A missense mutation in the cholesteryl ester transfer protein gene with possible dominant effects on plasma high density lipoproteins.

PubMed Central

Takahashi, K; Jiang, X C; Sakai, N; Yamashita, S; Hirano, K; Bujo, H; Yamazaki, H; Kusunoki, J; Miura, T; Kussie, P

1993-01-01

Plasma HDL are a negative risk factor for atherosclerosis. Cholesteryl ester transfer protein (CETP; 476 amino acids) transfers cholesteryl ester from HDL to other lipoproteins. Subjects with homozygous CETP deficiency caused by a gene splicing defect have markedly elevated HDL; however, heterozygotes have only mild increases in HDL. We describe two probands with a CETP missense mutation (442 D:G). Although heterozygous, they have threefold increases in HDL concentration and markedly decreased plasma CETP mass and activity, suggesting that the mutation has dominant effects on CETP and HDL in vivo. Cellular expression of mutant cDNA results in secretion of only 30% of wild type CETP activity. Moreover, coexpression of wild type and mutant cDNAs leads to inhibition of wild type secretion and activity. The dominant effects of the CETP missense mutation during cellular expression probably explains why the probands have markedly increased HDL in the heterozygous state, and suggests that the active molecular species of CETP may be multimeric. Images PMID:8408659

Tuning the Thermochemical Properties of Oxonol Dyes for Digital Versatile Disc Recordable: Reduction of Thermal Interference in High-Speed Recording

NASA Astrophysics Data System (ADS)

Morishima, Shin-Ichi; Wariishi, Koji; Mikoshiba, Hisashi; Inagaki, Yoshio; Shibata, Michihiro; Hashimoto, Hirokazu; Kubo, Hiroshi

To reduce thermal interference between adjacent recording marks on a recordable digital versatile disc, we examined the thermochemical behavior of oxonol dyes for digital versatile disc recordable (DVD-R). We found that oxonol dyes with Meldrum's acid skeleton exhibited an abrupt reduction in weight with increasing temperature without generating excessive heat that is the fundamental cause of thermal interference. DVD-R with the oxonol dyes suppressed fluctuation in the shapes of recorded marks, thereby attaining compatibility with high-speed recording.

Cardiovascular risk in chronic kidney disease: what is new in the pathogenesis and treatment?

PubMed

Bazyluk, Angelika; Malyszko, Jolanta; Zbroch, Edyta

2018-06-12

The prevalence of chronic kidney disease (CKD) has increased markedly over past decades due to the aging of the worldwide population. Despite the progress in the prevention and treatment, the cardiovascular (CV) morbidity and mortality remain high among patients with CKD. Although CKD is a progressive and irreversible condition, it is possible to slow decreasing kidney function, as well as the development and progression of associated with kidney disease comorbidities. Diabetes mellitus has become major cause of CKD worldwide. It is estimated that the prevalence of diabetes will increase from 425 million worldwide in 2017 to 629 million by 2045, substantially the percentage of diabetic nephropathy among CKD patients is set to rise markedly. The results of multicenter trials concerning novel antidiabetic drugs suggest that efficacy in reducing CV risk is independent of the improvement in glycemic control. This review discusses underlying causes of high CV risk and strategies reducing individual burden among CKD patients.

Gene expression analysis of microtubule affinity-regulating kinase 2 in non-small cell lung cancer.

PubMed

Marshall, Erin A; Ng, Kevin W; Anderson, Christine; Hubaux, Roland; Thu, Kelsie L; Lam, Wan L; Martinez, Victor D

2015-12-01

Lung cancer is the leading cause of cancer death worldwide, and has a five-year survival rate of 18% [1]. MARK2 is a serine/threonine-protein kinase, and is a key component in the phosphorylation of microtubule-associated proteins [2], [3]. A recent study published by Hubaux et al. found that microtubule affinity-regulating kinase 2 (MARK2) showed highly frequent DNA and RNA level disruption in lung cancer cell lines and independent non-small cell lung cancer (NSCLC) cohorts [4]. These alterations result in the acquisition of oncogenic properties in cell lines, such as increased viability and anchorage-independent growth. Furthermore, a microarray-based transcriptome analysis of three short hairpin RNA (shRNA)-mediated MARK2 knockdown lung adenocarcinoma cell lines (GEO#: GSE57966) revealed an association between MARK2 gene expression and cell cycle activation and DNA damage response. Here, we present a detailed description of transcriptome analysis to support the described role of MARK2 in promoting a malignant phenotype.

