrease in Adora1 mRNA level in the cerebral cortex (Cx). Administration of escitalopram or fluoxetine followed by caffeine withdrawal caused an increase in this gene expression, whereas administration of escitalopram, but not fluoxetine, on day 15th together with caffeine caused a decrease in Adora1 mRNA level in the Cx. Furthermore, antidepressant-like activity observed after joint administration of the tested drugs with caffeine was associated with decreased Slc6a15 mRNA level in the Cx. The results show that withdrawal of caffeine after its chronic intake may change activity of antidepressants with concomitant alterations within monoamine, adenosine and glutamate systems. Copyright © 2017 Elsevier Inc. All rights reserved.

Abnormal pituitary-gonadal axis may be responsible for rat decreased testicular function under simulated microgravity

NASA Astrophysics Data System (ADS)

Zhou, Yi; Tan, Xin; Zhu, Bao-an; Qi, Meng-di; Ding, Su-ling

Space flight and simulated microgravity lead to suppression of mammalian spermatogenesis and decreased plasma testosterone level. In order to explain the mechanism behind the depression, we used rat tail-suspended model to simulate weightless conditions. To prevent cryptorchidism caused by tail-suspension, some experimental animals received inguinal canal ligation. The results showed that mass of testis decreased significantly and seminiferous tubules became atrophied in rats after tail-suspension. The levels of plasma testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in tail-suspended rats with or without inguinal canal ligation decreased significantly compared with controls, and an increased level of plasma estradiol (E) was revealed in tail-suspended rats. The results indicate that besides the direct influence of fluid shift upon testis under short-term simulated microgravity, the pituitary function is also disturbed as a result of either immobilization stress or weight loss during tail-suspension treatment, which is responsible to some extent for the decreased testosterone secretion level and the atrophia of testis. The conversion of testosterone into E under simulated microgravity is another possible cause for the decline of plasma testosterone.

MRS of brain metabolite levels demonstrates the ability of scavenging of excess brain glutamate to protect against nerve agent induced seizures.

PubMed

Ruban, Angela; Biton, Inbal E; Markovich, Arik; Mirelman, David

2015-02-02

This study describes the use of in vivo magnetic resonance spectrocopy (MRS) to monitor brain glutamate and lactate levels in a paraoxon (PO) intoxication model. Our results show that the administration of recombinant glutamate-oxaloacetate transaminase (rGOT) in combination with oxaloacetate (OxAc) significantly reduces the brain-accumulated levels of glutamate. Previously we have shown that the treatment causes a rapid decrease of blood glutamate levels and creates a gradient between the brain and blood glutamate levels which leads to the efflux of excess brain glutamate into the blood stream thereby reducing its potential to cause neurological damage. The fact that this treatment significantly decreased the brain glutamate and lactate levels following PO intoxication suggests that it could become a new effective neuroprotective agent.

[Bone loss in lactating women and post-pregnancy osteoporosis].

PubMed

Hirata, Go; Chaki, Osamu

2011-09-01

Measurement of the bone mineral density have shown that lactating women had 1 to 3% decrease in bone mineral density. Post pregnancy osteoporosis is rare condition that causes fragile fracture mostly in vertebrae. The bone loss in lactating women is caused by calcium loss, decrease in estrogen level, and increase in PTHrP (parathyroid hormone related protein) level. Some data have shown that extended lactation and amenorrhea had an association with the degree of bone loss. Mostly, the bone loss of the lactating women recovers to the baseline level, soon after the weaning, and there is no long term effect. Post pregnancy osteoporosis should be concerned, when we see a lactating woman with fragile fracture of the vertebrae.

Gynecomastia.

PubMed

Leung, A K

1989-04-01

Gynecomastia may be physiologic, familial, pathologic, drug-induced or, in many cases, of unknown etiology. Breast enlargement is usually unilateral and asymptomatic. Mechanisms of gynecomastia involve increased estrogen stimulation, decreased testosterone levels or a decreased androgen/estrogen ratio. Hyperprolactinemia is not a cause. Treatment of gynecomastia should be directed at the underlying cause when one can be identified. Most cases are benign and can be managed by explanation, reassurance and observation.

N-Benzoyl-D-phenylalanine attenuates brain acetylcholinesterase in neonatal streptozotocin-diabetic rats.

PubMed

Ashokkumar, Natarajan; Pari, Leelavinothan; Ramkumar, Kunga Mohan

2006-09-01

The effect of hyperglycaemia due to experimental diabetes in male Wistar rats causes a decrease in the level of acetylcholinesterase (AChE) with significant increase in lipid peroxidative markers: thiobarbituric acid-reactive substances (TBARS) and hydroperoxides in brains of experimental animals. The decreased activity of both salt soluble and detergent soluble acetylcholinesterase observed in diabetes may be attributed to lack of insulin which causes specific alterations in the level of neurotransmitter, thus causing brain dysfunction. Administration of non-sulfonylurea drug N-benzoyl-D-phenylalanine (NBDP) could protect against direct action of lipid peroxidation on brain AChE and in this way it might be useful in the prevention of cholinergic neural dysfunction, which is one of the major complications in diabetes.

Chronic aspartame intake causes changes in the trans-sulphuration pathway, glutathione depletion and liver damage in mice.

PubMed

Finamor, Isabela; Pérez, Salvador; Bressan, Caroline A; Brenner, Carlos E; Rius-Pérez, Sergio; Brittes, Patricia C; Cheiran, Gabriele; Rocha, Maria I; da Veiga, Marcelo; Sastre, Juan; Pavanato, Maria A

2017-04-01

No-caloric sweeteners, such as aspartame, are widely used in various food and beverages to prevent the increasing rates of obesity and diabetes mellitus, acting as tools in helping control caloric intake. Aspartame is metabolized to phenylalanine, aspartic acid, and methanol. Our aim was to study the effect of chronic administration of aspartame on glutathione redox status and on the trans-sulphuration pathway in mouse liver. Mice were divided into three groups: control; treated daily with aspartame for 90 days; and treated with aspartame plus N-acetylcysteine (NAC). Chronic administration of aspartame increased plasma alanine aminotransferase (ALT) and aspartate aminotransferase activities and caused liver injury as well as marked decreased hepatic levels of reduced glutathione (GSH), oxidized glutathione (GSSG), γ-glutamylcysteine ​​(γ-GC), and most metabolites of the trans-sulphuration pathway, such as cysteine, S-adenosylmethionine (SAM), and S-adenosylhomocysteine ​​(SAH). Aspartame also triggered a decrease in mRNA and protein levels of the catalytic subunit of glutamate cysteine ligase (GCLc) and cystathionine γ-lyase, and in protein levels of methionine adenosyltransferase 1A and 2A. N-acetylcysteine prevented the aspartame-induced liver injury and the increase in plasma ALT activity as well as the decrease in GSH, γ-GC, cysteine, SAM and SAH levels and GCLc protein levels. In conclusion, chronic administration of aspartame caused marked hepatic GSH depletion, which should be ascribed to GCLc down-regulation and decreased cysteine levels. Aspartame triggered blockade of the trans-sulphuration pathway at two steps, cystathionine γ-lyase and methionine adenosyltransferases. NAC restored glutathione levels as well as the impairment of the trans-sulphuration pathway. Copyright © 2017. Published by Elsevier B.V.

Reversal of the toxic effects of cachectin by concurrent insulin administration.

PubMed

Fraker, D L; Merino, M J; Norton, J A

1989-06-01

Rats treated with recombinant human tumor necrosis factor-cachectin, 100 micrograms/kg ip twice daily for 5 consecutive days, had a 56% decrease in food intake, a 54% decrease in nitrogen balance, and a 23-g decrease in body weight gain vs. saline-treated controls. Concurrent neutral protamine hagedorn insulin administration of 2 U/100 g sc twice daily reversed all of these changes to control levels without causing any treatment deaths. The improvement seen with insulin was dose independent. Five days of cachectin treatment caused a severe interstitial pneumonitis, periportal inflammation in the liver, and an increase in wet organ weight in the heart, lungs, kidney, and spleen. Concurrent insulin treatment led to near total reversal of these histopathologic changes. Cachectin treatment did not significantly change blood glucose levels from control values of 130-140 mg/dl, but insulin plus cachectin caused a significant decrease in blood glucose from 1 through 12 h after injection. Administration of high-dose insulin can near totally reverse the nutritional and histopathologic toxicity of sublethal doses of cachectin in rats.

Hypoxia reduces testosterone synthesis in mouse Leydig cells by inhibiting NRF1-activated StAR expression

PubMed Central

Zou, Zhiran; Wang, Dan; Lu, Yapeng; Dong, Zhangji; Zhu, Li

2017-01-01

Male fertility disorders play a key role in half of all infertility cases. Reduction in testosterone induced by hypoxia might cause diseases in reproductive system and other organs. Hypoxic exposure caused a significant decrease of NRF1. Software analysis reported that the promoter region of steroidogenic acute regulatory protein (StAR) contained NRF1 binding sites, indicating NRF1 promoted testicular steroidogenesis. The purpose of this study is to determine NRF1 is involved in testosterone synthesis; and under hypoxia, the decrease of testosterone synthesis is caused by lower expression of NRF1. We designed both in vivo and in vitro experiments. Under hypoxia, the expressions of NRF1 in Leydig cells and testosterone level were significantly decreased both in vivo and in vitro. Overexpression and interference NRF1 could induced StAR and testosterone increased and decreased respectively. ChIP results confirmed the binding of NRF1 to StAR promoter region. In conclusion, decline of NRF1 expression downregulated the level of StAR, which ultimately resulted in a reduction in testosterone synthesis. PMID:28146428

Effect of plantain banana on gastric ulceration in NIDDM rats: role of gastric mucosal glycoproteins, cell proliferation, antioxidants and free radicals.

PubMed

Mohan Kumar, M; Joshi, M C; Prabha, T; Dorababu, M; Goel, R K

2006-04-01

Methanolic extract of Musa sapientum var. Paradisiaca (MSE, 100 mg/kg) was studied for its antiulcer and mucosal defensive factors in normal and non-insulin dependent diabetes mellitus (NIDDM) rats. NIDDM was induced by administering streptozotocin (STZ, 70 mg/kg, ip) to 5 days old rat pups. The animals showing blood glucose level >140mg/dL after 12 weeks of STZ administration were considered as NIDDM positive. Effects of MSE were compared with known ulcer protective drug, sucralfate (SFT, 500 mg/kg) and anti-diabetic drug glibenclamide (GLC, 0.6 mg/kg) when administered orally, once daily for 6 days against gastric ulcers (GU) induced by cold-restraint stress (CRS) and ethanol and subsequent changes in gastric mucosal glycoproteins, cell proliferation, free radicals (lipid peroxidation and nitric oxide) and anti-oxidants enzymes (super oxide dismutase and catalase) and glutathione (GSH) levels. MSE showed better ulcer protective effect in NIDDM rats compared with SFT and GLC in CRS-induced GU. NIDDM caused a significant decrease in gastric mucosal glycoprotein level without having any effect on cell proliferation. However, all the test drugs reversed the decrease in glycoprotein level in NIDDM rats, but cell proliferation was enhanced in case of MSE alone. Both CRS or NIDDM as such enhanced gastric mucosal LPO, NO and SOD, but decreased CAT levels while CRS plus NIDDM rats caused further increase in LPO and NO level without causing any further changes in SOD and CAT level. MSE pretreatment showed reversal in the levels of all the above parameters better than GLC. Ethanol caused a decrease in glutathione level which was further reduced in NIDDM-ethanol rats. MSE reversed the above changes significantly in both normal as well as in NIDDM rats, while GLC reversed it only in NIDDM rats. However, SFT was ineffective in reversing the changes induced by CRS or ethanol or when given in NIDDM-CRS or NIDDM-ethanol rats. The results indicated that the ulcer protective effect of MSE could be due to its predominant effect on mucosal glycoprotein, cell proliferation, free radicals and antioxidant systems.

Co-administration of betulinic acid and methamphetamine causes toxicity to dopaminergic and serotonergic nerve terminals in the striatum of late adolescent rats

PubMed Central

Killinger, Bryan; Shah, Mrudang; Moszczynska, Anna

2013-01-01

Psychostimulant methamphetamine (METH) is toxic to dopaminergic and serotonergic striatal nerve terminals in adult, but not in adolescent, brain. Betulinic acid (BA) and its derivatives are promising anti-HIV agents with some toxic properties. Many METH users, particularly young men, are HIV-positive; therefore, they might be treated with BA or its derivative for HIV infection. It is not known whether BA, or any of its derivatives, is neurotoxic in combination with METH in adolescent brain. The present study investigated the effects of BA and binge METH in the striatum in late adolescent rats. BA or METH alone did not decrease the levels of dopaminergic or serotonergic markers in the striatum whereas BA and METH together decreased these markers in a BA dose-dependent manner. BA and METH combination also caused decreases in the levels of mitochondrial complex I in the same manner; BA alone only slightly decreased the levels of the enzyme in striatal synaptosomes. BA or METH alone increased cytochrome c. METH alone decreased parkin, increased complex II and striatal BA levels. These results suggest that METH in combination with BA can be neurotoxic to dopaminergic and serotonergic striatal nerve terminals in late adolescent brain via mitochondrial dysfunction and parkin deficit. PMID:24151877

Decreased alertness

MedlinePlus

... involves the brain Liver failure Thyroid conditions that cause low thyroid hormone levels or very high thyroid hormone levels Brain disorders or injury, such as: Dementia or Alzheimer disease Head trauma Seizure Stroke Infections that affect ...

Tributyltin induces a G2/M cell cycle arrest in human amniotic cells via PP2A inhibition-mediated inactivation of the ERK1/2 cascades.

PubMed

Zhang, Yali; Guo, Zonglou; Xu, Lihong

2014-03-01

The molecular mechanisms underlying the cell cycle alterations induced by tributyltin (TBT), a highly toxic environmental contaminant, remain elusive. In this study, cell cycle progression and some key regulators in G2/M phase were investigated in human amniotic cells treated with TBT. Furthermore, protein phosphatase (PP) 2A and the ERK cascades were examined. The results showed that TBT caused a G2/M cell cycle arrest that was accompanied by a decrease in the total cdc25C protein level and an increase in the p-cdc2 level in the nucleus. TBT caused a decrease in PP2A activity and inhibited the ERK cascade by inactivating Raf-1, resulting in the dephosphorylation of MEK1/2, ERK1/2, and c-Myc. Taken together, TBT leads to a G2/M cell cycle arrest in FL cells, an increase in p-cdc2 and a decrease in the levels of total cdc25C protein, which may be caused by the PP2A inhibition-mediated inactivation of the ERK1/2 cascades. Copyright © 2014 Elsevier B.V. All rights reserved.

Effect of tributyltin (TBT) on ATP levels in human natural killer (NK) cells: relationship to TBT-induced decreases in NK function.

PubMed

Dudimah, Fred D; Odman-Ghazi, Sabah O; Hatcher, Frank; Whalen, Margaret M

2007-01-01

The purpose of this study was to investigate the role that tributyltin (TBT)-induced decreases in ATP levels may play in TBT-induced decreases in the tumor lysing (lytic) function of natural killer (NK) cells. NK cells are a subset of lymphocytes that act as an initial immune defense against tumor cells and virally infected cells. TBT is an environmental contaminant that has been detected in human blood, which has been shown to interfere with ATP synthesis. Previous studies have shown that TBT is able to decrease very significantly the lytic function of NK cells. In this study NK cells were exposed to various concentrations of TBT and to two other compounds that interfere with ATP synthesis (rotenone a complex I inhibitor and oligomycin an ATP synthase inhibitor) for various lengths of time before determining the levels of ATP and lytic function. Exposures of NK cells to 10, 25, 50 and 100 nm TBT did not significantly reduce ATP levels after 24 h. However, these same exposures caused significant decreases in cytotoxic function. Studies of brief 1 h exposures to a range of TBT, rotenone and oligomycin concentrations followed by 24 h, 48 h and 6 day periods in compound-free media prior to assaying for ATP levels or cytotoxic function showed that each of the compounds caused persistent decreases in ATP levels and lytic function of NK cells. Exposures to 0.05-5 microm rotenone or oligomycin for 1 h reduced ATP levels by 20-25% but did not have any measurable effect on the ability of NK cells to lyse tumor cells. ATP levels were also decreased by about 20-25% after 24 h or 48 h exposures to rotenone or oligomycin (0.5 microm ), and the lytic function was decreased by about 50%. The results suggest that TBT-induced decreases in ATP levels were not responsible for the loss of cytotoxic function seen at 1 h and 24 h. However, TBT-induced decreases of NK-ATP levels may be at least in part responsible for losses of NK-cytotoxic function seen after 48 h and 6 day exposures. Copyright 2006 John Wiley & Sons, Ltd.

Effect of caricapryl-99 seed alkaloid extract on the serum levels of sex hormones and pituitary gonadotrophins in male albino rats.

PubMed

Udoh, P B; Udoh, F V; Umoren, E B; James, U W; Okeke, C P; Agwu, B

2009-06-01

Activity of alkaloid extract of caricapryl-99 seeds [Carica papaya Linn seeds] on the serum levels of steroid hormones was studied in adult male albino rats. Three tolerated doses obtained from the graph of percentage toxicity [10, 50 and 150 mg/kg] were separately administered orally, daily for three days to three groups of male rats [n=5] while group four of 5 rats received the vehicle [corn oil] as control. The results showed that 10 mg/kg/d caused increase serum levels of FSH and estrogen but decrease in the serum levels of LH and testosterone compared to control; 50 mg/kg/d elevated the serum levels of FSH, estrogen but inhibited testosterone; while 150 mg/kg/d pretreatments caused a significant decrease [p<0.01] in the serum levels of FSH, LH and testosterone. The results suggest that caricapryl-99 treatment inhibited the serum level of the androgen, testosterone which might result in a male infertility.

Medium-chain triglycerides supplement therapy with a low-carbohydrate formula can supply energy and enhance ammonia detoxification in the hepatocytes of patients with adult-onset type II citrullinemia.

PubMed

Hayasaka, Kiyoshi; Numakura, Chikahiko; Yamakawa, Mitsunori; Mitsui, Tetsuo; Watanabe, Hisayoshi; Haga, Hiroaki; Yazaki, Masahide; Ohira, Hiromasa; Ochiai, Yasuo; Tahara, Toshiyuki; Nakahara, Tamio; Yamashiki, Noriyo; Nakayama, Takahiro; Kon, Takashi; Mitsubuchi, Hiroshi; Yoshida, Hiroshi

2018-04-12

Citrin, encoded by SLC25A13, constitutes the malate-aspartate shuttle, the main NADH-shuttle in the liver. Citrin deficiency causes neonatal intrahepatic cholestasis (NICCD) and adult-onset type II citrullinemia (CTLN2). Citrin deficiency is predicted to impair hepatic glycolysis and de novo lipogenesis, resulting in hepatic energy deficit. Secondary decrease in hepatic argininosuccinate synthetase (ASS1) expression has been considered a cause of hyperammonemia in CTLN2. We previously reported that medium-chain triglyceride (MCT) supplement therapy with a low-carbohydrate formula was effective in CTLN2 to prevent a relapse of hyperammonemic encephalopathy. We present the therapy for six CTLN2 patients. All the patients' general condition steadily improved and five patients with hyperammonemic encephalopathy recovered from unconsciousness in a few days. Before the treatment, plasma glutamine levels did not increase over the normal range and rather decreased to lower than the normal range in some patients. The treatment promptly decreased the blood ammonia level, which was accompanied by a decrease in plasma citrulline levels and an increase in plasma glutamine levels. These findings indicated that hyperammonemia was not only caused by the impairment of ureagenesis at ASS1 step, but was also associated with an impairment of glutamine synthetase (GS) ammonia-detoxification system in the hepatocytes. There was no decrease in the GS expressing hepatocytes. MCT supplement with a low-carbohydrate formula can supply the energy and/or substrates for ASS1 and GS, and enhance ammonia detoxification in hepatocytes. Histological improvement in the hepatic steatosis and ASS1-expression was also observed in a patient after long-term treatment.

Trends in educational inequalities in premature mortality in Belgium between the 1990s and the 2000s: the contribution of specific causes of deaths.

PubMed

Renard, Françoise; Gadeyne, Sylvie; Devleesschauwer, Brecht; Tafforeau, Jean; Deboosere, Patrick

2017-04-01

Reducing socioeconomic inequalities in mortality, a key public health objective may be supported by a careful monitoring and assessment of the contributions of specific causes of death to the global inequality. The 1991 and 2001 Belgian censuses were linked with cause-of-death data, each yielding a study population of over 5 million individuals aged 25-64, followed up for 5 years. Age-standardised mortality rates (ASMR) were computed by educational level (EL) and cause. Inequalities were measured through rate differences (RDs), rate ratios (RRs) and population attributable fractions (PAFs). We analysed changes in educational inequalities between the 1990s and the 2000s, and decomposed the PAF into the main causes of death. All-cause and avoidable ASMR decreased in all ELs and both sexes. Lung cancer, ischaemic heart disease (IHD), chronic obstructive pulmonary disease (COPD) and suicide in men, and IHD, stroke, lung cancer and COPD in women had the highest impact on population mortality. RDs decreased in men but increased in women. RRs and PAFs increased in both sexes, albeit more in women. In men, the impact of lung cancer and COPD inequalities on population mortality decreased while that of suicide and IHD increased. In women, the impact of all causes except IHD increased. Absolute inequalities decreased in men while increasing in women; relative inequalities increased in both sexes. The PAFs decomposition revealed that targeting mortality inequalities from lung cancer, IHD, COPD in both sexes, suicide in men and stroke in women would have the largest impact at population level. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The current status and the future of occupational safety and health in Korea.

PubMed

Kang, Seong-Kyu

2012-01-01

From the 1970s to 2000, the occupational accident rate in Korea showed a continuous decline. However, the rate has remained stagnant since 2000 even when the fatal injury rate has decreased 40% from that year. Injuries caused by being caught in objects have decreased while those caused by slips and falls on same level and falls from the height have increased. In 2010, the non-fatal injury rate per 100 employees was 0.63 while the fatal injury rate per 100,000 employees was 9.74. The construction industry accounted for 40.2% of all fatal injuries, and falls from the height caused 54.3% of the fatality. Musculoskeletal diseases accounted for 78.8% of the non-fatal occupational diseases while cardio-cerebrovascular diseases and pneumoconiosis are the two major fatal occupational diseases. Occupational diseases caused by chemical agents have decreased to 0.6% of all cases. However, there were several social disputes related to occupational diseases caused by low level of chemicals such as leukemia in a semiconductor company. Korea planned to reduce the fatal injury rate and total workday loss by 30% by 2015. In order to achieve this goal, the government will focus on vulnerable groups in collaboration with allies such as professional associations or organizations.

The Effect of Maternal Thyroid Disorders (Hypothyroidism and Hyperthyroidism) During Pregnancy and Lactation on Skin Development in Wistar Rat Newborns

PubMed Central

Amerion, Maryam; Tahajjodi, Somayye; Hushmand, Zahra; Mahdavi Shahri, Nasser; Nikravesh, Mohammad Reza; Jalali, Mahdi

2013-01-01

Objective(s): Previous studies have shown that thyroid hormones are necessary for normal development of many organs and because of the importance of skin as the largest and the most important organ in human body protection in spite of external environment, the study of thyroid hormones effects on skin development is considerable. In this survey we have tried to study the effects of maternal hypothyroidism on skin development in fetus during pregnancy and lactation by immunohistochemistry technique. Materials and Methods: Rats were divided into 4 groups, hypothyroids, hyperthyroids, hypothyroids are treated with levothyroxin and a control group. The rat mothers were exposed to PTU with 50 mg/lit dosage and levothyroxin with 1 mg/lit dosage and PTU and levothyroxin simultaneously and with the same dosage respectively in hypothyroid, hyperthyroid and treated hypothyroids with levothyroxin groups. After 14 days, blood sample was taken from mothers, and if thyroid hormones level had change well, mating was allowed. After pregnancy and delivery, 1th day dorsal skin (as the sample for pregnancy assay) and 10th day skin (as for lactation assay) was used for immunohystochemical and morphometric studies. Results: In this study it was observed that maternal hypothyroidism during pregnancy and lactation causes significant increase in laminin expression, in most areas of skin, and maternal hyperthyroidism during pregnancy and lactation causes significant decrease in laminin expression. Also significant decrease was observed in hair follicles number and epidermis thickness in hypothyroidism groups. Conclusion: This study showed maternal hypothyroidism causes significant decrease in epidermis thickness and hair follicles number and it causes less hair in fetus. Also maternal hypothyroidism causes large changes in laminin expression in different parts of skin. At the same time,maternal hyperthyroidism causes opposite results. In fact, thyroid hormones regulate laminin expression negatively which means increase in thyroid hormone level, decreases laminin expression. So changes in thyroid hormones level can influence skin development significantly. PMID:23826487

Antimicrobial resistance in Shigella spp. causing traveller's diarrhoea (1995-2010): a retrospective analysis.

PubMed

Pons, M J; Gomes, C; Martínez-Puchol, S; Ruiz, L; Mensa, L; Vila, J; Gascón, J; Ruiz, J

2013-01-01

Shigellosis is a global human health problem causing an important morbidity among travellers returning from tropical areas. This study was aimed to describe the evolution of antimicrobial resistance profile in Shigella spp. isolated between the years 1995-2010 in patients with traveller's diarrhoea (TD) returning from tropical areas. The levels of antimicrobial resistance were tested in a total of 191 Shigella spp. isolated during the period from 1995 to 2010. A decrease of cases of diarrhoea caused by Shigella has been observed in recent years. A wide spectrum of antibiotic resistance was observed among Shigella spp. These isolates showed high levels of resistance to tetracycline (84%), co-trimoxazole (75.5%), and ampicillin (45.5%). The resistance was low to ciprofloxacin (2.1%), azithromycin (3.9%) and furazolidone (8.4%). According to the period, in the case of ampicillin, amoxicillin plus clavulanic acid, chloramphenicol, values of resistance were significantly decreasing from 1995-2000 to 2001-2010, (62.5% vs. 28.4%, 19.8% vs. 6.6%, 23.4 vs. 10.4%, respectively). Meanwhile in nalidixic acid and tetracycline the evolution of resistance has increased over time. A decrease in the isolation number of Shigella spp. causing TD has been observed. Differential trends in the evolution of the levels of resistance to the tested antibacterial agents have been observed. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mercury, Lead, Cadmium, Arsenic, Chromium and Selenium in Feathers of Shorebirds during Migrating through Delaware Bay, New Jersey: Comparing the 1990s and 2011/2012

PubMed Central

Burger, Joanna; Tsipoura, Nellie; Niles, Lawrence J.; Gochfeld, Michael; Dey, Amanda; Mizrahi, David

2015-01-01

Understanding temporal changes in contaminant levels in coastal environments requires comparing levels of contaminants from the same species from different time periods, particularly if species are declining. Several species of shorebirds migrating through Delaware Bay have declined from the 1980s to the present. To evaluate some contaminants as cause for the declines, we examine levels of mercury, lead, cadmium, arsenic, chromium and selenium in feathers of red knot (Calidris canutus, N = 46 individuals), semipalmated sandpiper (Calidris pusilla, N = 70) and sanderling (Calidris alba, N = 32) migrating through Delaware Bay, New Jersey, USA, from 1991 to 1992 (N = 40), 1995 (N = 28), and 2011–2012 (N = 80) to determine if levels have changed. We found: (1) arsenic, chromium, and lead increased in red knot and decreased in semipalmated sandpiper; (2) cadmium decreased in semipalmated sandpipers; (3) mercury decreased in red knot and sanderlings; (4) selenium decreased in red knot and increased in semipalmated sandpipers. In 2011/2012 there were significant interspecific differences for arsenic, mercury and selenium. Except for selenium, the element levels were well below levels reported for feathers of other species. The levels in feathers in red knots, sanderling, and semipalmated sandpipers from Delaware Bay in 2011/2012 were well below levels in feathers that are associated with effect levels, except for selenium. Selenium levels ranged from 3.0 µg·g−1 dry weight to 5.8 µg·g−1 (semipalmated sandpiper), within the range known to cause adverse effects, suggesting the need for further examination of selenium levels in birds. The levels of all elements were well below those reported for other marine species, except for selenium, which was near levels suggesting possible toxic effects. PMID:29056651

[The medical organizational aspects of decreasing of preventable mortality in the case of traffic accident in municipal district].

PubMed

Voloshina, L V; Plutnitskiĭ, A N

2010-01-01

The article deals with the results of the study of such actual issue as decreasing of preventable mortality in the case of traffic accident in municipal district. The analysis was based on the mortality statistical data and the expertise of causes of lethal outcomes of traffic accidents. The results are used to develop the measures of improving the organization and quality of medical care of victims of road accident on the pre-hospital and hospital stages on the level of municipal health care to decrease the human losses caused by traffic accident.

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

Hendrick, G.K.; Frizzell, R.T.; Cherrington, A.D.

In the 7-days fasted conscious dog, unlike the postabsorptive conscious dog, somatostatin infusion results in decreased levels of nonesterified fatty acids (NEFA) and increased glucose utilization (R{sub d}) even when insulin and glucagon levels are held constant. The aim of this study was to determine whether NEFA replacement in such animals would prevent the increase in R{sub d}. In each of three protocols there was an 80-min tracer equilibration period, a 40-min basal period, and a 3-h test period. During the test period in the first protocol saline was infused, in the second protocol somatostatin was infused along with intraportalmore » replacement amounts of insulin and glucagon (hormone replacement), while in the third protocol somatostatin plus the pancreatic hormones were infused with concurrent heparin plus Intralipid infusion. Glucose turnover was assessed using (3-{sup 3}H)glucose. The peripheral levels of insulin, glucagon, and glucose were similar and constant in all three protocols; however, during somatostatin infusion, exogenous glucose infusion was necessary to maintain euglycemia. The NEFA level was constant during saline infusion and decreased in the hormone replacement protocol. In the hormone replacement plus NEFA protocol, the NEFA level did not change during the first 90-min period and then increased during the second 90-min period. After a prolonged fast in the dog, (1) somatostatin directly or indirectly inhibits adipose tissue NEFA release and causes a decrease in the plasma NEFA level, and (2) this decrease in the NEFA level causes an increase in R{sub d}.« less

Rising ground-water level in downtown Louisville, Kentucky, 1972-1977

USGS Publications Warehouse

Kernodle, J.M.; Whitesides, D.V.

1977-01-01

Ground-water levels in the alluvial aquifer in Louisville, Jefferson County, Kentucky, are rising at a rate which could cause wet basements and possible structural damage tc buildings in the downtown area by 1982. The predicted water level for 1982 is based on the nearly linear increase which has been observed from 1972 to 1977, during which period a rise of as much as 32 feet was recorded in water-level observation wells. Foremost among the possible causes of the rise is a decrease in withdrawal of ground water.

Administration of exogenous acylated ghrelin or rikkunshito, an endogenous ghrelin enhancer, improves the decrease in postprandial gastric motility in an acute restraint stress mouse model

PubMed Central

Nahata, M; Saegusa, Y; Sadakane, C; Yamada, C; Nakagawa, K; Okubo, N; Ohnishi, S; Hattori, T; Sakamoto, N; Takeda, H

2014-01-01

Background Physical or psychological stress causes functional disorders in the upper gastrointestinal tract. This study aims to elucidate the ameliorating effect of exogenous acylated ghrelin or rikkunshito, a Kampo medicine which acts as a ghrelin enhancer, on gastric dysfunction during acute restraint stress in mice. Methods Fasted and postprandial motor function of the gastric antrum was wirelessly measured using a strain gauge force transducer and solid gastric emptying was detected in mice exposed to restraint stress. Plasma corticosterone and ghrelin levels were also measured. To clarify the role of ghrelin on gastrointestinal dysfunction in mice exposed to stress, exogenous acylated ghrelin or rikkunshito was administered, then the mice were subjected to restraint stress. Key Results Mice exposed to restraint stress for 60 min exhibited delayed gastric emptying and increased plasma corticosterone levels. Gastric motility was decreased in mice exposed to restraint stress in both fasting and postprandial states. Restraint stress did not cause any change in plasma acylated ghrelin levels, but it significantly increased the plasma des-acyl ghrelin levels. Administration of acylated ghrelin or rikkunshito improved the restraint stress-induced delayed gastric emptying and decreased antral motility. Ameliorating effects of rikkunshito on stress-induced gastric dysfunction were abolished by simultaneous administration of a ghrelin receptor antagonist. Conclusions & Inferences Plasma acylated/des-acyl ghrelin imbalance was observed in acute restraint stress. Supplementation of exogenous acylated ghrelin or enhancement of endogenous ghrelin signaling may be useful in the treatment of decreased gastric function caused by stress. PMID:24684160

To Not Settle for Small Losses: Evidence for an Ecological Aspiration Level of Zero in Dynamic Decision-Making

PubMed Central

Pang, Bo; Blanco, Nathaniel J.; Maddox, W. Todd; Worthy, Darrell A.

2016-01-01

This work aimed to investigate how one’s aspiration level is set in decision-making involving losses and how people respond when all alternatives appear to be below the aspiration level. We hypothesized that the zero point would serve as an ecological aspiration level where losses cause participants to focus on improvements in payoffs. In two experiments, we investigated these issues by combining behavioral studies and computational modeling. Participants chose from two alternatives on each trial. A decreasing option consistently gave a larger immediate payoff, although it caused future payoffs for both options to decrease. Selecting an increasing option caused payoffs for both options to increase on future trials. We manipulated the incentive structure such that in the losses condition the smallest payoff for the decreasing option was a loss, whereas in the gains condition the smallest payoff for the decreasing option was a gain, while the differences in outcomes for the two options were kept equivalent across conditions. Participants selected the increasing option more often in the losses condition than in the gains condition, regardless of whether the increasing option was objectively optimal (Experiment 1) or suboptimal (Experiment 2). Further, computational modeling results revealed that participants in the losses condition exhibited heightened weight to the frequency of positive versus negative prediction errors, suggesting that they were more attentive to improvements and reductions in outcomes than to expected values. This supports our assertion that losses induce aspiration for larger payoffs. We discuss our results in the context of recent theories of how losses shape behavior. PMID:27246089

To not settle for small losses: evidence for an ecological aspiration level of zero in dynamic decision-making.

PubMed

Pang, Bo; Blanco, Nathaniel J; Maddox, W Todd; Worthy, Darrell A

2017-04-01

This work aimed to investigate how one's aspiration level is set in decision-making involving losses and how people respond when all alternatives appear to be below the aspiration level. We hypothesized that the zero point would serve as an ecological aspiration level where losses cause participants to focus on improvements in payoffs. In two experiments, we investigated these issues by combining behavioral studies and computational modeling. Participants chose from two alternatives on each trial. A decreasing option consistently gave a larger immediate payoff, although it caused future payoffs for both options to decrease. Selecting an increasing option caused payoffs for both options to increase on future trials. We manipulated the incentive structure such that in the losses condition the smallest payoff for the decreasing option was a loss, whereas in the gains condition the smallest payoff for the decreasing option was a gain, while the differences in outcomes for the two options were kept equivalent across conditions. Participants selected the increasing option more often in the losses condition than in the gains condition, regardless of whether the increasing option was objectively optimal (Experiment 1) or suboptimal (Experiment 2). Further, computational modeling results revealed that participants in the losses condition exhibited heightened weight to the frequency of positive versus negative prediction errors, suggesting that they were more attentive to improvements and reductions in outcomes than to expected values. This supports our assertion that losses induce aspiration for larger payoffs. We discuss our results in the context of recent theories of how losses shape behavior.

Subchronic sleep restriction causes tissue-specific insulin resistance.

PubMed

Rao, Madhu N; Neylan, Thomas C; Grunfeld, Carl; Mulligan, Kathleen; Schambelan, Morris; Schwarz, Jean-Marc

2015-04-01

Short sleep duration is associated with an increased risk of type 2 diabetes. Subchronic sleep restriction (SR) causes insulin resistance, but the mechanisms and roles of specific tissues are unclear. The purpose of this article was to determine whether subchronic SR altered (1) hepatic insulin sensitivity, (2) peripheral insulin sensitivity, and (3) substrate utilization. This was a randomized crossover study in which 14 subjects underwent 2 admissions separated by a washout period. Each admission had 2 acclimatization nights followed by 5 nights of either SR (4 hours time in bed) or normal sleep (8 hours time in bed). MAIN OUTCOME MEASURE/METHODS: Insulin sensitivity (measured by hyperinsulinemic-euglycemic clamp) and hepatic insulin sensitivity (measured by stable isotope techniques) were measured. In addition, we assayed stress hormone (24-hour urine free cortisol, metanephrine, and normetanephrine), nonesterified fatty acid (NEFA), and β-hydroxybutyrate (β-OH butyrate) levels. Resting energy expenditure (REE) and respiratory quotient (RQ) were measured by indirect calorimetry. Compared to normal sleep, whole-body insulin sensitivity decreased by 25% (P = .008) with SR and peripheral insulin sensitivity decreased by 29% (P = .003). Whereas hepatic insulin sensitivity (endogenous glucose production) did not change significantly, percent gluconeogenesis increased (P = .03). Stress hormones increased modestly (cortisol by 21%, P = .04; metanephrine by 8%, P = .014; normetanephrine by 18%, P = .002). Fasting NEFA and β-OH butyrate levels increased substantially (62% and 55%, respectively). REE did not change (P = 0.98), but RQ decreased (0.81 ± .02 vs 0.75 ± 0.02, P = .045). Subchronic SR causes unique metabolic disturbances characterized by peripheral, but not hepatic, insulin resistance; this was associated with a robust increase in fasting NEFA levels (indicative of increased lipolysis), decreased RQ, and increased β-OH butyrate levels (indicative of whole-body and hepatic fat oxidation, respectively). We postulate that elevated NEFA levels are partially responsible for the decrease in peripheral sensitivity and modulation of hepatic metabolism (ie, increase in gluconeogenesis without increase in endogenous glucose production). Elevated cortisol and metanephrine levels may contribute to insulin resistance by increasing lipolysis and NEFA levels.

Short-term exposure to nonylphenol induces pancreatic oxidative stress and alters liver glucose metabolism in adult female rats.

PubMed

Jubendradass, R; D'Cruz, Shereen Cynthia; Mathur, P P

2011-01-01

Nonylphenol is known to have estrogenic properties and has been reported to cause health hazards to animals and humans. The effects of nonylphenol on pancreas are not clearly elucidated. In this study, we sought to evaluate the effects of nonylphenol on the oxidative status of pancreas and consequential effects of nonylphenol on some of the end points of carbohydrate metabolism in the female rats. Rats were administered nonylphenol orally at the doses of 1.5, 15, and 150 mg/kg of body weight per day for 7 days. After 24 h of last dosing, the animals were sacrificed by cervical dislocation. The activities of pancreatic superoxide dismutase and catalase were significantly decreased with a concomitant increase in the levels of H2O2 and lipid peroxidation. Nonylphenol increased plasma insulin levels with a concomitant decrease in the levels of plasma glucose as compared to the control groups of rats. A dose-dependent increase in the activities of liver hexokinase and phosphofructokinase was recorded along with decreased activity of glycogen phosphorylase in liver. Western blot analysis revealed a significant decrease in the levels of GLUT-2. These results show that nonylphenol causes oxidative stress in pancreas and impairs liver glucose homeostasis. Copyright © 2010 Wiley Periodicals, Inc.

Protective role of Kv7 channels in oxygen and glucose deprivation-induced damage in rat caudate brain slices

PubMed Central

Barrese, Vincenzo; Taglialatela, Maurizio; Greenwood, Iain A; Davidson, Colin

2015-01-01

Ischemic stroke can cause striatal dopamine efflux that contributes to cell death. Since Kv7 potassium channels regulate dopamine release, we investigated the effects of their pharmacological modulation on dopamine efflux, measured by fast cyclic voltammetry (FCV), and neurotoxicity, in Wistar rat caudate brain slices undergoing oxygen and glucose deprivation (OGD). The Kv7 activators retigabine and ICA27243 delayed the onset, and decreased the peak level of dopamine efflux induced by OGD; and also decreased OGD-induced damage measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Retigabine also reduced OGD-induced necrotic cell death evaluated by lactate dehydrogenase activity assay. The Kv7 blocker linopirdine increased OGD-evoked dopamine efflux and OGD-induced damage, and attenuated the effects of retigabine. Quantitative-PCR experiments showed that OGD caused an ~6-fold decrease in Kv7.2 transcript, while levels of mRNAs encoding for other Kv7 subunits were unaffected; western blot experiments showed a parallel reduction in Kv7.2 protein levels. Retigabine also decreased the peak level of dopamine efflux induced by L-glutamate, and attenuated the loss of TTC staining induced by the excitotoxin. These results suggest a role for Kv7.2 in modulating ischemia-evoked caudate damage. PMID:25966943

Long-term protective effects of methamphetamine preconditioning against single-day methamphetamine toxic challenges.

PubMed

Hodges, A B; Ladenheim, B; McCoy, M T; Beauvais, G; Cai, N; Krasnova, I N; Cadet, J L

2011-03-01

Methamphetamine (METH) use is associated with neurotoxic effects which include decreased levels of dopamine (DA), serotonin (5-HT) and their metabolites in the brain. We have shown that escalating METH dosing can protect against METH induced neurotoxicity in rats sacrificed within 24 hours after a toxic METH challenge. The purpose of the current study was to investigate if the protective effects of METH persisted for a long period of time. We also tested if a second challenge with a toxic dose of METH would cause further damage to monoaminergic terminals. Saline-pretreated rats showed significant METH-induced decreases in striatal DA and 5-HT levels in rats sacrificed 2 weeks after the challenge. Rats that received two METH challenges showed no further decreases in striatal DA or 5-HT levels in comparison to the single METH challenge. In contrast, METH-pretreated rats showed significant protection against METH-induced striatal DA and 5-HT depletion. In addition, the METH challenge causes substantial decreases in cortical 5-HT levels which were not further potentiated by a second drug challenge. METH preconditioning provided almost complete protection against METH -induced 5-HT depletion. These results are consistent with the idea that METH pretreatment renders the brain refractory to METH-induced degeneration of brain monoaminergic systems.

Inhibition of mutant IDH1 decreases D-2-HG levels without affecting tumorigenic properties of chondrosarcoma cell lines.

PubMed

Suijker, Johnny; Oosting, Jan; Koornneef, Annemarie; Struys, Eduard A; Salomons, Gajja S; Schaap, Frank G; Waaijer, Cathelijn J F; Wijers-Koster, Pauline M; Briaire-de Bruijn, Inge H; Haazen, Lizette; Riester, Scott M; Dudakovic, Amel; Danen, Erik; Cleton-Jansen, Anne-Marie; van Wijnen, Andre J; Bovée, Judith V M G

2015-05-20

Mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 are found in a subset of benign and malignant cartilage tumors, gliomas and leukaemias. The mutant enzyme causes the production of D-2-hydroxyglutarate (D-2-HG), affecting CpG island and histone methylation. While mutations in IDH1/2 are early events in benign cartilage tumors, we evaluated whether these mutations play a role in malignant chondrosarcomas. Compared to IDH1/2 wildtype cell lines, chondrosarcoma cell lines harboring an endogenous IDH1 (n=3) or IDH2 mutation (n=2) showed up to a 100-fold increase in intracellular and extracellular D-2-HG levels. Specific inhibition of mutant IDH1 using AGI-5198 decreased levels of D-2-HG in a dose dependent manner. After 72 hours of treatment one out of three mutant IDH1 cell lines showed a moderate decrease in viability , while D-2-HG levels decreased >90%. Likewise, prolonged treatment (up to 20 passages) did not affect proliferation and migration. Furthermore, global gene expression, CpG island methylation as well as histone H3K4, -9, and -27 trimethylation levels remained unchanged. Thus, while IDH1/2 mutations cause enchondroma, malignant progression towards central chondrosarcoma renders chondrosarcoma growth independent of these mutations. Thus, monotherapy based on inhibition of mutant IDH1 appears insufficient for treatment of inoperable or metastasized chondrosarcoma patients.

Dietary intake of S-(α-carboxybutyl)-DL-homocysteine induces hyperhomocysteinemia in rats

PubMed Central

Strakova, Jana; Williams, Kelly T.; Gupta, Sapna; Schalinske, Kevin L.; Kruger, Warren D.; Rozen, Rima; Jiracek, Jiri; Li, Lucas; Garrow, Timothy A.

2010-01-01

Betaine homocysteine S-methyltransferase (BHMT) catalyzes the transfer of a methyl group from betaine to homocysteine forming dimethylglycine and methionine. We previously showed that inhibiting BHMT in mice by intraperitoneal injection of S-(α-carboxybutyl)-DL-homocysteine (CBHcy) results in hyperhomocysteinemia. In the present study, CBHcy was fed to rats to determine whether it could be absorbed and cause hyperhomocysteinemia as observed for the intraperitoneal administration of the compound in mice. We hypothesized that dietary administered CBHcy will be absorbed and will result in the inhibition of BHMT and cause hyperhomocysteinemia. Rats were meal-fed every 8 hours an L-amino acid-defined diet either containing or devoid of CBHcy (5 mg/meal) for 3 days. The treatment decreased liver BHMT activity by 90% and had no effect on methionine synthase, methylenetetrahydrofolate reductase, phosphatidylethanolamine N-methyltransferase and CTP:phosphocholine cytidylyltransferase activities. In contrast, cystathionine β-synthase activity and immunodetectable protein decreased (56 and 26%, respectively) and glycine N-methyltransferase activity increased (52%) in CBHcy-treated rats. Liver S-adenosylmethionine levels decreased by 25% in CBHcy-treated rats and S-adenosylhomocysteine levels did not change. Further, plasma choline decreased (22%) and plasma betaine increased (15-fold) in CBHcy-treated rats. The treatment had no effect on global DNA and CpG island methylation, liver histology and plasma markers of liver damage. We conclude that CBHcy mediated BHMT inhibition causes an elevation in total plasma homocysteine that is not normalized by the folate-dependent conversion of homocysteine to methionine. Further, metabolic changes caused by BHMT inhibition affect cystathionine β-synthase and glycine N-methyltransferase activities, which further deteriorate plasma homocysteine levels. PMID:20797482

Chronic methamphetamine administration causes differential regulation of transcription factors in the rat midbrain.

PubMed

Krasnova, Irina N; Ladenheim, Bruce; Hodges, Amber B; Volkow, Nora D; Cadet, Jean Lud

2011-04-25

Methamphetamine (METH) is an addictive and neurotoxic psychostimulant widely abused in the USA and throughout the world. When administered in large doses, METH can cause depletion of striatal dopamine terminals, with preservation of midbrain dopaminergic neurons. Because alterations in the expression of transcription factors that regulate the development of dopaminergic neurons might be involved in protecting these neurons after toxic insults, we tested the possibility that their expression might be affected by toxic doses of METH in the adult brain. Male Sprague-Dawley rats pretreated with saline or increasing doses of METH were challenged with toxic doses of the drug and euthanized two weeks later. Animals that received toxic METH challenges showed decreases in dopamine levels and reductions in tyrosine hydroxylase protein concentration in the striatum. METH pretreatment protected against loss of striatal dopamine and tyrosine hydroxylase. In contrast, METH challenges caused decreases in dopamine transporters in both saline- and METH-pretreated animals. Interestingly, METH challenges elicited increases in dopamine transporter mRNA levels in the midbrain in the presence but not in the absence of METH pretreatment. Moreover, toxic METH doses caused decreases in the expression of the dopamine developmental factors, Shh, Lmx1b, and Nurr1, but not in the levels of Otx2 and Pitx3, in saline-pretreated rats. METH pretreatment followed by METH challenges also decreased Nurr1 but increased Otx2 and Pitx3 expression in the midbrain. These findings suggest that, in adult animals, toxic doses of METH can differentially influence the expression of transcription factors involved in the developmental regulation of dopamine neurons. The combined increases in Otx2 and Pitx3 expression after METH preconditioning might represent, in part, some of the mechanisms that served to protect against METH-induced striatal dopamine depletion observed after METH preconditioning.

Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the Global Burden of Disease Study 2016.

PubMed

2017-09-16

Monitoring levels and trends in premature mortality is crucial to understanding how societies can address prominent sources of early death. The Global Burden of Disease 2016 Study (GBD 2016) provides a comprehensive assessment of cause-specific mortality for 264 causes in 195 locations from 1980 to 2016. This assessment includes evaluation of the expected epidemiological transition with changes in development and where local patterns deviate from these trends. We estimated cause-specific deaths and years of life lost (YLLs) by age, sex, geography, and year. YLLs were calculated from the sum of each death multiplied by the standard life expectancy at each age. We used the GBD cause of death database composed of: vital registration (VR) data corrected for under-registration and garbage coding; national and subnational verbal autopsy (VA) studies corrected for garbage coding; and other sources including surveys and surveillance systems for specific causes such as maternal mortality. To facilitate assessment of quality, we reported on the fraction of deaths assigned to GBD Level 1 or Level 2 causes that cannot be underlying causes of death (major garbage codes) by location and year. Based on completeness, garbage coding, cause list detail, and time periods covered, we provided an overall data quality rating for each location with scores ranging from 0 stars (worst) to 5 stars (best). We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to generate estimates for each location, year, age, and sex. We assessed observed and expected levels and trends of cause-specific deaths in relation to the Socio-demographic Index (SDI), a summary indicator derived from measures of average income per capita, educational attainment, and total fertility, with locations grouped into quintiles by SDI. Relative to GBD 2015, we expanded the GBD cause hierarchy by 18 causes of death for GBD 2016. The quality of available data varied by location. Data quality in 25 countries rated in the highest category (5 stars), while 48, 30, 21, and 44 countries were rated at each of the succeeding data quality levels. Vital registration or verbal autopsy data were not available in 27 countries, resulting in the assignment of a zero value for data quality. Deaths from non-communicable diseases (NCDs) represented 72·3% (95% uncertainty interval [UI] 71·2-73·2) of deaths in 2016 with 19·3% (18·5-20·4) of deaths in that year occurring from communicable, maternal, neonatal, and nutritional (CMNN) diseases and a further 8·43% (8·00-8·67) from injuries. Although age-standardised rates of death from NCDs decreased globally between 2006 and 2016, total numbers of these deaths increased; both numbers and age-standardised rates of death from CMNN causes decreased in the decade 2006-16-age-standardised rates of deaths from injuries decreased but total numbers varied little. In 2016, the three leading global causes of death in children under-5 were lower respiratory infections, neonatal preterm birth complications, and neonatal encephalopathy due to birth asphyxia and trauma, combined resulting in 1·80 million deaths (95% UI 1·59 million to 1·89 million). Between 1990 and 2016, a profound shift toward deaths at older ages occurred with a 178% (95% UI 176-181) increase in deaths in ages 90-94 years and a 210% (208-212) increase in deaths older than age 95 years. The ten leading causes by rates of age-standardised YLL significantly decreased from 2006 to 2016 (median annualised rate of change was a decrease of 2·89%); the median annualised rate of change for all other causes was lower (a decrease of 1·59%) during the same interval. Globally, the five leading causes of total YLLs in 2016 were cardiovascular diseases; diarrhoea, lower respiratory infections, and other common infectious diseases; neoplasms; neonatal disorders; and HIV/AIDS and tuberculosis. At a finer level of disaggregation within cause groupings, the ten leading causes of total YLLs in 2016 were ischaemic heart disease, cerebrovascular disease, lower respiratory infections, diarrhoeal diseases, road injuries, malaria, neonatal preterm birth complications, HIV/AIDS, chronic obstructive pulmonary disease, and neonatal encephalopathy due to birth asphyxia and trauma. Ischaemic heart disease was the leading cause of total YLLs in 113 countries for men and 97 countries for women. Comparisons of observed levels of YLLs by countries, relative to the level of YLLs expected on the basis of SDI alone, highlighted distinct regional patterns including the greater than expected level of YLLs from malaria and from HIV/AIDS across sub-Saharan Africa; diabetes mellitus, especially in Oceania; interpersonal violence, notably within Latin America and the Caribbean; and cardiomyopathy and myocarditis, particularly in eastern and central Europe. The level of YLLs from ischaemic heart disease was less than expected in 117 of 195 locations. Other leading causes of YLLs for which YLLs were notably lower than expected included neonatal preterm birth complications in many locations in both south Asia and southeast Asia, and cerebrovascular disease in western Europe. The past 37 years have featured declining rates of communicable, maternal, neonatal, and nutritional diseases across all quintiles of SDI, with faster than expected gains for many locations relative to their SDI. A global shift towards deaths at older ages suggests success in reducing many causes of early death. YLLs have increased globally for causes such as diabetes mellitus or some neoplasms, and in some locations for causes such as drug use disorders, and conflict and terrorism. Increasing levels of YLLs might reflect outcomes from conditions that required high levels of care but for which effective treatments remain elusive, potentially increasing costs to health systems. Bill & Melinda Gates Foundation. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

On the Influence of Anthropogenic Forcings on Changes in the Stratospheric Mean Age

NASA Technical Reports Server (NTRS)

Oman, Luke; Waugh, Darryn W.; Pawson, Steven; Stolarski, Richard S.; Newman, Paul A.

2009-01-01

A common feature of stratospheric simulations of the past or future is an increase in tropical upwelling and a decrease in mean age. Possible causes or these changes include (1) increases in tropical sea surface temperatures (SSTs) driven by increases in well-mixed greenhouse gases (WMGHGs), (2) the direct radiative effect of increases in WMGHGs, and (3) changes in ozone. Here we examine a suite of simulations from the Goddard Earth Observing System chemistry-climate model (GEOS CCM) to isolate the relative role of these three factors. Our analysis indicates that all three factors cause changes in the mean age, but the relative impact of each factor depends on the time period analyzed. Over the past 30-40 years ozone depletion is the major factor causing the decrease in mean age, with negligible changes due to direct radiative impact of WMGHG's. However, ozone is predicted to recover back to 1970 levels during the next 50-60 years, and this causes an increase in the mean age, whereas the continued increase in SSTs from increased levels of WMGHGs and the direct radiative impact of WMGHGs will still cause a decrease in the mean age. The net impact of these factors will still result in a decreasing mean age although the rate will be smaller than that of the past. The decreases in mean age are primarily caused by increases in upwelling in the tropical lower stratosphere. The increased upwelling from both increased tropical SSTs and polar ozone loss appears to be related to changes in zonal winds and increases in wave activity propagating into the stratosphere. The different contributions of changes in SSTs, WMGHGs, and ozone to the circulation of the stratosphere may help explain the large spread in the rate of change of tropical upwelling seen in previous studies.

Selenium Deficiency Influences the Expression of Selenoproteins and Inflammatory Cytokines in Chicken Aorta Vessels.

PubMed

Du, Qiang; Yao, Haidong; Yao, Linlin; Zhang, Ziwei; Lei, Xingen; Xu, Shiwen

2016-10-01

Selenium deficiency is known to cause cardiovascular diseases. However, the role of Se deficiency in causing oxidative damage and inflammation injury to the aorta vessels of chickens is not well known. In the present study, 180 1-day-old chickens were randomly divided into two groups, a low-Se group (L group) and a control-Se group (C group). The messenger RNA (mRNA) levels of 25 selenoproteins, the mRNA and protein expression levels of inflammatory cytokines (including NF-κB, TNF-α, COX-2, and PTGES), and the antioxidant levels in chicken aorta vessels were examined. The results showed that the mRNA levels of 25 selenoproteins and the activity of Gpx were decreased, while the mRNA and protein expression levels of inflammatory cytokines and the MDA content were increased by Se deficiency in chicken aorta vessels. The data from the present study indicated that Se deficiency decreases the expression of selenoproteins, reduces antioxidant function, and increases the expression of inflammatory factors in chicken aorta vessels.

Decrease of 5-hydroxymethylcytosine in rat liver with subchronic exposure to genotoxic carcinogens riddelliine and aristolochic acid.

PubMed

Lian, Christine Guo; Xu, Shuyun; Guo, Weimin; Yan, Jian; Frank, Maximilian Y M; Liu, Robert; Liu, Cynthia; Chen, Ying; Murphy, George F; Chen, Tao

2015-11-01

The level of 5-hydroxymethylcytosine (5-hmC) converted by ten-eleven translocation (TET) family is decreased in cancers. However, whether 5-hmC level is perturbed in early stages of carcinogenesis caused by genotoxic carcinogens is not defined. 5-hmC levels and TET2 expression were measured in liver of rats treated with genotoxic carcinogens, riddelliine, or aristolochic acid. Levels of 5-hmC and TET2 expression decreased in the liver of the carcinogens-treated rats. Loss of 5-hmC correlates well with documented induction of genetic mutations by the carcinogens, suggesting that TET2-mediated 5-hydroxymethylation plays an epigenetic role in early state of carcinogenesis. © 2014 Wiley Periodicals, Inc.

Decrease of 5-Hydroxymethylcytosine in Rat Liver with Subchronic Exposure to Genotoxic Carcinogens Riddelliine and Aristolochic Acid

PubMed Central

Lian, Christine Guo; Xu, Shuyun; Guo, Weimin; Yan, Jian; Frank, Maximilian Y M; Liu, Robert; Liu, Cynthia; Chen, Ying; Murphy, George F.; Chen, Tao

2018-01-01

The level of 5-hydroxymethylcytosine (5-hmC) converted by ten-eleven translocation (TET) family is decreased in cancers. However, whether 5-hmC level is perturbed in early stages of carcinogenesis caused by genotoxic carcinogens is not defined. 5-hmC levels and TET2 expression were measured in liver of rats treated with genotoxic carcinogens, riddelliine, or aristolochic acid. Levels of 5-hmC and TET2 expression decreased in the liver of the carcinogens-treated rats. Loss of 5-hmC correlates well with documented induction of genetic mutations by the carcinogens, suggesting that TET2-mediated 5-hydroxymethylation plays an epigenetic role in early state of carcinogenesis. PMID:25154389

Differential effects of exposure to parasites and bacteria on stress response in turbot Scophthalmus maximus simultaneously stressed by low water depth.

PubMed

Rodríguez-Quiroga, J J; Otero-Rodiño, C; Suárez, P; Nieto, T P; García Estévez, J M; San Juan, F; Soengas, J L

2017-07-01

The stress response of turbot Scophthalmus maximus was evaluated in fish maintained 8 days under different water depths, normal (NWD, 30 cm depth, total water volume 40 l) or low (LWD, 5 cm depth, total water volume 10 l), in the additional presence of infection-infestation of two pathogens of this species. This was caused by intraperitoneal injection of sublethal doses of the bacterium Aeromonas salmonicida subsp. salmonicida or the parasite Philasterides dicentrarchi (Ciliophora:Scuticociliatida). The LWD conditions were stressful for fish, causing increased levels of cortisol in plasma, decreased levels of glycogen in liver and nicotinamide adenine dinucleotide phosphate (NADP) and increased activities of G6Pase and GSase. The presence of bacteria or parasites in fish under NWD resulted in increased cortisol levels in plasma whereas in liver, changes were of minor importance including decreased levels of lactate and GSase activity. The simultaneous presence of bacteria and parasites in fish under NWD resulted a sharp increase in the levels of cortisol in plasma and decreased levels of glucose. Decreased levels of glycogen and lactate and activities of GSase and glutathione reductase (GR), as well as increased activities of glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH) and levels of nicotinamide adenine dinucleotide phosphate (NADPH) occurred in the same fish in liver. Finally, the presence of pathogens in S. maximus under stressful conditions elicited by LWD resulted in synergistic actions of both type of stressors in cortisol levels. In liver, the presence of bacteria or parasites induced a synergistic action on several variables such as decreased activities of G6Pase and GSase as well as increased levels of NADP and NADPH and increased activities of GPase, G6PDH and 6PGDH. © 2017 The Fisheries Society of the British Isles.

Genotoxic effect of ethacrynic acid and impact of antioxidants

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

Ward, William M.; Hoffman, Jared D.; Loo, George, E-mail: g_loo@uncg.edu

It is known that ethacrynic acid (EA) decreases the intracellular levels of glutathione. Whether the anticipated oxidative stress affects the structural integrity of DNA is unknown. Therefore, DNA damage was assessed in EA-treated HCT116 cells, and the impact of several antioxidants was also determined. EA caused both concentration-dependent and time-dependent DNA damage that eventually resulted in cell death. Unexpectedly, the DNA damage caused by EA was intensified by either ascorbic acid or trolox. In contrast, EA-induced DNA damage was reduced by N-acetylcysteine and by the iron chelator, deferoxamine. In elucidating the DNA damage, it was determined that EA increased themore » production of reactive oxygen species, which was inhibited by N-acetylcysteine and deferoxamine but not by ascorbic acid and trolox. Also, EA decreased glutathione levels, which were inhibited by N-acetylcysteine. But, ascorbic acid, trolox, and deferoxamine neither inhibited nor enhanced the capacity of EA to decrease glutathione. Interestingly, the glutathione synthesis inhibitor, buthionine sulfoxime, lowered glutathione to a similar degree as EA, but no noticeable DNA damage was found. Nevertheless, buthionine sulfoxime potentiated the glutathione-lowering effect of EA and intensified the DNA damage caused by EA. Additionally, in examining redox-sensitive stress gene expression, it was found that EA increased HO-1, GADD153, and p21mRNA expression, in association with increased nuclear localization of Nrf-2 and p53 proteins. In contrast to ascorbic acid, trolox, and deferoxamine, N-acetylcysteine suppressed the EA-induced upregulation of GADD153, although not of HO-1. Overall, it is concluded that EA has genotoxic properties that can be amplified by certain antioxidants. - Highlights: • Ethacrynic acid (EA) caused cellular DNA damage. • EA-induced DNA damage was potentiated by ascorbic acid or trolox. • EA increased ROS production, not inhibited by ascorbic acid or trolox. • EA decreased glutathione levels, not prevented by ascorbic acid or trolox. • Buthionine sulfoxime intensified the DNA damage caused by EA.« less

The effects of levosimendan exposure on oxidant/antioxidant status and trace element levels in the pulmonary artery of rats.

PubMed

Ay, Yasin; Aydın, Cemalettin; Basel, Halil; Bektaş, Hava; Bülüt, Gülay; Inan, Bekir; Ay, Nuray Kahraman; Demir, Ismail

2013-06-01

We investigated both the effect of levosimendan and the role of oxidant/antioxidant status and trace element levels in the pulmonary artery of rats. Fourteen male Wistar albino rats were randomly divided into two groups of seven animals each. Group 1 was not exposed to levosimendan and served as a control. Levosimendan (12 μg/kg) diluted in 10 ml 0.9 % NaCl was administered intraperitoneally to group 2. Animals of both groups were killed after 3 days, and their pulmonary arteries were harvested to determine changes in tissue oxidant/antioxidant status and trace element levels. The animals in both groups were killed 72 h after the levosimendan exposure treatment, and pulmonary arteries were harvested to determine levels of the lipid peroxidation product MDA and the antioxidant GSH as well as the decreased activity of antioxidant enzymes such as SOD, GSH-Px and CAT. It was found that MDA levels increased in pulmonary artery tissues of rats after levosimendan administration. The GSH level decreased in the pulmonary artery of rats after levosimendan treatment. Co, Mn, Fe, Cd and Pb levels were significantly higher (P < 0.001) and Mg, Zn and Cu levels significantly lower (P < 0.001) in the levosimendan group compared to the control group. These results suggest that levosimendan treatment caused an increase in free radical production and a decrease in antioxidant enzyme activity in the pulmonary artery of levosimendan-treated rats. It also caused a decrease or increase in the levels of many minerals in the pulmonary artery, which is an undesirable condition for normal pharmacological function.

Increased work in cardiac trabeculae causes decreased mitochondrial NADH fluorescence followed by slow recovery.

PubMed Central

Brandes, R; Bers, D M

1996-01-01

The oxidative phosphorylation rate in isolated mitochondria is stimulated by increased [ADP], resulting in decreased [NADH]. In intact hearts, however, increased mechanical work has generally not been shown to cause an increase in [ADP]. Therefore, increased [NADH] has been suggested as an alternative for stimulating the phosphorylation rate. Such a rise in [NADH] could result from stimulation of various substrate dehydrogenases by increased intracellular [Ca2+] (e.g., during increased pacing frequency). We have monitored mitochondrial [NADH] in isolated rat ventricular trabeculae, using a novel fluorescence spectroscopy method where a native fluorescence signal was used to correct for motion artifacts. Work was controlled by increased pacing frequency and assessed using time-averaged force. At low-pacing rates (approximately 0.1 Hz), [NADH] immediately decreased during contraction and then slowly recovered (approximately 5 s) before the next contraction. At higher rates, [NADH] initially decreased by an amount related to pacing rate (i.e., work). However, during prolonged stimulation, [NADH] slowly (approximately 60 s) recovered to a new steady-state level below the initial level. We conclude that 1) during increased work, oxidative phosphorylation is not initially stimulated by increased mitochondrial [NADH]; and 2) increased pacing frequency slowly causes stimulation of NADH production. Images FIGURE 2 FIGURE 4 PMID:8842239

Evaluation of the potential of triethanolamine to alter hepatic choline levels in female B6C3F1 mice.

PubMed

Stott, W T; Radtke, B J; Linscombe, V A; Mar, M-H; Zeisel, S H

2004-06-01

Triethanolamine (TEA), a widely used nongenotoxic alcohol-amine, has recently been reported to cause an increased incidence of liver tumors in female B6C3F1 mice, but not in males nor in Fischer 344 rats. Choline deficiency induces liver cancer in rodents, and TEA could compete with choline uptake into tissues. The potential of TEA to cause choline deficiency in the liver of these mice as a mode of tumorigenesis was investigated. Groups of female B6C3F1 mice were administered 0 (vehicle) or a maximum tolerated dosage (MTD) of 1000 mg/kg/day TEA (Trial I) and 0, 10, 100, 300, or 1000 mg/kg/day TEA (Trial II) in acetone vehicle via skin painting 5 days/week for 3 weeks. Female CDF(R) rats were also administered 0 or an MTD dosage of 250 mg/kg/day TEA (Trial II) in a similar manner. No clinical signs of toxicity were noted, and upon sacrifice, levels of hepatic choline, its primary storage form, phosphocholine (PCho), and its primary oxidation product, betaine, were determined. A statistically significant decrease in PCho and betaine, was observed at the high dosage (26-42%) relative to controls and a dose-related, albeit variable, decrease was noted in PCho levels. Choline levels were also decreased 13-35% at the high dose level in mice. No changes in levels of choline or metabolites were noted in treated rats. A subsequent evaluation of the potential of TEA to inhibit the uptake of (3)H-choline by cultured Chinese Hamster Ovary Cells revealed a dose-related effect upon uptake. It was concluded that TEA may cause liver tumors in mice via a choline-depletion mode of action and that this effect is likely caused by the inhibition of choline uptake by cells.

Evaluation of the Potential of Triethanolamine to Alter Hepatic Choline Levels in Female B6C3F1 Mice

PubMed Central

Stott, W. T.; Radtke, B. J.; Linscombe, V. A.; Mar, M-H; Zeisel, S. H.

2006-01-01

Triethanolamine (TEA), a widely used nongenotoxic alcoholamine, has recently been reported to cause an increased incidence of liver tumors in female B6C3F1 mice, but not in males nor in Fischer 344 rats. Choline deficiency induces liver cancer in rodents, and TEA could compete with choline uptake into tissues. The potential of TEA to cause choline deficiency in the liver of these mice as a mode of tumorigenesis was investigated. Groups of female B6C3F1 mice were administered 0 (vehicle) or a maximum tolerated dosage (MTD) of 1000 mg/kg/day TEA (Trial I) and 0, 10, 100, 300, or 1000 mg/kg/day TEA (Trial II) in acetone vehicle via skin painting 5 days/week for 3 weeks. Female CDF® rats were also administered 0 or an MTD dosage of 250 mg/kg/day TEA (Trial II) in a similar manner. No clinical signs of toxicity were noted, and upon sacrifice, levels of hepatic choline, its primary storage form, phosphocholine (PCho), and its primary oxidation product, betaine, were determined. A statistically significant decrease in PCho and betaine, was observed at the high dosage (26–42%) relative to controls and a dose-related, albeit variable, decrease was noted in PCho levels. Choline levels were also decreased 13–35% at the high dose level in mice. No changes in levels of choline or metabolites were noted in treated rats. A subsequent evaluation of the potential of TEA to inhibit the uptake of 3H-choline by cultured Chinese Hamster Ovary Cells revealed a dose-related effect upon uptake. It was concluded that TEA may cause liver tumors in mice via a choline-depletion mode of action and that this effect is likely caused by the inhibition of choline uptake by cells. PMID:15056812

Controlling of growth performance, lipid deposits and fatty acid composition of chicken meat through a probiotic, Lactobacillus johnsonii during subclinical Clostridium perfringens infection.

PubMed

Wang, Hesong; Ni, Xueqin; Liu, Lei; Zeng, Dong; Lai, Jing; Qing, Xiaodan; Li, Guangyao; Pan, Kangcheng; Jing, Bo

2017-02-10

Meat is considered as a major source of polyunsaturated fatty acid (PUFA) which is essential for humans, therefore its lipid level and fatty acid composition have drawn great attention. As no clinical sign can be found in chicks subclinically infected by Clostridium perfringens (CP), the meat may be purchased and eaten. The objective of the present study was to determine whether Lactobacillus johnsonii (LJ) can control the CP-caused impact on growth, lipid levels, fatty acid composition and other flavor or nutritional quality in the meat. 480 one-day-old chicks were divided into four groups and fed with basal diet (control and CP group). Supplemented with 1 × 10 5 (L-LJ) and 1 × 10 6 (H-LJ) colony-forming unit (cfu), CP diet was fed for 42 days. From day 19 to 22, birds of CP and LJ groups were administered with CP twice per day and the control was administered with liver broth. LJ-treated chickens were free from negative influences on growth performance and significant decrease of abdominal fat deposit., LJ inhibited CP-caused shearing force and drip loss increase and pH 40 min and 24 h decrease after sacrifice. In addition, LJ exhibited a positive effect on muscle lipid peroxidation by significantly increasing SOD, CAT and GSH-Px activity and decreasing MDA level. Besides, LJ attenuated the decrease of intramuscular fat, total cholesterol and triglyceride contents caused by CP infection. However, levels of total protein and most of amino acids were not changed. CP infection decreased C18:3n-3 (α-LA), C20:4n-6, C20:5n-3(EPA), C22:4n-6, C22:5n-3, C22:6n-3(DHA), total PUFA, n-3 PUFA and PUFA:SFA ratio and increased C14:0, total SFA and n-6:n-3 ratio. LJ was found to protect the muscle from these changes. Meanwhile, the 28-day gut permeability level was higher in CP group. These findings suggest that CP may affect the growth performance of chicks and negatively influence lipid content and fatty acid composition in chicken meat. Meanwhile, LJ treatment may be effective in controlling these changes by reducing the increased gut permeability caused by CP subclinical infection.

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.

Staurosporine potentiates platelet activating factor stimulated phospholipase C activity in rabbit platelets but does not block desensitization by platelet activating factor.

PubMed

Morrison, W J; Dhar, A; Shukla, S D

1989-01-01

The possible involvement of protein kinase C activation in regulating PAF-stimulated PLC activity was studied in rabbit platelets. PAF (100 nM for 5 seconds) stimulated incorporation of 32P into proteins and caused [3H]InsP3 levels to increase about 260% of control. These responses were compared after platelets were pretreated with either PAF, phorbol 12-myristate 13-acetate (PMA) or staurosporine and also after pretreatments with staurosporine followed by PAF or PMA. Pretreating platelets with staurosporine potentiated PAF-stimulated [3H]InsP3 levels by 54% and blocked protein phosphorylation. Pretreatments with PAF and PMA caused PAF-stimulated [3H]InsP3 levels to decrease to 115 and 136%, respectively. Staurosporine pretreatment blocked the decrease caused by the PMA pretreatment but not that by PAF. This study demonstrates that PAF-stimulated PLC activity is negatively affected by protein kinase C (PKC) activation and that inhibition of PKC activity did not prevent desensitization of PLC by PAF.

The effect of hypophysectomy on chloride balance in young-of-the-year bowfin, Amia calva.

PubMed

Duff, D; Hanson, R; Fleming, W R

1987-01-01

The effect of hypophysectomy on chloride balance was examined in young-of-the-year bowfin, Amia calva. Hypophysectomy resulted in decreased serum and total body chloride levels but not in serum and total body sodium levels. Hypophysectomy resulted in decreased chloride influx with no effect on chloride efflux or sodium fluxes. Prolactin therapy reversed the effect of hypophysectomy on electrolyte balance but caused a significant reduction in serum protein.

Effects of L-carnitine and coenzyme q10 on impaired spermatogenesis caused by isoproterenol in male rats.

PubMed

Ghanbarzadeh, S; Garjani, A; Ziaee, M; Khorrami, A

2014-09-01

Nowadays, cardiovascular diseases and male infertility are two big health problems in industrial countries.The aim of the present study was to investigate the protective role of coenzyme Q10 and L-Carnitine pretreatment in the impaired spermatogenesis caused by isoproterenol (ISO) in male rats.Thirty-two male Wistar rats were allocated in 4 groups. ISO was injected for 2 consecutive days (100 mg/kg) in ISO treated groups. Before ISO administration, pretreatment with Coenzyme Q10 (10 mg/kg/day) and L-Carnitine (350 mg/kg/day) were conducted for 20 consecutive days. Sex hormones level, malondialdehyde (MDA) and total antioxidant concentration as well as testis, epididymis and seminal vesicle weight were investigated.Increase in the concentration of MDA and decrease in total antioxidant level was observed following ISO administration. Accordingly, the sperm viability as well as testis, epididymis and seminal vesicle weights were decreased. In the case of sex hormones, the testosterone and LH levels were decreased and the concentration of FSH was increased. Pretreatment with L-carnitine and Coenzyme Q10 significantly decreased the MDA level and increased total antioxidant, LH and testosterone levels. Pretreatment with L-carnitine and Coenzyme Q10 also improved semen parameters and organs weight which were impaired by ISO administration.L-carnitine and Coenzyme Q10 pretreatment could protect spermatogenesis in male rats with ISO administration. © Georg Thieme Verlag KG Stuttgart · New York.

Exposure of Pregnant Mice to Perfluorobutanesulfonate Causes Hypothyroxinemia and Developmental Abnormalities in Female Offspring.

PubMed

Feng, Xuejiao; Cao, Xinyuan; Zhao, Shasha; Wang, Xiaoli; Hua, Xu; Chen, Lin; Chen, Ling

2017-02-01

Perfluorobutanesulfonate (PFBS) is widely used in many industrial products. We evaluated the influence of prenatal PFBS exposure on perinatal growth and development, pubertal onset, and reproductive and thyroid endocrine system in female mice. Here, we show that when PFBS (200 and 500 mg/kg/day) was orally administered to pregnant mice (PFBS-dams) on days 1-20 of gestation; their female offspring (PFBS-offspring) exhibited decreased perinatal body weight and delayed eye opening compared with control offspring. Vaginal opening and first estrus were also significantly delayed in PFBS-offspring, and diestrus was prolonged. Ovarian and uterine size, as well as follicle and corpus luteum numbers, were reduced in adult PFBS-offspring. Furthermore, pubertal and adult PFBS-offspring exhibited decreases in serum estrogen (E2) and progesterone (P4) levels with the elevation of luteinizing hormone levels. Notably, decreases in serum total thyroxine (T4) and 3,3', 5-triiodothyronine (T3) levels were observed in fetal, pubertal, and adult PFBS-offspring in conjunction with slight increases in thyroid-stimulating hormone (TSH) and thyrotropin-releasing hormone levels. In addition, PFBS-dams exhibited significant decreases in total T4 and T3 levels and free T4 levels and increases in TSH levels, but no changes in E2 and P4 levels. These results indicate that prenatal PFBS exposure (≥200 mg/kg/day) causes permanent hypothyroxinemia accompanied by deficits in perinatal growth, pubertal onset, and reproductive organ development in female mice. © 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.

Effects of the proposed Prosperity Reservoir on ground water and water quality in lower Center Creek basin, Missouri

USGS Publications Warehouse

Berkas, Wayne R.; Barks, James H.

1980-01-01

Effects of the proposed Prosperity Reservoir on ground water and water quality in lower Center Creek basin depend partly on the effectiveness of Grove Creek as a hydrologic boundary between the reservoir site and the Oronogo-Duenweg mining belt. Results of two dye traces indicate that Grove Creek probably is not an effective boundary. Therefore, higher water levels near the reservoir may cause more ground water to move into the mining belt and cause a greater discharge of zinc-laden mine water into Center Creek.Ground-water-level measurements and seepage runs on Center Creek indicate a relationship between ground-water levels, mine-water discharge and seepage, and base flow in Center Creek. From March to October 1979, ground-water levels generally decreased from 5 to 20 feet at higher elevations (recharge areas) and from 1 to 3 feet near Center Creek (discharge area); total mine water discharged to the surface before entering Center Creek decreased from 5.4 to 2.2 cubic feet per second; mine-water seepage directly to Center Creek decreased from an estimated 1.9 to 1.1 cubic feet per second; and the discharge of Center Creek near Carterville decreased from 184 to 42 cubic feet per second.Fertilizer industry wastes discharged into Grove Creek resulted in significant increases of nitrogen and phosphorus in lower Center Creek.

High shear induces platelet dysfunction leading to enhanced thrombotic propensity and diminished hemostatic capacity.

PubMed

Chen, Zengsheng; Mondal, Nandan K; Zheng, Shirong; Koenig, Steven C; Slaughter, Mark S; Griffith, Bartley P; Wu, Zhongjun J

2017-11-28

Thrombosis and bleeding are devastating adverse events in patients supported with blood-contacting medical devices (BCMDs). In this study, we delineated that high non-physiological shear stress (NPSS) caused platelet dysfunction that may contribute to both thrombosis and bleeding. Human blood was subjected to NPSS with short exposure time. Levels of platelet surface GPIbα and GPVI receptors as well as activation level of GPIIb/IIIa in NPSS-sheared blood were examined with flow cytometry. Adhesion of sheared platelets on fibrinogen, von Willibrand factor (VWF), and collagen was quantified with fluorescent microscopy. Ristocetin- and collagen-induced platelet aggregation was characterized by aggregometry. NPSS activated platelets in a shear and exposure time-dependent manner. The number of activated platelets increased with increasing levels of NPSS and exposure time, which corresponded well with increased adhesion of sheared platelets on fibrinogen. Concurrently, NPSS caused shedding of GPIbα and GPVI in a manner dependent on shear and exposure time. The loss of intact GPIbα and GPVI increased with increasing levels of NPSS and exposure time. The number of platelets adhered on VWF and collagen decreased with increasing levels of NPSS and exposure time, respectively. The decrease in the number of platelets adhered on VWF and collagen corresponded well with the loss in GPIbα and GPVI on platelet surface. Both ristocetin- and collagen-induced platelet aggregation in sheared blood decreased with increasing levels of NPSS and exposure time. The study clearly demonstrated that high NPSS causes simultaneous platelet activation and receptor shedding, resulting in a paradoxical effect on platelet function via two distinct mechanisms. The results from the study suggested that the NPSS could induce the concurrent propensity for both thrombosis and bleeding in patients.

MPV17 Loss Causes Deoxynucleotide Insufficiency and Slow DNA Replication in Mitochondria

PubMed Central

Dalla Rosa, Ilaria; Cámara, Yolanda; Durigon, Romina; Moss, Chloe F.; Vidoni, Sara; Akman, Gokhan; Hunt, Lilian; Johnson, Mark A.; Grocott, Sarah; Wang, Liya; Thorburn, David R.; Hirano, Michio; Poulton, Joanna; Taylor, Robert W.; Elgar, Greg; Martí, Ramon; Voshol, Peter; Holt, Ian J.; Spinazzola, Antonella

2016-01-01

MPV17 is a mitochondrial inner membrane protein whose dysfunction causes mitochondrial DNA abnormalities and disease by an unknown mechanism. Perturbations of deoxynucleoside triphosphate (dNTP) pools are a recognized cause of mitochondrial genomic instability; therefore, we determined DNA copy number and dNTP levels in mitochondria of two models of MPV17 deficiency. In Mpv17 ablated mice, liver mitochondria showed substantial decreases in the levels of dGTP and dTTP and severe mitochondrial DNA depletion, whereas the dNTP pool was not significantly altered in kidney and brain mitochondria that had near normal levels of DNA. The shortage of mitochondrial dNTPs in Mpv17-/- liver slows the DNA replication in the organelle, as evidenced by the elevated level of replication intermediates. Quiescent fibroblasts of MPV17-mutant patients recapitulate key features of the primary affected tissue of the Mpv17-/- mice, displaying virtual absence of the protein, decreased dNTP levels and mitochondrial DNA depletion. Notably, the mitochondrial DNA loss in the patients’ quiescent fibroblasts was prevented and rescued by deoxynucleoside supplementation. Thus, our study establishes dNTP insufficiency in the mitochondria as the cause of mitochondrial DNA depletion in MPV17 deficiency, and identifies deoxynucleoside supplementation as a potential therapeutic strategy for MPV17-related disease. Moreover, changes in the expression of factors involved in mitochondrial deoxynucleotide homeostasis indicate a remodeling of nucleotide metabolism in MPV17 disease models, which suggests mitochondria lacking functional MPV17 have a restricted purine mitochondrial salvage pathway. PMID:26760297

MANAGEMENT OF ENDOCRINE DISEASE: Hypothyroidism-associated hyponatremia: mechanisms, implications and treatment.

PubMed

Liamis, G; Filippatos, T D; Liontos, A; Elisaf, M S

2017-01-01

Patients with moderate to severe hypothyroidism and mainly patients with myxedema may exhibit reduced sodium levels (<135 mmol/L). The aim of this short review is the presentation of the mechanisms of hyponatremia and of the available data regarding its implications and treatment in patients with hypothyroidism. Hypothyroidism is one of the causes of hyponatremia, thus thyroid-stimulating hormone determination is mandatory during the evaluation of patients with reduced serum sodium levels. The main mechanism for the development of hyponatremia in patients with chronic hypothyroidism is the decreased capacity of free water excretion due to elevated antidiuretic hormone levels, which are mainly attributed to the hypothyroidism-induced decrease in cardiac output. However, recent data suggest that the hypothyroidism-induced hyponatremia is rather rare and probably occurs only in severe hypothyroidism and myxedema. Other possible causes and superimposed factors of hyponatremia (e.g. drugs, infections, adrenal insufficiency) should be considered in patients with mild/moderate hypothyroidism. Treatment of hypothyroidism and fluid restriction are usually adequate for the management of mild hyponatremia in patients with hypothyroidism. Patients with possible hyponatremic encephalopathy should be urgently treated according to current guidelines. Severe hypothyroidism may be the cause of hyponatremia. All hypothyroid patients with low serum sodium levels should be evaluated for other causes and superimposed factors of hyponatremia and treated accordingly. © 2017 European Society of Endocrinology.

Imperatorin ameliorates lipopolysaccharide induced memory deficit by mitigating proinflammatory cytokines, oxidative stress and modulating brain-derived neurotropic factor.

PubMed

Chowdhury, Amrita A; Gawali, Nitin B; Shinde, Prashant; Munshi, Renuka; Juvekar, Archana R

2018-04-26

Lipopolysaccharide (LPS), an endotoxin from the outer membrane of Gram negative bacteria has been reported to cause neuroinflammation and learning and memory deficits. There are reports describing the beneficial effects of Imperatorin (IMP), a naturally occurring furanocoumarin in central nervous system (CNS) disorders such as anxiety and epilepsy. In the current study, we investigated whether IMP protects against LPS mediated memory deficits and neuroinflammation. Mice pretreated with IMP (5, 10 mg/kg po) were administered LPS (250 μg/kg ip) for 7 days. Memory was evaluated in the Morris water maze (MWM) and Y maze. The mice were euthanised and different biochemical assessments were carried out to measure oxidative stress and acetyl choline esterase (AChE). Further, evaluation of proinflammatory cytokines such as tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) levels and brain derived neurotrophic factor (BDNF) in hippocampus and cortex of brain were performed. LPS administration caused poor memory retention in both, MWM and Y maze, and caused distinct oxidative stress since decrease in superoxide dismutase (SOD), reduced glutathione (GSH) levels and increased lipid peroxidation were observed. Also, a significant rise was observed in the levels of AChE. Moreover, a rise in TNF-α and IL-6 levels and depleted levels of BDNF were noted. IMP pretreatment reversed LPS induced behavioral and memory disturbances and significantly decreased the oxidative stress and AChE levels. It also reduced TNF-α and IL-6 levels and caused a significant upregulation of BDNF levels. Present study highlights the potential neuroprotective role of IMP against LPS mediated cognitive impairment and neuroinflammation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Application of the Finite Element Method to Reveal the Causes of Loss of Planeness of Hot-Rolled Steel Sheets during Laser Cutting

NASA Astrophysics Data System (ADS)

Garber, E. A.; Bolobanova, N. L.; Trusov, K. A.

2018-01-01

A finite element technique is developed to simulate the stresses and the strains during strip flattening to reveal the causes of the cutting-assisted loss of planeness of hot-rolled steel sheets processed in roller levelers. The loss of planeness is found to be caused by a nonuniform distribution of the flattening-induced longitudinal tensile stresses over the strip thickness and width. The application of tensile forces to a strip in a roller leveler decreases this nonuniformity and prevents loss of planeness in cutting.

Dieldrin exposure induces oxidative damage in the mouse nigrostriatal dopamine system

PubMed Central

Hatcher, Jaime M.; Richardson, Jason R.; Guillot, Thomas S.; McCormack, Alison L.; Di Monte, Donato A.; Jones, Dean P.; Pennell, Kurt D.; Miller, Gary W.

2007-01-01

Numerous epidemiological studies have shown an association between pesticide exposure and an increased risk of developing Parkinson’s disease (PD). Here, we provide evidence that the insecticide dieldrin causes specific oxidative damage in the nigrostriatal dopamine (DA) system. We report that exposure of mice to low levels of dieldrin for 30 days resulted in alterations in dopamine-handling as evidenced by a decrease in dopamine metabolites, DOPAC (31.7% decrease) and HVA (29.2% decrease) and significantly increased cysteinyl-catechol levels in the striatum. Furthermore, dieldrin resulted in a 53% decrease in total glutathione, an increase in the redox potential of glutathione, and a 90% increase in protein carbonyls. α-Synuclein protein expression was also significantly increased in the striatum (25% increase). Finally, dieldrin caused a significant decrease in striatal expression of the dopamine transporter as measured by 3H-WIN 35,428 binding and 3H-dopamine uptake. These alterations occurred in the absence of dopamine neuron loss in the substantia nigra pars compacta. These effects represent the ability of low doses of dieldrin to increase the vulnerability of nigrostriatal dopamine neurons by inducing oxidative stress and suggest that pesticide exposure may act as a promoter of PD. PMID:17291500

Antioxidant status and mineral contents in tissues of rutin and baicalin fed rats.

PubMed

Gao, Zhonghong; Xu, Huibi; Chen, Xiaojun; Chen, Hao

2003-08-08

The versatile benefit effects of flavonoids lead some nutritionists to believe that they are micronutrients. However, excess intake of flavonoids may cause side effects. In this paper, the effects produced by a higher intake of rutin and baicalin on antioxidant status as well as trace minerals such as iron, copper and zinc in rat tissues were studied. When rats were fed a rutin or baicalin containing diet (1%) for 20 days, the body weight gain was lower than that of the control group. Both rutin and baicalin caused significant a decrease of catalase activity and a moderate increase of total superoxide dismutase activity in the liver. The total antioxidant status of flavonoid fed rats was increased in the liver but decreased in the serum. In comparison to the control group, the lipid peroxidation level in the liver of the rutin fed group was significantly decreased; however, there was no statistical significance in the liver of the baicalin fed group and the brain of both flavonoids groups. The liver homogenates of both flavonoid fed rats significantly inhibited alkyl radical-induced lipid peroxidation. The iron contents in the liver of flavonoid fed rats were significantly decreased; rutin also caused zinc and copper decrease in the liver. These results indicated that high flavonoid intake can improve rat antioxidant systems in the liver; while it can also cause a trace mineral decrease and, in turn, reduce the activities of some metal-containing enzymes and may cause harmful effects on health.

Spaceflight has compartment- and gene-specific effects on mRNA levels for bone matrix proteins in rat femur

NASA Technical Reports Server (NTRS)

Evans, G. L.; Morey-Holton, E.; Turner, R. T.

1998-01-01

In the present study, we evaluated the possibility that the abnormal bone matrix produced during spaceflight may be associated with reduced expression of bone matrix protein genes. To test this possibility, we investigated the effects of a 14-day spaceflight (SLS-2 experiment) on steady-state mRNA levels for glyceraldehyde-3-phosphate dehydrogenase (GAPDH), osteocalcin, osteonectin, and prepro-alpha(1) subunit of type I collagen in the major bone compartments of rat femur. There were pronounced site-specific differences in the steady-state levels of expression of the mRNAs for the three bone matrix proteins and GAPDH in normal weight-bearing rats, and these relationships were altered after spaceflight. Specifically, spaceflight resulted in decreases in mRNA levels for GAPDH (decreased in proximal metaphysis), osteocalcin (decreased in proximal metaphysis), osteonectin (decreased in proximal and distal metaphysis), and collagen (decreased in proximal and distal metaphysis) compared with ground controls. There were no changes in mRNA levels for matrix proteins or GAPDH in the shaft and distal epiphysis. These results demonstrate that spaceflight leads to site- and gene-specific decreases in mRNA levels for bone matrix proteins. These findings are consistent with the hypothesis that spaceflight-induced decreases in bone formation are caused by concomitant decreases in expression of genes for bone matrix proteins.