The Physiological Suppressing Factors of Dry Forage Intake and the Cause of Water Intake Following Dry Forage Feeding in Goats — A Review

PubMed Central

Sunagawa, Katsunori; Nagamine, Itsuki

2016-01-01

The goats raised in the barn are usually fed on fresh grass. As dry forage can be stored for long periods in large amounts, dry forage feeding makes it possible to feed large numbers of goats in barns. This review explains the physiological factors involved in suppressing dry forage intake and the cause of drinking following dry forage feeding. Ruminants consume an enormous amount of dry forage in a short time. Eating rates of dry forage rapidly decreased in the first 40 min of feeding and subsequently declined gradually to low states in the remaining time of the feeding period. Saliva in large-type goats is secreted in large volume during the first hour after the commencement of dry forage feeding. It was elucidated that the marked suppression of dry forage intake during the first hour was caused by a feeding-induced hypovolemia and the loss of NaHCO3 due to excessive salivation during the initial stages of dry forage feeding. On the other hand, it was indicated that the marked decrease in feed intake observed in the second hour of the 2 h feeding period was related to ruminal distension caused by the feed consumed and the copious amount of saliva secreted during dry forage feeding. In addition, results indicate that the marked decreases in dry forage intake after 40 min of feeding are caused by increases in plasma osmolality and subsequent thirst sensations produced by dry forage feeding. After 40 min of the 2 h dry forage feeding period, the feed salt content is absorbed into the rumen and plasma osmolality increases. The combined effects of ruminal distension and increased plasma osmolality accounted for 77.6% of the suppression of dry forage intake 40 min after the start of dry forage feeding. The results indicate that ruminal distension and increased plasma osmolality are the main physiological factors in suppression of dry forage intake in large-type goats. There was very little drinking behavior observed during the first hour of the 2 h feeding period most water consumption occurring in the second hour. The cause of this thirst sensation during the second hour of dry forage feeding period was not hypovolemia brought about by excessive salivation, but rather increases in plasma osmolality due to the ruminal absorption of salt from the consumed feed. This suggests the water intake following dry forage feeding is determined by the level of salt content in the feed. PMID:26732440

Dehydration as a Cause of Chronic Kidney Disease: Role of Fructokinase

DTIC Science & Technology

2016-10-01

mediator system activated by hyperosmolarity is vasopressin. Vasopressin is considered a beneficial hormone as its primary action is to increase water...period, there is a marked increase in serum osmolality that occurs in association with an increase in serum copeptin (a more stable peptide derived...Carr IM, Markham AF, Hayward BE, Asipu A, and Bonthron DT. Both isoforms of ketohexokinase are dispensable for normal growth and development

Effects of drought stress on growth, solute accumulation and membrane stability of leafy vegetable, huckleberry (Solanum scabrum Mill.).

PubMed

Assaha, Dekoum Vincent Marius; Liu, Liyun; Ueda, Akihiro; Nagaoka, Toshinori; Saneoka, Hirofumi

2016-01-01

The present study sought to investigate the factors implicated in growth impairment of huckleberry (a leafy vegetable) under water stress conditions. To achieve this, seedlings of plant were subjected to control, mild stress and severe stress conditions for 30 days. Plant growth, plant water relation, gas exchange, oxidative stress damage, electrolyte leakage rate, mineral content and osmolyte accumulation were measured. Water deficit markedly decreased leaf, stem and root growth. Leaf photosynthetic rate was tremendously reduced by decrease in stomatal conductance under stress conditions. Malondialdehyde (MDA) content markedly increased under mild (82%) and severe (131%) stress conditions, while electrolyte leakage rate (ELR) increased by 59% under mild stress and 3-fold under severe stress. Mineral content in leafwas high in stressed plants, while proline content markedly increased under mild stress (12-fold) and severe stress (15-fold), with corresponding decrease in osmotic potential at full turgor and an increase in osmotic adjustment. These results suggest that maintenance of high mineral content and osmotic adjustment constitute important adaptations in huckleberry under water deficit conditions and that growth depression under drought stress would be mainly caused by increased electrolyte leakage resulting from membrane damage induced by oxidative stress.

Thermal effects of laser marking on microstructure and corrosion properties of stainless steel.