Rasburicase improves hyperuricemia in patients with acute kidney injury secondary to rhabdomyolysis caused by ecstasy intoxication and exertional heat stroke.

PubMed

Lin, Pei-Yi; Lin, Chun-Chen; Liu, Hsi-Che; Lee, Ming-Dar; Lee, Hung-Chang; Ho, Che-Sheng; Chiu, Nan-Chang; Peng, Chun-Chih; Huang, Fu-Yuan; Tsai, Jeng-Daw

2011-11-01

To report the successful use of rasburicase in two children with hyperuricemia secondary to severe rhabdomyolysis. : Case report. Pediatric intensive care unit in a freestanding quaternary hospital. Two pediatric patients with severe rhabdomyolysis and hyperuricemia caused by ecstasy intoxication and exertional heat stroke. Use of a single low dose (6 mg) of rasburicase, a urate oxidase enzyme. Rasburicase was administered on the first and second hospital days with a single low dose of 6 mg (0.086 mg/kg in patient A and 0.092 mg/kg in patient B). Within 24 hrs, the levels of serum uric acid in both patients decreased dramatically, and their creatinine levels decreased and urine output increased concurrently. Continuous improvements in the uric acid levels, creatinine levels, and urine output were noted during hospitalization. Rasburicase seems to be a safe and effective drug for improving hyperuricemia in patients with rhabdomyolysis and renal failure.

High-resolution emission spectra of pulsed terahertz quantum-cascade lasers

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

Ikonnikov, A. V., E-mail: antikon@ipm.sci-nnov.ru; Antonov, A. V.; Lastovkin, A. A.

The spectra of pulsed terahertz quantum-cascade lasers were measured with high spectral resolution. The characteristic line width at half maximum was 0.01 cm{sup -1}; it is controlled by laser temperature variations during the supply voltage pulse. It was shown that an increase in the laser temperature leads to a decrease in the emission frequency, which is caused by an increase in the effective refractive index of the active region. It was also found that a decrease in the supply voltage results in a decrease in the emission frequency, which is caused by a change in the energy of diagonal transitionsmore » between lasing levels.« less

Hearing Status in Pediatric Renal Transplant Recipients.

PubMed

Gulleroglu, Kaan; Baskin, Esra; Aydin, Erdinc; Ozluoglu, Levent; Moray, Gokhan; Haberal, Mehmet

2015-08-01

Renal transplant provides a long-term survival. Hearing impairment is a major factor in subjective health status. Status of hearing and the cause of hearing impairment in the pediatric renal transplant group have not been evaluated. Here, we studied to evaluate hearing status in pediatric renal transplant patients and to determine the factors that cause hearing impairment. Twenty-seven pediatric renal transplant recipients were investigated. All patients underwent audiologic assessment by means of pure-tone audiometry. The factors on hearing impairment were performed. Sensorineural hearing impairment was found in 17 patients. There was marked hearing impairment for the higher frequencies between 4000 and 8000 Hz. Sudden hearing loss developed in 2 patients, 1 of them had tinnitus. Decrease of speech understanding was found in 8 patients. The cyclosporine level was significantly high in patients with hearing impairment compared with group without hearing impairment. Cyclosporine levels also were found to be statistically significantly high when compared with the group with decrease of speech understanding and the group without decrease of speech understanding. Similar relations cannot be found between tacrolimus levels and hearing impairment and speech understanding. Sensorineural hearing impairment prevalence was high in pediatric renal transplant recipients when compared with the general population of children. Cyclosporine may be responsible for causing hearing impairment after renal transplant. We suggest that this effect is a dose-dependent toxicity.

Retinoic acid stimulates interstitial collagenase messenger ribonucleic acid in osteosarcoma cells

NASA Technical Reports Server (NTRS)

Connolly, T. J.; Clohisy, J. C.; Shilt, J. S.; Bergman, K. D.; Partridge, N. C.; Quinn, C. O.

1994-01-01

The rat osteoblastic osteosarcoma cell line UMR 106-01 secretes interstitial collagenase in response to retinoic acid (RA). The present study demonstrates by Northern blot analysis that RA causes an increase in collagenase messenger RNA (mRNA) at 6 h, which is maximal at 24 h (20.5 times basal) and declines toward basal level by 72 h. This stimulation is dose dependent, with a maximal response at 5 x 10(-7) M RA. Nuclear run-on assays show a greater than 20-fold increase in the rate of collagenase mRNA transcription between 12-24 h after RA treatment. Cycloheximide blocks RA stimulation of collagenase mRNA, demonstrating the need for de novo protein synthesis. RA not only causes an increase in collagenase secretion, but is known to decrease collagen synthesis in UMR 106-01 cells. In this study, the increase in collagenase mRNA is accompanied by a concomitant decrease in the level of alpha 1(I) procollagen mRNA, which is maximal at 24 h (70% decrease), with a return to near-control levels by 72 h. Nuclear run-on assays demonstrated that the decrease in alpha 1 (I) procollagen expression does not have a statistically significant transcriptional component. RA did not statistically decrease the stability of alpha 1 (I) procollagen mRNA (calculated t1/2 = 8.06 +/- 0.30 and 9.01 +/- 0.62 h in the presence and absence of RA, respectively). However, transcription and stability together probably contribute to the major decrease in stable alpha 1 (I) procollagen mRNA observed. Cycloheximide treatment inhibits basal level alpha 1 (I) procollagen mRNA accumulation, demonstrating the need for on-going protein synthesis to maintain basal expression of this gene.

Di-(2-ethylhexyl) phthalate and mono-(2-ethylhexyl) phthalate inhibit growth and reduce estradiol levels of antral follicles in vitro

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

Gupta, Rupesh K., E-mail: drrupesh@illinois.ed; Singh, Jeffery M., E-mail: jsingh20@illinois.ed; Leslie, Tracie C., E-mail: tleslie2@illinois.ed

2010-01-15

Any insult that affects survival of ovarian antral follicles can cause abnormal estradiol production and fertility problems. Phthalate esters (PEs) are plasticizers used in a wide range of consumer and industrial products. Exposure to these chemicals has been linked to reduced fertility in humans and animal models. Di-(2-ethylhexyl) phthalate (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP) decrease serum estradiol levels and aromatase (Arom) expression, prolong estrous cycles, and cause anovulation in animal and culture models. These observations suggest PEs directly target antral follicles. We therefore tested the hypothesis that DEHP (1-100 mug/ml) and MEHP (0.1-10 mug/ml) directly inhibit antral follicular growth andmore » estradiol production. Antral follicles from adult mice were cultured with DEHP or MEHP, and/or estradiol for 96 h. During culture, follicle size was measured every 24 h as a measurement of follicle growth. After culture, media were collected for measurement of estradiol levels and follicles were subjected to measurement of cylin-D-2 (Ccnd2), cyclin-dependant-kinase-4 (Cdk4), and Arom. We found that DEHP and MEHP inhibited growth of follicles and decreased estradiol production compared to controls at the highest doses. DEHP and MEHP also decreased mRNA expression of Ccnd2, Cdk4, and Arom at the highest dose. Addition of estradiol to the culture medium prevented the follicles from DEHP- and MEHP-induced inhibition of growth, reduction in estradiol levels, and decreased Ccnd2 and Cdk4 expression. Collectively, our results indicate that DEHP and MEHP may directly inhibit antral follicle growth via a mechanism that partially includes reduction in levels of estradiol production and decreased expression of cell cycle regulators.« less

General anesthetics cause mitochondrial dysfunction and reduction of intracellular ATP levels

PubMed Central

Kishikawa, Jun-ichi; Inoue, Yuki; Fujikawa, Makoto; Nishimura, Kenji; Nakanishi, Atsuko; Tanabe, Tsutomu; Imamura, Hiromi

2018-01-01

General anesthetics are indispensable for effective clinical care. Although, the mechanism of action of general anesthetics remains controversial, lipid bilayers and proteins have been discussed as their targets. In this study, we focused on the relationship between cellular ATP levels and general anesthetics. The ATP levels of nematodes and cultured mammalian cells were decreased by exposure to three general anesthetics: isoflurane, pentobarbital, and 1-phenoxy-2-propanol. Furthermore, these general anesthetics abolished mitochondrial membrane potential, resulting in the inhibition of mitochondrial ATP synthesis. These results suggest that the observed decrease of cellular ATP level is a common phenomenon of general anesthetics. PMID:29298324

Comprehensive electronic medical record implementation levels not associated with 30-day all-cause readmissions within Medicare beneficiaries with heart failure.

PubMed

Patterson, M E; Marken, P; Zhong, Y; Simon, S D; Ketcherside, W

2014-01-01

Regulatory standards for 30-day readmissions incentivize hospitals to improve quality of care. Implementing comprehensive electronic health record systems potentially decreases readmission rates by improving medication reconciliation at discharge, demonstrating the additional benefits of inpatient EHRs beyond improved safety and decreased errors. To compare 30-day all-cause readmission incidence rates within Medicare fee-for-service with heart failure discharged from hospitals with full implementation levels of comprehensive EHR systems versus those without. This retrospective cohort study uses data from the American Hospital Association Health IT survey and Medicare Part A claims to measure associations between hospital EHR implementation levels and beneficiary readmissions. Multivariable Cox regressions estimate the hazard ratio of 30-day all-cause readmissions within beneficiaries discharged from hospitals implementing comprehensive EHRs versus those without, controlling for beneficiary health status and hospital organizational factors. Propensity scores are used to account for selection bias. The proportion of heart failure patients with 30-day all-cause readmissions was 30%, 29%, and 32% for those discharged from hospitals with full, some, and no comprehensive EHR systems. Heart failure patients discharged from hospitals with fully implemented comprehensive EHRs compared to those with no comprehensive EHR systems had equivalent 30-day readmission incidence rates (HR = 0.97, 95% CI 0.73 - 1.3). Implementation of comprehensive electronic health record systems does not necessarily improve a hospital's ability to decrease 30-day readmission rates. Improving the efficiency of post-acute care will require more coordination of information systems between inpatient and ambulatory providers.

Involvement of SREBPs in 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced disruption of lipid metabolism in male guinea pig

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

Nishiumi, Shin; Yabushita, Yoshiyuki; Furuyashiki, Takashi

2008-06-15

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has multiple toxic effects causing a wasting syndrome characterized by a loss of body weight accompanied by a decrease in adipose tissue weight. To elucidate the mechanism behind this syndrome, we investigated the changes in lipid metabolism 7 and 21 days after a single intraperitoneal injection of TCDD at 1 {mu}g/kg body weight to male guinea pigs. TCDD caused the symptoms of the syndrome, body weight loss with a decrease in adipose tissue weight, while it increased the levels of triacylglycerols, total cholesterols, and free fatty acids in plasma. On day 7, TCDD decreased the levels of CCAAT/enhancermore » binding protein (C/EBP) {alpha}, peroxisome proliferator activated receptor {gamma}, and glucose transporter 4, adipogenesis-related factors, in adipose tissue, whereas the levels of retinoid X receptor {alpha}, C/EBP{beta}, C/EBP{delta}, and c-Myc remained unchanged. TCDD also reduced the levels of both p125 precursor and p68 active forms of sterol regulatory element binding protein (SREBP)-1 and -2, the lypogenesis-related factors, and downregulated their DNA binding activity in adipose tissue, while it raised the levels of their p68 active forms and increased their DNA binding activity in the liver. TCDD decreased mRNA and protein levels of acetyl-CoA carboxylase and HMG-CoA synthase in the liver and adipose tissue. Similar results were obtained on day 21. These results suggest that TCDD disrupts lipid metabolism through changes in the expression levels of the adipogenesis-related and lipogenesis-related proteins in the liver and adipose tissue, and SREBPs would be involved in the development of the wasting syndrome.« less

Chemotherapeutic Potential of G1 Cell Cycle Inhibitor Indole-3-Carbinol and Its More Potent N-Alkoxy Derivatives in Human Breast Cancer Xenografts in Mice

DTIC Science & Technology

2004-08-01

Results a. Indole-3-Carbinol treatment selectively downregulates ER- a levels in MCF 7 cells. It has been demonstrated that 13C treatment causes a marked...of ER a• is not a side effect of Gi1 cell cycle arrest in these cells, and that I3C can cause a decrease in ER a levels induced by tamoxifen. c. I3C... a levels and increases functional ER P3 levels as assessed by binding to a consensus ERE in vitro: As a step towards evaluating functional

Posttranslational stability of the heme biosynthetic enzyme ferrochelatase is dependent on iron availability and intact iron-sulfur cluster assembly machinery

PubMed Central

Crooks, Daniel R.; Ghosh, Manik C.; Haller, Ronald G.; Tong, Wing-Hang

2010-01-01

Mammalian ferrochelatase, the terminal enzyme in the heme biosynthetic pathway, possesses an iron-sulfur [2Fe-2S] cluster that does not participate in catalysis. We investigated ferrochelatase expression in iron-deficient erythropoietic tissues of mice lacking iron regulatory protein 2, in iron-deficient murine erythroleukemia cells, and in human patients with ISCU myopathy. Ferrochelatase activity and protein levels were dramatically decreased in Irp2−/− spleens, whereas ferrochelatase mRNA levels were increased, demonstrating posttranscriptional regulation of ferrochelatase in vivo. Translation of ferrochelatase mRNA was unchanged in iron-depleted murine erythroleukemia cells, and the stability of mature ferrochelatase protein was also unaffected. However, the stability of newly formed ferrochelatase protein was dramatically decreased during iron deficiency. Ferrochelatase was also severely depleted in muscle biopsies and cultured myoblasts from patients with ISCU myopathy, a disease caused by deficiency of a scaffold protein required for Fe-S cluster assembly. Together, these data suggest that decreased Fe-S cluster availability because of cellular iron depletion or impaired Fe-S cluster assembly causes reduced maturation and stabilization of apo-ferrochelatase, providing a direct link between Fe-S biogenesis and completion of heme biosynthesis. We propose that decreased heme biosynthesis resulting from impaired Fe-S cluster assembly can contribute to the pathogenesis of diseases caused by defective Fe-S cluster biogenesis. PMID:19965627

Iron Chelation Therapy with Deferasirox Results in Improvement of Liver Enzyme Level in Patients with Iron Overload-Associated Liver Dysfunction

PubMed Central

Miura, Yasuo; Matsui, Yusuke; Kaneko, Hitomi; Watanabe, Mitsumasa; Tsudo, Mitsuru

2010-01-01

Iron chelation therapy (ICT) has been applied for the patients with iron overload-associated liver dysfunction since it is one of the causes of death in patients with intractable hematological diseases requiring multiple red blood cell transfusions. Recently, deferasirox (DSX), a novel, once-daily oral iron chelator, was demonstrated to have similar efficacy to the conventional continuous infusion of deferoxamine on a decrease in serum ferritin (SF) level in heavily transfused patients. We show three cases of transfusion-mediated iron-overloaded patients with an elevated serum alanine aminotransaminase (ALT). All three patients who received the ICT with DSX showed a decrease in ALT level in association with a decrease in SF level. It is suggested that DSX therapy could be considered to expect the improvement of liver damage for iron-overloaded patients with an abnormal ALT level. PMID:20592762

Neuropharmacological and neurochemical properties of N-(2-cyanoethyl)-2-phenylethylamine, a prodrug of 2-phenylethylamine.

PubMed Central

Baker, G. B.; Coutts, R. T.; Rao, T. S.

1987-01-01

1 N-(2-cyanoethyl)-2-phenylethylamine (CEPEA) was examined as a possible prodrug of 2-phenylethylamine (PEA). 2 Pharmacokinetics of PEA and CEPEA were investigated in rat brain, blood and liver by gas chromatography with electron-capture detection (GC-ECD). Interactions of PEA and CEPEA with putative neurotransmitter amines were investigated by use of high performance liquid chromatography with electrochemical detection (h.p.l.c.-e.c.). 3 Administration of PEA caused transient increases in PEA concentrations which decreased rapidly in brain and blood and at a slower rate in liver. Administration of CEPEA caused sustained elevations of PEA concentrations and elimination of PEA was markedly decreased in these tissues relative to the situation after administration of PEA itself. 4 Administration of CEPEA caused more prolonged decreases in brain noradrenaline, dopamine and 5-hydroxytryptamine concentrations than those observed after PEA administration, although values increased to control levels eventually. PMID:2890391

Redox imbalance in rat tissues exposed with organophosphate pesticides and therapeutic potential of antioxidant vitamins.

PubMed

Ojha, Anupama; Srivastava, Nalini

2012-01-01

Organophosphate pesticides are among the most widely used synthetic chemicals for controlling domestic and agricultural pests. Present study was aimed to evaluate the potential of chlorpyrifos, parathion and malathion, to disturb glutathione homeostasis in rat tissues and to find out whether the pre-feeding of antioxidant vitamins has some ameliorating effect on the pesticide-induced alterations. The results showed that these pesticides, alone or in combination, caused decrease in the levels of GSH and the corresponding increase in the levels of GSSG, decreasing the GSH/GSSG ratio. The results also showed NADPH/NADP(+) and NADH/NAD(+) ratios were also decreased in the rat tissues on pesticide exposure. These pesticides, alone or in combination, caused increase in the activities of glutathione reductase and glucose-6-phosphate dehydrogenase in all the rat tissues studied. The findings show that these pesticides generate oxidative stress and prior feeding of mixture of antioxidant vitamins tend to reduce the toxicities of these pesticides. Copyright © 2011 Elsevier Inc. All rights reserved.

[The effect of N-stearoylethanolamine on liver phospholipid composition of rats with insulin resistance caused by alimentary obesity].

PubMed

Onopchenko, O V; Kosiakova, H V; Horid'ko, T M; Klimashevskyĭ, V M; Hula, N M

2014-01-01

We used alimentary obesity-induced insulin resistance (IR) model in rats to investigate the influence of N-stearoylethanolamine on the content of phospholipids and their fatty acid composition. Our results show that prolonged high-fat diet triggers considerable aberrations in the composition of main phospholipids in the liver and can be one of the causes of IR in rats. In particular, the increase of phosphatidylcholine, phosphatidylethanolamine and significant decrease of other phospholipids: lysophosphatidylcholine, lysophosphatidylethanolamine, sphingomyelin, phosphatidylinositol, phosphatidylserine and diphosphaglicerol were observed. The levels of monounsaturated (erucic, nervonic, oleic) and polyunsaturated (eicosatrienoic, docosatrienoic, arachidonic) fatty acids were increased; meanwhile the content of diunsaturated acids was decreased. The NSE administration (50 mg/kg of body weight) caused restoration of the phospholipids content in the liver of rats with diet-induced IR that highly correlated with the decrease in plasma insulin level and the improvement of insulin sensitivity. Moreover, the effect of NSE was accompanied by the normalization of fatty acids composition of phospholipids that could be related to modulating influence of NSE on the activity of the main fatty acid desaturases. It is known that the imbalance in phospholipid composition of the rat liver causes substantial metabolic alterations that are associated with the development of IR. Accordingly, the compensations of the imbalance by NSE can help to restore insulin sensitivity, inhibit the development of obesity, IR and type 2 diabetes.

Factor VII assay

MedlinePlus

Stable factor; Proconvertin; Autoprothrombin I ... be caused by an abnormally low level of factor VII. ... Decreased factor VII activity may be related to: Deficiency of factor VII Disorder in which the proteins that control ...

Factor V assay

MedlinePlus

Labile factor; Proaccelerin; Ac-globulin ... be caused by an abnormally low level of factor V. ... Decreased factor V activity may be related to: Deficiency of factor V Disorder in which the proteins that control ...

The impact of disulfide bond dynamics in wheat gluten protein on the development of fermented pastry crumb.

PubMed

Ooms, Nand; Jansens, Koen J A; Pareyt, Bram; Reyniers, Stijn; Brijs, Kristof; Delcour, Jan A

2018-03-01

Gluten proteins functionality during pastry production was examined by including redox agents in the ingredient bill. Addition of reducing and oxidizing agents respectively increased and decreased dough height during fermentation. The presence of large gas bubbles in the samples with oxidizing agents may have caused a 'stacking'-effect and a more effective dough lift. During baking, the level of extractable proteins decreased to comparable values for all samples, except when potassium iodate (KIO 3 ) was used in the recipe. As a result of its use, a lower level of gliadin was incorporated into the gluten polymer and dough layers tended to 'slide' apart during baking, thereby causing collapse. Most likely, KIO 3 caused glutenin oxidation within each individual dough layer to such extent during the dough stage that insufficient thiol groups were available for forming dough layer interconnections during baking, after margarine melting. Furthermore, addition of redox agents impacted the product's crumb structure. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Changes in glutamate release in the rat nucleus accumbens during food and pain reinforcement].

PubMed

Saul'skaia, N B; Mikhaĭlova, M O; Pudovkina, O L; Gorbachevskaia, A I

2000-01-01

In vivo microdialysis combined with HPLC-EC analysis was used to monitor extracellular glutamate in the n. accumbens of Sprague-Dawley rats during footshock and food delivery. The footshock presentation resulted in a delayed increase in extracellular glutamate level, whereas the food intake caused its decrease. The intra-accumbens infusion of glutamate reuptake blocker D,L-threo-beta-hydroxiaspartate (1 mM) completely prevented the food-induced decrease in glutamate level. The intra-accumbens infusion of sodium channel blocker tetrodotoxin (1 microM) led to an increase in glutamate extracellular level in the n. accumbens in response to food intake. The results suggest that the food-induced decrease in glutamate extracellular level in the n. accumbens occurs due to an enhancement of high-affinity glutamate uptake that is probably under the neuronal control during feeding.

Elevated fibroblast growth factor 23 levels as a cause of early post-renal transplantation hypophosphatemia.

PubMed

Han, S Y; Hwang, E A; Park, S B; Kim, H C; Kim, H T

2012-04-01

Hypophosphatemia is a common complication after renal transplantation. Hyperparathyroidism has long been thought to be the cause, but hypophosphatemia can persist after high parathyroid hormone (PTH) levels normalize. Furthermore, calcitriol levels remain inappropriately low after transplantation, suggesting that mechanisms other than PTH contribute. Fibroblast growth factor 23 (FGF-23) induces phosphaturia, inhibits calcitriol synthesis, and accumulates in chronic kidney disease. We performed prospective study to investigate if FGF-23 early after renal transplantation contributes to hypophosphatemia. We measured FGF-23 levels before and at 1, 2, 4, and 12 weeks after transplantation in 20 renal transplant recipients. Serum creatinine, calcium (Ca), phosphate (Pi), intact PTH (PTH), and 1,25-dihydroxy vitamin D (1,25(OH)(2)VitD) were measured at the same time. FGF-23 levels decreased by 97% at 4 weeks after renal transplantation (PRT) (7,471 ± 11,746 vs 225 ± 295 pg/mL; P < .05) but were still above normal. PTH and Pi levels also decreased significantly after renal transplantation, and Ca and 1,25(OH)(2)VitD slightly increased. PRT hypophosphatemia of <2.5 mg/dL developed in 15 (75%) and 12 (60%) patients at 4 weeks and 12 weeks respectively. Compared with nonhypophosphatemic patients, the levels of FGF-23 of hypophosphatemic patients were higher (303 ± 311 vs 10 ± 6.9 pg/mL; P = .02) at 4 weeks PRT. FGF-23 levels were inversely correlated with Pi (r(2) = 0.406; P = .011); PTH was not independently associated with Pi (r(2) = 0.132; P = .151). FGF-23 levels decrease dramatically after renal transplantation. During the early PRT period, Pi rapidly decreased, suggesting that FGF-23 is cleared by the kidney, but residual FGF-23 may contribute to the PRT hypophosphatemia. FGF-23, but not PTH levels, was independently associated with PRT hypophosphatemia. Copyright © 2012 Elsevier Inc. All rights reserved.

Daily total physical activity level and premature death in men and women: results from a large-scale population-based cohort study in Japan (JPHC study).

PubMed

Inoue, Manami; Iso, Hiroyasu; Yamamoto, Seiichiro; Kurahashi, Norie; Iwasaki, Motoki; Sasazuki, Shizuka; Tsugane, Shoichiro

2008-07-01

The impact of daily total physical activity level on premature deaths has not been fully clarified in non-Western, relatively lean populations. We prospectively examined the association between daily total physical activity level (METs/day) and subsequent risk of all-cause mortality and mortalities from cancer, heart disease, and cerebrovascular disease. A total of 83,034 general Japanese citizens ages 45-74 years who responded to the questionnaire in 1995-1999 were followed for any cause of death through December 2005. Mutlivariate-adjusted hazard ratios were calculated with a Cox proportional hazards model controlling for potential confounding factors. During follow-up, a total of 4564 deaths were recorded. Compared with subjects in the lowest quartile, increased daily total physical activity was associated with a significantly decreased risk of all-cause mortality in both sexes (hazard ratios for the second, third, and highest quartiles were: men, 0.79, 0.82, 0.73 and women, 0.75, 0.64, 0.61, respectively). The decreased risk was observed regardless of age, frequency of leisure-time sports or physical exercise, or obesity status, albeit with a degree of risk attenuation among those with a high body mass index. A significantly decreased risk was similarly observed for death from cancer and heart disease in both sexes, and from cerebrovascular disease in women. Greater daily total physical activity level, either from occupation, daily life, or leisure time, may be of benefit in preventing premature death.

Decreased Bone Mineral Density in Prader-Willi Syndrome: Comparison With Obese Subjects

PubMed Central

Butler, Merlin G.; Haber, Lawrence; Mernaugh, Ray; Carlson, Michael G.; Price, Ron; Feurer, Irene D.

2016-01-01

Bone density, anthropometric data, and markers of bone turnover were collected on 21 subjects diagnosed with Prader-Willi syndrome (PWS) and compared with 9 subjects with obesity of unknown cause. In addition, urinary N-telopeptide levels were obtained in all subjects. N-telopeptides are the peptide fragments of type I collagen, the major bone matrix material. During periods of active bone degradation or high bone turnover, high levels of N-telopeptides are excreted in the urine. However, no significant difference was detected in the urinary N-telopeptide levels when corrected for creatinine excretion (raw or transformed data) between our subjects with obesity or PWS and the observed effect size of the between-group difference was small. Although N-telopeptide levels were higher but not significantly different in the subjects with PWS compared with obese controls, the subjects with PWS had significantly decreased total bone and spine mineral density and total bone mineral content (all P < 0.001). No differences in N- telopeptide levels or bone mineral density were observed between subjects with PWS and chromosome 15q deletion or maternal disomy. Thus, decreased bone mineral density in subjects with PWS may relate to the lack of depositing bone mineral during growth when bones are becoming more dense (e.g., during adolescence), possibly because of decreased production of sex or growth hormones and/or long-standing hypotonia. It may not be caused by loss, or active degradation, of bone matrix measurable by the methods described in this study further supporting the possible need for hormone therapy during adolescence. PMID:11745993

Plant physiology and proteomics reveals the leaf response to drought in alfalfa (Medicago sativa L.)

PubMed Central

Aranjuelo, Iker; Molero, Gemma; Erice, Gorka; Avice, Jean Christophe; Nogués, Salvador

2011-01-01

Despite its relevance, protein regulation, metabolic adjustment, and the physiological status of plants under drought is not well understood in relation to the role of nitrogen fixation in nodules. In this study, nodulated alfalfa plants were exposed to drought conditions. The study determined the physiological, metabolic, and proteomic processes involved in photosynthetic inhibition in relation to the decrease in nitrogenase (Nase) activity. The deleterious effect of drought on alfalfa performance was targeted towards photosynthesis and Nase activity. At the leaf level, photosynthetic inhibition was mainly caused by the inhibition of Rubisco. The proteomic profile and physiological measurements revealed that the reduced carboxylation capacity of droughted plants was related to limitations in Rubisco protein content, activation state, and RuBP regeneration. Drought also decreased amino acid content such as asparagine, and glutamic acid, and Rubisco protein content indicating that N availability limitations were caused by Nase activity inhibition. In this context, drought induced the decrease in Rubisco binding protein content at the leaf level and proteases were up-regulated so as to degrade Rubisco protein. This degradation enabled the reallocation of the Rubisco-derived N to the synthesis of amino acids with osmoregulant capacity. Rubisco degradation under drought conditions was induced so as to remobilize Rubisco-derived N to compensate for the decrease in N associated with Nase inhibition. Metabolic analyses showed that droughted plants increased amino acid (proline, a major compound involved in osmotic regulation) and soluble sugar (D-pinitol) levels to contribute towards the decrease in osmotic potential (Ψs). At the nodule level, drought had an inhibitory effect on Nase activity. This decrease in Nase activity was not induced by substrate shortage, as reflected by an increase in total soluble sugars (TSS) in the nodules. Proline accumulation in the nodule could also be associated with an osmoregulatory response to drought and might function as a protective agent against ROS. In droughted nodules, the decrease in N2 fixation was caused by an increase in oxygen resistance that was induced in the nodule. This was a mechanism to avoid oxidative damage associated with reduced respiration activity and the consequent increase in oxygen content. This study highlighted that even though drought had a direct effect on leaves, the deleterious effects of drought on nodules also conditioned leaf responsiveness. PMID:20797998

Exposure of the blue mussel, Mytilus edulis, to gold nanoparticles and the pro-oxidant menadione.

PubMed

Tedesco, Sara; Doyle, Hugh; Blasco, Julian; Redmond, Gareth; Sheehan, David

2010-03-01

Relatively little is known about how gold nanoparticles (GNP) might interact in vivo with marine organisms. Mytilus edulis was exposed (24h) to approximately 15 nm GNP, menadione and both compounds simultaneously (GNP/menadione). GNP was detected by inductively coupled plasma-optical emission spectroscopy mainly in digestive gland of samples exposed to GNP though not GNP/menadione, perhaps due to impaired feeding. Thioredoxin reductase activity and malondialdehyde levels were determined in all tissues. Thioredoxin reductase inhibition was detected only in digestive gland exposed to menadione whilst malondialdehyde levels did not vary in response to treatment in all tissues. GNP caused a decrease in the reduced/oxidized glutathione ratio in digestive gland, but no difference was found in other tissues or for other treatments. One dimensional electrophoresis of proteins containing thiol groups was performed in all tissues and revealed a reduction in protein thiols for all treatments in digestive gland. Two dimensional electrophoresis of digestive gland extracts, from GNP and control groups, showed decreased levels of thiol proteins in response to GNP which we attribute to oxidation. Our results suggest that GNP causes a modest level of oxidative stress sufficient to oxidize thiols in glutathione and proteins but without causing lipid peroxidation or induction of thioredoxin reductase activity.

Reduction in mRNA and protein expression of a nicotinic acetylcholine receptor α8 subunit is associated with resistance to imidacloprid in the brown planthopper, Nilaparvata lugens.

PubMed

Zhang, Yixi; Wang, Xin; Yang, Baojun; Hu, Yuanyuan; Huang, Lixin; Bass, Chris; Liu, Zewen

2015-11-01

Target-site resistance is commonly caused by qualitative changes in insecticide target-receptors and few studies have implicated quantitative changes in insecticide targets in resistance. Here we show that resistance to imidacloprid in a selected strain of Nilaparvata lugens is associated with a reduction in expression levels of the nicotinic acetylcholine receptor (nAChR) subunit Nlα8. Synergism bioassays of the selected strain suggested resistance was conferred, in part, by a target-site mechanism. Sequencing of N. lugens nAChR subunit genes identified no mutations associated with resistance, however, a decrease in mRNA and protein levels of Nlα8 was observed during selection. RNA interference knockdown of Nlα8 decreased the sensitivity of N. lugens to imidacloprid, demonstrating that a decrease in Nlα8 expression is sufficient to confer resistance in vivo. Radioligand binding assays revealed that the affinity of the high-affinity imidacloprid-binding site of native nAChRs was reduced by selection, and reducing the amount of Nlα8 cRNA injected into Xenopus oocytes significantly decreased imidacloprid potency on recombinant receptors. Taken together, these results provide strong evidence that a decrease in Nlα8 levels confers resistance to imidacloprid in N. lugens, and thus provides a rare example of target-site resistance associated with a quantitative rather than qualitative change. In insects, target-site mutations often cause high resistance to insecticides, such as neonicotinoids acting on nicotinic acetylcholine receptors (nAChRs). Here we found that a quantitative change in target-protein level, decrease in mRNA and protein levels of Nlα8, contributed importantly to imidacloprid resistance in Nilaparvata lugens. This finding provides a new target-site mechanism of insecticide resistance. © 2015 International Society for Neurochemistry.

Effect of a single neonatal oxytocin treatment (hormonal imprinting) on the biogenic amine level of the adult rat brain: could oxytocin-induced labor cause pervasive developmental diseases?

PubMed

Hashemi, F; Tekes, Kornélia; Laufer, R; Szegi, P; Tóthfalusi, L; Csaba, G

2013-10-01

Perinatal single-hormone treatment causes hormonal imprinting with lifelong consequences in receptor-binding capacity, hormone production as well as in social and sexual behavior. In the present experiments, newborn rats were treated with a single dose of oxytocin, and the levels of biogenic amines and their metabolites were studied in 8 different brain regions and in the sera when the male and female animals were 4 months old. Both dopaminergic and serotonergic neurotransmission was found to be significantly influenced. The levels of 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindole acetic acid metabolites decreased in the hypothalamus and striatum. Dopamine, serotonin, norepinephrine, and 5-hydroxytryptophol levels were hardly altered, and there was no difference in the epinephrine levels. The results show that dopamine and serotonin metabolism of hypothalamus and striatum are deeply and lifelong influenced by a single neonatal oxytocin treatment Oxytocin imprinting resulted in decreased dopamine turnover in the hypothalamus and decreased serotonin turnover in the hypothalamus, medulla oblongata, and striatum of females. As the disturbance of brain dopamine and serotonin system has an important role in the development of pervasive developmental diseases (eg, autism) and neuropsychiatric disorders (eg, schizophrenia), the growing number of oxytocin-induced labor as a causal factor, cannot be omitted.

Therapeutic effect of magnesium sulphate on carbon monoxide toxicity-mediated brain lipid peroxidation.

PubMed

Yavuz, Y; Mollaoglu, H; Yürümez, Y; Ucok, K; Duran, L; Tünay, K; Akgün, L

2013-02-01

Carbon monoxide (CO) toxicity primarily results from cellular hypoxia caused by impedance of oxygen delivery. Studies show that CO may cause brain lipid peroxidation and leukocyte-mediated inflammatory changes in the brain. The aim of this study was to investigate whether magnesium sulphate could prevent or diminish brain lipid peroxidation caused by carbon monoxide toxicity in rats. Fourty rats were divided into five groups of 8 rats each. Group l was not received any agent during the experiment. Group 2 was inhaled CO gas followed by intraperitoneally normal saline 30 minutes (min) later. Group 3 was inhaled CO gas followed by 100 mg/kg magnesium sulphate intraperitoneally 30 min later. Group 2 and Group 3 rats was undergone laparotomy and craniotomy while still under anesthesia at 6 hour, and tissue sample was obtained from the cerebrum. Group 4 was inhaled CO gas followed by intraperitoneally normal saline 30 min later. Group 5 was inhaled CO gas followed by 100 mg/kg magnesium sulphate intraperitoneally 30 min later. Group 4 and Group 5 rats was undergone laparotomy and craniotomy while still under anesthesia at 24 hour, and tissue sample was obtained from the cerebrum. Nitric oxide levels were no significantly different between all groups. Malonyldialdehyde levels increased in intoxication group (group 2) and decreased in treatment group (group 3). Activities of superoxide dismutase decreased in intoxication group (group 2) and increased in treatment group (group 3). Activities of catalase increased in intoxication group (group 2) and decreased in treatment group (group 3). Activities of glutathione peroxidase (GSH-Px) decreased in intoxication group (group 4) and increased in treatment group (group 5). CO poisoning caused significant damage, detected within the first 6 hours. Due to antioxidant enzymes, especially GSH-Px activity reaching the top level within 24th hours, significant oxidative damage was not observed. The protective effect against oxidative damage of magnesium sulfate has been identified within the first 6 hours.

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

Shimizu, Masahito; Department of Medicine, Gifu University School of Medicine, Gifu 501-1194; Deguchi, Atsuko

The IGF/IGF-1R system, which includes the IGF, IGF-1R, and IGFBPs proteins, plays an important role in the development and growth of colorectal cancer. We previously reported that in the HT29 human colon cancer cell line EGCG, the major biologically active component of green tea, inhibits activation of the RTKs EGFR, HER2, and HER3, and that this is associated with inhibition of multiple downstream signaling pathways. Since IGF-1R is also a RTK, in this study we examined the effects of EGCG on the activity of IGF/IGF-1R system in human colon cancer cells. We found that the colon cancer cell lines Caco2,more » HT29, SW837, and SW480 express high levels of the IGF-1R receptor, and that both SW837 and SW480 cells display constitutive activation of this receptor. Treatment of SW837 cells with 20 {mu}g/ml of EGCG (the IC{sub 50} concentration for growth inhibition) caused within 6 h a decrease in the phosphorylated (i.e., activated) form of the IGF-1R protein. At 12 h, there was a decrease in the levels of both IGF-1 protein and mRNA and within 3-6 h there was an increase in the levels of both IGFBP-3 protein and mRNA. The increased expression of the latter protein was sustained for at least 48 h. When SW837 cells were treated with EGCG for a longer time, i.e., 96 h, a very low concentration (1.0 {mu}g/ml) of EGCG also caused inhibition of activation of IGF-1R, a decrease in the IGF-1 protein, and an increase in the IGFBP-3 protein. EGCG also caused a decrease in the levels of mRNAs that encode MMPs-7 and -9, proteins that proteolyze IGFBP-3. In addition, treatment with EGCG caused a transient increase in the expression of TGF-{beta}2, an inducer of IGFBP-3 expression. These findings expand the roles of EGCG as an inhibitor of critical RTKs involved in cell proliferation, providing further evidence that EGCG and related compounds may be useful in the chemoprevention or treatment of colorectal cancer.« less

Decreased miR-128 and increased miR-21 synergistically cause podocyte injury in sepsis.

PubMed

Wang, Shanshan; Wang, Jun; Zhang, Zengdi; Miao, Hongjun

2017-08-01

Glomerular podocytes are injured in sepsis. We studied, in a sepsis patient, whether microRNAs (miRNAs) play a role in the podocyte injury. Podocytes were cultured and treated with lipopolysaccharide (LPS). Filtration barrier function of podocyte was analyzed with albumin influx assay. Nephrin level was analyzed with reverse transcription polymerase chain reaction (RT-PCR) and western blot. MiRNAs were detected using miRNAs PCR Array and in situ hybridization. MiRNA target sites were evaluated with luciferase reporter assays. LPS impaired the filtration barrier function of podocytes. MiR-128 level was decreased and miR-21 level was increased in podocytes in vitro and in the sepsis patient. The decrease in miR-128 was sufficient to induce the loss of nephrin and the impairment of filtration barrier function, while the increase of miR-21 exacerbated the process. Snail and phosphatase and tensin homolog (PTEN) were identified as the targets of miR-128 and miR-21. Decreased miR-128 induced Snail expression, and the increased miR-21 stabilized Snail by regulating the PTEN/Akt/GSK3β pathway. Supplementation of miR-128 and inhibition of miR-21 suppressed Snail expression and prevented the podocyte injury induced by LPS. Our study suggests that decreased miR-128 and increased miR-21 synergistically cause podocyte injury and are the potential therapeutic targets in sepsis.

Mercury and autism: accelerating evidence?

PubMed

Mutter, Joachim; Naumann, Johannes; Schneider, Rainer; Walach, Harald; Haley, Boyd

2005-10-01

The causes of autism and neurodevelopmental disorders are unknown. Genetic and environmental risk factors seem to be involved. Because of an observed increase in autism in the last decades, which parallels cumulative mercury exposure, it was proposed that autism may be in part caused by mercury. We review the evidence for this proposal. Several epidemiological studies failed to find a correlation between mercury exposure through thimerosal, a preservative used in vaccines, and the risk of autism. Recently, it was found that autistic children had a higher mercury exposure during pregnancy due to maternal dental amalgam and thimerosal-containing immunoglobulin shots. It was hypothesized that children with autism have a decreased detoxification capacity due to genetic polymorphism. In vitro, mercury and thimerosal in levels found several days after vaccination inhibit methionine synthetase (MS) by 50%. Normal function of MS is crucial in biochemical steps necessary for brain development, attention and production of glutathione, an important antioxidative and detoxifying agent. Repetitive doses of thimerosal leads to neurobehavioral deteriorations in autoimmune susceptible mice, increased oxidative stress and decreased intracellular levels of glutathione in vitro. Subsequently, autistic children have significantly decreased level of reduced glutathione. Promising treatments of autism involve detoxification of mercury, and supplementation of deficient metabolites.

3,4-Methylenedioxymethamphetamine (MDMA) abuse may cause oxidative stress and potential free radical damage.

PubMed

Zhou, Jun F; Chen, Peng; Zhou, Ye H; Zhang, Liang; Chen, Huai H

2003-05-01

To investigate whether 3,4-methylenedioxymethamphetamine abuse (MDMA abuse) may cause oxidative stress and potential free radical damage in the bodies of MDMA abusers (MA), and to explore the mechanisms by which MDMA abuse may be causing oxidative stress. One hundred and twenty MA and 120 healthy volunteers (HV) were enrolled in a random control study design, in which the level of lipoperoxide (LPO) in erythrocytes, and the levels of Vitamin C (VC), Vitamin E (VE) and beta-carotene (beta-CAR) in plasma as well as the activities of superoxide dismutase (SOD) and catalase (CAT) in erythrocytes were determined by spectrophotometric methods. Compared with the average values of the above biochemical parameters in the HV group, the average value of LPO in erythrocytes in the MA group was significantly increased (P < 0.0001), while the average values of VC, VE and beta-CAR in plasma as well as those of SOD and CAT in erythrocytes in the MA group were significantly decreased (P < 0.0001). The analysis of bivariate correlations suggested that with the increase of the MDMA abuse dose and the MDMA abuse duration, the level of LPO in erythrocytes in the MA was increased (P < 0.0001), while the levels of VC, VE and beta-CAR in plasma as well as the activities of SOD and CAT in erythrocytes in the MA were decreased (P < 0.0001). The findings in this study suggest that MDMA abuse may cause oxidative stress and potential free radical damage to MA.

Downregulation of leptin receptor and kisspeptin/GPR54 in the murine hypothalamus contributes to male hypogonadism caused by high-fat diet-induced obesity.

PubMed

Zhai, Lingling; Zhao, Jian; Zhu, Yiming; Liu, Qiannan; Niu, Wenhua; Liu, Chengyin; Wang, Yi

2018-06-13

Obesity may lead to male hypogonadism, the underlying mechanism of which remains unclear. In the present study, we established a murine model of male hypogonadism caused by high-fat diet-induced obesity to verify the following hypotheses: 1) an increased leptin level may be related to decreased secretion of GnRH in obese males, and 2) repression of kisspeptin/GPR54 in the hypothalamus, which is associated with increased leptin levels, may account for the decreased secretion of GnRH and be involved in secondary hypogonadism (SH) in obese males. Male mice were fed high-fat diet for 19 weeks and divided by body weight gain into diet-induced obesity (DIO) and diet-induced obesity resistant (DIO-R) group. The effect of obesity on the reproductive organs in male mice was observed by measuring sperm count and spermatozoid motility, relative to testis and epididymis weight, testosterone levels, and pathologic changes. Leptin, testosterone, estrogen, and LH in serum were detected by ELISA method. Leptin receptor (Ob-R), Kiss1, GPR54, and GnRH mRNA were measured by real-time PCR in the hypothalamus. Expression of kisspeptin and Ob-R protein was determined by Western blotting. Expression of GnRH and GPR54 protein was determined by immunohistochemical analysis. We found that diet-induced obesity decreased spermatozoid motility, testis and epididymis relative coefficients, and plasma testosterone and luteinizing hormone levels. An increased number and volume of lipid droplets in Leydig cells were observed in the DIO group compared to the control group. Significantly, higher serum leptin levels were found in the DIO and DIO-R groups. The DIO and DIO-R groups showed significant downregulation of the GnRH, Kiss1, GPR54, and Ob-R genes. We also found decreased levels of GnRH, kisspeptin, GPR54, and Ob-R protein in the DIO and DIO-R groups. These lines of evidence suggest that downregulation of Ob-R and kisspeptin/GPR54 in the murine hypothalamus may contribute to male hypogonadism caused by high-fat diet-induced obesity.

A mutation in MT-TW causes a tRNA processing defect and reduced mitochondrial function in a family with Leigh syndrome.

PubMed

Duff, Rachael M; Shearwood, Anne-Marie J; Ermer, Judith; Rossetti, Giulia; Gooding, Rebecca; Richman, Tara R; Balasubramaniam, Shanti; Thorburn, David R; Rackham, Oliver; Lamont, Phillipa J; Filipovska, Aleksandra

2015-11-01

Leigh syndrome (LS) is a progressive mitochondrial neurodegenerative disorder, whose symptoms most commonly include psychomotor delay with regression, lactic acidosis and a failure to thrive. Here we describe three siblings with LS, but with additional manifestations including hypertrophic cardiomyopathy, hepatosplenomegaly, cholestatic hepatitis, and seizures. All three affected siblings were found to be homoplasmic for an m. 5559A>G mutation in the T stem of the mitochondrial DNA-encoded MT-TW by next generation sequencing. The m.5559A>G mutation causes a reduction in the steady state levels of tRNA(Trp) and this decrease likely affects the stability of other mitochondrial RNAs in the patient fibroblasts. We observe accumulation of an unprocessed transcript containing tRNA(Trp), decreased de novo protein synthesis and consequently lowered steady state levels of mitochondrial DNA-encoded proteins that compromise mitochondrial respiration. Our results show that the m.5559A>G mutation at homoplasmic levels causes LS in association with severe multi-organ disease (LS-plus) as a consequence of dysfunctional mitochondrial RNA metabolism. Copyright © 2015 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Cause-specific mortality by occupational skill level in Canada: a 16-year follow-up study.

PubMed

Tjepkema, M; Wilkins, R; Long, A

2013-09-01

Mortality data by occupation are not routinely available in Canada, so we analyzed census-linked data to examine cause-specific mortality rates across groups of occupations ranked by skill level. A 15% sample of 1991 Canadian Census respondents aged 25 years or older was previously linked to 16 years of mortality data (1991-2006). The current analysis is based on 2.3 million people aged 25 to 64 years at cohort inception, among whom there were 164 332 deaths during the follow-up period. Occupations coded according to the National Occupation Classification were grouped into five skill levels. Age-standardized mortality rates (ASMRs), rate ratios (RRs), rate differences (RDs) and excess mortality were calculated by occupational skill level for various causes of death. ASMRs were clearly graded by skill level: they were highest among those employed in unskilled jobs (and those without an occupation) and lowest for those in professional occupations. All-cause RRs for men were 1.16, 1.40, 1.63 and 1.83 with decreasing occupational skill level compared with professionals. For women the gradient was less steep: 1.23, 1.24, 1.32 and 1.53. This gradient was present for most causes of death. Rate ratios comparing lowest to highest skill levels were greater than 2 for HIV/AIDS, diabetes mellitus, suicide and cancer of the cervix as well as for causes of death associated with tobacco use and excessive alcohol consumption. Mortality gradients by occupational skill level were evident for most causes of death. These results provide detailed cause-specific baseline indicators not previously available for Canada.

Lipolysis, and not hepatic lipogenesis, is the primary modulator of triglyceride levels in streptozotocin-induced diabetic mice

PubMed Central

Willecke, Florian; Scerbo, Diego; Nagareddy, Prabhakara; Obunike, Joseph C; Barrett, Tessa J; Abdillahi, Mariane L.; Trent, Chad M.; Huggins, Lesley Ann; Fisher, Edward A; Drosatos, Konstantinos; Goldberg, Ira J.

2014-01-01

Objective Diabetic hypertriglyceridemia is thought to be primarily driven by increased hepatic de novo lipogenesis. However, experiments in animal models indicated that insulin deficiency should decrease hepatic de novo lipogenesis and reduce plasma triglyceride levels. Approach and Results To address the discrepancy between human data and genetically altered mouse models, we investigated whether insulin deficient diabetic mice had triglyceride changes that resemble those in diabetic humans. Streptozotocin (STZ)–induced insulin deficiency increased plasma triglyceride levels in mice. Contrary to the mouse models with impaired hepatic insulin receptor signalling, insulin deficiency did not reduce hepatic triglyceride secretion and de novo lipogenesis-related gene expression. Diabetic mice had a marked decrease in postprandial TG clearance, which was associated with decreased lipoprotein lipase (LpL) and PPARα mRNA levels in peripheral tissues and decreased LpL activity in skeletal muscle, heart and brown adipose tissue. Diabetic heterozygous LpL knockout mice had markedly elevated fasting plasma triglyceride levels and prolonged postprandial TG clearance. Conclusion Insulin deficiency causes hypertriglyceridemia by decreasing peripheral lipolysis and not by an increase in hepatic TG production and secretion. PMID:25395613

Clinical usefulness of a functional assay for the von Willebrand factor cleaving protease (ADAMTS 13) and its inhibitor in a patient with thrombotic thrombocytopenic purpura.

PubMed

Rick, M E; Austin, H; Leitman, S F; Krizek, D M; Aronson, D L

2004-02-01

Decreased von Willebrand factor cleaving protease activity (VWFCP, ADAMTS 13) leads to persistence of unusually large multimers of von Willebrand factor that bind to platelets, causing platelet aggregates, microangiopathic hemolysis, and thrombocytopenia in patients with thrombotic thrombocytopenic purpura (TTP). The clinical value of measuring ADAMTS 13 and its inhibitor is not fully defined; the case reported here illustrates the usefulness of the assay to help confirm the clinical diagnosis in a patient with other potential causes for thrombotic microangiopathy; the assay also helped in making treatment decisions. A patient with systemic lupus erythematosis (SLE) presented with fever and abdominal pain, thrombocytopenia, and anemia. Thrombotic microangiopathy was diagnosed by the appearance of schistocytes, decreasing platelet count, and evidence of hemolysis. ADAMTS 13 was decreased and an inhibitor was demonstrated in the patient's initial blood sample within 24 hr of admission. Plasma exchange was initiated, and serial assays showed increased ADAMTS 13 activity and decreased inhibitor after each plasma exchange; there was a rebound in inhibitor and a decrease in ADAMTS 13 activity prior to the next exchange that lessened over time. Increasing levels of protease activity correlated with clinical and laboratory improvement. Measurement of ADAMTS 13 activity and its inhibitor aided in the diagnosis of this complicated case of a patient with other potential causes for microangiopathic hemolysis. Subsequent levels correlated with the clinical course, and disappearance of the inhibitor indicated that long-term plasma exchange or other immunosuppressive treatment was not needed.

TiO2 nanoparticles cause mitochondrial dysfunction, activate inflammatory responses, and attenuate phagocytosis in macrophages: A proteomic and metabolomic insight.

PubMed

Chen, Qun; Wang, Ningning; Zhu, Mingjiang; Lu, Jianhong; Zhong, Huiqin; Xue, Xinli; Guo, Shuoyuan; Li, Min; Wei, Xinben; Tao, Yongzhen; Yin, Huiyong

2018-05-01

Titanium dioxide nanoparticles (TiO 2 NPs) are widely used in food and cosmetics but the health impact of human exposure remains poorly defined. Emerging evidence suggests that TiO 2 NPs may elicit immune responses by acting on macrophages. Our proteomic study showed that treatment of macrophages with TiO 2 NPs led to significant re-organization of cell membrane and activation of inflammation. These observations were further corroborated with transmission electron microscopy (TEM) experiments, which demonstrated that TiO 2 NPs were trapped inside of multi-vesicular bodies (MVB) through endocytotic pathways. TiO 2 NP caused significant mitochondrial dysfunction by increasing levels of mitochondrial reactive oxygen species (ROS), decreasing ATP generation, and decreasing metabolic flux in tricarboxylic acid (TCA) cycle from 13 C-labelled glutamine using GC-MS-based metabolic flux analysis. Further lipidomic analysis showed that TiO 2 NPs significantly decreased levels of cardiolipins, an important class of mitochondrial phospholipids for maintaining proper function of electron transport chains. Furthermore, TiO 2 NP exposure activates inflammatory responses by increasing mRNA levels of TNF-α, iNOS, and COX-2. Consistently, our targeted metabolomic analysis showed significantly increased production of COX-2 metabolites including PGD 2 , PGE 2 , and 15d-PGJ 2 . In addition, TiO 2 NP also caused significant attenuation of phagocytotic function of macrophages. In summary, our studies utilizing multiple powerful omic techniques suggest that human exposure of TiO 2 NPs may have profound impact on macrophage function through activating inflammatory responses and causing mitochondrial dysfunction without physical presence in mitochondria. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Ischemia causes muscle fatigue

NASA Technical Reports Server (NTRS)

Murthy, G.; Hargens, A. R.; Lehman, S.; Rempel, D. M.

2001-01-01

The purpose of this investigation was to determine whether ischemia, which reduces oxygenation in the extensor carpi radialis (ECR) muscle, causes a reduction in muscle force production. In eight subjects, muscle oxygenation (TO2) of the right ECR was measured noninvasively and continuously using near infrared spectroscopy (NIRS) while muscle twitch force was elicited by transcutaneous electrical stimulation (1 Hz, 0.1 ms). Baseline measurements of blood volume, muscle oxygenation and twitch force were recorded continuously, then a tourniquet on the upper arm was inflated to one of five different pressure levels: 20, 40, 60 mm Hg (randomized order) and diastolic (69 +/- 9.8 mm Hg) and systolic (106 +/- 12.8 mm Hg) blood pressures. Each pressure level was maintained for 3-5 min, and was followed by a recovery period sufficient to allow measurements to return to baseline. For each respective tourniquet pressure level, mean TO2 decreased from resting baseline (100% TO2) to 99 +/- 1.2% (SEM), 96 +/- 1.9%, 93 +/- 2.8%, 90 +/- 2.5%, and 86 +/- 2.7%, and mean twitch force decreased from resting baseline (100% force) to 99 +/- 0.7% (SEM), 96 +/- 2.7%, 93 +/- 3.1%, 88 +/- 3.2%, and 86 +/- 2.6%. Muscle oxygenation and twitch force at 60 mm Hg tourniquet compression and above were significantly lower (P < 0.05) than baseline value. Reduced twitch force was correlated in a dose-dependent manner with reduced muscle oxygenation (r = 0.78, P < 0.001). Although the correlation does not prove causation, the results indicate that ischemia leading to a 7% or greater reduction in muscle oxygenation causes decreased muscle force production in the forearm extensor muscle. Thus, ischemia associated with a modest decline in TO2 causes muscle fatigue.

Light interference as a possible stressor altering HSP70 and its gene expression levels in brain and hepatic tissues of golden spiny mice.

PubMed

Ashkenazi, Lilach; Haim, Abraham

2012-11-15

Light at night and light interference (LI) disrupt the natural light:dark cycle, causing alterations at physiological and molecular levels, partly by suppressing melatonin (MLT) secretion at night. Heat shock proteins (HSPs) can be activated in response to environmental changes. We assessed changes in gene expression and protein level of HSP70 in brain and hepatic tissues of golden spiny mice (Acomys russatus) acclimated to LI for two (SLI), seven (MLI) and 21 nights (LLI). The effect of MLT treatment on LI-mice was also assessed. HSP70 levels increased in brain and hepatic tissues after SLI, whereas after MLI and LLI, HSP70 decreased to control levels. Changes in HSP70 levels as a response to MLT occurred after SLI only in hepatic tissue. However, hsp70 expression following SLI increased in brain tissue, but not in hepatic tissue. MLT treatment and SLI caused a decrease in hsp70 levels in brain tissue and an increase in hsp70 in hepatic tissue. SLI acclimation elicited a stress response in A. russatus, as expressed by increased HSP70 levels and gene expression. Longer acclimation decreases protein and gene expression to their control levels. We conclude that for brain and hepatic tissues of A. russatus, LI is a short-term stressor. Our results also revealed that A. russatus can acclimate to LI, possibly because of its circadian system plasticity, which allows it to behave both as a nocturnal and as a diurnal rodent. To the best of our knowledge, this is the first study showing the effect of LI as a stressor at the cellular level, by activating HSP70.

The effect of cholesterol overload on mouse kidney and kidney-derived cells.

PubMed

Honzumi, Shoko; Takeuchi, Miho; Kurihara, Mizuki; Fujiyoshi, Masachika; Uchida, Masashi; Watanabe, Kenta; Suzuki, Takaaki; Ishii, Itsuko

2018-11-01

Dyslipidemia is one of the onset and risk factors of chronic kidney disease and renal function drop is seen in lipoprotein abnormal animal models. However, the detailed molecular mechanism of renal lipotoxicity has not been clarified. Therefore, the present study aimed to investigate the influence of cholesterol overload using mouse kidney tissue and kidney-derived cultured cells. C57BL/6 mice were fed normal diet (ND) or 1.25% cholesterol-containing high-cholesterol diet (HCD) for 11 weeks, and we used megalin as a proximal tubule marker for immunohistology. We added beta-very low density lipoprotein (βVLDL) to kidney-derived cells and examined the effect of cholesterol overload on megalin protein and mRNA expression level, cell proliferation and cholesterol content in cells. In the kidney of HCD mice, the gap between glomerulus and the surrounding Bowman's capsule decreased and the expression level of megalin decreased. After βVLDL treatment to the cells, the protein expression and mRNA expression level of megalin decreased and cell proliferation was restrained. We also observed an increase in cholesterol accumulation in the cell and free cholesterol/phospholipid ratios increased. These findings suggest that the increased cholesterol load on kidney contribute to the decrease of megalin and the overloaded cholesterol is taken into the renal tubule epithelial cells, causing suppression on cell proliferation, which may be the cause of kidney damage.

Daily intermittent decreases in serum levels of parathyroid hormone have an anabolic-like action on the bones of uremic rats with low-turnover bone and osteomalacia.

PubMed

Ishii, H; Wada, M; Furuya, Y; Nagano, N; Nemeth, E F; Fox, J

2000-02-01

The calcium receptor agonist (calcimimetic) compound NPS R-568 causes rapid decreases in circulating levels of parathyroid hormone (PTH) in rats and humans. We hypothesized that daily intermittent decreases in serum PTH levels may have different effects on bone than do chronically sustained decreases. To test this hypothesis, we compared two NPS R-568 dosing regimens in rats with chronic renal insufficiency induced by two intravenous injections of adriamycin. Fourteen weeks after the second adriamycin injection, creatinine clearance was reduced by 52%, PTH levels were elevated approximately 2.5-fold, and serum 25(OH)D3 and 1,25(OH)2D3 levels were reduced substantially. Treatment by daily per os gavage, which decreased PTH levels intermittently, or continuous subcutaneous infusion, which resulted in a sustained suppression of serum PTH levels, then began for 8 weeks. Despite the hyperparathyroidism, the adriamycin-injected rats developed a low-turnover bone lesion with osteomalacia (fourfold increase in osteoid volume in the proximal tibial metaphysis) and osteopenia (67% decrease in cancellous bone volume and an 18% reduction in bone mineral density at the distal femur). Daily administered (but not infused) NPS R-568 significantly increased cancellous bone volume solely by normalizing trabecular thickness, and increased femoral bone mineral density by 14%. These results indicate that daily intermittent, but not sustained, decreases in PTH levels have an "anabolic-like" effect on bones with a low-turnover lesion in this animal model of chronic renal insufficiency.

The evaluation of long-term effects of cinnamon bark and olive leaf on toxicity induced by streptozotocin administration to rats.

PubMed

Onderoglu, S; Sozer, S; Erbil, K M; Ortac, R; Lermioglu, F

1999-11-01

The effects of cinnamon bark and olive leaf have been investigated on streptozotocin-induced tissue injury, and some biochemical and haematological changes in rats. The effects on glycaemia were also evaluated. Long-term administration of olive leaf caused significant improvement in tissue injury induced by streptozotocin treatment; the effect of cinnamon bark was less extent. No effects on blood glucose levels were detected. However, significant decreases in some increased biochemical and haematological parameters of streptozotocin-treated rats were observed. Aspartate aminotransferase, urea and cholesterol levels were significantly decreased by treatment with both plant materials, and alanine aminotransferase by treatment with olive leaf. Cinnamon bark also caused a significant decrease in platelet counts. In addition, any visible toxicity, except decrease in body weight gain, attributable to the long-term use of plant materials was not established in normal rats. The data indicate that long-term use of olive leaf and cinnamon bark may provide benefit against diabetic conditions. Determination of underlying mechanism(s) of beneficial effects, toxicity to other systems and clinical assessments of related plant materials are major topics requiring further studies.

Decreased plasma ghrelin contributes to anorexia following novelty stress.

PubMed

Saegusa, Yayoi; Takeda, Hiroshi; Muto, Shuichi; Nakagawa, Koji; Ohnishi, Shunsuke; Sadakane, Chiharu; Nahata, Miwa; Hattori, Tomohisa; Asaka, Masahiro

2011-10-01

We hypothesized that anorexia induced by novelty stress caused by exposure to a novel environment may be due to activation of corticotropin-releasing factor (CRF) and subsequently mediated by decreasing peripheral ghrelin concentration via serotonin (5-HT) and melanocortin-4 receptors (MC4R). Each mouse was transferred from group-housed cages to individual cages to establish the novelty stress. We observed the effect of changes in feeding behavior in a novel environment using the method of transferring group-housed mice to individual cages. We investigated the effect of an intracerebroventricular injection of antagonists/agonists of CRF1/2 receptors (CRF1/2Rs), 5-HT(1B)/(2C) receptors (5-HT(1B)/(2C)R), and MC4R to clarify the role of each receptor on the decrease in food intake. Plasma ghrelin levels were also measured. The novelty stress caused a reduction in food intake that was abolished by administering a CRF1R antagonist. Three hours after the novelty stress, appetite reduction was associated with reduced levels of neuropeptide Y/agouti-related peptide mRNA, increased levels of proopiomelanocortin mRNA in the hypothalamus, and a decrease in plasma ghrelin level. Administering a CRF1R antagonist, a 5-HT(1B)/(2C)R antagonist, an MC4R antagonist, exogenous ghrelin, and an enhancer of ghrelin secretion, rikkunshito, resolved the reduction in food intake 3 h after the novelty stress by enhancing circulating ghrelin concentrations. We showed that anorexia during a novelty stress is a process in which CRF1R is activated at the early stage of appetite loss and is subsequently activated by a 5-HT(1B)/(2C)R and MC4R stimulus, leading to decreased peripheral ghrelin concentrations.

Dual behavior of N-acetylcysteine during ethanol-induced oxidative stress in embryonic chick brains.

PubMed

Bauer, Alison K; Fitzgerald, Mary; Ladzinski, Adam T; Lenhart Sherman, Sydney; Maddock, Benjamin H; Norr, Zoe M; Miller, Robert R

2017-10-01

Ethanol (EtOH) causes oxidative stress in embryos. Because N-acetylcysteine (NAC) failures and successes in ameliorating EtOH-induced oxidative stress have been reported, the objective was to determine if exogenous NAC ameliorated EtOH-induced oxidative stress within embryonic chick brains. Control eggs were injected with approximately 25 µl of water on day 0, 1, and 2 of development (E 0-2 ). Experimental eggs were injected with dosages of either 3.0 mmol EtOH/kg egg; 747 µmol NAC/kg egg; 3.0 mmol EtOH and 747 µmol NAC/kg egg; 1000 µmol NAC/kg egg; or 3.0 mmol EtOH and 1000 µmol NAC/kg during the first 3 days of development (E 0-2 ). At 11 days of development (E 11 ; late embryogenesis), brains were harvested and subsequently assayed for oxidative stress markers including the loss of long-chain membrane polyunsaturated fatty acids (PUFAs); the accumulation of lipid hydroperoxides (LPO); decreased glutathione (GSH) and glutathione/glutathione disulfide (GSSG) levels; and decreased glutathione peroxidase (GPx) activities. EtOH (3 mmol/kg egg), medium NAC (747 µmol/kg egg), and EtOH and medium NAC promoted oxidative stress. These treatments caused decreased brain membrane long-chain PUFAs; increased LPO levels; decreased GSH levels and GSH/GSSG levels; and decreased Se-dependent GPx activities. High NAC dosages (1000 µmol/kg egg) attenuated EtOH-induced oxidative stress within EtOH and high NAC-treated chick brains. Exogenous EtOH and/or medium NAC propagated oxidative stress. Meanwhile, high NAC ameliorated EtOH-induced oxidative stress.

The effects of vitamine C on lipid metabolism.

PubMed

Kotzé, J P

1975-09-20

Evidence is presented showing that vitamin C had definite effects on lipid metabolism. The stress of captivity on free-living baboons causes a decrease in serum vitamin C levels and an increase in serum cholesterol levels. Increased dietary intake of vitamin C during the initial stages of captivity significantly decreases the serum cholesterol values. Dietary vitamin C stimulates the synthesis of cholesterol from 14C-labelled acetate and mevalonate in baboon liver homogenates and increases the turnover rate of the cholesterol body pool. Vitamin C inhibits baboon cardiac lipoprotein lipase activity.

Interacting effects of ozone and CO2 on growth and physiological processes in northern forest trees

Treesearch

J. G. Isebrands; D. F. Karnosky

1996-01-01

Globally, surface-level concentrations of both CO2 and ozone (O3) are increasing annually. Because many studies have shown beneficial effects of increasing CO2, predictions have been made that elevated levels of CO2 would compensate for growth decreases caused by O3...

Cholinergic system modulates growth, apoptosis, and secretion of cholangiocytes from bile duct-ligated rats.

PubMed

LeSagE, G; Alvaro, D; Benedetti, A; Glaser, S; Marucci, L; Baiocchi, L; Eisel, W; Caligiuri, A; Phinizy, J L; Rodgers, R; Francis, H; Alpini, G

1999-07-01

To investigate the role of the cholinergic system in regulation of cholangiocyte functions, we evaluated the effects of vagotomy on cholangiocyte proliferation and secretion in rats that underwent bile duct ligation (BDL rats). After bile duct ligation (BDL), the vagus nerve was resected; 7 days later, expression of M3 acetylcholine receptor was evaluated. Cholangiocyte proliferation was assessed by morphometry and measurement of DNA synthesis. Apoptosis was evaluated by light microscopy and annexin-V staining. Ductal secretion was evaluated by measurement of secretin-induced choleresis, secretin receptor (SR) gene expression, and cyclic adenosine 3',5'-monophosphate (cAMP) levels. Vagotomy decreased the expression of M3 acetylcholine receptors in cholangiocytes. DNA synthesis and ductal mass were markedly decreased, whereas cholangiocyte apoptosis was increased by vagotomy. Vagotomy decreased ductal secretion. Forskolin treatment prevented the decrease in cAMP levels induced by vagotomy, maintained cholangiocyte proliferation, and decreased cholangiocyte apoptosis caused by vagotomy in BDL rats. Cholangiocyte secretion was also maintained by forskolin. Vagotomy impairs cholangiocyte proliferation and enhances apoptosis, leading to decreased ductal mass in response to BDL. Secretin-induced choleresis of BDL rats was virtually eliminated by vagotomy in association with decreased cholangiocyte cAMP levels. Maintenance of cAMP levels by forskolin administration prevents the effects of vagotomy on cholangiocyte proliferation, apoptosis, and secretion.

Rotor internal friction instability

NASA Technical Reports Server (NTRS)

Bently, D. E.; Muszynska, A.

1985-01-01

Two aspects of internal friction affecting stability of rotating machines are discussed. The first role of internal friction consists of decreasing the level of effective damping during rotor subsynchronous and backward precessional vibrations caused by some other instability mechanisms. The second role of internal frication consists of creating rotor instability, i.e., causing self-excited subsynchronous vibrations. Experimental test results document both of these aspects.

The Epidemic of Despair Among White Americans: Trends in the Leading Causes of Premature Death, 1999–2015

PubMed Central

Gennuso, Keith P.; Ugboaja, Donna C.; Remington, Patrick L.

2017-01-01

Objectives. To evaluate trends in premature death rates by cause of death, age, race, and urbanization level in the United States. Methods. We calculated cause-specific death rates using the Compressed Mortality File, National Center for Health Statistics data for adults aged 25 to 64 years in 2 time periods: 1999 to 2001 and 2013 to 2015. We defined 48 subpopulations by 10-year age groups, race/ethnicity, and county urbanization level (large urban, suburban, small or medium metropolitan, and rural). Results. The age-adjusted premature death rates for all adults declined by 8% between 1999 to 2001 and 2013 to 2015, with decreases in 39 of the 48 subpopulations. Most decreases in death rates were attributable to HIV, cardiovascular disease, and cancer. All 9 subpopulations with increased death rates were non-Hispanic Whites, largely outside large urban areas. Most increases in death rates were attributable to suicide, poisoning, and liver disease. Conclusions. The unfavorable recent trends in premature death rate among non-Hispanic Whites outside large urban areas were primarily caused by self-destructive health behaviors likely related to underlying social and economic factors in these communities. PMID:28817333

The Epidemic of Despair Among White Americans: Trends in the Leading Causes of Premature Death, 1999-2015.

PubMed

Stein, Elizabeth M; Gennuso, Keith P; Ugboaja, Donna C; Remington, Patrick L

2017-10-01

To evaluate trends in premature death rates by cause of death, age, race, and urbanization level in the United States. We calculated cause-specific death rates using the Compressed Mortality File, National Center for Health Statistics data for adults aged 25 to 64 years in 2 time periods: 1999 to 2001 and 2013 to 2015. We defined 48 subpopulations by 10-year age groups, race/ethnicity, and county urbanization level (large urban, suburban, small or medium metropolitan, and rural). The age-adjusted premature death rates for all adults declined by 8% between 1999 to 2001 and 2013 to 2015, with decreases in 39 of the 48 subpopulations. Most decreases in death rates were attributable to HIV, cardiovascular disease, and cancer. All 9 subpopulations with increased death rates were non-Hispanic Whites, largely outside large urban areas. Most increases in death rates were attributable to suicide, poisoning, and liver disease. The unfavorable recent trends in premature death rate among non-Hispanic Whites outside large urban areas were primarily caused by self-destructive health behaviors likely related to underlying social and economic factors in these communities.

Decreasing influenza impact in lodges: 1997-2000 Calgary Regional Health Authority.

PubMed

McLeod, L; Lau, W W

2001-01-01

Influenza causes high morbidity and hospitalization rates in residents of seniors lodges, I causing increased pressure on emergency departments and hospital beds every winter. This quasi-experimental study assessed the prevention of influenza outbreaks and their consequences in Calgary lodges. A multidisciplinary team worked to improve communication between health professionals, increase resident and staff immunization coverage, obtain weights and creatinines prior to influenza season, and facilitate amantadine prophylaxis during influenza A outbreaks. We had an increase in standing orders for amantadine and up to 56% of residents from one lodge had documented creatinine levels. Amantadine was administered to residents within two days of outbreak notification. Influenza morbidity in lodge outbreaks decreased from a rate of 37% to 9% over the three years and hospitalization rates decreased from 9% to 1%. We recommend that other regions consider a similar approach to decreasing influenza morbidity and hospitalization in lodge residents.

Metallothionein provides zinc-mediated protective effects against methamphetamine toxicity in SK-N-SH cells.

PubMed

Ajjimaporn, Amornpan; Swinscoe, John; Shavali, Shaik; Govitrapong, Piyarat; Ebadi, Manuchair

2005-11-30

Methamphetamine (METH) is a drug of abuse and neurotoxin that induces Parkinson's-like pathology after chronic usage by targeting dopaminergic neurons. Elucidation of the intracellular mechanisms that underlie METH-induced dopaminergic neuron toxicity may help in understanding the mechanism by which neurons die in Parkinson's disease. In the present study, we examined the role of reactive oxygen species (ROS) in the METH-induced death of human dopaminergic SK-N-SH cells and further assessed the neuroprotective effects of zinc and metallothionein (MT) against METH-induced toxicity in culture. METH significantly increased the production of reactive oxygen species, decreased intracellular ATP levels and reduced the cell viability. Pre-treatment with zinc markedly prevented the loss of cell viability caused by METH treatment. Zinc pre-treatment mainly increased the expression of metallothionein and prevented the generation of reactive oxygen species and ATP depletion caused by METH. Chelation of zinc by CaEDTA caused a significant decrease in MT expression and loss of protective effects of MT against METH toxicity. These results suggest that zinc-induced MT expression protects dopaminergic neurons via preventing the accumulation of toxic reactive oxygen species and halting the decrease in ATP levels. Furthermore, MT may prevent the loss of mitochondrial functions caused by neurotoxins. In conclusion, our study suggests that MT, a potent scavenger of free radicals is neuroprotective against dopaminergic toxicity in conditions such as drug of abuse and in Parkinson's disease.

Snoring and Nasal Congestion

MedlinePlus

... treat the various causes of nasal congestion include: Topical nasal steroid spray Topical nasal antihistamine spray Oral antibiotic (in case of ... include more than just the decrease in oxygen levels at night during the apnea episodes. They also ...

Lithium Decreases Glial Fibrillary Acidic Protein in a Mouse Model of Alexander Disease

PubMed Central

LaPash Daniels, Christine M.; Paffenroth, Elizabeth; Austin, Elizabeth V.; Glebov, Konstantin; Lewis, Diana; Walter, Jochen; Messing, Albee

2015-01-01

Alexander disease is a fatal neurodegenerative disease caused by mutations in the astrocyte intermediate filament glial fibrillary acidic protein (GFAP). The disease is characterized by elevated levels of GFAP and the formation of protein aggregates, known as Rosenthal fibers, within astrocytes. Lithium has previously been shown to decrease protein aggregates by increasing the autophagy pathway for protein degradation. In addition, lithium has also been reported to decrease activation of the transcription factor STAT3, which is a regulator of GFAP transcription and astrogliogenesis. Here we tested whether lithium treatment would decrease levels of GFAP in a mouse model of Alexander disease. Mice with the Gfap-R236H point mutation were fed lithium food pellets for 4 to 8 weeks. Four weeks of treatment with LiCl at 0.5% in food pellets decreased GFAP protein and transcripts in several brain regions, although with mild side effects and some mortality. Extending the duration of treatment to 8 weeks resulted in higher mortality, and again with a decrease in GFAP in the surviving animals. Indicators of autophagy, such as LC3, were not increased, suggesting that lithium may decrease levels of GFAP through other pathways. Lithium reduced the levels of phosphorylated STAT3, suggesting this as one pathway mediating the effects on GFAP. In conclusion, lithium has the potential to decrease GFAP levels in Alexander disease, but with a narrow therapeutic window separating efficacy and toxicity. PMID:26378915

Changes in the methylation status of DAT, SERT, and MeCP2 gene promoters in the blood cell in families exposed to alcohol during the periconceptional period.

PubMed

Lee, Bom-Yi; Park, So-Yeon; Ryu, Hyun-Mee; Shin, Chan-Young; Ko, Ki-Nam; Han, Jung-Yeol; Koren, Gideon; Cho, Youl-Hee

2015-02-01

Alcohol exposure has been shown to cause devastating effects on neurobehavioral development in numerous animal and human studies. The alteration of DNA methylation levels in gene-specific promoter regions has been investigated in some studies of human alcoholics. This study was aimed to investigate whether social alcohol consumption during periconceptional period is associated with epigenetic alteration and its generational transmission in the blood cells. We investigated patterns of alcohol intake in a prospective cohort of 355 pairs of pregnant women and their spouses who reported alcohol intake during the periconceptional period. A subpopulation of 164 families was established for the epigenetic study based on the availability of peripheral blood and cord blood DNA. The relative methylation changes of dopamine transporter (DAT), serotonin transporter (SERT), and methyl CpG binding protein 2 (MeCP2) gene promoters were analyzed using methylation-specific endonuclease digestion followed by quantitative real-time polymerase chain reaction. The relative methylation level of the DAT gene promoter was decreased in the group of mothers reporting above moderate drinking (p = 0.029) and binge drinking (p = 0.037) during pregnancy. The relative methylation level of the DAT promoter was decreased in the group of fathers reporting heavy binge drinking (p = 0.003). The relative methylation levels of the SERT gene promoter were decreased in the group of newborns of light drinking mothers before pregnancy (p = 0.012) and during pregnancy (p = 0.003). The methylation level in the MeCP2 promoter region of babies whose mothers reported above moderate drinking during pregnancy was increased (p = 0.02). In addition, methylation pattern in the DAT promoter region of babies whose fathers reported heavy binge drinking was decreased (p = 0.049). These findings suggest that periconceptional alcohol intake may cause epigenetic changes in specific locus of parental and newborn genomes as follows: Alcohol consumption decreases the methylation level of the DAT promoter region of the parent themselves, maternal alcohol drinking during the periconceptional period decreases the methylation level of the SERT promoter region of newborns, and maternal alcohol consumption increases the methylation level of the MeCP2 promoter region of newborns. Copyright © 2015 by the Research Society on Alcoholism.

Sunlight decreased genotoxicity of azadirachtin on root tip cells of Allium cepa and Eucrosia bicolor.

PubMed

Kwankua, W; Sengsai, S; Kuleung, C; Euawong, N

2010-07-01

Utilization of neem plant (Azadirachta indica A. Juss) extract for pest control in agriculture has raised concerns over contamination by the residues to the environment. Such residues, particularly azadirachtin (Aza), may cause deleterious effect to non-target organisms. This investigation was conducted to find out if Aza could be inactivated through exposures to sunlight. Activity of Aza was assessed as its ability to cause cytotoxic and genotoxic effects in the forms of nuclei abnormality and chromosome aberration as measured by mitotic index (MI) and mitotic aberration (MA). Varying concentrations of Aza were tested on Allium cepa and Eucrosia bicolor. It was found that the MI of all root tip meristematic cells of A. cepa and E. bicolor treated with 0.00005%, 0.00010%, 0.00015%, and 0.00020% (w/v) Aza-containing neem extract for 24h, were significantly lower than the controls. Complementary to the lower levels of MI, the Aza-treated groups showed higher MA levels in all cases investigated. Furthermore, the decreasing levels of MI and the increasing levels of MA related well with the increasing concentration of Aza. Microscopic examination of root tip meristematic cells revealed that the anomaly found most often were mitotic disturbances and chromosomal bridges. Exposures of 0.00020% (w/v) Aza to sunlight for 3 days and 7 days decreased Aza ability to induce cytotoxicity and genotoxicity, both in terms of MI and MA, to root tip meristematic cells in A. cepa and E. bicolor. Photodegradation of Aza upon exposure to direct sunlight was confirmed by HPLC. The study implicates that Aza would unlikely cause long term deleterious effects to the environment since it would be inactivated by sunlight. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Protective effect of Silybum marianum and Taraxacum officinale extracts against oxidative kidney injuries induced by carbon tetrachloride in rats.

PubMed

Karakuş, Ali; Değer, Yeter; Yıldırım, Serkan

2017-11-01

The protective effect of the extracts of the plants Silybum marianum and Taraxacum officinale by carbon tetrachloride (CCl 4 ) was researched. Sixty-six female Wistar albino rats were divided into six groups: Control, Silybum marianum, Taraxacum officinale, CCl 4 , Silybum marianum+ CCl 4 , Taraxacum officinale+CCl 4 . The Silybum marianum and Taraxacum officinale extracts were administered as 100 mg/kg/day by gavage. The CCl 4 was administered as 1.5 mL/kg (i.p.). At the end of the trial period, in the serums obtained from the animals, in the CCl 4 group it was found that the MDA level increased in the kidney tissue samples as well as in the ALP and GGT enzyme activities. It was also found that the GSH level and the GST enzyme activities decreased (p<.05). The microscopic evaluations showed that the CCl 4 caused a serious hydropic degeneration, coagulation necrosis, and mono-nuclear cell infiltration in the kidney cell. In the animals where CCl 4 and Silybum marianum and Taraxacum officinale extracts were applied together, it was found that the serum ALP and GGT enzyme activities decreased and that the MDA level decreased in the kidney tissue, and that the GSH level and GST enzyme activities increased. It was observed that the histopathological changes caused by the CCl 4 toxicity were corrected by applying the extracts. Eventually, it was determined that the Silybum marianum was more effective. Silybum marianum and Taraxacum officinale extracts which were used against histopathological changes in the kidney caused by toxication showed a corrective effect, which were supported by biochemical parameters.

Effects of ammonia-N stress on metabolic and immune function via the neuroendocrine system in Litopenaeus vannamei.

PubMed

Cui, Yanting; Ren, Xianyun; Li, Jian; Zhai, Qianqian; Feng, Yanyan; Xu, Yang; Ma, Li

2017-05-01

The purpose of this study was to evaluate the immunological responses, such as phenoloxidase (PO), antibacterial, and bacteriolytic activities, and metabolic variables, such as oxyhemocyanin, lactate, and glucose levels, of Litopenaeus vannamei exposed to ambient ammonia-N at 0, 2.5, 5, 7.5, and 10 mg/L for 0, 3, 6, 12, 24, and 48 h, and determine the effects of the eyestalk hormone on the metabolic and immune functions of unilateral eyestalk-ablated L. vannamei exposed to ambient ammonia-N at 10 mg/L. The actual concentrations of the control and test solutions were 0.04, 2.77, 6.01, 8.30, and 11.36 mg/L for ammonia-N and 0.01, 0.15, 0.32, 0.44, and 0.60 mg/L for NH 3 -N (unionized ammonia). The results showed a significant decrease in the PO, antibacterial, and bacteriolytic activities in the plasma as well as a significant increase in the glucose and lactate levels and decreased oxyhemocyanin levels in the hemolymph of L. vannamei exposed to elevated ammonia-N levels. These findings indicated that L. vannamei exposed to ammonia-N might demonstrate weakened metabolic and immunological responses. Moreover, eyestalk removal caused a dramatic decrease in PO, antibacterial, and bacteriolytic activities, which indicated that the eyestalk hormone in L. vannamei exhibited a higher immune response due to the induction of protective mechanisms against ammonia-N stress. Eyestalk removal also caused a dramatic decrease in glucose and lactate levels, suggesting that the eyestalk hormone is involved in glucose metabolism to meet the energy requirements under ammonia-N stress conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Brain glycogen decreases during prolonged exercise

PubMed Central

Matsui, Takashi; Soya, Shingo; Okamoto, Masahiro; Ichitani, Yukio; Kawanaka, Kentaro; Soya, Hideaki

2011-01-01

Abstract Brain glycogen could be a critical energy source for brain activity when the glucose supply from the blood is inadequate (hypoglycaemia). Although untested, it is hypothesized that during prolonged exhaustive exercise that induces hypoglycaemia and muscular glycogen depletion, the resultant hypoglycaemia may cause a decrease in brain glycogen. Here, we tested this hypothesis and also investigated the possible involvement of brain monoamines with the reduced levels of brain glycogen. For this purpose, we exercised male Wistar rats on a treadmill for different durations (30–120 min) at moderate intensity (20 m min−1) and measured their brain glycogen levels using high-power microwave irradiation (10 kW). At the end of 30 and 60 min of running, the brain glycogen levels remained unchanged from resting levels, but liver and muscle glycogen decreased. After 120 min of running, the glycogen levels decreased significantly by ∼37–60% in five discrete brain loci (the cerebellum 60%, cortex 48%, hippocampus 43%, brainstem 37% and hypothalamus 34%) compared to those of the sedentary control. The brain glycogen levels in all five regions after running were positively correlated with the respective blood and brain glucose levels. Further, in the cortex, the levels of methoxyhydroxyphenylglycol (MHPG) and 5-hydroxyindoleacetic acid (5-HIAA), potential involved in degradation of the brain glycogen, increased during prolonged exercise and negatively correlated with the glycogen levels. These results support the hypothesis that brain glycogen could decrease with prolonged exhaustive exercise. Increased monoamines together with hypoglycaemia should be associated with the development of decreased brain glycogen, suggesting a new clue towards the understanding of central fatigue during prolonged exercise. PMID:21521757

Toxic materials, fishing, and environmental variation: simulated effects on striped bass population trends

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

Goodyear, C.P.

1985-01-01

Decreased survival of larval striped bass Morone saxatilis resulting from toxic chemicals in the environment and decreased survival of adults caused by fishing both are suspected as agents contributing to the decline in the Chesapeake Bay stock since the mid-1970s. The relative power of each type of mortality to cause population declines was evaluated with simulation techniques. Equivalent levels of added mortality induced qualitatively identical and quantitatively similar trends in population simulations for all conditions examined except if strong density-dependent mortality preceded the contaminant toxicity. In this case the contaminant effect caused a greater reduction in yield, but the populationmore » did not tend toward extinction. The results indicate that the observed downward trend in the Chesapeake Bay population can be halted or reversed by a reduction in fishing mortality, even if contaminant toxicity is the proximate cause for the decline. 28 references, 1 figure, 1 table.« less

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

Saeed, Noha M.; El-Demerdash, Ebtehal; Abdel-Rahman, Hanaa M.

Methyl palmitate (MP) and ethyl palmitate (EP) are naturally occurring fatty acid esters reported as inflammatory cell inhibitors. In the current study, the potential anti-inflammatory activity of MP and EP was evaluated in different experimental rat models. Results showed that MP and EP caused reduction of carrageenan-induced rat paw edema in addition to diminishing prostaglandin E2 (PGE2) level in the inflammatory exudates. In lipopolysaccharide (LPS)-induced endotoxemia in rats, MP and EP reduced plasma levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). MP and EP decreased NF-κB expression in liver and lung tissues and ameliorated histopathological changes caused by LPS.more » Topical application of MP and EP reduced ear edema induced by croton oil in rats. In the same animal model, MP and EP reduced neutrophil infiltration, as indicated by decreased myeloperoxidase (MPO) activity. In conclusion, this study demonstrates the effectiveness of MP and EP in combating inflammation in several experimental models. -- Highlights: ► Efficacy of MP and EP in combating inflammation was displayed in several models. ► MP and EP reduced carrageenan-induced rat paw edema and prostaglandin E2 level. ► MP and EP decreased TNF-α and IL-6 levels in experimental endotoxemia. ► MP and EP reduced NF-κB expression and histological changes in rat liver and lung. ► MP and EP reduced croton oil-induced ear edema and neutrophil infiltration.« less

Cytochrome and Alternative Pathway Respiration in Tobacco (Effects of Salicylic Acid).

PubMed

Rhoads, D. M.; McIntosh, L.

1993-11-01

In suspension cultures of NT1 tobacco (Nicotiana tabacum L. cv Bright Yellow) cells the cytochrome pathway capacity increased between d 3 and d 4 following subculturing and reached the highest level observed on d 7. The capacity decreased significantly by d 10 and was at the same level on d 14. Both alternative pathway capacity and the amount of the 35-kD alternative oxidase protein increased significantly between d 5 and d 6, reached the highest point observed on d 7, remained constant until d 10, and decreased by d 14. The highest capacities of the alternative and cytochrome pathways and the highest amount of the 35-kD protein were attained on the day that cell cultures reached a stationary phase of growth. Addition of salicylic acid to cell cultures on d 4 caused a significant increase in alternative pathway capacity and a dramatic accumulation of the 35-kD protein by 12 h. The alternative pathway capacity and the protein level reached the highest level observed by 16 h after salicylic acid addition, and the cytochrome pathway capacity was at about the same level at each time point. The accumulation of the 35-kD alternative oxidase protein was significantly decreased by addition of actinomycin D 1 h before salicylic acid and was blocked by addition of cycloheximide. These results indicate that de novo transcription and translation were necessary for salicylic acid to cause the maximum accumulation of the 35-kD protein.

Cytochrome and Alternative Pathway Respiration in Tobacco (Effects of Salicylic Acid).

PubMed Central

Rhoads, D. M.; McIntosh, L.

1993-01-01

In suspension cultures of NT1 tobacco (Nicotiana tabacum L. cv Bright Yellow) cells the cytochrome pathway capacity increased between d 3 and d 4 following subculturing and reached the highest level observed on d 7. The capacity decreased significantly by d 10 and was at the same level on d 14. Both alternative pathway capacity and the amount of the 35-kD alternative oxidase protein increased significantly between d 5 and d 6, reached the highest point observed on d 7, remained constant until d 10, and decreased by d 14. The highest capacities of the alternative and cytochrome pathways and the highest amount of the 35-kD protein were attained on the day that cell cultures reached a stationary phase of growth. Addition of salicylic acid to cell cultures on d 4 caused a significant increase in alternative pathway capacity and a dramatic accumulation of the 35-kD protein by 12 h. The alternative pathway capacity and the protein level reached the highest level observed by 16 h after salicylic acid addition, and the cytochrome pathway capacity was at about the same level at each time point. The accumulation of the 35-kD alternative oxidase protein was significantly decreased by addition of actinomycin D 1 h before salicylic acid and was blocked by addition of cycloheximide. These results indicate that de novo transcription and translation were necessary for salicylic acid to cause the maximum accumulation of the 35-kD protein. PMID:12231986

Enhanced GSH synthesis by Bisphenol A exposure promoted DNA methylation process in the testes of adult rare minnow Gobiocypris rarus.

PubMed

Yuan, Cong; Zhang, Yingying; Liu, Yan; Zhang, Ting; Wang, Zaizhao

2016-09-01

DNA methylation is a commonly studied epigenetic modification. The mechanism of BPA on DNA methylation is poorly understood. The present study aims to explore whether GSH synthesis affects DNA methylation in the testes of adult male rare minnow Gobiocypris rarus in response to Bisphenol A (BPA). Male G. rarus was exposed to 1, 15 and 225μgL(-1) BPA for 7 days. The levels of global DNA methylation, hydrogen peroxide (H2O2) and glutathione (GSH) in the testes were analyzed. Meanwhile, the levels of enzymes involved in DNA methylation and de novo GSH synthesis, and the substrate contents for GSH production were measured. Furthermore, gene expression profiles of the corresponding genes of all studied enzymes were analyzed. Results indicated that BPA at 15 and 225μgL(-1) caused hypermethylation of global DNA in the testes. The 15μgL(-1) BPA resulted in significant decrease of ten-eleven translocation proteins (TETs) while 225μgL(-1) BPA caused significant increase of DNA methyltransferase proteins (DNMTs). Moreover, 225μgL(-1) BPA caused significant increase of H2O2 and GSH levels, and the de novo GSH synthesis was enhanced. These results indicated that the significant decrease of the level of TETs may be sufficient to cause the DNA hypermethylation by 15μgL(-1) BPA. However, the significantly increased of DNMTs contributed to the significant increase of DNA methylation levels by 225μgL(-1) BPA. Moreover, the elevated de novo GSH synthesis may promote the DNA methylation process. Copyright © 2016 Elsevier B.V. All rights reserved.

Oxytocin increases extrapancreatic glucagon secretion and glucose production in pancreatectomized dogs

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

Altszuler, N.; Puma, F.; Winkler, B.

1986-05-01

Infusion of oxytocin into normal dogs increases plasma levels of insulin and glucagon and glucose production and uptake. To determine whether infused oxytocin also increases glucagon secretion from extrapancreatic sites, pancreatectomized dogs, off insulin of 18 hr, were infused with oxytocin and plasma glucagon, and glucose production and uptake were measured using the (6-/sup 3/H)glucose primer-infusion technique. The diabetic dogs, in the control period, had elevated plasma glucose and glucagon levels, an increased rate of glucose production, and a relative decrease in glucose uptake (decreased clearance). Infusion of oxytocin (500 ..mu..U/kg/min) caused a rise in plasma glucagon and glucose levels,more » increased glucose production, and further decreased glucose clearance. it is concluded that oxytocin can stimulate secretion of extrapancreatic glucagon, which contributes to the increased glucose production.« less

Molecular mechanism of brain impairment caused by drinking-acquired fluorosis and selenium intervention.

PubMed

Zheng, Xiangren; Sun, Yan; Ke, Lulu; Ouyang, Wei; Zhang, Zigui

2016-04-01

This study investigated the molecular mechanism of brain impairment induced by drinking fluoridated water and selenium intervention. Results showed that the learning and memory of rats in NaF group significantly decreased. Moreover, the number of apoptotic cells, the expression levels of Cytc mRNA and protein, and the expression levels of Caspase-9 and Caspase-3 mRNA significantly increased; by contrast, Caspase-9 and Caspase-3 protein levels significantly decreased. Compared with the NaF group, the mRNA levels of Cytc and Caspase-9, as well as the protein levels of Cytc in NaF+Se group, significantly decreased. Conversely, the protein levels of Caspase-3 and Caspase-9, as well as the mRNA levels of Caspase-3, significantly increased. Thus, the mitochondrial CytC-Caspase-9-Caspase-3 apoptosis pathway in the hippocampus was one of the mechanisms leading to fluorosis-induced brain damage. Furthermore, the Cytc signaling molecules were possibly the key target molecules in fluorosis-induced apoptosis, and selenium could alleviate fluorosis-induced brain injury. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of the Waste Tire Resources Recovery Program and Environmental Health Policy in Taiwan

PubMed Central

Chen, Chia-Ching; Yamada, Tetsuji; Chiu, I-Ming; Liu, Yi-Kuen

2009-01-01

This paper examines the effectiveness of Taiwanese environmental health policies, whose aim is to improve environmental quality by reducing tire waste via the Tire Resource Recovery Program. The results confirm that implemented environmental health policies improve the overall health of the population (i.e. a decrease in death caused by bronchitis and other respiratory diseases). Current policy expenditures are far below the optimal level, as it is estimated that a ten percent increase in the subsidy would decrease the number of deaths caused by bronchitis and other respiratory diseases by 0.58% per county/city per year on average. PMID:19440434

HIV induces production of IL-18 from intestinal epithelial cells that increases intestinal permeability and microbial translocation

PubMed Central

Allam, Ossama; Samarani, Suzanne; Mehraj, Vikram; Jenabian, Mohammad-Ali; Tremblay, Cecile; Routy, Jean-Pierre; Amre, Devendra

2018-01-01

Interleukin-18 (IL-18) is a pleiotropic cytokine of the IL-1 family with multiple context dependent functions. We and others have shown that HIV infection is accompanied by increased circulating levels of IL-18 along with decreased levels of its antagonist, Interleukin-18 Binding Protein (IL-18BP). The infection is also accompanied by intestinal inflammation and decreased intestinal integrity as measured by intestinal permeability, regeneration and repair. However, little is known concerning the relation between high level of IL-18 associated with the viral infection and intestinal permeability. Here we demonstrate that HIV treatment increases production of IL-18 and decreases that of IL-18BP production in human intestinal epithelial cell (IEC) lines. IL-18 causes apoptosis of the IEC by activating caspase-1 and caspase-3. It induces epithelial barrier hyperpermeability by decreasing and disrupting both tight and adherens junction proteins, occludin, claudin 2 and beta-catenin. Disorganization of F-actin was also observed in the IEC that were exposed to the cytokine. Moreover IL-18 decreases transepithelial electrical resistance (TEER) in Caco-2 and increases permeability in HT29 monolayers. The cells’ treatment with IL-18 causes an increase in the expression of phosphorylated myosin II regulatory light-chain (p-MLC) and myosin light-chain kinase (MLCK), and a decrease in phosphorylated Signal Transducer and Activator of Transcription (p-STAT)-5. This increase in p-MLC is suppressed by a Rho-kinase (ROCK)-specific inhibitor. Interestingly, the levels of the cytokine correlate with those of LPS in the circulation in three different categories of HIV infected patients (HAART-naïve and HAART-treated HIV-infected individuals, and Elite controls) as well as in healthy controls. Collectively, these results suggest that the HIV-induced IL-18 plays a role in increased intestinal permeability and microbial translocation observed in HIV-infected individuals. PMID:29601578

Analysis of the influences of short-term levosimendan exposure on oxidant/antioxidant status and trace-element levels in the physiological status of the thoracic aorta of rats.

PubMed

Aydin, Cemalettin; Ay, Yasin; Basel, Halil; Kavak, Servet; Inan, Bekir; Bektaş, Hava; Gümrükçüoğlu, Hasan Ali; Ekim, Hasan; Demir, Halit

2012-12-01

The objective of this study was to evaluate the effect of levosimendan (chemical formula C₁₄H₁₂N₆O) exposure on oxidant/antioxidant status and trace-element levels in the thoracic aorta of rats. Eighteen male Wistar albino rats were randomly divided into two groups of eight animals each. Group 1 was not exposed to levosimendan and served as a control. Levosimendan (12 μg/kg) diluted in 10 ml 0.5 % dextrose was administered intraperitoneally to group 2. Animals of both groups were killed after 3 days, and their thoracic aortae were harvested for determination of changes in tissue oxidant/antioxidant status and trace-element levels. The animals in both groups were killed 72 h after levosimendan exposure, and thoracic aortae were harvested for determination of the lipid peroxidation product MDA and antioxidant GSH levels and the activities of antioxidant enzymes such as SOD, GSH-Px and CAT. It was found that MDA, GSH and CAT enzyme levels increased in thoracic aortae of rats after levosimendan administration. SOD and CA enzyme activities and the level of antioxidant GSH decreased in thoracic aortae of rats after levosimendan treatment. Pb, Cd and Fe levels of thoracic aortae were significantly higher (P < 0.001) and Mg, Mn, Zn and Cu were significantly lower (P < 0.001) in the levosimendan group compared to the control group. These results suggest that short-term levosimendan treatment caused an increase in free radical production and a decrease in antioxidant enzyme activity in thoracic aortae of levosimendan-treated rats. It also causes a decrease or increase in many mineral levels of the thoracic aorta, which is an undesirable condition for normal pharmacological function.

Cerebrospinal Fluid Progranulin, but Not Serum Progranulin, Is Reduced in GRN-Negative Frontotemporal Dementia.

PubMed

Wilke, Carlo; Gillardon, Frank; Deuschle, Christian; Hobert, Markus A; Jansen, Iris E; Metzger, Florian G; Heutink, Peter; Gasser, Thomas; Maetzler, Walter; Blauwendraat, Cornelis; Synofzik, Matthis

2017-01-01

Reduced progranulin levels are a hallmark of frontotemporal dementia (FTD) caused by loss-of-function (LoF) mutations in the progranulin gene (GRN). However, alterations of central nervous progranulin expression also occur in neurodegenerative disorders unrelated to GRN mutations, such as Alzheimer's disease. We hypothesised that central nervous progranulin levels are also reduced in GRN-negative FTD. Progranulin levels were determined in both cerebrospinal fluid (CSF) and serum in 75 subjects (37 FTD patients and 38 controls). All FTD patients were assessed by whole-exome sequencing for GRN mutations, yielding a target cohort of 34 patients without pathogenic mutations in GRN (GRN-negative cohort) and 3 GRN mutation carriers (2 LoF variants and 1 novel missense variant). Not only the GRN mutation carriers but also the GRN-negative patients showed decreased CSF levels of progranulin (serum levels in GRN-negative patients were normal). The decreased CSF progranulin levels were unrelated to patients' increased CSF levels of total tau, possibly indicating different destructive neuronal processes within FTD neurodegeneration. The patient with the novel GRN missense variant (c.1117C>T, p.P373S) showed substantially decreased CSF levels of progranulin, comparable to the 2 patients with GRN LoF mutations, suggesting a pathogenic effect of this missense variant. Our results indicate that central nervous progranulin reduction is not restricted to the relatively rare cases of FTD caused by GRN LoF mutations, but also contributes to the more common GRN-negative forms of FTD. Central nervous progranulin reduction might reflect a partially distinct pathogenic mechanism underlying FTD neurodegeneration and is not directly linked to tau alterations. © 2016 S. Karger AG, Basel.

Association of Trajectories of Higher-Level Functional Capacity with Mortality and Medical and Long-Term Care Costs Among Community-Dwelling Older Japanese.

PubMed

Taniguchi, Yu; Kitamura, Akihiko; Nofuji, Yu; Ishizaki, Tatsuro; Seino, Satoshi; Yokoyama, Yuri; Shinozaki, Tomohiro; Murayama, Hiroshi; Mitsutake, Seigo; Amano, Hidenori; Nishi, Mariko; Matsuyama, Yutaka; Fujiwara, Yoshinori; Shinkai, Shoji

2018-03-26

Higher-level functional capacity is crucial component for independent living in later life. We used repeated-measures analysis to identify aging trajectories in higher-level functional capacity. We then determined whether these trajectories were associated with all-cause mortality and examined differences in medical and long-term care costs between trajectories among community-dwelling older Japanese. 2,675 adults aged 65-90 years participated in annual geriatric health assessments and biennial health monitoring surveys during the period from October 2001 through August 2011. The average number of follow-up assessments was 4.0, and the total number of observations was 10,609. Higher-level functional capacity, which correspond to the fourth and fifth sublevels of Lawton's hierarchical model, was assessed with the Tokyo Metropolitan Institute of Gerontology-Index of Competence (TMIG-IC). We identified four distinct trajectory patterns (high-stable, late-onset decreasing, early-onset decreasing, and low-decreasing) on the TMIG-IC through age 65-90 years. As compared with the high-stable trajectory group, participants in the late-onset decreasing, early-onset decreasing, and low-decreasing TMIG-IC trajectory groups had adjusted hazard ratios for mortality of 1.22 (95% confidence interval: 1.01-1.47), 1.90 (1.53-2.36), and 2.87 (2.14-3.84), respectively. Participants with high-stable and late-onset decreasing higher-level functional capacity trajectories had lower mean monthly medical costs and long-term care costs. In contrast, mean total costs were higher for those with low-decreasing trajectories, after excluding the large increase in such costs at the end of life. People with a low-decreasing aging trajectory in higher-level functional capacity had higher risks of death and had high monthly total costs.

Effects of Acifluorfen on Endogenous Antioxidants and Protective Enzymes in Cucumber (Cucumis sativus L.) Cotyledons

PubMed Central

Kenyon, William H.; Duke, Stephen O.

1985-01-01

The herbicide acifluorfen (2-chloro-4-(trifluoromethyl)phenoxy-2-nitrobenzoate) causes strong photooxidative destruction of pigments and lipids in sensitive plant species. Antioxidants and oxygen radical scavengers slow the bleaching action of the herbicide. The effect of acifluorfen on glutathione and ascorbate levels in cucumber (Cucumis sativus L.) cotyledon discs was investigated to assess the relationship between herbicide activity and endogenous antioxidants. Acifluorfen decreased the levels of glutathione and ascorbate over 50% in discs exposed to less than 1.5 hours of white light (450 microeinsteins per square meter per second). Coincident increases in dehydroascorbate and glutathione disulfide were not observed. Acifluorfen also caused the rapid depletion of ascorbate in far-red light grown plants which were photosynthetically incompetent. Glutathione reductase, dehydroascorbate reductase, superoxide dismutase, ascorbate oxidase, ascorbate free radical reductase, peroxidase, and catalase activities rapidly decreased in acifluorfen-treated tissue exposed to white light. None of the enzymes were inhibited in vitro by the herbicide. Acifluorfen causes irreversible photooxidative destruction of plant tissue, in part, by depleting endogenous antioxidants and inhibiting the activities of protective enzymes. PMID:16664506

Autotransfusion from experimental hemothorax: levels of coagulation factors.

PubMed

Napoli, V M; Symbas, P J; Vroon, D H; Symbas, P N

1987-03-01

The coagulation system was investigated in five dogs undergoing autotransfusion from experimental hemothorax. One fourth of the blood volume was bled into the pleural space, drained, and autotransfused. The hemothorax blood showed: very prolonged PT and PTT; very low platelets and fibrinogen; midly elevated FDP; very low coagulation factors VIII, and V; reduced XII, prothrombin, X, XI, and VII. Partial clotting, mild fibrinolysis, and fibrin deposition over the pulmonary pleura seemed to cause incoagulability of hemothorax blood. Post autotransfusion arterial blood showed: normal PT and PTT; 25% decrease in platelets, and 31% decrease in fibrinogen from baseline values. There was also an overall 20% reduction of fibrinogen from baseline values. There was also an overall 20% reduction of all clotting factors, but their levels remained above 50% activity. It was concluded that autotransfusion from a hemothorax of 25% the blood volume in dogs causes a mild loss of hemostatic components, but does not significantly compromise the clotting mechanism.

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

Strayer, R.F.; Edwards, N.T.; Walton, B.T.

Contaminated soil samples collected from the site of a coal liquefaction product spill were used to study potential fates and effects of this synthetic fuel. Simulated weathering in the laboratory caused significant changes in residual oil composition. Soil column leachates contained high phenol levels that decreased exponentially over time. Toxicity tests demonstrated that the oil-contaminated soil was phytotoxic and caused embryotoxic and teratogenic effects on eggs of the cricket Acheta domesticus.

Decreased interferon-α production in response to CpG DNA dysregulates cytokine responses in patients with multiple sclerosis.

PubMed

Hirotani, Makoto; Niino, Masaaki; Fukazawa, Toshiyuki; Yaguchi, Hiroaki; Nakamura, Masakazu; Kikuchi, Seiji; Sasaki, Hidenao

2012-05-01

Type I interferons (IFNs), represented by IFN-α and β, activate immune effector cells belonging to the innate and adaptive immune systems. Plasmacytoid dendritic cells (pDCs) produce IFN-α in response to CpG DNA. We aimed to examine the impact of pDC-produced IFN-α on the adaptive immune system in Multiple Sclerosis (MS). Our results demonstrated that CpG DNA-induced IFN-α production was significantly decreased in PBMCs from MS patients. Decreased levels of IL-12 p70, IFN-γ, and IL-17 and increased level of IL-10 were found in CpG DNA-treated PBMCs of healthy subjects unlike in those from MS patients. In samples pre-treated with IFN-α and IFN-β, decreased levels of IL-12 p70, IFN-γ, and IL-17 and increased level of IL-10 were detected in PBMCs from MS patients. These results suggest that CpG DNA-induced decreased IFN-α production causes pro-inflammatory cytokine secretion, and either IFN-α or IFN-β induces anti-inflammatory cytokine secretion in the adaptive immune system in MS. Copyright © 2012 Elsevier Inc. All rights reserved.

A case of hyperammonemia with obstructive urinary tract infection by urease-producing bacteria.

PubMed

Goda, Toshiaki; Watanabe, Kotaro; Kobayashi, Junya; Nagai, Yasuharu; Ohara, Nobuyuki; Takahashi, Daisuke

2017-03-28

A 79-year-old woman was admitted emergently for disturbance of consciousness. Her consciousness level was Japan coma scale 20, and she presented with hypermyotonia. Brain magnetic resonance imaging and cerebrospinal fluid examination showed normal findings. Her blood tests showed an increased ammonia level of 291 μg/dl with normal liver function. We catheterized the bladder for urinary retention. Eight hours after admission, the blood level of ammonia decreased to 57 μg/dl and the patient's consciousness level improved. Corynebacterium pseudodiphtheriticum, which is a bacteria producing urease, was detected from a urine culture. It is important to recognize that obstructive urinary tract infection caused by urease-producing bacteria can cause hyperammonemia.

INTERNALIZATION AND DEGRADATION OF THE GLUTAMATE TRANSPORTER GLT-1 IN RESPONSE TO PHORBOL ESTER

PubMed Central

Susarla, Bala T.S.; Robinson, Michael B.

2008-01-01

Activation of protein kinase C (PKC) decreases the activity and cell surface expression of the predominant forebrain glutamate transporter, GLT-1. In the present study, C6 glioma were used as a model system to define the mechanisms that contribute to this decrease in cell surface expression and to determine the fate of internalized transporter. As was previously observed, phorbol 12-myristate 13-acetate (PMA) caused a decrease in biotinylated GLT-1. This effect was blocked by sucrose or by co-expression with a dominant-negative variant of dynamin 1, and it was attenuated by co-expression with a dominant-negative variant of the clathrin heavy chain. Depletion of cholesterol with methyl-β-cyclodextrin, co-expression with a dominant-negative caveolin-1 mutant (Cav1/S80E), co-expression with dominant-negative variants of Eps15 (epidermal-growth-factor receptor pathway substrate clone 15), or co-expression with dominant-negative Arf6 (T27N) had no effect on the PMA-induced loss of biotinylated GLT-1. Long-term treatment with PMA caused a time-dependent loss of biotinylated GLT-1 and decreased the levels of GLT-1 protein. Inhibitors of lysosomal degradation (chloroquine or ammonium chloride) or co-expression with a dominant-negative variant of a small GTPase implicated in trafficking to lysosomes (Rab7) prevented the PMA-induced decrease in protein and caused an intracellular accumulation of GLT-1. These results suggest that the PKC-induced redistribution of GLT-1 is dependent upon clathrin-mediated endocytosis. These studies identify a novel mechanism by which the levels of GLT-1 could be rapidly down-regulated via lysosomal degradation. The possibility that this mechanism may contribute to the loss of GLT-1 observed after acute insults to the CNS is discussed. PMID:17919781

Biomarkers and echocardiography for evaluating the improvement of the ventricular diastolic function after surgical relief of hydronephrosis

PubMed Central

Yeh, Huei-Ming; Lin, Ting-Tse; Yeh, Chih-Fan; Huang, Ho-Shiang; Chang, Sheng-Nan; Lin, Jou-Wei; Tsai, Chia-Ti; Lai, Ling-Ping; Huang, Yi-You

2017-01-01

The pathophysiology of cardio-renal syndrome (CRS) is complex. Hydronephrosis caused by urolithiasis may cause cytokine release and lead to cardiac dysfunction. The aim of this study was to evaluate cardiac function changes observed in patients who received double J placement using feasible biomarkers and echocardiography. This was a prospective, single-center study. Eighty-seven patients who presented with acute unilateral hydronephrosis and received ureteroscope stone manipulation were enrolled. Echocardiography and cytokines were measured on the day of the operation and 24 hours after the procedure. Changes before and after surgery were assessed by the paired t-test and Wilcoxon test. Correlation analyses between echocardiographic diastolic indices and cytokine levels were performed using Pearson’s correlation coefficients. Patients with hydronephrosis showed a higher left atrium volume index (LAVI), decreased E', and increased E/ E' ratio, which indicated diastolic dysfunction. Patients with hydronephrosis also exhibited decreased global strain rates during isovolumetric relaxation (SRIVR) and E/ SRIVR, which confirmed the diastolic dysfunction. Significant reductions in LAVI, increases in SRIVR and decreases in E/ SRIVR were observed after the operation. Biomarkers, such as TGF-β and serum NT-proBNP, were significantly decreased after surgery. In addition, a significant correlation was observed between the post-surgical decrease in TGF-β1 and increase in SRIVR. Unilateral hydronephrosis causes cardiac diastolic dysfunction, and relieving hydronephrosis could improve diastolic function. Improvements in cardiac dysfunction can be evaluated by echocardiography and measuring cytokine levels. The results of this study will inform efforts to improve the early diagnosis of CRS and prevent further deterioration of cardiac function when treating patients with hydronephrosis. PMID:29161313

Biomarkers and echocardiography for evaluating the improvement of the ventricular diastolic function after surgical relief of hydronephrosis.

PubMed

Yeh, Huei-Ming; Lin, Ting-Tse; Yeh, Chih-Fan; Huang, Ho-Shiang; Chang, Sheng-Nan; Lin, Jou-Wei; Tsai, Chia-Ti; Lai, Ling-Ping; Huang, Yi-You; Chu, Chun-Lin

2017-01-01

The pathophysiology of cardio-renal syndrome (CRS) is complex. Hydronephrosis caused by urolithiasis may cause cytokine release and lead to cardiac dysfunction. The aim of this study was to evaluate cardiac function changes observed in patients who received double J placement using feasible biomarkers and echocardiography. This was a prospective, single-center study. Eighty-seven patients who presented with acute unilateral hydronephrosis and received ureteroscope stone manipulation were enrolled. Echocardiography and cytokines were measured on the day of the operation and 24 hours after the procedure. Changes before and after surgery were assessed by the paired t-test and Wilcoxon test. Correlation analyses between echocardiographic diastolic indices and cytokine levels were performed using Pearson's correlation coefficients. Patients with hydronephrosis showed a higher left atrium volume index (LAVI), decreased E', and increased E/ E' ratio, which indicated diastolic dysfunction. Patients with hydronephrosis also exhibited decreased global strain rates during isovolumetric relaxation (SRIVR) and E/ SRIVR, which confirmed the diastolic dysfunction. Significant reductions in LAVI, increases in SRIVR and decreases in E/ SRIVR were observed after the operation. Biomarkers, such as TGF-β and serum NT-proBNP, were significantly decreased after surgery. In addition, a significant correlation was observed between the post-surgical decrease in TGF-β1 and increase in SRIVR. Unilateral hydronephrosis causes cardiac diastolic dysfunction, and relieving hydronephrosis could improve diastolic function. Improvements in cardiac dysfunction can be evaluated by echocardiography and measuring cytokine levels. The results of this study will inform efforts to improve the early diagnosis of CRS and prevent further deterioration of cardiac function when treating patients with hydronephrosis.

Effect of Letrozole, a selective aromatase inhibitor, on testicular activities in adult mice: Both in vivo and in vitro study.

PubMed

Verma, Rachna; Krishna, Amitabh

2017-01-15

The aim of present study was to evaluate the significance of estradiol (E2) in testicular activities and to find out the mechanism by which E2 regulates spermatogenesis in mice. To achieve this, both in vivo and in vitro effect of Letrozole on testis of adult mice was investigated. Letrozole-induced changes in testicular histology, cell proliferation (proliferating cell nuclear antigen; PCNA), cell survival (B cell lymphoma factor-2; Bcl2), apoptotic (cysteine-aspartic proteases; caspase-3), steroidogenic (side chain cleavage; SCC, 3β-hydroxy steroid dehydrogenase enzyme; 3β HSD, steroidogenic acute regulatory protein; StAR, aromatase and luteinizing hormone receptor; LH-R) markers, glucose level, and rate of expression of glucose transporter (GLUT) 8 and insulin receptor (IR) proteins in the testis along with changes in serum E2 and testosterone (T) levels were evaluated. Letrozole acts on testis and caused significant decrease in E2 synthesis, but increase in testosterone level and showed regressive changes in the spermatogenesis. Letrozole-induced changes in various testicular markers were compared with the changes in serum E2 level. The correlation study showed that decreased circulating E2 level may be responsible for decreased insulin receptor (IR) level in the testis. The decreased effects of insulin inhibited the glucose transport in the testis by suppressing GLUT8. The decreased level of testicular glucose may produce less lactate as energy support to developing germ cells consequently resulting in decreased cell proliferation and cell survival, but increased apoptosis. Thus, Letrozole suppresses spermatogenesis by reducing insulin sensitivity and glucose transport in the testis, but significantly increased testosterone level by promoting gonadotrophin release by decreased E2. Copyright © 2016 Elsevier Inc. All rights reserved.

False CAM alarms from radon fluctuations.

PubMed

Hayes, Robert

2003-11-01

The root cause of many false continuous air monitor (CAM) alarms is revealed for CAMs that use constant spectral shape assumptions in transuranic (TRU) alpha activity determination algorithms. This paper shows that when atmospheric radon levels continually decrease and bottom out at a minimum level, reduced false TRU count rates are not only expected but measured. Similarly, when the radon levels continually increase to a maximum level, elevated false TRU count rates were measured as predicted. The basis for expecting this dependence on changes in radon levels is discussed.

Therapeutic effects of date palm (Phoenix dactylifera L.) pollen extract on cadmium-induced testicular toxicity.

PubMed

El-Neweshy, M S; El-Maddawy, Z K; El-Sayed, Y S

2013-12-01

Cadmium (Cd) is a well-known testicular toxicant. This study was designed to explore the long-term effects of a single low dose of Cd on spermatogenesis, and testicular dysfunction and oxidative stress, and the therapeutic potential of date palm pollen extract (DPP) in averting such reproductive damage. Adult male Wistar rats received a single intraperitoneal injection of CdCl2 (0 or 1 mg kg(-1) ). Twenty-four hours later, they started receiving DPP (0 or 40 mg kg(-1) ) orally, once daily for 56 consecutive days. Cd exposure caused significant reproductive damage via reduced weight of the reproductive organs, which includes spermatological damage (decreased sperm count and motility and increased rates of sperm abnormalities), increased oxidative stress (increased malondialdehyde and decreased reduced glutathione levels), histological alterations (necrosis, inefficient to completely arrest spermatogenesis and a reduced Johnsen's score) and decreased serum testosterone level. DPP restored spermatogenesis and attenuated the toxic effects of Cd on the reproductive system to the levels observed in the control animals. These findings support the hypothesis that the testis is particularly sensitive to Cd, which can cause testicular damage and infertility. Treatment with DPP can ameliorate the deleterious effects of Cd, probably by activating testicular endocrine and antioxidant systems. © 2012 Blackwell Verlag GmbH.

Orange juice as dietary source of antioxidants for patients with hepatitis C under antiviral therapy.

PubMed

Gonçalves, Danielle; Lima, Claudia; Ferreira, Paula; Costa, Paulo; Costa, Angela; Figueiredo, Walter; Cesar, Thais

2017-01-01

Background: HCV causes alterations in liver metabolism, resulting in biochemical and nutritional disorders. Supplementation with antioxidants has been suggested to minimize the diseases effects. Objective: This study assessed whether orange juice, a source of citrus flavonoids and vitamin C, may contribute to the treatment of patients with chronic hepatitis C. Design: Anthropometric, hemodynamic, dietary, and biochemical parameters, CRP and liver enzymes were measured in 43 adult patients of both genders who were diagnosed with chronic hepatitis C and were under antiviral therapy. Twenty-three patients were supplemented with orange juice for eight consecutive weeks, while 20 were enrolled as control group. Results: Following regular use of orange juice, no alterations were found in body mass, fat, and waist circumference. The serum levels of total cholesterol, LDL-cholesterol, CRP and parameters of oxidative stress decreased in the orange juice group. Furthermore, the levels of the liver enzyme AST decreased in those who had high levels before the intervention. Conclusion: The orange juice was a convenient food in the diet of patients due to the increase in antioxidant capacity and decreased inflammation and cholesterol in blood serum, in addition to maintaining body mass, which protect against the harmful effects caused by the chronic hepatitis C virus.​​​.

Orange juice as dietary source of antioxidants for patients with hepatitis C under antiviral therapy

PubMed Central

Gonçalves, Danielle; Lima, Claudia; Ferreira, Paula; Costa, Paulo; Costa, Angela; Figueiredo, Walter; Cesar, Thais

2017-01-01

ABSTRACT Background: HCV causes alterations in liver metabolism, resulting in biochemical and nutritional disorders. Supplementation with antioxidants has been suggested to minimize the diseases effects. Objective: This study assessed whether orange juice, a source of citrus flavonoids and vitamin C, may contribute to the treatment of patients with chronic hepatitis C. Design: Anthropometric, hemodynamic, dietary, and biochemical parameters, CRP and liver enzymes were measured in 43 adult patients of both genders who were diagnosed with chronic hepatitis C and were under antiviral therapy. Twenty-three patients were supplemented with orange juice for eight consecutive weeks, while 20 were enrolled as control group. Results: Following regular use of orange juice, no alterations were found in body mass, fat, and waist circumference. The serum levels of total cholesterol, LDL-cholesterol, CRP and parameters of oxidative stress decreased in the orange juice group. Furthermore, the levels of the liver enzyme AST decreased in those who had high levels before the intervention. Conclusion: The orange juice was a convenient food in the diet of patients due to the increase in antioxidant capacity and decreased inflammation and cholesterol in blood serum, in addition to maintaining body mass, which protect against the harmful effects caused by the chronic hepatitis C virus.​​​ PMID:28469541

Hybrid dynamic stabilization: a biomechanical assessment of adjacent and supraadjacent levels of the lumbar spine.

PubMed

Mageswaran, Prasath; Techy, Fernando; Colbrunn, Robb W; Bonner, Tara F; McLain, Robert F

2012-09-01

The object of this study was to evaluate the effect of hybrid dynamic stabilization on adjacent levels of the lumbar spine. Seven human spine specimens from T-12 to the sacrum were used. The following conditions were implemented: 1) intact spine; 2) fusion of L4-5 with bilateral pedicle screws and titanium rods; and 3) supplementation of the L4-5 fusion with pedicle screw dynamic stabilization constructs at L3-4, with the purpose of protecting the L3-4 level from excessive range of motion (ROM) and to create a smoother motion transition to the rest of the lumbar spine. An industrial robot was used to apply continuous pure moment (± 2 Nm) in flexion-extension with and without a follower load, lateral bending, and axial rotation. Intersegmental rotations of the fused, dynamically stabilized, and adjacent levels were measured and compared. In flexion-extension only, the rigid instrumentation at L4-5 caused a 78% decrease in the segment's ROM when compared with the intact specimen. To compensate, it caused an increase in motion at adjacent levels L1-2 (45.6%) and L2-3 (23.2%) only. The placement of the dynamic construct at L3-4 decreased the operated level's ROM by 80.4% (similar stability as the fusion at L4-5), when compared with the intact specimen, and caused a significant increase in motion at all tested adjacent levels. In flexion-extension with a follower load, instrumentation at L4-5 affected only a subadjacent level, L5-sacrum (52.0%), while causing a reduction in motion at the operated level (L4-5, -76.4%). The dynamic construct caused a significant increase in motion at the adjacent levels T12-L1 (44.9%), L1-2 (57.3%), and L5-sacrum (83.9%), while motion at the operated level (L3-4) was reduced by 76.7%. In lateral bending, instrumentation at L4-5 increased motion at only T12-L1 (22.8%). The dynamic construct at L3-4 caused an increase in motion at T12-L1 (69.9%), L1-2 (59.4%), L2-3 (44.7%), and L5-sacrum (43.7%). In axial rotation, only the placement of the dynamic construct at L3-4 caused a significant increase in motion of the adjacent levels L2-3 (25.1%) and L5-sacrum (31.4%). The dynamic stabilization system displayed stability characteristics similar to a solid, all-metal construct. Its addition of the supraadjacent level (L3-4) to the fusion (L4-5) did protect the adjacent level from excessive motion. However, it essentially transformed a 1-level lumbar fusion into a 2-level lumbar fusion, with exponential transfer of motion to the fewer remaining discs.

Regulation of hepatic LDL receptors by mTORC1 and PCSK9 in mice

PubMed Central

Ai, Ding; Chen, Chiyuan; Han, Seongah; Ganda, Anjali; Murphy, Andrew J.; Haeusler, Rebecca; Thorp, Edward; Accili, Domenico; Horton, Jay D.; Tall, Alan R.

2012-01-01

Individuals with type 2 diabetes have an increased risk of atherosclerosis. One factor underlying this is dyslipidemia, which in hyperinsulinemic subjects with early type 2 diabetes is typically characterized by increased VLDL secretion but normal LDL cholesterol levels, possibly reflecting enhanced catabolism of LDL via hepatic LDLRs. Recent studies have also suggested that hepatic insulin signaling sustains LDLR levels. We therefore sought to elucidate the mechanisms linking hepatic insulin signaling to regulation of LDLR levels. In WT mice, insulin receptor knockdown by shRNA resulted in decreased hepatic mTORC1 signaling and LDLR protein levels. It also led to increased expression of PCSK9, a known post-transcriptional regulator of LDLR expression. Administration of the mTORC1 inhibitor rapamycin caused increased expression of PCSK9, decreased levels of hepatic LDLR protein, and increased levels of VLDL/LDL cholesterol in WT but not Pcsk9–/– mice. Conversely, mice with increased hepatic mTORC1 activity exhibited decreased expression of PCSK9 and increased levels of hepatic LDLR protein levels. Pcsk9 is regulated by the transcription factor HNF1α, and our further detailed analyses suggest that increased mTORC1 activity leads to activation of PKCδ, reduced activity of HNF4α and HNF1α, decreased PCSK9 expression, and ultimately increased hepatic LDLR protein levels, which result in decreased circulating LDL levels. We therefore suggest that PCSK9 inhibition could be an effective way to reduce the adverse side effect of increased LDL levels that is observed in transplant patients taking rapamycin as immunosuppressive therapy. PMID:22426206

Prolonged treatment with imatinib mesylate in patients with advanced chronic myeloid leukemia causes a reduction of bcr/abl mRNA levels independent of cytogenetic response.

PubMed

Cariani, E; Capucci, M; Micheletti, M; Spalenza, F; Zanella, I; Albertini, A; Rossi, G

2003-06-01

Bcr/abl mRNA levels were monitored in 13 patients with chronic myeloid leukemia receiving imatinib mesylate over a period of 78 weeks. During treatment median bcr/abl mRNA levels progressively declined from 77.2 normalized dose (nD) at baseline to 11.28 nD after 13 weeks ( P<0.05) and to 1.28 nD after 78 weeks ( P<0.05). After 13 weeks, bcr/abl mRNA levels were significantly lower in cytogenetic responders compared to nonresponders ( P<0.05), but subsequent decrease in the transcript levels caused the loss of any correlation to the cytogenetic status. These results suggest that bcr/abl mRNA levels may reflect cytogenetic response only during the early phases of imatinib therapy.

Investigation of the Photocurrent in Hot-Wall-Epitaxy-Grown BaIn2S4 Layers

NASA Astrophysics Data System (ADS)

You, S. H.; Hong, K. J.; Jeong, T. S.; Youn, C. J.

2015-12-01

The photocurrent (PC) of hot-wall-epitaxy-grown BaIn2S4 layers was studied at different temperatures and for different photoresponse intensities. With increasing temperature, the position of the PC spectra tended to shift toward longer wavelength. These PC peaks corresponded to band-to-band transitions caused by intrinsic transitions from the valence band states to the conduction band states. Also, the bandgap variations were well matched by the equation E g( T) = E g(0) - 3.79 × 10-3 T 2/( T + 499), where E g(0) was estimated to be 3.0597 eV, 3.2301 eV, and 3.2606 eV for transitions corresponding to the valence band states Γ 4(z), Γ 5(x), and Γ 5(y), respectively. By use of the selection rule and results from the PC spectroscopy, the crystal field and the spin-orbit splitting were found to be 0.1703 and 0.0306 eV, respectively. Thus, the PC intensity gradually decreased with decreasing temperature. The decrease of PC intensity was caused by the presence of trapping centers associated with native defects in the BaIn2S4 layers. The trap level was found to be a shallow donor-level type of 20.4 meV, 1.6 meV below the conduction band. Consequently, these trap levels, which are related to native defects in BaIn2S4 layers, are believed to limit PC intensity with decreasing temperature.

The Inactivation of RabGAP Function of AS160 Promotes Lysosomal Degradation of GLUT4 and Causes Postprandial Hyperglycemia and Hyperinsulinemia.

PubMed

Xie, Bingxian; Chen, Qiaoli; Chen, Liang; Sheng, Yang; Wang, Hong Yu; Chen, Shuai

2016-11-01

The AS160 (Akt substrate of 160 kDa) is a Rab-GTPase activating protein (RabGAP) with several other functional domains, and its deficiency in mice or human patients lowers GLUT4 protein levels and causes severe insulin resistance. How its deficiency causes diminished GLUT4 proteins remains unknown. We found that the deletion of AS160 decreased GLUT4 levels in a cell/tissue-autonomous manner. Consequently, skeletal muscle-specific deletion of AS160 caused postprandial hyperglycemia and hyperinsulinemia. The pathogenic effects of AS160 deletion are mainly, if not exclusively, due to the loss of its RabGAP function since the RabGAP-inactive AS160 R917K mutant mice phenocopied the AS160 knockout mice. The inactivation of RabGAP of AS160 promotes lysosomal degradation of GLUT4, and the inhibition of lysosome function could restore GLUT4 protein levels. Collectively, these findings demonstrate that the RabGAP activity of AS160 maintains GLUT4 protein levels in a cell/tissue-autonomous manner and its inactivation causes lysosomal degradation of GLUT4 and postprandial hyperglycemia and hyperinsulinemia. © 2016 by the American Diabetes Association.

Interaction of dietary vitamin E with Eimeria maxima infections in chickens.

PubMed

Allen, P C; Fetterer, R H

2002-01-01

In two trials, broiler chickens, processed similarly to those placed in commercial operation, were fed, from 1 d of age, a range (13 to 200 ppm) of DL-alpha-tocopheryl acetate (VE-AC) levels, and the effects on the pathology of Eimeria maxima infections were assessed at 6 d postinoculation (PI). In Trial 1, dietary levels of VE-AC had little significant effect on variables characterizing pathology except for the number of oocysts shed, which was significantly increased in chicks treated with higher VE-AC levels. The infection was judged to be mild based on moderate lesion scores (2.2+/-0.2), lack of significant effects on weight gain (7+/-1.6% decrease), moderate reduction in plasma carotenoids (21+/-2%) and small increases in plasma NO2-+NO3- (141+/-12%). In uninfected and infected chickens, plasma alpha-tocopherol (AT) increased with dietary levels of VE-AC; however, E. maxima infection caused a fairly constant decrease in AT of 35.3+/-3.2% across these levels. Plasma gamma-tocopherol (GT) levels were unaffected by dietary VE-AC or E. maxima infection. In Trial 2, pathology, again, was relatively unaffected by dietary VE-AC level. The infection was judged to be severe based on lesion scores (3.5+/-0.1), reduction in weight gain (30.7+/-3%), plasma carotenoids (72.4+/-1.5%), uric acid (16.3+/-3.4), albumin (37.8+/-2.8%), large increases (261+/-8%) in plasma NO2-+NO3-, and high numbers of oocysts shed per chick (4.12+/-0.4 x 10(7)). Plasma AT again increased with increasing dietary VE-AC levels in uninfected and infected chicks, but the mean decrease across VE-AC levels caused by E. maxima infection was 73.14+/-3.3%. GT levels were erratic and unrelated to dietary VEAC or infection. Thus, in processed broiler chickens, high dietary VE-AC did not prevent or lessen the pathology caused by mild or severe infections with E. maxima. The main effect of E. maxima infection appeared to be reduction in plasma AT levels. We postulate that this reduction may be due to malabsorption of AT, which results from physical damage to the absorptive mucosa, reduction in esterases required to hydrolyze the VE-AC, and a generalized lipid malabsorption, preventing movement of the free AT to circulating blood and infected tissues.

Coastal ocean acidification: The other eutrophication problem

EPA Science Inventory

Increased nutrient loading into estuaries causes the accumulation of algal biomass, and microbial degradation of this organic matter decreases oxygen levels and contributes towards hypoxia. A second, often overlooked consequence of microbial degradation of organic matter is the p...

Choline Deficiency Causes Colonic Type II Natural Killer T (NKT) Cell Loss and Alleviates Murine Colitis under Type I NKT Cell Deficiency

PubMed Central

Sagami, Shintaro; Ueno, Yoshitaka; Tanaka, Shinji; Fujita, Akira; Niitsu, Hiroaki; Hayashi, Ryohei; Hyogo, Hideyuki; Hinoi, Takao; Kitadai, Yasuhiko; Chayama, Kazuaki

2017-01-01

Serum levels of choline and its derivatives are lower in patients with inflammatory bowel disease (IBD) than in healthy individuals. However, the effect of choline deficiency on the severity of colitis has not been investigated. In the present study, we investigated the role of choline deficiency in dextran sulfate sodium (DSS)-induced colitis in mice. Methionine-choline-deficient (MCD) diet lowered the levels of type II natural killer T (NKT) cells in the colonic lamina propria, peritoneal cavity, and mesenteric lymph nodes, and increased the levels of type II NKT cells in the livers of wild-type B6 mice compared with that in mice fed a control (CTR) diet. The gene expression pattern of the chemokine receptor CXCR6, which promotes NKT cell accumulation, varied between colon and liver in a manner dependent on the changes in the type II NKT cell levels. To examine the role of type II NKT cells in colitis under choline-deficient conditions, we assessed the severity of DSS-induced colitis in type I NKT cell-deficient (Jα18-/-) or type I and type II NKT cell-deficient (CD1d-/-) mice fed the MCD or CTR diets. The MCD diet led to amelioration of inflammation, decreases in interferon (IFN)-γ and interleukin (IL)-4 secretion, and a decrease in the number of IFN-γ and IL-4-producing NKT cells in Jα18-/- mice but not in CD1d-/- mice. Finally, adaptive transfer of lymphocytes with type II NKT cells exacerbated DSS-induced colitis in Jα18-/- mice with MCD diet. These results suggest that choline deficiency causes proinflammatory type II NKT cell loss and alleviates DSS-induced colitis. Thus, inflammation in DSS-induced colitis under choline deficiency is caused by type II NKT cell-dependent mechanisms, including decreased type II NKT cell and proinflammatory cytokine levels. PMID:28095507

Choline Deficiency Causes Colonic Type II Natural Killer T (NKT) Cell Loss and Alleviates Murine Colitis under Type I NKT Cell Deficiency.

PubMed

Sagami, Shintaro; Ueno, Yoshitaka; Tanaka, Shinji; Fujita, Akira; Niitsu, Hiroaki; Hayashi, Ryohei; Hyogo, Hideyuki; Hinoi, Takao; Kitadai, Yasuhiko; Chayama, Kazuaki

2017-01-01

Serum levels of choline and its derivatives are lower in patients with inflammatory bowel disease (IBD) than in healthy individuals. However, the effect of choline deficiency on the severity of colitis has not been investigated. In the present study, we investigated the role of choline deficiency in dextran sulfate sodium (DSS)-induced colitis in mice. Methionine-choline-deficient (MCD) diet lowered the levels of type II natural killer T (NKT) cells in the colonic lamina propria, peritoneal cavity, and mesenteric lymph nodes, and increased the levels of type II NKT cells in the livers of wild-type B6 mice compared with that in mice fed a control (CTR) diet. The gene expression pattern of the chemokine receptor CXCR6, which promotes NKT cell accumulation, varied between colon and liver in a manner dependent on the changes in the type II NKT cell levels. To examine the role of type II NKT cells in colitis under choline-deficient conditions, we assessed the severity of DSS-induced colitis in type I NKT cell-deficient (Jα18-/-) or type I and type II NKT cell-deficient (CD1d-/-) mice fed the MCD or CTR diets. The MCD diet led to amelioration of inflammation, decreases in interferon (IFN)-γ and interleukin (IL)-4 secretion, and a decrease in the number of IFN-γ and IL-4-producing NKT cells in Jα18-/- mice but not in CD1d-/- mice. Finally, adaptive transfer of lymphocytes with type II NKT cells exacerbated DSS-induced colitis in Jα18-/- mice with MCD diet. These results suggest that choline deficiency causes proinflammatory type II NKT cell loss and alleviates DSS-induced colitis. Thus, inflammation in DSS-induced colitis under choline deficiency is caused by type II NKT cell-dependent mechanisms, including decreased type II NKT cell and proinflammatory cytokine levels.

Maternal exercise decreases maternal deprivation induced anxiety of pups and correlates to increased prefrontal cortex BDNF and VEGF.

PubMed

Uysal, Nazan; Sisman, Ali Riza; Dayi, Ayfer; Aksu, Ilkay; Cetin, Ferihan; Gencoglu, Celal; Tas, Aysegul; Buyuk, Erkan

2011-11-21

Maternal deprivation (MD) may cause neuropsychiatric disorders such as anxiety disorder by negatively affecting the cognitive functions and behavior in pups. The aim of this study is to investigate whether maternal exercise during pregnancy has beneficial effects on anxiety that increases with MD, and on the levels of VEGF and BDNF which have anxiolytic effects on the prefrontal cortex, the anxiety-related region of the brain. The anxiety level in the deprivation group was greater than the control group and found more in male than female pups. The prefrontal cortex VEGF and BDNF levels were decreased in the deprivation group compared to control group while serum corticosterone levels were increased in the deprivation group. Anxiety and serum corticosterone levels were decreased in maternally exercised female and male pups, while the prefrontal cortex VEGF and BDNF levels were increased, compared to sedentary mother's pups. These results indicate that maternal exercise may attenuate the negative effect of stresses such as maternal deprivation that can be encountered early in life. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

[A case of hyperammonemia resulting from urinary tract infection caused by urease-producing bacteria in a Parkinson's disease patient with drug-induced urinary retention].

PubMed

Yasunishi, Masahiro; Koumura, Akihiro; Hayashi, Yuichi; Nishida, Shohei; Inuzuka, Takashi

2017-01-01

A 71-year-old woman with a 9-year history of Parkinson's disease was admitted to our hospital emergently because of consciousness disturbance. Her consciousness level was 200 on the Japan coma scale (JCS), and she presented with tenderness and distension of the lower abdomen. Brain computed tomography showed normal findings. Blood tests showed an increased ammonia level (209 μg/dl) with normal AST and ALT levels. We catheterized the bladder for urinary retention. Five hours after admission, the blood ammonia level decreased to 38 μg/dl, and her consciousness level improved dramatically. Corynebacterium urearyticum, a bacterial species that produces urease, was detected by urine culture. Therefore, she was diagnosed with hyperammonemic encephalopathy resulting from urinary tract infection caused by urease-producing bacteria. In this case, urologic active agents had been administered to treat neurogenic bladder. We suspect that these drugs caused urinary obstruction and urinary tract infection. It is important to recognize that obstructive urinary tract infection caused by urease-producing bacteria can cause hyperammonemia. Neurological disorders, such as Parkinson's disease, tend to complicate neurogenic bladder. This disease should be considered in elderly patients with Parkinson's disease who are receiving urologic active drugs.

Hypocalcaemia after treatment with [177Lu-DOTA 0,Tyr3]octreotate.

PubMed

van Vliet, Esther I; de Herder, Wouter W; de Rijke, Yolanda B; Zillikens, M Carola; Kam, Boen L R; Teunissen, Jaap J M; Peeters, Robin P; Krenning, Eric P; Kwekkeboom, Dik J

2013-12-01

The aim of this study was to explore the possible mechanisms involved in an observed decline in serum calcium levels in patients with a neuroendocrine tumour (NET) treated with [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-octreotate). In 47 patients with NET who were normocalcaemic at baseline, serum calcium, albumin, creatinine, alkaline phosphatase, gamma glutamyl transpeptidase, magnesium, phosphate and 25-hydroxyvitamin D were prospectively analysed at baseline and up to 6 months after treatment. Parathyroid hormone (PTH), 1,25-dihydroxyvitamin D3, type 1 aminoterminal propeptide of procollagen, bone-specific alkaline phosphatase, carboxyterminal crosslinking telopeptide of bone collagen, collagen type I crosslinked N-telopeptide, and creatinine and calcium in 24-h urine samples, were evaluated at baseline and at 3 and 6 months. Another 153 patients with NET were included in a retrospective study to estimate the occurrence of hypocalcaemia in a larger patient group. In the prospectively included patients, the mean serum calcium level decreased significantly after treatment (2.31 ± 0.01 to 2.26 ± 0.02 mmol/l, p = 0.02). Eight patients (17%) showed a marked decrease in serum calcium levels with a nadir of ≤ 2.10 mmol/l. In five patients (11%), calcium substitution therapy was prescribed. PTH increased significantly (5.9 ± 0.6 to 6.7 ± 0.8 pmol/l, p = 0.02), presumably in response to the decreasing serum calcium levels. 25-Hydroxyvitamin D remained stable after treatment. Creatinine levels increased significantly (73 ± 3 to 77 ± 3 μmol/l, p = 0.01), but not enough to explain the hypocalcaemia. Phosphate levels remained unaffected. In the retrospectively analysed patients, the mean serum calcium level decreased significantly from 2.33 ± 0.01 at baseline to a nadir of 2.24 ± 0.01 mmol/l at 18 months after treatment (p < 0.001). Of the 153 patients, 33 (22%) showed a serum calcium nadir of ≤ 2.10 mmol/l, and 11 (7%) received calcium substitution therapy. The mean serum calcium level decreased significantly after treatment with (177)Lu-octreotate, resulting in mild hypocalcaemia in about 20% of patients. We excluded several potential causes of this hypocalcaemia, so the cause remains unknown. Serum calcium levels should be monitored after peptide receptor radionuclide therapy, and calcium substitution therapy should be initiated if appropriate.

Effects of sulfate on microcystin production, photosynthesis, and oxidative stress in Microcystis aeruginosa.

PubMed

Chen, Lei; Gin, Karina Y H; He, Yiliang

2016-02-01

Increasing sulfate in freshwater systems, caused by human activities and climate change, may have negative effects on aquatic organisms. Microcystis aeruginosa (M. aeruginosa) is both a major primary producer and a common toxic cyanobacterium, playing an important role in the aquatic environment. This study first investigated the effects of sulfate on M. aeruginosa. The experiment presented here aims at analyzing the effects of sulfate on physiological indices, molecular levels, and its influencing mechanism. The results of our experiment showed that sulfate (at 40, 80, and 300 mg L(-1)) inhibited M. aeruginosa growth, increased both intracellular and extracellular toxin contents, and enhanced the mcyD transcript level. Sulfate inhibited the photosynthesis of M. aeruginosa, based on the decrease in pigment content and the down-regulation of photosynthesis-related genes after sulfate exposure. Furthermore, sulfate decreased the maximum electron transport rate, causing the cell to accumulate surplus electrons and form reactive oxygen species (ROS). Sulfate also increased the malondialdehyde (MDA) content, which showed that sulfate damaged the cytomembrane. This damage contributed to the release of intracellular toxin to the culture medium. Although sulfate increased superoxide dismutase (SOD) activities, expression of sod, and total antioxidant capacity in M. aeruginosa, it still overwhelmed the antioxidant system since the ROS level simultaneously increased, and finally caused oxidative stress. Our results indicate that sulfate has direct effects on M. aeruginosa, inhibits photosynthesis, causes oxidative stress, increases toxin production, and affects the related genes expression in M. aeruginosa.

Influence of ethynylestradiol and methyltestosterone on the hypothalamo-hypophyseal-gonadal axis of adult air-breathing catfish, Clarias gariepinus.

PubMed

Swapna, I; Senthilkumaran, B

2009-11-27

Adult male and female air-breathing catfish Clarias gariepinus were treated with ethynylestradiol (EE(2)) and methyltestosterone (MT) at concentrations of 1microg/L, respectively for 21 days. EE(2) treatment caused disappearance of spermatids/sperm from several testicular lumen/lobules in males while MT treatment to females led to precocious ovarian development. EE(2) caused significant fluid retention in all tissues including peritoneal cavity and seminal vesicles. Immunocytochemical localization of catfish GnRH (cfGnRH) and luteinizing hormone (LH) in preoptic area-hypothalamus (POA-H) and pituitary, respectively, revealed decreased immunoreactivity (ir-) following EE(2) treatment in males. MT treatment however caused no observable change in cfGnRH ir- and a significant increase in LH ir- in females. Semi-quantitative RT-PCR analysis indicated that cfGnRH transcripts in POA-H decreased significantly following EE(2) and MT treatment in males and females, respectively. Levels of POA-H dopamine (inhibitory monoamine for gonadotropin [GTH] synthesis and release) increased following EE(2) and MT treatment in males and females while levels of serotonin and norepinephrine (GTH-stimulatory monoamines) decreased significantly. The results demonstrate a direct in vivo effect of sex steroid analogs on cfGnRH-LH axis and monoaminergic system vis-à-vis on gonads in addition to probable direct action on gonads.

Peroxiredoxin 1 protects the pea aphid Acyrthosiphon pisum from oxidative stress induced by Micrococcus luteus infection.

PubMed

Zhang, Yongdong; Lu, Zhiqiang

2015-05-01

Reactive oxygen species (ROSs) are generated in organisms in response to infections caused by invading microbes. However, excessive ROSs will inflict oxidative damage on the host. Peroxiredoxins (Prxs) are antioxidative enzymes that may eliminate ROSs efficiently. In this study, ApPrx1 from the pea aphid Acyrthosiphon pisum was cloned, and its function was investigated in vitro and in vivo. In the presence of DTT, recombinant ApPrx1 protein from Escherichia coli showed antioxidative activity by eliminating H2O2 effectively. The H2O2 levels were significantly higher in Micrococcus luteus-infected aphids than in uninfected aphids, and ApPrx1 expression was remarkably up-regulated when the aphids were infected with M. luteus or injected with H2O2. When ApPrx1 expression was reduced by dsRNA injection, the survival of the aphids decreased significantly after M. luteus infection. Knockdown of ApPrx1 decreased M. luteus loads inside the aphids 48h post-infection. While under infection conditions, the H2O2 levels were much higher in ApPrx1 knockdown aphids than in dsGFP-injected aphids, indicating that the decreased survival of the aphids was caused by increased oxidative stress. Taken together, our results reveal that ApPrx1 plays a protective role in oxidative stress caused by bacterial infection. Copyright © 2015 Elsevier Inc. All rights reserved.

Inadequate Antioxidative Responses in Kidneys of Brain-Dead Rats.

PubMed

Hoeksma, Dane; Rebolledo, Rolando A; Hottenrott, Maximilia; Bodar, Yves S; Wiersema-Buist, Janneke J; Van Goor, Harry; Leuvenink, Henri G D

2017-04-01

Brain death (BD)-related lipid peroxidation, measured as serum malondialdehyde (MDA) levels, correlates with delayed graft function in renal transplant recipients. How BD affects lipid peroxidation is not known. The extent of BD-induced organ damage is influenced by the speed at which intracranial pressure increases. To determine possible underlying causes of lipid peroxidation, we investigated the renal redox balance by assessing oxidative and antioxidative processes in kidneys of brain-dead rats after fast and slow BD induction. Brain death was induced in 64 ventilated male Fisher rats by inflating a 4.0F Fogarty catheter in the epidural space. Fast and slow inductions were achieved by an inflation speed of 0.45 and 0.015 mL/min, respectively, until BD confirmation. Healthy non-brain-dead rats served as reference values. Brain-dead rats were monitored for 0.5, 1, 2, or 4 hours, after which organs and blood were collected. Increased MDA levels became evident at 2 hours of slow BD induction at which increased superoxide levels, decreased glutathione peroxidase (GPx) activity, decreased glutathione levels, increased inducible nitric oxide synthase and heme-oxygenase 1 expression, and increased plasma creatinine levels were evident. At 4 hours after slow BD induction, superoxide, MDA, and plasma creatinine levels increased further, whereas GPx activity remained decreased. Increased MDA and plasma creatinine levels also became evident after 4 hours fast BD induction. Brain death leads to increased superoxide production, decreased GPx activity, decreased glutathione levels, increased inducible nitric oxide synthase and heme-oxygenase 1 expression, and increased MDA and plasma creatinine levels. These effects were more pronounced after slow BD induction. Modulation of these processes could lead to decreased incidence of delayed graft function.

Hydrolyzable tannins as "quantitative defenses": limited impact against Lymantria dispar caterpillars on hybrid poplar.

PubMed

Barbehenn, Raymond V; Jaros, Adam; Lee, Grace; Mozola, Cara; Weir, Quentin; Salminen, Juha-Pekka

2009-04-01

The high levels of tannins in many tree leaves are believed to cause decreased insect performance, but few controlled studies have been done. This study tested the hypothesis that higher foliar tannin levels produce higher concentrations of semiquinone radicals (from tannin oxidation) in caterpillar midguts, and that elevated levels of radicals are associated with increased oxidative stress in midgut tissues and decreased larval performance. The tannin-free leaves of hybrid poplar (Populus tremulaxP. alba) were treated with hydrolyzable tannins, producing concentrations of 0%, 7.5% or 15% dry weight, and fed to Lymantria dispar caterpillars. As expected, larvae that ingested control leaves contained no measurable semiquinone radicals in the midgut, those that ingested 7.5% hydrolyzable tannin contained low levels of semiquinone radicals, and those that ingested 15% tannin contained greatly increased levels of semiquinone radicals. Ingested hydrolyzable tannins were also partially hydrolyzed in the midgut. However, increased levels of semiquinone radicals in the midgut were not associated with oxidative stress in midgut tissues. Instead, it appears that tannin consumption was associated with increased metabolic costs, as measured by the decreased efficiency of conversion of digested matter to body mass (ECD). Decreased ECD, in turn, decreased the overall efficiency of conversion of ingested matter to body mass (ECI). Contrary to our hypothesis, L. dispar larvae were able to maintain similar growth rates across all tannin treatment levels, in part, because of compensatory feeding. We conclude that hydrolyzable tannins act as "quantitative defenses" in the sense that high levels appear to be necessary to increase levels of semiquinone radicals in the midguts of caterpillars. However, these putative resistance factors are not sufficient to decrease the performance of tannin-tolerant caterpillars such as L. dispar.

Changes in mortality after the recent economic crisis in South Korea.

PubMed

Kim, Hanjoong; Song, Young Jong; Yi, Jee Jeon; Chung, Woo Jin; Nam, Chung Mo

2004-07-01

To examine the changes in all cause mortality and cause-specific mortality after the economic crisis in South Korea. Monthly mortality data for an entire country was used and intervention analysis applied to compare mortality after the crisis with mortality which would have occurred if the trends before the crisis had continued. All cause mortality began to increase about 1 year after the crisis, while cardiovascular increased immediately. Transport accidents decreased significantly during the year following the crisis and then regressed towards the pre-economic crisis level. Suicides increased rapidly and maintained an upward trend but subsequently reduced towards the pre-economic crisis level. This study has shown an evidence of a relationship between economic crisis and mortality.

Gene regulation of atrial natriuretic peptide A, B, and C receptors in rat glomeruli.

PubMed

Itoh, K; Nonoguchi, H; Shiraishi, N; Tomita, K

1999-01-01

Atrial natriuretic peptide (ANP) has three types of receptor. We investigated the gene regulation of three types of ANP receptors (ANPR-A, B, and C) in rat glomeruli using reverse transcription coupled with competitive polymerase chain reaction (PCR). Competitive PCR revealed that ANPR-C mRNA expression was most abundant (ANPR-C > A > B) in glomeruli from control rats among mRNA expressions of three receptors, which were 20- to 15,000-fold higher than those in inner medullary collecting ducts. Two days' dehydration caused reversible decreases of ANPR-A, B, and C mRNAs by 50-80%. To determine the mechanisms of down-regulation of mRNA expression, isolated glomeruli were incubated in isotonic or hypertonic solution. Hyperosmolality induced by NaCl, mannitol or raffinose caused significant increases of ANPR-A, B, and C mRNA expression. Hypertonicity by urea showed smaller effects. ANP stimulated the expression of ANPR-A, B, and C mRNA in vitro. These results indicate that dehydration caused reversible decreases of ANPR-A, B, and C mRNA expression in glomeruli, and these decreases were not caused by increased plasma osmolality but probably by lower circulating levels of ANP.

Salinity stress inhibits bean leaf expansion by reducing turgor, not wall extensibility

NASA Technical Reports Server (NTRS)

Neumann, P. M.; Van Volkenburgh, E.; Cleland, R. E.

1988-01-01

Treatment of bean (Phaseolus vulgaris L.) seedlings with low levels of salinity (50 or 100 millimolar NaCl) decreased the rate of light-induced leaf cell expansion in the primary leaves over a 3 day period. This decrease could be due to a reduction in one or both of the primary cellular growth parameters: wall extensibility and cell turgor. Wall extensibility was assessed by the Instron technique. Salinity did not decrease extensibility and caused small increases relative to the controls after 72 hours. On the other hand, 50 millimolar NaCl caused a significant reduction in leaf bulk turgor at 24 hours; adaptive decreases in leaf osmotic potential (osmotic adjustment) were more than compensated by parallel decreases in xylem tension potential and the leaf apoplastic solute potential, resulting in a decreased leaf water potential. It is concluded that in bean seedlings, mild salinity initially affects leaf growth rate by a decrease in turgor rather than by a reduction in wall extensibility. Moreover, long-term salinization (10 days) resulted in an apparent mechanical adjustment, i.e. an increase in wall extensibility, which may help counteract reductions in turgor and maintain leaf growth rates.

Modeling the chemical kinetics of atmospheric plasma for cell treatment in a liquid solution

NASA Astrophysics Data System (ADS)

Kim, H. Y.; Lee, H. W.; Kang, S. K.; Wk. Lee, H.; Kim, G. C.; Lee, J. K.

2012-07-01

Low temperature atmospheric pressure plasmas have been known to be effective for living cell inactivation in a liquid solution but it is not clear yet which species are key factors for the cell treatment. Using a global model, we elucidate the processes through which pH level in the solution is changed from neutral to acidic after plasma exposure and key components with pH and air variation. First, pH level in a liquid solution is changed by He+ and He(21S) radicals. Second, O3 density decreases as pH level in the solution decreases and air concentration decreases. It can be a method of removing O3 that causes chest pain and damages lung tissue when the density is very high. H2O2, HO2, and NO radicals are found to be key factors for cell inactivation in the solution with pH and air variation.

The 800 Pound Gorilla: The Threat and Taming of Global Climate Change

ERIC Educational Resources Information Center

Hansen, Jim

2008-01-01

This article provides two case studies that examine the current and future consequences of continued global warming at the current business-as-usual pace and at a decreased (new alternative forms of energy) level. Cause and effect relationships, such as the varying levels of CO[subscript 2] (carbon dioxide) emissions and the effect it has on…

Diabetic ketosis during hyperglycemic crisis is associated with decreased all-cause mortality in patients with type 2 diabetes mellitus.

PubMed

Kruljac, Ivan; Ćaćić, Miroslav; Ćaćić, Petra; Ostojić, Vedran; Štefanović, Mario; Šikić, Aljoša; Vrkljan, Milan

2017-01-01

Patients with type 2 diabetes mellitus have impaired ketogenesis due to high serum insulin and low growth hormone levels. Evidence exists that ketone bodies might improve kidney and cardiac function. In theory, improved ketogenesis in diabetics may have positive effects. We aimed to assess the impact of diabetic ketosis on all-cause mortality in patients with type 2 diabetes mellitus presenting with hyperglycemic crisis. We analyzed 486 patients with diabetic ketosis and 486 age and sex-matched patients with non-ketotic hyperglycemia presenting to the emergency department. Cox proportional hazard models were used to analyze the link between patient characteristics and mortality. During an observation time of 33.4 months, death of any cause occurred in 40.9 % of the non-ketotic hyperglycemia group and 30.2 % of the DK group (hazard ratio in the diabetic ketosis group, 0.63; 95 % confidence interval 0.48-0.82; P = 0.0005). Patients with diabetic ketosis had a lower incidence of symptomatic heart failure and had improved renal function. They used less furosemide and antihypertensive drugs, more metformin and lower insulin doses, all of which was independently associated with decreased mortality. Plasma glucose and glycated hemoglobin levels were similar in both groups. Patients with hyperglycemic crisis and diabetic ketosis have decreased all-cause mortality when compared to those with non-ketotic hyperglycemia. diabetic ketosis might be a compensatory mechanism rather than a complication in patients with hyperglycemic crises, but further prospective studies are warranted.

Decreased microRNA levels lead to deleterious increases in neuronal M2 muscarinic receptors in Spinal Muscular Atrophy models

PubMed Central

O'Hern, Patrick J; do Carmo G. Gonçalves, Inês; Brecht, Johanna; López Soto, Eduardo Javier; Simon, Jonah; Chapkis, Natalie; Lipscombe, Diane; Kye, Min Jeong; Hart, Anne C

2017-01-01

Spinal Muscular Atrophy (SMA) is caused by diminished Survival of Motor Neuron (SMN) protein, leading to neuromuscular junction (NMJ) dysfunction and spinal motor neuron (MN) loss. Here, we report that reduced SMN function impacts the action of a pertinent microRNA and its mRNA target in MNs. Loss of the C. elegans SMN ortholog, SMN-1, causes NMJ defects. We found that increased levels of the C. elegans Gemin3 ortholog, MEL-46, ameliorates these defects. Increased MEL-46 levels also restored perturbed microRNA (miR-2) function in smn-1(lf) animals. We determined that miR-2 regulates expression of the C. elegans M2 muscarinic receptor (m2R) ortholog, GAR-2. GAR-2 loss ameliorated smn-1(lf) and mel-46(lf) synaptic defects. In an SMA mouse model, m2R levels were increased and pharmacological inhibition of m2R rescued MN process defects. Collectively, these results suggest decreased SMN leads to defective microRNA function via MEL-46 misregulation, followed by increased m2R expression, and neuronal dysfunction in SMA. DOI: http://dx.doi.org/10.7554/eLife.20752.001 PMID:28463115

Rheinanthrone, a metabolite of sennoside A, triggers macrophage activation to decrease aquaporin-3 expression in the colon, causing the laxative effect of rhubarb extract.

PubMed

Kon, Risako; Ikarashi, Nobutomo; Nagoya, Chika; Takayama, Tomoko; Kusunoki, Yoshiki; Ishii, Makoto; Ueda, Harumi; Ochiai, Wataru; Machida, Yoshiaki; Sugita, Kazuyuki; Sugiyama, Kiyoshi

2014-02-27

Aquaporin-3 (AQP3) is expressed in mucosal epithelial cells in the colon and is important for regulating fecal water content. We examined the role of AQP3 in the laxative effect of rhubarb extract. After orally administering rhubarb extract or its major component (sennoside A) to rats, the fecal water content, AQP3 expression and prostaglandin E2 (PGE2) concentrations in the colon were examined. The mechanism by which sennoside A decreases the expression of AQP3 was examined using the human colon cancer HT-29 cells and macrophage-derived Raw264.7 cells. During diarrhea by rhubarb extract administration, the PGE2 levels in the colon increased while the AQP3 expression significantly decreased. Similar changes were also observed when sennoside A was administered. When sennoside A or its metabolites, rheinanthrone and rhein were added to Raw264.7 cells, a significant increase in the PGE2 concentration was observed only in cells treated with rheinanthrone. Fifteen minutes after adding PGE2 to the HT-29 cells, the AQP3 expression decreased to approximately 40% of the control. When pretreated with indomethacin, sennoside A neither decreased the AQP3 expression nor induced diarrhea. Sennoside A may decrease AQP3 expression in the colon to inhibit water transport from the luminal to the vascular side, leading to a laxative effect. The decreases in the levels of AQP3 are caused by rheinanthrone, which is a metabolite of sennoside A, this metabolite activates the macrophages in the colon and increases the secretion of PGE2; PGE2 acts as a paracrine factor and decreases AQP3 expression in colon mucosal epithelial cells. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Reduction of Nuak1 Decreases Tau and Reverses Phenotypes in a Tauopathy Mouse Model.

PubMed

Lasagna-Reeves, Cristian A; de Haro, Maria; Hao, Shuang; Park, Jeehye; Rousseaux, Maxime W C; Al-Ramahi, Ismael; Jafar-Nejad, Paymaan; Vilanova-Velez, Luis; See, Lauren; De Maio, Antonia; Nitschke, Larissa; Wu, Zhenyu; Troncoso, Juan C; Westbrook, Thomas F; Tang, Jianrong; Botas, Juan; Zoghbi, Huda Y

2016-10-19

Many neurodegenerative proteinopathies share a common pathogenic mechanism: the abnormal accumulation of disease-related proteins. As growing evidence indicates that reducing the steady-state levels of disease-causing proteins mitigates neurodegeneration in animal models, we developed a strategy to screen for genes that decrease the levels of tau, whose accumulation contributes to the pathology of both Alzheimer disease (AD) and progressive supranuclear palsy (PSP). Integrating parallel cell-based and Drosophila genetic screens, we discovered that tau levels are regulated by Nuak1, an AMPK-related kinase. Nuak1 stabilizes tau by phosphorylation specifically at Ser356. Inhibition of Nuak1 in fruit flies suppressed neurodegeneration in tau-expressing Drosophila, and Nuak1 haploinsufficiency rescued the phenotypes of a tauopathy mouse model. These results demonstrate that decreasing total tau levels is a valid strategy for mitigating tau-related neurodegeneration and reveal Nuak1 to be a novel therapeutic entry point for tauopathies. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of gluten-free breads, with varying functional supplements, on the biochemical parameters and antioxidant status of rat serum.

PubMed

Świeca, Michał; Reguła, Julita; Suliburska, Joanna; Złotek, Urszula; Gawlik-Dziki, Urszula

2015-09-01

This paper examines the effects of gluten-free bread enriched with functional ingredients (milk powder, poppy, sunflower and pumpkin seeds, egg yolk, carum, hazel nuts and amaranth) on the morphological and biochemical parameters and antioxidant status of rats serum. Rats were provided test diets--gluten-free breads and water ad libitum. After 14 days, the animals were weighed and killed. A hazel nut-amaranth bread diet significantly increased the level of thrombocytes when compared to control bread. A mixed bread diet significantly decreased cholesterol levels in rats. All fortified breads decreased triglyceride levels and alanine transaminase activity and caused an increase in antiradical activity of the serum. In rats fed with poppy-milk bread, milk-seed bread and mixed bread, a marked decrease in superoxide dismutase activity was found. Enriched breads reduced the levels of triglyceride and improved the antiradical properties of serum, although the physiological relevance of this needs to be confirmed by human studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Influence of cobalt, tantaum and tungsten on the high temperature mechanical properties of single crystal nickel-base superalloys. Ph.D. Thesis - Case Western Reserve Univ.

NASA Technical Reports Server (NTRS)

Nathal, M. V.

1984-01-01

For alloys with the baseline refractory metal level of 3 percent Ta and 10 percent W, decreases in Co level from 10 to 0 percent resulted in increased tensile strength and creep resistance. Substitution of W for Ta resulted in decreased creep life at high stresses but improved life at low stresses. Substitution of Ni for Ta caused large reductions in tensile strength and creep resistance, and corresponding increases in ductility. For these alloys with low Ta plus W totals, strength was independent of Co level. The increases in tensile strength with increases in refractory metal content were related to the increases in gamma volume fraction and solid solution hardening. Increases in strength as Co level decreased were considered to be the result of coherency strain hardening from the increased lattice mismatch. Dislocation shear through the gamma-gamma interface is considered to be the rate limiting step in the deformation process.

Inhibitory effect of leonurine on the formation of advanced glycation end products.

PubMed

Huang, Lianqi; Yang, Xin; Peng, Anlin; Wang, Hui; Lei, Xiang; Zheng, Ling; Huang, Kun

2015-02-01

Long-term hyperglycemia is a typical symptom of diabetes mellitus (DM) which can cause a high level of protein glycation and lead to the formation of advanced glycation end products (AGEs). The accumulation of AGEs in turn deteriorates DM and its complications. Insulin, the only hormone that directly decreases blood sugar in vivo, is vulnerable to glycation which causes the loss of its biological activity. In this study, we used a porcine insulin (PI)-methylglyoxal (MGO) model to investigate the inhibitory effect of leonurine (LN), a natural alkaloid extracted from Herba leonuri, on AGE formation. Assays including AGE-specific fluorescence, and fructosamine level and carbonyl group content determination showed that LN can dose-dependently suppress PI glycation. A significantly decreased cross-linking level on the glycated PI was also proven by SDS-PAGE electrophoresis. A further liquid chromatography-mass spectrometry study suggested that LN may inhibit PI glycation through trapping MGO and keeping it from reacting with PI. Our results thus indicate that LN is a promising anti-glycation agent for the prevention of diabetes and its complications via inhibiting AGE formation.

The dynamics of human cognition: Increasing global integration coupled with decreasing segregation found using iEEG.

PubMed

Cruzat, Josephine; Deco, Gustavo; Tauste-Campo, Adrià; Principe, Alessandro; Costa, Albert; Kringelbach, Morten L; Rocamora, Rodrigo

2018-05-15

Cognitive processing requires the ability to flexibly integrate and process information across large brain networks. How do brain networks dynamically reorganize to allow broad communication between many different brain regions in order to integrate information? We record neural activity from 12 epileptic patients using intracranial EEG while performing three cognitive tasks. We assess how the functional connectivity between different brain areas changes to facilitate communication across them. At the topological level, this facilitation is characterized by measures of integration and segregation. Across all patients, we found significant increases in integration and decreases in segregation during cognitive processing, especially in the gamma band (50-90 Hz). We also found higher levels of global synchronization and functional connectivity during task execution, again particularly in the gamma band. More importantly, functional connectivity modulations were not caused by changes in the level of the underlying oscillations. Instead, these modulations were caused by a rearrangement of the mutual synchronization between the different nodes as proposed by the "Communication Through Coherence" Theory. Copyright © 2018 Elsevier Inc. All rights reserved.

Labour Market Segregation and Gender Differences in Sickness Absence: Trends in 2005-2013 in Finland.

PubMed

Leinonen, Taina; Viikari-Juntura, Eira; Husgafvel-Pursiainen, Kirsti; Virta, Lauri J; Laaksonen, Mikko; Autti-Rämö, Ilona; Solovieva, Svetlana

2018-04-18

Women have higher sickness absence rate than men, but less is known of changes in this difference over time. We examined gender differences in sickness absence trends focusing on gender segregation in the labour market. We used large nationwide register data on Finnish wage earners aged 25-59 and generalized estimation equations based on repeated logistic regression to estimate the annual risk of sickness absence lasting at least 2 weeks. Between 2005 and 2013, the age-adjusted proportion (%) of employees with all-cause sickness absence decreased from the initial levels of 10.6 among men and 15.1 among women by 16.7 and 13.6%, respectively. Among both genders, the largest decrease in sickness absence coincided with the peak of the economic recession in 2009. In sickness absence due to all causes and musculoskeletal diseases, also the excess decrease among men mainly occurred in 2009, and in sickness absence due to mental disorders 2 years later. In sickness absence due to all causes and musculoskeletal diseases, the increasing gender difference was mainly attributable to a larger decrease in sickness absence at the time of the recession in male-dominated groups, such as in manual and manufacturing work, than in other sectors and occupational classes. In mental disorders, the increasing gender difference was partly attributable to a later smaller decrease in sickness absence among female-dominated lower non-manual and lower income employment groups. The increasing gender differences did not result from differential distributional changes in employment or sociodemographic factors among the employed male and female populations. In fact, widening of the gender gap in sickness absence due to all causes and musculoskeletal diseases would have been even larger without faster increase among women in the educational level and in non-manual employment. Sickness absence decreased especially in male-dominated employment groups, resulting in a larger decrease in absences among men compared with women. More research is needed to ascertain whether these differential changes are attributable, for example, to reduced willingness to seek medical advice or increased presenteeism in male-dominated groups, or to increased work pressures in female-dominated groups. Selection mechanisms, i.e. men's increased ill-health-related exit from work through other routes than sickness absence, also cannot be ruled out.

The effects of physical therapeutic agents on serum levels of stress hormones in patients with osteoarthritis

PubMed Central

Tönük, Şükrü Burak; Serin, Erdinc; Ayhan, Fikriye Figen; Yorgancioglu, Zeynep Rezan

2016-01-01

Abstract To investigate the effects of physical agents on the levels of stress hormones in patients with osteoarthritis (OA). Transcutaneous electrical nerve stimulation, hot packs, and therapeutic ultrasound were applied to the lumbar region and knees of patients with OA. Blood samples were taken for the measurement of the serum levels of glucose, insulin (INS), growth hormone (GH), prolactin (PRL), cortisol (COR), and plasma adrenocorticotropic hormone (ACTH) immediately before and after the 1st session, to investigate the acute effects of those physical agents on the endocrine system. The hormone levels were also measured every 5 sessions in a total of 10 sessions. The treatment response was also evaluated by using the visual analogue scale (VAS), Roland Morris Disability Questionnaire (RMDQ), and Western Ontario and McMaster Universities Arthritis Index (WOMAC) throughout the therapy period. After the 1st session, there was a decrease in INS levels and a mild decrease in PRL levels (P = 0.001 and P < 0.05, respectively). Throughout the 10-session therapy period, the INS levels increased, whereas the ACTH and COR levels decreased (P < 0.05 for all). The VAS-spine, RMDQ, VAS-knee, and WOMAC scores decreased (P = 0.001 for VAS-spine and P < 0.001 for all others). A positive correlation was detected between the changes in serum COR and WOMAC-pain score (P < 0.05). Although the combination therapy caused changes in INS level accompanied with steady glucose levels, the application of physical agents did not adversely affect the hormone levels. The decrease in ACTH and COR levels may be attributed to the analgesic effect of agents and may be an indicator of patient comfort through a central action. PMID:27583888

Phytotoxic effects of nickel on yield and concentration of macro- and micro-nutrients in sunflower (Helianthus annuus L.) achenes.

PubMed

Ahmad, Muhammad Sajid Aqeel; Ashraf, Muhammad; Hussain, Mumtaz

2011-01-30

The phytotoxic effects of varying levels of nickel (0, 10, 20, 30, and 40 mg L(-1)) on growth, yield and accumulation of macro- and micro-nutrients in leaves and achenes of sunflower (Helianthus annuus L.) were appraised in this study. A marked reduction in root and shoot fresh biomass was recorded at higher Ni levels. Nickel stress also caused a substantial decrease in all macro- and micro-nutrients in leaves and achenes. The lower level of Ni (10 mg L(-1)) had a non-significant effect on various yield attributes, but higher Ni levels considerably decreased these parameters. Higher Ni levels decreased the concentrations of Ca, Mn and Fe in achenes. In contrast, achene N, K, Zn, Mn and Cu decreased consistently with increasing level of Ni, even at lower level (10 mg L(-1)). Sunflower hybrid Hysun-33 had better yield and higher most of the nutrients in achenes as compared with SF-187. The maximum reduction in all parameters was observed at the maximum level of nickel (40 mg L(-1)) where almost all parameters were reduced more than 50% of those of control plants. In conclusion, the pattern of uptake and accumulation of different nutrients in sunflower plants were nutrient- and cultivar-specific under Ni-stress. Copyright © 2010 Elsevier B.V. All rights reserved.

Chronic Hyperinsulinaemic Hypoglycaemia in Rats Is Accompanied by Increased Body Weight, Hyperleptinaemia, and Decreased Neuronal Glucose Transporter Levels in the Brain.

PubMed

Jensen, Vivi F H; Mølck, Anne-Marie; Chapman, Melissa; Alifrangis, Lene; Andersen, Lene; Lykkesfeldt, Jens; Bøgh, Ingrid B

2017-01-01

The brain is vulnerable to hypoglycaemia due to a continuous need of energy substrates to meet its high metabolic demands. Studies have shown that severe acute insulin-induced hypoglycaemia results in oxidative stress in the rat brain, when neuroglycopenia cannot be evaded despite increased levels of cerebral glucose transporters. Compensatory measures in the brain during chronic insulin-induced hypoglycaemia are less well understood. The present study investigated how the brain of nondiabetic rats copes with chronic insulin-induced hypoglycaemia for up to eight weeks. Brain level of different substrate transporters and redox homeostasis was evaluated. Hyperinsulinaemia for 8 weeks consistently lowered blood glucose levels by 30-50% (4-6 mM versus 7-9 mM in controls). The animals had increased food consumption, body weights, and hyperleptinaemia. During infusion, protein levels of the brain neuronal glucose transporter were decreased, whereas levels of lipid peroxidation products were unchanged. Discontinued infusion was followed by transient systemic hyperglycaemia and decreased food consumption and body weight. After 4 weeks, plasma levels of lipid peroxidation products were increased, possibly as a consequence of hyperglycaemia-induced oxidative stress. The present data suggests that chronic moderate hyperinsulinaemic hypoglycaemia causes increased body weight and hyperleptinaemia. This is accompanied by decreased neuronal glucose transporter levels, which may be leptin-induced.

Electrically controlled crossing of energy levels in quantum dots in two-dimensional topological insulators

NASA Astrophysics Data System (ADS)

Sukhanov, Aleksei A.

2017-05-01

We study the energy spectra of bound states in quantum dots (QDs) formed by an electrostatic potential in two-dimensional topological insulator (TI) and their transformation with changes in QD depth and radius. It is found that, unlike a trivial insulator, the energy difference between the levels of the ground state and first excited state can decrease with decreasing the radius and increasing the depth of the QD so that these levels intersect under some critical condition. The crossing of the levels results in unusual features of optical properties caused by intraceneter electron transitions. In particular, it leads to significant changes of light absorption due to electron transitions between such levels and to the transient electroluminescence induced by electrical tuning of QD and TI parameters. In the case of magnetic TIs, the polarization direction of the absorbed or emitted circularly polarized light is changed due to the level crossing.

Efficacy of Metarhizium anisopliae isolate MAX-2 from Shangri-la, China under desiccation stress

PubMed Central

2014-01-01

Background Metarhizium anisopliae, a soil-borne entomopathogen found worldwide, is an interesting fungus for biological control. However, its efficacy in the fields is significantly affected by environmental conditions, particularly moisture. To overcome the weakness of Metarhizium and determine its isolates with antistress capacity, the efficacies of four M. anisopliae isolates, which were collected from arid regions of Yunnan Province in China during the dry season, were determined at different moisture levels, and the efficacy of the isolate MAX-2 from Shangri-la under desiccation stress was evaluated at low moisture level. Results M. anisopliae isolates MAX-2, MAC-6, MAL-1, and MAQ-28 showed gradient descent efficacies against sterile Tenebrio molitor larvae, and gradient descent capacities against desiccation with the decrease in moisture levels. The efficacy of MAX-2 showed no significant differences at 35% moisture level than those of the other isolates. However, significant differences were found at 8% to 30% moisture levels. The efficacies of all isolates decreased with the decrease in moisture levels. MAX-2 was relatively less affected by desiccation stress. Its efficacy was almost unaffected by the decrease at moisture levels > 25%, but slowly decreased at moisture levels < 25%. By contrast, the efficacies of other isolates rapidly decreased with the decrease in moisture levels. MAX-2 caused different infection characteristics on T. molitor larvae under desiccation stress and in wet microhabitat. Local black patches were found on the cuticles of the insects, and the cadavers dried without fungal growth under desiccation stress. However, dark black internodes and fungal growth were found after death of the insects in the wet microhabitat. Conclusions MAX-2 showed significantly higher efficacy and superior antistress capacity than the other isolates under desiccation stress. The infection of sterile T. molitor larvae at low moisture level constituted a valid laboratory bioassay system in evaluating M. anisopliae efficacy under desiccation stress. PMID:24383424

Efficacy of Metarhizium anisopliae isolate MAX-2 from Shangri-la, China under desiccation stress.

PubMed

Chen, Zi-Hong; Xu, Ling; Yang, Feng-lian; Ji, Guang-Hai; Yang, Jing; Wang, Jian-Yun

2014-01-03

Metarhizium anisopliae, a soil-borne entomopathogen found worldwide, is an interesting fungus for biological control. However, its efficacy in the fields is significantly affected by environmental conditions, particularly moisture. To overcome the weakness of Metarhizium and determine its isolates with antistress capacity, the efficacies of four M. anisopliae isolates, which were collected from arid regions of Yunnan Province in China during the dry season, were determined at different moisture levels, and the efficacy of the isolate MAX-2 from Shangri-la under desiccation stress was evaluated at low moisture level. M. anisopliae isolates MAX-2, MAC-6, MAL-1, and MAQ-28 showed gradient descent efficacies against sterile Tenebrio molitor larvae, and gradient descent capacities against desiccation with the decrease in moisture levels. The efficacy of MAX-2 showed no significant differences at 35% moisture level than those of the other isolates. However, significant differences were found at 8% to 30% moisture levels. The efficacies of all isolates decreased with the decrease in moisture levels. MAX-2 was relatively less affected by desiccation stress. Its efficacy was almost unaffected by the decrease at moisture levels > 25%, but slowly decreased at moisture levels < 25%. By contrast, the efficacies of other isolates rapidly decreased with the decrease in moisture levels. MAX-2 caused different infection characteristics on T. molitor larvae under desiccation stress and in wet microhabitat. Local black patches were found on the cuticles of the insects, and the cadavers dried without fungal growth under desiccation stress. However, dark black internodes and fungal growth were found after death of the insects in the wet microhabitat. MAX-2 showed significantly higher efficacy and superior antistress capacity than the other isolates under desiccation stress. The infection of sterile T. molitor larvae at low moisture level constituted a valid laboratory bioassay system in evaluating M. anisopliae efficacy under desiccation stress.

Adaptive Adjustment in Taraxacum Officinale Wigg. in the Conditions of Overburden Dump

NASA Astrophysics Data System (ADS)

Legoshchina, Olga; Egorova, Irina; Neverova, Olga

2017-11-01

Morphological and anatomical features of the leaves and roots of Taraxacum officinale Wigg., growing under the conditions of the rocky dump of the Kedrovsky coal mine of the Kemerovo region, were studied. It was revealed that the specific environmental conditions of the dump cause morphological and anatomical changes in the leaves and roots of the dandelion. At the level of morphology, a decrease in the average leaf area, a thickening of leaf blades, a tendency to decrease the number of leaves in the rosette, a significant decrease in the mass and length of the roots. At the level of the anatomical structure of the leaves, there is a significant increase in the thickness of the mesophyll, a tendency to decrease the thickness of the tissues of the upper and lower epidermis, a decrease in the number of cells in 1 mm2 and an increase in the size of stomata in the tissues of the lower and upper epidermis, a decrease in the number of stomata by 1 mm2 and a stomatal index on the upper epidermis. At the level of the anatomical structure of the roots, the radius of the root decreases, the radius of the cortex and phloem, the diameter of the xylem.

Amplitudes of solar modulation of low energy cosmic rays

NASA Technical Reports Server (NTRS)

Von Rosenvinge, T. T.; Paizis, C.

1982-01-01

There have been differences of opinion regarding the origin and behavior of the solar modulation of galactic cosmic rays. It has been shown that the return to solar maximum intensity levels beginning in early 1978 was dominated by Forbush decreases. These Forbush decreases were caused by radially moving interplanetary shocks resulting from large solar flares. The present investigation is concerned with solar modulation effects which were observed during the previous solar minimum. The effects were associated with high-speed streams in the solar wind. These streams caused the formation of corotating interaction regions with both forward and reverse shocks. The modulation effects seen near earth are intimately connected with these shocks.

Inhibition of the ERK phosphorylation plays a role in terbinafine-induced p21 up-regulation and DNA synthesis inhibition in human vascular endothelial cells

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

Ho, P.-Y.; Hsu, S.-P.; Liang, Y.-C.

2008-05-15

Previously, we showed that terbinafine (TB) induces cell-cycle arrest in cultured human umbilical vein endothelial cells (HUVEC) through an up-regulation of the p21 protein. The aim of this study is to delineate the molecular mechanisms underlying TB-induced increase of p21 protein. RT-PCR analysis demonstrated that the mRNA levels of p21 and p53 were increased in the TB-treated HUVEC. The p21 promoter activity was also increased by TB treatment. Transfection of HUVEC with p53 dominant negative (DN) abolished the TB-induced increases of p21 promoter activity and protein level, suggesting that the TB-induced increase of p21 is p53-dependent. Western blot analysis demonstratedmore » that TB decreased the levels of phosphorylated extracellular signal-regulated kinase (ERK). Over-expression of mitogen-activated protein kinase (MEK)-1, the immediate upstream activator kinase of ERK, abolished the TB-induced increases of p21 and p53 protein and decrease of thymidine incorporation. The ERK inhibitor (PD98059) enhanced the TB-induced inhibition of thymidine incorporation into HUVEC. Taken together, these data suggest that the decrease of ERK activity plays a role in the TB-induced up-regulation of p21 in HUVEC. On the other hand, pretreatment of the cells with geranylgeraniol (GGOH), farnesol (FOH), or Ras inhibitor peptide did not affect the TB-induced decrease of thymidine incorporation. Taken together, our results suggest that TB might cause a decrease of MEK, which in turn up-regulates p53 through the inhibition of ERK phosphorylation, and finally causes an increase of p21 expression and cell-cycle arrest.« less

Voxel-based statistical analysis of cerebral glucose metabolism in patients with permanent vegetative state after acquired brain injury.