PubMed

Švantner, M; Kučera, M; Smazalová, E; Houdková, Š; Čerstvý, R

2016-12-01

Laser marking is an advanced technique used for modification of surface optical properties. This paper presents research on the influence of laser marking on the corrosion properties of stainless steel. Processes during the laser beam-surface interaction cause structure and color changes and can also be responsible for reduction of corrosion resistance of the surface. Corrosion tests, roughness, microscopic, energy dispersive x-ray, grazing incidence x-ray diffraction, and ferrite content analyses were carried out. It was found that increasing heat input is the most crucial parameter regarding the degradation of corrosion resistance of stainless steel. Other relevant parameters include the pulse length and pulse frequency. The authors found a correlation between laser processing parameters, grazing incidence x-ray measurement, ferrite content, and corrosion resistance of the affected surface. Possibilities and limitations of laser marking of stainless steel in the context of the reduction of its corrosion resistance are discussed.

Rejection elicits emotional reactions but neither causes immediate distress nor lowers self-esteem: a meta-analytic review of 192 studies on social exclusion.

PubMed

Blackhart, Ginette C; Nelson, Brian C; Knowles, Megan L; Baumeister, Roy F

2009-11-01

Competing predictions about the effect of social exclusion were tested by meta-analyzing findings from studies of interpersonal rejection, ostracism, and similar procedures. Rejection appears to cause a significant shift toward a more negative emotional state. Typically, however, the result was an emotionally neutral state marked by low levels of both positive and negative affect. Acceptance caused a slight increase in positive mood and a moderate increase in self-esteem. Self-esteem among rejected persons was no different from neutral controls. These findings are discussed in terms of belongingness motivation, sociometer theory, affective numbing, and self-esteem defenses.

Deanol affects choline metabolism in peripheral tissues of mice.

PubMed

Haubrich, D R; Gerber, N H; Pflueger, A B

1981-08-01

Administration of 2-dimethylaminoethanol (deanol) to mice induced an increase in both the concentration and the rate of turnover of free choline in blood. Treatment with deanol also caused an increase in the concentration of choline in kidneys, and markedly inhibited the rates of oxidation and phosphorylation of intravenously administered [3H-methyl]choline. In the liver, deanol inhibited the rate of phosphorylation of [3H-methyl]choline, but did not inhibit its rate of oxidation or cause an increase in the level of free choline. These findings suggest that deanol increases the choline concentration in blood by inhibition of its metabolism in tissues. Deanol may ultimately produce its central cholinergic effects by inhibition of choline metabolism in peripheral tissues, causing free choline choline to accumulate in blood, enter the brain, and stimulate cholinergic receptors.

INVESTIGATIONS INTO THE CAUSES OF AMPHIBIAN MALFORMATIONS IN THE LAKE CHAMPLAIN BASIN OF NEW ENGLAND (AWARDED PROJECT)

EPA Science Inventory

The concurrent geographic extent and rate of amphibian malformations appear to have markedly increased above background levels in recent years in many states and Canadian provinces as documented by the North American Reporting Center for Amphibian Malformations (www.npwrc.usgs.go...

New insights on the hard-to-boil massecuite phenomenon in raw sugar manufacture

USDA-ARS?s Scientific Manuscript database

Hard-to-boil (HTB) massecuites (mixture of sucrose crystals in molasses) with markedly low heat transfer properties are a sporadic but continuing problem in sugarcane factories, which causes raw sugar and molasses production to decrease and increase, respectively. It usually occurs after severely d...

76 FR 15315 - Agency Forms Undergoing Paperwork Reduction Act Review

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-21

... threats. Surge is defined as a marked increase in demand for resources such as personnel, space and material. Health care providers manage both routine surge (predictable fluctuations in demand associated with the weekly calendar, for example) as well as unusual surge (larger fluctuations in demand caused...

Mössbauer study of conductive oxide glass

NASA Astrophysics Data System (ADS)

Matsuda, Koken; Kubuki, Shiro; Nishida, Tetsuaki

2014-10-01

Heat treatment of barium iron vanadate glass, BaO - Fe2O3- V2O5, at temperatures higher than crystallization temperature causes a marked decrease in resistivity (ρ) from several MΩcm to several Ωcm. 57Fe Mössbauer spectrum of heat-treated vanadate glass shows a marked decrease in quadrupole splitting (Δ) of FeIII, reflecting a structural relaxation, i.e., an increased symmetry of "distorted" FeO4 and VO4 tetrahedra which are connected to each other by sharing corner oxygen atoms. Structural relaxation of 3D-network of vanadate glass accompanies a decrease in the activation energy for the conduction, reflecting a decreased energy gap between the donor level and conduction band. A marked increase in the conductivity was observed in CuO- or Cu2O -containing barium iron vanadate glass after heat treatment at 450 °C for 30 min or more. "n-type semiconductor model combined with small polaron hopping theory" was proposed in order to explain the high conductivity.

THE EFFECTS OF IONIZING RADIATIONS ON THE BIOCHEMISTRY OF MAMMALIAN TISSUES. III. STUDIES ON THE TOXICITY AND MECHANISM OF ACTION OF 2-MERCAPTOETHYLAMINE

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

Hietbrink, B.E.; Yam, K.M.

1964-10-31

A study was conducted to determine the effect of dibenzyline, dihydroergotamine, and adrenal demedullation on the mercaptoethylamine-induced increase in the blood glucose level of adult female rats. The results of these studies showed that the administration of dibenzyline or dihydroergotamine 10 min before 200 mg/kg of MEA inhibited the marked increase in blood glucose levels usually observed following this dose of MEA and substantially reduced the duration of action of this sulfur-containing compound. Adrenal demedullation almost completely prevented the increase in blood glucose levels caused by 200 mg/ kg of MEA. MEA caused a marked hypoglycemia in the demedullated animalsmore » during the latter part of the 5-hr observation period. Results of experiments on the influence of chronic administration of MEA on the blood glucose level of the rat indicated that repeated doses of MEA do not appear to cause drug tolerance. Studies on the influence of MEA on the acetylcholinesterase activity of the brain and serum of rats indicated that the gross toxic symptoms observed following the administration of MEA were not due to cholinesterase inhibition. The results of preliminary studies on the influence of sodium pentobarbital on the acute toxicity of MEA indicated that 25 mg/kg of pentobarbital prevented the lethal effect of doses of MEA as great as 325 mg/kg. (auth)« less

Alterations by peroxisome proliferators of acyl composition of hepatic phosphatidylcholine in rats, mice and guinea-pigs. Role of stearoyl-CoA desaturase.

PubMed Central

Kawashima, Y; Hirose, A; Kozuka, H

1986-01-01

Rats, mice and guinea-pigs were administered p-chlorophenoxyisobutyric acid (clofibric acid) or 2,2'-(decamethylenedithio)diethanol (tiadenol). The treatments of rats and mice with either clofibric acid or tiadenol increased markedly the activities of stearoyl-CoA desaturase, palmitoyl-CoA chain elongation, 1-acylglycerophosphate (1-acyl-GP) acyltransferase and 1-acylglycerophosphocholine (1-acyl-GPC) acyltransferase, but not 2-acylglycerophosphocholine (2-acyl-GPC) acyltransferase in liver microsomes. The treatment of guinea-pigs with clofibric acid did not cause any change in the activities of these enzymes. The treatment of guinea-pigs with tiadenol caused a slight, but significant, increase in the activities of 1-acyl-GP acyltransferase and 1-acyl-GPC acyltransferase. The treatment of rats and mice with either clofibric acid or tiadenol increased markedly the proportion of 18:1 and decreased greatly the proportion of 18:0 in liver microsomal phosphatidylcholine. However, there is a considerable difference in the effects of the two peroxisome proliferators on the composition of polyunsaturated fatty acids in phosphatidylcholine between rats and mice. The treatment of guinea-pigs with either of the two peroxisome proliferators caused no change in acyl composition of phosphatidylcholine. The possible role of stearoyl-CoA desaturation in the regulation of acyl composition of phosphatidylcholine was discussed. PMID:2874791

Stretch marks

MedlinePlus

Stretch marks can appear when there is rapid stretching of the skin. The marks appear as parallel ... often disappear after the cause of the skin stretching is gone. Avoiding rapid weight gain helps reduce ...

Increased incidence of invasive group A streptococcal infections in Sweden, January 2012-February 2013.

PubMed

Darenberg, J; Henriques-Normark, B; Lepp, T; Tegmark-Wisell, K; Tegnell, A; Widgren, K

2013-04-04

The incidence of invasive group A streptococcal infections in Sweden was 6.1 per 100,000 population in 2012, the highest since the disease became notifiable in 2004. Furthermore, January and February 2013 marked a dramatic increase of cases notified, partly explainable by an increase of emm1/T1 isolates, a type previously shown to cause severe invasive disease more often than other types. Healthcare providers in Sweden and health authorities in neighbouring countries have been informed about this increase.