PubMed

Kim, Yong Wook; Kim, Hyoung Seop; An, Young-Sil; Im, Sang Hee

2010-10-01

Permanent vegetative state is defined as the impaired level of consciousness longer than 12 months after traumatic causes and 3 months after non-traumatic causes of brain injury. Although many studies assessed the cerebral metabolism in patients with acute and persistent vegetative state after brain injury, few studies investigated the cerebral metabolism in patients with permanent vegetative state. In this study, we performed the voxel-based analysis of cerebral glucose metabolism and investigated the relationship between regional cerebral glucose metabolism and the severity of impaired consciousness in patients with permanent vegetative state after acquired brain injury. We compared the regional cerebral glucose metabolism as demonstrated by F-18 fluorodeoxyglucose positron emission tomography from 12 patients with permanent vegetative state after acquired brain injury with those from 12 control subjects. Additionally, covariance analysis was performed to identify regions where decreased changes in regional cerebral glucose metabolism significantly correlated with a decrease of level of consciousness measured by JFK-coma recovery scale. Statistical analysis was performed using statistical parametric mapping. Compared with controls, patients with permanent vegetative state demonstrated decreased cerebral glucose metabolism in the left precuneus, both posterior cingulate cortices, the left superior parietal lobule (P(corrected) < 0.001), and increased cerebral glucose metabolism in the both cerebellum and the right supramarginal cortices (P(corrected) < 0.001). In the covariance analysis, a decrease in the level of consciousness was significantly correlated with decreased cerebral glucose metabolism in the both posterior cingulate cortices (P(uncorrected) < 0.005). Our findings suggest that the posteromedial parietal cortex, which are part of neural network for consciousness, may be relevant structure for pathophysiological mechanism in patients with permanent vegetative state after acquired brain injury.

Beneficial effects of exercise and its molecular mechanisms on depression in rats

PubMed Central

Zheng, Hang; Liu, Yanyou; Li, Wei; Yang, Bo; Chen, Dengbang; Wang, Xiaojia; Jiang, Zhou; Wang, Hongxing; Wang, Zhengrong; Cornelisson, G.; Halberg, F.

2008-01-01

Exercise showed the beneficial effects on mental health in depressed sufferers, whereas, its underlying mechanisms remained unresolved. This study utilized the chronic unpredictable stress (CNS) animal model of depression to evaluate the effects of exercise on depressive behaviors and spatial performance in rats. Furthermore, we tested the hypothesis that the capacity of exercise to reverse the harmful effects of CNS was relative to the hypothalamo–pituitary–adrenal (HPA) system and brain-derived neurotrophic factor (BDNF) in the hippocampus. Animal groups were exposed to CNS for 4 weeks with and without access to voluntary wheel running. Stressed rats consumed significantly less of a 1% sucrose solution during CNS and exhibited a significant decrease in open field behavior. On the other hand, they showed impaired spatial performance in Morris water maze test 2 weeks after the end of CNS. Further, CNS significantly decreased hippocampal BDNF mRNA levels. However, voluntary exercise improved or even reversed these harmful behavioral effects in stressed rats. Furthermore, exercise counteracted a decrease in hippocampal BDNF mRNA caused by CNS. In addition, we also found that CMS alone increased circulating corticosterone (CORT) significantly and decreased hippocampal glucocorticoid receptor (GR) mRNA. At the same time, exercise alone increased CORT moderately and did not affect hippocampal GR mRNA levels. While, when both CNS and exercise were combined, exercise reduced the increase of CORT and the decrease of GR caused by CMS. The results demonstrated that: (1) exercise reversed the harmful effects of CNS on mood and spatial performance in rats and (2) the behavioral changes induced by exercise and/or CNS might be associated with hippocampal BDNF levels, and in addition, the HPA system might play different roles in the two different processes. PMID:16290283

Unraveling the concentration-dependent metabolic response of Pseudomonas sp. HF-1 to nicotine stress by ¹H NMR-based metabolomics.

PubMed

Ye, Yangfang; Wang, Xin; Zhang, Limin; Lu, Zhenmei; Yan, Xiaojun

2012-07-01

Nicotine can cause oxidative damage to organisms; however, some bacteria, for example Pseudomonas sp. HF-1, are resistant to such oxidative stress. In the present study, we analyzed the concentration-dependent metabolic response of Pseudomonas sp. HF-1 to nicotine stress using ¹H NMR spectroscopy coupled with multivariate data analysis. We found that the dominant metabolites in Pseudomonas sp. HF-1 were eight aliphatic organic acids, six amino acids, three sugars and 11 nucleotides. After 18 h of cultivation, 1 g/L nicotine caused significant elevation of sugar (glucose, trehalose and maltose), succinate and nucleic acid metabolites (cytidine, 5'-CMP, guanine 2',3'-cyclic phosphate and adenosine 2',3'-cyclic phosphate), but decrease of glutamate, putrescine, pyrimidine, 2-propanol, diethyl ether and acetamide levels. Similar metabolomic changes were induced by 2 g/L nicotine, except that no significant change in trehalose, 5'-UMP levels and diethyl ether were found. However, 3 g/L nicotine led to a significant elevation in the two sugars (trehalose and maltose) levels and decrease in the levels of glutamate, putrescine, pyrimidine and 2-propanol. Our findings indicated that nicotine resulted in the enhanced nucleotide biosynthesis, decreased glucose catabolism, elevated succinate accumulation, severe disturbance in osmoregulation and complex antioxidant strategy. And a further increase of nicotine level was a critical threshold value that triggered the change of metabolic flow in Pseudomonas sp. HF-1. These findings revealed the comprehensive insights into the metabolic response of nicotine-degrading bacteria to nicotine-induced oxidative toxicity.

Multimodel Assessment of the Factors Driving Stratospheric Ozone Evolution over the 21st Century

NASA Technical Reports Server (NTRS)

Oman, L. D.; Plummer, D. A.; Waugh, D. W.; Austin, J.; Scinocca, J. F.; Douglass, A. R.; Salawitch, R. J.; Canty, T.; Akiyoshi, H.; Bekki, S.;

Omega-3 polyunsaturated fatty acid docosahexaenoic acid and its role in exhaustive-exercise-induced changes in female rat ovulatory cycle.

PubMed

Mostafa, Abeer F; Samir, Shereen M; Nagib, R M

2018-04-01

Exhaustive exercises can cause delayed menarche or menstrual cycle irregularities in females. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are incorporated into a wide range of benefits in many physiological systems. Our work aimed to assess the role of ω-3 PUFA docosahexaenoic acid (DHA) on the deleterious effects of exhaustive exercise on the female reproductive system in rats. Virgin female rats were randomly divided into 4 groups (12 rats in each): control group, omega-3 group treated with DHA, exhaustive exercise group, and exhaustive exercised rats treated with DHA. Omega-3 was given orally to the rats once daily for 4 estrous cycles. Exhaustive exercises revealed lower levels in progesterone and gonadotropins together with histopathological decrease in number of growing follicles and corpora lutea. Moreover, the exercised rats showed low levels of ovarian antioxidants with high level of caspase-3 and plasma cortisol level that lead to disruption of hypothalamic-pituitary-gonadal axis. ω-3 PUFA DHA has beneficial effects on the number of newly growing follicles in both sedentary and exercised rats with decreasing the level of caspase-3 and increasing the antioxidant activity in ovaries. Exhaustive exercises can cause ovulatory problems in female rats that can be improved by ω-3 supplementation.

EFFECTS OF THE ORGANOCHLORINE PESTICIDE METHOXYCHLOR ON DOPAMINE METABOLITES AND TRANSPORTERS IN THE MOUSE BRAIN

PubMed Central

Schuh, Rosemary A.; Richardson, Jason R.; Gupta, Rupesh K.; Flaws, Jodi A.; Fiskum, Gary

2009-01-01

Pesticide exposure has been suggested as an increased risk factor in developing Parkinson’s disease (PD). While the molecular mechanism underlying this association is not clear, several studies have demonstrated a role for mitochondrial dysfunction and oxidative damage in PD. Although data on specific pesticides associated with PD are often lacking, several lines of evidence point to the potential involvement of the organochlorine class of pesticides. Previously, we have found that the organochlorine pesticide methoxychlor (mxc) causes mitochondrial dysfunction and oxidative stress in isolated mitochondria. Here, we sought to determine whether mxc-induced mitochondrial dysfunction results in oxidative damage and dysfunction of the dopamine system. Adult female CD1 mice were dosed with either vehicle (sesame oil) or mxc (16, 32, or 64 mg/kg/day) for 20 consecutive days. Following treatment, we observed a dose-related increase in protein carbonyl levels in non-synaptic mitochondria, indicating oxidative modification of mitochondrial proteins which may lead to mitochondrial dysfunction. Mxc exposure also caused a dose-related decrease in striatal levels of dopamine (16–31%), which were accompanied by decreased levels of the dopamine transporter (DAT; 35–48%) and the vesicular monoamine transporter 2 (VMAT2; 21–44%). Because mitochondrial dysfunction, oxidative damage, and decreased levels of DAT and VMAT2 are found in PD patients, our data suggests that mxc should be investigated as a possible candidate involved in the association of pesticides with increased risk for PD, particularly in highly-exposed populations. PMID:19459224

Coagulopathy in Zellweger spectrum disorders: a role for vitamin K.

PubMed

Zeynelabidin, Sara; Klouwer, Femke C C; Meijers, Joost C M; Suijker, Monique H; Engelen, Marc; Poll-The, Bwee Tien; van Ommen, C Heleen

2018-03-01

Zellweger spectrum disorders (ZSDs) are caused by an impairment of peroxisome biogenesis, resulting in multiple metabolic abnormalities. This leads to a range of symptoms, including hepatic dysfunction and coagulopathy. This study evaluated the incidence and severity of coagulopathy and the effect of vitamin K supplementation orally and IV in ZSD. Data were retrospectively retrieved from the medical records of 30 ZSD patients to study coagulopathy and the effect of vitamin K orally on proteins induced by vitamin K absence (PIVKA-II) levels. Five patients from the cohort with a prolonged prothrombin time, low factor VII, and elevated PIVKA-II levels received 10 mg of vitamin K IV. Laboratory results, including thrombin generation, at baseline and 72 h after vitamin K administration were examined. In the retrospective cohort, four patients (13.3%) experienced intracranial bleedings and 14 (46.7%) reported minor bleeding. No thrombotic events occurred. PIVKA-II levels decreased 38% after start of vitamin K therapy orally. In the five patients with a coagulopathy, despite treatment with oral administration of vitamin K, vitamin K IV caused an additional decrease (23%) of PIVKA-II levels and increased thrombin generation. Bleeding complications frequently occur in ZSD patients due to liver disease and vitamin K deficiency. Vitamin K deficiency is partly corrected by vitamin K supplementation orally, and vitamin K administered IV additionally improves vitamin K status, as shown by further decrease of PIVKA-II and improved thrombin generation.

Ozone-Induced Rice Grain Yield Loss Is Triggered via a Change in Panicle Morphology That Is Controlled by ABERRANT PANICLE ORGANIZATION 1 Gene

PubMed Central

Tsukahara, Keita; Sawada, Hiroko; Kohno, Yoshihisa; Matsuura, Takakazu; Mori, Izumi C.; Terao, Tomio; Ioki, Motohide; Tamaoki, Masanori

2015-01-01

Rice grain yield is predicted to decrease in the future because of an increase in tropospheric ozone concentration. However, the underlying mechanisms are unclear. Here, we investigated the responses to ozone of two rice (Oryza Sativa L.) cultivars, Sasanishiki and Habataki. Sasanishiki showed ozone-induced leaf injury, but no grain yield loss. By contrast, Habataki showed grain yield loss with minimal leaf injury. A QTL associated with grain yield loss caused by ozone was identified in Sasanishiki/Habataki chromosome segment substitution lines and included the ABERRANT PANICLE ORGANIZATION 1 (APO1) gene. The Habataki allele of the APO1 locus in a near-isogenic line also resulted in grain yield loss upon ozone exposure, suggesting APO1 involvement in ozone-induced yield loss. Only a few differences in the APO1 amino acid sequences were detected between the cultivars, but the APO1 transcript level was oppositely regulated by ozone exposure: i.e., it increased in Sasanishiki and decreased in Habataki. Interestingly, the levels of some phytohormones (jasmonic acid, jasmonoyl-L-isoleucine, and abscisic acid) known to be involved in attenuation of ozone-induced leaf injury tended to decrease in Sasanishiki but to increase in Habataki upon ozone exposure. These data indicate that ozone-induced grain yield loss in Habataki is caused by a reduction in the APO1 transcript level through an increase in the levels of phytohormones that reduce leaf damage. PMID:25923431

Long-term administration with levonorgestrel decreases allopregnanolone levels and alters GABA(A) receptor subunit expression and anxiety-like behavior.

PubMed

Porcu, Patrizia; Mostallino, Maria Cristina; Sogliano, Cristiana; Santoru, Francesca; Berretti, Roberta; Concas, Alessandra

2012-08-01

Fluctuations in the concentrations of the neuroactive steroid allopregnanolone are thought to influence γ-amino-butyric acid type A (GABA(A)) receptor gene expression and function. Long-term treatment with ethinyl estradiol (EE) plus levonorgestrel (LNG), two of the most widely used steroids in the hormonal contraceptive pill, decreases allopregnanolone levels in rat cerebral cortex and plasma, alters GABA(A) receptor expression and induces anxiety-like behavior. We evaluated which component of the hormonal contraceptive pill is responsible for the aforementioned changes. Female rats were injected subcutaneously (s.c.) with EE (0.030 mg) or LNG (0.125 mg) once a day for 4 weeks. Compared to the respective vehicle-treated control groups, EE decreased cerebral cortical levels of allopregnanolone, progesterone and pregnenolone by 76, 72 and 33%, respectively and hippocampal levels by 52, 56 and 50%, respectively. Likewise, LNG decreased cerebral cortical levels of allopregnanolone, progesterone and pregnenolone by 75, 68 and 33%, respectively, and hippocampal levels by 55, 65 and 60%, respectively. Administration of LNG, but not EE, increased the abundance of the γ2 subunit peptide in cerebral cortex and hippocampus by 38 and 59%, respectively. Further, LNG, but not EE, decreased the time spent and the number of entries into the open arms of the elevated plus maze by 56 and 43%, respectively, an index of anxiety-like behavior. These results suggest that alterations in GABA(A) receptor subunit expression and anxiety-like behavior induced by long-term treatment with combined EE/LNG appear to be caused by LNG. Given that both EE and LNG decrease allopregnanolone levels in a similar manner, these results further suggest that changes in allopregnanolone levels are not associated with GABA(A) receptor expression. Copyright © 2012 Elsevier Inc. All rights reserved.

Effects of Elevated CO2 and Temperature on Yield and Fruit Quality of Strawberry (Fragaria × ananassa Duch.) at Two Levels of Nitrogen Application

PubMed Central

Sun, Peng; Mantri, Nitin; Lou, Heqiang; Hu, Ya; Sun, Dan; Zhu, Yueqing; Dong, Tingting; Lu, Hongfei

2012-01-01

We investigated if elevated CO2 could alleviate the negative effect of high temperature on fruit yield of strawberry (Fragaria × ananassa Duch. cv. Toyonoka) at different levels of nitrogen and also tested the combined effects of CO2, temperature and nitrogen on fruit quality of plants cultivated in controlled growth chambers. Results show that elevated CO2 and high temperature caused a further 12% and 35% decrease in fruit yield at low and high nitrogen, respectively. The fewer inflorescences and smaller umbel size during flower induction caused the reduction of fruit yield at elevated CO2 and high temperature. Interestingly, nitrogen application has no beneficial effect on fruit yield, and this may be because of decreased sucrose export to the shoot apical meristem at floral transition. Moreover, elevated CO2 increased the levels of dry matter-content, fructose, glucose, total sugar and sweetness index per dry matter, but decreased fruit nitrogen content, total antioxidant capacity and all antioxidant compounds per dry matter in strawberry fruit. The reduction of fruit nitrogen content and antioxidant activity was mainly caused by the dilution effect of accumulated non-structural carbohydrates sourced from the increased net photosynthetic rate at elevated CO2. Thus, the quality of strawberry fruit would increase because of the increased sweetness and the similar amount of fruit nitrogen content, antioxidant activity per fresh matter at elevated CO2. Overall, we found that elevated CO2 improved the production of strawberry (including yield and quality) at low temperature, but decreased it at high temperature. The dramatic fluctuation in strawberry yield between low and high temperature at elevated CO2 implies that more attention should be paid to the process of flower induction under climate change, especially in fruits that require winter chilling for reproductive growth. PMID:22911728

Aldosterone and parathyroid hormone: a precarious couple for cardiovascular disease.

PubMed

Tomaschitz, Andreas; Ritz, Eberhard; Pieske, Burkert; Fahrleitner-Pammer, Astrid; Kienreich, Katharina; Horina, Jörg H; Drechsler, Christiane; März, Winfried; Ofner, Michael; Pieber, Thomas R; Pilz, Stefan

2012-04-01

Animal and human studies support a clinically relevant interaction between aldosterone and parathyroid hormone (PTH) levels and suggest an impact of the interaction on cardiovascular (CV) health. This review focuses on mechanisms behind the bidirectional interactions between aldosterone and PTH and their potential impact on the CV system. There is evidence that PTH increases the secretion of aldosterone from the adrenals directly as well as indirectly by activating the renin-angiotensin system. Upregulation of aldosterone synthesis might contribute to the higher risk of arterial hypertension and of CV damage in patients with primary hyperparathyroidism. Furthermore, parathyroidectomy is followed by decreased blood pressure levels and reduced CV morbidity as well as lower renin and aldosterone levels. In chronic heart failure, the aldosterone activity is inappropriately elevated, causing salt retention; it has been argued that the resulting calcium wasting causes secondary hyperparathyroidism. The ensuing intracellular calcium overload and oxidative stress, caused by PTH and amplified by the relative aldosterone excess, may increase the risk of CV events. In the setting of primary aldosteronism, renal and faecal calcium loss triggers increased PTH secretion which in turn aggravates aldosterone secretion and CV damage. This sequence explains why adrenalectomy and blockade of the mineralocorticoid receptor tend to decrease PTH levels in patients with primary aldosteronism. In view of the reciprocal interaction between aldosterone and PTH and the potentially ensuing CV damage, studies are urgently needed to evaluate diagnostic and therapeutic strategies addressing the interaction between the two hormones.

Brain dialysis: in vivo metabolism of dopamine and serotonin by monoamine oxidase A but not B in the striatum of unrestrained rats.

PubMed

Kato, T; Dong, B; Ishii, K; Kinemuchi, H

1986-04-01

A dialysis cannula was implanted into rat striatum while the animals were anesthetized, and the area was perfused with Ringer solution while the animals were unanesthetized after at least 3 days following surgery. Concentrations of the metabolites of 3,4-dihydroxyphenylethylamine (DA) and 5-hydroxytryptamine (5-HT) in the perfusate were determined by HPLC with electrochemical detection. Levels of the DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the perfusate significantly decreased after pargyline administration (50 mg/kg i.p.), which may inhibit not only monoamine oxidase (MAO)-B but also MAO-A in these high doses. The level of the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) also decreased after pargyline treatment, although change in the relative level of 5-HIAA was less than that of DOPAC or HVA. To clarify the mechanisms for the metabolism of monoamines in rat striatum, highly specific MAO-A and -B inhibitors were used in the following experiments. Treatment with l-deprenyl (10 mg/kg), a specific inhibitor for MAO-B, did not cause any statistically significant change in DOPAC, HVA, and 5-HIAA levels. No significant change was found in rat striatal homogenates at 2 h after the same treatment with l-deprenyl. In contrast, low-dose treatment (1 mg/kg) with clorgyline, a specific inhibitor for MAO-A, caused a significant decrease in levels of these three metabolites in both the perfusates and tissue homogenates. In addition to the above three metabolites, the level of 3-methoxytyramine, which is an indicator of the amount of DA released, greatly increased after treatment with a low dose (1 mg/kg) of clorgyline.(ABSTRACT TRUNCATED AT 250 WORDS)

Epigenetic silencing of miR-218 by the lncRNA CCAT1, acting via BMI1, promotes an altered cell cycle transition in the malignant transformation of HBE cells induced by cigarette smoke extract

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

Lu, Lu; Xu, Hui; Luo, Fei

Cigarette smoking is the strongest risk factor for the development of lung cancer, the leading cause of cancer-related deaths. However, the molecular mechanisms leading to lung cancer are largely unknown. A long-noncoding RNA (lncRNA), CCAT1, regarded as cancer-associated, has been investigated extensively. Moreover, the molecular mechanisms of lncRNAs in regulation of microRNAs (miRNAs) induced by cigarette smoke remain unclear. In the present investigation, cigarette smoke extract (CSE) caused an altered cell cycle and increased CCAT1 levels and decreased miR-218 levels in human bronchial epithelial (HBE) cells. Depletion of CCAT1 attenuated the CSE-induced decreases of miR-218 levels, suggesting that miR-218 ismore » negatively regulated by CCAT1 in HBE cells exposed to CSE. The CSE-induced increases of BMI1 levels and blocked by CCAT1 siRNA were attenuated by an miR-218 inhibitor. Moreover, in CSE-transformed HBE cells, the CSE-induced cell cycle changes and elevated neoplastic capacity were reversed by CCAT1 siRNA or BMI1 siRNA. This epigenetic silencing of miR-218 by CCAT1 induces an altered cell cycle transition through BMI1 and provides a new mechanism for CSE-induced lung carcinogenesis. - Highlights: • CSE exposure induces increases of CCAT1 levels and decreases of miR-218 levels. • CCAT1 negatively regulates miR-218 expression. • CCAT1, regulated by miR-218, via BMI1, is involved in the CSE-induced altered cell cycle transition.« less

Sea level during the Phanerozoic - what causes the fluctuations

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

Harrison, C.G.A.

1985-01-01

All possible causes of sea level change have been analyzed in order to explain the fall of sea level since the Cretaceous. The most important effect is the decrease in volume of the ridge crests due to an overall decrease in the rate of spreading since the Cretaceous. Other factors in order of decreasing importance are the reduction of the thermal bulge which accompanied the episode of Pacific volcanism between 110 and 70 my bp, the production of continental ice, the effect of the collision of India with Asia, and cooling of the ocean water. Sedimentation variation in the deepmore » ocean has the effect of raising sea level a modest amount. The net variation in sea level during the past 80 million years has been a reduction by about 280 m after having allowed for isostatic adjustment of the ocean floor. This is considerably larger, than sea level calculated from the amount of continental flooding, and it is proposed that the discrepancy is due to a change in the continental hypsographic curve following the breakup of Pangea. This hypothesis is born out by studies of flooding during the Phanerozoic which reveal that flooding was very low at the beginning of the Mesozoic during a time of continental agglomeration, and high during much of the Paleozoic, which was a time of continental separation. In the Cambrian there is evidence for an increase in flooding with time, and at the beginning of the Cambrian flooding was not much greater than at the beginning of the Mesozoic, suggesting that it marked a time just subsequent to the break up of a super continent.« less

Effects of Six Weeks Endurance Training and Aloe Vera Supplementation on COX-2 and VEGF Levels in Mice with Breast Cancer

PubMed

Shirali, Saeed; Barari, Alireza; Hosseini, Seyed Ahmad; Khodadi, Elaheh

2017-01-01

The aim of this study was to determine effects of six weeks endurance training and Aloe Vera supplementation on COX-2 and VEGF levels in mice with breast cancer. For this purpose, 35 rats were randomly divided into 5 groups: control (healthy) and 4 cancer groups: control (cancer only), training, Aloe Vera and Aloe Vera + training. Breast cancer tumors were generated in mice by implantind. The training program comprised six weeks of swimming training accomplished in three sessions per week. Training time started with 10 minutes on the first day and increased to 60 minutes in the second week and the water flow rate was increased from 7 to 15 liters per minute at a constant rate. Aloe Vera extract at a dose of 300 mg/kg BW was administrated to rats by intraperitoneal injection. At the end of the study period, rats were anesthetized and blood samples were taken. Significant differences were concluded at p<0.05 with Kolmogorov-Smirnov and Tukey tests to analyze the data. The results showed significant increase in levels of serum. COX-2 and VEGF levels in the cancer group compared with the healthy group. Administration of Aloe Vera extract caused significant decrease in the COX-2 level in the cancer group. Also, in the training (swimming exercise) and Aloe Vera + training cancer groups, we observed significant decrease in the VEGF level as compared to controls. Our results suggest that Aloe Vera and training inhibit the COX pathway and cause decrease production of prostaglandin E2. Hence administration of Aloe Vera in combination with endurance training might synergistically improve the host milieu in mice bearing breast cancers. Creative Commons Attribution License

Relation of Total and Cardiovascular Death Rates to Climate System, Temperature, Barometric Pressure, and Respiratory Infection.

PubMed

Schwartz, Bryan G; Qualls, Clifford; Kloner, Robert A; Laskey, Warren K

2015-10-15

A distinct seasonal pattern in total and cardiovascular death rates has been reported. The factors contributing to this pattern have not been fully explored. Seven locations (average total population 71,354,000) were selected where data were available including relatively warm, cold, and moderate temperatures. Over the period 2004 to 2009, there were 2,526,123 all-cause deaths, 838,264 circulatory deaths, 255,273 coronary heart disease deaths, and 135,801 ST-elevation myocardial infarction (STEMI) deaths. We used time series and multivariate regression modeling to explore the association between death rates and climatic factors (temperature, dew point, precipitation, barometric pressure), influenza levels, air pollution levels, hours of daylight, and day of week. Average seasonal patterns for all-cause and cardiovascular deaths were very similar across the 7 locations despite differences in climate. After adjusting for multiple covariates and potential confounders, there was a 0.49% increase in all-cause death rate for every 1°C decrease. In general, all-cause, circulatory, coronary heart disease and STEMI death rates increased linearly with decreasing temperatures. The temperature effect varied by location, including temperature's linear slope, cubic fit, positional shift on the temperature axis, and the presence of circulatory death increases in locally hot temperatures. The variable effect of temperature by location suggests that people acclimatize to local temperature cycles. All-cause and circulatory death rates also demonstrated sizable associations with influenza levels, dew point temperature, and barometric pressure. A greater understanding of how climate, temperature, and barometric pressure influence cardiovascular responses would enhance our understanding of circulatory and STEMI deaths. Copyright © 2015 Elsevier Inc. All rights reserved.

Dramatic water-level fluctuations in lakes under intense human impact: modelling the effect of vegetation, climate and hydrogeology

NASA Astrophysics Data System (ADS)

Vainu, M.

2012-04-01

Lakes form a highly important ecosystem in the glacial terrain of northern Europe and America, but their hydrology remains understudied. When the water-level of a lake drops significantly and rises again in a time span of half a century and the widespread explanation of the fluctuations seems insufficient, then it raises a question: how do different anthropogenic and natural processes actually affect the formation of a lakes' water body. The abovementioned scenario applies to three small closed-basin Estonian lakes (L. Ahnejärv, L. Kuradijärv and L. Martiska) analysed in the current study. These lakes suffered a major water-level drop (up to 3.8 m) between 1946 and 1987 and a major rise between 1987 and 2010, from 1 m (L. Ahnejärv) to 2.5 m (L. Kuradijärv). Decreasing and increasing groundwater abstraction near the lakes has been widely considered to be the only reason for the fluctuations. It is true that the most severe drop in the lake levels did occur after 1972 when groundwater abstraction for drinking water started in the vicinity of the lakes. However, the lake levels started to fall before the groundwater abstraction began and for the time being the lake levels have risen to a higher level than in the 1970s when the quantity of annually abstracted groundwater was similar to nowadays. Therefore the processes affecting the formation of the lakes' water body prove to be more complex than purely the hydrogeological change caused by groundwater abstraction. A new deterministic water balance model (where the evaporation from the lake surface was calculated by Penman equation and the catchment runoff by Thornthwaite-Mather soil-moisture model), compiled for the study, coupled with LiDAR-based GIS-modelling of the catchments was used to identify the different factors influencing the lakes' water level. The modelling results reveal that the moderate drop in lake water levels before the beginning of groundwater abstraction was probably caused by the growth of a coniferous forest on the lake catchments, due to which evapotranspiration and subsequently runoff from the catchment decreased. The forest had been destroyed by wildfires during World War II. The water-level rise that the lakes have gone through in the last 20 years has in the case of L. Ahnejärv been caused by changing meteorological conditions (precipitation, air temperature and wind speed). In the case of Lakes Kuradijärv and Martiska the change has been caused by both the raise of groundwater level (caused by the decreasing groundwater abstraction) and the change of meteorological conditions. Therefore the vegetation change on the catchment and changes in meteorological conditions have played as important or, at times, even more important role in the water-level fluctuations than changes in the hydrogeological conditions. Although concentrating on three specific lakes in a specific region, the result of the study indicate the complexity of factors influencing the amount of water stored in a lake at a certain moment. Therefore it manifests a need for improved models in order to improve lake management around the world.

Red blood cell decreases of microgravity

NASA Technical Reports Server (NTRS)

Johnson, P. C.

1985-01-01

Postflight decreases in red blood cell mass (RBCM) have regularly been recorded after exposure to microgravity. These 5-25 percent decreases do not relate to the mission duration, workload, caloric intake or to the type of spacecraft used. The decrease is accompanied by normal red cell survivals, increased ferritin levels, normal radioactive iron studies, and increases in mean red blood cell volume. Comparable decreases in red blood cell mass are not found after bed rest, a commonly used simulation of the microgravity state. Inhibited bone marrow erythropoiesis has not been proven to date, although reticulocyte numbers in the peripheral circulation are decreased about 50 percent. To date, the cause of the microgravity induced decreases in RBCM is unknown. Increased splenic trapping of circulating red blood cells seem the most logical way to explain the results obtained.

Muscle Dysfunction in Androgen Deprivation: Role of Ryanodine Receptor

DTIC Science & Technology

2016-11-01

undergoing ORX have reduced muscle specific force due to calcium leak through RyR1, which is caused by high levels of TGFβ released from the bone during... leak could be causing long-term effects, such as decreased muscle mass, body weight and forelimb grip strength. 15. SUBJECT TERMS Prostate Cancer...calcium leak and contractile dysfunction in chronic muscle fatigue, heart failure and muscular dystrophy (13-16). RyR1 is the skeletal muscle

Low physical activity as a predictor for total and cardiovascular disease mortality in middle-aged men and women in Finland.

PubMed

Barengo, Noël C; Hu, Gang; Lakka, Timo A; Pekkarinen, Heikki; Nissinen, Aulikki; Tuomilehto, Jaakko

2004-12-01

To investigate separately for men and women whether moderate or high leisure time physical activity, occupational physical activity, and commuting activity are associated with a reduced cardiovascular disease (CVD) and all-cause mortality, independent of CVD risk factors and other forms of physical activity. Prospective follow-up of 15,853 men and 16,824 women aged 30-59 years living in eastern and south-western Finland (median follow-up time 20 years). CVD and all-cause mortality were lower (9-21%) in men and women (2-17%) who were moderately or highly physically active during leisure time. Moderate and high levels of occupational physical activity decreased CVD and all-cause mortality by 21-27% in both sexes. Women spending daily 15 min or more in walking or cycling to and from work had a reduced CVD and all-cause mortality before adjustment for occupational and leisure time physical activity. Commuting activity was not associated with CVD or all-cause mortality in men. Moderate and high levels of leisure time and occupational physical activity are associated with a reduced CVD and all-cause mortality among both sexes. Promoting already moderate levels of leisure time and occupational physical activity are essential to prevent premature CVD and all-cause mortality.

Endogenous GABA levels in the pontine reticular formation are greater during wakefulness than during rapid eye movement sleep.

PubMed

Vanini, Giancarlo; Wathen, Bradley L; Lydic, Ralph; Baghdoyan, Helen A

2011-02-16

Studies using drugs that increase or decrease GABAergic transmission suggest that GABA in the pontine reticular formation (PRF) promotes wakefulness and inhibits rapid eye movement (REM) sleep. Cholinergic transmission in the PRF promotes REM sleep, and levels of endogenous acetylcholine (ACh) in the PRF are significantly greater during REM sleep than during wakefulness or non-REM (NREM) sleep. No previous studies have determined whether levels of endogenous GABA in the PRF vary as a function of sleep and wakefulness. This study tested the hypothesis that GABA levels in cat PRF are greatest during wakefulness and lowest during REM sleep. Extracellular GABA levels were measured during wakefulness, NREM sleep, REM sleep, and the REM sleep-like state (REM(Neo)) caused by microinjecting neostigmine into the PRF. GABA levels varied significantly as a function of sleep and wakefulness, and decreased significantly below waking levels during REM sleep (-42%) and REM(Neo) (-63%). The decrease in GABA levels during NREM sleep (22% below waking levels) was not statistically significant. Compared with NREM sleep, GABA levels decreased significantly during REM sleep (-27%) and REM(Neo) (-52%). Comparisons of REM sleep and REM(Neo) revealed no differences in GABA levels or cortical EEG power. GABA levels did not vary significantly as a function of dialysis site within the PRF. The inverse relationship between changes in PRF levels of GABA and ACh during REM sleep indicates that low GABAergic tone combined with high cholinergic tone in the PRF contributes to the generation of REM sleep.

Endogenous GABA levels in the pontine reticular formation are greater during wakefulness than during REM sleep

PubMed Central

Vanini, Giancarlo; Wathen, Bradley L.; Lydic, Ralph; Baghdoyan, Helen A.

2011-01-01

Studies using drugs that increase or decrease GABAergic transmission suggest that GABA in the pontine reticular formation (PRF) promotes wakefulness and inhibits rapid eye movement (REM) sleep. Cholinergic transmission in the PRF promotes REM sleep, and levels of endogenous acetylcholine (ACh) in the PRF are significantly greater during REM sleep than during wakefulness or non-REM (NREM) sleep. No previous studies have determined whether levels of endogenous GABA in the PRF vary as a function of sleep and wakefulness. This study tested the hypothesis that GABA levels in cat PRF are greatest during wakefulness and lowest during REM sleep. Extracellular GABA levels were measured during wakefulness, NREM sleep, REM sleep, and the REM sleep-like state (REMNeo) caused by microinjecting neostigmine into the PRF. GABA levels varied significantly as a function of sleep and wakefulness, and decreased significantly below waking levels during REM sleep (−42%) and REMNeo (−63%). The decrease in GABA levels during NREM sleep (22% below waking levels) was not statistically significant. Compared to NREM sleep, GABA levels decreased significantly during REM sleep (−27%) and REMNeo (−52%). Comparisons of REM sleep and REMNeo revealed no differences in GABA levels or cortical EEG power. GABA levels did not vary significantly as a function of dialysis site within the PRF. The inverse relationship between changes in PRF levels of GABA and ACh during REM sleep indicates that low GABAergic tone combined with high cholinergic tone in the PRF contributes to the generation of REM sleep. PMID:21325533

Direct and indirect effects of the fungicide Carbendazim in tropical freshwater microcosms.

PubMed

Daam, Michiel A; Satapornvanit, Kriengkrai; Van den Brink, Paul J; Nogueira, António J A

2010-02-01

Direct and indirect effects of the fungicide carbendazim on ecosystem structure and functioning were studied < or =8 weeks after application (nominal concentrations: 0, 3.3, 33, 100, and 1000 microg/L) to outdoor microcosms in Thailand. Direct effects on macroinvertebrates are discussed in detail in a separate article. The present article presents the effects on other end points and discusses the hypothesized ecologic effect chain. Negative treatment effects on the zooplankton community were only recorded for the highest carbendazim treatment (NOEC(community) = 100 microg/L). The rotifer Keratella tropica, cladocerans (Moina micrura, Ceriodaphnia cornuta, and Diaphanosoma sp.), and cyclopoid copepods were decreased or even eliminated at this treatment level. The decrease in zooplankton and macroinvertebrate abundances was accompanied by an increase in numbers of several tolerant invertebrates, presumably caused by a release from competition and predation. The death of sensitive invertebrates probably also led to an overall decreased grazing pressure because increased levels of chlorophyll-a and bloom of the floating macrophyte Wolffia sp. were noted. The increase in primary producers is discussed to be the probable cause of changes in physicochemical water conditions, eventually resulting in an anoxic water layer during the last 3 weeks of the experiment. This is likely to have resulted in decreased invertebrate abundances noted in that period. Furthermore, the decreased decomposition of Musa (banana) leaves observed 8 weeks after application is considered to be the indirect effect of a decreased microbial activity resulting from these anoxic water conditions, rather than a direct toxic effect of carbendazim.

Advanced Analysis to Distinguish between Physical Decrease and Inactivation of Viable Phages in Aerosol by Quantitating Phage-Specific Particles.

PubMed

Shimasaki, Noriko; Nojima, Yasuhiro; Sakakibara, Masaya; Kikuno, Ritsuko; Iizuka, Chiori; Okaue, Akira; Okuda, Shunji; Shinohara, Katsuaki

2018-01-01

　Recent studies have investigated the efficacy of air-cleaning products against pathogens in the air. A standard method to evaluate the reduction in airborne viruses caused by an air cleaner has been established using a safe bacteriophage instead of pathogenic viruses; the reduction in airborne viruses is determined by counting the number of viable airborne phages by culture, after operating the air cleaner. The reduction in the number of viable airborne phages could be because of "physical decrease" or "inactivation". Therefore, to understand the mechanism of reduction correctly, an analysis is required to distinguish between physical decrease and inactivation. The purpose of this study was to design an analysis to distinguish between the physical decrease and inactivation of viable phi-X174 phages in aerosols. We established a suitable polymerase chain reaction (PCR) system by selecting an appropriate primer-probe set for PCR and validating the sensitivity, linearity, and specificity of the primer-probe set to robustly quantify phi-X174-specific airborne particles. Using this quantitative PCR system and culture assay, we performed a behavior analysis of the phage aerosol in a small chamber (1 m 3 ) at different levels of humidity, as humidity is known to affect the number of viable airborne phages. The results revealed that the reduction in the number of viable airborne phages was caused not only by physical decrease but also by inactivation under particular levels of humidity. Our study could provide an advanced analysis to differentiate between the physical decrease and inactivation of viable airborne phages.

Predictive Control of the Blood Glucose Level in Type I Diabetic Patient Using Delay Differential Equation Wang Model.

PubMed

Esna-Ashari, Mojgan; Zekri, Maryam; Askari, Masood; Khalili, Noushin

2017-01-01

Because of increasing risk of diabetes, the measurement along with control of blood sugar has been of great importance in recent decades. In type I diabetes, because of the lack of insulin secretion, the cells cannot absorb glucose leading to low level of glucose. To control blood glucose (BG), the insulin must be injected to the body. This paper proposes a method for BG level regulation in type I diabetes. The control strategy is based on nonlinear model predictive control. The aim of the proposed controller optimized with genetics algorithms is to measure BG level each time and predict it for the next time interval. This merit causes a less amount of control effort, which is the rate of insulin delivered to the patient body. Consequently, this method can decrease the risk of hypoglycemia, a lethal phenomenon in regulating BG level in diabetes caused by a low BG level. Two delay differential equation models, namely Wang model and Enhanced Wang model, are applied as controller model and plant, respectively. The simulation results exhibit an acceptable performance of the proposed controller in meal disturbance rejection and robustness against parameter changes. As a result, if the nutrition of the person decreases instantly, the hypoglycemia will not happen. Furthermore, comparing this method with other works, it was shown that the new method outperforms previous studies.

Predictive Control of the Blood Glucose Level in Type I Diabetic Patient Using Delay Differential Equation Wang Model

PubMed Central

Esna-Ashari, Mojgan; Zekri, Maryam; Askari, Masood; Khalili, Noushin

2017-01-01

Because of increasing risk of diabetes, the measurement along with control of blood sugar has been of great importance in recent decades. In type I diabetes, because of the lack of insulin secretion, the cells cannot absorb glucose leading to low level of glucose. To control blood glucose (BG), the insulin must be injected to the body. This paper proposes a method for BG level regulation in type I diabetes. The control strategy is based on nonlinear model predictive control. The aim of the proposed controller optimized with genetics algorithms is to measure BG level each time and predict it for the next time interval. This merit causes a less amount of control effort, which is the rate of insulin delivered to the patient body. Consequently, this method can decrease the risk of hypoglycemia, a lethal phenomenon in regulating BG level in diabetes caused by a low BG level. Two delay differential equation models, namely Wang model and Enhanced Wang model, are applied as controller model and plant, respectively. The simulation results exhibit an acceptable performance of the proposed controller in meal disturbance rejection and robustness against parameter changes. As a result, if the nutrition of the person decreases instantly, the hypoglycemia will not happen. Furthermore, comparing this method with other works, it was shown that the new method outperforms previous studies. PMID:28487828

The protective effects of pomegranate on liver and remote organs caused by experimental obstructive jaundice model.

PubMed

Yilmaz, E E; Arikanoğlu, Z; Turkoğlu, A; Kiliç, E; Yüksel, H; Gümüş, M

2016-01-01

We aimed to investigate the protective potential of pomegranate extract on the liver and remote organs in rats with obstructive jaundice. The rats were split into 4 groups. In Group 1 (G1) (sham group) rats, the common bile duct was mobilized without any ligation. Group 2 (G2) received a combination of the sham operation and synchronous treatment with pomegranate. Group 3 (G3) received common bile duct ligation (CBDL). Group 4 (G4) were subjected to CBDL and treatment with pomegranate. After 8 days, we measured total oxidative status (TOS) and antioxidant capacity in the rats' liver tissue and remote organs, and evaluated blood levels of malondialdehyde and total antioxidant capacity (TAC). G3 rats showed significantly raised malondialdehyde level as compared to G1 rats (p < 0.001). Following the pomegranate therapy, a decrease in malondialdehyde was observed (p = 0.015). TAC levels were significantly raised in the G3 rats compared to the G1 rats (p = 0.004). TAC levels dropped after pomegranate therapy (p = 0.011). CBDL caused elevated TOS levels in the liver and remote organs, with a statistically significant increase in the lung tissue (p = 0.002). TOS levels in the CBDL groups decreased after pomegranate treatment (p < 0.001). This study reveals the marked protective effect of pomegranate on the liver and remote organs in obstructive jaundice.

Autophagy activation promotes removal of damaged mitochondria and protects against renal tubular injury induced by albumin overload.

PubMed

Tan, Jin; Wang, Miaohong; Song, Shuling; Miao, Yuyang; Zhang, Qiang

2018-01-10

Proteinuria (albuminuria) is an important cause of aggravating tubulointerstitial injury. Previous studies have shown that autophagy activation can alleviate renal tubular epithelial cell injury caused by urinary protein, but the mechanism is not clear. Here, we investigated the role of clearance of damaged mitochondria in this protective effect. We found that albumin overload induces a significant increase in turnover of LC3-II and decrease in p62 protein level in renal proximal tubular (HK-2) cells in vitro. Albumin overload also induces an increase in mitochondrial damage. ALC, a mitochondrial torpent, alleviates mitochondrial damage induced by albumin overload and also decreases autophagy, while mitochondrial damage revulsant CCCP further increases autophagy. Furthermore, pretreatment of HK-2 cells with rapamycin reduced the amount of damaged mitochondria and the level of apoptosis induced by albumin overload. In contrast, blocking autophagy with chloroquine exerted an opposite effect. Taken together, our results indicated autophagy activation promotes removal of damaged mitochondria and protects against renal tubular injury caused by albumin overload. This further confirms previous research that autophagy activation is an adaptive response in renal tubular epithelial cells after urinary protein overload.

Curcumin and folic acid abrogated methotrexate induced vascular endothelial dysfunction.

PubMed

Sankrityayan, Himanshu; Majumdar, Anuradha S

2016-01-01

Methotrexate, an antifolate drug widely used in rheumatoid arthritis, psoriasis, and cancer, is known to cause vascular endothelial dysfunction by causing hyperhomocysteinemia, direct injury to endothelium or by increasing the oxidative stress (raising levels of 7,8-dihydrobiopterin). Curcumin is a naturally occurring polyphenol with strong antioxidant and anti-inflammatory action and therapeutic spectra similar to that of methotrexate. This study was performed to evaluate the effects of curcumin on methotrexate induced vascular endothelial dysfunction and also compare its effect with that produced by folic acid (0.072 μg·g(-1)·day(-1), p.o., 2 weeks) per se and in combination. Male Wistar rats were exposed to methotrexate (0.35 mg·kg(-1)·day(-1), i.p.) for 2 weeks to induce endothelial dysfunction. Methotrexate exposure led to shedding of endothelium, decreased vascular reactivity, increased oxidative stress, decreased serum nitrite levels, and increase in aortic collagen deposition. Curcumin (200 mg·kg(-1)·day(-1) and 400 mg·kg(-1)·day(-1), p.o.) for 4 weeks prevented the increase in oxidative stress, decrease in serum nitrite, aortic collagen deposition, and also vascular reactivity. The effects were comparable with those produced by folic acid therapy. The study shows that curcumin, when concomitantly administered with methotrexate, abrogated its vascular side effects by preventing an increase in oxidative stress and abating any reduction in physiological nitric oxide levels.

Distinct cerebellar engrams in short-term and long-term motor learning.

PubMed

Wang, Wen; Nakadate, Kazuhiko; Masugi-Tokita, Miwako; Shutoh, Fumihiro; Aziz, Wajeeha; Tarusawa, Etsuko; Lorincz, Andrea; Molnár, Elek; Kesaf, Sebnem; Li, Yun-Qing; Fukazawa, Yugo; Nagao, Soichi; Shigemoto, Ryuichi

2014-01-07

Cerebellar motor learning is suggested to be caused by long-term plasticity of excitatory parallel fiber-Purkinje cell (PF-PC) synapses associated with changes in the number of synaptic AMPA-type glutamate receptors (AMPARs). However, whether the AMPARs decrease or increase in individual PF-PC synapses occurs in physiological motor learning and accounts for memory that lasts over days remains elusive. We combined quantitative SDS-digested freeze-fracture replica labeling for AMPAR and physical dissector electron microscopy with a simple model of cerebellar motor learning, adaptation of horizontal optokinetic response (HOKR) in mouse. After 1-h training of HOKR, short-term adaptation (STA) was accompanied with transient decrease in AMPARs by 28% in target PF-PC synapses. STA was well correlated with AMPAR decrease in individual animals and both STA and AMPAR decrease recovered to basal levels within 24 h. Surprisingly, long-term adaptation (LTA) after five consecutive daily trainings of 1-h HOKR did not alter the number of AMPARs in PF-PC synapses but caused gradual and persistent synapse elimination by 45%, with corresponding PC spine loss by the fifth training day. Furthermore, recovery of LTA after 2 wk was well correlated with increase of PF-PC synapses to the control level. Our findings indicate that the AMPARs decrease in PF-PC synapses and the elimination of these synapses are in vivo engrams in short- and long-term motor learning, respectively, showing a unique type of synaptic plasticity that may contribute to memory consolidation.

Prolactin levels during short- and long-term cross-sex hormone treatment: an observational study in transgender persons.

PubMed

Nota, N M; Dekker, M J H J; Klaver, M; Wiepjes, C M; van Trotsenburg, M A; Heijboer, A C; den Heijer, M

2017-08-01

The cause of prolactin alterations in transgender persons is often assigned to oestrogens, but the precise cause and time course during different phases of cross-sex hormone treatment (CHT) remain unclear. In this study, we prospectively examined prolactin levels in 55 female-to-males (FtMs) and 61 male-to-females (MtFs) during the first year of CHT. Because long-term prolactin data were not available in this population, we studied these levels in a retrospective population of 25 FtMs and 38 MtFs who underwent gonadectomy. FtMs were treated with testosterone and MtFs with estradiol, with or without the anti-androgen cyproterone acetate (CPA) (after gonadectomy CPA is cessated). During the first year of CHT, prolactin decreased with 25% (95CI: -33%, -12%) in FtMs and increased with 193% (95CI: 156%, 219%) in MtFs. Eighteen MtFs developed hyperprolactinemia (≥0.6 IU L -1 ). In the retrospective population, post-gonadectomy levels in FtMs were lower than baseline levels (-39%; 95CI: -51%, -20%) while in MtFs post-gonadectomy levels and baseline levels were comparable (-6%; 95CI: -24%, 15%). No hyperprolactinemia was found after gonadectomy. In conclusion, in FtMs, prolactin decreased consistently during CHT and in MtFs, prolactin increased during pre-surgical CHT but normalised after gonadectomy. It is likely that CPA induces increasing prolactin levels in MtFs. © 2016 Blackwell Verlag GmbH.

Depletion of the outer radiation belt during low activity years

NASA Astrophysics Data System (ADS)

Lazutin, Leonid L.

2017-05-01

During the years of high and moderate activity, the energetic flux of electrons at geostationary region increases compensated by the losses and as a result, the overall level of the population persists. The transitions from high to low intensity and back by 3-4 orders of magnitude are fast within hours and caused by the magnetic disturbances, storms and substorms. During the years of the low activity, the balance of increases and losses is violated; the whole flux of electrons is reduced. Particularly noticeable was the devastation of the outer belt during the minimum of 2009-2010 years. The slow type of decreases became most active. The transition from the fast type to the slow type of decreases was created by the prolonged periods of the low substorm activity. The slow type of intensity decreases is mostly probable caused by the losses on the magnetopause.

A urinary metabonomics analysis of long-term effect of acetochlor exposure on rats by ultra-performance liquid chromatography/mass spectrometry.

PubMed

Li, Longxue; Wang, Maoqing; Chen, Shuhong; Zhao, Wei; Zhao, Yue; Wang, Xu; Zhang, Yang

2016-03-01

The study was to assess the long-term toxic effects of acetochlor on rats. Two different doses (42.96 and 107.4 mg/kg body weight/day) of acetochlor were administered to Wistar rats through their food for over 24 weeks. Rat urine samples were collected at two time-points for the measurements of the metabonomics profiles with ultra-performance liquid chromatography-mass spectrometry (UPLC-MSMS). The results of clinical chemistry and histopathology suggested that long-term use of acetochlor in rats caused liver and kidney damage, and dysfunction of antioxidant system. The urinary metabonomics analysis indicated that the high and low-dose exposure of acetochlor could cause alterations of these metabonomics in urine in the rat. Significant changes of the levels of hippuric acid (0.403-fold decrease), citric acid (0.430-fold decrease), pantothenic acid (0.486-fold decrease), uracil (0.419-fold decrease), β-Alanine (0.325-fold decrease), nonanedioic acid (0.445-fold decrease), L-tyrosine (0.410-fold decrease), D-glucuronic acid (8.389-fold increase) and 2-ethyl-6-methyl-N-methyl-2-chloro-acetanilide in urine were observed. In addition, it may interfere with the fatty acid synthesis, the pyrimidine degradation and pantothenate biosynthesis. The level of 2-ethyl-6-methyl-N-methyl-2-chloro-acetanilide is detected in all treated groups which is not found in the control groups, indicating which can be used as an early, sensitive marker of acetochlor exposure in rat. This study illustrates the important utility of metabonomics approaches to understand the toxicity of long-term exposure of acetochlor. Copyright © 2015. Published by Elsevier Inc.

Glutamine-mediated protection from neuronal cell death depends on mitochondrial activity.

PubMed

Stelmashook, E V; Lozier, E R; Goryacheva, E S; Mergenthaler, P; Novikova, S V; Zorov, D B; Isaev, N K

2010-09-27

The specific aim of this study was to elucidate the role of mitochondria in a neuronal death caused by different metabolic effectors and possible role of intracellular calcium ions ([Ca(2+)](i)) and glutamine in mitochondria- and non-mitochondria-mediated cell death. Inhibition of mitochondrial complex I by rotenone was found to cause intensive death of cultured cerebellar granule neurons (CGNs) that was preceded by an increase in intracellular calcium concentration ([Ca(2+)](i)). The neuronal death induced by rotenone was significantly potentiated by glutamine. In addition, inhibition of Na/K-ATPase by ouabain also caused [Ca(2+)](i) increase, but it induced neuronal cell death only in the absence of glucose. Treatment with glutamine prevented the toxic effect of ouabain and decreased [Ca(2+)](i). Blockade of ionotropic glutamate receptors prevented neuronal death and significantly decreased [Ca(2+)](i), demonstrating that toxicity of rotenone and ouabain was at least partially mediated by activation of these receptors. Activation of glutamate receptors by NMDA increased [Ca(2+)](i) and decreased mitochondrial membrane potential leading to markedly decreased neuronal survival under glucose deprivation. Glutamine treatment under these conditions prevented cell death and significantly decreased the disturbances of [Ca(2+)](i) and changes in mitochondrial membrane potential caused by NMDA during hypoglycemia. Our results indicate that glutamine stimulates glutamate-dependent neuronal damage when mitochondrial respiration is impaired. However, when mitochondria are functionally active, glutamine can be used by mitochondria as an alternative substrate to maintain cellular energy levels and promote cell survival. (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Endogenous lycopene improves ethanol production under acetic acid stress in Saccharomyces cerevisiae.

PubMed

Pan, Shuo; Jia, Bin; Liu, Hong; Wang, Zhen; Chai, Meng-Zhe; Ding, Ming-Zhu; Zhou, Xiao; Li, Xia; Li, Chun; Li, Bing-Zhi; Yuan, Ying-Jin

2018-01-01

Acetic acid, generated from the pretreatment of lignocellulosic biomass, is a significant obstacle for lignocellulosic ethanol production. Reactive oxidative species (ROS)-mediated cell damage is one of important issues caused by acetic acid. It has been reported that decreasing ROS level can improve the acetic acid tolerance of Saccharomyces cerevisiae . Lycopene is known as an antioxidant. In the study, we investigated effects of endogenous lycopene on cell growth and ethanol production of S. cerevisiae in acetic acid media. By accumulating endogenous lycopene during the aerobic fermentation of the seed stage, the intracellular ROS level of strain decreased to 1.4% of that of the control strain during ethanol fermentation. In the ethanol fermentation system containing 100 g/L glucose and 5.5 g/L acetic acid, the lag phase of strain was 24 h shorter than that of control strain. Glucose consumption rate and ethanol titer of yPS002 got to 2.08 g/L/h and 44.25 g/L, respectively, which were 2.6- and 1.3-fold of the control strain. Transcriptional changes of INO1 gene and CTT1 gene confirmed that endogenous lycopene can decrease oxidative stress and improve intracellular environment. Biosynthesis of endogenous lycopene is first associated with enhancing tolerance to acetic acid in S. cerevisiae . We demonstrate that endogenous lycopene can decrease intracellular ROS level caused by acetic acid, thus increasing cell growth and ethanol production. This work innovatively   puts forward a new strategy for second generation bioethanol production during lignocellulosic fermentation.

Hydroquinone Increases 5-Hydroxymethylcytosine Formation through Ten Eleven Translocation 1 (TET1) 5-Methylcytosine Dioxygenase*

PubMed Central

Coulter, Jonathan B.; O'Driscoll, Cliona M.; Bressler, Joseph P.

2013-01-01

DNA methylation regulates gene expression throughout development and in a wide range of pathologies such as cancer and neurological disorders. Pathways controlling the dynamic levels and targets of methylation are known to be disrupted by chemicals and are therefore of great interest in both prevention and clinical contexts. Benzene and its metabolite hydroquinone have been shown to lead to decreased levels of DNA methylation, although the mechanism is not known. This study employs a cell culture model to investigate the mechanism of hydroquinone-mediated changes in DNA methylation. Exposures that do not affect HEK293 cell viability led to genomic and methylated reporter DNA demethylation. Hydroquinone caused reactivation of a methylated reporter plasmid that was prevented by the addition of N-acetylcysteine. Hydroquinone also caused an increase in Ten Eleven Translocation 1 activity and global levels of 5-hydroxymethylcytosine. 5-Hydroxymethylcytosine was found enriched at LINE-1 prior to a decrease in both 5-hydroxymethylcytosine and 5-methylcytosine. Ten Eleven Translocation-1 knockdown decreased 5-hydroxymethylcytosine formation following hydroquinone exposure as well as the induction of glutamate-cysteine ligase catalytic subunit and 14-3-3σ. Finally, Ten Eleven Translocation 1 knockdown decreased the percentage of cells accumulating in G2+M following hydroquinone exposure, indicating that it may have a role in cell cycle changes in response to toxicants. This work demonstrates that hydroquinone exposure leads to active and functional DNA demethylation in HEK293 cells in a mechanism involving reactive oxygen species and Ten Eleven Translocation 1 5-methylcytosine dioxygenase. PMID:23940045

Hydroquinone increases 5-hydroxymethylcytosine formation through ten eleven translocation 1 (TET1) 5-methylcytosine dioxygenase.

PubMed

Coulter, Jonathan B; O'Driscoll, Cliona M; Bressler, Joseph P

2013-10-04

DNA methylation regulates gene expression throughout development and in a wide range of pathologies such as cancer and neurological disorders. Pathways controlling the dynamic levels and targets of methylation are known to be disrupted by chemicals and are therefore of great interest in both prevention and clinical contexts. Benzene and its metabolite hydroquinone have been shown to lead to decreased levels of DNA methylation, although the mechanism is not known. This study employs a cell culture model to investigate the mechanism of hydroquinone-mediated changes in DNA methylation. Exposures that do not affect HEK293 cell viability led to genomic and methylated reporter DNA demethylation. Hydroquinone caused reactivation of a methylated reporter plasmid that was prevented by the addition of N-acetylcysteine. Hydroquinone also caused an increase in Ten Eleven Translocation 1 activity and global levels of 5-hydroxymethylcytosine. 5-Hydroxymethylcytosine was found enriched at LINE-1 prior to a decrease in both 5-hydroxymethylcytosine and 5-methylcytosine. Ten Eleven Translocation-1 knockdown decreased 5-hydroxymethylcytosine formation following hydroquinone exposure as well as the induction of glutamate-cysteine ligase catalytic subunit and 14-3-3σ. Finally, Ten Eleven Translocation 1 knockdown decreased the percentage of cells accumulating in G2+M following hydroquinone exposure, indicating that it may have a role in cell cycle changes in response to toxicants. This work demonstrates that hydroquinone exposure leads to active and functional DNA demethylation in HEK293 cells in a mechanism involving reactive oxygen species and Ten Eleven Translocation 1 5-methylcytosine dioxygenase.

Thermoregulatory and Cardiovascular Consequences of a Transient Thyrotoxicosis and Recovery in Male Mice.

PubMed

Hoefig, Carolin S; Harder, Lisbeth; Oelkrug, Rebecca; Meusel, Moritz; Vennström, Björn; Brabant, Georg; Mittag, Jens

2016-07-01

Thyroid hormones play a major role in body homeostasis, regulating energy expenditure and cardiovascular function. Given that obese people or athletes might consider rapid weight loss as beneficial, voluntary intoxication with T4 preparations is a growing cause for thyrotoxicosis. However, the long-lasting effects of transient thyrotoxicosis are poorly understood. Here we examined metabolic, thermoregulatory, and cardiovascular function upon induction and recovery from a 2-week thyrotoxicosis in male C57BL/6J mice. Our results showed that T4 treatment caused tachycardia, decreased hepatic glycogen stores, and higher body temperature as expected; however, we did not observe an increase in brown fat thermogenesis or decreased tail heat loss, suggesting that these tissues do not contribute to the hyperthermia induced by thyroid hormone. Most interestingly, when the T4 treatment was ended, a pronounced bradycardia was observed in the animals, which was likely caused by a rapid decline of T3 even below baseline levels. On the molecular level, this was accompanied by an overexpression of cardiac phospholamban and Serca2a mRNA, supporting the hypothesis that the heart depends more on T3 than T4. Our findings therefore demonstrate that a transient thyrotoxicosis can have pathological effects that even persist beyond the recovery of serum T4 levels, and in particular the observed bradycardia could be of clinical relevance when treating hyperthyroid patients.

The protective effect of N-acetylcysteine on oxidative stress in the brain caused by the long-term intake of aspartame by rats.

PubMed

Finamor, Isabela A; Ourique, Giovana M; Pês, Tanise S; Saccol, Etiane M H; Bressan, Caroline A; Scheid, Taína; Baldisserotto, Bernardo; Llesuy, Susana F; Partata, Wânia A; Pavanato, Maria A

2014-09-01

Long-term intake of aspartame at the acceptable daily dose causes oxidative stress in rodent brain mainly due to the dysregulation of glutathione (GSH) homeostasis. N-Acetylcysteine provides the cysteine that is required for the production of GSH, being effective in treating disorders associated with oxidative stress. We investigated the effects of N-acetylcysteine treatment (150 mg kg(-1), i.p.) on oxidative stress biomarkers in rat brain after chronic aspartame administration by gavage (40 mg kg(-1)). N-Acetylcysteine led to a reduction in the thiobarbituric acid reactive substances, lipid hydroperoxides, and carbonyl protein levels, which were increased due to aspartame administration. N-Acetylcysteine also resulted in an elevation of superoxide dismutase, glutathione peroxidase, glutathione reductase activities, as well as non-protein thiols, and total reactive antioxidant potential levels, which were decreased after aspartame exposure. However, N-acetylcysteine was unable to reduce serum glucose levels, which were increased as a result of aspartame administration. Furthermore, catalase and glutathione S-transferase, whose activities were reduced due to aspartame treatment, remained decreased even after N-acetylcysteine exposure. In conclusion, N-acetylcysteine treatment may exert a protective effect against the oxidative damage in the brain, which was caused by the long-term consumption of the acceptable daily dose of aspartame by rats.

Short-term and long-term effects of transient exogenous cortisol manipulation on oxidative stress in juvenile brown trout.

PubMed

Birnie-Gauvin, Kim; Peiman, Kathryn S; Larsen, Martin H; Aarestrup, Kim; Willmore, William G; Cooke, Steven J

2017-05-01

In the wild, animals are exposed to a growing number of stressors with increasing frequency and intensity, as a result of human activities and human-induced environmental change. To fully understand how wild organisms are affected by stressors, it is crucial to understand the physiology that underlies an organism's response to a stressor. Prolonged levels of elevated glucocorticoids are associated with a state of chronic stress and decreased fitness. Exogenous glucocorticoid manipulation reduces an individual's ability to forage, avoid predators and grow, thereby limiting the resources available for physiological functions like defence against oxidative stress. Using brown trout ( Salmo trutta ), we evaluated the short-term (2 weeks) and long-term (4 months over winter) effects of exogenous cortisol manipulations (versus relevant shams and controls) on the oxidative status of wild juveniles. Cortisol caused an increase in glutathione over a 2 week period and appeared to reduce glutathione over winter. Cortisol treatment did not affect oxidative stress levels or low molecular weight antioxidants. Cortisol caused a significant decrease in growth rates but did not affect predation risk. Over-winter survival in the stream was associated with low levels of oxidative stress and glutathione. Thus, oxidative stress may be a mechanism by which elevated cortisol causes negative physiological effects. © 2017. Published by The Company of Biologists Ltd.

Hard-to-cook phenomenon in chickpeas (Cicer arietinum L): effect of accelerated storage on quality.

PubMed

Reyes-Moreno, C; Okamura-Esparza, J; Armienta-Rodelo, E; Gómez-Garza, R M; Milán-Carrillo, J

2000-01-01

Storage, at high temperature (> or = 25 degrees C) and high relative humidity (> or = 65%), causes development of hard to cook (HTC) phenomenon in grain legumes. The objective of this work was to study the effect of storage simulating tropical conditions on chickpeas quality. The hardening of the Surutato 77, Mocorito 88, and Blanco Sinaloa 92 chickpea varieties was produced using adverse storage (32 +/- 1 degrees C, RH = 75%, 160 days) conditions. For all samples, the Hunter 'L' values decreased and deltaE values increased during storage, meaning a loss of color lightness and development of darkening. Accelerated storage caused a significant decrease in the water absorption capacities and cooking times of whole seeds, cotyledons and seed coats of all samples, being more pronounced in The Blanco Sinaloa 92 variety. Furthermore, storage produced significant decreases in the seed coat tannin content of the three materials; this parameter increased significantly in the cotyledon. In all samples, the levels of phytic acid decreased significantly with the seed hardness. Hardening of chickpea grains caused a decrease in the in vitro protein digestibilities of all varieties. These results suggest that both the cotyledon and seed coat play a significant role in the process of chickpea hardening. Blanco Sinaloa 92 and Mocorito 88 might be classified as varieties with high and low proneness, respectively, to the development of the HTC condition.

Traumatic Fractures of the Cervical Spine: Analysis of Changes in Incidence, Cause, Concurrent Injuries, and Complications Among 488,262 Patients from 2005 to 2013.

PubMed

Passias, Peter G; Poorman, Gregory W; Segreto, Frank A; Jalai, Cyrus M; Horn, Samantha R; Bortz, Cole A; Vasquez-Montes, Dennis; Diebo, Bassel G; Vira, Shaleen; Bono, Olivia J; De La Garza-Ramos, Rafael; Moon, John Y; Wang, Charles; Hirsch, Brandon P; Zhou, Peter L; Gerling, Michael; Koller, Heiko; Lafage, Virginie

2018-02-01

The causes and epidemiology of traumatic cervical spine fracture have not been described with sufficient power or recency. Our goal is to describe demographics, incidence, cause, spinal cord injuries (SCIs), concurrent injuries, treatments, and complications of traumatic cervical spine fractures. A retrospective review was carried out of the Nationwide Inpatient Sample. International Classification of Disease, Ninth Revision E-codes identified trauma cases from 2005 to 2013. Patients with cervical fracture were isolated. Demographics, incidence, cause, fracture levels, concurrent injuries, surgical procedures, and complications were analyzed. t tests elucidated significance for continuous variables and χ 2 for categorical variables. Level of significance was P < 0.05. A total of 488,262 patients were isolated (age, 55.96 years; male, 60.0%; white, 77.5%). Incidence (2005, 4.1% vs. 2013, 5.4%), Charlson Comorbidity Index (2005, 0.6150 vs. 2013, 1.1178), and total charges (2005, $71,228.60 vs. 2013, $108,119.29) have increased since 2005, whereas length of stay decreased (2005, 9.22 vs. 2013, 7.86) (all P < 0.05). The most common causes were motor vehicle accident (29.3%), falls (23.7%), and pedestrian accidents (15.7%). The most frequent fracture types were closed at C2 (32.0%) and C7 (20.9%). Concurrent injury rates have significantly increased since 2005 (2005, 62.3% vs. 2013, 67.6%). Common concurrent injuries included fractures to the rib/sternum/larynx/trachea (19.6%). Overall fusion rates have increased since 2005 (2005, 15.7% vs. 2013, 18.0%), whereas decompressions and halo insertion rates have decreased (all P < 0.05). SCIs have significantly decreased since 2005, except for upper cervical central cord syndrome. Complication rates have significantly increased since 2005 (2005, 31.6% vs. 2013, 36.2%). Common complications included anemia (7.7%), mortality (6.6%), and acute respiratory distress syndrome (6.6%). Incidence, complications, concurrent injuries, and fusions have increased since 2005. Length of stay, SCIs, decompressions, and halo insertions have decreased. Indicated trends should guide future research in management guidelines. Copyright © 2017 Elsevier Inc. All rights reserved.

Soluble Programmed Death 1 (PD-1) Is Decreased in Patients With Immune Thrombocytopenia (ITP): Potential Involvement of PD-1 Pathway in ITP Immunopathogenesis.

PubMed

Birtas Atesoglu, Elif; Tarkun, Pinar; Demirsoy, Esra Terzi; Geduk, Ayfer; Mehtap, Ozgur; Batman, Adnan; Kaya, Fatih; Cekmen, Mustafa Baki; Gulbas, Zafer; Hacıhanefioglu, Abdullah

2016-04-01

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by dysregulation of T cells. Programmed death (PD) 1 and programmed death 1 ligand 1 (PD-L1) are cosignaling molecules, and the major role of the PD-1 pathway is the inhibition of self-reactive T cells and to protect against autoimmune diseases. We measured levels of serum soluble PD 1 (sPD-1) and serum soluble PD-L1 (sPD-L1) in 67 patients with ITP (24 newly diagnosed ITP [ndITP], 43 chronic ITP [cITP]) and 21 healthy controls (HCs). We determined decreased serum sPD-1 levels both in patients with ndITP and in patients with cITP when compared to HC. Moreover, there was a positive correlation between sPD-1 levels and platelet counts. The sPD-L1 levels were decreased in patients with ndITP when compared to patients with cITP. This is the first study investigating PD-1 signaling pathway in ITP. Decreased sPD-1 levels may have a role in ITP pathogenesis as without the inhibitory regulation of PD-1, sustained activation of T cells may cause inflammatory responses which is the case in ITP. © The Author(s) 2014.

Role of DNA Replication Defects in Breast Cancer

DTIC Science & Technology

2009-10-01

Several recent studies have indicated that decreased levels of the MCM2-7 DNA replication proteins can lead to genomic instability (GIN) and cancer...exceeding that required for DNA replication under normal circumstances, we found that heterozygosity for 2 or more different MCMs caused genomic

Nominal dysphasia and euphoria caused by EBV encephalitis

PubMed Central

Carman, Kursat Bora; Yakut, Ayten; Ekici, Arzu; Isikay, Sedat

2013-01-01

Encephalitis is an uncommon neurological complication of Ebstein-Barr virus (EBV) infection and usually presents with confusion, decreased level of consciousness, fever, epileptic seizure, emotional instability and chorea. We present a patient with EBV encephalitis, characterised by nominal dysphasia, euphoria and personality changes. PMID:23307455

A huge bladder calculus causing acute renal failure.

PubMed

Komeya, Mitsuru; Sahoda, Tamami; Sugiura, Shinpei; Sawada, Takuto; Kitami, Kazuo

2013-02-01

A 81-year-old male was referred to our emergency outpatient unit due to acute renal failure. The level of serum creatinine was 276 μmol/l. A CT scan showed bilateral hydronephroureter, large bladder stone (7 cm × 6 cm × 6 cm) and bladder wall thickness. He was diagnosed as post renal failure due to bilateral hydronephroureter. Large bladder stone is thought to be the cause of bilateral hydronephroureter and renal failure. To improve renal failure, we performed open cystolithotomy and urethral catheterization. Three days after the surgery, the level of serum creatinine decreased to 224 μmol/l. He was discharged from our hospital with uneventful course. Bladder calculus is thought to be a rare cause of renal failure. We summarize the characteristics of bladder calculus causing renal failure. We should keep that long-term pyuria and urinary symptom, and repeated urinary tract infection can cause huge bladder calculus and renal failure in mind.

Hypocretin and GABA interact in the pontine reticular formation to increase wakefulness.

PubMed

Brevig, Holly N; Watson, Christopher J; Lydic, Ralph; Baghdoyan, Helen A

2010-10-01

Hypocretin-1/orexin A administered directly into the oral part of rat pontine reticular formation (PnO) causes an increase in wakefulness and extracellular gamma-aminobutyric acid (GABA) levels. The receptors in the PnO that mediate these effects have not been identified. Therefore, this study tested the hypothesis that the increase in wakefulness caused by administration of hypocretin-1 into the PnO occurs via activation of GABAA receptors and hypocretin receptors. Within/between subjects. University of Michigan. Twenty-three adult male Crl:CD*(SD) (Sprague Dawley) rats. Microinjection of hypocretin-1, bicuculline (GABAA receptor antagonist), SB-334867 (hypocretin receptor-1 antagonist), and Ringer solution (vehicle control) into the PnO. Hypocretin-1 caused a significant concentration-dependent increase in wakefulness and decrease in rapid eye movement (REM) sleep and non-REM (NREM) sleep. Coadministration of SB-334867 and hypocretin-1 blocked the hypocretin-1-induced increase in wakefulness and decrease in both the NREM and REM phases of sleep. Coadministration of bicuculline and hypocretin-1 blocked the hypocretin-1-induced increase in wakefulness and decrease in NREM sleep caused by hypocretin-1. The increase in wakefulness caused by administering hypocretin-1 to the PnO is mediated by hypocretin receptors and GABAA receptors in the PnO. These results show for the first time that hypocretinergic and GABAergic transmission in the PnO can interact to promote wakefulness.

Decreased survival of rainbow trout exposed to no. 2 fuel oil caused by sublethal preexposure

USGS Publications Warehouse

Steadman, B. L.; Stubblefield, W. A.; Lapoint, T. W.; Bergman, H.L.; Kaiser, M.S.

1991-01-01

Rainbow trout (Oncorhynchus mykiss) were exposed for 21 d to sublethal levels of No. 2 fuel oil (2FO). The four exposure concentrations ranged from 12 to 100 mg/L 2FO dispersed in water and resulted in 0 to 12% mortality. Following this exposure period (preexposure) the ability of preexposed trout to survive exposure to acutely lethal levels of 2FO was observed. Preexposure to either 50 or 100 mg/L 2FO consistently resulted in decreased survival and a lower LC50 for a given observation period. Unfortunately, because the LC50 determinations were not obtained independently, they could not be used to test statistically the effects of preexposure on survival. Therefore, two proportional hazard modeling techniques were applied to the data to test for effects due to preexposure. Both modeling techniques indicated that preexposure results in decreased survival of rainbow trout exposed to acutely toxic levels of 2FO. Thus, in contrast to preexposure to metals, which results in acclimation, preexposure to 2FO results in decreased survival.

Low glucose utilization and neurodegenerative changes caused by sodium fluoride exposure in rat's developmental brain.

PubMed

Jiang, Chunyang; Zhang, Shun; Liu, Hongliang; Guan, Zhizhong; Zeng, Qiang; Zhang, Cheng; Lei, Rongrong; Xia, Tao; Wang, Zhenglun; Yang, Lu; Chen, Yihu; Wu, Xue; Zhang, Xiaofei; Cui, Yushan; Yu, Linyu; Wang, Aiguo

2014-03-01

Fluorine, a toxic and reactive element, is widely prevalent throughout the environment and can induce toxicity when absorbed into the body. This study was to explore the possible mechanisms of developmental neurotoxicity in rats treated with different levels of sodium fluoride (NaF). The rats' intelligence, as well as changes in neuronal morphology, glucose absorption, and functional gene expression within the brain were determined using the Morris water maze test, transmission electron microscopy, small-animal magnetic resonance imaging and Positron emission tomography and computed tomography, and Western blotting techniques. We found that NaF treatment-impaired learning and memory in these rats. Furthermore, NaF caused neuronal degeneration, decreased brain glucose utilization, decreased the protein expression of glucose transporter 1 and glial fibrillary acidic protein, and increased levels of brain-derived neurotrophic factor in the rat brains. The developmental neurotoxicity of fluoride may be closely associated with low glucose utilization and neurodegenerative changes.

Environmental assessment of MMT fuel additive.

PubMed

Lynam, D R; Pfeifer, G D; Fort, B F; Gelbcke, A A

1990-04-01

Methylcyclopentadienyl Manganese Tricarbonyl (MMT) has been shown to be an effective octane enhancer in gasoline. It is presently used in the U.S. in leaded gasoline and in Canada in both leaded and unleaded gasoline. Because MMT has a low vapor pressure and a short half-life in sunlight, it is unlikely that significant concentrations of MMT could occur in the environment as a result of its use as a gasoline additive. Greater than 99.9% of the manganese from MMT is converted into inorganic oxides of manganese during the combustion of MMT-containing gasoline. Authors of several health assessments on MMT concluded the increase in environmental levels of manganese oxides would be slight compared to the natural background levels of manganese and would present no health hazards. Studies showed that MMT usage had no effect on CO emissions, caused a slight decrease in NOx emissions, and a slight increase in HC emissions. MMT usage caused a decrease in NOx + HC emissions in one test and had no effect in another.

Effects of DDT and Triclosan on Tumor-cell Binding Capacity and Cell-Surface Protein Expression of Human Natural Killer Cells

PubMed Central

Hurd-Brown, Tasia; Udoji, Felicia; Martin, Tamara; Whalen, Margaret M.

2012-01-01

1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT) and triclosan (TCS) are organochlorine (OC) compounds that contaminate the environment, are found in human blood, and have been shown to decrease the tumor-cell killing (lytic) function of human natural killer (NK) cells. NK cells defend against tumor cells and virally infected cells. They bind to these targets, utilizing a variety of cell surface proteins. This study examined concentrations of DDT and TCS that decrease lytic function for alteration of NK binding to tumor targets. Levels of either compound that caused loss of binding function were then examined for effects on expression of cell-surface proteins needed for binding. NK cells exposed to 2.5 μM DDT for 24 h (which caused a greater than 55% loss of lytic function) showed a decrease in NK binding function of about 22%, and a decrease in CD16 cell-surface protein of 20%. NK cells exposed to 5 μM TCS for 24 h showed a decrease in ability to bind tumor cells of 37% and a decrease in expression of CD56 of about 34%. This same treatment caused a decrease in lytic function of greater than 87%. These results indicated that only a portion of the loss of NK lytic function seen with exposures to these compounds could be accounted for by loss of binding function. They also showed that loss of binding function is accompanied by a loss cell-surface proteins important in binding function. PMID:22729613

Effects of sodium fluoride on MAPKs signaling pathway in the gills of a freshwater teleost, Cyprinus carpio.

PubMed

Cao, Jinling; Chen, Jianjie; Wang, Jundong; Klerks, Paul; Xie, Lingtian

2014-07-01

Exposure to elevated levels of fluoride can cause a variety of adverse effects in fish. Previously we showed that fluoride causes injuries and apoptosis in the gills of Cyprinus carpio. In this study, the effects of fluoride on caspase-3 activity and on accumulation of proteins in the MAPKs pathways were evaluated using Western blotting and immunohistochemistry methods in vivo and in vitro. In vivo experiments showed that the caspase-3 activity increased with fluoride exposure level in a dose-dependent pattern Western blotting and immunohistochemistry results indicated that ERK relative activation tended to decrease as a function of fluoride exposure concentration. In contrast, relative activation of JNK increased with fluoride exposure level. Fluoride exposure did not appear to affect p38 activation. Furthermore, pretreatment of branchial cells with MAPK-specific inhibitors effectively prevented JNK induction and ERK inhibition, respectively, as well as reversed caspase-3 activity in fluoride-treated branchial cells. Our results indicate that activation of JNK and inactivation of ERK were caused by increased ROS and decreased antioxidant capacity in the gills of chronically exposed C. carpio described previously, which eventually caused the observed apoptosis in the fluoride-exposed gills and cells in C. carpio. JNK activation and ERK inactivation mechanism play a crucial role in gill impairment induced by chronic fluorosis. These findings contribute to a better understanding of the initial molecular and cellular events in the gill of fish chronically exposed to fluoride. Copyright © 2014 Elsevier B.V. All rights reserved.

VIIRS On-Orbit Optical Anomaly - Investigation, Analysis, Root Cause Determination and Lessons Learned

NASA Technical Reports Server (NTRS)

Iona, Glenn; Butler, James; Guenther, Bruce; Graziani, Larissa; Johnson, Eric; Kennedy, Brian; Kent, Criag; Lambeck, Robert; Waluschka, Eugne; Xiong, Xiaoxiong

2012-01-01

A gradual, but persistent, decrease in the optical throughput was detected during the early commissioning phase for the Suomi National Polar-Orbiting Partnership (SNPP) Visible Infrared Imager Radiometer Suite (VIIRS) Near Infrared (NIR) bands. Its initial rate and unknown cause were coincidently coupled with a decrease in sensitivity in the same spectral wavelength of the Solar Diffuser Stability Monitor (SDSM) raising concerns about contamination or the possibility of a system-level satellite problem. An anomaly team was formed to investigate and provide recommendations before commissioning could resume. With few hard facts in hand, there was much speculation about possible causes and consequences of the degradation. Two different causes were determined as will be explained in this paper. This paper will describe the build and test history of VIIRS, why there were no indicators, even with hindsight, of an on-orbit problem, the appearance of the on-orbit anomaly, the initial work attempting to understand and determine the cause, the discovery of the root cause and what Test-As-You-Fly (TAYF) activities, can be done in the future to greatly reduce the likelihood of similar optical anomalies. These TAYF activities are captured in the lessons learned section of this paper.

[Analysis of the trend and impact of mortality due to external causes: Mexico, 2000-2013].

PubMed

Dávila Cervantes, Claudio Alberto; Pardo Montaño, Ana Melisa

2016-01-01

The objective of this study was to analyze mortality due to the main external causes of death (traffic accidents, other accidents, homicides and suicides) in Mexico, calculating the years of life lost between 0 and 100 years of age and their contribution to the change in life expectancy between 2000 and 2013, at the national level, by sex and age group. Data came from mortality vital statistics of the Instituto Nacional de Estadística y Geografía (INEGI) [National Institute of Statistics and Geography]. The biggest impact in mortality due to external causes occurred in adolescent and adult males 15-49 years of age; mortality due to these causes remained constant in males and slightly decreased in females. Mortality due to traffic accidents and other accidents decreased, with a positive contribution to life expectancy, but this effect was canceled out by the increase in mortality due to homicides and suicides. Mortality due to external causes can be avoided through interventions, programs and prevention strategies as well as timely treatment. It is necessary to develop multidisciplinary studies on the dynamics of the factors associated with mortality due to these causes.

Differential effects of cathinone compounds and MDMA on body temperature in the rat, and pharmacological characterization of mephedrone-induced hypothermia

PubMed Central

Shortall, SE; Green, AR; Swift, KM; Fone, KCF; King, MV

2013-01-01

Background and Purpose Recreational users report that mephedrone has similar psychoactive effects to 3,4-methylenedioxymethamphetamine (MDMA). MDMA induces well-characterized changes in body temperature due to complex monoaminergic effects on central thermoregulation, peripheral blood flow and thermogenesis, but there are little preclinical data on the acute effects of mephedrone or other synthetic cathinones. Experimental Approach The acute effects of cathinone, methcathinone and mephedrone on rectal and tail temperature were examined in individually housed rats, with MDMA included for comparison. Rats were killed 2 h post-injection and brain regions were collected for quantification of 5-HT, dopamine and major metabolites. Further studies examined the impact of selected α-adrenoceptor and dopamine receptor antagonists on mephedrone-induced changes in rectal temperature and plasma catecholamines. Key Results At normal room temperature, MDMA caused sustained decreases in rectal and tail temperature. Mephedrone caused a transient decrease in rectal temperature, which was enhanced by α1-adrenoceptor and dopamine D1 receptor blockade, and a prolonged decrease in tail temperature. Cathinone and methcathinone caused sustained increases in rectal temperature. MDMA decreased 5-HT and/or 5-hydroxyindoleacetic acid (5-HIAA) content in several brain regions and reduced striatal homovanillic acid (HVA) levels, whereas cathinone and methcathinone increased striatal HVA and 5-HIAA. Cathinone elevated striatal and hypothalamic 5-HT. Mephedrone elevated plasma noradrenaline levels, an effect prevented by α-adrenoceptor and dopamine receptor antagonists. Conclusions and Implications MDMA and cathinones have different effects on thermoregulation, and their acute effects on brain monoamines also differ. These findings suggest that the adverse effects of cathinones in humans cannot be extrapolated from previous observations on MDMA. PMID:23043631

Differential effects of cathinone compounds and MDMA on body temperature in the rat, and pharmacological characterization of mephedrone-induced hypothermia.

PubMed

Shortall, S E; Green, A R; Swift, K M; Fone, K C F; King, M V

2013-02-01

Recreational users report that mephedrone has similar psychoactive effects to 3,4-methylenedioxymethamphetamine (MDMA). MDMA induces well-characterized changes in body temperature due to complex monoaminergic effects on central thermoregulation, peripheral blood flow and thermogenesis, but there are little preclinical data on the acute effects of mephedrone or other synthetic cathinones. The acute effects of cathinone, methcathinone and mephedrone on rectal and tail temperature were examined in individually housed rats, with MDMA included for comparison. Rats were killed 2 h post-injection and brain regions were collected for quantification of 5-HT, dopamine and major metabolites. Further studies examined the impact of selected α-adrenoceptor and dopamine receptor antagonists on mephedrone-induced changes in rectal temperature and plasma catecholamines. At normal room temperature, MDMA caused sustained decreases in rectal and tail temperature. Mephedrone caused a transient decrease in rectal temperature, which was enhanced by α(1) -adrenoceptor and dopamine D(1) receptor blockade, and a prolonged decrease in tail temperature. Cathinone and methcathinone caused sustained increases in rectal temperature. MDMA decreased 5-HT and/or 5-hydroxyindoleacetic acid (5-HIAA) content in several brain regions and reduced striatal homovanillic acid (HVA) levels, whereas cathinone and methcathinone increased striatal HVA and 5-HIAA. Cathinone elevated striatal and hypothalamic 5-HT. Mephedrone elevated plasma noradrenaline levels, an effect prevented by α-adrenoceptor and dopamine receptor antagonists. MDMA and cathinones have different effects on thermoregulation, and their acute effects on brain monoamines also differ. These findings suggest that the adverse effects of cathinones in humans cannot be extrapolated from previous observations on MDMA. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Mutant Huntingtin Causes a Selective Decrease in the Expression of Synaptic Vesicle Protein 2C.

PubMed

Peng, Chaohua; Zhu, Gaochun; Liu, Xiangqian; Li, He

2018-04-30

Huntington's disease (HD) is a neurodegenerative disease caused by a polyglutamine expansion in the huntingtin (Htt) protein. Mutant Htt causes synaptic transmission dysfunctions by interfering in the expression of synaptic proteins, leading to early HD symptoms. Synaptic vesicle proteins 2 (SV2s), a family of synaptic vesicle proteins including 3 members, SV2A, SV2B, and SV2C, plays important roles in synaptic physiology. Here, we investigated whether the expression of SV2s is affected by mutant Htt in the brains of HD transgenic (TG) mice and Neuro2a mouse neuroblastoma cells (N2a cells) expressing mutant Htt. Western blot analysis showed that the protein levels of SV2A and SV2B were not significantly changed in the brains of HD TG mice expressing mutant Htt with 82 glutamine repeats. However, in the TG mouse brain there was a dramatic decrease in the protein level of SV2C, which has a restricted distribution pattern in regions particularly vulnerable in HD. Immunostaining revealed that the immunoreactivity of SV2C was progressively weakened in the basal ganglia and hippocampus of TG mice. RT-PCR demonstrated that the mRNA level of SV2C progressively declined in the TG mouse brain without detectable changes in the mRNA levels of SV2A and SV2B, indicating that mutant Htt selectively inhibits the transcriptional expression of SV2C. Furthermore, we found that only SV2C expression was progressively inhibited in N2a cells expressing a mutant Htt containing 120 glutamine repeats. These findings suggest that the synaptic dysfunction in HD results from the mutant Htt-mediated inhibition of SV2C transcriptional expression. These data also imply that the restricted distribution and decreased expression of SV2C contribute to the brain region-selective pathology of HD.

Impact of Different Levels of iPTH on All-Cause Mortality in Dialysis Patients with Secondary Hyperparathyroidism after Parathyroidectomy

PubMed Central

Xie, Xi Sheng; Zhang, Rui; Xiao, Yue Fei; Jin, Cheng Gang; Li, Yan Bo; Wang, Lin; Zhang, Xiao Xuan; Du, Shu Tong

2017-01-01

Background Secondary hyperparathyroidism (SHPT) usually required parathyroidectomy (PTX) when drugs treatment is invalid. Analysis was done on the impact of different intact parathyroid hormone (iPTH) after the PTX on all-cause mortality. Methods An open, retrospective, multicenter cohort design was conducted. The sample included 525 dialysis patients with SHPT who had undergone PTX. Results 404 patients conformed to the standard, with 36 (8.91%) deaths during the 11 years of follow-up. One week postoperatively, different levels of serum iPTH were divided into four groups: A: ≤20 pg/mL; B: 21–150 pg/mL; C: 151–600 pg/mL; and D: >600 pg/mL. All-cause mortality in groups with different iPTH levels appeared as follows: A (8.29%), B (3.54%), C (10.91%), and D (29.03%). The all-cause mortality of B was the lowest, with D the highest. We used group A as reference (hazard ratio (HR) = 1) compared with the other groups, and HRs on groups B, C, and D appeared as 0.57, 1.43, and 3.45, respectively. Conclusion The all-cause mortality was associated with different levels of iPTH after the PTX. We found that iPTH > 600 pg/mL appeared as a factor which increased the risk of all-cause mortality. When iPTH levels were positively and effectively reducing, the risk of all-cause mortality also decreased. The most appropriate level of postoperative iPTH seemed to be 21–150 pg/mL. PMID:28656147

Intestinal ischemia-reperfusion suppresses biliary excretion of hepatic organic anion transporting polypeptides substrate.

PubMed

Maruyama, Hajime; Ogura, Jiro; Fujikawa, Asuka; Terada, Yusuke; Tsujimoto, Takashi; Koizumi, Takahiro; Kuwayama, Kaori; Kobayashi, Masaki; Yamaguchi, Hiroaki; Iseki, Ken

2013-01-01

Intestinal ischemia-reperfusion (I/R) causes gut dysfunction and promotes multi-organ failure. The liver and kidney can be affected by multi-organ failure after intestinal I/R. Organic anion transporting polypeptides (OATPs) and organic anion transporters (OATs) are recognized in a broad spectrum from endogenous compounds to xenobiotics, including clinically important drugs. Therefore, it is important for understanding the pharmacokinetics to obtain evidence of alterations in OATPs and OATs expression and transport activities. In the present study, we investigated the expression of rat Oatps and Oats after intestinal I/R. We used intestinal ischemia-reperfusion (I/R) model rats. Real-time PCR and Western blotting were used to assess mRNA and protein expression levels. Plasma concentration and biliary excretion of sulfobromophthalein (BSP), which is used as a model compound of organic anion drugs, were measured after intravenous administration in intestinal I/R rats. Although Oat1 and Oat3 mRNA levels were not altered in the kidney, Oatp1a1, Oatp1b2 and Oatp2b1 mRNA levels in the liver were significantly decreased at 1-6 h after intestinal I/R. Moreover, Oatp1a1 and Oatp2b1 protein expression levels were decreased at 1 h after intestinal I/R. Plasma concentration of BSP, which is a typical substrate of Oatps, in intestinal I/R rats reperfused 1 h was increased than that in sham-operated rats. Moreover, the area under the concentration-time curve (AUC₀₋₉₀) in intestinal I/R rats reperfused 1 h was significantly increased than that in sham-operated rats. The total clearance (CL(tot)) and the biliary clearance (CL(bile)) in intestinal I/R rats reperfused 1 h were significantly decreased than those in sham-operated rats. Oatp1a1 and Oatp2b1 expression levels are decreased by intestinal I/R. The decreases in these transporters cause alteration of pharmacokinetics of organic anion compound. The newly found influence of intestinal I/R on the expression and function of Oatps may be a key to perform appropriate drug therapy.

Mobbing vocalizations as a coping response in the common marmoset.

PubMed

Cross, N; Rogers, L J

2006-02-01

Using a non-invasive method of sampling saliva followed by assay for cortisol levels, we found that common marmosets (Callithrix jacchus) show a decrease in cortisol levels after seeing a snake-model stimulus that reliably elicits mobbing (tsik) calls. In fact, there was a significant positive correlation between the number of tsik vocalizations made and the magnitude of the decrease in the cortisol concentrations. Furthermore, marmosets with higher levels of cortisol prior to being exposed to the stimulus produce more tsik calls than those with lower levels of cortisol. Subsequent experiments showed that, in response to 15 min of isolation with no visual or auditory contact with conspecifics (a traditional stressor), cortisol levels increased significantly. However, playback of the mobbing calls of a familiar conspecific to individual isolated marmosets not only prevented the rise in cortisol, but also actually caused a decrease in the levels of this hormone. This suggests that the mobbing calls serve to calm the marmoset after experiencing a stressful situation. This finding results in a greater understanding as to the role of physiological responses during communication in this species and could have implications for the welfare of marmosets in captivity.

Consideration on the Long Ecological Half-Life Component of (137)Cs in Demersal Fish Based on Field Observation Results Obtained after the Fukushima Accident.

PubMed

Tagami, Keiko; Uchida, Shigeo

2016-02-16

Radiocesium concentrations in most marine fish collected off the coast of Fukushima and surrounding prefectures have decreased with time, and four years after the Fukushima Daiichi Nuclear Power Plant accident occurred, radiocesium concentrations have generally fallen below the detectable level (ca. < 10 Bq kg(-1)-raw). Only in some demersal fish species have detectable concentration levels still been found, and even these species have showed slow radiocesium decreases. The food web was considered as the major factor causing this phenomenon; however, slow elimination rates of radiocesium from these fish species also could be the cause. The latter effect was examined by considering that the (137)Cs concentration decreasing trend in fish could be fit with a set of three exponentially decreasing components; that is, having short, intermediate, and long biological half-lives. The long ecological half-life component was calculated using a 400-1500 d period of monitoring results for Japanese rockfish (Sebastes cheni) and compared with previous reported laboratory results for biological half-life. The obtained ecological half-lives ranged from 274-365 d, and these values agreed with the biological half-life of this fish species. This result implied that the long biological half-lives of radiocesium in some demersal fish species made their radiocesium contamination periods longer.

Evaluating the causes of photovoltaics cost reduction: Why is PV different?

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

Trancik, Jessika; McNerney, James; Kavlak, Goksin

The goals of this project were to quantify sources of cost reduction in photovoltaics (PV), improve theories of technological evolution, develop new analytical methods, and formu- late guidelines for continued cost reduction in photovoltaics. A number of explanations have been suggested for why photovoltaics have come down in cost rapidly over time, including increased production rates, significant R&D expenditures, heavy patenting ac- tivity, decreasing material and input costs, scale economies, reduced plant construction costs, and higher conversion efficiencies. We classified these proposed causes into low- level factors and high-level drivers. Low-level factors include technical characteristics, such as module efficiency ormore » wafer area, which are easily posed in terms of variables of a cost equation. High-level factors include scale economies, research and development (R&D), and learning-by-doing.« less

Light-induced V{sub oc} increase and decrease in high-efficiency amorphous silicon solar cells

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

Stuckelberger, M., E-mail: michael.stuckelberger@epfl.ch; Riesen, Y.; Despeisse, M.

High-efficiency amorphous silicon (a-Si:H) solar cells were deposited with different thicknesses of the p-type amorphous silicon carbide layer on substrates of varying roughness. We observed a light-induced open-circuit voltage (V{sub oc}) increase upon light soaking for thin p-layers, but a decrease for thick p-layers. Further, the V{sub oc} increase is enhanced with increasing substrate roughness. After correction of the p-layer thickness for the increased surface area of rough substrates, we can exclude varying the effective p-layer thickness as the cause of the substrate roughness dependence. Instead, we explain the observations by an increase of the dangling-bond density in both themore » p-layer—causing a V{sub oc} increase—and in the intrinsic absorber layer, causing a V{sub oc} decrease. We present a mechanism for the light-induced increase and decrease, justified by the investigation of light-induced changes of the p-layer and supported by Advanced Semiconductor Analysis simulation. We conclude that a shift of the electron quasi-Fermi level towards the conduction band is the reason for the observed V{sub oc} enhancements, and poor amorphous silicon quality on rough substrates enhances this effect.« less

Effects of Weight Reduction on Obesity STUDIES OF LIPID AND CARBOHYDRATE METABOLISM IN NORMAL AND HYPERLIPOPROTEINEMIC SUBJECTS

PubMed Central

Olefsky, Jerrold; Reaven, Gerald M.; Farquhar, John W.

1974-01-01

Considerable controversy exists over the purported role of obesity in causing hyperglycemia, hyperlipemia, hyperinsulinemia, and insulin resistance; and the potential beneficial effects of weight reduction remain incompletely defined. Hypertriglyceridemia is one of the metabolic abnormalities proposed to accompany obesity, and in order to help explain the mechanisms leading to this abnormality we have proposed the following sequential hypothesis: insulin resistance → hyperinsulinemia → accelerated hepatic triglyceride(TG) production → elevated plasma TG concentrations. To test this hypothesis and to gain insight into both the possible role of obesity in causing the above metabolic abnormalities and the potential benefit of weight reduction we studied the effects of weight loss on various aspects of carbohydrate and lipid metabolism in a group of 36 normal and hyperlipoproteinemic subjects. Only weak to absent correlations (r = 0.03 — 0.46) were noted between obesity and the metabolic variables measured. This points out that in our study group obesity cannot be the sole, or even the major, cause of these abnormalities in the first place. Further, we have observed marked decreases after weight reduction in fasting plasma TG (mean value: pre-weight reduction, 319 mg/100 ml; post-weight reduction, 180 mg/100 ml) and cholesterol (mean values: pre-weight reduction, 282 mg/100 ml; post-weight reduction, 223 mg/100 ml) levels, with a direct relationship between the magnitude of the fall in plasma lipid values and the height of the initial plasma TG level. We have also noted significant decreases after weight reduction in the insulin and glucose responses during the oral glucose tolerance test (37% decrease and 12% decrease, respectively). Insulin and glucose responses to liquid food before and after weight reduction were also measured and the overall post-weight reduction decrease in insulin response was 48% while the glucose response was relatively unchanged. In a subgroup of patients we studied both the degree of cellular insulin resistance and the rate of hepatic very low density (VLDL) TG production before and after weight reduction. These subjects demonstrated significant decreases after weight reduction in both degree of insulin resistance (33% decrease) and VLDL-TG production rates (40% decrease). Thus, weight reduction has lowered each of the antecedent variables (insulin resistance, hyperinsulinemia, and VLDL-TG production) that according to the above hypothesis lead to hypertriglyceridemia, and we believe the overall scheme is greatly strengthened. Furthermore, the consistent decreases in plasma TG and cholesterol levels seen in all subjects lead us to conclude that weight reduction is an important therapeutic modality for patients with endogenous hypertriglyceridemia. Images PMID:4357617

Serum alkaline phosphatase activity during zinc deficiency and long-term inflammatory stress.

PubMed

Naber, T H; Baadenhuysen, H; Jansen, J B; van den Hamer, C J; van den Broek, W

1996-05-30

A decrease in serum zinc can be caused by a real zinc deficiency but can also be caused by an apparent zinc deficiency, e.g. in inflammatory stress. The aim of this study was to evaluate the diagnostic power of serum alkaline phosphatase (AP) activity in the discrimination between pathophysiologic states of "real" and "apparent" zinc deficiency. A decrease in serum zinc was induced in growing and adult rats, by providing a diet low in zinc and by causing inflammatory stress. AP activity was determined using reagents low or enriched in zinc. Serum AP was decreased in zinc-deficient adult rats (P < 0.01). In zinc-deficient growing rats AP activity was not different from normal rats but AP activity decreased rapidly. In the same growing rats a significant difference was found in AP activities determined using buffers low and enriched in zinc (P < 0.001) between both groups of rats. After inducing inflammatory stress a decrease in AP activity (P < 0.01) and serum zinc (P < 0.001) was seen during the first few days. After the initial phase of inflammation AP activity normalized, serum zinc showed a rise which after correction for the decrease in serum albumin reached the level of the control rats. A difference in AP activity in buffers low and enriched in zinc was observed only during the first few days after induction of inflammatory stress (P < 0.001). Probably the method of measurement of the difference in enzyme activity, using buffers low and enriched in zinc, can be used as an indication for zinc deficiency in situations with changing AP enzyme concentrations. AP activity is decreased during the initial phase of inflammatory stress due to a decrease in serum zinc.

[Immunologic indexes, enzyme status of lymphocytes and functional activity of blood neutrophils in children with infectious mononucleosis caused by Epstein-Barr virus].

PubMed

Kurtasova, L M; Tolstikova, A E; Savchenko, A A

2013-01-01

Explore the immunological parameters, levels of activity of NAD(P)-dependent dehydrogenases lymphocytes, interferon status parameters, phagocytic activity and chemiluminescence response of neutrophils in the blood of children in the acute phase of infectious mononucleosis caused by the Epstein-Barr virus. 65 children at the age of 4-6 years old with infectious mononucleosis caused by EBV in acute phase were observed. Such indexes as cell-mediated, humoral and interferon immunity, NAD(P)-depended dehydrogenases activity in blood lymphocyte, phagocytes activity, levels of spontaneous and induced chemiluminescence ofperipheral blood neutrophils were studied. Children with EVB-infection have immunophenotype spectrum changes and changes of enzymes status of blood lymphocytes against the increasing in leucocytes and the useful increasing in lymphocytes. The useful increasing in IgA, IgM, IgG contenting in serum blood were found. The decreasing of spontaneous production of IFN alpha and the decreasing of induced production of IFNalpha, IFNgamma were determined. The breach of phagocytes activity and chemiluminescent response of blood neutrophils were found. The children in the acute phase of infectious mononucleosis caused by the Epstein-Barr virus, there are changes in the immune status, changes the activity of NAD(P)-dependent dehydrogenases in blood lymphocytes, marked changes in functional and metabolic state of peripheral blood neutrophils.

Effect of Food Deprivation on Formalin-Induced Nociceptive Behaviors and Beta-Endorphin and Sex Hormones Concentration in Rats

PubMed Central

Sarookhani, Mohammad-Reza; Ghasemi-Dashkhasan, Elmira; Heidari-Oranjaghi, Nima; Azhdari-Zarmehri, Hassan; Erami, Elaheh; Hosseini, Sedighe-Sadat

2014-01-01

Background: The present study examined the possible role of endogenous opioidergic system in effect of food deprivation on formalin-induced nociceptive behaviors in male and female rats. Also, we investigated the effect of food deprivation on the plasma level of beta-endorphin and sex hormones. Methods: Food was withdrawn 48 h prior to performing the formalin test, but water continued to be available ad libitum. The formalin was injected into hind plantar paw. Results: There is significant difference between male and female control rats during phase 2B. Following 48-h food deprivation, both male and female rats exhibited enhanced nociceptive behavior in response to formalin. Food deprivation for 12 and 24 h increased and for 48 h decreased beta-endorphin level in male and female rats. Food deprivation for 24 h decreased testosterone level in male, while it had no significant effect on female rats and food deprivation for 48 h decreased testosterone level in both sexes. Food deprivation for 24 h increased estradiol level in female and that for 48 h had no significant effect on male and female rats. Conclusions: The present study demonstrates the existence of food deprivation for 48 h causes enhancement of nociception in the formalin test in male and female rats that has correlation with decrease in plasma beta-endorphin and testosterone levels. PMID:24518552

Bisphenol A alters n-6 fatty acid composition and decreases antioxidant enzyme levels in rat testes: a LC-QTOF-based metabolomics study.

PubMed

Chen, Minjian; Xu, Bin; Ji, Wenliang; Qiao, Shanlei; Hu, Nan; Hu, Yanhui; Wu, Wei; Qiu, Lianglin; Zhang, Ruyang; Wang, Yubang; Wang, Shoulin; Zhou, Zuomin; Xia, Yankai; Wang, Xinru

2012-01-01

Male reproductive toxicity induced by exposure to bisphenol A (BPA) has been widely reported. The testes have proven to be a major target organ of BPA toxicity, so studying testicular metabolite variation holds promise for the discovery of mechanisms linked to the toxic effects of BPA on reproduction. Male Sprague-Dawley rats were orally administered doses of BPA at the levels of 0, 50 mg/kg/d for 8 weeks. We used an unbiased liquid chromatography-quadrupole time-of-flight (LC-QTOF)-based metabolomics approach to discover, identify, and analyze the variation of testicular metabolites. Two n-6 fatty acids, linoleic acid (LA) and arachidonic acid (AA) were identified as potential testicular biomarkers. Decreased levels of LA and increased levels of AA as well as AA/LA ratio were observed in the testes of the exposed group. According to these suggestions, testicular antioxidant enzyme levels were detected. Testicular superoxide dismutase (SOD) declined significantly in the exposed group compared with that in the non-exposed group, and the glutathione peroxidase (GSH-Px) as well as catalase (CAT) also showed a decreasing trend in BPA treated group. BPA caused testicular n-6 fatty acid composition variation and decreased antioxidant enzyme levels. This study emphasizes that metabolomics brings the promise of biomarkers identification for the discovery of mechanisms underlying reproductive toxicity.

Unchanged Levels of Soluble CD14 and IL-6 Over Time Predict Serious Non-AIDS Events in HIV-1-Infected People

PubMed Central

Sunil, Meena; Nigalye, Maitreyee; Somasunderam, Anoma; Martinez, Maria Laura; Yu, Xiaoying; Arduino, Roberto C.; Bell, Tanvir K.

2016-01-01

Abstract HIV-1-infected persons have increased risk of serious non-AIDS events (SNAEs) despite suppressive antiretroviral therapy. Increased circulating levels of soluble CD14 (sCD14), soluble CD163 (sCD163), and interleukin-6 (IL-6) at a single time point have been associated with SNAEs. However, whether changes in these biomarker levels predict SNAEs in HIV-1-infected persons is unknown. We hypothesized that greater decreases in inflammatory biomarkers would be associated with fewer SNAEs. We identified 39 patients with SNAEs, including major cardiovascular events, end stage renal disease, decompensated cirrhosis, non-AIDS-defining malignancies, and death of unknown cause, and age- and sex-matched HIV-1-infected controls. sCD14, sCD163, and IL-6 were measured at study enrollment (T1) and proximal to the event (T2) or equivalent duration in matched controls. Over ∼34 months, unchanged rather than decreasing levels of sCD14 and IL-6 predicted SNAEs. Older age and current illicit substance abuse, but not HCV coinfection, were associated with SNAEs. In a multivariate analysis, older age, illicit substance use, and unchanged IL-6 levels remained significantly associated with SNAEs. Thus, the trajectories of sCD14 and IL-6 levels predict SNAEs. Interventions to decrease illicit substance use may decrease the risk of SNAEs in HIV-1-infected persons. PMID:27344921

Chronic ethanol feeding causes depression of mitochondrial elongation factor Tu in the rat liver: implications for the mitochondrial ribosome.

PubMed

Weiser, Brian; Gonye, Gregory; Sykora, Peter; Crumm, Sara; Cahill, Alan

2011-05-01

Chronic ethanol feeding is known to negatively impact hepatic energy metabolism. Previous studies have indicated that the underlying lesion responsible for this may lie at the level of the mitoribosome. The aim of this study was to characterize the structure of the hepatic mitoribosome in alcoholic male rats and their isocalorically paired controls. Our experiments revealed that chronic ethanol feeding resulted in a significant depletion of both structural (death-associated protein 3) and functional [elongation factor thermo unstable (EF-Tu)] mitoribosomal proteins. In addition, significant increases were found in nucleotide elongation factor thermo stable (EF-Ts) and structural mitochondrial ribosomal protein L12 (MRPL12). The increase in MRPL12 was found to correlate with an increase in the levels of the 39S large mitoribosomal subunit. These changes were accompanied by decreased levels of nuclear- and mitochondrially encoded respiratory subunits, decreased amounts of intact respiratory complexes, decreased hepatic ATP levels, and depressed mitochondrial translation. Mathematical modeling of ethanol-mediated changes in EF-Tu and EF-Ts using prederived kinetic data predicted that the ethanol-mediated decrease in EF-Tu levels could completely account for the impaired mitochondrial protein synthesis. In conclusion, chronic ethanol feeding results in a depletion of mitochondrial EF-Tu levels within the liver that is mathematically predicted to be responsible for the impaired mitochondrial protein synthesis seen in alcoholic animals.

Serum paraoxonase activity and oxidative stress levels in patients with cutaneous anthrax.

PubMed

Karadas, S; Aslan, M; Ceylan, M R; Sunnetcioglu, M; Bozan, N; Kara, H; Demir, H

2017-07-01

Anthrax is a bacterial disease caused by the aerobic sporeforming bacterium Bacillus anthracis. It has been suggested that oxidative stress plays an important role in the pathogenesis of B. anthracis. The aim of this study was to investigate serum paraoxonase 1 (PON1) activity, catalase activity, malondialdehyde (MDA) levels, and superoxide dismutase (SOD) levels in patients with cutaneous anthrax. Fifteen patients with cutaneous anthrax and 15 healthy controls were enrolled in this study. The serum MDA levels, SOD levels, paraoxonase, arylesterase, and catalase activities were measured using a spectrophotometer. The serum SOD levels, paraoxonase, arylesterase, and catalase activities were significantly lower in patients with cutaneous anthrax than in controls (for all, p < 0.001), whereas MDA levels were significantly higher ( p < 0.001). No significant correlation was found between serum paraoxonase activity, arylesterase activity, SOD levels, and MDA levels (all, p > 0.05) in patients with cutaneous anthrax. The current study was the first to show decreased antioxidant levels and increased oxidant levels in patients with cutaneous anthrax. Therefore, decreased PON1 activity may play a role in the pathogenesis of cutaneous anthrax.

[The effect of vestibuloprotectors on the cyclic nucleotide system in experimental motion sickness].

PubMed

Leshchiniuk, I I; Konovalova, E O; Kvitchataia, A I; Shamraĭ, V G; Bobkov, Iu G

1989-01-01

Changes in the blood plasma cyclic nucleotide (cAMP and cGMP) level under the effect of vestibuloprotectors: bemytil and etoxibemytil were studied in rats with experimental motion sickness. It is established that rotation causes increase in the cAMP level and decrease in the cGMP level. The effect of the vestibuloprotectors is determined by the dose of the drug and is aimed first of all at maintaining a stable cAMP level in vestibular exertion. Under conditions of this experiment etoxibemytil was more effective than bemytil.

Retrospective, Demographic, and Clinical Investigation of the Causes of Postoperative Infection in Patients With Lumbar Spinal Stenosis Who Underwent Posterior Stabilization.

PubMed

Yaldiz, Can; Yaldiz, Mahizer; Ceylan, Nehir; Kacira, Ozlem Kitiki; Ceylan, Davut; Kacira, Tibet; Kizilcay, Gokhan; Tanriverdi, Taner

2015-07-01

Owing to the increasing population of elderly patients, a large number of patients with degenerative spondylosis are currently being surgically treated. Although basic measures for decreasing postoperative surgical infections (PSIs) are considered, it still remains among the leading causes of morbidity and mortality. The aim of this retrospective analysis is to present possible causes leading to PSI in patients who underwent surgery for lumbar degenerative spondylosis and highlight how it can be avoided to decrease morbidity and mortality. The study included 540 patients who underwent posterior stabilization due to degenerative lumbar stenosis between January 2013 and January 2014. The data before and after surgery was retrieved from the hospital charts. Patients with degenerative lumbar stenosis who were operated upon in this study had >2 levels of laminectomy and facetectomy. For this reason, posterior stabilization was performed for all the patients included in this study. Determining the causes of postoperative infection (PI) following spinal surgeries performed with instrumentation is a struggle. Seventeen different parameters that may be related to PI were evaluated in this study. The presence of systemic diseases, unknown glove perforations, and perioperative blood transfusions were among the parameters that increased the prevalence of PI. Alternatively, prolene sutures, double-layered gloves, and the use of rifampicin Sv (RIS) decreased the incidence of PI. Although the presence of systemic diseases, unnoticed glove perforations, and perioperative blood transfusions increased PIs, prolene suture material, double-layered gloves, and the use of RIS decreased PIs.

Structural, functional and blood perfusion changes in the rat retina associated with elevated intraocular pressure, measured simultaneously with a combined OCT+ERG system

PubMed Central

Tan, Bingyao; MacLellan, Benjamin; Mason, Erik

2018-01-01

Acute elevation of intraocular pressure (IOP) to ischemic and non-ischemic levels can cause temporary or permanent changes in the retinal morphology, function and blood flow/blood perfusion. Previously, such changes in the retina were assessed separately with different methods in clinical studies and animal models. In this study, we used a combined OCT+ ERG system in combination with Doppler OCT and OCT angiography (OCTA) imaging protocols, in order to evaluate simultaneously and correlate changes in the retinal morphology, the retinal functional response to visual stimulation, and the retinal blood flow/blood perfusion, associated with IOP elevation to ischemic and non-ischemic levels in rats. Results from this study suggest that the inner retina responds faster to IOP elevation to levels greater than 30 mmHg with significant reduction of the total retinal blood flow (TRBF), decrease of the capillaries’ perfusion and reduction of the ON bipolar cells contribution to the ERG traces. Furthermore, this study showed that ischemic levels of IOP elevation cause an additional significant decrease in the ERG photoreceptor response in the posterior retina. Thirty minutes after IOP normalization, retinal morphology, blood flow and blood perfusion recovered to baseline values, while retinal function did not recover completely. PMID:29509807

Determinants of all cause mortality in Poland.

PubMed

Genowska, Agnieszka; Jamiołkowski, Jacek; Szpak, Andrzej; Pajak, Andrzej

2012-01-01

The study objective was to evaluate quantitatively the relationship between demographic characteristics, socio-economic status and medical care resources with all cause mortality in Poland. Ecological study was performed using data for the population of 66 subregions of Poland, obtained from the Central Statistical Office of Poland. The information on the determinants of health and all cause mortality covered the period from 1st January 2005 to 31st December 2010. Results for the repeated measures were analyzed using Generalized Estimating Equations GEE model. In the model 16 independent variables describing health determinants were used, including 6 demographic variables, 6 socio-economic variables, 4 medical care variables. The dependent variable, was age standardized all cause mortality rate. There was a large variation in all cause mortality, demographic features, socio-economic characteristics, and medical care resources by subregion. All cause mortality showed weak associations with demographic features, among which only the increased divorce rate was associated with higher mortality rate. Increased education level, salaries, gross domestic product (GDP) per capita, local government expenditures per capita and the number of non-governmental organizations per 10 thousand population was associated with decrease in all cause mortality. The increase of unemployment rate was related with a decrease of all cause mortality. Beneficial relationship between employment of medical staff and mortality was observed. Variation in mortality from all causes in Poland was explained partly by variation in socio-economic determinants and health care resources.

Sodium valproate induces mitochondrial respiration dysfunction in HepG2 in vitro cell model.

PubMed

Komulainen, Tuomas; Lodge, Tiffany; Hinttala, Reetta; Bolszak, Maija; Pietilä, Mika; Koivunen, Peppi; Hakkola, Jukka; Poulton, Joanna; Morten, Karl J; Uusimaa, Johanna

2015-05-04

Sodium valproate (VPA) is a potentially hepatotoxic antiepileptic drug. Risk of VPA-induced hepatotoxicity is increased in patients with mitochondrial diseases and especially in patients with POLG1 gene mutations. We used a HepG2 cell in vitro model to investigate the effect of VPA on mitochondrial activity. Cells were incubated in glucose medium and mitochondrial respiration-inducing medium supplemented with galactose and pyruvate. VPA treatments were carried out at concentrations of 0-2.0mM for 24-72 h. In both media, VPA caused decrease in oxygen consumption rates and mitochondrial membrane potential. VPA exposure led to depleted ATP levels in HepG2 cells incubated in galactose medium suggesting dysfunction in mitochondrial ATP production. In addition, VPA exposure for 72 h increased levels of mitochondrial reactive oxygen species (ROS), but adversely decreased protein levels of mitochondrial superoxide dismutase SOD2, suggesting oxidative stress caused by impaired elimination of mitochondrial ROS and a novel pathomechanism related to VPA toxicity. Increased cell death and decrease in cell number was detected under both metabolic conditions. However, immunoblotting did not show any changes in the protein levels of the catalytic subunit A of mitochondrial DNA polymerase γ, the mitochondrial respiratory chain complexes I, II and IV, ATP synthase, E3 subunit dihydrolipoyl dehydrogenase of pyruvate dehydrogenase, 2-oxoglutarate dehydrogenase and glutathione peroxidase. Our results show that VPA inhibits mitochondrial respiration and leads to mitochondrial dysfunction, oxidative stress and increased cell death, thus suggesting an essential role of mitochondria in VPA-induced hepatotoxicity. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Nitric oxide-mediated modulation of iron regulatory proteins: implication for cellular iron homeostasis.

PubMed

Kim, Sangwon; Ponka, Prem

2002-01-01

Iron regulatory proteins (IRP1 and IRP2) control the synthesis of transferrin receptors (TfR) and ferritin by binding to iron-responsive elements (IREs) that are located in the 3' untranslated region (UTR) and the 5' UTR of their respective mRNAs. Cellular iron levels affect binding of IRPs to IREs and consequently expression of TfR and ferritin. Moreover, NO(.), a redox species of nitric oxide that interacts primarily with iron, can activate IRP1 RNA-binding activity resulting in an increase in TfR mRNA levels and a decrease in ferritin synthesis. We have shown that treatment of RAW 264.7 cells (a murine macrophage cell line) with NO(+) (nitrosonium ion, which causes S-nitrosylation of thiol groups) resulted in a rapid decrease in RNA-binding of IRP2, followed by IRP2 degradation, and these changes were associated with a decrease in TfR mRNA levels and a dramatic increase in ferritin synthesis. Moreover, we demonstrated that stimulation of RAW 264.7 cells with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) increased IRP1 binding activity, whereas RNA-binding of IRP2 decreased and was followed by a degradation of this protein. Furthermore, the decrease of IRP2 binding/protein levels was associated with a decrease in TfR mRNA levels and an increase in ferritin synthesis in LPS/IFN-gamma-treated cells, and these changes were prevented by inhibitors of inducible nitric oxide synthase. These results suggest that NO(+)-mediated degradation of IRP2 plays a major role in iron metabolism during inflammation.

Hindlimb unweighting induces changes in the p38MAPK contractile pathway of the rat abdominal aorta.

PubMed

Summers, Scott Matthew; Hayashi, Yuichiro; Nguyen, Steven Vu; Nguyen, Thu Minh; Purdy, Ralph Earl

2009-07-01

Hindlimb unweighting (HLU) of rats is a model used to mimic the cephalic fluid shift potentially involved in the orthostatic intolerance experienced by astronauts. Certain arteries in these rats exhibit a decreased contractile response to adrenergic agonists. It was shown previously that this may be caused by changes in thick filament regulation (Summers et al., Vascul Pharmacol 48: 208-214, 2008). In the present study, it was hypothesized that HLU also modifies thin filament regulation by effects on p38(MAPK) and ERK. Abdominal aorta rings from 20-day HLU rats and untreated controls were subjected to phenylephrine and phorbol 12,13-dibutyrate (PDBU) concentration response curves in the presence and absence of two inhibitors: the p38(MAPK) inhibitor SB-203580 and the MEK inhibitor U-0126. SB-203580 decreased control sensitivity to both agonists, but HLU sensitivity was not significantly affected. U-0126, which blocks enzymes immediately upstream of ERK, affected sensitivity to both agonists equally between control and HLU. Western blot analysis revealed no change in total levels of p38(MAPK) and its downstream target heat shock protein 27 but did reveal a decrease in phosphorylated levels of both after stimulation with PDBU and phenylephrine after HLU treatment. Neither total ERK nor phosphorylated levels after stimulation were affected by HLU. Total levels of caldesmon, a molecule downstream of both pathways, were decreased, but phosphorylated levels after stimulation were decreased by roughly twice as much. The results of this study demonstrate that HLU downregulates p38(MAPK), but not ERK, signaling. In turn, this may decrease actin availability for contraction.

Responses of prophenoloxidase system and related defence parameters of Litopenaeus vannamei to low salinity

NASA Astrophysics Data System (ADS)

Pan, Luqing; Xie, Peng; Hu, Fawen

2010-09-01

In this study, we investigated the effects of low salinity (26 and 21) on the prophenoloxidase (proPO) system and related defence parameters in the shrimp Litopenaeus vannamei. The results showed that low salinity induced a significant increase of dopamine (DA) concentration in haemolymph at 6 h of the experiment; on the other hand, total haemocyte count (THC), differential haemocyte count (DHC) and PO activity decreased over time to the lowest level at 24 h and remained low thereafter. Serine Protease (SP) and Proteinase Inhibitor (PI) activity in the two lower salinity treatments decreased to the lowest level at 12 and 24 h, respectively, and both recovered to the control level at 72 h. In contrast, α2- macroglobulin (α2M) activity in the two lower salinity treatments peaked at 24 h and then decreased to the control level at 72 h. Therefore, it may be concluded that stress-induced DA plays an important temporary role in neurotransmission and causes immune response in L. vannamei in adapting to salinity changes.

Different Cholinesterase Inhibitor Effects on CSF Cholinesterases in Alzheimer Patients

PubMed Central

Nordberg, Agneta; Darreh-Shori, Taher; Peskind, Elaine; Soininen, Hilkka; Mousavi, Malahat; Eagle, Gina; Lane, Roger

2014-01-01

Background The current study aimed to compare the effects of different cholinesterase inhibitors on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities and protein levels, in the cerebrospinal fluid (CSF) of Alzheimer disease (AD) patients. Methods and Findings AD patients aged 50–85 years were randomized to open-label treatment with oral rivastigmine, donepezil or galantamine for 13 weeks. AChE and BuChE activities were assayed by Ellman’s colorimetric method. Protein levels were assessed by enzyme-linked immunosorbent assay (ELISA). Primary analyses were based on the Completer population (randomized patients who completed Week 13 assessments). 63 patients were randomized to treatment. Rivastigmine was associated with decreased AChE activity by 42.6% and decreased AChE protein levels by 9.3%, and decreased BuChE activity by 45.6% and decreased BuChE protein levels by 21.8%. Galantamine decreased AChE activity by 2.1% and BuChE activity by 0.5%, but increased AChE protein levels by 51.2% and BuChE protein levels by10.5%. Donepezil increased AChE and BuChE activities by 11.8% and 2.8%, respectively. Donepezil caused a 215.2%increase in AChE and 0.4% increase in BuChE protein levels. Changes in mean AChE-Readthrough/Synaptic ratios, which might reflect underlying neurodegenerative processes, were 1.4, 0.6, and 0.4 for rivastigmine, donepezil and galantamine, respectively. Conclusion The findings suggest pharmacologically-induced differences between rivastigmine, donepezil and galantamine. Rivastigmine provides sustained inhibition of AChE and BuChE, while donepezil and galantamine do not inhibit BuChE and are associated with increases in CSF AChE protein levels. The clinical implications require evaluation. PMID:19199870

Different cholinesterase inhibitor effects on CSF cholinesterases in Alzheimer patients.

PubMed

Nordberg, Agneta; Darreh-Shori, Taher; Peskind, Elaine; Soininen, Hilkka; Mousavi, Malahat; Eagle, Gina; Lane, Roger

2009-02-01

The current study aimed to compare the effects of different cholinesterase inhibitors on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities and protein levels, in the cerebrospinal fluid (CSF) of Alzheimer disease (AD) patients. AD patients aged 50-85 years were randomized to open-label treatment with oral rivastigmine, donepezil or galantamine for 13 weeks. AChE and BuChE activities were assayed by Ellman's colorimetric method. Protein levels were assessed by enzyme-linked immunosorbent assay (ELISA). Primary analyses were based on the Completer population (randomized patients who completed Week 13 assessments). 63 patients were randomized to treatment. Rivastigmine was associated with decreased AChE activity by 42.6% and decreased AChE protein levels by 9.3%, and decreased BuChE activity by 45.6% and decreased BuChE protein levels by 21.8%. Galantamine decreased AChE activity by 2.1% and BuChE activity by 0.5%, but increased AChE protein levels by 51.2% and BuChE protein levels by 10.5%. Donepezil increased AChE and BuChE activities by 11.8% and 2.8%, respectively. Donepezil caused a 215.2% increase in AChE and 0.4% increase in BuChE protein levels. Changes in mean AChE-Readthrough/Synaptic ratios, which might reflect underlying neurodegenerative processes, were 1.4, 0.6, and 0.4 for rivastigmine, donepezil and galantamine, respectively. The findings suggest pharmacologically-induced differences between rivastigmine, donepezil and galantamine. Rivastigmine provides sustained inhibition of AChE and BuChE, while donepezil and galantamine do not inhibit BuChE and are associated with increases in CSF AChE protein levels. The clinical implications require evaluation.

Methoxychlor reduces estradiol levels by altering steroidogenesis and metabolism in mouse antral follicles in vitro

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

Basavarajappa, Mallikarjuna S., E-mail: mbasava2@illinois.edu; Craig, Zelieann R., E-mail: zelieann@illinois.edu; Hernandez-Ochoa, Isabel, E-mail: mihernandez@cinvestav.mx

2011-06-15

The organochlorine pesticide methoxychlor (MXC) is a known endocrine disruptor that affects adult rodent females by causing reduced fertility, persistent estrus, and ovarian atrophy. Since MXC is also known to target antral follicles, the major producer of sex steroids in the ovary, the present study was designed to test the hypothesis that MXC decreases estradiol (E{sub 2}) levels by altering steroidogenic and metabolic enzymes in the antral follicles. To test this hypothesis, antral follicles were isolated from CD-1 mouse ovaries and cultured with either dimethylsulfoxide (DMSO) or MXC. Follicle growth was measured every 24 h for 96 h. In addition,more » sex steroid hormone levels were measured using enzyme-linked immunosorbent assays (ELISA) and mRNA expression levels of steroidogenic enzymes as well as the E{sub 2} metabolic enzyme Cyp1b1 were measured using qPCR. The results indicate that MXC decreased E{sub 2}, testosterone, androstenedione, and progesterone (P{sub 4}) levels compared to DMSO. In addition, MXC decreased expression of aromatase (Cyp19a1), 17{beta}-hydroxysteroid dehydrogenase 1 (Hsd17b1), 17{alpha}-hydroxylase/17,20-lyase (Cyp17a1), 3{beta} hydroxysteroid dehydrogenase 1 (Hsd3b1), cholesterol side-chain cleavage (Cyp11a1), steroid acute regulatory protein (Star), and increased expression of Cyp1b1 enzyme levels. Thus, these data suggest that MXC decreases steroidogenic enzyme levels, increases metabolic enzyme expression and this in turn leads to decreased sex steroid hormone levels. - Highlights: > MXC inhibits steroidogenesis > MXC inhibits steroidogenic enzymes > MXC induces metabolic enzymes« less

ICESat/GLAS-derived changes in the water level of Hulun Lake, Inner Mongolia, from 2003 to 2009

NASA Astrophysics Data System (ADS)

Li, Chunlan; Wang, Jun; Hu, Richa; Yin, Shan; Bao, Yuhai; Li, Yuwei

2017-07-01

Hulun Lake is the largest freshwater lake in northern Inner Mongolia and even minor changes in its level may have major effects on the ecology of the lake and the surrounding area. In this study, we used high-precision elevation data for the interval from 2003-2009 measured by the Geoscience Laser Altimetry System (GLAS) on board the Ice, Cloud, and land Elevation Satellite (ICESat) to assess annual and seasonal water level variations of Hulun Lake. The altimetry data of 32 satellite tracks were processed using the RANdom SAmple Consensus algorithm (RANSAC) to eliminate elevation outliers, and subsequently the Normalized Difference Water Index (NDWI) was used to delineate the area of the lake. From 2003-2009, the shoreline of Hulun Lake retreated westwards, which was especially notable in the southern part of the lake. There was only a small decrease in water level, from 530.72 m to 529.22 m during 2003-2009, an average rate of 0.08 m/yr. The area of the lake decreased at a rate of 49.52 km2/yr, which was mainly the result of the shallow bathymetry in the southern part of the basin. The decrease in area was initially rapid, then much slower, and finally rapid again. Generally, the lake extent and water level decreased due to higher temperatures, intense evaporation, low precipitation, and decreasing runoff. And their fluctuations were caused by a decrease in intraannual temperature, evaporation, and a slight increase in precipitation. Overall, a combination of factors related to climate change were responsible for the variations of the water level of Hulun Lake during the study interval. The results improve our understanding of the impact of climate change on Hulun Lake and may facilitate the formulation of response strategies.

ICESat/GLAS-derived changes in the water level of Hulun Lake, Inner Mongolia, from 2003 to 2009

NASA Astrophysics Data System (ADS)

Li, Chunlan; Wang, Jun; Hu, Richa; Yin, Shan; Bao, Yuhai; Li, Yuwei

2018-06-01

Hulun Lake is the largest freshwater lake in northern Inner Mongolia and even minor changes in its level may have major effects on the ecology of the lake and the surrounding area. In this study, we used high-precision elevation data for the interval from 2003-2009 measured by the Geoscience Laser Altimetry System (GLAS) on board the Ice, Cloud, and land Elevation Satellite (ICESat) to assess annual and seasonal water level variations of Hulun Lake. The altimetry data of 32 satellite tracks were processed using the RANdom SAmple Consensus algorithm (RANSAC) to eliminate elevation outliers, and subsequently the Normalized Difference Water Index (NDWI) was used to delineate the area of the lake. From 2003-2009, the shoreline of Hulun Lake retreated westwards, which was especially notable in the southern part of the lake. There was only a small decrease in water level, from 530.72 m to 529.22 m during 2003-2009, an average rate of 0.08 m/yr. The area of the lake decreased at a rate of 49.52 km2/yr, which was mainly the result of the shallow bathymetry in the southern part of the basin. The decrease in area was initially rapid, then much slower, and finally rapid again. Generally, the lake extent and water level decreased due to higher temperatures, intense evaporation, low precipitation, and decreasing runoff. And their fluctuations were caused by a decrease in intraannual temperature, evaporation, and a slight increase in precipitation. Overall, a combination of factors related to climate change were responsible for the variations of the water level of Hulun Lake during the study interval. The results improve our understanding of the impact of climate change on Hulun Lake and may facilitate the formulation of response strategies.

Decreased expression of thyroid receptor-associated protein 220 in temporal lobe tissue of patients with refractory epilepsy

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

Li Jinmei; Wang Xuefeng; Xi Zhiqin

2006-10-06

Purpose: TRAP220 (thyroid hormone receptor-associated protein) functions as a coactivator for nuclear receptors and stimulates transcription by recruiting the TRAP mediator complex to hormone responsive promoter regions. Thus, TRAP220 enhances the function of thyroid/steroid hormone receptors such as thyroid hormone and oestrogen receptors. This study investigated the expression of TRAP220 mRNA and protein level in epileptic brains comparing with human control. Methods: We examined the expression of TRAP220 mRNA and protein levels in temporal lobes from patients with chronic pharmacoresistant epilepsy who have undergone surgery. Results: Expression of TRAP220 mRNA and protein was shown to be decreased significantly in themore » temporal cortex of the patients with epilepsy. Conclusions: Our work showed that a decrease in TRAP220 mRNA and protein levels may be involved in the pathophysiology of epilepsy and may be associated with impairment of the brain caused by frequent seizures.« less

Testing the neurovascular hypothesis of Alzheimer's disease: LRP-1 antisense reduces blood-brain barrier clearance, increases brain levels of amyloid-beta protein, and impairs cognition.

PubMed

Jaeger, Laura B; Dohgu, Shinya; Hwang, Mark C; Farr, Susan A; Murphy, M Paul; Fleegal-DeMotta, Melissa A; Lynch, Jessica L; Robinson, Sandra M; Niehoff, Michael L; Johnson, Steven N; Kumar, Vijaya B; Banks, William A

2009-01-01

Decreased clearance is the main reason amyloid-beta protein (Abeta) is increased in the brains of patients with Alzheimer's disease (AD). The neurovascular hypothesis states that this decreased clearance is caused by impairment of low density lipoprotein receptor related protein-1 (LRP-1), the major brain-to-blood transporter of Abeta at the blood-brain barrier (BBB). As deletion of the LRP-1 gene is a lethal mutation, we tested the neurovascular hypothesis by developing a cocktail of phosphorothioate antisenses directed against LRP-1 mRNA. We found these antisenses in comparison to random antisense selectively decreased LRP-1 expression, reduced BBB clearance of Abeta42, increased brain levels of Abeta42, and impaired learning ability and recognition memory in mice. These results support dysfunction of LRP-1 at the BBB as a mechanism by which brain levels of Abeta could increase and AD would be promoted.

[The adrenergic mechanisms are involved in the pulmonary hemodynamics changes following experimental myocardial ischemia in rabbits].

PubMed

Evlakhov, V I; Poiasov, I Z

2012-05-01

In acute experiments in anesthetized rabbits the changes of the pulmonary hemodynamics following myocardial ischemia in the region of the descendent left coronary artery were studied in control animals and after the blockade of alpha-adrenoreceptors by phentolamine or N-cholinoreceptors of autonomic ganglia by hexamethonium. Following myocardial ischemia in control animals the pulmonary artery pressure and flow decreased, the pulmonary vascular resistance was elevated not significantly, the cardiac output decreased more than pulmonary artery flow. Following myocardial ischemia after the blockade of alpha-adrenoreceptors the pulmonary artery flow and cardiac output decreased in the same level and the pulmonary vascular resistance was decreased. In these conditions the pulmonary artery pressure decreased more than in control animals, meanwhile the pulmonary artery flow was decreased in the same level as in the last case. Following myocardial ischemia after the blockade of N-cholinoreceptors the pulmonary hemodynamics changes were the same as they were following myocardial ischemia in the control rabbits, the cardiac output decreased more than pulmonary artery flow. The disbalance of the cardiac output and pulmonary artery flow changes in the case of myocardial ischemia was caused by the pulmonary vessel reactions following activations of the humoral adrenergic mechanisms.

Sexual characteristics of male guppies Poecilia reticulata serve as effect biomarkers of estrogens

NASA Astrophysics Data System (ADS)

Tian, Hua; Li, Yun; Wang, Wei; Zhao, Fei; Gao, Su; Ru, Shaoguo

2017-10-01

Guppies (Poecilia reticulata) are considered a candidate model species for the identification and testing of endocrine-disrupting chemicals. Male guppies may be used to address the challenge of making potential linkages between alterations of biomarkers, both at the cellular and organ level, and adverse outcomes. In the present study, a predictive relationship between sex characteristics and reproductive output was observed in male guppies that underwent a long-term toxicity test with 0.5 μg/L 17β-estradiol administered during the juvenile period. Radioimmunoassay and western blot analyses demonstrated that 17β-estradiol exposure caused a significant increase in testicular 17β-estradiol levels as well as the induction of exposure biomarkers, namely hepatic vitellogenin. Exposure to 17β-estradiol also caused a significant decrease in testosterone levels, which consequently reduced the gonadosomatic index, sperm counts, and the coloration index. These changes of male sexual characteristics further translated into adverse influences on reproduction, as measured by a decrease in off spring production and survival rate. Our results suggest that the above-mentioned sexual characteristics of male guppies may be considered potential in vivo biomarkers of estrogen effects on reproduction.

A dual-parameter tilted fiber Bragg grating-based sensor for liquid level and temperature monitoring

NASA Astrophysics Data System (ADS)

Osuch, Tomasz; Jurek, Tomasz; Markowski, Konrad; Jedrzejewski, Kazimierz

2016-09-01

In this paper, the concept and experimental characterization of tilted fiber Bragg grating (TFBG) based sensor for temperature and liquid level measurement are presented. It is shown that, when liquid level increases the peak amplitudes of cladding modes linearly decreases (in dB). In turn, changes in temperature causes a shift of the TFBG transmission spectrum, which can be accurately measured by monitoring the Bragg wavelength corresponding to the liquid level independent core mode. The main advantages of proposed sensor are simple design as well as linear responses to liquid level and temperature.

Role of nitric oxide in cellular iron metabolism.

PubMed

Kim, Sangwon; Ponka, Prem

2003-03-01

Iron regulatory proteins (IRP1 and IRP2) control the synthesis of transferrin receptors (TfR) and ferritin by binding to iron-responsive elements (IREs) which are located in the 3' untranslated region (UTR) and the 5' UTR of their respective mRNAs. Cellular iron levels affect binding of IRPs to IREs and consequently expression of TfR and ferritin. Moreover, NO*, a redox species of nitric oxide that interacts primarily with iron, can activate IRP1 RNA-binding activity resulting in an increase in TfR mRNA levels. We have shown that treatment of RAW 264.7 cells (a murine macrophage cell line) with NO+ (nitrosonium ion, which causes S-nitrosylation of thiol groups) resulted in a rapid decrease in RNA-binding of IRP2, followed by IRP2 degradation, and these changes were associated with a decrease in TfR mRNA levels. Moreover, we demonstrated that stimulation of RAW 264.7 cells with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) increased IRP1 binding activity, whereas RNA-binding of IRP2 decreased and was followed by a degradation of this protein. Furthermore, the decrease of IRP2 binding/protein levels was associated with a decrease in TfR mRNA levels in LPS/IFN-gamma-treated cells, and these changes were prevented by inhibitors of inducible nitric oxide synthase. These results suggest that NO+-mediated degradation of IRP2 plays a major role in iron metabolism during inflammation.

The effect of leptin and resveratrol on JAK/STAT pathways and Sirt-1 gene expression in the renal tissue of ischemia/reperfusion induced rats.

PubMed

Erkasap, S; Erkasap, N; Bradford, B; Mamedova, L; Uysal, O; Ozkurt, M; Ozyurt, R; Kutlay, O; Bayram, B

2017-01-01

Our study aimed to investigate the possible modifying effects of leptin and combined use of resveratrol on rat renal I/R injury and their relationship on signal pathways and apoptosis-related mechanisms. Renal ischemia-reperfusion (I/R) injury is an important cause of acute renal failure. Male Sprague Dawley rats were divided into 5 groups: Control, I/R, I/R+leptin, I/R+resveratrol and I/R+leptin+resveratrol. Leptin (10 μg/kg BW) was administered (i.p.) 30 min prior to I/R. Resveratrol was administered by gavage at 20 mg/kg BW per d for 12 d prior to I/R. The left renal artery was exposed to 1 h of ischemia and 1 h of reperfusion. Resveratrol treatment alone increased TNF-α, TNF-α R1, NF-κB, SIRT-1, STAT1 and STAT3 mRNA levels and decreased caspase 3 protein levels. Leptin treatment alone significantly decreased the caspase 3 protein levels. The combined use of resveratrol and leptin significantly increased STAT3, and caspase 3 mRNA levels, and decreased the caspase 3 protein levels. Apoptosis was significantly decreased especially in the leptin and leptin+resveratrol groups. The present study suggest that a combined use of resveratrol and leptin has preventive and regulatory effects on renal I/R injury; the mechanism involves decreasing apoptosis, likely by altering the JAK/STAT pathway and SIRT1 expression (Fig. 8, Ref. 24).

Tributyltin or triphenyltin inhibits aromatase activity in the human granulosa-like tumor cell line KGN.

PubMed

Saitoh, M; Yanase, T; Morinaga, H; Tanabe, M; Mu, Y M; Nishi, Y; Nomura, M; Okabe, T; Goto, K; Takayanagi, R; Nawata, H

2001-11-23

The superimposition of male sex organs (penis and vas deferens) in a female gastropod, called imposex, is widely attributed to the exposure to tributyltin (TBT) compounds, used world-wide in antifouling paints for ships. It has been hypothesized that the TBT-induced imposex is mediated by an increasing androgen level relative to the estrogen level, namely a decreased conversion of androgens to estrogens (i.e., aromatization). In the present study, we tested this hypothesis by examining the effects of TBT or triphenyltin (TPT) on the aromatase activity in a cultured human granulosa-like tumor cell line, KGN, which was recently established by our group. Treatment with more than 1000 ng/ml TBT compounds was very toxic to the cells and caused immediate cell death within 24 h, while 200 ng/ml was found to cause apoptosis of the cells. Treatment of the KGN cells for more than 48 h with 20 ng/ml TBT or TPT, which is a concentration level reported to cause imposex in marine species, did not affect cell proliferation but significantly suppressed the aromatase activity determined by a [(3)H]H(2)O release assay. Treatment with 20 ng/ml TBT compounds for 7 days also resulted in a reduction of the E2 production from Delta 4-androstenedione stimulated by db-cAMP. The changes in the aromatase activity by TBT compounds were associated with comparable changes in P450arom mRNA assessed by RT-PCR. The luciferase activity of the P450arom promoter II (1 kb) decreased after the addition of 20 ng/ml TBT compounds in transfected KGN cells either in a basic state or in states stimulated by db-cAMP. The Ad4BP-dependent increase in the luciferase activity of P450arom promoter II was also downregulated by such treatments. These results indicate that TBT compounds inhibited the aromatase activity and also decreased the P450arom mRNA level at the transcriptional level in KGN cells. The direct inhibitory effect of TBT compounds on the aromatase activity may therefore partly explain the induction of imposex by these compounds in female species. Copyright 2001 Academic Press.

Regulation of drainage canals on the groundwater level in a typical coastal wetlands

NASA Astrophysics Data System (ADS)

Liu, Qiang; Mou, Xia; Cui, Baoshan; Ping, Fan

2017-12-01

Activities related to reclamation alter wetland hydrological regimes and inevitably cause changes to groundwater level, which can result in the ecological degradation of coastal wetlands. Decreasing the groundwater level by the construction of drainage canals is an approach that has been widely used to control levels of root zone soil salinity as well as to protect freshwater wetlands or to expand agricultural land area in coastal wetlands. In this study, we assessed the influences of different drainage canal designs on the groundwater level using the Visual MODFLOW (VMOD) interface. We also provided an optimized drainage canal design suitable for the Yellow River Delta (YRD). Results showed that: (i) the groundwater level decreased in areas close to drainage canals, while only negligible effects were found on the groundwater level in areas with no drainage canals; (ii) the influence of drainage canals on the groundwater level decreased as distance increased; and (iii) a drainage canal network design of a depth of 5 m, with canal configuration of north-south direction and canal spacing of 1000 m was more effective in reducing the groundwater level in the study area. Our findings indicated that changes in groundwater level by the construction of drainage canals could help in our understanding of how groundwater influences freshwater wetlands and also aid in maintaining the integrity of coastal wetlands.

A metabolomics-driven approach reveals metabolic responses and mechanisms in the rat heart following myocardial infarction.

PubMed

Nam, Miso; Jung, Youngae; Ryu, Do Hyun; Hwang, Geum-Sook

2017-01-15

Myocardial infarction (MI) is caused by myocardial necrosis resulting from prolonged ischemia. However, the biological mechanisms underlying MI remain unclear. We evaluated metabolic and lipidomic changes in rat heart tissue from sham and MI at 1h, 1day and 10day after coronary ligation, using global profiling based on metabolomics. A time-dependent increase or decrease in polar and lipid metabolite levels was measured. The S-adenosylmethionine (SAM) concentration and the SAM/S-adenosylhomocysteine (SAH) ratio gradually decreased in a time-dependent manner and were significantly downregulated 10days after MI. Transcriptome analysis revealed that the levels of coenzyme Q (Coq)-3 and Coq5, both of which are SAM-dependent methyltransferases, were decreased in the MI groups. These results suggested that dysregulation of SAM may be related to down regulated COQ biosynthetic pathway. In addition, short-chain (C3) and medium-chain (C4-C12) acylcarnitine levels gradually decreased, whereas long-chain acylcarnitine (C14-18) levels increased, owing to a defect in β-oxidation during ischemia. These changes are related to energy-dependent metabolic pathways, and a subsequent decrease in adenosine triphosphate concentration was observed. The comprehensive integration of various omics data provides a novel means of understanding the underlying pathophysiological mechanisms of MI. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Water-level decline in the Apalachicola River, Florida, from 1954 to 2004, and effects on floodplain habitats

USGS Publications Warehouse

Light, Helen M.; Vincent, Kirk R.; Darst, Melanie R.; Price, Franklin D.

2006-01-01

From 1954 to 2004, water levels declined in the nontidal reach of the Apalachicola River, Florida, as a result of long-term changes in stage-discharge relations. Channel widening and deepening, which occurred throughout much of the river, apparently caused the declines. The period of most rapid channel enlargement began in 1954 and occurred primarily as a gradual erosional process over two to three decades, probably in response to the combined effect of a dam located at the head of the study reach (106 miles upstream from the mouth of the river), river straightening, dredging, and other activities along the river. Widespread recovery has not occurred, but channel conditions in the last decade (1995-2004) have been relatively stable. Future channel changes, if they occur, are expected to be minor. The magnitude and extent of water-level decline attributable to channel changes was determined by comparing pre-dam stage (prior to 1954) and recent stage (1995-2004) in relation to discharge. Long-term stage data for the pre-dam period and recent period from five streamflow gaging stations were related to discharge data from a single gage just downstream from the dam, by using a procedure involving streamflow lag times. The resulting pre-dam and recent stage-discharge relations at the gaging stations were used in combination with low-flow water-surface profile data from the U.S. Army Corps of Engineers to estimate magnitude of water-level decline at closely spaced locations (every 0.1 mile) along the river. The largest water-level declines occurred at the lowest discharges and varied with location along the river. The largest water-level decline, 4.8 feet, which occurred when sediments were scoured from the streambed just downstream from the dam, has been generally known and described previously. This large decline progressively decreased downstream to a magnitude of 1 foot about 40 river miles downstream from the dam, which is the location that probably marks the downstream limit of the influence of the dam on bed scour. Downstream from that location, previously unreported water-level declines progressively increased to 3 feet at a location 68 miles downstream from the dam, probably as a result of various channel modifications conducted in that part of the river. Water-level declines in the river have substantially changed long-term hydrologic conditions in more than 200 miles of off-channel floodplain sloughs, streams, and lakes and in most of the 82,200 acres of floodplain forests in the nontidal reach of the Apalachicola River. Decreases in duration of floodplain inundation at low discharges were large in the upstream-most 10 miles of the river (20-45 percent) and throughout most of the remaining 75 miles of the nontidal reach (10-25 percent). As a consequence of this decreased inundation, the quantity and quality of floodplain habitats for fish, mussels, and other aquatic organisms have declined, and wetland forests of the floodplain are changing in response to drier conditions. Water-level decline caused by channel change is probably the most serious anthropogenic impact that has occurred so far in the Apalachicola River and floodplain. This decline has been exacerbated by long-term reductions in spring and summer flow, especially during drought periods. Although no trends in total annual flow volumes were detected, long-term decreases in discharge for April, May, July, and August were apparent, and water-level declines during drought conditions resulting from decreased discharge in those 4 months were similar in magnitude to the water-level declines caused by channel changes. The observed changes in seasonal discharge are probably caused by a combination of natural climatic changes and anthropogenic activities in the Apalachicola-Chattahoochee-Flint River Basin. Continued research is needed for geomorphic studies to assist in the design of future floodplain restoration efforts and for hydrologic studies to monitor change

Correlation of Zn2+ content with aflatoxin content of corn.

PubMed Central

Failla, L J; Lynn, D; Niehaus, W G

1986-01-01

Forty-nine samples from the 1983 Virginia corn harvest were analyzed for aflatoxin, zinc, copper, iron, and manganese content. Values (mean +/- standard deviation) were as follows: aflatoxin, 117 +/- 360 micrograms/kg; zinc, 22.5 +/- 3.4 mg/kg; copper, 2.27 +/- 0.56 mg/kg; iron, 40.8 +/- 18.7 mg/kg; and manganese, 5.1 +/- 1.1 mg/kg. Aflatoxin levels positively correlated with zinc (Spearman correlation coefficient, 0.385; P less than 0.006) and copper levels (Spearman correlation coefficient, 0.573; P less than 0.0001). Based on biochemical data in the literature, we believe that the correlation with zinc is important and that there may be a cause-and-effect relationship between zinc levels in corn and aflatoxin levels which are produced upon infection with Aspergillus flavus or A. parasiticus. Control of aflatoxin contamination in field corn by decreasing the zinc levels may be feasible, but no methods to decrease zinc levels are currently available. PMID:3729406

Salt stress causes cell wall damage in yeast cells lacking mitochondrial DNA.

PubMed

Gao, Qiuqiang; Liou, Liang-Chun; Ren, Qun; Bao, Xiaoming; Zhang, Zhaojie

2014-03-03

The yeast cell wall plays an important role in maintaining cell morphology, cell integrity and response to environmental stresses. Here, we report that salt stress causes cell wall damage in yeast cells lacking mitochondrial DNA (ρ 0 ). Upon salt treatment, the cell wall is thickened, broken and becomes more sensitive to the cell wall-perturbing agent sodium dodecyl sulfate (SDS). Also, SCW11 mRNA levels are elevated in ρ 0 cells. Deletion of SCW11 significantly decreases the sensitivity of ρ 0 cells to SDS after salt treatment, while overexpression of SCW11 results in higher sensitivity. In addition, salt stress in ρ 0 cells induces high levels of reactive oxygen species (ROS), which further damages the cell wall, causing cells to become more sensitive towards the cell wall-perturbing agent.

Role of neuropeptide Y and proopiomelanocortin in fluoxetine-induced anorexia.

PubMed

Myung, Chang-Seon; Kim, Bom-Taeck; Choi, Si Ho; Song, Gyu Yong; Lee, Seok Yong; Jahng, Jeong Won

2005-06-01

Fluoxetine is an anorexic agent known to reduce food intake and weight gain. However, the molecular mechanism by which fluoxetine induces anorexia has not been well-established. We examined mRNA expression levels of neuropeptide Y (NPY) and proopiomelanocortin (POMC) in the brain regions of rats using RT-PCR and in situ hybridization techniques after 2 weeks of administering fluoxetine daily. Fluoxetine persistently suppressed food intake and weight gain during the experimental period. The pair-fed group confirmed that the reduction in body weight in the fluoxetine treated rats resulted primarily from decreased food intake. RT-PCR analyses showed that mRNA expression levels of both NPY and POMC were markedly reduced by fluoxetine treatment in all parts of the brain examined, including the hypothalamus. POMC mRNA in situ signals were significantly decreased, NPY levels tended to increase in the arcuate nucleus (ARC) of fluoxetine treated rats (compared to the vehicle controls). In the pair-fed group, NPY mRNA levels did not change, but the POMC levels decreased (compared with the vehicle controls). These results reveal that the chronic administration of fluoxetine decreases expression levels in both NPY and POMC in the brain, and suggests that fluoxetine-induced anorexia may not be mediated by changes in the ARC expression of either NPY or POMC. It is possible that a fluoxetine raised level of 5-HT play an inhibitory role in the orectic action caused by a reduced expression of ARC POMC (alpha-MSH).

[Analysis of the binding capacity of the benzodiazepine site of gabaa receptor in mice C57BL/6 and BALB/C pretreated with anxiolytics].

PubMed

Iarkova, M A

2011-01-01

The level of specific 3H-flunitrazepam binding in synaptosomal membranes of C57BL/6 and BALB/c mice brain underwent to the stress of different types has been studied. Mild stress (Elevated Plus Maze) was shown to induce the decrease of benzodiazepine binding in BALB/c mice only, while the strong one (Exposure to a predator) was revealed to cause this decrease in both strains. Behavioral effects of different non-benzodiazepine drugs possessing anxiolytic properties (Afobazol, Ladasten and Noopept) was accompanied with the normalization of the level of benzodiazepine reception, reduced by the stress of both modalities.

Effects of polyphenols from seed shells of Japanese horse chestnut (Aesculus turbinata BLUME) on methotrexate-induced intestinal injury in rats.

PubMed

Sugiyama, Akihiko; Kimura, Hideto; Ogawa, Satoshi; Yokota, Kazushige; Takeuchi, Takashi

2011-05-01

The purpose of this study was to evaluate the effects of polyphenols from seed shells of Japanese horse chestnut (JHP) on methotrexate (MTX)-induced intestinal injury in rats. MTX application caused intestinal morphological injury and increase in malondialdehyde (MDA) levels, decrease in levels of glutathione (GSH) and glutathione peroxidase (GSH-Px) activities in small intestine. However, oral administration of JHP ameliorated MTX-induced intestinal injury and inhibited the increase in MDA and the decrease in GSH and GSH-Px activity in small intestine. In conclusion, our results indicated that oral administration of JHP alleviated MTX-induced intestinal injury through its antioxidant properties.

Long-term dynamics of death rates of emphysema, asthma, and pneumonia and improving air quality

PubMed Central

Kravchenko, Julia; Akushevich, Igor; Abernethy, Amy P; Holman, Sheila; Ross, William G; Lyerly, H Kim

2014-01-01

Background The respiratory tract is a major target of exposure to air pollutants, and respiratory diseases are associated with both short- and long-term exposures. We hypothesized that improved air quality in North Carolina was associated with reduced rates of death from respiratory diseases in local populations. Materials and methods We analyzed the trends of emphysema, asthma, and pneumonia mortality and changes of the levels of ozone, sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and particulate matters (PM2.5 and PM10) using monthly data measurements from air-monitoring stations in North Carolina in 1993–2010. The log-linear model was used to evaluate associations between air-pollutant levels and age-adjusted death rates (per 100,000 of population) calculated for 5-year age-groups and for standard 2000 North Carolina population. The studied associations were adjusted by age group-specific smoking prevalence and seasonal fluctuations of disease-specific respiratory deaths. Results Decline in emphysema deaths was associated with decreasing levels of SO2 and CO in the air, decline in asthma deaths–with lower SO2, CO, and PM10 levels, and decline in pneumonia deaths–with lower levels of SO2. Sensitivity analyses were performed to study potential effects of the change from International Classification of Diseases (ICD)-9 to ICD-10 codes, the effects of air pollutants on mortality during summer and winter, the impact of approach when only the underlying causes of deaths were used, and when mortality and air-quality data were analyzed on the county level. In each case, the results of sensitivity analyses demonstrated stability. The importance of analysis of pneumonia as an underlying cause of death was also highlighted. Conclusion Significant associations were observed between decreasing death rates of emphysema, asthma, and pneumonia and decreases in levels of ambient air pollutants in North Carolina. PMID:25018627

Long-term dynamics of death rates of emphysema, asthma, and pneumonia and improving air quality.

PubMed

Kravchenko, Julia; Akushevich, Igor; Abernethy, Amy P; Holman, Sheila; Ross, William G; Lyerly, H Kim

2014-01-01

The respiratory tract is a major target of exposure to air pollutants, and respiratory diseases are associated with both short- and long-term exposures. We hypothesized that improved air quality in North Carolina was associated with reduced rates of death from respiratory diseases in local populations. We analyzed the trends of emphysema, asthma, and pneumonia mortality and changes of the levels of ozone, sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and particulate matters (PM2.5 and PM10) using monthly data measurements from air-monitoring stations in North Carolina in 1993-2010. The log-linear model was used to evaluate associations between air-pollutant levels and age-adjusted death rates (per 100,000 of population) calculated for 5-year age-groups and for standard 2000 North Carolina population. The studied associations were adjusted by age group-specific smoking prevalence and seasonal fluctuations of disease-specific respiratory deaths. Decline in emphysema deaths was associated with decreasing levels of SO2 and CO in the air, decline in asthma deaths-with lower SO2, CO, and PM10 levels, and decline in pneumonia deaths-with lower levels of SO2. Sensitivity analyses were performed to study potential effects of the change from International Classification of Diseases (ICD)-9 to ICD-10 codes, the effects of air pollutants on mortality during summer and winter, the impact of approach when only the underlying causes of deaths were used, and when mortality and air-quality data were analyzed on the county level. In each case, the results of sensitivity analyses demonstrated stability. The importance of analysis of pneumonia as an underlying cause of death was also highlighted. Significant associations were observed between decreasing death rates of emphysema, asthma, and pneumonia and decreases in levels of ambient air pollutants in North Carolina.

[A patient with depression due to digitalis poisoning].

PubMed

Schouten, J; van der Aa, G C

1984-04-01

A 85 year old lady suffering from depression is described. The depression was caused by digoxin intoxication. At first this was not recognized because of the low level of creatinine in the serum. This was the result of the decreased lean body mass, the patient weighing only 40 kilo!

PERSISTENT EPISODIC ACIDIFICATION OF STREAMS LINKED TO ACID RAIN EFFECTS ON SOIL

EPA Science Inventory

Episodic acidification of streams, identified in the late 1980s as one of the most significant environmental problems caused by acidic deposition, had not been evaluated since the early 1990s despite decreasing levels of acidic deposition over the past decade. This analysis indic...

Selenium Deficiency Induces Autophagy in Immune Organs of Chickens.

PubMed

Khoso, Pervez Ahmed; Pan, Tingru; Wan, Na; Yang, Zijiang; Liu, Ci; Li, Shu

2017-05-01

The aim of the present study was to investigate the effects of selenium (Se) deficiency on autophagy-related genes and on ultrastructural changes in the spleen, bursa of Fabricius, and thymus of chickens. The Se deficiency group was fed a basal diet containing Se at 0.033 mg/kg and the control group was fed the same basal diet containing Se at 0.15 mg/kg. The messenger RNA (mRNA) levels of the autophagy genes microtubule-associated protein 1 light chain 3 (LC3)-I, LC3-II, Beclin 1, dynein, autophagy associated gene 5 (ATG5), and target of rapamycin complex 1 (TORC1) were assessed using real-time qPCR. The protein levels of LC3-II, Beclin 1, and dynein were investigated using western blot analysis. Furthermore, the ultrastructure was observed using an electron microscope. The results indicated that spleen mRNA levels of LC3-I, LC3-II, Beclin 1, dynein, ATG5, and TORC1 and the protein levels of LC3-II, Beclin 1, and dynein were increased in the Se deficiency group compared with the control group. In the bursa of Fabricius, the mRNA levels of LC3-I, LC3-II, Beclin 1, dynein, ATG5, and TORC1 and the protein levels of Beclin 1 and dynein were increased; furthermore, the protein level of LC3-II was decreased in the Se deficiency group compared to the control group. In the thymus, the mRNA levels of LC3-I, Beclin 1, and ATG5 increased; the levels of LC3-II, dynein, and TORC1 were decreased; the protein level of Beclin 1 increased; and the levels of LC3-II and dynein decreased in the Se deficiency group compared to those in the control group. Further cellular morphological changes, such as autophagy vacuoles, autolysosomes, and lysosomal degradation, were observed in the spleen, bursa of Fabricius, and thymus of the Se-deficiency group. In summary, Se deficiency caused changes in autophagy-related genes, which increased the autophagic process and also caused structural damages to the immune organs of chickens.

Molecular mechanisms of intrauterine growth restriction.

PubMed

Gurugubelli Krishna, Rao; Vishnu Bhat, B

2017-07-10

Intrauterine growth restriction (IUGR) is a pregnancy specific disease characterized by decreased growth rate of fetus than the normal growth potential at particular gestational age. In the current scenario it is a leading cause of fetal and neonatal morbidity and mortality. In the last decade exhilarating experimental studies from several laboratories have provided fascinating proof for comprehension of molecular basis of IUGR. Atypical expression of enzymes governed by TGFβ causes the placental apoptosis and altered expression of TGFβ due to hyper alimentation causes impairment of lung function. Crosstalk of cAMP with protein kinases plays a prominent role in the regulation of cortisol levels. Increasing levels of NOD1 proteins leads to development of IUGR by increasing the levels of inflammatory mediators. Increase in leptin synthesis in placental trophoblast cells is associated with IUGR. In this review, we emphasize on the regulatory mechanisms of IUGR and its associated diseases. They may help improve the in-utero fetal growth and provide a better therapeutic intervention for prevention and treatment of IUGR.

Developmental and environmental regulation of antifreeze proteins in the mealworm beetle Tenebrio molitor.

PubMed

Graham, L A; Walker, V K; Davies, P L

2000-11-01

The yellow mealworm beetle, Tenebrio molitor, contains a family of small Cys-rich and Thr-rich thermal hysteresis proteins that depress the hemolymph freezing point below the melting point by as much as 5. 5 degrees C (DeltaT = thermal hysteresis). Thermal hysteresis protein expression was evaluated throughout development and after exposure to altered environmental conditions. Under favorable growth conditions, small larvae (11-13 mg) had only low levels of thermal hysteresis proteins or thermal hysteresis protein message, but these levels increased 10-fold and 18-fold, respectively, by the final larval instar (> 190 mg), resulting in thermal hysteresis > 3 degrees C. Exposure of small larvae (11-13 mg) to 4 weeks of cold (4 degrees C) caused an approximately 20-fold increase in thermal hysteresis protein concentration, well in excess of the less than threefold developmental increase seen after 4 weeks at 22 degrees C. Exposure of large larvae (100-120 mg) to cold caused 12-fold and sixfold increases in thermal hysteresis protein message and protein levels, respectively, approximately double the maximum levels they would have attained in the final larval instar at 22 degrees C. Thus, thermal hysteresis increased to similar levels (> 4 degrees C) in the cold, irrespective of the size of the larvae (the overwintering stage). At pupation, thermal hysteresis protein message levels decreased > 20-fold and remained low thereafter, but thermal hysteresis activity decreased much more slowly. Exposure to cold did not reverse this decline. Desiccation or starvation of larvae had comparable effects to cold exposure, but surprisingly, short daylength photoperiod or total darkness had no effect on either thermal hysteresis or message levels. As all environmental conditions that caused increased thermal hysteresis also inhibited growth, we postulate that developmental arrest is a primary factor in the regulation of T. molitor thermal hysteresis proteins.

Neuromuscular pharmacodynamics of mivacurium in adults with major burns.

PubMed

Han, T-H; Martyn, J A J

2011-05-01

Mivacurium is metabolized by plasma pseudocholinesterase (PChE) enzyme, which is decreased in burns. We tested whether the decreased metabolism of mivacurium due to decreased PChE activity can overcome the pharmacodynamic resistance to non-depolarizing relaxants previously seen in major burns. Thirty adults with 35 (13)% [mean (sd)] burn were studied at 5-91 post-burn days and 31 non-burns matched controls. Mivacurium 0.2 mg kg(-1) was administered as a single bolus. Neuromuscular block was monitored with single-twitch response using TOF-Watch™. Onset time (drug administration to maximal twitch suppression) and spontaneous recovery were measured. Onset time was significantly prolonged in burns when compared with non-burns (115 vs 90 s; P<0.001). The PChE levels were lower in burns [1432 (916) vs 2866 (731) IU litre(-1); P<0.001] and the neuromuscular recovery to 50% of baseline twitch height was prolonged in burns (41 vs 26 min; P<0.001). There was a significant correlation between PChE and time to 50% recovery for the whole group together (r=-0.6; P<0.001). The dibucaine numbers were not different. The prolonged onset time suggests resistance to neuromuscular effects, whereas the prolonged recovery suggests increased sensitivity. This divergent response can be explained by qualitative and quantitative changes in acetylcholine receptor expression causing resistance and decreased PChE activity causing sensitivity. Despite using a relatively large dose of mivacurium (0.2 mg kg(-1)) in the presence of decreased PChE levels, this did not overcome the resistance resulting from up-regulated receptors.

Schistosomiasis japonica and childhood nutritional status in northeastern Leyte, the Philippines: a randomized trial of praziquantel versus placebo.

PubMed

McGarvey, S T; Aligui, G; Graham, K K; Peters, P; Olds, G R; Olveda, R

1996-05-01

The hypothesis that infection with Schistosoma japonicum causes decreased nutritional status was studied in a randomized trial among 170 males and females, mean (SD) age 11.4 (3.5) years, residing in an endemic region of northeastern Leyte, Philippines. The S. japonicum-infected children were randomized to receive praziquantel or placebo and followed-up six months after randomization. Stature, weight, triceps, subscapular, and calf skinfold thicknesses and their sum, and hemoglobin level were measured at baseline and follow-up. Schistosoma japonicum eggs were detected in Kato-Katz stool smears and the intensity of infection was assessed by quantitative egg count. Intensities of hookworm, ascaris, and trichuris infections were also measured. The six-month levels of the anthropometric measures and hemoglobin were adjusted for age and their baseline levels and then compared between the praziquantel and placebo groups. Treatment interactions were also analyzed by sex. Baseline anthropometric and hemoglobin levels and parasite infection intensities were the same in the two groups. At six months, the praziquantel group had significantly higher hemoglobin levels (P < 0.001) and sum of skinfolds (P < 0.001) than the placebo group. Males had a significantly greater increase in hemoglobin levels with treatment than did females. The hemoglobin increase was not due to changes in hookworm intensity. The results show that schistosomiasis japonica caused decreased nutritional status in children and probably is partly responsible for the malnutrition and reduction in growth for age described in prior cross-sectional studies.

[Effects of magnesium valproate on endocrine system and reproductive functions of female epileptics].

PubMed

Xiang, Li; Ding, Jun-Qing; Huang, Xi-Shun

2011-08-09

To explore the effects of valproate (VPA) on endocrine system in adolescent and reproductive female patients with epilepsy. A total of 30 adolescent and reproductive female patients with a diagnosis of epilepsy at our hospital during July 2009 to March 2010 were recruited. All cases with magnesium VPA alone were included. The levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), estradiol (E2), progesterone (P) and testosterone (T) were detected respectively at pre-therapy and 3, 6 and 12 months post-therapy. And the changes of menstruation and ovaries were recorded. The serum concentration of PRL was lower at 3 and 6 months post-therapy than that at pre-therapy. There was significant difference (P = 0.010 and 0.014). The serum concentration of E2 significantly decreased after a 3-month therapy of valproate (P < 0.05). While comparing the parameter's level between the initial test and at a 3, 6 and 12-month follow-up, the level of P significantly decreased in the later groups than that of the former one while the level of T showed a marked increase. The levels of FSH and LH were not significantly different at pre- and post-therapy. And 6 (20%) of them presented with menstrual dysfunctions and 3 (10%) polycystic ovary. The valproate therapy can not only cause the changes of endocrine system and hormonal levels, but also induce such endocrine dysfunction syndromes as menstrual suspension and polycystic ovary. It eventually causes polycystic ovary syndrome.

Glucose rapidly decreases plasma membrane GLUT4 content in rat skeletal muscle.

PubMed

Marette, A; Dimitrakoudis, D; Shi, Q; Rodgers, C D; Klip, A; Vranic, M

1999-02-01

We have previously demonstrated that chronic hyperglycemia per se decreases GLUT4 glucose transporter expression and plasma membrane content in mildly streptozotocin- (STZ) diabetic rats (Biochem. J. 284, 341-348, 1992). In the present study, we investigated the effect of an acute rise in glycemia on muscle GLUT4 and GLUT1 protein contents in the plasma membrane, in the absence of insulin elevation. Four experimental groups of rats were analyzed in the postabsorptive state: 1. Control rats. 2. Hyperglycemic STZ-diabetic rats with moderately reduced fasting insulin levels. 3. STZ-diabetic rats made normoglycemic with phlorizin treatment. 4. Phlorizin-treated (normoglycemic) STZ-diabetic rats infused with glucose for 40 min. The uniqueness of the latter model is that glycemia can be rapidly raised without any concomitant increase in plasma insulin levels. Plasma membranes were isolated from hindlimb muscle and GLUT1 and GLUT4 proteins amounts determined by Western blot analysis. As predicted, STZ-diabetes caused a significant decrease in the abundance of GLUT4 in the isolated plasma membranes. Normalization of glycemia for 3 d with phlorizin treatment restored plasma membrane GLUT4 content in muscle of STZ-diabetic rats. A sudden rise in glycemia over a period of 40 min caused the GLUT4 levels in the plasma membrane fraction to decrease to those of nontreated STZ-diabetic rats. In contrast to the GLUT4 transporter, plasma membrane GLUT1 abundance was not changed by the acute glucose challenge. It is concluded that glucose can have regulatory effect by acutely reducing plasma membrane GLUT4 protein contents in rat skeletal muscle. We hypothesize that this glucose-induced downregulation of plasma membrane GLUT4 could represent a protective mechanism against excessive glucose uptake under hyperglycemic conditions accompanied by insulin resistance.

SLAP deficiency decreases dsDNA autoantibody production

PubMed Central

Peterson, Lisa K.; Pennington, Luke F.; Shaw, Laura A.; Brown, Meredith; Treacy, Eric C.; Friend, Samantha F.; Hatlevik, Øyvind; Rubtsova, Kira; Rubtsov, Anatoly V.; Dragone, Leonard L.

2014-01-01

Src-like adaptor protein (SLAP) adapts c-Cbl, an E3 ubiquitin ligase, to activated components of the BCR signaling complex regulating BCR levels and signaling in developing B cells. Based on this function, we asked whether SLAP deficiency could decrease the threshold for tolerance and eliminate development of autoreactive B cells in two models of autoantibody production. First, we sensitized mice with a dsDNA mimetope that causes an anti-dsDNA response. Despite equivalent production of anti-peptide antibodies compared to BALB/c controls, SLAP−/− mice did not produce anti-dsDNA. Second, we used the 56R tolerance model. SLAP−/− 56R mice had decreased levels of dsDNA-reactive antibodies compared to 56R mice due to skewed light chain usage. Thus, SLAP is a critical regulator of B-cell development and function and its deficiency leads to decreased autoreactive B cells that are otherwise maintained by inefficient receptor editing or failed negative selection. PMID:24440645

SLAP deficiency decreases dsDNA autoantibody production.

PubMed

Peterson, Lisa K; Pennington, Luke F; Shaw, Laura A; Brown, Meredith; Treacy, Eric C; Friend, Samantha F; Hatlevik, Øyvind; Rubtsova, Kira; Rubtsov, Anatoly V; Dragone, Leonard L

2014-02-01

Src-like adaptor protein (SLAP) adapts c-Cbl, an E3 ubiquitin ligase, to activated components of the BCR signaling complex regulating BCR levels and signaling in developing B cells. Based on this function, we asked whether SLAP deficiency could decrease the threshold for tolerance and eliminate development of autoreactive B cells in two models of autoantibody production. First, we sensitized mice with a dsDNA mimetope that causes an anti-dsDNA response. Despite equivalent production of anti-peptide antibodies compared to BALB/c controls, SLAP(-/-) mice did not produce anti-dsDNA. Second, we used the 56R tolerance model. SLAP(-/-) 56R mice had decreased levels of dsDNA-reactive antibodies compared to 56R mice due to skewed light chain usage. Thus, SLAP is a critical regulator of B-cell development and function and its deficiency leads to decreased autoreactive B cells that are otherwise maintained by inefficient receptor editing or failed negative selection. Copyright © 2013 Elsevier Inc. All rights reserved.

Changes in plasma volume during bed rest - Effects of menstrual cycle and estrogen administration

NASA Technical Reports Server (NTRS)

Fortney, S. M.; Beckett, W. S.; Carpenter, A. J.; Davis, J.; Drew, H.

1988-01-01

The effect of increased blood estrogen concentration, caused either during normal menstrual cycles or by exogenous administration of premarin, on the bed-rest (BR) induced decrease in plasma volume (PV) was investigated. In women who underwent duplicate 11-day BR without estrogen supplementation, the PV was found to decrease significantly, during the first 5 days of BR, to a lower level at which it remained for the rest of the BR period. In women who began BR in the periovulatory stage of the menstrual cycle, the loss of PV was delayed, while women who began BR during other stages of the cycle exhibited the usual trend of the PV decrease during the BR. In women who underwent a single 12-day BR period while taking premarin (1.25 mg/day), PV was found to decrease during the first 4-5 days of BR, but then returned toward the pre-BR level during the remainder of the BR, indicating that estrogens have a role in stabilizing body fluid volume.

Levothyroxine rescues the lead-induced hypothyroidism and impairment of long-term potentiation in hippocampal CA1 region of the developmental rats

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

Wu Chuanyun; Liu Bing; Wang Huili

Lead (Pb) exposure during development has been associated with impaired long-term potentiation (LTP). Hypothyroidism happening upon subjects with occupational exposure to Pb is suggestive of an adverse effect of Pb on thyroid homeostasis, leading to the hypothesis that Pb exposure may alter thyroid hormone homeostasis. Hippocampus is one of the targets of Pb exposure, and is sensitive to and dependent on thyroid hormones, leading us to explore whether levothyroxine (L-T{sub 4}) administration could alter the thyroid disequilibrium and impairment of LTP in rat hippocampus caused by Pb exposure. Our results show that Pb exposure caused a decrease in triiodothyronine (T{submore » 3}) and tetraiodothyronine (T{sub 4}) levels accompanied by a dramatic decrease of TSH and application of L-T{sub 4} restored these changes to about control levels. Hippocampal and blood Pb concentration were significantly reduced following L-T{sub 4} treatment. L-T{sub 4} treatment rescued the impairment of LTP induced by the Pb exposure. These results suggest that Pb exposure may lead to thyroid dysfunction and induce hypothyroidism and provide a direct electrophysiological proof that L-T{sub 4} relieves chronic Pb exposure-induced impairment of synaptic plasticity. - Highlights: > Lead may interfere with thyroid hormone homeostasis and induce hypothyroidism. > Levothyroxine decreases the hippocampal and blood Pb concentration. > Levothyroxine amends the T{sub 3}, T{sub 4} and TSH levels in blood. > Levothyroxine rescues the impaired LTP in CA1.« less

In vitro effects of diethylstilbestrol, genistein, 4-tert-butylphenol, and 4-tert-octylphenol on steroidogenic activity of isolated immature rat ovarian follicles

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

Myllymaeki, Sari; Haavisto, Tapio; Vainio, Minna

2005-04-01

Isolated rat ovarian follicles grow and produce steroid hormones in vitro and so provide a good model for studying the effects of hormonally active compounds on follicular steroidogenesis. We have evaluated the effects of diethylstilbestrol (DES), genistein (GEN) and two alkylphenols, 4-tert-butylphenol (BP) and 4-tert-octylphenol (OP) on the growth, survival, and steroid hormone and cAMP production by isolated 14-day-old rat (Sprague-Dawley) ovarian follicles. During a 5-day culture, FSH was obligatory for follicle growth and increased estradiol and testosterone secretion in a dose-dependent manner. DES (10{sup -6} M) caused the strongest decline in estradiol and testosterone levels but did not havemore » detectable effects on either cAMP production or aromatase enzyme activity. GEN caused a prominent decrease in cAMP and testosterone levels without significant changes in secreted estradiol. The latter, apparently, was due to a dose-dependent stimulation of aromatase enzyme activity in the presence of genistein. Both BP and OP decreased estradiol and testosterone secretion in a dose-dependent manner while no effect on aromatase activity was observed. OP, unlike BP, decreased forskolin-induced cAMP levels. Xenoestrogens at the used concentrations did not interfere with the growth and survival of the follicles. The results indicate that isolated ovarian follicles representing intact morphological and functional units offer a sensitive model system for elucidating the female-specific reproductive effects of environmental chemicals.« less

Asthma causes inflammation of human pulmonary arteries and decreases vasodilatation induced by prostaglandin I2 analogs.

PubMed

Foudi, Nabil; Badi, Aouatef; Amrane, Mounira; Hodroj, Wassim

2017-12-01

Asthma is a chronic inflammatory disease associated with increased cardiovascular events. This study assesses the presence of inflammation and the vascular reactivity of pulmonary arteries in patients with acute asthma. Rings of human pulmonary arteries obtained from non-asthmatic and asthmatic patients were set up in organ bath for vascular tone monitoring. Reactivity was induced by vasoconstrictor and vasodilator agents. Protein expression of inflammatory markers was detected by western blot. Prostanoid releases and cyclic adenosine monophosphate (cAMP) levels were quantified using specific enzymatic kits. Protein expression of cluster of differentiation 68, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and cyclooxygenase-2 was significantly increased in arteries obtained from asthmatic patients. These effects were accompanied by an alteration of vasodilatation induced by iloprost and treprostinil, a decrease in cAMP levels and an increase in prostaglandin (PG) E 2 and PGI 2 synthesis. The use of forskolin (50 µmol/L) has restored the vasodilatation and cAMP release. No difference was observed between the two groups in reactivity induced by norepinephrine, angiotensin II, PGE 2 , KCl, sodium nitroprusside, and acetylcholine. Acute asthma causes inflammation of pulmonary arteries and decreases vasodilation induced by PGI 2 analogs through the impairment of cAMP pathway.

Effect of Two Ginger Varieties on Arginase Activity in Hypercholesterolemic Rats.

PubMed

Akinyemi, Ayodele Jacob; Oboh, Ganiyu; Ademiluyi, Adedayo Oluwaseun; Boligon, Aline Augusti; Athayde, Margareth Linde

2016-04-01

Recently, ginger has been used in traditional Chinese medicine as an herbal therapy for treating several cardiovascular diseases, however, information on its mechanism of action is limited. The present study assessed the effect of two ginger varieties (Zingiber officinale and Curcuma longa) on the arginase activity, atherogenic index, levels of liver thiobarbituric acid reactive substances (TBARSs), and plasma lipids in rats fed with a high-cholesterol (2%) diet for 14 days. Following the treatment period, it was found that feeding a high-cholesterol diet to rats caused significant (p < 0.05) increases in arginase activity, atherogenic index, levels of TBARS, total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C) with a concomitant decrease in high-density lipoprotein cholesterol (HDL-C). However, both ginger and turmeric (2% and 4%) caused significant (p < 0.05) decreases in arginase activity and the atherogenic index, and prevented hypercholesterolemia by decreasing the TC, TGs, and LDL-C while increasing the HDL-C when compared with the controls. In conclusion, dietary supplementation with both types of rhizomes (ginger and turmeric) inhibited arginase activity and prevented hypercholesterolemia in rats that received a high-cholesterol diet. Therefore, these activities of ginger and turmeric represent possible mechanisms underlying its use in herbal medicine to treat several cardiovascular diseases. Copyright © 2015. Published by Elsevier B.V.

Mechanism for the decrease in the FIP1L1-PDGFRalpha protein level in EoL-1 cells by histone deacetylase inhibitors.

PubMed

Ishihara, Kenji; Kaneko, Motoko; Kitamura, Hajime; Takahashi, Aki; Hong, Jang Ja; Seyama, Toshio; Iida, Koji; Wada, Hiroshi; Hirasawa, Noriyasu; Ohuchi, Kazuo

2008-01-01

Acetylation and deacetylation of proteins occur in cells in response to various stimuli, and are reversibly catalyzed by histone acetyltransferase and histone deacetylase (HDAC), respectively. EoL-1 cells have an FIP1L1-PDGFRA fusion gene that causes transformation of eosinophilic precursor cells into leukemia cells. The HDAC inhibitors apicidin and n-butyrate suppress the proliferation of EoL-1 cells and induce differentiation into eosinophils by a decrease in the protein level of FIP1L1-PDGFRalpha without affecting the mRNA level for FIP1L1-PDGFRA. In this study, we analyzed the mechanism by which the protein level of FIP1L1-PDGFRalpha is decreased by apicidin and n-butyrate. EoL-1 cells were incubated in the presence of the HDAC inhibitors apicidin, trichostatin A or n-butyrate. The protein levels of FIP1L1-PDGFRalpha and phosphorylated eIF-2alpha were determined by Western blotting. Actinomycin D and cycloheximide were used to block RNA synthesis and protein synthesis, respectively, in the chasing experiment of the amount of FIP1L1-PDGFRalpha protein. When apicidin- and n-butyrate-treated EoL-1 cells were incubated in the presence of actinomycin D, the decrease in the protein level of FIP1L1-PDGFRalpha was significantly enhanced when compared with controls. In contrast, the protein levels were not changed by cycloheximide among these groups. Apicidin and n-butyrate induced the continuous phosphorylation of eIF-2alpha for up to 8 days. The decrease in the level of FIP1L1-PDGFRalpha protein by continuous inhibition of HDAC may be due to the decrease in the translation rate of FIP1L1-PDGFRA. Copyright 2008 S. Karger AG, Basel.

AIDS as a leading cause of death among young adults in Italy.

PubMed

Conti, S; Farchi, G; Prati, S

1994-12-01

The objective of this study is to describe the impact of AIDS on the mortality of young adult (aged 25 to 44 years) in Italy, at both the national and regional level. We analyzed the official mortality data for Italy: the most recent data available being from 1990. General mortality trends show that while mortality among young women is still decreasing (i.e. from a standardized rate of 83.8 per 100,000 in 1980 to 68.4 in 1990), mortality among young men began to rise in the mid-1980s, after a steady decrease over many years. Among the 25-34 year olds, however, this reversal in trend is more marked, notwithstanding a decrease or stabilization in most major causes of death. In fact it coincides with the appearance and spread of AIDS in Italy, which has affected young men in particular. (The peak age group for AIDS deaths is the 25-34 year olds). Mortality data from 1990 reveal that AIDS is the fourth leading cause of death in Italy among men between the ages of 25 and 44 years. Among 25-34 year-old men, however, AIDS is the second leading cause of death, after road accidents. AIDS also contributes greatly to the general mortality in individual regions, both among 25-44 year-old men (Lombardy, Liguria, Lazio, Emilia-Romagna, Tuscany), and especially among 25-34 year-old men (Lombardy, Liguria, Lazio, Sardinia, where it is the number one cause of death, Emilia-Romagna, Tuscany, and Veneto, where it is the number two cause of death).