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

Yin, Shengyong; Chen, Xinhua; Xie, Haiyang

Previous studies showed nanosecond pulsed electric field (nsPEF) can ablate solid tumors including hepatocellular carcinoma (HCC) but its effect on cell membrane is not fully understood. We hypothesized nsPEF disrupt the microdomains on outer-cellular membrane with direct mechanical force and as a result the plasma membrane permeability increases to facilitate the small molecule intake. Three HCC cells were pulsed one pulse per minute, an interval longer than nanopore resealing time. The cationized ferritin was used to mark up the electronegative microdomains, propidium iodide (PI) for membrane permeabilization, energy dispersive X-ray spectroscopy (EDS) for the negative cell surface charge and cisplatinmore » for inner-cellular cytotoxicity. We demonstrated that the ferritin marked-microdomain and negative cell surface charge were disrupted by nsPEF caused-mechanical force. The cell uptake of propidium and cytotoxicity of DNA-targeted cisplatin increased with a dose effect. Cisplatin gains its maximum inner-cellular cytotoxicity when combining with nsPEF stimulation. We conclude that nsPEF disrupt the microdomains on the outer cellular membrane directly and increase the membrane permeabilization for PI and cisplatin. The microdomain disruption and membrane infiltration changes are caused by the mechanical force from the changes of negative cell surface charge.« less

Effects of cyclooxygenase inhibitors on the alterations in lung mechanics caused by endotoxemia in the unanesthetized sheep.

PubMed

Snapper, J R; Hutchison, A A; Ogletree, M L; Brigham, K L

1983-07-01

The effects of Escherichia coli endotoxin on lung mechanics, hemodynamics, gas exchange, and lung fluid and solute exchange were studied in 12 chronically instrumented unanesthetized sheep. A possible role for cyclooxygenase products of arachidonate metabolism as mediators of the endotoxin-induced alterations in lung mechanics was investigated by studying sheep before and after cyclooxygenase inhibition with sodium meclofenamate and ibuprofen. Sheep were studied three times in random order: (a) sodium meclofenamate (or ibuprofen) infusion alone; (b) E. coli endotoxin alone; and (c) meclofenamate (or ibuprofen) and endotoxin. Meclofenamate alone had no effect on any of the variables measured. Endotoxin alone caused early marked changes in lung mechanics: resistance to airflow across the lungs (RL) increased 10-fold, dynamic lung compliance (Cdyn) decreased 80% and functional residual capacity (FRC) decreased by greater than 30%. The alveolar-to-arterial oxygen difference (delta AaPO2) increased markedly following endotoxemia. In the presence of sufficient meclofenamate to inhibit accumulation of thromboxane-B2 and 6-keto-prostaglandin F1 alpha in lung lymph, endotoxin caused no increase in RL, Cdyn decreased by less than 40%, and FRC decreased by only 6%. Meclofenamate significantly attenuated the hypoxemia and early pulmonary hypertension caused by endotoxemia but had no effect on the late increases in lung fluid and solute exchange. Ibuprofen had similar effects to those observed with meclofenamate. We conclude that both the pulmonary hypertension and changes in lung mechanics observed after endotoxemia may be mediated, at least in part, by constrictor prostaglandins or thromboxanes and that gas exchange may be improved by preventing endogenous synthesis of these mediators.

Effect of fibre laser marking on surface properties and corrosion resistance of a Fe-Ni-Cr alloy

NASA Astrophysics Data System (ADS)

Astarita, Antonello; Mandolfino, Chiara; Lertora, Enrico; Gambaro, Carla; Squillace, Antonino; Scherillo, Fabio

2017-10-01

Fiber laser techniques are increasing their use in many applications, including modification of material surface properties. In particular they are often used for materials' marking as a non-contact processing. In spite of this, the impact of the laser beam on the surface causes metallurgical and morphological changes. The developments during the laser-material interaction can also affect other surface properties, especially corrosion properties which are crucial in the case of Iron-Nickel alloys. Effect of laser marking on a Fe-Cr-Ni alloy using a Tm-fibre laser (IPG Photonics TRL1904; maximum power: 50W, wavelength: 1904 nm), is described in this paper. In order to evaluate the effect of the laser on corrosion properties a specific ageing test in salt spray has been performed. Moreover, superficial morphology analyses have been performed on samples before and after corrosion tests. Possibilities and limitations of laser marking on these alloys have been discussed, in particular from the point of view of the marked surface corrosion resistance preservation.

Health impacts of the July 2010 heat wave in Québec, Canada.