The efficacy of a neonatal screening programme in decreasing the hospitalization rate of patients with G6PD deficiency in southern Iran.

PubMed

Cohan, Nader; Karimi, Mehran; Khalili, Amir Hossein; Falahzadeh, Mohammad Hossein; Samadi, Behrang; Mahdavi, Mohammad Reza

2010-01-01

To investigate whether a neonatal screening programme for G6PD deficiency has decreased hospitalization for acute haemolytic attack in the Fars province of southern Iran. A total of 850 patients registered with G6PD deficiency were included in the study. Variables including age, sex, time and cause of hospitalization, cause of haemolytic crisis, positive history of blood transfusion, G6PD enzyme deficiency, blood urea nitrogen (BUN) and creatinine were recorded based on a standard questionnaire. All patients were analysed for G6PD enzyme level based on a quantitative test. Five hundred and fifty-three patients were hospitalized before the introduction of the neonatal screening programme (2001-2004) and 297 afterwards (2005-2008). Of those patients hospitalized after the introduction of the screening programme, 237 were wrongly classified as normal and 60 were recorded as having G6PD enzyme deficiency by the neonatal screening programme. The main causes of haemolytic crisis in G6PD-deficient patients were fava bean consumption (88.2%), underlying infection (10.9%) and drugs (0.8%). Our study showed the effectiveness of the neonatal screening programme in decreasing the hospitalization rate.

Dephosphorylation and inactivation of NPR2 guanylyl cyclase in granulosa cells contributes to the LH-induced decrease in cGMP that causes resumption of meiosis in rat oocytes

PubMed Central

Egbert, Jeremy R.; Shuhaibar, Leia C.; Edmund, Aaron B.; Van Helden, Dusty A.; Robinson, Jerid W.; Uliasz, Tracy F.; Baena, Valentina; Geerts, Andreas; Wunder, Frank; Potter, Lincoln R.; Jaffe, Laurinda A.

2014-01-01

In mammals, the meiotic cell cycle of oocytes starts during embryogenesis and then pauses. Much later, in preparation for fertilization, oocytes within preovulatory follicles resume meiosis in response to luteinizing hormone (LH). Before LH stimulation, the arrest is maintained by diffusion of cyclic (c)GMP into the oocyte from the surrounding granulosa cells, where it is produced by the guanylyl cyclase natriuretic peptide receptor 2 (NPR2). LH rapidly reduces the production of cGMP, but how this occurs is unknown. Here, using rat follicles, we show that within 10 min, LH signaling causes dephosphorylation and inactivation of NPR2 through a process that requires the activity of phosphoprotein phosphatase (PPP)-family members. The rapid dephosphorylation of NPR2 is accompanied by a rapid phosphorylation of the cGMP phosphodiesterase PDE5, an enzyme whose activity is increased upon phosphorylation. Later, levels of the NPR2 agonist C-type natriuretic peptide decrease in the follicle, and these sequential events contribute to the decrease in cGMP that causes meiosis to resume in the oocyte. PMID:25183874

Glutamine synthetase activity and glutamate uptake in hippocampus and frontal cortex in portal hypertensive rats

PubMed Central

Acosta, Gabriela Beatriz; Fernández, María Alejandra; Roselló, Diego Martín; Tomaro, María Luján; Balestrasse, Karina; Lemberg, Abraham

2009-01-01

AIM: To study glutamine synthetase (GS) activity and glutamate uptake in the hippocampus and frontal cortex (FC) from rats with prehepatic portal vein hypertension. METHODS: Male Wistar rats were divided into sham-operated group and a portal hypertension (PH) group with a regulated stricture of the portal vein. Animals were sacrificed by decapitation 14 d after portal vein stricture. GS activity was determined in the hippocampus and FC. Specific uptake of radiolabeled L-glutamate was studied using synaptosome-enriched fractions that were freshly prepared from both brain areas. RESULTS: We observed that the activity of GS increased in the hippocampus of PH rats, as compared to control animals, and decreased in the FC. A significant decrease in glutamate uptake was found in both brain areas, and was more marked in the hippocampus. The decrease in glutamate uptake might have been caused by a deficient transport function, significantly and persistent increase in this excitatory neurotransmitter activity. CONCLUSION: The presence of moderate ammonia blood levels may add to the toxicity of excitotoxic glutamate in the brain, which causes alterations in brain function. Portal vein stricture that causes portal hypertension modifies the normal function in some brain regions. PMID:19533812

[Mortality by avoidable causes in preschool children].

PubMed

Lurán, Albenia; López, Elizabeth; Pinilla, Consuelo; Sierra, Pedro

2009-03-01

The infant-mortality rate in children aged less than five is an indicator of the general state of health of a population and directly reflects the quality of life and the level of socio-economic development of a country. Avoidable mortality was assessed in preschool children as a reflection of Colombia quality of life and socio-economic development. Mortality trends were analyzed in preschool children aged less than five throughout Colombia during a 20-year period from 1985-2004, and focused on mortality causes that were considered avoidable. This was a descriptive, retrospective study; the sources of information were Departamento Administrativo Nacional de Estadística records of deaths and population projections 1985-2004. Mortality rate due to avoidable causes was the statistical indicator. In children aged less than one, the reducible mortality due to "early diagnosis and medical treatment" occupied the first place amongst causes for every year of the study period and accounted for more than 50% of recorded deaths. In children aged 1 to 4, the category "other important reducible causes" was associated with 40% of recorded deaths-deaths due mainly to respiratory diseases. Over the 20-year period, the avoidable mortality rate decreased by 34% in children aged less than one, in children 1-4, it decreased by 23%. Although the infant-mortality rate in preschool children was reduced, the decrease was small, from 80% to 77%. The situation requires more analysis with respect to strategies in public health, particularly concerning preventable diseases of the infancy.

p-Aminophenol-induced hepatotoxicity in hamsters: role of glutathione.

PubMed

Fu, Xin; Chen, Theresa S; Ray, Mukunda B; Nagasawa, Herbert T; Williams, Walter M

2004-01-01

p-Aminophenol (PAP) is a widely used industrial chemical and a known nephrotoxin. Recently, it was found to also cause hepatotoxicity and glutathione (GSH) depletion in mice. The exact mechanism of liver toxicity is not known. The aims of this study were to determine whether PAP can cause acute hepatotoxicity in hamsters and to further investigate the role of GSH in PAP-induced toxicity. PAP was administered ip to hamsters in doses of 200-800 mg/kg. Liver damage at 24 h after PAP administration was assessed by elevations in plasma enzyme activities and histopathologic examination. GSH and cysteine (Cys) levels in liver at 4 h were determined by HPLC. PAP decreased hepatic GSH concentration to 8% and Cys to 30% of vehicle control values. It increased plasma glutamic pyruvic transaminase (GPT) activity by 47-fold and sorbitol dehydrogenase (SDH) activity by 113-fold. PAP also caused severe centrilobular hepatocellular necrosis. 2(RS)-n-Propylthiazolidine-4(R)-carboxylic acid (PTCA), a Cys precursor, attenuated the PAP-induced decreases in hepatic sulfhydryl levels; GSH and Cys were 39% and 78% of vehicle controls, respectively. PTCA also attenuated the PAP-induced elevations in plasma enzyme activities and hepatic necrosis. It was concluded that PAP hepatotoxicity is associated with depletion of hepatic GSH and can be prevented by PTCA. Copyright 2004 Wiley Periodicals, Inc.

Effect of Diet and Exercise on the Peripheral Immune System in Young Balb/c Mice

PubMed Central

Martínez-Carrillo, B. E.; Jarillo-Luna, R. A.; Campos-Rodríguez, R.; Valdés-Ramos, R.; Rivera-Aguilar, V.

2015-01-01

Although diet and exercise clearly have an influence on immune function, studies are scarce on the effect caused by exercise and the consumption of a carbohydrate-rich or fat-rich diet on the peripheral immune system. The aim of the present study was to evaluate the effect of exercise and the two aforementioned unbalanced diets on young Balb/c mice, especially in relation to BMI, the level of glucose, and the percentage of lymphocyte subpopulations in peripheral blood. The changes found were then related to the synthesis of leptin and adiponectin as well as the production of oxidative stress. The increase in BMI found with the carbohydrate-rich and fat-rich diets showed correlation with the levels of leptin and adiponectin. An increase in leptin and a decrease in adiponectin directly correlated with an increase in total lymphocytes and CD4+ cells and with a decrease in B cells. The increase in leptin also correlated with an increase in CD8+ cells. Glycemia and oxidative stress increased with the two unbalanced diets, negatively affecting the proliferation of total lymphocytes and the percentage of B cells, apparently by causing alterations in proteins through carbonylation. These alterations caused by an unbalanced diet were not modified by moderate exercise. PMID:26634209

Molecular basis of vascular damage caused by cigarette smoke exposure and a new approach to the treatment: Alpha-linolenic acid.

PubMed

Kaplan, Halil Mahir; Kuyucu, Yurdun; Polat, Sait; Pazarci, Percin; Yegani, Arash Alizadeh; Şingirik, Ergin; Ertuğ, Peyman

2018-06-01

Exposure to cigarette smoke (CS) causes vessel damage and mechanism of this damage has not yet been clearly identified. Therefore, in this study we aimed to investigate whether vessel damage due to the CS exposure will be prevented by the alpha-linolenic acid (ALA) or not which has anti-inflammatory effect in mice. For this reason, mice were grouped as controls (with and without CS) and ALA (with and without CS). The CS application continued 5 days a week for two months. At the end of two months, the mice were killed by cervical dislocation and their blood and thoracic aortas were isolated. ALA Treatment increased acetylcholine relaxations. CS decreased acetylcholine relaxation. CS with ALA treatment increased acetylcholine relaxations versus just CS treatment. CS caused rising in cyclooxigenase-2 and phospholipase A2 levels. This rise is inhibited with ALA treatment. CS decreased eNOS levels. But this result was not statistically significant. Furthermore, according to electron microscopic study CS damaged both smooth muscle and endothelium. While ALA treatment prevented smooth muscle damage it didn't prevent endothelial damage. Using cigarette and CS exposure is a risk factor for cardiovascular disease. Our study showed that this disease. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Effects of sediment characteristics on the toxicity of chromium(III) and chromium(VI) to the amphipod, Hyalella azteca

USGS Publications Warehouse

Besser, J.M.; Brumbaugh, W.G.; Kemble, N.E.; May, T.W.; Ingersoll, C.G.

2004-01-01

We evaluated the influence of sediment characteristics, acid-volatile sulfide (AVS) and organic matter (OM), on the toxicity of chromium (Cr) in freshwater sediments. We conducted chronic (28-42-d) toxicity tests with the amphipod Hyalella azteca exposed to Cr(VI) and Cr(III) in water and in spiked sediments. Waterborne Cr(VI) caused reduced survival of amphipods with a median lethal concentration (LC50) of 40 ??g/L. Cr(VI) spiked into test sediments with differing levels of AVS resulted in graded decreases in AVS and sediment OM. Only Cr(VI)-spiked sediments with low AVS concentrations (<1 ??mol/g) caused significant amphipod mortality. Waterborne Cr(III) concentrations near solubility limits caused decreased survival of amphipods at pH 7 and pH 8 but not at pH 6. Sediments spiked with high levels of Cr(III) did not affect amphipod survival but had minor effects on growth and inconsistent effects on reproduction. Pore waters of some Cr(III)-spiked sediments contained measurable concentrations of Cr(VI), but observed toxic effects did not correspond closely to Cr concentrations in sediment or pore waters. Our results indicate that risks of Cr toxicity are low in freshwater sediments containing substantial concentrations of AVS.

Serum potassium decline during hospitalization for acute decompensated heart failure is a predictor of 6-month mortality, independent of N-terminal pro-B-type natriuretic peptide levels: An individual patient data analysis.

PubMed

Salah, Khibar; Pinto, Yigal M; Eurlings, Luc W; Metra, Marco; Stienen, Susan; Lombardi, Carlo; Tijssen, Jan G; Kok, Wouter E

2015-09-01

Limited data exist for the role of serum potassium changes during hospitalization for acute decompensated heart failure (ADHF). The present study investigated the long-term prognostic value of potassium changes during hospitalization in patients admitted for ADHF. Our study is a pooled individual patient data analysis assembled from 3 prospective cohorts comprising 754 patients hospitalized for ADHF. The endpoint was all-cause mortality within 180 days after discharge. Serum potassium levels and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured at admission and at discharge. A percentage decrease >15% in serum potassium levels occurred in 96 (13%) patients, and an absolute decrease of >0.7 mmol/L in serum potassium levels occurred in 85 (12%) patients; and both were predictors of poor outcome independent of admission or discharge serum potassium. After the addition of other strong predictors of mortality-a 30% change in NT-proBNP during hospitalization, discharge levels of NT-proBNP, renal markers, and other relevant clinical variables-the multivariate hazard ratio of serum potassium percentage reduction of >15% remained an independent predictor of 180-day mortality (hazard ratio 2.06, 95% CI 1.14-3.73). A percentage serum potassium decline of >15% is an independent predictor of 180-day all-cause mortality on top of baseline potassium levels, NT-proBNP levels, renal variables, and other relevant clinical variables. This suggest that patients hospitalized for ADHF with a decline of >15% in serum potassium levels are at risk and thus monitoring and regulating of serum potassium level during hospitalization are needed in these patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Hypothalamic control of pituitary and adrenal hormones during hypothermia.

PubMed

Okuda, C; Miyazaki, M; Kuriyama, K

1986-01-01

In order to investigate neuroendocrinological mechanisms of hypothermia, we determined the changes in plasma concentrations of corticosterone (CS), prolactin (PRL), and thyrotropin (TSH), and their correlations with alterations in hypothalamic dopamine (DA) and thyrotropin releasing hormone (TRH), in rats restrained and immersed in a water bath at various temperatures. A graded decrease of body temperature induced a progressive increase in the plasma level of CS, whereas that of PRL showed a drastic decrease. The plasma level of TSH also showed an increase during mild hypothermia (about 35 degrees C), but this increase was not evident during profound hypothermia (below 24 degrees C). The changes in these hormones were readily reversed by rewarming animals. Although DA content in the hypothalamus was not affected, its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), showed an increase following the decrease of body temperature. Pretreatment of the animals with sulpiride, a D2-antagonist, prevented the hypothermia-induced inhibition of PRL release. Hypothalamic TRH was significantly decreased during mild hypothermia, and it returned to control levels after rewarming. These results suggest that the decrease in plasma PRL induced by hypothermia may be associated with the activation of hypothalamic DA neurons, whereas the increase in plasma TSH during mild hypothermia seems to be caused by the increased release of TRH in the hypothalamus.

Experimental research on preventing mechanical phlebitis arising from indwelling needles in intravenous therapy by external application of mirabilite

PubMed Central

Lu, Yanyan; Hao, Chunyan; He, Wubin; Tang, Can; Shao, Zhenya

2018-01-01

Various types of complications arising from intravenous indwelling needles have become a challenge in clinical care. It is urgent to seek a simple and cost-effective method for prevention and treatment of phlebitis. We investigated the roles of mirabilite in preventing and treating phlebitis caused by intravenous indwelling needles and provide guidance for prevention and treatment of mechanical phlebitis caused by intravenous indwelling needles. A total of 57 healthy congeneric big-eared New Zealand rabbits were randomly divided into 3 groups: blank control, indwelling needle, and group with external application of mirabilite. The ear vein of each rabbit was punctured with an intravenous indwelling needle. The ear vein specimens were taken at 3, 5, and 7 days after indwelling. The hematoxylin and eosin stained pathological tissue sections of the ear veins of the rabbits in each group were observed. The expression levels of IL-1 and IL-6, and tumour necrosis factor-α (TNF-α) in the vascular tissue of the ear veins of the rabbits in each group were detected with the immunofluorescence method. In the blank control group, there was no inflammatory cellular infiltration and no proliferation of fibrous tissue around the vascular wall. With the increase of the indwelling time, proliferation of fibrous tissue in vascular wall, increased inflammatory cellular infiltration and organized thrombus in the vascular tissue occurred in the ear veins of the rabbits in the indwelling needle group and group with external application of mirabilite. Compared with the indwelling needle group, the group with external application of mirabilite had significantly decreased fibrous tissue in the vascular wall and significantly decreased inflammatory cellular infiltration. At the same point in indwelling time, the expression levels of IL-1, IL-6, and TNF-α in the indwelling needle and group with external application of mirabilite were significantly higher than that in the blank control group (P<0.05). The expression levels of IL-1, IL-6, and TNF-α in the group with external application of mirabilite were lower than that in the indwelling needle group (P<0.05). The expression levels of IL-1, IL-6, and TNF-α are positively correlated with the indwelling time within the same group at different points in time. In conclusion, external application of mirabilite can significantly decrease infiltration of venous inflammatory cells of the rabbit ear margin, proliferation of fibrous tissue and thrombosis in the vascular wall, significant decrease the expression levels of IL-1, IL-6, and TNF-α in the mechanical phlebitis caused by intravenous indwelling needles, and decrease the inflammatory responses of the ear veins of rabbits. PMID:29250150

Experimental research on preventing mechanical phlebitis arising from indwelling needles in intravenous therapy by external application of mirabilite.

PubMed

Lu, Yanyan; Hao, Chunyan; He, Wubin; Tang, Can; Shao, Zhenya

2018-01-01

Various types of complications arising from intravenous indwelling needles have become a challenge in clinical care. It is urgent to seek a simple and cost-effective method for prevention and treatment of phlebitis. We investigated the roles of mirabilite in preventing and treating phlebitis caused by intravenous indwelling needles and provide guidance for prevention and treatment of mechanical phlebitis caused by intravenous indwelling needles. A total of 57 healthy congeneric big-eared New Zealand rabbits were randomly divided into 3 groups: blank control, indwelling needle, and group with external application of mirabilite. The ear vein of each rabbit was punctured with an intravenous indwelling needle. The ear vein specimens were taken at 3, 5, and 7 days after indwelling. The hematoxylin and eosin stained pathological tissue sections of the ear veins of the rabbits in each group were observed. The expression levels of IL-1 and IL-6, and tumour necrosis factor-α (TNF-α) in the vascular tissue of the ear veins of the rabbits in each group were detected with the immunofluorescence method. In the blank control group, there was no inflammatory cellular infiltration and no proliferation of fibrous tissue around the vascular wall. With the increase of the indwelling time, proliferation of fibrous tissue in vascular wall, increased inflammatory cellular infiltration and organized thrombus in the vascular tissue occurred in the ear veins of the rabbits in the indwelling needle group and group with external application of mirabilite. Compared with the indwelling needle group, the group with external application of mirabilite had significantly decreased fibrous tissue in the vascular wall and significantly decreased inflammatory cellular infiltration. At the same point in indwelling time, the expression levels of IL-1, IL-6, and TNF-α in the indwelling needle and group with external application of mirabilite were significantly higher than that in the blank control group (P<0.05). The expression levels of IL-1, IL-6, and TNF-α in the group with external application of mirabilite were lower than that in the indwelling needle group (P<0.05). The expression levels of IL-1, IL-6, and TNF-α are positively correlated with the indwelling time within the same group at different points in time. In conclusion, external application of mirabilite can significantly decrease infiltration of venous inflammatory cells of the rabbit ear margin, proliferation of fibrous tissue and thrombosis in the vascular wall, significant decrease the expression levels of IL-1, IL-6, and TNF-α in the mechanical phlebitis caused by intravenous indwelling needles, and decrease the inflammatory responses of the ear veins of rabbits.

The bidirectional effects of hypothyroidism and hyperthyroidism on anxiety- and depression-like behaviors in rats.

PubMed

Yu, Dafu; Zhou, Heng; Yang, Yuan; Jiang, Yong; Wang, Tianchao; Lv, Liang; Zhou, Qixin; Yang, Yuexiong; Dong, Xuexian; He, Jianfeng; Huang, Xiaoyan; Chen, Jijun; Wu, Kunhua; Xu, Lin; Mao, Rongrong

2015-03-01

Thyroid hormone disorders have long been linked to depression, but the causal relationship between them remains controversial. To address this question, we established rat models of hypothyroidism using (131)iodine ((131)I) and hyperthyroidism using levothyroxine (LT4). Serum free thyroxine (FT4) and triiodothyronine (FT3) significantly decreased in the hypothyroid of rats with single injections of (131)I (5mCi/kg). These rats exhibited decreased depression-like behaviors in forced swimming test and sucrose preference tests, as well as decreased anxiety-like behaviors in an elevated plus maze. Diminished levels of brain serotonin (5-HT) and increased levels of hippocampal brain-derived neurotrophic factor (BDNF) were found in the hypothyroid rats compared to the control saline-vehicle administered rats. LT4 treatment reversed the decrease in thyroid hormones and depression-like behaviors. In contrast, hyperthyroidism induced by weekly injections of LT4 (15μg/kg) caused a greater than 10-fold increase in serum FT4 and FT3 levels. The hyperthyroid rats exhibited higher anxiety- and depression-like behaviors, higher brain 5-HT level, and lower hippocampal BDNF levels than the controls. Treatment with the antidepressant imipramine (15mg/kg) diminished serum FT4 levels as well as anxiety- and depression-like behaviors in the hyperthyroid rats but led to a further increase in brain 5-HT levels, compared with the controls or the hypothyroid rats. Together, our results suggest that hypothyroidism and hyperthyroidism have bidirectional effects on anxiety- and depression-like behaviors in rats, possibly by modulating hippocampal BDNF levels. Copyright © 2015 Elsevier Inc. All rights reserved.

Habitat Selection by African Buffalo (Syncerus caffer) in Response to Landscape-Level Fluctuations in Water Availability on Two Temporal Scales

PubMed Central

Bennitt, Emily; Bonyongo, Mpaphi Casper; Harris, Stephen

2014-01-01

Seasonal fluctuations in water availability cause predictable changes in the profitability of habitats in tropical ecosystems, and animals evolve adaptive behavioural and spatial responses to these fluctuations. However, stochastic changes in the distribution and abundance of surface water between years can alter resource availability at a landscape scale, causing shifts in animal behaviour. In the Okavango Delta, Botswana, a flood-pulsed ecosystem, the volume of water entering the system doubled between 2008 and 2009, creating a sudden change in the landscape. We used African buffalo (Syncerus caffer) to test the hypotheses that seasonal habitat selection would be related to water availability, that increased floodwater levels would decrease forage abundance and affect habitat selection, and that this would decrease buffalo resting time, reduce reproductive success and decrease body condition. Buffalo selected contrasting seasonal habitats, using habitats far from permanent water during the rainy season and seasonally-flooded habitats close to permanent water during the early and late flood seasons. The 2009 water increase reduced forage availability in seasonally-flooded habitats, removing a resource buffer used by the buffalo during the late flood season, when resources were most limited. In response, buffalo used drier habitats in 2009, although there was no significant change in the time spent moving or resting, or daily distance moved. While their reproductive success decreased in 2009, body condition increased. A protracted period of high water levels could prove detrimental to herbivores, especially to smaller-bodied species that require high quality forage. Stochastic annual fluctuations in water levels, predicted to increase as a result of anthropogenically-induced climate change, are likely to have substantial impacts on the functioning of water-driven tropical ecosystems, affecting environmental conditions within protected areas. Buffer zones around critical seasonal resources are essential to allow animals to engage in compensatory behavioural and spatial mechanisms in response to changing environmental conditions. PMID:24983377

Effect of 18β-glycyrrhetinic acid on cerebral vasospasm caused by asymmetric dimethylarginine after experimental subarachnoid hemorrhage in rats.

PubMed

Zhao, Dong; Liu, Qi; Ji, Yunxiang; Wang, Ganggang; He, Xuejun; Tian, Weidong; Xu, Hui; Lei, Ting; Wang, Yezhong

2015-06-01

Cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) is characterized by the severe constriction of an artery, which often leads to unfavorable outcomes. CVS after SAH is closely associated with asymmetric dimethylarginine (ADMA) and connexin. The effect of 18β-glycyrrhetinic acid (18β-GA), an inhibitor of gap junction, on ADMA, connexin, and CVS after SAH were investigated. Sprague-Dawley rats (n  =  120), weighing 300-350 g, were divided into the control group, sham, SAH, and SAH + 18β-GA groups. In the SAH group, blood was injected into the prechiasmatic cistern of the rats, and 18β-GA (10 mg/kg) was intraperitoneally injected. The neurological score, basilar artery diameter, ADMA, and connexin protein contents (Cx40, Cx43, and Cx45) were measured using Kaoutzanis scoring system, pressure myograph, enzyme linked immunosorbent assay kit, and Western blot, respectively, 1, 3, 5, 7, and 14 days after SAH. The neurological score significantly decreased 3, 5, 7, and 14 days after SAH. The basilar artery diameter significantly decreased, and the ADMA level in the cerebrospinal fluid (CSF) significantly increased at all time points. The level of Cx40 significantly decreased on days 3, 5, 7, and 14, and the level of Cx43 and Cx45 significantly increased at all time points. ADMA and Cx43 are positively correlated. However, the upregulated level of ADMA, Cx43, and Cx45 were attenuated. The neurology result significantly improved in the SAH + 18β-GA group. Treatment with 18β-GA in SAH rats decreases Cx43 and Cx45 in basilar artery and ADMA in CSF. ADMA is probably involved in the pathophysiological events of CVS after SAH by altering connexin proteins. The mechanism of connexin protein changes caused by ADMA needs to be further studied.

Habitat selection by African buffalo (Syncerus caffer) in response to landscape-level fluctuations in water availability on two temporal scales.

PubMed

Bennitt, Emily; Bonyongo, Mpaphi Casper; Harris, Stephen

2014-01-01

Seasonal fluctuations in water availability cause predictable changes in the profitability of habitats in tropical ecosystems, and animals evolve adaptive behavioural and spatial responses to these fluctuations. However, stochastic changes in the distribution and abundance of surface water between years can alter resource availability at a landscape scale, causing shifts in animal behaviour. In the Okavango Delta, Botswana, a flood-pulsed ecosystem, the volume of water entering the system doubled between 2008 and 2009, creating a sudden change in the landscape. We used African buffalo (Syncerus caffer) to test the hypotheses that seasonal habitat selection would be related to water availability, that increased floodwater levels would decrease forage abundance and affect habitat selection, and that this would decrease buffalo resting time, reduce reproductive success and decrease body condition. Buffalo selected contrasting seasonal habitats, using habitats far from permanent water during the rainy season and seasonally-flooded habitats close to permanent water during the early and late flood seasons. The 2009 water increase reduced forage availability in seasonally-flooded habitats, removing a resource buffer used by the buffalo during the late flood season, when resources were most limited. In response, buffalo used drier habitats in 2009, although there was no significant change in the time spent moving or resting, or daily distance moved. While their reproductive success decreased in 2009, body condition increased. A protracted period of high water levels could prove detrimental to herbivores, especially to smaller-bodied species that require high quality forage. Stochastic annual fluctuations in water levels, predicted to increase as a result of anthropogenically-induced climate change, are likely to have substantial impacts on the functioning of water-driven tropical ecosystems, affecting environmental conditions within protected areas. Buffer zones around critical seasonal resources are essential to allow animals to engage in compensatory behavioural and spatial mechanisms in response to changing environmental conditions.

Hyperglycemia of Diabetic Rats Decreased by a Glucagon Receptor Antagonist

NASA Astrophysics Data System (ADS)

Johnson, David G.; Ulichny Goebel, Camy; Hruby, Victor J.; Bregman, Marvin D.; Trivedi, Dev

1982-02-01

The glucagon analog [l-Nα-trinitrophenylhistidine, 12-homoarginine]-glucagon (THG) was examined for its ability to lower blood glucose concentrations in rats made diabetic with streptozotocin. In vitro, THG is a potent antagonist of glucagon activation of the hepatic adenylate cyclase assay system. Intravenous bolus injections of THG caused rapid decreases (20 to 35 percent) of short duration in blood glucose. Continuous infusion of low concentrations of the inhibitor led to larger sustained decreases in blood glucose (30 to 65 percent). These studies demonstrate that a glucagon receptor antagonist can substantially reduce blood glucose levels in diabetic animals without addition of exogenous insulin.

Mutations of human NARS2, encoding the mitochondrial asparaginyl-tRNA synthetase, cause nonsyndromic deafness and Leigh syndrome.

PubMed

Simon, Mariella; Richard, Elodie M; Wang, Xinjian; Shahzad, Mohsin; Huang, Vincent H; Qaiser, Tanveer A; Potluri, Prasanth; Mahl, Sarah E; Davila, Antonio; Nazli, Sabiha; Hancock, Saege; Yu, Margret; Gargus, Jay; Chang, Richard; Al-Sheqaih, Nada; Newman, William G; Abdenur, Jose; Starr, Arnold; Hegde, Rashmi; Dorn, Thomas; Busch, Anke; Park, Eddie; Wu, Jie; Schwenzer, Hagen; Flierl, Adrian; Florentz, Catherine; Sissler, Marie; Khan, Shaheen N; Li, Ronghua; Guan, Min-Xin; Friedman, Thomas B; Wu, Doris K; Procaccio, Vincent; Riazuddin, Sheikh; Wallace, Douglas C; Ahmed, Zubair M; Huang, Taosheng; Riazuddin, Saima

2015-03-01

Here we demonstrate association of variants in the mitochondrial asparaginyl-tRNA synthetase NARS2 with human hearing loss and Leigh syndrome. A homozygous missense mutation ([c.637G>T; p.Val213Phe]) is the underlying cause of nonsyndromic hearing loss (DFNB94) and compound heterozygous mutations ([c.969T>A; p.Tyr323*] + [c.1142A>G; p.Asn381Ser]) result in mitochondrial respiratory chain deficiency and Leigh syndrome, which is a neurodegenerative disease characterized by symmetric, bilateral lesions in the basal ganglia, thalamus, and brain stem. The severity of the genetic lesions and their effects on NARS2 protein structure cosegregate with the phenotype. A hypothetical truncated NARS2 protein, secondary to the Leigh syndrome mutation p.Tyr323* is not detectable and p.Asn381Ser further decreases NARS2 protein levels in patient fibroblasts. p.Asn381Ser also disrupts dimerization of NARS2, while the hearing loss p.Val213Phe variant has no effect on NARS2 oligomerization. Additionally we demonstrate decreased steady-state levels of mt-tRNAAsn in fibroblasts from the Leigh syndrome patients. In these cells we show that a decrease in oxygen consumption rates (OCR) and electron transport chain (ETC) activity can be rescued by overexpression of wild type NARS2. However, overexpression of the hearing loss associated p.Val213Phe mutant protein in these fibroblasts cannot complement the OCR and ETC defects. Our findings establish lesions in NARS2 as a new cause for nonsyndromic hearing loss and Leigh syndrome.

Activation of p44/42 in Human Natural Killer Cells Decreases Cell-surface Protein Expression: Relationship to Tributyltin-induced alterations of protein expression

PubMed Central

Dudimah, Fred D.; Abraha, Abraham; Wang, Xiaofei; Whalen, Margaret M.

2010-01-01

Tributyltin (TBT) activates the mitogen activated protein kinase (MAPK), p44/42 in human natural killer (NK) cells. TBT also reduces NK cytotoxic function and decreases the expression of several NK-cell proteins. To understand the role that p44/42 activation plays in TBT-induced loss of NK cell function, we have investigated how selective activation of p44/42 by phorbol 12-myristate 13-acetate (PMA) affects NK cells. Previously we showed that PMA caused losses of lytic function similar to those seen with TBT exposures. Here we examined activation of p44/42 in the regulation of NK-cell protein expression and how this regulation may explain the protein expression changes seen with TBT exposures. NK cells exposed to PMA were examined for levels of cell-surface proteins, granzyme mRNA, and perforin mRNA expression. The expression of CD11a, CD16, CD18, and CD56 were reduced, perforin mRNA levels were unchanged and granzyme mRNA levels were increased. To verify that activation of p44/42 was responsible for the alterations seen in CD11a, CD16, CD18, and CD56 with PMA, NK cells were treated with the p44/42 pathway inhibitor (PD98059) prior to PMA exposures. In the presence of PD98059, PMA caused no decreases in the expression of the cell-surface proteins. Results of these studies indicate that the activation of p44/42 may lead to the loss of NK cell cytotoxic function by decreasing the expression of CD11a, CD16, CD18, and CD56. Further, activation of p44/42 appears to be at least in part responsible for the TBT-induced decreases in expression of CD16, CD18, and CD56. PMID:20883105

Soft-food diet induces oxidative stress in the rat brain.

PubMed

Yoshino, Fumihiko; Yoshida, Ayaka; Hori, Norio; Ono, Yumie; Kimoto, Katsuhiko; Onozuka, Minoru; Lee, Masaichi Chang-il

2012-02-02

Decreased dopamine (DA) release in the hippocampus may be caused by dysfunctional mastication, although the mechanisms involved remain unclear. The present study examined the effects of soft- and hard-food diets on oxidative stress in the brain, and the relationship between these effects and hippocampal DA levels. The present study showed that DA release in the hippocampus was decreased in rats fed a soft-food diet. Electron spin resonance studies using the nitroxyl spin probe 3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl directly demonstrated a high level of oxidative stress in the rat brain due to soft-food diet feeding. In addition, we confirmed that DA directly react with reactive oxygen species such as hydroxyl radical and superoxide. These observations suggest that soft-food diet feeding enhances oxidative stress, which leads to oxidation and a decrease in the release of DA in the hippocampus of rats. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Response of broiler breeder females to feed restriction below recommended levels. 1. Growth and reproductive performance.

PubMed

Fattori, T R; Wilson, H R; Harms, R H; Miles, R D

1991-01-01

Arbor Acre broiler breeders were used to determine the effects on growth and reproductive performance of quantitative feed restriction below breeder recommended levels. Feed treatments were: 8% above standard (+8%); standard feeding program (STD); and 8 (-8%), 16 (-16%), and 24% (-24%) below standard. Proportional decreases in feed allocation resulted in corresponding decreases in body weight, frequency of double-yolked eggs, and number of days in production. Egg weight, fertility, hatchability, and female mortality to 64 wk of age were not significantly (P greater than or equal to .05) affected by the reduction in feed intake. Shell quality was significantly improved with the -16 and -24% feed treatments. A delay in sexual maturity caused a significant (P less than or equal to .05) decrease in average rate of lay (%hen-day) but not in total settable eggs for treatments -16 and -24% to 64 wk of age.

Acanthoic acid protectsagainst ethanol-induced liver injury: Possible role of AMPK activation and IRAK4 inhibition.

PubMed

Yao, You-Li; Han, Xin; Song, Jian; Zhang, Jing; Li, Ya-Mei; Lian, Li-Hua; Wu, Yan-Ling; Nan, Ji-Xing

2017-11-05

The aim of this study was to investigate the effects of acanthoic acid (AA) on the regulation of inflammatory response, lipid accumulation, and fibrosis via AMPK- IRAK4 signaling against chronic alcohol consumption in mice. Ethanol-induced liver injury was induced in male mice by Lieber-DeCarli diet for 28d. And mice in AA groups were gavaged with AA (20 or 40mg/kg) for 28d. AA treatment significantly decreased serum AST and TG, hepatic TG levels, serum ethanol and LPS levels compared with chronic ethanol administration. AA ameliorated histological changes, lipid droplets, hepatic fibrosis, and inflammation induced by ethanol. AA significantly increased the expressions of p-LKB1, p-AMPK, and SIRT1 caused by chronic ethanol administration, and attenuated the increasing protein expressions of IRAK1 and IRAK4.siRNA against AMPKα1 blocked AMPKα1 and increased IRAK4 protein expressions, compared with control-siRNA-transfected group, while AA treatment significantly decreased IRAK4 expressions compared with AMPKα1-siRNA-transfected group. AMPK-siRNA also blocked the decreased effect of AA on inflammatory factors. AA decreased over-expression of IRAK4 and inflammation under ethanol plus LPS challenge. AA recruited LKB1-AMPK phosphorylation and activated SIRT1 to regulate alcoholic liver injury, especially, inhibited IRAK1/4 signaling pathway to regulate lipid metabolism, hepatic fibrosis and inflammation caused by alcohol consumption. Copyright © 2017 Elsevier B.V. All rights reserved.

Hydronephrosis alters cardiac ACE2 and Mas receptor expression in mice.

PubMed

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

2015-06-01

Hydronephrosis is characterized by substantial loss of tubules and affects renin secretion in the kidney. However, whether alterations of angiotensin-converting enzyme (ACE), ACE2 and Mas receptor in the heart are observed in hydronephrosis is unknown. Thus, we assessed these components in hydronephrotic mice treated with AT1 receptor blockade and ACE inhibitor. Hydronephrosis was induced by left ureteral ligation in Balb/C mice except sham-operated animals. The levels of cardiac ACE, ACE2 and Mas receptor were measured after treatment of losartan or enalapril. Hydronephrosis led to an increase of ACE level and a decrease of ACE2 and Mas receptor in the heart. Losartan decreased cardiac ACE level, but ACE2 and Mas receptor levels significantly increased in hydronephrotic mice (p < 0.01). Enalapril increased ACE2 levels (p < 0.01), but did not affect Mas receptor in the heart. Plasma renin activity (PRA) and Ang II decreased in hydronephrotic mice, but significantly increased after treatment with losartan or enalapril. Hydronephrosis increased cardiac ACE and suppressed ACE2 and Mas receptor levels. AT1 blockade caused sustained activation of cardiac ACE2 and Mas receptor, but ACE inhibitor had the limitation of such activation of Mas receptor in hydronephrotic animals. © The Author(s) 2015.

Effect of n-type doping level on direct band gap electroluminescence intensity for asymmetric metal/Ge/metal diodes

NASA Astrophysics Data System (ADS)

Maekura, T.; Tanaka, K.; Motoyama, C.; Yoneda, R.; Yamamoto, K.; Nakashima, H.; Wang, D.

2017-10-01

The direct band gap electroluminescence (EL) intensity was investigated for asymmetric metal/Ge/metal diodes fabricated on n-type Ge with doping levels in the range of 4.0 × 1013-3.1 × 1018 cm-3. Up to a doping level of 1016 cm-3 order, commercially available (100) n-Ge substrates were used. To obtain a doping level higher than 1017 cm-3 order, which is commercially unavailable, n+-Ge/p-Ge structures were fabricated by Sb doping on p-type (100) Ge substrates with an in-diffusion at 600 °C followed by a push-diffusion at 700 °C-850 °C. The EL intensity was increased with increasing doping level up to 1.0 × 1018 cm-3. After that, it was decreased with a further increase in n-type doping level. This EL intensity decrease is explained by the decreased number of holes in the active region. One reason is the difficulty in hole injection through the PtGe/n-Ge contact due to the occurring of tunneling electron current. Another reason is the loss of holes caused by both the small thickness of n+-Ge layer and the existence of n+p junction.

Evaluation of treadmill exercise effect on muscular lipid profiles of diabetic fatty rats by nanoflow liquid chromatography-tandem mass spectrometry

NASA Astrophysics Data System (ADS)

Lee, Jong Cheol; Kim, Il Yong; Son, Yeri; Byeon, Seul Kee; Yoon, Dong Hyun; Son, Jun Seok; Song, Han Sol; Song, Wook; Seong, Je Kyung; Moon, Myeong Hee

2016-07-01

We compare comprehensive quantitative profiling of lipids at the molecular level from skeletal muscle tissues (gastrocnemius and soleus) of Zucker diabetic fatty rats and Zucker lean control rats during treadmill exercise by nanoflow liquid chromatography-tandem mass spectrometry. Because type II diabetes is caused by decreased insulin sensitivity due to excess lipids accumulated in skeletal muscle tissue, lipidomic analysis of muscle tissues under treadmill exercise can help unveil the mechanism of lipid-associated insulin resistance. In total, 314 lipid species, including phospholipids, sphingolipids, ceramides, diacylglycerols (DAGs), and triacylglycerols (TAGs), were analyzed to examine diabetes-related lipid species and responses to treadmill exercise. Most lysophospholipid levels increased with diabetes. While DAG levels (10 from the gastrocnemius and 13 from the soleus) were >3-fold higher in diabetic rats, levels of most of these decreased after exercise in soleus but not in gastrocnemius. Levels of 5 highly abundant TAGs (52:1 and 54:3 in the gastrocnemius and 48:2, 50:2, and 52:4 in the soleus) displaying 2-fold increases in diabetic rats decreased after exercise in the soleus but not in the gastrocnemius in most cases. Thus, aerobic exercise has a stronger influence on lipid levels in the soleus than in the gastrocnemius in type 2 diabetic rats.

Cholinergic Basal Forebrain Lesion Decreases Neurotrophin Signaling without Affecting Tau Hyperphosphorylation in Genetically Susceptible Mice.

PubMed

Turnbull, Marion T; Coulson, Elizabeth J

2017-01-01

Alzheimer's disease (AD) is a progressive, irreversible neurodegenerative disease that destroys memory and cognitive function. Aggregates of hyperphosphorylated tau protein are a prominent feature in the brain of patients with AD, and are a major contributor to neuronal toxicity and disease progression. However, the factors that initiate the toxic cascade that results in tau hyperphosphorylation in sporadic AD are unknown. Here we investigated whether degeneration of basal forebrain cholinergic neurons (BFCNs) and/or a resultant decrease in neurotrophin signaling cause aberrant tau hyperphosphorylation. Our results reveal that the loss of BFCNs in pre-symptomatic pR5 (P301L) tau transgenic mice results in a decrease in hippocampal brain-derived neurotrophic factor levels and reduced TrkB receptor activation. However, there was no exacerbation of the levels of phosphorylated tau or its aggregation in the hippocampus of susceptible mice. Furthermore the animals' performance in a hippocampal-dependent learning and memory task was unaltered, and no changes in hippocampal synaptic markers were observed. This suggests that tau pathology is likely to be regulated independently of BFCN degeneration and the corresponding decrease in hippocampal neurotrophin levels, although these features may still contribute to disease etiology.

Bisphenol A Alters n-6 Fatty Acid Composition and Decreases Antioxidant Enzyme Levels in Rat Testes: A LC-QTOF-Based Metabolomics Study

PubMed Central

Qiao, Shanlei; Hu, Nan; Hu, Yanhui; Wu, Wei; Qiu, Lianglin; Zhang, Ruyang; Wang, Yubang; Wang, Shoulin; Zhou, Zuomin; Xia, Yankai; Wang, Xinru

2012-01-01

Background Male reproductive toxicity induced by exposure to bisphenol A (BPA) has been widely reported. The testes have proven to be a major target organ of BPA toxicity, so studying testicular metabolite variation holds promise for the discovery of mechanisms linked to the toxic effects of BPA on reproduction. Methodology/Principal Findings Male Sprague-Dawley rats were orally administered doses of BPA at the levels of 0, 50 mg/kg/d for 8 weeks. We used an unbiased liquid chromatography-quadrupole time-of-flight (LC-QTOF)-based metabolomics approach to discover, identify, and analyze the variation of testicular metabolites. Two n-6 fatty acids, linoleic acid (LA) and arachidonic acid (AA) were identified as potential testicular biomarkers. Decreased levels of LA and increased levels of AA as well as AA/LA ratio were observed in the testes of the exposed group. According to these suggestions, testicular antioxidant enzyme levels were detected. Testicular superoxide dismutase (SOD) declined significantly in the exposed group compared with that in the non-exposed group, and the glutathione peroxidase (GSH-Px) as well as catalase (CAT) also showed a decreasing trend in BPA treated group. Conclusions/Significance BPA caused testicular n-6 fatty acid composition variation and decreased antioxidant enzyme levels. This study emphasizes that metabolomics brings the promise of biomarkers identification for the discovery of mechanisms underlying reproductive toxicity. PMID:23024759

Food restriction attenuates oxidative stress in brown adipose tissue of striped hamsters acclimated to a warm temperature.

PubMed

Zhang, Ji-Ying; Zhao, Xiao-Ya; Wang, Gui-Ying; Wang, Chun-Ming; Zhao, Zhi-Jun

2016-05-01

It has been suggested that the up-regulation of uncoupling proteins (UCPs) decreases reactive oxygen species (ROS) production, in which case there should be a negative relationship between UCPs expression and ROS levels. In this study, the effects of temperature and food restriction on ROS levels and metabolic rate, UCP1 mRNA expression and antioxidant levels were examined in the brown adipose tissue (BAT) of the striped hamsters (Cricetulus barabensis). The metabolic rate and food intake of hamsters which had been restricted to 80% of ad libitum food intake, and acclimated to a warm temperature (30°C), decreased significantly compared to a control group. Hydrogen peroxide (H2O2) levels were 42.9% lower in food restricted hamsters than in the control. Malonadialdehyde (MDA) levels of hamsters acclimated to 30°C that were fed ad libitum were significantly higher than those of the control group, but 60.1% lower than hamsters that had been acclimated to the same temperature but subject to food restriction. There were significantly positive correlations between H2O2 and, MDA levels, catalase activity, and total antioxidant capacity. Cytochrome c oxidase activity and UCP1 mRNA expression significantly decreased in food restricted hamsters compared to the control. These results suggest that warmer temperatures increase oxidative stress in BAT by causing the down-regulation of UCP1 expression and decreased antioxidant activity, but food restriction may attenuate the effects. Copyright © 2016 Elsevier Ltd. All rights reserved.

Possible mechanism of the potent vasoconstrictor actions of ryanodine on femoral arteries from spontaneously hypertensive rats.

PubMed Central

Asano, M.; Kuwako, M.; Nomura, Y.; Ito, K. M.; Ito, K.; Uyama, Y.; Imaizumi, Y.; Watanabe, M.

1996-01-01

1. The Ca2+ buffering function of sarcoplasmic reticulum (SR) in the resting state of arteries from spontaneously hypertensive rats (SHR) was examined. Differences in the effects of ryanodine that removes the function of SR, on tension and cellular Ca2+ level were assessed in endothelium-denuded strips of femoral arteries from 13-week-old SHR and normotensive Wistar-Kyoto rats (WKY). 2. The addition of ryanodine to the resting strips caused a concentration-dependent contraction in SHR. This contraction was extremely small in WKY. In the presence of 10(-5) M ryanodine, caffeine (20 mM) failed to cause a further contraction in SHR, but it caused a small contraction in WKY. After washout of the strips with a Krebs solution, the resting tone was greatly elevated in SHR when compared with WKY. 3. The elevated resting tone in SHR strips was abolished by 10(-7) M nifedipine. The ryanodine-induced contraction was also abolished by 10(-7) M nifedipine. Nifedipine itself caused a relaxation from the resting tone of SHR strips, suggesting the maintenance of myogenic tone. 4. In strips preloaded with fura-PE3, the addition of 10(-5) M ryanodine caused a large and moderate elevation of cytosolic Ca2+ level ([Ca2+]i) in SHR and WKY, respectively. After washout, the resting [Ca2+]i was greatly elevated in SHR. The ryanodine-induced elevation of [Ca2+]i was decreased by 5 x 10(-6) M verapamil in SHR. Verapamil itself caused a decrease in resting [Ca2+]i which was significantly greater in SHR than in WKY, and caused a relaxation only in SHR. 5. The resting Ca2+ influx in arteries measured by a 5 min incubation with 45Ca was significantly increased in SHR when compared with WKY. The resting Ca2+ influx was not increased by 10(-5) M ryanodine in both SHR and WKY. The net cellular Ca2+ uptake in arteries measured by a 30 min incubation with 45Ca was decreased by 10(-5) M ryanodine in both strains. 6. The resting Ca2+ influx was decreased by 10(-7) M nifedipine in the SHR artery, but it was unchanged in the WKY artery. 7. These results suggest that (1) the Ca2+ influx via L-type voltage-dependent Ca2+ channels was increased in the resting state of the SHR femoral artery, (2) the greater part of the increased Ca2+ influx was buffered by Ca2+ uptake into the SR and some Ca2+ reached the myofilaments resulting in the maintenance of the myogenic tone, and (3) therefore the functional removal of SR by ryanodine caused a potent contraction in this artery. PMID:8799577

Investigation of ischemia modified albumin, oxidant and antioxidant markers in acute myocardial infarction

PubMed Central

Hazini, Ahmet; Işıldak, İbrahim; Alpdağtaş, Saadet; Önül, Abdullah; Şenel, Ünal; Kocaman, Tuba; Dur, Ali; Iraz, Mustafa; Uyarel, Hüseyin

2015-01-01

Introduction Acute myocardial infarction (AMI) is still one of the most common causes of death worldwide. In recent years, for diagnosis of myocardial ischemia, a new parameter, called ischemia modified albumin (IMA), which is thought to be more advantageous than common methods, has been researched. Aim In this study, systematic analysis of parameters considered to be related to myocardial ischemia has been performed, comparing between control and myocardial ischemia groups. Material and methods We selected 40 patients with AMI and 25 healthy controls for this study. Ischemia modified albumin levels, glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) antioxidant enzyme activities and non-enzymatic antioxidants such as retinol, α-tocopherol, β-carotene and ascorbic acid levels were investigated in both groups. Glutathione (GSH) and malondialdehyde (MDA) levels, which are indicators of oxidative stress, were compared between patient and control groups. Results Ischemia modified albumin levels were found significantly higher in the AMI diagnosed group when compared with controls. The MDA level was elevated in the patient group, whereas the GSH level was decreased. SOD, GPx and CAT enzyme levels were decreased in the patient group, where it could be presumed that oxidative stress causes the cardiovascular diseases. Conclusions Due to the increased oxidative stress, non-enzymatic and enzymatic antioxidant capacity was affected. Systematic investigation of parameters related to myocardial infarction has been performed, and it is believed that such parameters can contribute to protection and early diagnosis of AMI and understanding the mechanism of development of the disease. PMID:26677379

Imposex in Reishia clavigera as an Indicator to Assess Recovery of TBT Pollution After a Total Ban in South Korea.

PubMed

Kim, Nam Sook; Hong, Sang Hee; Shin, Kyung-Hoon; Shim, Won Joon

2017-08-01

The temporal changes in the frequency and degree of imposex and tributyltin (TBT) levels in gastropod (Reishia clavigera) were evaluated in Jinhae Bay, 5 and 10 years after the total ban on TBT usage in South Korea. The frequency and degree of imposex decreased significantly after the ban, accompanied by an increase in the female-to-male ratio. The TBT concentrations in R. clavigera also decreased significantly after the ban. There were good correlations between the TBT concentration in rock shell and both the degree of imposex and the female-to-male ratio. The total TBT ban effectively reduced the TBT levels and the frequency and degree of imposex in R. clavigera. However, the current low exposure level in the study area is still sufficient to cause imposex in R. clavigera. More time is needed to reduce the TBT levels to levels that do not have adverse biological effects on R. clavigera.

Pea Fiber and Wheat Bran Fiber Show Distinct Metabolic Profiles in Rats as Investigated by a 1H NMR-Based Metabolomic Approach

PubMed Central

Liu, Guangmang; Xiao, Liang; Fang, Tingting; Cai, Yimin; Jia, Gang; Zhao, Hua; Wang, Jing; Chen, Xiaoling; Wu, Caimei

2014-01-01

This study aimed to examine the effect of pea fiber (PF) and wheat bran fiber (WF) supplementation in rat metabolism. Rats were assigned randomly to one of three dietary groups and were given a basal diet containing 15% PF, 15% WF, or no supplemental fiber. Urine and plasma samples were analyzed by NMR-based metabolomics. PF significantly increased the plasma levels of 3-hydroxybutyrate, and myo-inositol as well as the urine levels of alanine, hydroxyphenylacetate, phenylacetyglycine, and α-ketoglutarate. However, PF significantly decreased the plasma levels of isoleucine, leucine, lactate, and pyruvate as well as the urine levels of allantoin, bile acids, and trigonelline. WF significantly increased the plasma levels of acetone, isobutyrate, lactate, myo-inositol, and lipids as well as the urine levels of alanine, lactate, dimethylglycine, N-methylniconamide, and α-ketoglutarate. However, WF significantly decreased the plasma levels of amino acids, and glucose as well as the urine levels of acetate, allantoin, citrate, creatine, hippurate, hydroxyphenylacetate, and trigonelline. Results suggest that PF and WF exposure can promote antioxidant activity and can exhibit common systemic metabolic changes, including lipid metabolism, energy metabolism, glycogenolysis and glycolysis metabolism, protein biosynthesis, and gut microbiota metabolism. PF can also decrease bile acid metabolism. These findings indicate that different fiber diet may cause differences in the biofluid profile in rats. PMID:25541729

Severe hypertriglyceridemia, reduced high density lipoprotein, and neonatal death in lipoprotein lipase knockout mice. Mild hypertriglyceridemia with impaired very low density lipoprotein clearance in heterozygotes.

PubMed Central

Weinstock, P H; Bisgaier, C L; Aalto-Setälä, K; Radner, H; Ramakrishnan, R; Levak-Frank, S; Essenburg, A D; Zechner, R; Breslow, J L

1995-01-01

Lipoprotein lipase (LPL)-deficient mice have been created by gene targeting in embryonic stem cells. At birth, homozygous knockout pups have threefold higher triglycerides and sevenfold higher VLDL cholesterol levels than controls. When permitted to suckle, LPL-deficient mice become pale, then cyanotic, and finally die at approximately 18 h of age. Before death, triglyceride levels are severely elevated (15,087 +/- 3,805 vs 188 +/- 71 mg/dl in controls). Capillaries in tissues of homozygous knockout mice are engorged with chylomicrons. This is especially significant in the lung where marginated chylomicrons prevent red cell contact with the endothelium, a phenomenon which is presumably the cause of cyanosis and death in these mice. Homozygous knockout mice also have diminished adipose tissue stores as well as decreased intracellular fat droplets. By crossbreeding with transgenic mice expressing human LPL driven by a muscle-specific promoter, mouse lines were generated that express LPL exclusively in muscle but not in any other tissue. This tissue-specific LPL expression rescued the LPL knockout mice and normalized their lipoprotein pattern. This supports the contention that hypertriglyceridemia caused the death of these mice and that LPL expression in a single tissue was sufficient for rescue. Heterozygous LPL knockout mice survive to adulthood and have mild hypertriglyceridemia, with 1.5-2-fold elevated triglyceride levels compared with controls in both the fed and fasted states on chow, Western-type, or 10% sucrose diets. In vivo turnover studies revealed that heterozygous knockout mice had impaired VLDL clearance (fractional catabolic rate) but no increase in transport rate. In summary, total LPL deficiency in the mouse prevents triglyceride removal from plasma, causing death in the neonatal period, and expression of LPL in a single tissue alleviates this problem. Furthermore, half-normal levels of LPL cause a decrease in VLDL fractional catabolic rate and mild hypertriglyceridemia, implying that partial LPL deficiency has physiological consequences. Images PMID:8675619

Decreased serum L-arginine and L-citrulline levels in major depression.

PubMed

Hess, S; Baker, G; Gyenes, G; Tsuyuki, R; Newman, S; Le Melledo, Jean-Michel

2017-11-01

It has been suggested that endothelial dysfunction caused by a decreased endothelial production of nitric oxide (NO) may contribute to the consistently observed increased risk of developing cardiovascular disease (CVD) in physically healthy patients suffering from major depression (MD). NO is a gas synthesized from Larginine (a conditionally essential amino acid) and oxygen by endothelial nitric oxide synthase (eNOS). The end products of NO production include both NO and L-citrulline. NO is rapidly reduced to the anions nitrite and nitrate, classically referred to as NO metabolites. Their measurement has been used as a surrogate measurement for endothelial NO production. We and others have shown decreased levels of NO metabolites in the serum of MD patients. The mechanism of this decreased production of NO by the endothelium has not yet been elucidated. The purpose of this study is to assess serum levels of L-arginine and L-citrulline in patients with MD. Levels of L-arginine and L-citrulline were measured in 35 unmedicated physically healthy MD patients and 36 healthy controls (HCs). L-arginine and L-citrulline concentrations were significantly lower in MD patients than in healthy controls (L-arginine, 73.54 + 21.53 μmol/L and 84.89 + 25.16, p = 0.04 μmol/L and L-citrulline 31.58 + 6.05 μmol/L and 35.19 + 6.85 μmol/L, p = 0.03, respectively). The decrease in L-arginine levels in MD patients is a possible explanation for the decrease in NO metabolites in MD patients and therefore may contribute, through endothelial dysfunction, to the increased CV risk associated with MD.

Retrospective, Demographic, and Clinical Investigation of the Causes of Postoperative Infection in Patients With Lumbar Spinal Stenosis Who Underwent Posterior Stabilization

PubMed Central

Yaldiz, Can; Yaldiz, Mahizer; Ceylan, Nehir; Kacira, Ozlem Kitiki; Ceylan, Davut; Kacira, Tibet; Kizilcay, Gokhan; Tanriverdi, Taner

2015-01-01

Abstract Owing to the increasing population of elderly patients, a large number of patients with degenerative spondylosis are currently being surgically treated. Although basic measures for decreasing postoperative surgical infections (PSIs) are considered, it still remains among the leading causes of morbidity and mortality. The aim of this retrospective analysis is to present possible causes leading to PSI in patients who underwent surgery for lumbar degenerative spondylosis and highlight how it can be avoided to decrease morbidity and mortality. The study included 540 patients who underwent posterior stabilization due to degenerative lumbar stenosis between January 2013 and January 2014. The data before and after surgery was retrieved from the hospital charts. Patients with degenerative lumbar stenosis who were operated upon in this study had >2 levels of laminectomy and facetectomy. For this reason, posterior stabilization was performed for all the patients included in this study. Determining the causes of postoperative infection (PI) following spinal surgeries performed with instrumentation is a struggle. Seventeen different parameters that may be related to PI were evaluated in this study. The presence of systemic diseases, unknown glove perforations, and perioperative blood transfusions were among the parameters that increased the prevalence of PI. Alternatively, prolene sutures, double-layered gloves, and the use of rifampicin Sv (RIS) decreased the incidence of PI. Although the presence of systemic diseases, unnoticed glove perforations, and perioperative blood transfusions increased PIs, prolene suture material, double-layered gloves, and the use of RIS decreased PIs. PMID:26200620

Trends in Mortality Among Females in the United States, 1900–2010: Progress and Challenges

PubMed Central

Chang, Man-Huei; Parrish, R. Gibson; Teutsch, Steven M.; Jones, Wanda K.

2018-01-01

Introduction We analyzed trends in US female mortality rates by decade from 1900 through 2010, assessed age and racial differences, and proposed explanations and considered implications. Methods We conducted a descriptive study of trends in mortality rates from major causes of death for females in the United States from 1900 through 2010. We analyzed all-cause unadjusted death rates (UDRs) for males and females and for white and nonwhite males and females from 1900 through 2010. Data for blacks, distinct from other nonwhites, were available beginning in 1970 and are reported for this and following decades. We also computed age-adjusted all-cause death rates (AADRs) by the direct method using age-specific death rates and the 2000 US standard population. Data for the analysis of decadal trends in mortality rates were obtained from yearly tabulations of causes of death from published compilations and from public use computer data files. Results In 1900, UDRs and AADRs were higher for nonwhites than whites and decreased more rapidly for nonwhite females than for white females. Reductions were highest among younger females and lowest among older females. Rates for infectious diseases decreased the most. AADRs for heart disease increased 96.5% in the first 5 decades, then declined by 70.6%. AADRs for cancer rose, then decreased. Stroke decreased steadily. Unintentional motor vehicle injury AADRs increased, leveled off, then decreased. Differences between white and nonwhite female all-cause AADRs almost disappeared during the study period (5.4 per 100,000); differences in white and black AADRs remained high (121.7 per 100,000). Conclusion Improvements in social and environmental determinants of health probably account for decreased mortality rates among females in the early 20th century, partially offset by increased smoking. In the second half of the century, other public health and clinical measures contributed to reductions. The persistent prevalence of risk behaviors and underuse of preventive and medical services indicate opportunities for increased female longevity, particularly in racial minority populations. PMID:29522701

[Carbohydrate restriction in the larval diet causes oxidative stress in adult insects of Drosophila melanogaster].

PubMed

Rovenko, B M; Lushchak, V I; Lushchak, O V

2013-01-01

The influence of 20 and 1% glucose and fructose, which were components of larval diet, on the level of oxidized proteins and lipids, low molecular mass antioxidant content as well as activities of antioxidant and associated enzymes in adult fruit fly Drosophila melanogaster were investigated. The restriction of carbohydrates in larval diet leads to oxidative stress in adult insects. It is supported by 40-50% increased content of protein carbonyl groups and by 60-70% decreased level of protein thiol groups as well as by a 4-fold increase of lipid peroxide content in 2-day-old flies of both sexes, developed on the diet with 1% carbohydrates. Oxidative stress, induced by carbohydrate restriction of the larval diet, caused the activation of antioxidant defence, differently exhibited in male and female fruit flies. Caloric restriction increased activity of superoxide dismutase and thioredoxin reductase associating only in males with 2-fold higher activity of NADPH-producing enzymes--glucose-6-phosphate dehydrogenase and isocitrate dehydrogenase. Carbohydrate restriction in the larval diet caused the increase of uric acid content, but the decrease in catalase activity in males. In females the values of these parameters were changed in opposite direction compared with males. The obtained results let us conclude the different involvement of low molecular mass antioxidants, glutathione and uric acid, and antioxidant enzyme catalase in the protection of male and female fruit fly macromolecules against oxidative damages, caused by calorie restriction of larval diet.

Toxic effects and possible mechanisms of hydrogen sulfide and/or ammonia on porcine oocyte maturation in vitro.

PubMed

Yang, Lei-Lei; Zhao, Yong; Luo, Shi-Ming; Ma, Jun-Yu; Ge, Zhao-Jia; Shen, Wei; Yin, Shen

2018-03-15

Previous studies suggest that hydrogen sulfide (H 2 S) and ammonia (NH 3 ) are two major air pollutants which can cause damage to porcine health. However, the mechanisms underlying toxic effects of these compounds on porcine oocyte maturation are not clear. To clarify the mechanism, we evaluated the oocyte quality by detecting some events during oocytes maturation. In our study, porcine oocytes were cultured with different concentrations of Na 2 S and/or NH 4 Cl in vitro and the rate of the first polar body extrusion decreased significantly. Also, actin filament was seriously disrupted to damage the cytoskeleton which resulted in reduced rate of oocyte maturation. We explored the reactive oxygen species (ROS) generation and found that the ROS level was increased significantly after Na 2 S treatment but not after NH 4 Cl treatment. Moreover, early stage apoptosis rate was significantly increased and autophagy protein LC3 B expression level was higher in oocytes treated with Na 2 S and/or NH 4 Cl, which might be caused by ROS elevation. Additionally, exposure to Na 2 S and/or NH 4 Cl also caused ROS generation and early apoptosis in cumulus cells, which might further affect oocyte maturation in vitro. In summary, our data suggested that exposure to H 2 S and/or NH 3 decreased porcine oocyte maturation in vitro, which might be caused by actin disruption, ROS generation, early apoptosis and autophagy. Copyright © 2017 Elsevier B.V. All rights reserved.

Trends in Infectious Disease Mortality, South Korea, 1983–2015

PubMed Central

Choe, Young June; Choe, Seung-Ah

2018-01-01

We used national statistics from 1983–2015 to evaluate trends in mortality caused by infectious diseases in South Korea. Age-standardized mortality from infectious disease decreased from 43.5/100,000 population in 1983 to 16.5/100,000 in 1996, and then increased to 44.6/100,000 in 2015. Tuberculosis was the most common cause of death in 1983 and respiratory tract infections in 2015. We observed a significant decline in infant deaths caused by infectious diseases, but mortality in persons age >65 years increased from 135 deaths/100,000 population in 1996 to 307/100,000 in 2015. The relative inequality indices for respiratory tract infections, sepsis, and tuberculosis tended to increase over time. Although substantial progress has been achieved in terms of infant mortality, death rates from infectious disease has not decreased overall. Elderly populations with lower education levels and subgroups susceptible to respiratory infections and sepsis should be the focus of preventive policies. PMID:29350153

Causes of the great mass extinction of marine organisms in the Late Devonian

NASA Astrophysics Data System (ADS)

Barash, M. S.

2016-11-01

The second of the five great mass extinctions of the Phanerozoic occurred in the Late Devonian. The number of species decreased by 70-82%. Major crises occurred at the Frasnian-Famennian and Devonian-Carboniferous boundary. The lithological and geochemical compositions of sediments, volcanic deposits, impactites, carbon and oxygen isotope ratios, evidence of climate variability, and sea level changes reflect the processes that led the critical conditions. Critical intervals are marked by layers of black shales, which were deposited in euxinic or anoxic environments. These conditions were the main direct causes of the extinctions. The Late Devonian mass extinction was determined by a combination of impact events and extensive volcanism. They produced similar effects: emissions of harmful chemical compounds and aerosols to cause greenhouse warming; darkening of the atmosphere, which prevented photosynthesis; and stagnation of oceans and development of anoxia. Food chains collapsed and biological productivity decreased. As a result, all vital processes were disturbed and a large portion of the biota became extinct.

Occupational social class and mortality in a population of men economically active: the contribution of education and employment situation.

PubMed

Regidor, Enrique; Ronda, Elena; Martínez, David; Calle, M Elisa; Navarro, Pedro; Domínguez, Vicente

2005-01-01

This study examines how education and employment situation contribute to the association between a classification of occupational class based on skill assets and mortality from different causes of death. Data were obtained by linking records from the 1996 population census for Spanish men aged 35-64 residing in Madrid with 1996 and 1997 mortality records. The risk of mortality was higher in skilled, semi-skilled and unskilled workers than in higher and lower managerial and professional workers. Adjusting for educational level substantially decreased the magnitude of the gradient. The decrease in the gradient after adjusting for employment situation was much smaller. Except in the case of mortality from respiratory diseases, the mortality gradient disappeared after adjusting for both variables. These results show that education and, to a much lesser degree, employment situation explain part of the social gradient observed in mortality from all causes and from broad causes of death, except from respiratory diseases.

Genotoxicity testing of peptides: Folate deprivation as a marker of exaggerated pharmacology

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

Guérard, Melanie, E-mail: melanie.guerard@roche.com; Zeller, Andreas; Festag, Matthias

2014-09-15

The incidence of micronucleated-cells is considered to be a marker of a genotoxic event and can be caused by direct- or indirect-DNA reactive mechanisms. In particular, small increases in the incidence of micronuclei, which are not associated with toxicity in the target tissue or any structurally altering properties of the compound, trigger the suspicion that an indirect mechanism could be at play. In a bone marrow micronucleus test of a synthetic peptide (a dual agonist of the GLP-1 and GIP receptors) that had been integrated into a regulatory 13-week repeat-dose toxicity study in the rat, small increases in the incidencemore » of micronuclei had been observed, together with pronounced reductions in food intake and body weight gain. Because it is well established that folate plays a crucial role in maintaining genomic integrity and pronounced reductions in food intake and body weight gain were observed, folate levels were determined from plasma samples initially collected for toxicokinetic analytics. A dose-dependent decrease in plasma folate levels was evident after 4 weeks of treatment at the mid and high dose levels, persisted until the end of the treatment duration of 13-weeks and returned to baseline levels during the recovery period of 4 weeks. Based on these properties, and the fact that the compound tested (peptide) per se is not expected to reach the nucleus and cause DNA damage, the rationale is supported that the elevated incidence of micronucleated polychromatic erythrocytes is directly linked to the exaggerated pharmacology of the compound resulting in a decreased folate level. - Highlights: • A synthetic peptide has been evaluated for potential genotoxicity • Small increases in an integrated (13-weeks) micronucleus test were observed • Further, animals had a pronounced reductions in food intake and body weight gain • A dose-dependent decrease in plasma folate levels was evident from week 4 onwards • Elevated micronuclei-incidence due to the exaggerated pharmacology.« less

Chlorogenic acid levels in leaves of coffee plants supplied with silicon and infected by Hemileia vastatrix

USDA-ARS?s Scientific Manuscript database

Rust, caused by Hemileia vastatrix, is the main disease that decreases coffee production in Brazil. New and enhanced methods to reduce rust intensity that can be integrated with modern genetic and chemical approaches need to be investigated. Considering that many plant species supplied with silico...

Reinforcement and the Overjustification Effect.

ERIC Educational Resources Information Center

Williams, Bruce W.

Reward contingencies and other extrinsic constraints on behavior can lead to reduced levels of interest in and/or decreased engagement in a target activity in a subsequent noncontingent situation. It has been hypothesized that this effect is caused by a change in the self-perceived locus of motivation from intrinsic to extrinsic. It follows from…

Haemoglobin function in vertebrates: evolutionary changes in cellular regulation in hypoxia.

PubMed

Nikinmaa, M

2001-11-15

The evolution of erythrocytic hypoxia responses is reviewed by comparing the cellular control of haemoglobin-oxygen affinity in agnathans, teleost fish and terrestrial vertebrates. The most ancient response to hypoxic conditions appears to be an increase in cell volume, which increases the haemoglobin-oxygen affinity in lampreys. In teleost fish, an increase of cell volume in hypoxic conditions is also evident. The volume increase is coupled to an increase in erythrocyte pH. These changes are caused by an adrenergic activation of sodium/proton exchange across the erythrocyte membrane. The mechanism is important in acute hypoxia and is followed by a decrease in cellular adenosine triphosphate (ATP) and guanosine triphosphate (GTP) concentrations in continued hypoxia. In hypoxic bird embryos, the ATP levels are also reduced. The mechanisms by which hypoxia decreases cellular ATP and GTP concentrations remains unknown, although at least in bird embryos cAMP-dependent mechanisms have been implicated. In mammals, hypoxia responses appear to occur mainly via modulation of cellular organic phosphate concentrations. In moderate hypoxia, 2,3-diphosphoglycerate levels are increased as a result of alkalosis caused by increased ventilation.

Impaired complex IV activity in response to loss of LRPPRC function can be compensated by mitochondrial hyperfusion

PubMed Central

Rolland, Stéphane G.; Motori, Elisa; Memar, Nadin; Hench, Jürgen; Frank, Stephan; Winklhofer, Konstanze F.; Conradt, Barbara

2013-01-01

Mitochondrial morphology changes in response to various stimuli but the significance of this is unclear. In a screen for mutants with abnormal mitochondrial morphology, we identified MMA-1, the Caenorhabditis elegans homolog of the French Canadian Leigh Syndrome protein LRPPRC (leucine-rich pentatricopeptide repeat containing). We demonstrate that reducing mma-1 or LRPPRC function causes mitochondrial hyperfusion. Reducing mma-1/LRPPRC function also decreases the activity of complex IV of the electron transport chain, however without affecting cellular ATP levels. Preventing mitochondrial hyperfusion in mma-1 animals causes larval arrest and embryonic lethality. Furthermore, prolonged LRPPRC knock-down in mammalian cells leads to mitochondrial fragmentation and decreased levels of ATP. These findings indicate that in a mma-1/LRPPRC–deficient background, hyperfusion allows mitochondria to maintain their functions despite a reduction in complex IV activity. Our data reveal an evolutionary conserved mechanism that is triggered by reduced complex IV function and that induces mitochondrial hyperfusion to transiently compensate for a drop in the activity of the electron transport chain. PMID:23878239

Ultrastructural changes during spermatogenesis, biochemical and hormonal evidences of testicular toxicity caused by TBT in freshwater prawn Macrobrachium rosenbergii (De Man, 1879).

PubMed

Revathi, Peranandam; Iyapparaj, Palanisamy; Vasanthi, Lourduraj Arockia; Munuswamy, Natesan; Krishnan, Muthukalingan

2014-10-01

The present investigation documents the impact of tributyltin (TBT) on the ultrastructural variation of spermatogenesis in freshwater prawn Macrobrachium rosenbergii. The environmentally realistic concentration of TBT can cause damages to the endocrine and reproductive physiology of crustaceans. In this context, three concentrations viz. 10, 100, and 1000 ng/L were selected and exposed to prawns for 90 days. The TBT exposed prawn exhibited decrease the reproductive activity as evidenced by sperm count and sperm length compared to control. Histopathological results revealed the retarded testicular development, abnormal structure of seminiferous tubule, decrease in the concentration of spermatozoa, diminution of seminiferous tubule membrane, abundance of spermatocytes and vacuolation in testis of treated prawns. Ultrastructural study also confirmed the impairment of spermatogenesis in treated prawns. Furthermore, radioimmunoassay (RIA) clearly documented the reduction of testosterone level in TBT exposed groups. Thus, TBT substantially reduced the level of male sex hormone as well as biochemical constituents which ultimately led to impairment of spermatogenesis in the freshwater male prawn M. rosenbergii. Copyright © 2013 Wiley Periodicals, Inc., a Wiley company.

Developmental neurotoxicity of Propylthiouracil (PTU) in rats: Relationship between transient hypothyroxinemia during development and long-lasting behavioural and functional changes

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

Axelstad, Marta; Hansen, Pernille Reimar; Boberg, Julie

2008-10-01

Markedly lowered thyroid hormone levels during development may influence a child's behaviour, intellect, and auditory function. Recent studies, indicating that even small changes in the mother's thyroid hormone status early in pregnancy may cause adverse effects on her child, have lead to increased concern for thyroid hormone disrupting chemicals in the environment. The overall aim of the study was therefore to provide a detailed knowledge on the relationship between thyroid hormone levels during development and long-lasting effects on behaviour and hearing. Groups of 16-17 pregnant rats (HanTac:WH) were dosed with PTU (0, 0.8, 1.6 or 2.4 mg/kg/day) from gestation daymore » (GD) 7 to postnatal day (PND) 17, and the physiological and behavioural development of rat offspring was assessed. Both dams and pups in the higher dose groups had markedly decreased thyroxine (T{sub 4}) levels during the dosing period, and the weight and histology of the thyroid glands were severely affected. PTU exposure caused motor activity levels to decrease on PND 14, and to increase on PND 23 and in adulthood. In the adult offspring, learning and memory was impaired in the two highest dose groups when tested in the radial arm maze, and auditory function was impaired in the highest dose group. Generally, the results showed that PTU-induced hypothyroxinemia influenced the developing rat brain, and that all effects on behaviour and loss of hearing in the adult offspring were significantly correlated to reductions in T{sub 4} during development. This supports the hypothesis that decreased T{sub 4} may be a relevant predictor for long-lasting developmental neurotoxicity.« less

Role of leptin in delayed embryonic development in the Indian short-nosed fruit bat, Cynopterus sphinx.

PubMed

Banerjee, A; Meenakumari, K J; Krishna, A

2010-08-01

An adiposity-associated rise in leptin occurs at the time of delayed embryonic development in Cynopterus sphinx. The aim of present study was to examine the mechanism by which leptin may inhibit progesterone, and therefore could be responsible for delayed development. The study showed a significant increase in circulating leptin level during the period of increased fat accumulation, which coincided with significant decrease in serum progesterone level and delayed embryonic development in C. sphinx. The study showed increased Ob-R expression in the corpus luteum and in the utero-embryonic unit during the period of delayed embryonic development. The in vitro study showed suppressive effect of leptin on progesterone synthesis. The effect of high dose of leptin on ovarian steroidogenesis was found to be mediated through decreased expression of StAR and LH-R proteins in the ovary. The treatment with leptin caused increased expression of STAT 3 and iNOS proteins in the ovary, which correlated with decreased expression of StAR protein in the ovary. The inhibitory effects of leptin on progesterone synthesis in the ovary are thus mediated through STAT 3 and iNOS-NO signaling pathways. This study further demonstrated low expression of PCNA coinciding with the increased concentration of the leptin receptor in the utero-embryonic unit and high circulating leptin level during November. In conclusion, adiposity associated increased leptin level during November-December might play role in suppressing progesterone synthesis in the corpus luteum as well as suppressing the rate of cell-proliferation in the utero-embryonic unit thereby causing delayed embryonic development in C. sphinx. Copyright 2010 Elsevier Inc. All rights reserved.

Developmental neurotoxicity of propylthiouracil (PTU) in rats: relationship between transient hypothyroxinemia during development and long-lasting behavioural and functional changes.

PubMed

Axelstad, Marta; Hansen, Pernille Reimar; Boberg, Julie; Bonnichsen, Mia; Nellemann, Christine; Lund, Søren Peter; Hougaard, Karin Sørig; Hass, Ulla

2008-10-01

Markedly lowered thyroid hormone levels during development may influence a child's behaviour, intellect, and auditory function. Recent studies, indicating that even small changes in the mother's thyroid hormone status early in pregnancy may cause adverse effects on her child, have lead to increased concern for thyroid hormone disrupting chemicals in the environment. The overall aim of the study was therefore to provide a detailed knowledge on the relationship between thyroid hormone levels during development and long-lasting effects on behaviour and hearing. Groups of 16-17 pregnant rats (HanTac:WH) were dosed with PTU (0, 0.8, 1.6 or 2.4 mg/kg/day) from gestation day (GD) 7 to postnatal day (PND) 17, and the physiological and behavioural development of rat offspring was assessed. Both dams and pups in the higher dose groups had markedly decreased thyroxine (T(4)) levels during the dosing period, and the weight and histology of the thyroid glands were severely affected. PTU exposure caused motor activity levels to decrease on PND 14, and to increase on PND 23 and in adulthood. In the adult offspring, learning and memory was impaired in the two highest dose groups when tested in the radial arm maze, and auditory function was impaired in the highest dose group. Generally, the results showed that PTU-induced hypothyroxinemia influenced the developing rat brain, and that all effects on behaviour and loss of hearing in the adult offspring were significantly correlated to reductions in T(4) during development. This supports the hypothesis that decreased T(4) may be a relevant predictor for long-lasting developmental neurotoxicity.

Effects of polyamine levels on the degradation of short-lived and long-lived proteins in cultured L-132 human lung cells.

PubMed Central

Corella, D; Guillén, M; Hernández, J M; Hernández-Yago, J

1998-01-01

Biogenic polyamines have important regulatory functions in various biological processes and it has also been suggested that they could modulate intracellular protein degradation. For an overall assessment of the role of polyamines in this process, we have investigated the effect that the decrease in intracellular polyamine levels caused by inhibitors of polyamine biosynthesis brings about on the degradation of the pools of short- and long-lived proteins in cultured L-132 human lung cells. Treatment of cells with 100 microM (2R,5R)-delta-methyl acetylenic putrescine (MAP), a potent enzyme-activated irreversible inhibitor of ornithine decarboxylase, or with 100 microM MAP plus 50 microM N-butyl 1,3-diaminopropane, a specific inhibitor of spermine synthase, caused a similar decrease (65-70% of control) in the total intracellular levels of polyamines, although they affected the concentrations of spermidine and spermine differently. The effect of the two treatments on protein degradation was essentially the same. In polyamine-depleted cells we observed an inhibition of degradation in long-lived proteins of 16% (P<0.05), with a significant increase in the half-life (t12) of this pool from 100.5 to 120.1 h. This was concomitant with an increase of 26% (P<0. 05) in degradation in short-lived proteins, with a significant decrease in the t12 of this pool from 0.85 to 0.67 h. Recovery of polyamine levels by the addition of 50 microM spermidine to polyamine-depleted cells resulted in a restoration of the degradation rates in both pools of proteins. The way(s) by which polyamines could modulate proteolysis are discussed. PMID:9716494

Altered Levels of Zinc and N-methyl-D-aspartic Acid Receptor Underlying Multiple Organ Dysfunctions After Severe Trauma

PubMed Central

Wang, Guanghuan; Yu, Xiaojun; Wang, Dian; Xu, Xiaohu; Chen, Guang; Jiang, Xuewu

2015-01-01

Background Severe trauma can cause secondary multiple organ dysfunction syndrome (MODS) and death. Oxidative stress and/or excitatory neurotoxicity are considered as the final common pathway in nerve cell injuries. Zinc is the cofactor of the redox enzyme, and the effect of the excitatory neurotoxicity is related to N-methyl-D-aspartic acid receptor (NMDAR). Material/Methods We investigated the levels of zinc and brainstem NMDAR in a rabbit model of severe trauma. Zinc and serum biochemical profiles were determined. Immunohistochemistry was used to detect brainstem N-methyl-D-aspartic acid receptor 1 (NR1), N-methyl-D-aspartic acid receptor 2A (NR2A), and N-methyl-D-aspartic acid receptor 2B (NR2B) expression. Results Brain and brainstem Zn levels increased at 12 h, but serum Zn decreased dramatically after the trauma. NR1 in the brainstem dorsal regions increased at 6 h after injury and then decreased. NR2A in the dorsal regions decreased to a plateau at 12 h after trauma. The levels of NR2B were lowest in the death group in the brainstem. Serum zinc was positively correlated with NR2A and 2B and negatively correlated with zinc in the brain. Correlations were also found between the brainstem NR2A and that of the dorsal brainstem, as well as between brainstem NR2A and changes in NR2B. There was a negative correlation between zinc and NR2A. Conclusions Severe trauma led to an acute reduction of zinc enhancing oxidative stress and the changes of NMDAR causing the neurotoxicity of the nerve cells. This may be a mechanism for the occurrence of MODS or death after trauma. PMID:26335029

Fear of causing harm: use of mannequin-based simulation to decrease student anxiety prior to interacting with female teaching associates.

PubMed

Pugh, Carla M; Obadina, Eniola T; Aidoo, Kofi A

2009-01-01

There is a paucity of research assessing the potential benefits of mannequin trainers when preparing students to interact with teaching associates. The goal of this study was to better understand the effects of mannequin-based simulators on student comfort toward learning specific aspects of the clinical female pelvic exam. First-year medical students (N = 344) were surveyed before and after a mannequin-based simulation curriculum to assess their comfort levels toward learning the female pelvic exam. Causing harm was the top cause of student anxiety toward learning the pelvic exam. Although the mannequin-based simulation curriculum was effective in significantly increasing (p < .001) student comfort levels toward learning the pelvic exam, the majority of students progressed from being "very uncomfortable" with the exam to being "somewhat comfortable." We suggest that mannequin-based simulators be used prior to students' learning experience with pelvic exam teaching associates.

National and sub-national under-five mortality profiles in Peru: a basis for informed policy decisions.

PubMed

Huicho, Luis; Trelles, Miguel; Gonzales, Fernando

2006-07-04

Information on profiles for under-five causes of death is important to guide choice of child-survival interventions. Global level data have been published, but information at country level is scarce. We aimed at defining national and departmental trends and profiles of under-five mortality in Peru from 1996 through 2000. We used the Ministry of Health registered under-five mortality data. For correction of under-registration, a model life-table that fitted the age distribution of the population and of registered deaths was identified for each year. The mortality rates corresponding to these model life-tables were then assigned to each department in each particular year. Cumulative reduction in under-five mortality rate in the 1996-2000 period was estimated calculating the annual reduction slope for each department. Departmental level mortality profiles were constructed. Differences in mortality profiles and in mortality reduction between coastal, andean and jungle regions were also assessed. At country level, only 4 causes (pneumonia, diarrhoea, neonatal diseases and injuries) accounted for 68% of all deaths in 1996, and for 62% in 2000. There was 32.7% of under-five death reduction from 1996 to 2000. Diarrhoea and pneumonia deaths decreased by 84.5% and 41.8%, respectively, mainly in the andean region, whereas deaths due to neonatal causes and injuries decreased by 37.2% and 21.7%. For 1996-2000 period, the andean, coast and jungle regions accounted for 52.4%, 33.1% and 14.4% of deaths, respectively. These regions represent 41.0%, 46.4% and 12.6% of under-five population. Both diarrhoea and pneumonia constitute 30.6% of under-five deaths in the andean region. As a proportion, neonatal deaths remained stable in the country from 1996 to 2000, accounting for about 30% of under-five deaths, whereas injuries and "other" causes, including congenital anomalies, increased by about 5%. Under-five mortality declined substantially in all departments from 1996 to 2000, which is explained mostly by reduction in diarrhoea and pneumonia deaths, particularly in the andean region. There is the need to emphasize interventions to reduce neonatal deaths and emerging causes of death such as injuries and congenital anomalies.

Nitrogen nutrition and temporal effects of enhanced carbon dioxide on soybean growth

NASA Technical Reports Server (NTRS)

Vessey, J. K.; Henry, L. T.; Raper, C. D. Jr

1990-01-01

Plants grown on porous media at elevated CO2 levels generally have low concentrations of tissue N and often appear to require increased levels of external N to maximize growth response. This study determines if soybean [Glycine max (L.) Merr. Ransom'] grown hydroponically at elevated CO2 requires increases in external NO3- concentrations beyond levels that are optimal at ambient CO2 to maintain tissue N concentrations and maximize the growth response. This study also investigates temporal influences of elevated CO2 on growth responses by soybean. Plants were grown vegetatively for 34 d in hydroponic culture at atmospheric CO2 concentrations of 400, 650, and 900 microliters L-1 and during the final 18 d at NO3- concentrations of 0.5, 1.0, 5.0 and 10.0 mM in the culture solution. At 650 and 900 microliters L-1 CO2, plants had maximum increases of 31 and 45% in dry weight during the experimental period. Plant growth at 900 microliters L-1 CO2 was stimulated earlier than at 650 microliters L-1. During the final 18 d of the experiment, the relative growth rates (RGR) of plants grown at elevated CO2 declined. Elevated CO2 caused increases in total N and total NO3(-)-N content and leaf area but not leaf number. Enhancing CO2 levels also caused a decrease in root:shoot ratios. Stomatal resistance increased by 2.1- and 2.8-fold for plants at the 650 and 900 microliters L-1 CO2, respectively. Nitrate level in the culture solutions had no effect on growth or on C:N ratios of tissues, nor did increases in CO2 levels cause a decrease in N concentration of plant tissues. Hence, increases in NO3- concentration of the hydroponic solution were not necessary to maintain the N status of the plants or to maximize the growth response to elevated CO2.

Two Cases of Transiently Elevated Serum CEA Levels in Severe Hypothyroidism without Goiter.

PubMed

Sekizaki, Tomonori; Yamamoto, Chiho; Nomoto, Hiroshi

2018-04-27

Carcinoembryonic antigen (CEA), the level of which is known to increase in both patients with gastrointestinal cancers and those with non-neoplastic conditions, is one of the most widely-used tumor markers. Hypothyroidism is a common endocrinological disorder in which CEA levels can rise, and is sometimes overlooked as a diagnosis in the absence of typical symptoms or thyroid enlargement. We report the cases of two patients with non-goiterous severe hypothyroidism with markedly elevated CEA levels that effectively decreased with levothyroxine replacement therapy alone. Hypothyroidism should be considered as an important cause of unexplained high serum CEA levels in order to avoid unnecessary medical examination.

Downregulation of Glutathione Biosynthesis Contributes to Oxidative Stress and Liver Dysfunction in Acute Kidney Injury

PubMed Central

Siow, Yaw L.; Isaak, Cara K.

2016-01-01

Ischemia-reperfusion is a common cause for acute kidney injury and can lead to distant organ dysfunction. Glutathione is a major endogenous antioxidant and its depletion directly correlates to ischemia-reperfusion injury. The liver has high capacity for producing glutathione and is a key organ in modulating local and systemic redox balance. In the present study, we investigated the mechanism by which kidney ischemia-reperfusion led to glutathione depletion and oxidative stress. The left kidney of Sprague-Dawley rats was subjected to 45 min ischemia followed by 6 h reperfusion. Ischemia-reperfusion impaired kidney and liver function. This was accompanied by a decrease in glutathione levels in the liver and plasma and increased hepatic lipid peroxidation and plasma homocysteine levels. Ischemia-reperfusion caused a significant decrease in mRNA and protein levels of hepatic glutamate-cysteine ligase mediated through the inhibition of transcription factor Nrf2. Ischemia-reperfusion inhibited hepatic expression of cystathionine γ-lyase, an enzyme responsible for producing cysteine (an essential precursor for glutathione synthesis) through the transsulfuration pathway. These results suggest that inhibition of glutamate-cysteine ligase expression and downregulation of the transsulfuration pathway lead to reduced hepatic glutathione biosynthesis and elevation of plasma homocysteine levels, which, in turn, may contribute to oxidative stress and distant organ injury during renal ischemia-reperfusion. PMID:27872680

Postrenal acute kidney injury in a patient with unilateral ureteral obstruction caused by urolithiasis: A case report.

PubMed

Kazama, Itsuro; Nakajima, Toshiyuki

2017-10-01

In patients with bilateral ureteral obstruction, the serum creatinine levels are often elevated, sometimes causing postrenal acute kidney injury (AKI). In contrast, those with unilateral ureteral obstruction present normal serum creatinine levels, as long as their contralateral kidneys are preserved intact. However, the unilateral obstruction of the ureter could affect the renal function, as it humorally influences the renal hemodynamics. A 66-year-old man with a past medical history of hypertension and diabetes mellitus came to our outpatient clinic because of right abdominal dullness. Unilateral ureteral obstruction caused by a radio-opaque calculus in the right upper ureter and a secondary renal dysfunction. As oral hydration and the use of calcium antagonists failed to allow the spontaneous stone passage, extracorporeal shock wave lithotripsy (ESWL) was performed. Immediately after the passage of the stone, the number of red blood cells in the urine was dramatically decreased and the serum creatinine level almost returned to the normal range with the significant increase in glomerular filtration rate. Unilateral ureteral obstruction by the calculus, which caused reflex vascular constriction and ureteral spasm in the contralateral kidney, was thought to be responsible for the deteriorating renal function.

Response of the antioxidant enzymes of the erythrocyte and alterations in the serum biomarkers in rats following oral administration of nanoparticles.

PubMed

Canli, Esin G; Atli, Gülüzar; Canli, Mustafa

2017-03-01

In this study, Al 2 O 3 , CuO and TiO 2 nanoparticles (NPs) were administered to mature female rats (Rattus norvegicus var. albinos) via oral gavage (0, 0.5, 5, 50mg/kg b.w./day) for 14days to investigate their effects on 14 serum biomarkers and 4 antioxidant enzyme (catalase, superoxide dismutase, glutathione peroxidase, glutathione S-transferase) activities in the erythrocyte. Data showed that Al 2 O 3 did not cause any significant (P>0.05) change in the parameters, except few cases, while CuO and TiO 2 caused significant alterations in antioxidant system parameters of the erythrocytes. Activities of catalase and superoxide dismutase significantly decreased in CuO and TiO 2 administered rats. Oppositely, glutathione peroxidase activity increased in CuO and TiO 2 administered rats. There were no significant alterations in the activity of glutathione S-transferase in the erythrocytes. Levels of glucose, cholesterol, bilirubin, triglyceride, triiodothyronine (T3), estradiol, prolactin and immunoglobulin M (IgM) in the serum altered after some of NP administrations, whereas cortisol, protein, creatinine, blood urea nitrogen (BUN), thyroxine (T4) and immunoglobulin G (IgG) levels in the serum did not change significantly after any of NP administration. There were outstanding increases in the levels of bilirubin and prolactin and decreases in the levels of triglyceride and estradiol. The present study demonstrated that the antioxidant enzymes in the erythrocyte were generally affected from copper and titanium NPs, while aluminium and copper NPs caused more significant alterations in serum biomarkers. Copyright © 2017 Elsevier B.V. All rights reserved.

Antioxidant effect of Spirulina (Arthrospira) maxima in a neurotoxic model caused by 6-OHDA in the rat striatum.

PubMed

Tobón-Velasco, J C; Palafox-Sánchez, Victoria; Mendieta, Liliana; García, E; Santamaría, A; Chamorro-Cevallos, G; Limón, I Daniel

2013-08-01

There is evidence to support that an impaired energy metabolism and the excessive generation of reactive oxygen species (ROS) contribute to brain injury in neurodegenerative disorders such as Parkinson's disease (PD), whereas diets enriched in foods with an antioxidant action may modulate its progression. Several studies have proved that the antioxidant components produced by Spirulina, a microscopic blue-green alga, might prevent cell death by decreasing free radicals, inhibiting lipoperoxidation and upregulating the antioxidant enzyme systems. In our study, we investigated the protective effect of the Spirulina maxima (S. maxima) against the 6-OHDA-caused toxicity in the rat striatum. The S. maxima (700 mg/kg/day, vo) was administered for 40 days before and 20 days after a single injection of 6-OHDA (16 μg/2 μL) into the dorsal striatum. At 20-day postsurgery, the brain was removed and the striatum was obtained to evaluate the indicators of toxicity, such as nitric oxide levels, ROS formation, lipoperoxidation, and mitochondrial activity. These variables were found significantly stimulated in 6-OHDA-treated rats and were accompanied by declines in dopamine levels and motor activity. In contrast, the animals that received the chronic treatment with S. maxima had a restored locomotor activity, which is associated with the decreased levels of nitric oxide, ROS, and lipoperoxidation in the striatum, although mitochondrial functions and dopamine levels remained preserved. These findings suggest that supplementation with antioxidant phytochemicals (such as contained in S. maxima) represents an effective neuroprotective strategy against 6-OHDA-caused neurotoxicity vía free radical production to preserve striatal dopaminergic neurotransmission in vivo.

Flow Cytometric Analysis of Presynaptic Nerve Terminals Isolated from Rats Subjected to Hypergravity

NASA Astrophysics Data System (ADS)

Borisova, Tatiana

2008-06-01

Flow cytometric studies revealed an insignificant decrease in cell size heterogeneity and cytoplasmic granularity of rat brain nerve terminals (synaptosomes) isolated from animals subjected to centrifuge-induced hypergravity as compared to control ones. The analysis of plasma membrane potential using the potentiometric optical dye rhodamine 6G showed a decrease in fluorescence intensity by 10 % at steady state level in hypergravity synaptosomes. To monitor synaptic vesicle acidification we used pH-sensitive fluorescent dye acridine orange and demonstrated a lower fluorescence intensity level at steady state (10%) after hypergravity as compared to controls. Thus, exposure to hypergravity resulted in depolarization of the synaptosomal plasma membrane and diminution in synaptic vesicle acidification that may be a cause leading to altered synaptic neurotransmission.

Effect of oxide films on hydrogen permeability of candidate Stirling engine heater head tube alloys

NASA Technical Reports Server (NTRS)

Schuon, S. R.; Misencik, J. A.

1981-01-01

The effect of oxide films developed in situ from CO/CO2 doped hydrogen on high pressure hydrogen permeability at 820 C was studied on N-155, A-286, IN 800, 19-9DL, Nitronic 40, HS-188, and IN 718 tubing in a Stirling materials simulator. The hydrogen permeability decreased with increasing dopant levels of CO or CO2 and corresponding decreases in oxide porosity. Minor reactive alloying elements strongly influenced permeability. At high levels of CO or CO2, a liquid oxide formed on alloys with greater than 50 percent Fe. This caused increased permeability. The oxides formed on the inside tube walls were analyzed and their effective permeabilities were calculated.

Electrolyte depletion in white-nose syndrome bats

USGS Publications Warehouse

Cryan, Paul M.; Meteyer, Carol Uphoff; Blehert, David S.; Lorch, Jeffrey M.; Reeder, DeeAnn M.; Turner, Gregory G.; Webb, Julie; Behr, Melissa; Verant, Michelle L.; Russell, Robin E.; Castle, Kevin T.

2013-01-01

The emerging wildlife disease white-nose syndrome is causing widespread mortality in hibernating North American bats. White-nose syndrome occurs when the fungus Geomyces destructans infects the living skin of bats during hibernation, but links between infection and mortality are underexplored. We analyzed blood from hibernating bats and compared blood electrolyte levels to wing damage caused by the fungus. Sodium and chloride tended to decrease as wing damage increased in severity. Depletion of these electrolytes suggests that infected bats may become hypotonically dehydrated during winter. Although bats regularly arouse from hibernation to drink during winter, water available in hibernacula may not contain sufficient electrolytes to offset winter losses caused by disease. Damage to bat wings from G. destructans may cause life-threatening electrolyte imbalances.

Comparison of magnetic properties of austenitic stainless steel after ion irradiation

NASA Astrophysics Data System (ADS)

Xu, Chaoliang; Liu, Xiangbing; Xue, Fei; Li, Yuanfei; Qian, Wangjie

2018-07-01

Specimens of austenitic stainless steel (ASS) were irradiated with H, Fe and Xe ions at room temperature. The vibrating sample magnetometer (VSM) and grazing incidence X-ray diffraction (GIXRD) were used to analyze the magnetic properties and martensite formation. The magnetic hysteresis loops indicated that higher irradiation damage causes more significant magnetization phenomenon. Under the same damage level, Xe irradiation causes the most significant magnetization, Fe irradiation is the second, and H irradiation is the least. A similar martensite amount variation with irradiation can be obtained. The coercivity Hc increases first to 2 dpa and then decreases continuously with irradiation damage for Xe irradiation. At the same damage lever, H irradiation causes a largest Hc and Xe irradiation causes a minimal one.

Metformin induces oxidative stress in white adipocytes and raises uncoupling protein 2 levels.

PubMed

Anedda, Andrea; Rial, Eduardo; González-Barroso, M Mar

2008-10-01

Metformin is a drug widely used to treat type 2 diabetes. It enhances insulin sensitivity by improving glucose utilization in tissues like liver or muscle. Metformin inhibits respiration, and the decrease in cellular energy activates the AMP-activated protein kinase that in turn switches on catabolic pathways. Moreover, metformin increases lipolysis and beta-oxidation in white adipose tissue, thereby reducing the triglyceride stores. The uncoupling proteins (UCPs) are transporters that lower the efficiency of mitochondrial oxidative phosphorylation. UCP2 is thought to protect against oxidative stress although, alternatively, it could play an energy dissipation role. The aim of this work was to analyse the involvement of UCP2 on the effects of metformin in white adipocytes. We studied the effect of this drug in differentiating 3T3-L1 adipocytes and found that metformin causes oxidative stress since it increases the levels of reactive oxygen species (ROS) and lowers the aconitase activity. Variations in UCP2 protein levels parallel those of ROS. Metformin also increases lipolysis in these cells although only when the levels of ROS and UCP2 have decreased. Hence, UCP2 does not appear to be needed to facilitate fatty acid oxidation. Furthermore, treatment of C57BL/6 mice with metformin also augmented the levels of UCP2 in epididymal white adipose tissue. We conclude that metformin treatment leads to the overexpression of UCP2 in adipocytes to minimize the oxidative stress that is probably due to the inhibition of respiration caused by the drug.

[Effect of sibutramine (meridia) on body composition, peptide YY3-36 and serotonin levels in patients with exogenous constitutional obesity].

PubMed

Vlasova, Iu Iu; Ametov, A S

2010-01-01

To evaluate the impact of gradual weight loss and the positive effect of sibutramine on metabolic parameters and the levels of serotonin and neuropeptide YY3-36 levels in patients with exogenous constitutional obesity (ECO). The study included 36 patients (24 women and 12 men; mean age 37.56 +/- 0.9 years) with a verified diagnosis of ECO. The height, body weight, waist and hip circumference (WC and HC), and body mass index (BMI) were determined. Adipose tissue content was estimated by a bioimpedance method using an adipose mass analyzer. Serum peptide YY3-36 levels were measured by enzyme immunoassay and blood serotonin concentrations were estimated by high performance liquid chromatography with an electrochemical method. 12-week sibutramine therapy caused a significant reduction in body weight, WC, HC, and BMI (p < 0.05) in all the patients. At the same time they were found to have a considerable body composition change (total body and visceral fat was decreased, total body water increased, and systemic metabolism was lowered). The mean peptide YY3-36 level was significantly decreased. Sibutramine did not affect the serum content of total serotonin in the sera of patients. Sibutramine used in the combined therapy in patients with ECO contributes to an effective and steady-state weight loss. Sibutramine treatment causes a reduction in total neuropeptide YY3-36, systemic metabolism, and adipose tissue at the expense of the visceral depot.

Effect of Androctonus bicolor scorpion venom on serum electrolytes in rats: A 24-h time-course study.

PubMed

Al-Asmari, A; Khan, H A; Manthiri, R A

2016-03-01

Black fat-tailed scorpion (Androctonus bicolor) belongs to the family Buthidae and is one of the most venomous scorpions in the world. The effects of A. bicolor venom on serum electrolytes were not known and therefore investigated in this study. Adult male Wistar rats were randomly divided into seven groups with five animals in each group. One of the groups served as control and received vehicle only. The animals in the remaining groups received a single subcutaneous injection of crude A. bicolor venom (200 μg/kg bodyweight) and were killed at different time intervals including 30 min, 1 h, 2 h, 4 h, 8 h, and 24 h after venom injection. The results showed that scorpion venom caused significant increase in serum sodium levels within 30 min after injection which slightly subsided after 1 h and then persisted over 24 h. Serum potassium levels continued to significantly increase until 4 h and then slightly subsided. There were significant decreases in serum magnesium (Mg(+)) levels following scorpion venom injection, at all the time points during the course of study. Serum calcium levels were significantly increased during the entire course of study, whereas serum chloride was significantly decreased. In conclusion, A. bicolor envenomation in rats caused severe and persistent hypomagnesemia with accompanied hypernatremia, hyperkalemia, and hypercalcemia. It is important to measure serum Mg(+) levels in victims of scorpion envenomation, and patients with severe Mg(+) deficiency should be treated accordingly. © The Author(s) 2015.

Thermal stability of deep level defects induced by high energy proton irradiation in n-type GaN

NASA Astrophysics Data System (ADS)

Zhang, Z.; Farzana, E.; Sun, W. Y.; Chen, J.; Zhang, E. X.; Fleetwood, D. M.; Schrimpf, R. D.; McSkimming, B.; Kyle, E. C. H.; Speck, J. S.; Arehart, A. R.; Ringel, S. A.

2015-10-01

The impact of annealing of proton irradiation-induced defects in n-type GaN devices has been systematically investigated using deep level transient and optical spectroscopies. Moderate temperature annealing (>200-250 °C) causes significant reduction in the concentration of nearly all irradiation-induced traps. While the decreased concentration of previously identified N and Ga vacancy related levels at EC - 0.13 eV, 0.16 eV, and 2.50 eV generally followed a first-order reaction model with activation energies matching theoretical values for NI and VGa diffusion, irradiation-induced traps at EC - 0.72 eV, 1.25 eV, and 3.28 eV all decrease in concentration in a gradual manner, suggesting a more complex reduction mechanism. Slight increases in concentration are observed for the N-vacancy related levels at EC - 0.20 eV and 0.25 eV, which may be due to the reconfiguration of other N-vacancy related defects. Finally, the observed reduction in concentrations of the states at EC - 1.25 and EC - 3.28 eV as a function of annealing temperature closely tracks the detailed recovery behavior of the background carrier concentration as a function of annealing temperature. As a result, it is suggested that these two levels are likely to be responsible for the underlying carrier compensation effect that causes the observation of carrier removal in proton-irradiated n-GaN.

Exposure to Hypoxia at High Altitude (5380 m) for 1 Year Induces Reversible Effects on Semen Quality and Serum Reproductive Hormone Levels in Young Male Adults.

PubMed

He, Jiang; Cui, Jianhua; Wang, Rui; Gao, Liang; Gao, Xiaokang; Yang, Liu; Zhang, Qiong; Cao, Jinjun; Yu, Wuzhong

2015-09-01

This study investigated the effect of hypoxia at high altitude on the semen quality and the serum reproductive hormone levels in male adults. A total of 52 male soldiers were enrolled in this cohort study. They were exposed to hypoxia at high altitude (5380 m) for 12 months when undergoing a service. After exposure, they were followed up for 6 months. The samples of semen and peripheral blood were collected at 1 month before exposure (M0), 6 months of exposure (M6), 12 months of exposure (M12), and 6 months after exposure (M18). The semen quality was assessed with computer-assisted analysis system, and the serum levels of reproductive hormones, including prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone were analyzed by ELISA. Compared with those at M0, total sperm count, sperm density, motility, survival rate, and serum levels of LH, PRL and testosterone were significantly decreased, whereas the liquefaction time was significantly prolonged and serum FSH level was significantly increased at M6 (p<0.05). At M12, total sperm count and sperm density increased, whereas sperm motility, survival rate, and the liquefaction time further decreased. Sperm velocities, progression ratios, and lateral head displacements were also decreased. Serum FSH level decreased while serum LH, PRL, and testosterone levels increased. Compared with those at M6, the changes in these detected parameters of semen and hormone at M12 were significant (p<0.05). At M18, all these detected parameters except testosterone level returned to levels comparable to those before exposure. In conclusion, hypoxia at high altitude causes adverse effects on semen quality and reproductive hormones, and these effects are reversible.

Therapeutic apheresis for severe hypertriglyceridemia in pregnancy.

PubMed

Basar, Rafet; Uzum, Ayse Kubat; Canbaz, Bulent; Dogansen, Sema Ciftci; Kalayoglu-Besisik, Sevgi; Altay-Dadin, Senem; Aral, Ferihan; Ozbey, Nese Colak

2013-05-01

During pregnancy, a progressive increase in serum triglyceride (TG) and cholesterol levels is observed whereas TG levels mostly remain <300 mg/dl. In women with genetic forms of hypertriglyceridemia, pregnancy may cause extremely elevated TG levels leading to potentially life-threatening pancreatitis attacks and chylomicronemia syndrome. The only safe medical treatment option during pregnancy is ω-3 fatty acids, which have moderate TG lowering effects. Therapeutic apheresis could be used as primary treatment approach during pregnancy. We reported the effect of double filtration apheresis in one pregnant women with severe hypertriglyceridemia, therapeutic plasmapheresis and double filtration methods in the other severe hypertriglyceridemic pregnant woman; a 32-year-old pregnant woman (patient 1) with a history of hypertriglyceridemia-induced acute pancreatitis during pregnancy and a 30-year-old pregnant woman with extremely high TG levels (12,000 mg/dl) leading to chylomicronemia syndrome (patient 2). Medical nutrition therapy and ω-3 fatty acids were also provided. Double filtration apheresis (patient 1) and plasmapheresis + double filtration apheresis (patient 2) were used. When we calculated the TG levels before and after therapeutic apheresis, maximum decrease achieved with double filtration apheresis was 46.3 % for patient 1 and 37.3 % for patient 2. However, with plasmapheresis TG level declined by 72 % in patient 2. Plasmapheresis seemed to be more efficient to decrease TG levels. Iron deficiency anemia was the main complication apart from technical difficulties by lipemic obstruction of tubing system. Healthy babies were born. Delivery led to decreases in TG levels. It is concluded that during pregnancy therapeutic apheresis is an effective method to decrease extremely high TG levels and risks of its potentially life-threatening complications.

Comparison of the effects of gemfibrozil and clofibric acid on peroxisomal enzymes and cholesterol synthesis of rat hepatocytes.

PubMed

Hashimoto, F; Taira, S; Hayashi, H

1998-11-01

We studied whether the peroxisomal proliferation, induction of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) and activation of cholesterol synthesis by gemfibrozil shown in whole body (Hashimoto F., Ishikawa T., Hamada S. and Hayashi H., Biochemical. Pharm., 49, 1213-1221 (1995)) is also detected at a culture cell level, and we made a comparative analysis of the effects of clofibric acid. Gemfibrozil at 0.25 mM increased the activity of some peroxisomal enzymes (catalase and the cyanide-insensitive fatty acyl-CoA oxidizing system) after incubation for 72 h. However, contrary to whole body experiments, gemfibrozil decreased the activity of HMG-CoA reductase and cholesterol synthesis from [14C]acetate. At 1 mM, gemfibrozil decreased not only the activity of HMG-CoA reductase and cholesterol synthesis, but also the protein content of the cells and peroxisomal enzyme activity, indicating nonspecific inhibition at this concentration. Clofibric acid (0.25 and 1 mM) increased the activity of peroxisomal enzymes, but decreased the activity of HMG-CoA reductase and cholesterol synthesis. With respect to the direct effect on HMG-CoA reductase in the cell homogenate, gemfibrozil at 0.25 mm did not affect the activity, but it clearly inhibited the activity at 2 mM and above. Clofibric acid at 2 mM hardly affected the activity, but it clearly decreased the activity at 5 mM and over. That is, gemfibrozil directly inhibited the activity more strongly than clofibric acid. The direct inhibition of the enzyme itself required higher concentrations of both agents than did inhibition at the culture cell level. These results suggest that the cytotoxicity of gemfibrozil is greater than that of clofibric acid, and that gemfibrozil, as well as clofibric acid, can induce peroxisomal enzymes in the culture cell level. In contrast to whole body results, gemfibrozil may suppress cholesterol synthesis from [14C]acetate through the inhibition of HMG-CoA reductase at the culture cell level. The decreases in the reductase activity caused by gemfibrozil and clofibric acid at the culture cell level may not be caused by the direct inhibition of the enzyme.

Annual summary of vital statistics: 2005.

PubMed

Hamilton, Brady E; Miniño, Arialdi M; Martin, Joyce A; Kochanek, Kenneth D; Strobino, Donna M; Guyer, Bernard

2007-02-01

The general fertility rate in 2005 was 66.7 births per 1000 women aged 15 to 44 years, the highest level since 1993. The birth rate for teen mothers (aged 15 to 19 years) declined by 2% between 2004 and 2005, falling to 40.4 births per 1000 women, the lowest ever recorded in the 65 years for which there are consistent data. The birth rates for women > or = 30 years of age rose in 2005 to levels not seen in almost 40 years. Childbearing by unmarried women also increased to historic record levels for the United States in 2005. The cesarean-delivery rate rose by 4% in 2005 to 30.2% of all births, another record high. The preterm birth rate continued to rise (to 12.7% in 2005), as did the rate for low birth weight births (8.2%). The infant mortality rate was 6.79 infant deaths per 1000 live births in 2004, not statistically different from the rate in 2003. Pronounced differences in infant mortality rates by race and Hispanic origin continue, with non-Hispanic black newborns more than twice as likely as non-Hispanic white and Hispanic infants to die within 1 year of birth. The expectation of life at birth reached a record high in 2004 of 77.8 years for all gender and race groups combined. Death rates in the United States continued to decline, with death rates decreasing for 9 of the 15 leading causes. The crude death rate for children aged 1 to 19 years did not decrease significantly between 2003 and 2004. Of the 10 leading causes of death for 2004 in this age group, only the rates for influenza and pneumonia showed a significant decrease. The death rates increased for intentional self-harm (suicide), whereas rates for other causes did not change significantly for children. A large proportion of childhood deaths continue to occur as a result of preventable injuries.

Effect of Different Cooking Methods on Histamine Levels in Selected Foods

PubMed Central

Chung, Bo Young; Park, Sook Young; Byun, Yun Sun; Son, Jee Hee; Choi, Yong Won; Cho, Yong Se

2017-01-01

Background Histamine in food is known to cause food poisoning and allergic reactions. We usually ingest histamine in cooked food, but there are few studies about the influence of cooking method on the histamine level. Objective The purpose of this study was to determine the influence of cooking methods on the concentration of histamine in foods. Methods The foods chosen were those kinds consumed frequently and cooked by grilling, boiling, and frying. The histamine level of the food was measured using enzyme-linked immunosorbent assay. Results Grilled seafood had higher histamine levels than raw or boiled seafood. For meat, grilling increased the histamine level, whereas boiling decreased it. For eggs, there was not much difference in histamine level according to cooking method. Fried vegetables had higher histamine levels than raw vegetables. And fermented foods didn't show much difference in histamine level after being boiled. Conclusion The histamine level in food has changed according to the cooking method used to prepare it. Frying and grilling increased histamine level in foods, whereas boiling had little influence or even decreased it. The boiling method might be helpful to control the effect of histamine in histamine-sensitive or susceptible patients, compared with frying and grilling. PMID:29200758

US County-Level Trends in Mortality Rates for Major Causes of Death, 1980-2014.

PubMed

Dwyer-Lindgren, Laura; Bertozzi-Villa, Amelia; Stubbs, Rebecca W; Morozoff, Chloe; Kutz, Michael J; Huynh, Chantal; Barber, Ryan M; Shackelford, Katya A; Mackenbach, Johan P; van Lenthe, Frank J; Flaxman, Abraham D; Naghavi, Mohsen; Mokdad, Ali H; Murray, Christopher J L

2016-12-13

County-level patterns in mortality rates by cause have not been systematically described but are potentially useful for public health officials, clinicians, and researchers seeking to improve health and reduce geographic disparities. To demonstrate the use of a novel method for county-level estimation and to estimate annual mortality rates by US county for 21 mutually exclusive causes of death from 1980 through 2014. Redistribution methods for garbage codes (implausible or insufficiently specific cause of death codes) and small area estimation methods (statistical methods for estimating rates in small subpopulations) were applied to death registration data from the National Vital Statistics System to estimate annual county-level mortality rates for 21 causes of death. These estimates were raked (scaled along multiple dimensions) to ensure consistency between causes and with existing national-level estimates. Geographic patterns in the age-standardized mortality rates in 2014 and in the change in the age-standardized mortality rates between 1980 and 2014 for the 10 highest-burden causes were determined. County of residence. Cause-specific age-standardized mortality rates. A total of 80 412 524 deaths were recorded from January 1, 1980, through December 31, 2014, in the United States. Of these, 19.4 million deaths were assigned garbage codes. Mortality rates were analyzed for 3110 counties or groups of counties. Large between-county disparities were evident for every cause, with the gap in age-standardized mortality rates between counties in the 90th and 10th percentiles varying from 14.0 deaths per 100 000 population (cirrhosis and chronic liver diseases) to 147.0 deaths per 100 000 population (cardiovascular diseases). Geographic regions with elevated mortality rates differed among causes: for example, cardiovascular disease mortality tended to be highest along the southern half of the Mississippi River, while mortality rates from self-harm and interpersonal violence were elevated in southwestern counties, and mortality rates from chronic respiratory disease were highest in counties in eastern Kentucky and western West Virginia. Counties also varied widely in terms of the change in cause-specific mortality rates between 1980 and 2014. For most causes (eg, neoplasms, neurological disorders, and self-harm and interpersonal violence), both increases and decreases in county-level mortality rates were observed. In this analysis of US cause-specific county-level mortality rates from 1980 through 2014, there were large between-county differences for every cause of death, although geographic patterns varied substantially by cause of death. The approach to county-level analyses with small area models used in this study has the potential to provide novel insights into US disease-specific mortality time trends and their differences across geographic regions.

[Current trends in the depopulation process in the northwestern economic region of Russia].

PubMed

Semenov, S P; Dobroskok, V A

1996-01-01

Current demographic trends in the northwestern region of Russia, one of the regions most affected by depopulation, are analyzed. The author discusses the general decline in the standard of living and the decrease in the funding available for providing social services, as well as unemployment in the local military industry, as the main causes of the deterioration of the demographic situation. Data are presented by sex. Fertility seems to have reached its lowest level and mortality its highest in 1994, with a modest improvement in both indicators since then. The author compares trends among various ethnic groups and geographic regions. High levels of mortality among the young, and the contribution of alcoholism to mortality rates, continue to give cause for concern.

The Influence of Red Fruit Oil on Creatin Kinase Level at Maximum Physical Activity

NASA Astrophysics Data System (ADS)

Apollo Sinaga, Fajar; Hotliber Purba, Pangondian

2018-03-01

Heavy physical activities can cause the oxidative stress which resulting in muscle damage with an indicator of elevated levels of Creatin Kinase (CK) enzyme. The oxidative stress can be prevented or reduced by antioxidant supplementation. One of natural resources which contain antioxidant is Red Fruit (Pandanus conoideus) Oil (RFO). This study aims to see the effect of Red Fruit Oil on Creatin Kinase (CK) level at maximum physical activity. This study is an experimental research by using the design of randomized control group pretest-posttest. This study was using 24 male mice divided into four groups, the control group was given aquadest, the treatment groups P1, P2, and P3 were given the RFO orally of 0.15 ml/kgBW, 0.3 ml/kgBW, and 0.6 ml/kgBW, respectively, for a month. The level of CK was checked for all groups at the beginning of study and after the maximum physical activity. The obtained data were then tested statistically by using t-test and ANOVA. The result shows the RFO supplementation during exercise decreased the CK level in P1, P2, and P3 groups with p<0.05, and the higher RFO dosage resulted in decreased CK level at p<0.05. The conclusion of this study is the Red Fruit Oil could decrease the level of CK at maximum physical activity.

Analysis of the Complex Forbush Decreases of June 2015

NASA Astrophysics Data System (ADS)

Lara, A.; Santiago, A.

2016-12-01

We investigated the sudden increase of the counting rates observed by muon telescopes during the main phase of the June 20, 2015 Forbush decrease. We analyzed the probability that this peak was caused by a shock reacceleration of solar energetic particles accelerated by the solar flare occurred on June 22, 2015. To study this event, we used ground level cosmic ray detectors, GOES proton intensities, observations of the geomagnetic activity index (Dst) and interplanetary magnetic field data observed by ACE and WIND spacecraft available from the OMNI database.

Plasma thyroxine changes of the Apollo crewmen

NASA Technical Reports Server (NTRS)

Sheinfeld, M.; Leach, C. S.; Johnson, P. C.

1975-01-01

Blood drawn from Apollo crew members prior to the mission, at recovery, and postmission, was used to examine the effect Apollo mission activities have on thyroid hormone levels. At recovery, statistically significant increases in thyroxine and the free thyroxine index were found. Serum cholesterol and triglycerides were decreased. No change of statistical significance was found in the T3 binding percentage, total serum proteins, and albumin. We conclude that Apollo activities and environment caused the postmission increase in plasma thyroxine. The prolonged postmission decreases in serum cholesterol may be one result of the increased thyroxine activity.

Circulating Hepcidin-25 Is Reduced by Endogenous Estrogen in Humans.

PubMed

Lehtihet, Mikael; Bonde, Ylva; Beckman, Lena; Berinder, Katarina; Hoybye, Charlotte; Rudling, Mats; Sloan, John H; Konrad, Robert J; Angelin, Bo

2016-01-01

Hepcidin reduces iron absorption by binding to the intestinal iron transporter ferroportin, thereby causing its degradation. Although short-term administration of testosterone or growth hormone (GH) has been reported to decrease circulating hepcidin levels, little is known about how hepcidin is influenced in human endocrine conditions associated with anemia. We used a sensitive and specific dual-monoclonal antibody sandwich immunoassay to measure hepcidin-25 in patients (a) during initiation of in vitro fertilization when endogenous estrogens were elevated vs. suppressed, (b) with GH deficiency before and after 12 months substitution treatment, (c) with hyperthyroidism before and after normalization, and (d) with hyperprolactinemia before and after six months of treatment with a dopamine agonist. In response to a marked stimulation of endogenous estrogen production, median hepcidin levels decreased from 4.85 to 1.43 ng/mL (p < 0.01). Hyperthyroidism, hyperprolactinemia, or GH substitution to GH-deficient patients did not influence serum hepcidin-25 levels. In humans, gonadotropin-stimulated endogenous estrogen markedly decreases circulating hepcidin-25 levels. No clear and stable correlation between iron biomarkers and hepcidin-25 was seen before or after treatment of hyperthyroidism, hyperprolactinemia or growth hormone deficiency.

Circulating Hepcidin-25 Is Reduced by Endogenous Estrogen in Humans

PubMed Central

Lehtihet, Mikael; Bonde, Ylva; Beckman, Lena; Berinder, Katarina; Hoybye, Charlotte; Rudling, Mats; Sloan, John H.; Konrad, Robert J.; Angelin, Bo

2016-01-01

Objective Hepcidin reduces iron absorption by binding to the intestinal iron transporter ferroportin, thereby causing its degradation. Although short-term administration of testosterone or growth hormone (GH) has been reported to decrease circulating hepcidin levels, little is known about how hepcidin is influenced in human endocrine conditions associated with anemia. Research design and methods We used a sensitive and specific dual–monoclonal antibody sandwich immunoassay to measure hepcidin-25 in patients (a) during initiation of in vitro fertilization when endogenous estrogens were elevated vs. suppressed, (b) with GH deficiency before and after 12 months substitution treatment, (c) with hyperthyroidism before and after normalization, and (d) with hyperprolactinemia before and after six months of treatment with a dopamine agonist. Results In response to a marked stimulation of endogenous estrogen production, median hepcidin levels decreased from 4.85 to 1.43 ng/mL (p < 0.01). Hyperthyroidism, hyperprolactinemia, or GH substitution to GH-deficient patients did not influence serum hepcidin-25 levels. Conclusions In humans, gonadotropin-stimulated endogenous estrogen markedly decreases circulating hepcidin-25 levels. No clear and stable correlation between iron biomarkers and hepcidin-25 was seen before or after treatment of hyperthyroidism, hyperprolactinemia or growth hormone deficiency. PMID:26866603

Comparing the effects of two Swedish massage techniques on the vital signs and anxiety of healthy women

PubMed Central

Gholami-Motlagh, Farzaneh; Jouzi, Mina; Soleymani, Bahram

2016-01-01

Background: Anxiety is an inseparable part of our lives and a serious threat to health. Therefore, it is necessary to use certain strategies to prevent disorders caused by anxiety and adjust the vital signs of people. Swedish massage is one of the most recognized techniques for reducing anxiety. This study aims to compare the effects of two massage techniques on the vital signs and anxiety of healthy women. Materials and Methods: This quasi-experimental study with a two-group, crossover design was conducted on 20 healthy women who were selected by simple sampling method and were randomly assigned to BNC (Back, Neck, and Chest) or LAF (Leg, Arm, and Face) groups. Massage therapy was carried out for a 14-week period (two 4-week massage therapy sessions and 6 weeks washout stage). Gathered data were analyzed using paired t-test with a significance level of P < 0.05. Results: Both BNC and LAF methods caused a significant decrease in systolic BP in the first stage (P = 0.02, 0.00); however, diastolic BP showed significant decrease only in BNC group (P = 0.01). The mean average of body temperature of LAF group showed a significant decrease in the first stage (P = 0.0.3), and pulse and respiratory rate showed significant decrease in both groups during the second stage (P = 0.00). In addition, anxiety scores showed no significant difference before and after massage therapy (P < 0.05). Conclusions: Massage therapy caused a decrease in systolic BP, pulse, and respiratory rate. It can be concluded that massage therapy was useful for decreasing the vital signs associated with anxiety in healthy women. PMID:27563325

Rotating night shifts too quickly may cause anxiety and decreased attentional performance, and impact prolactin levels during the subsequent day: a case control study.

PubMed

Chang, Yu-San; Chen, Hsiang-Lan; Wu, Yu-Hsuan; Hsu, Chung-Yao; Liu, Ching-Kuan; Hsu, Chin

2014-08-05

We investigated circadian changes and effects on mood, sleep-related hormones and cognitive performance when nurses worked consecutive night shifts in a rapidly rotating shift system. Daytime cognitive function, sleep propensity and sleep-related hormones (growth hormone, cortisol, prolactin, thyrotropin) were compared after participants worked two and four consecutive night shifts. Twenty-three off-duty nurses, 20 nurses working two consecutive night shifts and 16 nurses working four consecutive night shifts were enrolled. All participants completed the Maintenance of Wakefulness Test, State-Trait Anxiety Inventory, Stanford Sleepiness Scale, visual attention tasks (VAT), Wisconsin Card Sorting Test, and modified Multiple Sleep Latency Test. Hormone levels were also measured four times throughout the day, at 2-h intervals. During the day, the participants in the night shift groups were less able to maintain wakefulness, had poor performance on VAT, and higher thyrotropin levels than did those in the off-duty group. Participants who worked two night shifts were better able to maintain wakefulness, had higher anxiety scale scores, poorer initial performance and lack of learning effect on VAT, and higher prolactin levels compared with those who worked four night shifts. There were no differences in cortisol levels between the two- and four- shift groups. Rotating night shifts too quickly may cause anxiety and decreased attentional performance, and may impact daytime prolactin levels after night shifts. It is possible that the two-shift group had a higher cortisol level than did the four-shift group, which would be consistent with the group's higher state anxiety scores. The negative findings may be due to the small sample size. Further studies on the effects of consecutive night shifts on mood and cortisol levels during the daytime after sleep restriction would be valuable.

Effects of kale ingestion on pharmacokinetics of acetaminophen in rats.

PubMed

Yamasaki, Izumi; Uotsu, Nobuo; Yamaguchi, Kohji; Takayanagi, Risa; Yamada, Yasuhiko

2011-12-01

Kale is a cruciferous vegetable (Brassicaceae) that contains a large amount of health-promoting phytochemicals. The chronic ingestion of cabbage of the same family is known to accelerate conjugating acetaminophen (AA) and decrease the plasma AA level. Therefore, we examined to clarify the effects of kale on the pharmacokinetics of AA, its glucuronide (AA-G) and sulfate (AA-S). AA was orally administered to rats pre-treated with kale or cabbage (2000 mg/kg/day) for one week. Blood samples were collected from the jugular vein, and the concentrations of AA, AA-G and AA-S were determined. In results, kale ingestion induced an increase in the area under the concentration-time curve (AUC) and a decrease in the clearance of AA, whereas cabbage had almost no influence. In addition, there were significant differences in the AUC of AA-G between the control and kale groups. mRNA expression levels of UDP-glucuronosyltransferases, the enzymes involved in glucuronidation, in the kale group were significantly higher than those in the control group. In conclusion, kale ingestion increased the plasma concentrations of both AA and AA-G. The results suggest that kale ingestion accelerates the glucuronidation of AA, but an increase of plasma AA levels has a different cause than the cause of glucuronidation.

A partial loss of function allele of Methyl-CpG-binding protein 2 predicts a human neurodevelopmental syndrome

PubMed Central

Samaco, Rodney C.; Fryer, John D.; Ren, Jun; Fyffe, Sharyl; Chao, Hsiao-Tuan; Sun, Yaling; Greer, John J.; Zoghbi, Huda Y.; Neul, Jeffrey L.

2008-01-01

Rett Syndrome, an X-linked dominant neurodevelopmental disorder characterized by regression of language and hand use, is primarily caused by mutations in methyl-CpG-binding protein 2 (MECP2). Loss of function mutations in MECP2 are also found in other neurodevelopmental disorders such as autism, Angelman-like syndrome and non-specific mental retardation. Furthermore, duplication of the MECP2 genomic region results in mental retardation with speech and social problems. The common features of human neurodevelopmental disorders caused by the loss or increase of MeCP2 function suggest that even modest alterations of MeCP2 protein levels result in neurodevelopmental problems. To determine whether a small reduction in MeCP2 level has phenotypic consequences, we characterized a conditional mouse allele of Mecp2 that expresses 50% of the wild-type level of MeCP2. Upon careful behavioral analysis, mice that harbor this allele display a spectrum of abnormalities such as learning and motor deficits, decreased anxiety, altered social behavior and nest building, decreased pain recognition and disrupted breathing patterns. These results indicate that precise control of MeCP2 is critical for normal behavior and predict that human neurodevelopmental disorders will result from a subtle reduction in MeCP2 expression. PMID:18321864

Spatial Variations of Heavy Metals in the Soils of Vegetable-Growing Land along Urban-Rural Gradient of Nanjing, China

PubMed Central

Fang, Shi-Bo; Hu, Hao; Sun, Wan-Chun; Pan, Jian-Jun

2011-01-01

China has experienced rapid urbanization in recent years. The acceleration of urbanization has created wealth and opportunity as well as intensified ecological and environmental problems, especially soil pollution. Our study concentrated on the variation of heavy metal content due to urbanization in the vegetable-growing soil. Laws and other causes of the spatial-temporal variation in heavy metal content of vegetable-growing soils were analyzed for the period of urbanization in Nanjing (the capital of Jiangsu province in China). The levels of Cu, Zn, Pb, Cd and Hg in samples of vegetable-growing soil were detected. The transverse, vertical spatio-temporal variation of heavy metals in soil was analyzed on the base of field investigations and laboratory analysis. The results show that: (1) in soil used for vegetable production, the levels of heavy metals decreased gradually from urban to rural areas; the levels of the main heavy metals in urban areas are significantly higher than suburban and rural areas; (2) the means of the levels of heavy metals, calculated by subtracting the sublayer (15–30 cm) from the toplayer (0–15 cm), are all above zero and large in absolute value in urban areas, but in suburban and rural areas, the means are all above or below zero and small in absolute value. The causes of spatial and temporal variation were analyzed as follows: one cause was associated with mellowness of the soil and the length of time the soil had been used for vegetable production; the other cause was associated with population density and industrial intensity decreasing along the urban to rural gradient (i.e., urbanization levels can explain the distribution of heavy metals in soil to some extent). Land uses should be planned on the basis of heavy metal pollution in soil, especially in urban and suburban regions. Heavily polluted soils have to be expected from food production. Further investigation should be done to determine whether and what kind of agricultural production could be established near urban centers. PMID:21776203

The postmitotic Saccharomyces cerevisiae after spaceflight showed higher viability

NASA Astrophysics Data System (ADS)

Yi, Zong-Chun; Li, Xiao-Fei; Wang, Yan; Wang, Jie; Sun, Yan; Zhuang, Feng-Yuan

2011-06-01

The budding yeast Saccharomyces cerevisiae has been proposed as an ideal model organism for clarifying the biological effects caused by spaceflight conditions. The postmitotic S. cerevisiae cells onboard Practice eight recoverable satellite were subjected to spaceflight for 15 days. After recovery, the viability, the glycogen content, the activities of carbohydrate metabolism enzymes, the DNA content and the lipid peroxidation level in yeast cells were analyzed. The viability of the postmitotic yeast cells after spaceflight showed a three-fold increase as compared with that of the ground control cells. Compared to the ground control cells, the lipid peroxidation level in the spaceflight yeast cells markedly decreased. The spaceflight yeast cells also showed an increase in G2/M cell population and a decrease in Sub-G1 cell population. The glycogen content and the activities of hexokinase and succinate dehydrogenase significantly decreased in the yeast cells after spaceflight. In contrast, the activity of malate dehydrogenase showed an obvious increase after spaceflight. These results suggested that microgravity or spaceflight could promote the survival of postmitotic S. cerevisiae cells through regulating carbohydrate metabolism, ROS level and cell cycle progression.

Effect of intramammary injection of rboGM-CSF on milk levels of chemiluminescence activity, somatic cell count, and Staphylococcus aureus count in Holstein cows with S. aureus subclinical mastitis

PubMed Central

2004-01-01

Abstract The effect of intramammary injection of recombinant bovine granulocyte-macrophage colony-stimulating factor (rboGM-CSF, 400 μg/10 mL) on quarter milk levels of chemiluminescence (CL) activity, and somatic cell count (SCC) and shedding pattern of Staphylococcus aureus was investigated. Ten Holstein cows, naturally infected with S. aureus were used, with either early-stage or late-stage subclinical mastitis. Injection of rboGM-CSF caused a remarkable increase in milk CL activity with a peak at 6 h after the cytokine injection in the early- and late-stage groups. In the early-stage group, milk SCC stayed around preinjection level at 6 h, rose significantly on days 1 and 2, and was followed by a smooth and significant decline to an under preinjection level (below 200 000 cells/mL) on day 7 postinjection. Alternatively, in the late-stage group, milk SCC rose significantly at 6 h after the cytokine injection and maintained high levels thereafter. The milk S. aureus count decreased drastically by the cytokine injection in the early-stage group. The bacterial count was moderately decreased in the late-stage group, but increased back to preinoculation levels on day 7 after the cytokine injection. The results suggest that the rboGM-CSF has a potential as a therapeutic agent for S. aureus infection causing subclinical mastitis of dairy cows, if the cytokine is applied at the initial stage of infection. PMID:15352542

Murine model for congenital CMV infection and hearing impairment

PubMed Central

2011-01-01

Background Congenital cytomegalovirus (CMV) infection is the leading cause of sensorineural hearing loss (SNHL), and SNHL is the most frequent sequela of congenital CMV infection. But the pathogenic mechanism remains unknown, and there is no ideal CMV intrauterine infection animal model to study the mechanisms by which SNHL develops. Methods We established the congenital murine cytomegalovirus (MCMV) infection model by directly injecting the virus into the placenta on day 12.5 of gestation. Then, we observed the development and the MCMV congenital infection rate of the fetuses on the day they were born. Furthermore, we detected the auditory functions, the conditions of the MCMV infection, and the histological change of the inner ears of 28-day-old and 70-day-old offspring. Results Both the fetal loss rate and the teratism rate of offspring whose placentas were inoculated with MCMV increased, and their body length, head circumference, and weight decreased. The hearing level of offspring both decreased at both 28- and 70-days post birth; the 70-day-old mice developed lower hearing levels than did the 28-day old mice. No significant inflammatory changes in the cochleae of the mice were observed. MCMV DNA signals were mainly detected in the spiral ganglion neurons and the endolymph area, but not in the perilymph area. The number of neurons decreased, and their ultrastructures changed. Moreover, with age, the number of neurons dramatically decreased, and the ultrastructural lesions of neurons became much more severe. Conclusions The results suggest that the direct injection of MCMV into the placenta may efficiently cause fetal infection and disturb the intrauterine development of the fetus, and placental inoculation itself has no obvious adverse effects on offspring. The reduction in the number of spiral ganglion neurons and the ultrastructural lesions of the neurons may be the major cause of congenital CMV infection-induced progressive SNHL. PMID:21320351

Murine model for congenital CMV infection and hearing impairment.

PubMed

Juanjuan, Chen; Yan, Feng; Li, Chen; Haizhi, Liu; Ling, Wang; Xinrong, Wang; Juan, Xiao; Tao, Liu; Zongzhi, Yin; Suhua, Chen

2011-02-15

Congenital cytomegalovirus (CMV) infection is the leading cause of sensorineural hearing loss (SNHL), and SNHL is the most frequent sequela of congenital CMV infection. But the pathogenic mechanism remains unknown, and there is no ideal CMV intrauterine infection animal model to study the mechanisms by which SNHL develops. We established the congenital murine cytomegalovirus (MCMV) infection model by directly injecting the virus into the placenta on day 12.5 of gestation. Then, we observed the development and the MCMV congenital infection rate of the fetuses on the day they were born. Furthermore, we detected the auditory functions, the conditions of the MCMV infection, and the histological change of the inner ears of 28-day-old and 70-day-old offspring. Both the fetal loss rate and the teratism rate of offspring whose placentas were inoculated with MCMV increased, and their body length, head circumference, and weight decreased. The hearing level of offspring both decreased at both 28- and 70-days post birth; the 70-day-old mice developed lower hearing levels than did the 28-day old mice. No significant inflammatory changes in the cochleae of the mice were observed. MCMV DNA signals were mainly detected in the spiral ganglion neurons and the endolymph area, but not in the perilymph area. The number of neurons decreased, and their ultrastructures changed. Moreover, with age, the number of neurons dramatically decreased, and the ultrastructural lesions of neurons became much more severe. The results suggest that the direct injection of MCMV into the placenta may efficiently cause fetal infection and disturb the intrauterine development of the fetus, and placental inoculation itself has no obvious adverse effects on offspring. The reduction in the number of spiral ganglion neurons and the ultrastructural lesions of the neurons may be the major cause of congenital CMV infection-induced progressive SNHL.

Puberty is delayed in male mice with dextran sodium sulfate colitis out of proportion to changes in food intake, body weight, and serum levels of leptin.

PubMed

Deboer, Mark D; Li, Yongli

2011-01-01

In boys, inflammatory bowel disease often results in delayed puberty associated with decreased bone mineral density and decreased linear growth. Our goal was to investigate whether pubertal timing and levels of leptin differed between prepubertal male mice with colitis and food-restricted (FR) mice maintained at a similar weight. We induced colitis in 32-d-old male mice using dextran sodium sulfate (DSS), resulting in 10 d of worsening colitis. We followed up these mice for separation of the prepuce from the glans penis as a marker of pubertal progression. Compared with free-feeding control mice, DSS and FR mice had significantly lower weight on d 7-10 of treatment. DSS mice had later puberty than control and FR mice. DSS mice also had smaller testes, lower FSH levels, increased systemic cytokines, and increased colonic inflammation by histology. Leptin levels were similar between DSS and FR mice, whereas both had decreases in leptin compared with controls. We conclude that DSS colitis causes delayed puberty in sexually immature male mice beyond what is seen among FR mice of similar weight, food intake, and leptin levels. These experiments provide support for the hypothesis that pubertal delay in colitis is influenced by factors beyond poor weight gain alone.

Potential Biomarker Peptides Associated with Acute Alcohol-Induced Reduction of Blood Pressure

PubMed Central

Wakabayashi, Ichiro; Marumo, Mikio; Nonaka, Daisuke; Shimomura, Tomoko; Eguchi, Ryoji; Lee, Lyang-Ja; Tanaka, Kenji; Hatake, Katsuhiko

2016-01-01

The purpose of this study was to explore the peptides that are related to acute reduction of blood pressure after alcohol drinking. Venous blood was collected from male healthy volunteers before and after drinking white wine (3 ml/kg weight) containing 13% of ethanol. Peptidome analysis for serum samples was performed using a new target plate, BLOTCHIP®. Alcohol caused significant decreases in systolic and diastolic blood pressure levels at 45 min. The peptidome analysis showed that the levels of three peptides of m/z 1467, 2380 and 2662 changed significantly after drinking. The m/z 1467 and 2662 peptides were identified to be fragments of fibrinogen alpha chain, and the m/z 2380 peptide was identified to be a fragment of complement C4. The intensities of the m/z 2380 and m/z 1467 peptides before drinking were associated with % decreases in systolic and diastolic blood pressure levels at 45 min after drinking compared with the levels before drinking, while there were no significant correlations between the intensity of the m/z 2662 peptide and % decreases in systolic and diastolic blood pressure levels after drinking. The m/z 1467 and 2380 peptides are suggested to be markers for acute reduction of blood pressure after drinking alcohol. PMID:26815288

Efficacy of Glutathione in Ameliorating Sulfur Mustard Analog-Induced Toxicity in Cultured Skin Epidermal Cells and in SKH-1 Mouse Skin In Vivo

PubMed Central

Tewari-Singh, Neera; Agarwal, Chapla; Huang, Jie; Day, Brian J.; White, Carl W.

2011-01-01

Exposure to chemical warfare agent sulfur mustard (HD) is reported to cause GSH depletion, which plays an important role in HD-linked oxidative stress and skin injury. Using the HD analog 2-chloroethyl ethyl sulfide (CEES), we evaluated the role of GSH and its efficacy in ameliorating CEES-caused skin injury. Using mouse JB6 and human HaCaT epidermal keratinocytes, we observed both protective and therapeutic effects of exogenous GSH (1 or 10 mM) in attenuating a CEES-caused decrease in cell viability and DNA synthesis, as well as S and G2M phase arrest in cell cycle progression. However, the protective effect of GSH was stronger than its ability to reverse CEES-induced cytotoxic effect. The observed effect of GSH could be associated with an increase in intracellular GSH levels after its treatment before or after CEES exposure, which strongly depleted cellular GSH levels. N-Acetyl cysteine, a GSH precursor, also showed both protective and therapeutic effects against CEES-caused cytotoxicity. Buthionine sulfoximine, which reduces cellular GSH levels, caused an increased CEES cytotoxicity in both JB6 and HaCaT cells. In further studies translating GSH effects in cell culture, pretreatment of mice with 300 mg/kg GSH via oral gavage 1 h before topical application of CEES resulted in significant protection against CEES-caused increase in skin bifold and epidermal thickness, apoptotic cell death, and myeloperoxidase activity, which could be associated with increased skin GSH levels. Together, these results highlight GSH efficacy in ameliorating CEES-caused skin injury and further support the need for effective antioxidant countermeasures against skin injury by HD exposure. PMID:20974699

Efficacy of glutathione in ameliorating sulfur mustard analog-induced toxicity in cultured skin epidermal cells and in SKH-1 mouse skin in vivo.

PubMed

Tewari-Singh, Neera; Agarwal, Chapla; Huang, Jie; Day, Brian J; White, Carl W; Agarwal, Rajesh

2011-02-01

Exposure to chemical warfare agent sulfur mustard (HD) is reported to cause GSH depletion, which plays an important role in HD-linked oxidative stress and skin injury. Using the HD analog 2-chloroethyl ethyl sulfide (CEES), we evaluated the role of GSH and its efficacy in ameliorating CEES-caused skin injury. Using mouse JB6 and human HaCaT epidermal keratinocytes, we observed both protective and therapeutic effects of exogenous GSH (1 or 10 mM) in attenuating a CEES-caused decrease in cell viability and DNA synthesis, as well as S and G(2)M phase arrest in cell cycle progression. However, the protective effect of GSH was stronger than its ability to reverse CEES-induced cytotoxic effect. The observed effect of GSH could be associated with an increase in intracellular GSH levels after its treatment before or after CEES exposure, which strongly depleted cellular GSH levels. N-Acetyl cysteine, a GSH precursor, also showed both protective and therapeutic effects against CEES-caused cytotoxicity. Buthionine sulfoximine, which reduces cellular GSH levels, caused an increased CEES cytotoxicity in both JB6 and HaCaT cells. In further studies translating GSH effects in cell culture, pretreatment of mice with 300 mg/kg GSH via oral gavage 1 h before topical application of CEES resulted in significant protection against CEES-caused increase in skin bifold and epidermal thickness, apoptotic cell death, and myeloperoxidase activity, which could be associated with increased skin GSH levels. Together, these results highlight GSH efficacy in ameliorating CEES-caused skin injury and further support the need for effective antioxidant countermeasures against skin injury by HD exposure.

Physiological responses to temperature and haeme synthesis modifiers in earthworm Lumbricus terrestris (Annelida: Oligochaeta).

PubMed

Khan, M A Q; Khan, Munawwar Ali; Hurlock, Peter; Ahmed, S A

2012-01-01

Earthworms (Lumbricus terrestris) acclimated at 2° and 6°C above their average habitat temperature (10°C) had respectively 15 and 40% higher rate of respiration than those at habitat temperature. At 14°C, the rate of respiration and blood hemoglobin (Hb) concentration both increased by ∼60 and 50%, respectively, of the values at habitat temperature. At higher temperatures the rate of respiration and Hb synthesis started decreasing. At 20-23°C, the respiration and Hb concentration decreased respectively by about 85% and 35% of that at 14°C. Decrease in blood Hb concentration at higher temperatures appeared to be due to the lowering of the activity of blood enzyme δ-aminolaevulinic acid dehydratase (ALAD). Exposure of 20-23°C-acclimated pale worms to ALAD inhibitor (lead), lowered the already compromised rate of respiration and blood Hb concentration; while exposure to hexachlorobenzene (HCB, inducer of haeme synthesis) and ferric chloride (enhancer of haeme synthesis) did not overcome the inhibitory effect of high temperature on Hb synthesis. At 20-23°C the affinity of Hb for oxygen also decreased as indicated by the lowering of oxy-Hb (HbO) concentration in blood. The lowering of concentration of blood Hb and its affinity for oxygen may lower the amount of oxygen delivered to cells, which may limit the level of aerobic metabolism (glycolysis, oxidative phosphorylation), as indicated by an increase in blood glucose concentration and a decrease in in vitro activities of mitochondrial electron transport system components (ETS) namely NADH-cytochrome c reductase, succinate dehydrogenase, cytochrome c oxidase, and ATPases. Although the oxygen concentration in air, at sea level, does not decrease significantly from 6° to 20-23°C (lack of hypoxia), lowering of both Hb and HbO concentrations by high temperature may cause significant hypoxemia. The latter may lead to inhibition of the activity of muscle mitochondrial respiratory enzymes (ETS). The resulting inhibition of ATP synthesis and hydrolysis may cause deficit of energy needed for peristalsis/fictive locomotion of body and heart muscles (as indicated by a decrease in heart rate) to facilitate diffusion and transport of gases. The upper critical temperature (20-23°C) also slows down the heart rate and causes hyperosmotic stress (hypovolemia). Thus, a rise in soil temperature above 18°C, which inhibits Hb synthesis, Hb oxygenation, and mitochondrial ETS activity, and slows down the heart rate and causes hyperosmotic stress, can make this and higher temperatures lethal to populations of these earthworms, especially in the presence of metabolic inhibitors and respiratory poisons. Copyright © 2010 Wiley Periodicals, Inc.

Combined oral contraceptives and body weight: do oral contraceptives cause weight gain? A primate model.

PubMed

Edelman, A; Jensen, J T; Bulechowsky, M; Cameron, J

2011-02-01

The aim of this study was to determine if oral contraceptive (OC) use affects body weight, body composition and metabolism in primates. Reproductive-age female rhesus monkeys of normal and obese BMI were studied to document baseline weight stability, then treated continuously with an OC (dosed to achieve equivalent human serum levels for a 30 µg ethinyl estradiol/150 µg levonorgestrel preparation) for 237 days. Monkeys were monitored for changes in body weight, levels of physical activity (measured by a triaxial Actical accelerometer), food/caloric intake, percent body fat (dual energy X-ray absorptiometry, DEXA) and metabolism (24 h metabolic rate and serum metabolic substrate and hormone concentrations). All 10 monkeys completed the study protocol with no adverse events. While body weight (-0.73% change) and percent body fat (-1.78% change) of the normal BMI group did not significantly decrease from baseline, obese monkeys showed a significant decrease in body weight (-8.58% change, P < 0.01) and percent body fat (-12.13% change P = 0.02) with OC treatment. In both the obese (P = 0.03) and the normal BMI (P = 0.01) groups, there was a significant increase in basal metabolic rate with OC use. No changes were seen in food intake, activity level or % lean muscle mass with OC use for either BMI-based group. Overall, OC use appears to cause a slight increase in basal metabolic rate in female monkeys, leading to a decrease in body weight and percent body fat in obese individuals.

Protective effect of aged garlic extract (AGE) on the apoptosis of intestinal epithelial cells caused by methotrexate.

PubMed

Li, Tiesong; Ito, Kousei; Sumi, Shin-Ichiro; Fuwa, Toru; Horie, Toshiharu

2009-04-01

Methotrexate (MTX) causes intestinal damage, resulting in diarrhea. The side effects often disturb the cancer chemotherapy. We previously reported that AGE protected the small intestine of rats from the MTX-induced damage. In the present paper, the mechanism of the protection of AGE against the MTX-induced damage of small intestine was investigated, using IEC-6 cells originating from rat jejunum crypt. The viability and apoptosis of IEC-6 cells were examined in the presence of MTX and/or AGE. The viability of IEC-6 cells exposed to MTX was decreased by the increase of MTX concentration. The MTX-induced loss of viable IEC-6 cells was almost completely prevented by the presence of more than 0.1% AGE. In IEC-6 cells exposed to MTX, the cromatin condensation, DNA fragmentation, caspase-3 activation and cytochrome c release were observed. These were preserved to the control levels by the presence of AGE. MTX markedly decreased intracellular GSH in IEC-6 cells, but the presence of AGE in IEC-6 cells with MTX preserved intracellular GSH to the control level. IEC-6 cells in G2/M stage markedly decreased 72 h after the MTX treatment, which was preserved to the control level by the presence of AGE. These results indicated that AGE protected IEC-6 cells from the MTX-induced damage. The MTX-induced apoptosis of IEC-6 cells was shown to be depressed by AGE. AGE may be useful for the cancer chemotherapy with MTX, since AGE reduces the MTX-induced intestinal damage.

Lawsonia inermis - an alternative treatment for hyperthyroidism?

PubMed

Zumrutdal, E; Karateke, F; Daglioglu, K; Gulkaya, M; Colak, O; Koksal, F

2014-01-01

The goal of our study was to determine the effects of Lawsonia inermis (L. inermis) in mice, in which hyperthyroidism had been caused by thyroid stimulant hormone (TSH). The first phase of the study aimed to detect the effects of L. inermis on the amount of ionized hydrogen (pH) in cells. For this aim, the effect of L. inermis on pH levels in the liver tissues of mice, in whom Escherichia coli (E. coli) had caused peritonitis, was examined. In the second phase of the study, the effect of L. inermis on the serum T4 levels in the 24th and 48th hour in mice, whose thyroid cells showed an increased activity by TSH was measured. In the first phase, in mice, in whom E.coli had caused peritonitis, the pH in the liver tissue of the group that had been given L. inermis was found to be significantly alkaline (p<0.05). In the second phase, in mice, in whom TSH had caused hyperthyroidism, it was noted that serum total T4 levels were significantly lower than in the group that had been given L. inermis in the 48th hour (p<0.05). In our study, we detected that L. inermis significantly decreased serum total T4 levels in the 48th hour in mice in whom TSH had caused hyperthyroidism. These results suggest that L. inermis can be used as an alternative treatment for the Graves' disease (Tab. 2, Fig. 1, Ref. 34).

Placenta-derived hypo-serotonin situations in the developing forebrain cause autism.

PubMed

Sato, Kohji

2013-04-01

Autism is a pervasive developmental disorder that is characterized by the behavioral traits of impaired social cognition and communication, and repetitive and/or obsessive behavior and interests. Although there are many theories and speculations about the pathogenetic causes of autism, the disruption of the serotonergic system is one of the most consistent and well-replicated findings. Recently, it has been reported that placenta-derived serotonin is the main source in embryonic day (E) 10-15 mouse forebrain, after that period, the serotonergic fibers start to supply serotonin into the forebrain. E 10-15 is the very important developing period, when cortical neurogenesis, migration and initial axon targeting are processed. Since all these events have been considered to be involved in the pathogenesis of autism and they are highly controlled by serotonin signals, the paucity of placenta-derived serotonin should have potential importance when the pathogenesis of autism is considered. I, thus, postulate a hypothesis that placenta-derived hypo-serotonin situations in the developing forebrain cause autism. The hypothesis is as follows. Various factors, such as inflammation, dysfunction of the placenta, together with genetic predispositions cause a decrease of placenta-derived serotonin levels. The decrease of placenta-derived serotonin levels leads to hypo-serotonergic situations in the forebrain of the fetus. The paucity of serotonin in the forebrain leads to mis-wiring in important regions which are responsible for the theory of mind. The paucity of serotonin in the forebrain also causes over-growth of serotonergic fibers. These disturbances result in network deficiency and aberration of the serotonergic system, leading to the autistic phenotypes. Copyright © 2013 Elsevier Ltd. All rights reserved.

A Deafness- and Diabetes-associated tRNA Mutation Causes Deficient Pseudouridinylation at Position 55 in tRNAGlu and Mitochondrial Dysfunction*

PubMed Central

Wang, Meng; Liu, Hao; Zheng, Jing; Chen, Bobei; Zhou, Mi; Fan, Wenlu; Wang, Hen; Liang, Xiaoyang; Zhou, Xiaolong; Eriani, Gilbert; Jiang, Pingping; Guan, Min-Xin

2016-01-01

Several mitochondrial tRNA mutations have been associated with maternally inherited diabetes and deafness. However, the pathophysiology of these tRNA mutations remains poorly understood. In this report, we identified the novel homoplasmic 14692A→G mutation in the mitochondrial tRNAGlu gene among three Han Chinese families with maternally inherited diabetes and deafness. The m.14692A→G mutation affected a highly conserved uridine at position 55 of the TΨC loop of tRNAGlu. The uridine is modified to pseudouridine (Ψ55), which plays an important role in the structure and function of this tRNA. Using lymphoblastoid cell lines derived from a Chinese family, we demonstrated that the m.14692A→G mutation caused loss of Ψ55 modification and increased angiogenin-mediated endonucleolytic cleavage in mutant tRNAGlu. The destabilization of base-pairing (18A-Ψ55) caused by the m.14692A→G mutation perturbed the conformation and stability of tRNAGlu. An approximately 65% decrease in the steady-state level of tRNAGlu was observed in mutant cells compared with control cells. A failure in tRNAGlu metabolism impaired mitochondrial translation, especially for polypeptides with a high proportion of glutamic acid codons such as ND1, ND6, and CO2 in mutant cells. An impairment of mitochondrial translation caused defective respiratory capacity, especially reducing the activities of complexes I and IV. Furthermore, marked decreases in the levels of mitochondrial ATP and membrane potential were observed in mutant cells. These mitochondrial dysfunctions caused an increasing production of reactive oxygen species in the mutant cells. Our findings may provide new insights into the pathophysiology of maternally inherited diabetes and deafness, which is primarily manifested by the deficient nucleotide modification of mitochondrial tRNAGlu. PMID:27519417

Environmentally relevant levels of λ-cyhalothrin, fenvalerate, and permethrin cause developmental toxicity and disrupt endocrine system in zebrafish (Danio rerio) embryo.

PubMed

Zhang, Quan; Zhang, Yi; Du, Jie; Zhao, Meirong

2017-10-01

Synthetic pyrethroids (SPs) are one of the most widely used pesticides and frequently detected in the aquatic environment. Previous studies have shown that SPs posed high aquatic toxicity, but information on the developmental toxicity and endocrine disruption on zebrafish (Danio rerio) at environmentally relevant concentrations is limited. In this study, zebrafish embryos were employed to examine the adverse effects of λ-cyhalothrin (LCT), fenvalerate (FEN), and permethrin (PM) at 2.5, 10, 25, 125, 500 nM for 96 h. The results showed these 3 SPs caused dose-dependent mortality, malformation rate, and hatching rate. Thyroid hormone triiodothyronine (T 3 ) levels were significantly decreased after exposure to LCT and FEN. Quantitative real-time PCR analysis was then performed on a series of nuclear receptors (NRs) genes involved in the hypothalamic-pituitary-gonadal (HPG), hypothalamic-pituitary-thyroid (HPT), hypothalamic-pituitary-adrenocortical (HPA) axes, and oxidative-stress-related system. Our results showed that LCT, FEN, and PM downregulated AR expression while upregulated ER1 expression, and caused alteration to ER2a and ER2b expression. As for the expression of TRα and TRβ, they were both decreased following exposure to the 3 SPs. LCT and PM downregulated the MR expression and FEN induced MR expression. In addition, the expression of GR was increased after treating with LCT, while it was suppressed after exposure to FEN and PM. The 3 SPs also caused various alterations to the expression of genes including AhRs, PPARα, and PXR. These findings suggest that these 3 SPs may cause developmental toxicity to zebrafish larvae by disrupting endocrine signaling at environmentally relevant concentrations. Copyright © 2017. Published by Elsevier Ltd.

Grape seed polyphenolic extract specifically decreases aβ*56 in the brains of Tg2576 mice.

PubMed

Liu, Peng; Kemper, Lisa J; Wang, Jun; Zahs, Kathleen R; Ashe, Karen H; Pasinetti, Giulio M

2011-01-01

Amyloid-β (Aβ) oligomers, found in the brains of Alzheimer's disease (AD) patients and transgenic mouse models of AD, cause synaptotoxicity and memory impairment. Grape seed polyphenolic extract (GSPE) inhibits Aβ oligomerization in vitro and attenuates cognitive impairment and AD-related neuropathology in the brains of transgenic mice. In the current study, GSPE was administered to Tg2576 mice for a period of five months. Treatment significantly decreased brain levels of Aβ*56, a 56-kDa Aβ oligomer previously shown to induce memory dysfunction in rodents, without changing the levels of transgenic amyloid-β protein precursor, monomeric Aβ, or other Aβ oligomers. These results thus provide the first demonstration that a safe and affordable intervention can lower the levels of a memory-impairing Aβ oligomer in vivo and strongly suggest that GSPE should be further tested as a potential prevention and/or therapy for AD.

Food combination based on a pre-hispanic Mexican diet decreases metabolic and cognitive abnormalities and gut microbiota dysbiosis caused by a sucrose-enriched high-fat diet in rats.

PubMed

Avila-Nava, Azalia; Noriega, Lilia G; Tovar, Armando R; Granados, Omar; Perez-Cruz, Claudia; Pedraza-Chaverri, José; Torres, Nimbe

2017-01-01

There is few information about the possible health effects of a food combination based on a pre-hispanic Mexican diet (PMD). This diet rich in fiber, polyphenols, a healthy ratio of omega 6/omega 3 fatty acids, and vegetable protein could improve carbohydrate and lipid metabolism, gut microbiota and cognitive function. We examined the effect of a PMD in a sucrose enriched high-fat model. The PMD contains corn, beans, tomato, nopal, chia and pumpkin seeds in dehydrated form. Following induction of obesity, rats were fed PMD. PMD consumption decreased glucose intolerance, body weight gain, serum and liver triglycerides and leptin. In addition, PMD decreased the size of the adipocytes, and increased the protein abundance of UCP-1, PPAR-α, PGC1-α and Tbx-1 in white adipose tissue. Finally, the PMD significant decreased hepatic levels of ROS, oxidized proteins and GSSG/GSH ratio and an increase in the relative abundance of Bifidobacteria and the improvement of cognitive function. Consumption of a PMD decreased the glucose intolerance and the biochemical abnormalities caused by the obesity by increasing the abundance of proteins involved in fatty acid oxidation, decreasing the oxidative stress and modifying the gut microbiota. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Arabidopsis serotonin N-acetyltransferase knockout mutant plants exhibit decreased melatonin and salicylic acid levels resulting in susceptibility to an avirulent pathogen.

PubMed

Lee, Hyoung Yool; Byeon, Yeong; Tan, Dun-Xian; Reiter, Russel J; Back, Kyoungwhan

2015-04-01

Serotonin N-acetyltransferase (SNAT) is the penultimate enzyme in the melatonin biosynthesis pathway in plants. We examined the effects of SNAT gene inactivation in two Arabidopsis T-DNA insertion mutant lines. After inoculation with the avirulent pathogen Pseudomonas syringe pv. tomato DC3000 harboring the elicitor avrRpt2 (Pst-avrRpt2), melatonin levels in the snat knockout mutant lines were 50% less than in wild-type Arabidopsis Col-0 plants. The snat knockout mutant lines exhibited susceptibility to pathogen infection that coincided with decreased induction of defense genes including PR1, ICS1, and PDF1.2. Because melatonin acts upstream of salicylic acid (SA) synthesis, the reduced melatonin levels in the snat mutant lines led to decreased SA levels compared to wild-type, suggesting that the increased pathogen susceptibility of the snat mutant lines could be attributed to decreased SA levels and subsequent attenuation of defense gene induction. Exogenous melatonin treatment failed to induce defense gene expression in nahG Arabidopsis plants, but restored the induction of defense gene expression in the snat mutant lines. In addition, melatonin caused translocation of NPR1 (nonexpressor of PR1) protein from the cytoplasm into the nucleus indicating that melatonin-elicited pathogen resistance in response to avirulent pathogen attack is SA-dependent in Arabidopsis. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The changing nature of death on the trauma service.

PubMed

Kahl, Jessica E; Calvo, Richard Y; Sise, Michael J; Sise, C Beth; Thorndike, Jonathan F; Shackford, Steven R

2013-08-01

Recent innovations in care have improved survival following injury. Coincidentally, the population of elderly injured patients with preexisting comorbidities has increased. We hypothesized that this increase in elderly injured patients may have combined with recent care innovations to alter the causes of death after trauma. We reviewed demographics, injury characteristics, and cause of death of in-hospital deaths of patients admitted to our Level I trauma service from 2000 through 2011. Cause of death was classified as acute hemorrhagic shock; severe traumatic brain injury or high spinal cord injury; complications of preexisting medical condition only (PM); survivable trauma combined with complications of preexisting medical condition (TCoM); multiple-organ failure, sepsis, or adult respiratory distress syndrome (MOF/S/ARDS), or trauma not otherwise categorized (e.g., asphyxiation). Major trauma care advances implemented on our service during the period were identified, and trends in the causes of death were analyzed. Of the 27,276 admissions, 819 (3%) eligible nonsurvivors were identified for the cause-of-death analyses. Causes of death were severe traumatic brain injury or high spinal cord injury at 44%, acute hemorrhagic shock at 28%, PM at 11%, TCoM at 10%, MOF/S/ARDS at 2%, and trauma not otherwise categorized at 5%. Mean age at death increased across the study interval (range, 47-57 years), while mean Injury Severity Score (ISS) decreased (range, 28-35). There was a significant increase in deaths because of TCoM (3.3-20.9%) and PM (6.7-16.4%), while deaths caused by MOF/S/ARDS decreased from 5% to 0% by 2007. Compared with year 2000, the annual adjusted mortality rate decreased consistently starting in 2009, after the 2002 to 2007 adoption of four major trauma practice guidelines. Mortality caused by preexisting medical conditions has increased, while markedly fewer deaths resulted from the complications of injury. Future improvements in outcomes will require improvement in the management of elderly trauma patients with comorbid conditions.

Immunomodulatory and antioxidant protective effect of Sarcocornia perennis L. (swampfire) in lead intoxicated rat.

PubMed

Gargouri, Manel; Hamed, Houda; Akrouti, Amel; Christian, Magné; Ksouri, Riadh; El Feki, Abdelfattah

2017-11-01

Lead (Pb) is a very toxic metal present in the environment, causing disturbances of several functions. Preventive or curative effects of halophytic plants against these disorders may be a promising and safe therapeutic strategy. Thus, this study was designed to evaluate in vivo immunomodulatory and antioxidant effects of Sarcocornia perennis extract (Sp) against lead toxicity in rats. Groups of six animals each were treated with plant extract (via food), 6 g/L lead acetate (via drinking water) or a combination of both. At the end of the three-week period, rat exposure to lead caused reduction of liver weight but an increase of that of kidney. Moreover, lead intoxication-induced oxidative stress manifested by significant increases of inflammatory cytokines (except IL-10) and lipid peroxidation (TBARS), compared with the control group. Meanwhile, interleukin-10 (IL-10) and glutathione levels (GSH), as well as antioxidant activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), were decreased. Considering liver and renal markers, lead treatment induced a significant increase in the activities of aminotransferases (AST, ALT), and in the levels of urea, creatinine and phosphorous, whereas total plasma protein, albumin and calcium levels were significantly decreased. S. perennis extract alone did not induce any significant changes in hepatic or renal markers, whereas the antioxidant markers were significantly increased. S. perennis supplementation significantly reduced the lead-induced elevation of serum IL-1ß, IL-6, TNF-α, IFN-γ and TBARS but increased the IL-10 and antioxidant enzyme activities. Overall, plant components ameliorated hepatorenal damages caused by lead.

Gemfibrozil disrupts the metabolism of circulating lipids in bobwhite quails.

PubMed

Bussière-Côté, Sophie; Omlin, Teye; de Càssia Pinheiro, Eliana; Weber, Jean-Michel

2016-01-01

The circulating lipids of birds play essential roles for egg production and as an energy source for flight and thermogenesis. How lipid-lowering pharmaceuticals geared to prevent heart disease in humans and that are routinely released in the environment affect their metabolism is unknown. This study assesses the impact of the popular drug gemfibrozil (GEM) on the plasma phospholipids (PL), neutral lipids (NL), and nonesterified fatty acids (NEFA) of bobwhite quails (Colinus virginianus). Results show that bird lipoproteins are rapidly altered by GEM, even at environmentally-relevant doses. After 4 days of exposure, pharmacological amounts cause an 83% increase in circulating PL levels, a major decrease in average lipoprotein size measured as a 56% drop in the NL/PL ratio, and important changes in the fatty acid composition of PL and NEFA (increases in fatty acid unsaturation). The levels of PL carrying all individual fatty acids except arachidonate are strongly stimulated. The large decrease in bird lipoprotein size may reflect the effects seen in humans: lowering of LDL that can cause atherosclerosis and stimulation of HDL that promote cholesterol disposal. Lower (environmental) doses of GEM cause a reduction of %palmitate in all the plasma lipid fractions of quails, but particularly in the core triacylglycerol of lipoproteins (NL). No changes in mRNA levels of bird peroxisome proliferator-activated receptor (PPAR) could be demonstrated. The disrupting effects of GEM on circulating lipids reported here suggest that the pervasive presence of this drug in the environment could jeopardize reproduction and migratory behaviours in wild birds. Copyright © 2015 Elsevier Inc. All rights reserved.

Reconstructing satellite images to quantify spatially explicit land surface change caused by fires and succession: A demonstration in the Yukon River Basin of interior Alaska

USGS Publications Warehouse

Huang, Shengli; Jin, Suming; Dahal, Devendra; Chen, Xuexia; Young, Claudia; Liu, Heping; Liu, Shuguang

2013-01-01

Land surface change caused by fires and succession is confounded by many site-specific factors and requires further study. The objective of this study was to reveal the spatially explicit land surface change by minimizing the confounding factors of weather variability, seasonal offset, topography, land cover, and drainage. In a pilot study of the Yukon River Basin of interior Alaska, we retrieved Normalized Difference Vegetation Index (NDVI), albedo, and land surface temperature (LST) from a postfire Landsat image acquired on August 5th, 2004. With a Landsat reference image acquired on June 26th, 1986, we reconstructed NDVI, albedo, and LST of 1987–2004 fire scars for August 5th, 2004, assuming that these fires had not occurred. The difference between actual postfire and assuming-no-fire scenarios depicted the fires and succession impact. Our results demonstrated the following: (1) NDVI showed an immediate decrease after burning but gradually recovered to prefire levels in the following years, in which burn severity might play an important role during this process; (2) Albedo showed an immediate decrease after burning but then recovered and became higher than prefire levels; and (3) Most fires caused surface warming, but cooler surfaces did exist; time-since-fire affected the prefire and postfire LST difference but no absolute trend could be found. Our approach provided spatially explicit land surface change rather than average condition, enabling a better understanding of fires and succession impact on ecological consequences at the pixel level.

Effect of saffron (Crocus sativus L.) on sodium valporate induced cytogenetic and testicular alterations in albino rats.

PubMed

Sakr, Saber A; Zowail, Mohamed E; Marzouk, Amera M

2014-09-01

The present study investigated the cytogenetic and testicular damage induced by the antiepileptic drug, sodium valporate (SVP) in albino rats and the effect of saffron aqueous extracts. Treating rats with SVP caused a significant increase in the chromosomal aberrations either structural or numerical and decreased the mitotic index. Besides, animals administered SVP showed DNA damage appeared in the single strand breaks (comet assay). Testis of SVP-treated rats showed many histopathological changes. A significant decrease in seminiferous tubules and their epithelial heights diameters and inhibition of spermatogenesis was recorded. In addition, the number of sperm head abnormalities was increased. Biochemical results revealed an increase in malondialdhyde (MDA) which is lipid peroxidation marker and a significant decrease in the level of serum antioxidant enzyme, catalase (CAT) and reducing antioxidant power (RAP). Animals given SVP and saffron showed an improvement in chromosomal aberrations, mitotic index, DNA damage and testicular alterations caused by SVP. Moreover, MDA decreased and CAT and RAP increased. It is concluded from the present results that the ameliorative effects of saffron extract against SVP-induced cytogenetic and testicular damage in albino rats may be due to the presence of one or more antioxidant components of saffron.

Red light-regulated growth. I. Changes in the abundance of indoleacetic acid and a 22-kilodalton auxin-binding protein in the maize mesocotyl

NASA Technical Reports Server (NTRS)

Jones, A. M.; Cochran, D. S.; Lamerson, P. M.; Evans, M. L.; Cohen, J. D.

1991-01-01

We examined the changes in the levels of indoleacetic acid (IAA), IAA esters, and a 22-kilodalton subunit auxin-binding protein (ABP1) in apical mesocotyl tissue of maize (Zea mays L.) during continuous red light (R) irradiation. These changes were compared with the kinetics of R-induced growth inhibition in the same tissue. Upon the onset of continuous irradiation, growth decreased in a continuous manner following a brief lag period. The decrease in growth continued for 5 hours, then remained constant at 25% of the dark rate. The abundance of ABP1 and the level of free IAA both decreased in the mesocotyl. Only the kinetics of the decrease in IAA within the apical mesocotyl correlated with the initial change in growth, although growth continued to decrease even after IAA content reached its final level, 50% of the dark control. This decrease in IAA within the mesocotyl probably occurs primarily by a change in its transport within the shoot since auxin applied as a pulse move basipetally in R-irradiated tissue at the same rate but with half the area as dark control tissue. In situ localization of auxin in etiolated maize shoots revealed that R-irradiated shoots contained less auxin in the epidermis than the dark controls. Irradiated mesocotyl grew 50% less than the dark controls even when incubated in an optimal level of auxin. However, irradiated and dark tissue contained essentially the same amount of radioactivity after incubation in [14C]IAA indicating that the light treatment does not affect the uptake into the tissue through the cut end, although it is possible that a small subset of cells within the mesocotyl is affected. These observations support the hypothesis that R causes a decrease in the level of auxin in epidermal cells of the mesocotyl, consequently constraining the growth of the entire mesocotyl.

Artificially decreased vapour pressure deficit in field conditions modifies foliar metabolite profiles in birch and aspen

PubMed Central

Lihavainen, Jenna; Keinänen, Markku; Keski-Saari, Sarita; Kontunen-Soppela, Sari; Sõber, Anu; Oksanen, Elina

2016-01-01

Relative air humidity (RH) is expected to increase in northern Europe due to climate change. Increasing RH reduces the difference of water vapour pressure deficit (VPD) between the leaf and the atmosphere, and affects the gas exchange of plants. Little is known about the effects of decreased VPD on plant metabolism, especially under field conditions. This study was conducted to determine the effects of artificially decreased VPD on silver birch (Betula pendula Roth.) and hybrid aspen (Populus tremula L.×P. tremuloides Michx.) foliar metabolite and nutrient profiles in a unique free air humidity manipulation (FAHM) field experiment during the fourth season of humidity manipulation, in 2011. Long-term exposure to decreased VPD modified nutrient homeostasis in tree leaves, as demonstrated by a lower N concentration and N:P ratio in aspen leaves, and higher Na concentration and lower K:Na ratio in the leaves of both species in decreased VPD than in ambient VPD. Decreased VPD caused a shift in foliar metabolite profiles of both species, affecting primary and secondary metabolites. Metabolic adjustment to decreased VPD included elevated levels of starch and heptulose sugars, sorbitol, hemiterpenoid and phenolic glycosides, and α-tocopherol. High levels of carbon reserves, phenolic compounds, and antioxidants under decreased VPD may modify plant resistance to environmental stresses emerging under changing climate. PMID:27255929

Effects of A NBC (Nuclear, Biological, and Chemical) Nutrient Solution on Physiological and Psychological Status during Sustained Activity in the Heat

DTIC Science & Technology

1987-07-17

of sugar (3). Kety (14) reported that a significant decrease in the blood glucose level is consistently associated with manifestations of impaired...Brozek J, Keys A. Relationship of speed of motor reaction to blood sugar level during acute starvation in man, abstracted. Fed Proc 1945;4:28. 9. Blom...profound low blood sugar can cause irreversible brain damage (21,30). Since hypoglycemia did not develop, it was not possible to assess the effects of

An RNA-Seq study reveals genetic responses of diverse wild soybean accessions to increased ozone levels

USDA-ARS?s Scientific Manuscript database

Ozone is a pollutant widely known to cause decrease in productivity in many plant species, including soybean. While cultivated soybean response to ozone has been studied, less work has been done to identify sources of resistance from wild relatives. This study presents a putative SNP marker on Chrom...

Lung Function and Inflammatory responses in healthy young adults exposed to 0.06 ppm Ozone for 6.6 hours

EPA Science Inventory

Rationale: Exposure to ozone causes a decrease in spirometric lung function and an increase in airway inflammation in healthy young adults at concentrations as low as 0.08 ppm close to the the National Ambient Air Quality Standard for ground level ozone. Objectives: To test wheth...

Organophosphate pesticides-induced changes in the redox status of rat tissues and protective effects of antioxidant vitamins.

PubMed

Mishra, Vibhuti; Srivastava, Nalini

2015-04-01

Organophosphates (OPs) pesticides are among the most toxic synthetic chemicals purposefully added in the environment. The common use of OP insecticides in public health and agriculture results in an environmental pollution and a number of acute and chronic poisoning events. Present study was aimed to evaluate the potential of monocrotophos and quinalphos to effect the redox status and glutathione (GSH) homeostasis in rat tissues and find out whether antioxidant vitamins have some protection on the pesticide-induced alterations. The results showed that these pesticides alone or in combination, caused decrease in the levels of GSH and the corresponding increase in the levels of GSSG, decreasing the GSH/GSSG ratio. The results also showed that NADPH/NADP(+) and NADH/NAD(+) ratios were decreased in the liver and brain of rats on exposure with mococrotophos, quinalphos, and their mixture. These pesticides, alone or in combination, caused alterations in the activities of GSH reductase and glucose-6-phosphate dehydrogenase in the rat tissues. However, the expression of the GSH recycling enzymes did not show significant alterations as compared to control. From the results, it can be concluded that these pesticides generate oxidative stress but their effects were not synergistic when given together and prior feeding of antioxidant vitamins tend to reduce the toxicities of these pesticides. Copyright © 2013 Wiley Periodicals, Inc.

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

Rawal, Nina; Corti, Olga; CNRS, UMR 7225, Paris

Parkinson's disease (PD) is caused by degeneration of the dopaminergic (DA) neurons of the substantia nigra but the molecular mechanisms underlying the degenerative process remain elusive. Several reports suggest that cell cycle deregulation in post-mitotic neurons could lead to neuronal cell death. We now show that Parkin, an E3 ubiquitin ligase linked to familial PD, regulates {beta}-catenin protein levels in vivo. Stabilization of {beta}-catenin in differentiated primary ventral midbrain neurons results in increased levels of cyclin E and proliferation, followed by increased levels of cleaved PARP and loss of DA neurons. Wnt3a signaling also causes death of post-mitotic DA neuronsmore » in parkin null animals, suggesting that both increased stabilization and decreased degradation of {beta}-catenin results in DA cell death. These findings demonstrate a novel regulation of Wnt signaling by Parkin and suggest that Parkin protects DA neurons against excessive Wnt signaling and {beta}-catenin-induced cell death.« less

Study of space charge layer in silver bromide microcrystals by means of ultraviolet photoelectron spectroscopy

NASA Astrophysics Data System (ADS)

Tani, Tadaaki; Inami, Yoshiyasu

2000-09-01

Ultraviolet photoelectron spectroscopy has been successfully used to measure the heights of the tops of the valence bands of the surfaces of AgBr layers on Ag substrates for the verification of the space charge layer model. According to this model, the positive space charge layer (composed of negative charges with excess negative kink sites on the surface and corresponding positive charges with interstitial silver ions in the interior) is formed in silver halides, causing the difference in the electronic energy levels between their surface and interior. The depression of the positive space charge layer of AgBr caused by such adsorbates as photographic stabilizers and antifoggants was estimated from the decrease in the ionic conductivity of cubic AgBr microcrystals by the adsorbates. It was confirmed by the decrease in the heights of the tops of the valence bands of the surfaces of AgBr layers caused by the adsorbates in the presence of thin gelatin membranes on their surfaces. This result provided the explanation for the fact that the adsorbates increased the number of the microcrystals which formed latent image centers on the surface and decreased the number of the microcrystals, which formed latent image centers in the interior.

Impact of potassium bromate and potassium iodate in a pound cake system.

PubMed

Wilderjans, Edith; Lagrain, Bert; Brijs, Kristof; Delcour, Jan A

2010-05-26

This study investigates the impact of the oxidants potassium bromate and potassium iodate (8, 16, 32, 64, and 128 micromol/g dry matter of egg white protein) on pound cake making. The impact of the oxidants on egg white characteristics was studied in a model system. Differential scanning calorimetry showed that the oxidants caused egg white to denature later. During heating in a rapid visco analyzer, the oxidants caused the free sulfhydryl (SH) group levels to decrease more intensively and over a smaller temperature range. The oxidants made the proteins more resistant to decreases in protein extractability in sodium dodecyl sulfate containing buffer during cake recipe mixing and less resistant to such decreases during cake baking. We assume that, during baking, the degree to which SH/disulfide exchange and SH oxidation can occur depends on the properties of the protein at the onset of the process. In our view, the prevention of extractability loss during mixing increased the availability of SH groups and caused more such loss during baking. During cooling, all cakes baked with added oxidants showed less collapse. On the basis of the presented data, we put forward that only those protein reactions that occur during baking contribute to the formation of a network that supports final cake structure and prevents collapse.

Increasing expression and decreasing degradation of SMN ameliorate the spinal muscular atrophy phenotype in mice

PubMed Central

Kwon, Deborah Y.; Motley, William W.; Fischbeck, Kenneth H.; Burnett, Barrington G.

2011-01-01

Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by reduced levels of the survival motor neuron (SMN) protein. Here we show that the proteasome inhibitor, bortezomib, increases SMN in cultured cells and in peripheral tissues of SMA model mice. Bortezomib-treated animals had improved motor function, which was associated with reduced spinal cord and muscle pathology and improved neuromuscular junction size, but no change in survival. Combining bortezomib with the histone deacetylase inhibitor trichostatin A (TSA) resulted in a synergistic increase in SMN protein levels in mouse tissue and extended survival of SMA mice more than TSA alone. Our results demonstrate that a combined regimen of drugs that decrease SMN protein degradation and increase SMN gene transcription synergistically increases SMN levels and improves the lifespan of SMA model mice. Moreover, this study indicates that while increasing SMN levels in the central nervous system may help extend survival, peripheral tissues can also be targeted to improve the SMA disease phenotype. PMID:21693563

T-lymphoid, megakaryocyte, and granulocyte development are sensitive to decreases in CBFβ dosage.

PubMed Central

Talebian, Laleh; Li, Zhe; Guo, Yalin; Gaudet, Justin; Speck, Maren E.; Sugiyama, Daisuke; Kaur, Prabhjot; Pear, Warren S.; Maillard, Ivan; Speck, Nancy A.

2007-01-01

The family of core-binding factors includes the DNA-binding subunits Runx1-3 and their common non–DNA-binding partner CBFβ. We examined the collective role of core-binding factors in hematopoiesis with a hypomorphic Cbfb allelic series. Reducing CBFβ levels by 3- or 6-fold caused abnormalities in bone development, megakaryocytes, granulocytes, and T cells. T-cell development was very sensitive to an incremental reduction of CBFβ levels: mature thymocytes were decreased in number upon a 3-fold reduction in CBFβ levels, and were virtually absent when CBFβ levels were 6-fold lower. Partially penetrant consecutive differentiation blocks were found among early T-lineage progenitors within the CD4−CD8− double-negative 1 and downstream double-negative 2 thymocyte subsets. Our data define a critical CBFβ threshold for normal T-cell development, and situate an essential role for core-binding factors during the earliest stages of T-cell development. PMID:16940420

System for verifiable CT radiation dose optimization based on image quality. part II. process control system.

PubMed

Larson, David B; Malarik, Remo J; Hall, Seth M; Podberesky, Daniel J

2013-10-01

To evaluate the effect of an automated computed tomography (CT) radiation dose optimization and process control system on the consistency of estimated image noise and size-specific dose estimates (SSDEs) of radiation in CT examinations of the chest, abdomen, and pelvis. This quality improvement project was determined not to constitute human subject research. An automated system was developed to analyze each examination immediately after completion, and to report individual axial-image-level and study-level summary data for patient size, image noise, and SSDE. The system acquired data for 4 months beginning October 1, 2011. Protocol changes were made by using parameters recommended by the prediction application, and 3 months of additional data were acquired. Preimplementation and postimplementation mean image noise and SSDE were compared by using unpaired t tests and F tests. Common-cause variation was differentiated from special-cause variation by using a statistical process control individual chart. A total of 817 CT examinations, 490 acquired before and 327 acquired after the initial protocol changes, were included in the study. Mean patient age and water-equivalent diameter were 12.0 years and 23.0 cm, respectively. The difference between actual and target noise increased from -1.4 to 0.3 HU (P < .01) and the standard deviation decreased from 3.9 to 1.6 HU (P < .01). Mean SSDE decreased from 11.9 to 7.5 mGy, a 37% reduction (P < .01). The process control chart identified several special causes of variation. Implementation of an automated CT radiation dose optimization system led to verifiable simultaneous decrease in image noise variation and SSDE. The automated nature of the system provides the opportunity for consistent CT radiation dose optimization on a broad scale. © RSNA, 2013.

Vital Signs: Disparities in Tobacco-Related Cancer Incidence and Mortality - United States, 2004-2013.

PubMed

Henley, S Jane; Thomas, Cheryll C; Sharapova, Saida R; Momin, Behnoosh; Massetti, Greta M; Winn, Deborah M; Armour, Brian S; Richardson, Lisa C

2016-11-11

Tobacco use causes at least 12 types of cancer and is the leading preventable cause of cancer. Data from the United States Cancer Statistics dataset for 2004-2013 were used to assess incidence and death rates and trends for cancers that can be caused by tobacco use (tobacco-related cancers: oral cavity and pharynx; esophagus; stomach; colon and rectum; liver; pancreas; larynx; lung, bronchus, and trachea; kidney and renal pelvis; urinary bladder; cervix; and acute myeloid leukemia) by sex, age, race, ethnicity, state, county-level poverty and educational attainment, and cancer site. Each year during 2009-2013, on average, 660,000 persons in the United States received a diagnosis of a tobacco-related cancer, and 343,000 persons died from these cancers. Tobacco-related cancer incidence and death rates were higher among men than women; highest among black men and women; higher in counties with low proportion of college graduates or high level of poverty; lowest in the West; and differed two-fold among states. During 2004-2013, incidence of tobacco-related cancer decreased 1.3% per year and mortality decreased 1.6% per year, with decreases observed across most groups, but not at the same rate. Tobacco-related cancer declined during 2004-2013. However, the burden remains high, and disparities persist among certain groups with higher rates or slower declines in rates. The burden of tobacco-related cancers can be reduced through efforts to prevent and control tobacco use and other comprehensive cancer control efforts focused on reducing cancer risk, detecting cancer early, improving cancer treatments, helping more persons survive cancer, improving cancer survivors' quality of life, and better assisting communities disproportionately impacted by cancer.

Differential regulation of preprotachykinin-A mRNA expression in striatum by excitation of hippocampal neurons.

PubMed

Brené, S; Lindefors, N; Herrera-Marschitz, M; Persson, H

1993-07-01

In this report we have studied the influence of hippocampal neurons on neuropeptide mRNA expression in both dorsal and ventral striatum in the rat. Intrahippocampal unilateral kainic acid injections were performed in control animals and in animals with a unilateral 6-hydroxydopamine-induced dopamine deafferentation of the striatum. In situ hybridization combined with quantitative image analysis was used to study the expression of preprotachykinin A mRNA encoding the neuropeptides substance P and neurokinin A. The 6-hydroxydopamine-induced lesion caused a decrease of preprotachykinin A mRNA levels in the ipsilateral dorsal striatum and in both sides of the ventral striatum. In normal rats, the intrahippocampal kainic acid injection caused a twofold increase in preprotachykinin A mRNA in the limbic parts of the striatum, which are innervated by the hippocampus. No effect of the kainic acid injection was seen in the lateral parts of the dorsal striatum, a region which does not appear to be innervated by the hippocampus. Animals with a 6-hydroxydopamine lesion showed a similar kainic acid-mediated increase in preprotachykinin A mRNA in parts of the ventral striatum. In the dopamine-lesioned dorsal striatum and ventral striatum the decreased preprotachykinin A mRNA levels were normalized by the intrahippocampal kainic acid injection. These results show that kainic acid-mediated excitation of hippocampal neurons causes a dopamine-independent induction of preprotachykinin A mRNA expression in parts of the ventral striatum, and reverses the dopamine deafferentation-induced decrease of preprotachykinin A mRNA in both dorsal and ventral striatum. Combined, our results suggest that hippocampal neurons can regulate preprotachykinin A mRNA expression in both the ventral and the dorsal striatum.

Antioxidant responses to azinphos methyl and carbaryl during the embryonic development of the toad Rhinella (Bufo) arenarum Hensel.

PubMed

Ferrari, Ana; Lascano, Cecilia I; Anguiano, Olga L; D'Angelo, Ana M Pechen de; Venturino, Andrés

2009-06-04

Amphibian embryos are naturally exposed to prooxidant conditions throughout their development. Environmental exposure to contaminants may affect their capacity to respond to challenging conditions, to progress in a normal ontogenesis, and finally to survive and succeed in completing metamorphosis. We studied the effects of the exposure to two anticholinesterase agents, the carbamate carbaryl and the organophosphate azinphos methyl, on the antioxidant defenses of developing embryos of the toad Rhinella (Bufo) arenarum. Reduced glutathione (GSH) levels were increased early by carbaryl, but were decreased by both pesticides at the end of embryonic development. The GSH-dependent enzymes glutathione reductase and glutathione peroxidases showed oscillating activity patterns that could be attributed to an induction of activity in response to oxidative stress and inactivation by excess of reactive oxygen species. Glutathione-S-transferases, which may participate in the conjugation of lipid peroxide products in addition to pesticide detoxification, showed an increase of activity at the beginning and at the end of development. Catalase also showed variations in the activity suggesting, successively, induction and inactivation in response to pesticide exposure-induced oxidative stress. Superoxide dismutase activity was increased by carbaryl and transiently decreased by azinphos methyl exposure. Judging from the depletion in GSH levels and glutathione reductase inhibition at the end of embryonic development, the oxidative stress caused by azinphos methyl seemed to be greater than that caused by carbaryl, which might be in turn related with a higher number of developmental alterations caused by the organophosphate. GSH content is a good biomarker of oxidative stress in the developing embryos exposed to pesticides. The antioxidant enzymes are in turn revealing the balance between their protective capacity and the oxidative damage to the enzyme molecules, decreasing their activity.

Multi-Model Assessment of the Factors Driving Stratospheric Ozone Evolution Over the 21st Century

NASA Technical Reports Server (NTRS)

Oman, L. D.; Plummer, D. A.; Waugh, D. W.; Austin, J.; Scinocca, J.; Douglass, A. R.; Salawitch, R. J.; Canty, T.; Akiyoshi, H.; Bekki, S.;

Decreased H3K9ac level of StAR mediated testicular dysplasia induced by prenatal dexamethasone exposure in male offspring rats.

PubMed

Liu, Min; Chen, Biao; Pei, Linguo; Zhang, Qi; Zou, Yunfei; Xiao, Hao; Zhou, Jin; Chen, Liaobin; Wang, Hui

2018-06-11

Prenatal dexamethasone exposure (PDE) could induce testicular developmental toxicity in adults. The present study aims to confirm its intrauterine origination, and to explore its potential intrauterine programming mechanism. The pregnant rats were respectively injected subcutaneously with 0.2 and 0.8 mg/kg⋅d dexamethasone during gestational days (GD) 9 to 20. The testes and serum of offspring rats were collected on GD20 and postnatal week (PW) 12. In vivo, PDE significantly induced the abnormal testicular morphology in offspring from GD20 to PW12. Moreover, the serum and intratesticular testosterone levels and the expression of testicular steroidogenic acute regulatory protein (StAR) were reduced by PDE. The expression levels of glucocorticoid receptor (GR) and histone deacetylase 7 (HDAC7) were increased in fetal testes. Furthermore, the histone 3 lysine 9 acetylation (H3K9ac) level in the StAR promoter was decreased by PDE from GD20 to PW12. In vitro, mouse Leydig tumour cell line (MLTC-1) cells were treated with dexamethasone (20, 100 and 500 nM), and the testosterone production and StAR expression were reduced. Moreover, dexamethasone increased the expression of HDAC7 by activating GR, which decreased the H3K9ac level in the StAR promoter. Taken together, PDE caused testicular dysplasia before and after birth in male offspring rats, and its mechanism was related to the low-expressional programming of StAR mediated by decreasing H3K9ac level. Copyright © 2018. Published by Elsevier B.V.

Regulation of gene expression and biochemical changes in small intestine of newborn diabetic rats by exogenous ghrelin.

PubMed

Karatug, Ayse; Sacan, Ozlem; Coskun, Zeynep Mine; Bolkent, Sehnaz; Yanardag, Refiye; Turk, Neslihan; Bolkent, Sema

2012-01-01

The aim of this study was to investigate (i) the cholecystokinin, somatostatin and apelin mRNA levels, (ii) the changes in levels and localization of these peptides, (iii) relation between these peptides, (iv) antiapoptotic effects and (v) antioxidant effects of ghrelin. The rats were divided into four groups second day after birth. These groups were respectively treated with physiological saline, ghrelin (100μg/kg/day), streptozotocin (100mg/kg), ghrelin and streptozotocin. After four weeks, small intestine and blood samples were taken from rats. Cholecystokinin mRNA and peptide, somatostatin mRNA, release to duodenal lumen of apelin peptide and apelin mRNA signals decreased in ghrelin-treated diabetic rats compared to the diabetic group. There was no statistically significant difference among the four groups for somatostatin and apelin peptides. Caspase-3 signals were not observed only in diabetic group treated with ghrelin. Caspase-8 signals were increased while PCNA signals were decreased in diabetic group given ghrelin compared to diabetic group. Small intestine CAT, SOD, GP(x) and GST activities and GSH levels were decreased and LPO, PC levels were increased in diabetic rats. Administration of ghrelin to diabetic rats caused an increase in intestinal CAT, SOD, GP(x) and GST activities and GSH levels, while PC levels decreased. As a result, we observed positive changes in diabetic rats treated with ghrelin in both microscopic and biochemical studies. We can suggest that ghrelin may be an important hormone for the treatment of diabetes. Copyright © 2011 Elsevier Inc. All rights reserved.

Dietary Manganese Modulates PCB126 Toxicity, Metal Status, and MnSOD in the Rat

PubMed Central

Wang, Bingxuan; Klaren, William D.; Wels, Brian R.; Simmons, Donald L.; Olivier, Alicia K.; Wang, Kai; Robertson, Larry W.; Ludewig, Gabriele

2016-01-01

PCB126 (3,3′,4,4′,5-pentachlorobiphenyl) is a potent aryl hydrocarbon receptor agonist and induces oxidative stress. Because liver manganese (Mn) levels decrease in response to PCB126, a Mn dietary study was designed to investigate the role of Mn in PCB126 toxicity. Male Sprague Dawley rats received diets containing 0, 10, or 150 ppm added Mn for 3 weeks, followed by a single ip injection of corn oil or PCB126 (5 µmol/kg body weight). After 2 weeks, Mn, Cu, Zn, and Fe levels in the heart, liver, and liver mitochondria, and Mn-containing superoxide dismutase (MnSOD) and metallothionein mRNA, MnSOD protein, and MnSOD activity were determined. Mn levels in liver, heart, and liver mitochondria were strongly decreased by the Mn-deficient diet. Small effects on Fe levels and a stepwise increase in MnSOD activity with dietary Mn were also visible. PCB126 caused profound changes in Cu (up), Zn, Fe, and Mn (down) in liver, but not in heart, and differing effects (Cu, Zn, and Fe up, Mn down) in liver mitochondria. Liver MnSOD and metallothionein mRNA levels and MnSOD protein were increased but MnSOD activity was decreased by PCB126. PCB126-induced liver enlargement was dose-dependently reduced with increasing dietary Mn. These changes in metals homeostasis and MnSOD activity in liver but not heart may be a/the mechanism of PCB126 liver-specific toxicity. Specifically, transport of Fenton metals (Cu, Fe) into and Mn out of the mitochondria, a probable mechanism for lower MnSOD activity, may be a/the cause of PCB126-induced oxidative stress. The role of metallothioneins needs further evaluation. Dietary Mn slightly alleviated PCB126-induced toxicities. PMID:26660635

Behavioral and Electrophysiological Characterization of Dyt1 Heterozygous Knockout Mice

PubMed Central

Yokoi, Fumiaki; Chen, Huan-Xin; Dang, Mai Tu; Cheetham, Chad C.; Campbell, Susan L.; Roper, Steven N.; Sweatt, J. David; Li, Yuqing

2015-01-01

DYT1 dystonia is an inherited movement disorder caused by mutations in DYT1 (TOR1A), which codes for torsinA. Most of the patients have a trinucleotide deletion (ΔGAG) corresponding to a glutamic acid in the C-terminal region (torsinAΔE). Dyt1 ΔGAG heterozygous knock-in (KI) mice, which mimic ΔGAG mutation in the endogenous gene, exhibit motor deficits and deceased frequency of spontaneous excitatory post-synaptic currents (sEPSCs) and normal theta-burst-induced long-term potentiation (LTP) in the hippocampal CA1 region. Although Dyt1 KI mice show decreased hippocampal torsinA levels, it is not clear whether the decreased torsinA level itself affects the synaptic plasticity or torsinAΔE does it. To analyze the effect of partial torsinA loss on motor behaviors and synaptic transmission, Dyt1 heterozygous knock-out (KO) mice were examined as a model of a frame-shift DYT1 mutation in patients. Consistent with Dyt1 KI mice, Dyt1 heterozygous KO mice showed motor deficits in the beam-walking test. Dyt1 heterozygous KO mice showed decreased hippocampal torsinA levels lower than those in Dyt1 KI mice. Reduced sEPSCs and normal miniature excitatory post-synaptic currents (mEPSCs) were also observed in the acute hippocampal brain slices from Dyt1 heterozygous KO mice, suggesting that the partial loss of torsinA function in Dyt1 KI mice causes action potential-dependent neurotransmitter release deficits. On the other hand, Dyt1 heterozygous KO mice showed enhanced hippocampal LTP, normal input-output relations and paired pulse ratios in the extracellular field recordings. The results suggest that maintaining an appropriate torsinA level is important to sustain normal motor performance, synaptic transmission and plasticity. Developing therapeutics to restore a normal torsinA level may help to prevent and treat the symptoms in DYT1 dystonia. PMID:25799505

Behavioral and electrophysiological characterization of Dyt1 heterozygous knockout mice.

PubMed

Yokoi, Fumiaki; Chen, Huan-Xin; Dang, Mai Tu; Cheetham, Chad C; Campbell, Susan L; Roper, Steven N; Sweatt, J David; Li, Yuqing

2015-01-01

DYT1 dystonia is an inherited movement disorder caused by mutations in DYT1 (TOR1A), which codes for torsinA. Most of the patients have a trinucleotide deletion (ΔGAG) corresponding to a glutamic acid in the C-terminal region (torsinA(ΔE)). Dyt1 ΔGAG heterozygous knock-in (KI) mice, which mimic ΔGAG mutation in the endogenous gene, exhibit motor deficits and deceased frequency of spontaneous excitatory post-synaptic currents (sEPSCs) and normal theta-burst-induced long-term potentiation (LTP) in the hippocampal CA1 region. Although Dyt1 KI mice show decreased hippocampal torsinA levels, it is not clear whether the decreased torsinA level itself affects the synaptic plasticity or torsinA(ΔE) does it. To analyze the effect of partial torsinA loss on motor behaviors and synaptic transmission, Dyt1 heterozygous knock-out (KO) mice were examined as a model of a frame-shift DYT1 mutation in patients. Consistent with Dyt1 KI mice, Dyt1 heterozygous KO mice showed motor deficits in the beam-walking test. Dyt1 heterozygous KO mice showed decreased hippocampal torsinA levels lower than those in Dyt1 KI mice. Reduced sEPSCs and normal miniature excitatory post-synaptic currents (mEPSCs) were also observed in the acute hippocampal brain slices from Dyt1 heterozygous KO mice, suggesting that the partial loss of torsinA function in Dyt1 KI mice causes action potential-dependent neurotransmitter release deficits. On the other hand, Dyt1 heterozygous KO mice showed enhanced hippocampal LTP, normal input-output relations and paired pulse ratios in the extracellular field recordings. The results suggest that maintaining an appropriate torsinA level is important to sustain normal motor performance, synaptic transmission and plasticity. Developing therapeutics to restore a normal torsinA level may help to prevent and treat the symptoms in DYT1 dystonia.

Cyfip1 Regulates Presynaptic Activity during Development.

PubMed

Hsiao, Kuangfu; Harony-Nicolas, Hala; Buxbaum, Joseph D; Bozdagi-Gunal, Ozlem; Benson, Deanna L

2016-02-03

Copy number variations encompassing the gene encoding Cyfip1 have been associated with a variety of human diseases, including autism and schizophrenia. Here we show that juvenile mice hemizygous for Cyfip1 have altered presynaptic function, enhanced protein translation, and increased levels of F-actin. In developing hippocampus, reduced Cyfip1 levels serve to decrease paired pulse facilitation and increase miniature EPSC frequency without a change in amplitude. Higher-resolution examination shows these changes to be caused primarily by an increase in presynaptic terminal size and enhanced vesicle release probability. Short hairpin-mediated knockdown of Cyfip1 coupled with expression of mutant Cyfip1 proteins indicates that the presynaptic alterations are caused by dysregulation of the WAVE regulatory complex. Such dysregulation occurs downstream of Rac1 as acute exposure to Rac1 inhibitors rescues presynaptic responses in culture and in hippocampal slices. The data serve to highlight an early and essential role for Cyfip1 in the generation of normally functioning synapses and suggest a means by which changes in Cyfip1 levels could impact the generation of neural networks and contribute to abnormal and maladaptive behaviors. Several developmental brain disorders have been associated with gene duplications and deletions that serve to increase or decrease levels of encoded proteins. Cyfip1 is one such protein, but the role it plays in brain development is poorly understood. We asked whether decreased Cyfip1 levels altered the function of developing synapses. The data show that synapses with reduced Cyfip1 are larger and release neurotransmitter more rapidly. These effects are due to Cyfip1's role in actin polymerization and are reversed by expression of a Cyfip1 mutant protein retaining actin regulatory function or by inhibiting Rac1. Thus, Cyfip1 has a more prominent early role regulating presynaptic activity during a stage of development when activity helps to define neural pathways. Copyright © 2016 the authors 0270-6474/16/361564-13$15.00/0.

Uncoupling of intestinal mitochondrial oxidative phosphorylation and inhibition of cyclooxygenase are required for the development of NSAID-enteropathy in the rat.

PubMed

Somasundaram, S; Sigthorsson, G; Simpson, R J; Watts, J; Jacob, M; Tavares, I A; Rafi, S; Roseth, A; Foster, R; Price, A B; Wrigglesworth, J M; Bjarnason, I

2000-05-01

The pathogenesis of NSAID-induced gastrointestinal damage is believed to involve a nonprostaglandin dependent effect as well as prostaglandin dependent effects. One suggestion is that the nonprostaglandin mechanism involves uncoupling of mitochondrial oxidative phosphorylation. To assess the role of uncoupling of mitochondrial oxidative phosphorylation in the pathogenesis of small intestinal damage in the rat. We compared key pathophysiologic events in the small bowel following (i) dinitrophenol, an uncoupling agent (ii) parenteral aspirin, to inhibit cyclooxygenase without causing a 'topical' effect and (iii) the two together, using (iv) indomethacin as a positive control. Dinitrophenol altered intestinal mitochondrial morphology, increased intestinal permeability and caused inflammation without affecting gastric permeability or intestinal prostanoid levels. Parenteral aspirin decreased mucosal prostanoids without affecting intestinal mitochondria in vivo, gastric or intestinal permeability. Aspirin caused no inflammation or ulcers. When dinitrophenol and aspirin were given together the changes in intestinal mitochondrial morphology, permeability, inflammation and prostanoid levels and the macro- and microscopic appearances of intestinal ulcers were similar to indomethacin. These studies allow dissociation of the contribution and consequences of uncoupling of mitochondrial oxidative phosphorylation and cyclooxygenase inhibition in the pathophysiology of NSAID enteropathy. While uncoupling of enterocyte mitochondrial oxidative phosphorylation leads to increased intestinal permeability and low grade inflammation, concurrent decreases in mucosal prostanoids appear to be important in the development of ulcers.

[The role of RNA splicing in the pathogenesis of spinal muscular atrophy and development of its therapeutics].

PubMed

Sahashi, Kentaro; Sobue, Gen

2014-12-01

Loss-of-function mutations in SMN1 cause spinal muscular atrophy (SMA), a leading genetic cause of infant mortality. Degeneration of alpha-motor neurons that results in progressive paralysis is a pathological hallmark of SMA. Recently, peripheral-tissue involvement has also been reported in SMA. Patients have low levels of functional SMN which is attributed to alternative splicing in SMN2, a gene closely-related to SMN1. This decrease in the expression of SMN, a ubiquitously expressed protein involved in promoting snRNP assembly required for splicing, is responsible for SMA. However, the mechanism through which decrease in SMN levels causes SMA remains unclear. Currently, no curative treatment is available for SMA, but SMN restoration is thought to be necessary and sufficient for cure. Antisense oligonucleotides (ASOs) can be designed to specifically alter splicing patterns of target pre-mRNAs. We identified an ASO that redirects SMN2 splicing and is currently in clinical trials for use as RNA-targeting therapeutics. Further, we have also reported a novel application of splicing-modulating ASOs--creation of animal phenocopy models of diseases by inducing mis-splicing. Exploring the relationship between the spatial and temporal effects of therapeutic and pathogenic ASOs yields relevant insights into the roles of SMN in SMA pathogenesis and into its normal physiological functions. This knowledge, in turn, contributes to the ongoing development of targeted therapeutics.

Comparative assessment of onion and garlic extracts on endogenous hepatic and renal antioxidant status in rat.

PubMed

Suru, Stephen M; Ugwu, Chidiebere E

2015-07-01

Despite growing claims of functional health benefits in folkloric medicine, the safety of chronic/elevated intakes of onion and garlic cannot be assumed. Therefore, this study assesses oral administration of varied doses of onion and garlic on some biomarkers of hepatic and renal functions in rats. Animals were divided into five groups: control group received vehicle and extract-treated groups received varied doses of onion or garlic extract (0.5 mL and 1.0 mL/100 g bwt/day) for 6 weeks. Both doses of onion caused marked (p<0.05) increase in hepatic and renal levels of glutathione (GSH), glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT) and marked (p<0.05) decrease in malondialdehyde (MDA). Treatment with low dose of garlic elicited similar trend except in hepatic CAT, renal SOD and GST levels. A high dose of garlic only caused marked (p<0.05) increase in hepatic GST, renal GST, and SOD. Both doses of onion and low dose of garlic significantly (p<0.05) enhanced renal Na+/K+-ATPase activity. Only a high dose of onion caused significant (p<0.05) increase in hepatic aspartate transaminase (AST), alkaline phosphatase (ALP), and decrease in plasma AST activities. These findings suggest antioxidant enhancing capability for both doses of onion and low dose of garlic, while high dose of garlic elicited pro-oxidant conditions.

Mechanisms of sulfur mustard analog 2-chloroethyl ethyl sulfide-induced DNA damage in skin epidermal cells and fibroblasts.

PubMed

Inturi, Swetha; Tewari-Singh, Neera; Gu, Mallikarjuna; Shrotriya, Sangeeta; Gomez, Joe; Agarwal, Chapla; White, Carl W; Agarwal, Rajesh

2011-12-15

Employing mouse skin epidermal JB6 cells and dermal fibroblasts, here we examined the mechanisms of DNA damage by 2-chloroethyl ethyl sulfide (CEES), a monofunctional analog of sulfur mustard (SM). CEES exposure caused H2A.X and p53 phosphorylation as well as p53 accumulation in both cell types, starting at 1h, that was sustained for 24h, indicating a DNA-damaging effect of CEES, which was also confirmed and quantified by alkaline comet assay. CEES exposure also induced oxidative stress and oxidative DNA damage in both cell types, measured by an increase in mitochondrial and cellular reactive oxygen species and 8-hydroxydeoxyguanosine levels, respectively. In the studies distinguishing between oxidative and direct DNA damage, 1h pretreatment with glutathione (GSH) or the antioxidant Trolox showed a decrease in CEES-induced oxidative stress and oxidative DNA damage. However, only GSH pretreatment decreased CEES-induced total DNA damage measured by comet assay, H2A.X and p53 phosphorylation, and total p53 levels. This was possibly due to the formation of GSH-CEES conjugates detected by LC-MS analysis. Together, our results show that CEES causes both direct and oxidative DNA damage, suggesting that to rescue SM-caused skin injuries, pleiotropic agents (or cocktails) are needed that could target multiple pathways of mustard skin toxicities. Copyright © 2011 Elsevier Inc. All rights reserved.

Increasing procaspase 8 expression using repurposed drugs to induce HIV infected cell death in ex vivo patient cells

PubMed Central

Sampath, Rahul; Cummins, Nathan W.; Natesampillai, Sekar; Bren, Gary D.; Chung, Thomas D.; Baker, Jason; Henry, Keith; Pagliuzza, Amélie; Badley, Andrew D.

2017-01-01

HIV persists because a reservoir of latently infected CD4 T cells do not express viral proteins and are indistinguishable from uninfected cells. One approach to HIV cure suggests that reactivating HIV will activate cytotoxic pathways; yet when tested in vivo, reactivating cells do not die sufficiently to reduce cell-associated HIV DNA levels. We recently showed that following reactivation from latency, HIV infected cells generate the HIV specific cytotoxic protein Casp8p41 which is produced by HIV protease cleaving procaspase 8. However, cell death is prevented, possibly due to low procaspase 8 expression. Here, we tested whether increasing procaspase 8 levels in CD4 T cells will produce more Casp8p41 following HIV reactivation, causing more reactivated cells to die. Screening 1277 FDA approved drugs identified 168 that increased procaspase 8 expression by at least 1.7-fold. Of these 30 were tested for anti-HIV effects in an acute HIVIIIb infection model, and 9 drugs at physiologic relevant levels significantly reduced cell-associated HIV DNA. Primary CD4 T cells from ART suppressed HIV patients were treated with one of these 9 drugs and reactivated with αCD3/αCD28. Four drugs significantly increased Casp8p41 levels following HIV reactivation, and decreased total cell associated HIV DNA levels (flurbiprofen: p = 0.014; doxycycline: p = 0.044; indomethacin: p = 0.025; bezafibrate: P = 0.018) without effecting the viability of uninfected cells. Thus procaspase 8 levels can be increased pharmacologically and, in the context of HIV reactivation, increase Casp8p41 causing death of reactivating cells and decreased HIV DNA levels. Future studies will be required to define the clinical utility of this or similar approaches. PMID:28628632

Increased ophthalmic acid production is supported by amino acid catabolism under fasting conditions in mice.

PubMed

Kobayashi, Sho; Lee, Jaeyong; Takao, Toshifumi; Fujii, Junichi

2017-09-23

Glutathione (GSH) plays pivotal roles in antioxidation and detoxification. The transsulfuration pathway, in conjunction with methionine metabolism, produces equimolar amounts of cysteine (Cys) and 2-oxobutyric acid (2OB). The resulting 2OB is then converted into 2-aminobutyric acid (2AB) by a transaminase and is utilized as a substitute for Cys by the GSH-synthesizing machinery to produce ophthalmic acid (OPT). By establishing a method for simultaneously measuring Cys, GSH, and OPT by liquid chromatography-mass spectrometry, we found that fasting causes an elevation in OPT levels in the liver and blood plasma, even though the levels of Cys and GSH are decreased. Autophagy was activated, but the levels of GSH/OPT-synthesizing enzymes remained unchanged. After 6 h of fasting, the mice were given 1% 2AB and/or 5% glucose in the drinking water for an additional 24 h and the above metabolites analyzed. 2AB administration caused an increase in OPT levels, and, when glucose was co-administered with 2AB, the levels of OPT were elevated further but GSH levels were decreased somewhat. These results suggest that, while Cys is utilized for glyconeogenesis under fasting conditions, reaching levels that were insufficient for the synthesis of GSH, 2OB was preferentially converted to 2AB via amino acid catabolism and was utilized as a building block for OPT. Thus the consumption of Cys and the parallel elevation of 2AB under fasting conditions appeared to force γ-glutamylcysteine synthetase to form γ-glutamyl-2AB, despite the fact that the enzyme has a higher Km value for 2AB than Cys. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of mitochondrial dysfunction and oxidative stress on endogenous levels of coenzyme Q(10) in human cells.

PubMed

Yen, Hsiu-Chuan; Chen, Feng-Yuan; Chen, Shih-Wei; Huang, Yu-Hsiang; Chen, Yun-Ru; Chen, Chih-Wei

2011-01-01

Little is known about the regulation of endogenous CoQ(10) levels in response to mitochondrial dysfunction or oxidative stress although exogenous CoQ(10) has been extensively used in humans. In this study, we first demonstrated that acute treatment of antimycin A, an inhibitor of mitochondrial complex III, and the absence of mitochondrial DNA suppressed CoQ(10) levels in human 143B cells. Because these two conditions also enhanced formation of reactive oxygen species (ROS), we further investigated whether oxidative stress or mitochondrial dysfunction primarily contributed to the decrease of CoQ(10) levels. Results showed that H(2)O(2) augmented CoQ(10) levels, but carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP), a chemical uncoupler, decreased CoQ(10) levels in 143B cells. However, H(2)O(2) and FCCP both increased mRNA levels of multiple COQ genes for biosynthesis of CoQ(10) . Our findings suggest that ROS induced CoQ(10) biosynthesis, whereas mitochondrial energy deficiency caused secondary suppression of CoQ(10) levels possibly due to impaired import of COQ proteins into mitochondria. Copyright © 2011 Wiley Periodicals, Inc.

Glucose monitoring system using nanopellets.

PubMed

Rajasekaran, C; Nirmala, Madian; Jayanthi, K B

2017-02-01

The combination of the fields of software engineering, gadgets, and science has stood out among the most revolutionary future innovations. Health issues have been the focus of various engaging and explanatory studies. One such health-related dilemma is diabetes. Diabetes at its serious stage results in impaired vision. Increase in the glucose level is a critical parameter that could result in hyperglycaemia, hypoglycaemia, massive heart attack, strokes, and aneurysms. Monitoring the glucose level in blood is one of the control measures for diabetes in the affected population. A glucose monitoring framework interminably measures and screens the glucose level in blood. A novel framework for measuring the glucose level is proposed in this study. This study employs nanopellets that evaluate the glucose level. When the glucose level increases or decreases, it is continuously recorded and displayed using a microcontroller (mixed signal processor (MSP) 430). The data are then sent to the physician through global system for mobile communication. The typical blood glucose level of human being ranges from 70 to 110 mg/dl. When the insulin level builds up to certain point, hyperglycaemia occurs. When decreases, hypoglycaemia occurs. Hyperglycaemia leads to cataracts, oedema, hypertension, polyuria, and polydipsia. Hypoglycaemia causes perplexity, energy, insensateness, coma, and death.

Effects of systemic carbidopa on dopamine synthesis in rat hypothalamus and striatum

NASA Technical Reports Server (NTRS)

Kaakkola, S.; Tuomainen, P.; Wurtman, R. J.; Maennistoe, P. T.

1991-01-01

Significant concentrations of carbidopa (CD) were found in rat hypothalamus, striatum, and in striatal microdialysis efflux after intraperitoneal administration of the drug. Efflux levels peaked one hour after administration of 100 mg/kg at 0.37 microg/kg or about 2 percent of serum levels. Concurrent CD levels in hypothalamus and striatum were about 2.5 percent and 1.5 percent, respectively, of corresponding serum levels. Levels of dopamine and its principal metabolites in striatal efflux were unaffected. The removal of the brain blood by saline perfusion decreased the striatal and hypothalamic CD concentrations only by 33 percent and 16 percent, respectively. In other rats receiving both CD and levodopa (LD), brain L-dopa, dopamine, and 3,4-dihydroxyphenvlacetic acid (DOPAC) levels after one hour tended to be proportionate to LD dose. When the LD dose remained constant, increasing the CD dose dose-dependently enhanced L-dopa levels in the hypothalamus and striatum. However, dopamine levels did not increase but, in contrast, decreased dose-dependently (although significantly only in the hypothalamus). CD also caused dose-dependent decrease in striatal 3-O-methyldopa (3-OMD) and in striatal and hypothalamic homovanillic acid (HVA), when the LD dose was 50 mg/kg. We conclude that, at doses exceedimg 50 mg/kg, sufficient quantities of CD enter the brain to inhibit dopamine formation, especially in the hypothalamus. Moreover, high doses of LD/CD, both of which are themselves catechols, can inhibit the O-methylation of brain catecholamines formed from the LD.

Effects of systemic carbidopa on dopamine synthesis in rat hypothalamus and striatum

NASA Technical Reports Server (NTRS)

Kaakkola, S.; Tuomainen, P.; Wurtman, R. J.; Mannisto, P. T.

1992-01-01

Significant concentrations of carbidopa (CD) were found in rat hypothalamus, striatum, and in striatal microdialysis efflux after intraperitoneal administration of the drug. Efflux levels peaked one hour after administration of 100 mg/kg at 0.37 micrograms/ml, or about 2% of serum levels. Concurrent CD levels in hypothalamus and striatum were about 2.5% and 1.5%, respectively, of corresponding serum levels. Levels of dopamine and its principal metabolites in striatal efflux were unaffected. The removal of the brain blood by saline perfusion decreased the striatal and hypothalamic CD concentrations only by 33% and 16%, respectively. In other rats receiving both CD and levodopa (LD), brain L-dopa, dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels after one hour tended to be proportionate to LD dose. When the LD dose remained constant, increasing the CD dose dose-dependently enhanced L-dopa levels in the hypothalamus and striatum. However dopamine levels did not increase but, in contrast, decreased dose-dependently (although significantly only in the hypothalamus). CD also caused dose-dependent decrease in striatal 3-O-methyldopa (3-OMD) and in striatal and hypothalamic homovanillic acid (HVA), when the LD dose was 50 mg/kg. We conclude that, at doses exceeding 50 mg/kg, sufficient quantities of CD enter the brain to inhibit dopamine formation, especially in the hypothalamus. Moreover, high doses of LD/CD, both of which are themselves catechols, can inhibit the O-methylation of brain catecholamines formed from the LD.

1-Methyl-4-phenylpyridinium-induced alterations of glutathione status in immortalized rat dopaminergic neurons

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

Drechsel, Derek A.; Liang, L.-P.; Patel, Manisha

2007-05-01

Decreased glutathione levels associated with increased oxidative stress are a hallmark of numerous neurodegenerative diseases, including Parkinson's disease. GSH is an important molecule that serves as an anti-oxidant and is also a major determinant of cellular redox environment. Previous studies have demonstrated that neurotoxins can cause changes in reduced and oxidized GSH levels; however, information regarding steady state levels remains unexplored. The goal of this study was to characterize changes in cellular GSH levels and its regulatory enzymes in a dopaminergic cell line (N27) following treatment with the Parkinsonian toxin, 1-methyl-4-phenylpyridinium (MPP{sup +}). Cellular GSH levels were initially significantly decreasedmore » 12 h after treatment, but subsequently recovered to values greater than controls by 24 h. However, oxidized glutathione (GSSG) levels were increased 24 h following treatment, concomitant with a decrease in GSH/GSSG ratio prior to cell death. In accordance with these changes, ROS levels were also increased, confirming the presence of oxidative stress. Decreased enzymatic activities of glutathione reductase and glutamate-cysteine ligase by 20-25% were observed at early time points and partly account for changes in GSH levels after MPP{sup +} exposure. Additionally, glutathione peroxidase activity was increased 24 h following treatment. MPP{sup +} treatment was not associated with increased efflux of glutathione to the medium. These data further elucidate the mechanisms underlying GSH depletion in response to the Parkinsonian toxin, MPP{sup +}.« less

Determination of Sodium, Potassium, Magnesium, and Calcium Minerals Level in Fresh and Boiled Broccoli and Cauliflower by Atomic Absorption Spectrometry

NASA Astrophysics Data System (ADS)

Nerdy

2018-01-01

Vegetables from the cabbage family vegetables consumed by many people, which is known healthful, by eaten raw, boiled, or cooked (stir fry or soup). Vegetables like broccoli and cauliflower contain vitamins, minerals, and fiber. This study aims to determine the decrease percentage of sodium, potassium, magnesium, and calcium minerals level caused by boiled broccoli and cauliflower by atomic absorption spectrometry. Boiled broccoli and cauliflower prepared by given boiled treatment in boiling water for 3 minutes. Fresh and boiled broccoli and cauliflower carried out dry destruction, followed by quantitative analysis of sodium, potassium, magnesium, and calcium minerals respectively at a wavelength of 589.0 nm; 766.5 nm; 285.2 nm; and 422.7 nm, using atomic absorption spectrometry methods. After the determination of the sodium, potassium, magnesium, and calcium minerals level followed by validation of analytical methods with accuracy, precision, linearity, range, limit of detection (LOD), and limit of quantitation (LOQ) parameters. Research results show a decrease in the sodium, potassium, magnesium, and calcium minerals level in boiled broccoli and cauliflower compared with fresh broccoli and cauliflower. Validation of analytical methods gives results that spectrometry methods used for determining sodium, potassium, magnesium, and calcium minerals level are valid. It concluded that the boiled gives the effect of decreasing the minerals level significantly in broccoli and cauliflower.

Evidence for the free radical/oxidative stress theory of ageing from the CHANCES consortium: a meta-analysis of individual participant data.

PubMed

Schöttker, Ben; Brenner, Hermann; Jansen, Eugène H J M; Gardiner, Julian; Peasey, Anne; Kubínová, Růžena; Pająk, Andrzej; Topor-Madry, Roman; Tamosiunas, Abdonas; Saum, Kai-Uwe; Holleczek, Bernd; Pikhart, Hynek; Bobak, Martin

2015-12-15

The free radical/oxidative stress theory of ageing has received considerable attention, but the evidence on the association of oxidative stress markers with mortality is sparse. We measured derivatives of reactive oxygen metabolite (D-ROM) levels as a proxy for the reactive oxygen species concentration and total thiol levels (TTL) as a proxy for the redox control status in 10,622 men and women (age range, 45-85 years), from population-based cohorts from Germany, Poland, Czech Republic, and Lithuania, of whom 1,702 died during follow-up. Both oxidative stress markers were significantly associated with all-cause mortality independently from established risk factors (including inflammation) and from each other in all cohorts. Regarding cause-specific mortality, compared to low D-ROM levels (≤ 340 Carr U), very high D-ROM levels (>500 Carr U) were strongly associated with both cardiovascular (relative risk (RR), 5.09; 95 % CI, 2.67-9.69) and cancer mortality (RR, 4.34; 95 % CI, 2.31-8.16). TTL was only associated with CVD mortality (RR, 1.30; 95 % CI, 1.15-1.48, for one-standard-deviation-decrease). The strength of the association of TTL with CVD mortality increased with age of the participants (RR for one-standard-deviation-decrease in those aged 70-85 years was 1.65; 95 % CI, 1.22-2.24). In these four population-based cohort studies from Central and Eastern Europe, the oxidative stress serum markers D-ROM and TTL were independently and strongly associated with all-cause and CVD mortality. In addition, D-ROM levels were also strongly associated with cancer mortality. This study provides epidemiological evidence supporting the free radical/oxidative stress theory of ageing and suggests that d-ROMs and TTL are useful oxidative stress markers associated with premature mortality.

Synoptic characteristics of heavy snowfalls at Busan of Korea caused by polar lows over the East/Japan Sea

NASA Astrophysics Data System (ADS)

Choi, Jae-Won; Cha, Yumi; Kim, Hae-Dong

2018-02-01

The results of the present study prove that snowfall occurred due to the polar low (PL) in the Korean Peninsula and six cases of snowfall exceeding a snow depth of 2 cm over the past 16 years in Busan, South Korea. A strong northwesterly air current with a cold outbreak at the lower level passed through the Korean Peninsula and penetrated into the East/Japan Sea causing the generation and characteristics of a PL. However, a northeasterly air current due to a synoptic low (SL) in East Japan approached the east coast via the East/Japan Sea, which generated a wind field with mesoscale cyclonic circulation. In the center of this cyclone, a strong positive vorticity region was revealed from the lower level to the upper level. The air temperature in the center of the PL was warmer than the surrounding areas at the lower level. As the PL developed and the air temperature decreased, a rapid tropopause drop followed due to the effect of the cold core along with the cutoff low at the mid-level or the higher level. As a result, the stratification became more unstable. The PL moved into Busan as the cold core at the upper level rapidly moved to the lower latitudes, which formed an unstable region around Busan. The PL decayed because the cutoff low, the cold core, and the positive vorticity region at the upper level quickly moved to the east, thereby causing the stratification to stabilize. Also, because the approach to the Japanese Archipelago caused an increase in surface friction, the original structure could no longer be maintained.

Role of reactive oxygen species in arsenic-induced transformation of human lung bronchial epithelial (BEAS-2B) cells

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

Zhang, Zhuo, E-mail: zhuo.zhang@uky.edu; Pratheeshkumar, Poyil; Budhraja, Amit

Highlights: • Short term exposure of cells to arsenic causes ROS generation. • Chronical exposure of cells to arsenic causes malignant cell transformation. • Inhibition of ROS generation reduces cell transformation by arsenic. • Arsenic-transformed cells exhibit reduced capacity of generating ROS. • Arsenic-transformed cells exhibit increased levels of antioxidants. - Abstract: Arsenic is an environmental carcinogen, its mechanisms of carcinogenesis remain to be investigated. Reactive oxygen species (ROS) are considered to be important. A previous study (Carpenter et al., 2011) has measured ROS level in human lung bronchial epithelial (BEAS-2B) cells and arsenic-transformed BEAS-2B cells and found that ROSmore » levels were higher in transformed cells than that in parent normal cells. Based on these observations, the authors concluded that cell transformation induced by arsenic is mediated by increased cellular levels of ROS. This conclusion is problematic because this study only measured the basal ROS levels in transformed and parent cells and did not investigate the role of ROS in the process of arsenic-induced cell transformation. The levels of ROS in arsenic-transformed cells represent the result and not the cause of cell transformation. Thus question concerning whether ROS are important in arsenic-induced cell transformation remains to be answered. In the present study, we used expressions of catalase (antioxidant against H{sub 2}O{sub 2}) and superoxide dismutase 2 (SOD2, antioxidant against O{sub 2}{sup ·−}) to decrease ROS level and investigated their role in the process of arsenic-induced cell transformation. Our results show that inhibition of ROS by antioxidant enzymes decreased arsenic-induced cell transformation, demonstrating that ROS are important in this process. We have also shown that in arsenic-transformed cells, ROS generation was lower and levels of antioxidants are higher than those in parent cells, in a disagreement with the previous report. The present study has also shown that the arsenic-transformed cells acquired apoptosis resistance. The inhibition of catalase to increase ROS level restored apoptosis capability of arsenic-transformed BEAS-2B cells, further showing that ROS levels are low in these cells. The apoptosis resistance due to the low ROS levels may increase cells proliferation, providing a favorable environment for tumorigenesis of arsenic-transformed cells.« less

Protective effect of [6]-gingerol on the ethanol-induced teratogenesis of cultured mouse embryos.

PubMed

Yon, Jung-Min; Baek, In-Jeoung; Lee, Se-Ra; Kim, Mi-Ra; Hong, Jin Tae; Yong, Hwanyul; Lee, Beom Jun; Yun, Young Won; Nam, Sang-Yoon

2012-01-01

Excessive ethanol consumption during pregnancy causes fetal alcohol syndrome. We investigated the effect of [6]-gingerol on ethanol-induced embryotoxicity using a whole embryo culture system. The morphological changes of embryos and the gene expression patterns of the antioxidant enzymes cytosolic glutathione peroxidase (cGPx), cytoplasmic Cu/Zn superoxide dismutase (SOD1), and Mn-SOD (SOD2), and SOD activity were examined in the cultured mouse embryos exposed to ethanol (5 μL/3 mL) and/or [6]-gingerol (1×10(-8) or 1×10(-7) μg/mL) for 2 days. In ethanol-exposed embryos, the standard morphological score of embryos was significantly decreased compared with those of the control (vehicle) group. However, cotreatment of embryos with [6]-gingerol and ethanol significantly improved all of the developmental parameters except crownrump length and head length, compared with those of the ethanol alone group. The mRNA expression levels of cGPx and SOD2, not SOD1, were decreased consistently, SOD activity were significantly decreased compared with the control group. However, the decreases in mRNA levels of antioxidant enzymes and SOD activity were significantly restored to the control levels by [6]-gingerol supplement. These results indicate that [6]-gingerol has a protective effect against ethanol-induced teratogenicity during mouse embryogenesis.

Physiological response of rats to delivery of helium and xenon: implications for hyperpolarized noble gas imaging

NASA Technical Reports Server (NTRS)

Ramirez, M. P.; Sigaloff, K. C.; Kubatina, L. V.; Donahue, M. A.; Venkatesh, A. K.; Albert, M. S.; ALbert, M. S. (Principal Investigator)

2000-01-01

The physiological effects of various hyperpolarized helium and xenon MRI-compatible breathing protocols were investigated in 17 Sprague-Dawley rats, by continuous monitoring of blood oxygen saturation, heart rate, EKG, temperature and endotracheal pressure. The protocols included alternating breaths of pure noble gas and oxygen, continuous breaths of pure noble gas, breath-holds of pure noble gas for varying durations, and helium breath-holds preceded by two helium rinses. Alternate-breath protocols up to 128 breaths caused a decrease in oxygen saturation level of less than 5% for either helium or xenon, whereas 16 continuous-breaths caused a 31.5% +/- 2.3% decrease in oxygen saturation for helium and a 30.7% +/- 1. 3% decrease for xenon. Breath-hold protocols up to 25 s did not cause the oxygen saturation to fall below 90% for either of the noble gases. Oxygen saturation values below 90% are considered pathological. At 30 s of breath-hold, the blood oxygen saturation dropped precipitously to 82% +/- 0.6% for helium, and to 76.5% +/- 7. 4% for xenon. Breath-holds longer than 10 s preceded by pre-rinses caused oxygen saturation to drop below 90%. These findings demonstrate the need for standardized noble gas inhalation procedures that have been carefully tested, and for continuous physiological monitoring to ensure the safety of the subject. We find short breath-hold and alternate-breath protocols to be safe procedures for use in hyperpolarized noble gas MRI experiments. Copyright 2000 John Wiley & Sons, Ltd.

2'-Hydroxyflavanone: A novel strategy for targeting breast cancer.

PubMed

Singhal, Jyotsana; Nagaprashantha, Lokesh; Chikara, Shireen; Awasthi, Sanjay; Horne, David; Singhal, Sharad S

2017-09-26

Breast cancer is the most common cancer in women that is driven by cross-talk with hormonal and cellular signaling pathways. The natural phytochemicals, due to broad-spectrum anti-inflammatory and anti-cancerous properties, present with novel opportunities for targeting breast cancer. Intake of citrus fruits is known to reduce the risk for incidence of breast cancer. Hence, we tested the efficacy of citrus flavonoid 2'-hydroxyflavanone (2HF) in breast cancer. 2HF inhibited survival, clonogenic ability, cell cycle progression and induced apoptosis in breast cancer cells. 2HF also decreased VEGF levels and inhibited migratory capacity of breast cancer cells. Administration of 2HF led to regression of triple-negative MDA-MB-231 tumors in the mice xenograft model. 2HF decreased the levels of RLIP76 both in vitro studies and in vivo MDA-MB-231 xenograft model of breast cancer. Western blot and histopathological analyses of resected tumors showed a decline in the levels of survival and proliferation markers Ki67, pAkt, survivin, and cell cycle proteins CDK4 and cyclin B1. 2HF treatment led to inhibition of angiogenesis as determined by decreased VEGF levels in vitro and angiogenesis marker CD31 in vivo . 2HF reversed the pro-/anti-apoptotic ratio of BAX/BCL-2 by decreasing anti-apoptotic protein BCL-2 and increasing pro-apoptotic proteins BAX and BIM in vivo . 2HF also decreased the mesenchymal markers vimentin and fibronectin along with causing a parallel increase in pro-differentiation protein E-cadherin. Collectively, the ability of 2HF to decrease RLIP76, VEGF and regulate critical proliferative, apoptotic and differentiation proteins together provides strong rationale to further develop 2HF based interventions for targeting breast cancer.

Can an Integrated Approach Reduce Child Vulnerability to Anaemia? Evidence from Three African Countries

PubMed Central

Siekmans, Kendra; Receveur, Olivier; Haddad, Slim

2014-01-01

Addressing the complex, multi-factorial causes of childhood anaemia is best done through integrated packages of interventions. We hypothesized that due to reduced child vulnerability, a “buffering” of risk associated with known causes of anaemia would be observed among children living in areas benefiting from a community-based health and nutrition program intervention. Cross-sectional data on the nutrition and health status of children 24–59 mo (N = 2405) were obtained in 2000 and 2004 from program evaluation surveys in Ghana, Malawi and Tanzania. Linear regression models estimated the association between haemoglobin and immediate, underlying and basic causes of child anaemia and variation in this association between years. Lower haemoglobin levels were observed in children assessed in 2000 compared to 2004 (difference -3.30 g/L), children from Tanzania (-9.15 g/L) and Malawi (-2.96 g/L) compared to Ghana, and the youngest (24–35 mo) compared to oldest age group (48–59 mo; -5.43 g/L). Children who were stunted, malaria positive and recently ill also had lower haemoglobin, independent of age, sex and other underlying and basic causes of anaemia. Despite ongoing morbidity, risk of lower haemoglobin decreased for children with malaria and recent illness, suggesting decreased vulnerability to their anaemia-producing effects. Stunting remained an independent and unbuffered risk factor. Reducing chronic undernutrition is required in order to further reduce child vulnerability and ensure maximum impact of anaemia control programs. Buffering the impact of child morbidity on haemoglobin levels, including malaria, may be achieved in certain settings. PMID:24598692

Can an integrated approach reduce child vulnerability to anaemia? Evidence from three African countries.

PubMed

Siekmans, Kendra; Receveur, Olivier; Haddad, Slim

2014-01-01

Addressing the complex, multi-factorial causes of childhood anaemia is best done through integrated packages of interventions. We hypothesized that due to reduced child vulnerability, a "buffering" of risk associated with known causes of anaemia would be observed among children living in areas benefiting from a community-based health and nutrition program intervention. Cross-sectional data on the nutrition and health status of children 24-59 mo (N=2405) were obtained in 2000 and 2004 from program evaluation surveys in Ghana, Malawi and Tanzania. Linear regression models estimated the association between haemoglobin and immediate, underlying and basic causes of child anaemia and variation in this association between years. Lower haemoglobin levels were observed in children assessed in 2000 compared to 2004 (difference -3.30 g/L), children from Tanzania (-9.15 g/L) and Malawi (-2.96 g/L) compared to Ghana, and the youngest (24-35 mo) compared to oldest age group (48-59 mo; -5.43 g/L). Children who were stunted, malaria positive and recently ill also had lower haemoglobin, independent of age, sex and other underlying and basic causes of anaemia. Despite ongoing morbidity, risk of lower haemoglobin decreased for children with malaria and recent illness, suggesting decreased vulnerability to their anaemia-producing effects. Stunting remained an independent and unbuffered risk factor. Reducing chronic undernutrition is required in order to further reduce child vulnerability and ensure maximum impact of anaemia control programs. Buffering the impact of child morbidity on haemoglobin levels, including malaria, may be achieved in certain settings.

N-acetylcysteine prevents the geldanamycin cytotoxicity by forming geldanamycin-N-acetylcysteine adduct.

PubMed

Mlejnek, Petr; Dolezel, Petr

2014-09-05

Geldanamycin (GDN) is a benzoquinone ansamycin antibiotic with anti-proliferative activity on tumor cells. GDN cytotoxicity has been attributed to the disruption of heat shock protein 90 (Hsp90) binding and stabilizing client proteins, and by the induction of oxidative stress with concomitant glutathione (GSH) depletion. The later mechanism of cytotoxicity can be abrogated by N-acetylcysteine (NAC). It was suggested that NAC prevents GDN cytotoxicity mainly by the restoring of glutathione (GSH) level (Clark et al., 2009). Here we argue that NAC does not protect cells from the GDN cytotoxicity by restoring the level of GSH. A detailed LC/MS/MS analysis of cell extracts indicated formation of GDN adducts with GSH. The amount of the GDN-GSH adduct is proportional to the GDN concentration and increases with incubation time. While nanomolar and low micromolar GDN concentrations induce cell death without an apparent GSH decrease, only much higher micromolar GDN concentrations cause a significant GSH decrease. Therefore, only high micromolar GDN concentrations can cause cell death which might be related to GSH depletion. Addition of NAC leads to the formation of adducts with GDN which diminish formation of GDN adducts with GSH. NAC also forms stable adducts with GDN extracellularly. Although NAC induces an increase in the GSH pool, this effect is not crucial for abrogation of GDN cytotoxicity. Indeed, the presence of NAC in the growth medium causes a rapid conversion of GDN into the GDN-NAC adduct, which is the real cause of the abrogated GDN cytotoxicity. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Effects of interferon-gamma and lipopolysaccharide on macrophage iron metabolism are mediated by nitric oxide-induced degradation of iron regulatory protein 2.

PubMed

Kim, S; Ponka, P

2000-03-03

Iron regulatory proteins (IRP-1 and IRP-2) control the synthesis of transferrin receptors (TfR) and ferritin by binding to iron-responsive elements, which are located in the 3'-untranslated region and the 5'-untranslated region of their respective mRNAs. Cellular iron levels affect binding of IRPs to iron-responsive elements and consequently expression of TfR and ferritin. Moreover, NO(*), a redox species of nitric oxide that interacts primarily with iron, can activate IRP-1 RNA binding activity resulting in an increase in TfR mRNA levels. Recently we found that treatment of RAW 264.7 cells (a murine macrophage cell line) with NO(+) (nitrosonium ion, which causes S-nitrosylation of thiol groups) resulted in a rapid decrease in RNA binding of IRP-2 followed by IRP-2 degradation, and these changes were associated with a decrease in TfR mRNA levels (Kim, S., and Ponka, P. (1999) J. Biol. Chem. 274, 33035-33042). In this study, we demonstrated that stimulation of RAW 264.7 cells with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) increased IRP-1 binding activity, whereas RNA binding of IRP-2 decreased and was followed by a degradation of this protein. Moreover, the decrease of IRP-2 binding/protein levels was associated with a decrease in TfR mRNA levels in LPS/IFN-gamma-treated cells, and these changes were prevented by inhibitors of inducible nitric oxide synthase. Furthermore, LPS/IFN-gamma-stimulated RAW 264.7 cells showed increased rates of ferritin synthesis. These results suggest that NO(+)-mediated degradation of IRP-2 plays a major role in iron metabolism during inflammation.

Time course of saliva and serum melatonin levels after ingestion of melatonin.

PubMed

Shirakawa, S; Tsuchiya, S; Tsutsumi, Y; Kotorii, T; Uchimura, N; Sakamoto, T; Yamada, S

1998-04-01

Salival and serum melatonin levels after melatonin ingestion were measured by gas chromatography-mass spectrometry. Ingestion of 3 mg melatonin caused a marked increase in serum melatonin (3561+/-1201 pg/mL) within 20 min, followed by a gradual decrease, but the level still remained higher than the basal level at 240 min after the ingestion. The saliva melatonin 60 min after the ingestion showed the highest level (1177+/-403 pg/mL) which was one-third of the plasma level. The saliva melatonin level was highly correlated with the serum level throughout the experimental period (r=0.82, P=0.0001). These data indicate that the measurement of saliva melatonin level may be a suitable indicator for the melatonin secretion into general circulation.

Changes in leaf area, nitrogen content and canopy photosynthesis in soybean exposed to an ozone concentration gradient.

PubMed

Oikawa, Shimpei; Ainsworth, Elizabeth A

2016-08-01

Influences of ozone (O3) on light-saturated rates of photosynthesis in crop leaves have been well documented. To increase our understanding of O3 effects on individual- or stand level productivity, a mechanistic understanding of factors determining canopy photosynthesis is necessary. We used a canopy model to scale photosynthesis from leaf to canopy, and analyzed the importance of canopy structural and leaf ecophysiological characteristics in determining canopy photosynthesis in soybean stands exposed to 9 concentrations of [O3] (37-116 ppb; 9-h mean). Light intensity and N content peaked in upper canopy layers, and sharply decreased through the lower canopy. Plant leaf area decreased with increasing [O3] allowing for greater light intensity to reach lower canopy levels. At the leaf level, light-saturated photosynthesis decreased and dark respiration increased with increasing [O3]. These data were used to calculate daily net canopy photosynthesis (Pc). Pc decreased with increasing [O3] with an average decrease of 10% for an increase in [O3] of 10 ppb, and which was similar to changes in above-ground dry mass production of the stands. Absolute daily net photosynthesis of lower layers was very low and thus the decrease in photosynthesis in the lower canopy caused by elevated [O3] had only minor significance for total canopy photosynthesis. Sensitivity analyses revealed that the decrease in Pc was associated with changes in leaf ecophysiology but not with decrease in leaf area. The soybean stands were very crowded, the leaves were highly mutually shaded, and sufficient light for positive carbon balance did not penetrate to lower canopy leaves, even under elevated [O3]. Copyright © 2016 Elsevier Ltd. All rights reserved.

Consequences of SPAK inactivation on Hyperkalemic Hypertension caused by WNK1 mutations: evidence for differential roles of WNK1 and WNK4.

PubMed

Rafael, Chloé; Soukaseum, Christelle; Baudrie, Véronique; Frère, Perrine; Hadchouel, Juliette

2018-02-19

Mutations of the gene encoding WNK1 [With No lysine (K) kinase 1] or WNK4 cause Familial Hyperkalemic Hypertension (FHHt). Previous studies have shown that the activation of SPAK (Ste20-related Proline/Alanine-rich Kinase) plays a dominant role in the development of FHHt caused by WNK4 mutations. The implication of SPAK in FHHt caused by WNK1 mutation has never been investigated. To clarify this issue, we crossed WNK1 +/FHHt mice with SPAK knock-in mice in which the T-loop Thr243 residue was mutated to alanine to prevent activation by WNK kinases. We show that WNK1 +/FHHT :SPAK 243A/243A mice display an intermediate phenotype, between that of control and SPAK 243A/243A mice, with normal blood pressure but hypochloremic metabolic alkalosis. NCC abundance and phosphorylation levels also decrease below the wild-type level in the double-mutant mice but remain higher than in SPAK 243A/243A mice. This is different from what was observed in WNK4-FHHt mice in which SPAK inactivation completely restored the phenotype and NCC expression to wild-type levels. Although these results confirm that FHHt caused by WNK1 mutations is dependent on the activation of SPAK, they suggest that WNK1 and WNK4 play different roles in the distal nephron.

Nephrotoxic effects of lead nitrate exposure in diabetic and nondiabetic rats: Involvement of oxidative stress and the protective role of sodium selenite.

PubMed

Baş, Hatice; Kalender, Yusuf

2016-10-01

Heavy metals are known to be toxic to organisms. The present study was undertaken to evaluate the protective effect of sodium selenite against lead nitrate (LN)-induced nephrotoxicity in diabetic and nondiabetic rats. Animals were divided into eight groups where the first was served as a control, whereas the remaining groups were treated with sodium selenite (1 mg/kg b.w.), LN (22.5 mg/kg b.w.) and a combination of LN and sodium selenite and diabetic forms of these groups. Changes in antioxidant enzyme activities, malondialdehide levels, serum urea, uric acid, creatinine levels, body, and kidney weights and histopathological changes were determined after 28 days. LN caused severe histopathological changes, increment in urea, uric acid, creatinine, and MDA levels, also decreasing in antioxidant enzyme activities, body, and kidney weights. In sodium selenite + LN group, we observed the protective effect of sodium selenite on examining parameters. Also diabetes caused alterations on these parameters compared with nondiabetic animals. We found that sodium selenite did not show protective effect on diabetes caused damages. As a result, LN caused nephrotoxicity and sodium selenite alleviated this toxicity but sodium selenite did not protect kidneys against diabetes mediated toxicity. Also, LN caused more harmfull effects in diabetic groups compared with nondiabetic groups. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1229-1240, 2016. © 2015 Wiley Periodicals, Inc.

Simulated water budgets and ground-water/surface-water interactions in Bushkill and parts of Monocacy Creek watersheds, Northampton County, Pennsylvania: A preliminary study with identification of data needs

USGS Publications Warehouse

Risser, Dennis W.

2006-01-01

This report, prepared in cooperation with the Department of Environmental Protection, Office of Mineral Resources Management, provides a preliminary analysis of water budgets and generalized ground-water/surface-water interactions for Bushkill and parts of Monocacy Creek watersheds in Northampton County, Pa., by use of a ground-water flow model. Bushkill Creek watershed was selected for study because it has areas of rapid growth, ground-water withdrawals from a quarry, and proposed stream-channel modifications, all of which have the potential for altering ground-water budgets and the interaction between ground water and streams. Preliminary 2-dimensional, steady-state simulations of ground-water flow by the use of MODFLOW are presented to show the status of work through September 2005 and help guide ongoing data collection in Bushkill Creek watershed. Simulations were conducted for (1) predevelopment conditions, (2) a water table lowered for quarry operations, and (3) anthropogenic changes in hydraulic conductivity of the streambed and aquifer. Preliminary results indicated under predevelopment conditions, the divide between the Bushkill and Monocacy Creek ground-water basins may not have been coincident with the topographic divide and as much as 14 percent of the ground-water discharge to Bushkill Creek may have originated from recharge in the Monocacy Creek watershed. For simulated predevelopment conditions, Schoeneck Creek and parts of Monocacy Creek were dry, but Bushkill Creek was gaining throughout all reaches. Simulated lowering of the deepest quarry sump to an altitude of 147 feet for quarry operations caused ground-water recharge and streamflow leakage to be diverted to the quarry throughout about 14 square miles and caused reaches of Bushkill and Little Bushkill Creeks to change from gaining to losing streams. Lowering the deepest quarry sump to an altitude of 100 feet caused simulated ground-water discharge to the quarry to increase about 4 cubic feet per second. Raising the deepest sump to an altitude of 200 feet caused the simulated discharge to the quarry to decrease about 14 cubic feet per second.Decreasing the hydraulic conductivity of the streambed of Bushkill Creek in the reach of large losses of flow caused simulated ground-water levels to decline and ground-water discharge to a quarry to decrease from 74 to 45 cubic feet per second.Decreasing the hydraulic conductivity of a hypothesized highly transmissive zone with a plug of relatively impermeable material caused ground-water levels to increase east of the plug and decline west of the plug, and decreased the discharge to a quarry from 74 to 53 cubic feet per second. Preliminary results of the study have significant limitations, which need to be recognized by the user. The results demonstrated the usefulness of ground-water modeling with available data sets, but as more data become available through field studies, a more complete evaluation could be conducted of the preliminary assumptions in the conceptual model, model sensitivity, and effects of boundary conditions. Additional streamflow and ground-water-level measurements would be needed to better quantify recharge and aquifer properties, particularly the anisotropy of carbonate rocks. Measurements of streamflow losses at average, steady-state hydrologic conditions could provide a more accurate estimate of ground-water recharge from this source, which directly affects water budgets and contributing areas simulated by the model.

Alterations in Hormone Levels After Adjuvant Chemoradiation in Male Rectal Cancer Patients

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

Yoon, Frederick H.; Perera, Francisco; Fisher, Barbara

Purpose: To evaluate follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels after postoperative chemoradiation in men with rectal cancer. Methods and Materials: Forty-three men with rectal cancer had baseline and postchemoradiation FSH, LH, and testosterone measured. Adjuvant chemoradiation consisted of two 5-day cycles of bolus 5-fluorouracil (5-FU) every 4 weeks at a dose of 500 mg/m{sup 2}/d followed by concurrent chemoradiation followed by two additional 5-day cycles of 5-FU at a dose of 450 mg/m{sup 2}/d. Continuous-infusion 5-FU at 225 mg/m{sup 2}/d was given during radiation. Pelvic radiation consisted of a three- or four-field technique with a median dosemore » of 54.0 Gy in 30 fractions. Results: Median follow-up was 6.1 years. Mean baseline FSH levels increased from 5.3 to a peak of 23.9 IU/L (p < 0.001) 13-24 months after chemoradiation. Mean baseline LH levels increased from 4.3 to a peak of 8.5 IU/L (p < 0.001) within 6 months after chemoradiation. Mean testosterone levels decreased from 15.4 nmol/L at baseline to 8.0 nmol/L more than 4 years after chemoradiation. Mean testosterone to mean LH ratio decreased from 4.4 at baseline to 1.1 after 48 months posttreatment, suggesting a continued decrease in Leydig cell function with time. Testicular dose was measured in 5 patients. Median dose was 4 Gy (range, 1.5-8.9 Gy). Conclusions: Chemoradiation in men with rectal cancer causes persistent increases in FSH and LH levels and decreases in testosterone levels.« less

Effects of lead nitrate and sodium selenite on DNA damage and oxidative stress in diabetic and non-diabetic rat erythrocytes and leucocytes.

PubMed

Baş, Hatice; Kalender, Yusuf; Pandir, Dilek; Kalender, Suna

2015-05-01

The adverse effects of lead nitrate (LN) and the preventive role of sodium selenite were investigated in diabetic and non-diabetic rat blood by measuring trolox equivalent antioxidant capacity (TEAC), ferric reducing antioxidant power (FRAP), malondialdehyde (MDA) levels and activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) also by evaluating DNA damage with comet assay. LN increased the levels of MDA, tail DNA%, mean tail length and tail moment, decreased the enzymes activities, FRAP and TEAC values. In sodium selenite+LN group, we observed the protective effect of sodium selenite on examining parameters. Diabetes caused alterations on these parameters, too. We found that sodium selenite did not protect against diabetes caused damages. As a result, LN caused toxic effects on blood cells and sodium selenite alleviated this toxicity but it did not show preventive effect against diabetes. Also, LN caused more harmfull effects in diabetic groups than non-diabetic groups. Copyright © 2015 Elsevier B.V. All rights reserved.

Prevalence and causes of low vision and blindness in Baotou

PubMed Central

Zhang, Guisen; Li, Yan; Teng, Xuelong; Wu, Qiang; Gong, Hui; Ren, Fengmei; Guo, Yuxia; Liu, Lei; Zhang, Han

2016-01-01

Abstract The aim of this study was to investigate the prevalence and causes of low vision and blindness in Baotou, Inner Mongolia. A cross-sectional study was carried out. Multistage sampling was used to select samples. The visual acuity was estimated using LogMAR and corrected by pinhole as best-corrected visual acuity. There were 7000 samples selected and 5770 subjects included in this investigation. The overall bilateral prevalence rates of low vision and blindness were 3.66% (95% CI: 3.17–4.14) and 0.99% (95% CI: 0.73–1.24), respectively. The prevalence of bilateral low vision, blindness, and visual impairment increased with age and decreased with education level. The main leading cause of low vision and blindness was cataract. Diabetic retinopathy and age-related macular degeneration were found to be the second leading causes of blindness in Baotou. The low vision and blindness were more prevalent in elderly people and subjects with low education level in Baotou. Cataract was the main cause for visual impairment and more attention should be paid to fundus diseases. In order to prevent blindness, much more eye care programs should be established. PMID:27631267

Prevalence and causes of low vision and blindness in Baotou: A cross-sectional study.

PubMed

Zhang, Guisen; Li, Yan; Teng, Xuelong; Wu, Qiang; Gong, Hui; Ren, Fengmei; Guo, Yuxia; Liu, Lei; Zhang, Han

2016-09-01

The aim of this study was to investigate the prevalence and causes of low vision and blindness in Baotou, Inner Mongolia.A cross-sectional study was carried out. Multistage sampling was used to select samples. The visual acuity was estimated using LogMAR and corrected by pinhole as best-corrected visual acuity.There were 7000 samples selected and 5770 subjects included in this investigation. The overall bilateral prevalence rates of low vision and blindness were 3.66% (95% CI: 3.17-4.14) and 0.99% (95% CI: 0.73-1.24), respectively. The prevalence of bilateral low vision, blindness, and visual impairment increased with age and decreased with education level. The main leading cause of low vision and blindness was cataract. Diabetic retinopathy and age-related macular degeneration were found to be the second leading causes of blindness in Baotou.The low vision and blindness were more prevalent in elderly people and subjects with low education level in Baotou. Cataract was the main cause for visual impairment and more attention should be paid to fundus diseases. In order to prevent blindness, much more eye care programs should be established.

Associations and Trends in Cause-Specific Rates of Death Among Persons Reported with HIV Infection, 23 U.S. Jurisdictions, Through 2011.

PubMed

Adih, William K; Selik, Richard M; Hall, H Irene; Babu, Aruna Surendera; Song, Ruiguang

2016-01-01

Published death rates for persons with HIV have not distinguished deaths due to HIV from deaths due to other causes. Cause-specific death rates would allow better assessment of care needs. Using data reported to the US national HIV surveillance system, we examined a) associations between selected decedent characteristics and causes of death during 2007-2011, b) trends in rates of death due to underlying causes among persons with AIDS during 1990-2011, and among all persons with diagnosed HIV infection (with or without AIDS) during 2000-2011. During 2007-2011, non-HIV-attributable causes of death with the highest rates per 1,000 person-years were heart disease (2.0), non-AIDS cancers other than lung cancer (1.4), and accidents (0.8). During 1990-2011, among persons with AIDS, the annual rate of death due to HIV-attributable causes decreased by 89% (from 122.0 to 13.2), and the rate due to non-HIV-attributable-causes decreased by 57% (from 20.0 to 8.6), while the percentage of deaths caused by non-HIV-attributable causes increased from 11% to 43%. During 2000-2011, among persons with HIV infection, the rate of death due to HIV-attributable causes decreased by 69% (from 26.4 to 8.3), and the rate due to non-HIV-attributable causes decreased by 28% (from 10.5 to 7.6), while the percentage of deaths caused by non-HIV-attributable causes increased from 25% to 48%. Among HIV-infected persons, as rates of death due to HIV-attributable causes decreased, rates due to non-HIV-attributable causes also decreased, but the percentages of deaths due to non-HIV-attributable causes, such as heart disease and non-AIDS cancers increased.

Posttranscriptional silencing of the lncRNA MALAT1 by miR-217 inhibits the epithelial–mesenchymal transition via enhancer of zeste homolog 2 in the malignant transformation of HBE cells induced by cigarette smoke extract

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

Lu, Lu; Luo, Fei; Liu, Yi

Lung cancer is regarded as the leading cause of cancer-related deaths, and cigarette smoking is one of the strongest risk factors for the development of lung cancer. However, the mechanisms for cigarette smoke-induced lung carcinogenesis remain unclear. The present study investigated the effects of an miRNA (miR-217) on levels of an lncRNA (MALAT1) and examined the role of these factors in the epithelial–mesenchymal transition (EMT) induced by cigarette smoke extract (CSE) in human bronchial epithelial (HBE) cells. In these cells, CSE caused decreases of miR-217 levels and increases in lncRNA MALAT1 levels. Over-expression of miR-217 with a mimic attenuated themore » CSE-induced increase of MALAT1 levels, and reduction of miR-217 levels by an inhibitor enhanced expression of MALAT1. Moreover, the CSE-induced increase of MALAT1 expression was blocked by an miR-217 mimic, indicating that miR-217 negatively regulates MALAT1 expression. Knockdown of MALAT1 reversed CSE-induced increases of EZH2 (enhancer of zeste homolog 2) and H3K27me3 levels. In addition to the alteration from epithelial to spindle-like mesenchymal morphology, chronic exposure of HBE cells to CSE increased the levels of EZH2, H3K27me3, vimentin, and N-cadherin and decreased E-cadherin levels, effects that were reversed by MALAT1 siRNA or EZH2 siRNA. The results indicate that miR-217 regulation of EZH2/H3K27me3 via MALAT1 is involved in CSE-induced EMT and malignant transformation of HBE cells. The posttranscriptional silencing of MALAT1 by miR-217 provides a link, through EZH2, between ncRNAs and the EMT and establishes a mechanism for CSE-induced lung carcinogenesis. - Highlights: • CSE exposure decreases miR-217 levels and increases MALAT1 levels. • miR-217 negatively regulates MALAT1 expression. • MALAT1, via EZH2, is involved in the EMT of CSE-transformed HBE cells.« less

Perindopril increases the swallowing reflex by inhibiting substance P degradation and tyrosine hydroxylase activation in a rat model of dysphagia.

PubMed

Ikeda, Jun-ichi; Kojima, Natsuki; Saeki, Kohji; Ishihara, Miki; Takayama, Makoto

2015-01-05

Patients with hypertension have a high risk of ischemic stroke and subsequent stroke-associated pneumonia. Stroke-associated pneumonia is most likely to develop in patients with dysphagia. The present study was designed to compare the ameliorative effects of different treatments in rat model of dysphagia. Spontaneously hypertensive rats were treated with bilateral common carotid artery occlusion (BCAO) to induce chronic cerebral hypoperfusion causing disorders of the swallowing reflex. Angiotensin-converting enzyme (ACE) inhibitors (perindopril, imidapril and enalapril), an angiotensin II type 1-receptor blocker (losartan), a vasodilator (hydralazine) and an indirect dopamine agonist (amantadine) were dissolved in drinking water and administered to the rats for six weeks. The blood pressure, the swallowing reflex under anesthesia, the substance P content in the striatum and the tyrosine hydroxylase (TH) expression in the substantial nigra were measured. Compared to the vehicle control, the decrease in the swallowing reflex induced by BCAO was attenuated significantly by enalapril, imidapril and perindopril, but only slightly by losartan. Hydralazine had no effect on the swallowing reflex. Amantadine significantly attenuated the decreased swallowing reflex but increased the blood pressure. Cerebral hypoperfusion for six weeks decreased the TH expression and substance P level. Perindopril improved both the TH expressions and substance P level, but imidapril, enalapril and amantadine only improved the substance P level. The present findings indicate that perindopril could be useful for preventing dysphagia in the chronic stage of stroke by attenuating the decrease in TH expression and the decrease in the substance P level. Copyright © 2014 Elsevier B.V. All rights reserved.

Thyroid function tests in patients taking thyroid medication in Germany: Results from the population-based Study of Health in Pomerania (SHIP).

PubMed

Hannemann, Anke; Friedrich, Nele; Haring, Robin; Krebs, Alexander; Völzke, Henry; Alte, Dietrich; Nauck, Matthias; Kohlmann, Thomas; Schober, Hans-Christof; Hoffmann, Wolfgang; Wallaschofski, Henri

2010-08-16

Studies from iodine-sufficient areas have shown that a high proportion of patients taking medication for thyroid diseases have thyroid stimulating hormone (TSH) levels outside the reference range. Next to patient compliance, inadequate dosing adjustment resulting in under- and over-treatment of thyroid disease is a major cause of poor therapy outcomes. Using thyroid function tests, we aim to measure the proportions of subjects, who are under- or over-treated with thyroid medication in a previously iodine-deficient area. Data from 266 subjects participating in the population-based Study of Health in Pomerania (SHIP) were analysed. All subjects were taking thyroid medication. Serum TSH levels were measured using immunochemiluminescent procedures. TSH levels of < 0.27 or > 2.15 mIU/L in subjects younger than 50 years and < 0.19 or > 2.09 mIU/L in subjects 50 years and older, were defined as decreased or elevated, according to the established reference range for the specific study area. Our analysis revealed that 56 of 190 (29.5%) subjects treated with thyroxine had TSH levels outside the reference range (10.0% elevated, 19.5% decreased). Of the 31 subjects taking antithyroid drugs, 12 (38.7%) had TSH levels outside the reference range (9.7% elevated, 29.0% decreased). These proportions were lower in the 45 subjects receiving iodine supplementation (2.2% elevated, 8.9% decreased). Among the 3,974 SHIP participants not taking thyroid medication, TSH levels outside the reference range (2.8% elevated, 5.9% decreased) were less frequent. In concordance with previous studies in iodine-sufficient areas, our results indicate that a considerable number of patients taking thyroid medication are either under- or over-treated. Improved monitoring of these patients' TSH levels, compared to the local reference range, is recommended.

The effects of gamma radiation, UV and visible light on ATP levels in yeast cells depend on cellular melanization.

PubMed

Bryan, Ruth; Jiang, Zewei; Friedman, Matthew; Dadachova, Ekaterina

2011-10-01

Previously we have shown that growth of melanized fungi is stimulated by low levels of gamma radiation. The goal of this study was to examine the effects of visible light, UV light, and gamma radiation on the energy level (ATP concentration) in melanized Cryptococcus neoformans cells. Melanized C. neoformans cells as well as non-melanized controls were subjected to visible, UV or gamma radiation, and ATP was quantified by measuring the amount of light emitted by the ATP-dependent reaction of luciferase with luciferin. We found that all three forms of radiation led to a reduction in the ATP levels in melanized C. neoformans cells. This points to a universal melanin-related mechanism underlying observation of ATP decrease in irradiated melanized cells. In contrast, in non-melanized cells visible light led to increase in ATP levels; gamma radiation did not cause any changes while UV exposure resulted in some ATP decrease, however, much less pronounced than in melanized cells. Copyright © 2011 British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Berberine exerts renoprotective effects by regulating the AGEs-RAGE signaling pathway in mesangial cells during diabetic nephropathy.

PubMed

Qiu, Yuan-Ye; Tang, Li-Qin; Wei, Wei

2017-03-05

In this study, we explored the effect of berberine treatment on the AGEs-RAGE pathway in a rat model of diabetic nephropathy, and we investigated the mechanism by which key factors caused kidney injury and the effects of berberine. In vivo, berberine improved fasting blood glucose, body weight, the majority of biochemical and renal function parameters and histopathological changes in the diabetic kidney. Western blotting and immunohistochemistry revealed significant increases in the levels of AGEs, RAGE, P-PKC-β and TGF-β1 in injured kidneys, and these levels were markedly decreased by treatment with berberine. In vitro, berberine inhibited mesangial cell proliferation. Cells treated with berberine showed reduced levels of AGEs, accompanied by decreased RAGE, p-PKC and TGF-β1 levels soon afterwards. Berberine exhibited renoprotective effects in diabetic nephropathy rats, and the molecular mechanism was associated with changes in the levels and regulation of the AGEs-RAGE-PKC-β-TGF-β1 signaling pathway. Copyright © 2017 Elsevier B.V. All rights reserved.

Serum levels of sex steroid hormones and matrix metalloproteinases after intra-articular glucocorticoid treatment in female patients with rheumatoid arthritis.

PubMed

Weitoft, T; Larsson, A; Rönnblom, L

2008-03-01

To study metalloproteinase activity and sex steroid hormone production in serum after intra-articular glucocorticoid treatment for knee synovitis. 18 female patients with rheumatoid arthritis and synovitis of the knee with need for intra-articular glucocorticoid treatment were included in this study. Serum samples of matrix metalloproteinases (MMP-1/TIMP complex and MMP-3), dehydroepiandrosterone sulphate, testosterone, oestradiol, steroid hormone binding globulin, follicle stimulating hormone and luteinising hormone were collected before injection with 20 mg triamcinolone hexacetonide, and 24 h, 48 h, 1 week and 2 weeks after injection, respectively. Serum levels of MMP-3 were significantly decreased, but MMP-1/TIMP complex was unaffected. Dehydroepiandrosterone sulphate, testosterone and oestradiol levels all decreased and tended to return to baseline levels during the observation period. Steroid hormone binding globulin, follicle stimulating hormone and luteinising hormone levels were unchanged. Intra-articular glucocorticoid treatment causes a temporary, but considerable suppression of sex steroid hormone secretion. The reduction of MMP-3 indicates an inhibition of the inflammatory, but probably also the cartilage destructive processes within the treated joint.

Effect of coffee consumption on all-cause and total cancer mortality: findings from the JACC study.

PubMed

Tamakoshi, Akiko; Lin, Yingsong; Kawado, Miyuki; Yagyu, Kiyoko; Kikuchi, Shogo; Iso, Hiroyasu

2011-04-01

Coffee consumption is known to be related to various health conditions. Recently, its antioxidant effects have been suggested to be associated with all-cause or cancer mortality by various cohort studies. However, there has been only one small Asian cohort study that has assessed this association. Thus, we tried to assess the association of coffee with all-cause and total cancer mortality by conducting a large-scale cohort study in Japan. A total of 97,753 Japanese men and women aged 40-79 years were followed for 16 years. Hazard ratios and 95% confidence intervals of all-cause and total cancer mortality in relation to coffee consumption were calculated from proportional-hazards regression models. A total of 19,532 deaths occurred during the follow-up period; 34.8% of these deaths were caused by cancer. The all-cause mortality risk decreased with increasing coffee consumption in both men and women, with a risk elevation at the highest coffee consumption level (≥4 cups/day) compared with the 2nd highest consumption level in women, although the number of subjects evaluated at this level was small. No association was found between coffee consumption and total cancer mortality among men, whereas a weak inverse association was found among women. The present cohort study among the Japanese population suggested that there are beneficial effects of coffee on all-cause mortality among both men and women. Furthermore, the results showed that coffee consumption might not be associated with an increased risk of total cancer mortality.

Feasibility of metronomic chemotherapy with tegafur-uracil, cisplatin, and dexamethasone for docetaxel-refractory prostate cancer

PubMed Central

Kubota, Hiroki; Fukuta, Katsuhiro; Yamada, Kenji; Hirose, Masahito; Naruyama, Hiromichi; Yanai, Yoshimasa; Yamada, Yasuyuki; Watase, Hideki; Kawai, Noriyasu; Tozawa, Keiichi; Yasui, Takahiro

2017-01-01

Objectives: To evaluate the efficacy of tegafur–uracil (UFT), a prodrug of 5-fluorouracil, plus cisplatin and dexamethasone in patients with docetaxel-refractory prostate cancers. Methods: Twenty-five patients with docetaxel-refractory prostate cancer were administered oral UFT plus intravenous cisplatin (UFT-P therapy) and dexamethasone. Treatment responses were assessed monthly via prostate-specific antigen (PSA) level measurements. Treatment-related adverse events and overall survival were also assessed. Results: UFT-P therapy resulted in decreased PSA levels in 14 (56%) patients and increased PSA levels in 11 (44%). In patients with increased PSA levels, 7 (64%) of the 11 patients displayed decreased PSA doubling times. The UFT-P therapy response rate was 84% (21/25 patients). Imaging studies revealed that tumor shrinkage during UFT-P therapy occurred in 1 patient in whom bilateral hydronephrosis caused by lymph node metastasis improved. The median survival time from docetaxel initiation was 36 months. In UFT-P-treated patients, the median PSA progression and overall survival times were 6 and 14 months, respectively. UFT-P treatment-related adverse events were mild diarrhea, general fatigue, and anorexia. Treatment was not discontinued for any of the patients. UFT-P therapy did not cause serious hepatic or renal dysfunction or pancytopenia. Conclusions: UFT-P therapy is a safe and effective treatment for patients with docetaxel-refractory prostate cancer, although large-scale, multicenter, prospective studies are needed to validate these findings. PMID:29255528

Biomarkers of Plasmodium falciparum Infection during Pregnancy in Women Living in Northeastern Tanzania

PubMed Central

Boström, Stéphanie; Ibitokou, Samad; Oesterholt, Mayke; Schmiegelow, Christentze; Persson, Jan-Olov; Minja, Daniel; Lusingu, John; Lemnge, Martha; Fievet, Nadine; Deloron, Philippe; Luty, Adrian J. F.; Troye-Blomberg, Marita

2012-01-01

In pregnant women, Plasmodium falciparum infections are an important cause of maternal morbidity as well as fetal and neonatal mortality. Erythrocytes infected by these malaria-causing parasites accumulate through adhesive interactions in placental intervillous spaces, thus evading detection in peripheral blood smears. Sequestered infected erythrocytes induce inflammation, offering the possibility of detecting inflammatory mediators in peripheral blood that could act as biomarkers of placental infection. In a longitudinal, prospective study in Tanzania, we quantified a range of different cytokines, chemokines and angiogenic factors in peripheral plasma samples, taken on multiple sequential occasions during pregnancy up to and including delivery, from P. falciparum-infected women and matched uninfected controls. The results show that during healthy, uninfected pregnancies the levels of most of the panel of molecules we measured were largely unchanged except at delivery. In women with P. falciparum, however, both comparative and longitudinal assessments consistently showed that the levels of IL-10 and IP-10 increased significantly whilst that of RANTES decreased significantly, regardless of gestational age at the time the infection was detected. ROC curve analysis indicated that a combination of increased IL-10 and IP-10 levels and decreased RANTES levels might be predictive of P. falciparum infections. In conclusion, our data suggest that host biomarkers in peripheral blood may represent useful diagnostic markers of P. falciparum infection during pregnancy, but placental histology results would need to be included to verify these findings. PMID:23155405

Opposing Effects of Maternal Hypo- and Hyperthyroidism on the Stability of Thalamocortical Synapses in the Visual Cortex of Adult Offspring.

PubMed

Strobl, Marie-Therese J; Freeman, Daniel; Patel, Jenica; Poulsen, Ryan; Wendler, Christopher C; Rivkees, Scott A; Coleman, Jason E

2017-05-01

Insufficient or excessive thyroid hormone (TH) levels during fetal development can cause long-term neurological and cognitive problems. Studies in animal models of perinatal hypo- and hyperthyroidism suggest that these problems may be a consequence of the formation of maladaptive circuitry in the cerebral cortex, which can persist into adulthood. Here we used mouse models of maternal hypo- and hyperthyroidism to investigate the long-term effects of altering thyroxine (T4) levels during pregnancy (corresponding to embryonic days 6.5-18.5) on thalamocortical (TC) axon dynamics in adult offspring. Because perinatal hypothyroidism has been linked to visual processing deficits in humans, we performed chronic two-photon imaging of TC axons and boutons in primary visual cortex (V1). We found that a decrease or increase in maternal serum T4 levels was associated with atypical steady-state dynamics of TC axons and boutons in V1 of adult offspring. Hypothyroid offspring exhibited axonal branch and bouton dynamics indicative of an abnormal increase in TC connectivity, whereas changes in hyperthyroid offspring were indicative of an abnormal decrease in TC connectivity. Collectively, our data suggest that alterations to prenatal T4 levels can cause long-term synaptic instability in TC circuits, which could impair early stages of visual processing. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

N-(3-Benzoylphenyl)-1H-Indole-2-Carboxamide decreases triglyceride levels by downregulation of Apoc3 gene expression in acute hyperlipidemic rat model.

PubMed

Hamadneh, Lama; Al-Essa, Luay; Hikmat, Suhair; Al-Qirim, Tariq; Abu Sheikha, Ghassan; Al-Hiari, Yusuf; Azmy, Nisrin; Shattat, Ghassan

2017-07-01

Hyperlipidemia is a known cause of coronary vascular diseases, which is a major cause of death in many parts of the world. Targeting several pathways that lead to increase in lipid profiles is of great potential to control diseases. 1H-indole-2-carboxamide derivatives were tested for their hypolipidemic activity at the molecular level in comparison with bezafibrate. The gene expression profiles of lipoprotein signaling and cholesterol metabolism and fatty acid metabolism PCR arrays were determined in rats with acute hyperlipidemia induced by Triton WR1339. Lipid profiles of serum from treated rats showed significant hypolipidemic effect by the compounds. Several genes of potential interest were reported to be overexpressed by Triton WR1339 including Apoc3, Apob, Hmgcs2, Apoa1, Apoe, Apof, acsl1, and Decr1. Most of the overexpressed genes were downregulated by N-(3-Benzoylphenyl)-1H-Indole-2-Carboxamide with significant decreases in Apoc3, Apob, Acaa2, Acsl1, and Slc247a5 gene expression levels. N-(4-Benzoylphenyl)-1H-Indole-2-Carboxamide and bezafibrate did not significantly affect the gene expression levels which were increased with acute hyperlipidemia induced by Triton WR1339. In conclusion, gene expression profiling identified the possible mechanism in which Triton WR1339 induces its acute hyperlipidemic effect which was reversed by the use of N-(3-Benzoylphenyl)-1H-Indole-2-Carboxamide.

Profiling secondary metabolites of needles of ozone-fumigated white pine (Pinus strobus) clones by thermally assisted hydrolysis/methylation GC/MS.

PubMed

Shadkami, F; Helleur, R J; Cox, R M

2007-07-01

Plant secondary metabolites have an important role in defense responses against herbivores and pathogens, and as a chemical barrier to elevated levels of harmful air pollutants. This study involves the rapid chemical profiling of phenolic and diterpene resin acids in needles of two (ozone-tolerant and ozone-sensitive) white pine (Pinus strobus) clones, fumigated with different ozone levels (control, and daily events peaking at 80 and 200 ppb) for 40 days. The phenolic and resin acids were measured using thermally assisted hydrolysis and methylation (THM) gas chromatography/mass spectrometry. Short-term fumigation affected the levels of two phenolic acids, i.e., 3-hydroxybenzoic and 3,4-dihydroxybenzoic acids, in that both showed a substantial decrease in concentration with increased ozone dose. The decrease in concentration of these THM products may be caused by inhibition of the plant's shikimate biochemical pathway caused by ozone exposure. The combined occurrence of these two ozone-sensitive indicators has a role in biomonitoring of ozone levels and its impact on forest productivity. In addition, chromatographic profile differences in the major diterpene resin acid components were observed between ozone-tolerant and ozone-sensitive clones. The resin acids anticopalic, 3-oxoanticopalic, 3beta-hydroxyanticopalic, and 3,4-cycloanticopalic acids were present in the ozone-sensitive pine; however, only anticopalic acid was present in the ozone-tolerant clone. This phenotypic variation in resin acid composition may be useful in distinguishing populations that are differentially adapted to air pollutants.