PubMed

Bustinza, Ray; Lebel, Germain; Gosselin, Pierre; Bélanger, Diane; Chebana, Fateh

2013-01-21

One of the consequences of climate change is the increased frequency and intensity of heat waves which can cause serious health impacts. In Québec, July 2010 was marked by an unprecedented heat wave in recent history. The purpose of this study is to estimate certain health impacts of this heat wave. The crude daily death and emergency department admission rates during the heat wave were analyzed in relation to comparison periods using 95% confidence intervals. During the heat wave, the crude daily rates showed a significant increase of 33% for deaths and 4% for emergency department admissions in relation to comparison periods. No displacement of mortality was observed over a 60-day horizon. The all-cause death indicator seems to be sufficiently sensitive and specific for surveillance of exceedences of critical temperature thresholds, which makes it useful for a heat health-watch system. Many public health actions combined with the increased use of air conditioning in recent decades have contributed to a marked reduction in mortality during heat waves. However, an important residual risk remains, which needs to be more vigorously addressed by public health authorities in light of the expected increase in the frequency and severity of heat waves and the aging of the population.

Abnormal cardiovascular response to exercise in hypertension: contribution of neural factors.

PubMed

Mitchell, Jere H

2017-06-01

During both dynamic (e.g., endurance) and static (e.g., strength) exercise there are exaggerated cardiovascular responses in hypertension. This includes greater increases in blood pressure, heart rate, and efferent sympathetic nerve activity than in normal controls. Two of the known neural factors that contribute to this abnormal cardiovascular response are the exercise pressor reflex (EPR) and functional sympatholysis. The EPR originates in contracting skeletal muscle and reflexly increases sympathetic efferent nerve activity to the heart and blood vessels as well as decreases parasympathetic efferent nerve activity to the heart. These changes in autonomic nerve activity cause an increase in blood pressure, heart rate, left ventricular contractility, and vasoconstriction in the arterial tree. However, arterial vessels in the contracting skeletal muscle have a markedly diminished vasoconstrictor response. The markedly diminished vasoconstriction in contracting skeletal muscle has been termed functional sympatholysis. It has been shown in hypertension that there is an enhanced EPR, including both its mechanoreflex and metaboreflex components, and an impaired functional sympatholysis. These conditions set up a positive feedback or vicious cycle situation that causes a progressively greater decrease in the blood flow to the exercising muscle. Thus these two neural mechanisms contribute significantly to the abnormal cardiovascular response to exercise in hypertension. In addition, exercise training in hypertension decreases the enhanced EPR, including both mechanoreflex and metaboreflex function, and improves the impaired functional sympatholysis. These two changes, caused by exercise training, improve the muscle blood flow to exercising muscle and cause a more normal cardiovascular response to exercise in hypertension. Copyright © 2017 the American Physiological Society.

Researching design and transportation systems for sustainable communities : what can we learn and how can it be applied in Rhode Island.

DOT National Transportation Integrated Search

2009-01-29

There has been a marked growth of interest in the topic of sustainable communities and sustainable transportation due to increased concerns about global warming and climate change. One of the leading causes is urbanization and its impacts on people a...

International Students at the University of California: The Impact on Writing Center Practice

ERIC Educational Resources Information Center

Cross, Sue; Holten, Christine; Picciotto, Madeleine; Ruble, Kelley

2015-01-01

The dramatically increasing number of international students at University of California (UC) campuses has had a marked effect on its campus writing centers, causing a reconsideration of personnel, pedagogy, training, services, and cross-campus partnerships. In this article, writing center administrators and staff at 3 UC campuses--UC Irvine,…

Role of Spm-Cer-S1P signalling pathway in MMP-2 mediated U46619-induced proliferation of pulmonary artery smooth muscle cells: protective role of epigallocatechin-3-gallate.

PubMed

Chowdhury, Animesh; Sarkar, Jaganmay; Chakraborti, Tapati; Chakraborti, Sajal

2015-10-01

During remodelling of pulmonary artery, marked proliferation of pulmonary artery smooth muscle cells (PASMCs) occurs, which contributes to pulmonary hypertension. Thromboxane A2 (TxA2) has been shown to produce pulmonary hypertension. The present study investigates the inhibitory effect of epigallocatechin-3-gallate (EGCG) on the TxA2 mimetic, U46619-induced proliferation of PASMCs. U46619 at a concentration of 10 nM induces maximum proliferation of bovine PASMCs. Both pharmacological and genetic inhibitors of p(38)MAPK, NF-κB and MMP-2 significantly inhibit U46619-induced cell proliferation. EGCG markedly abrogate U46619-induced p(38)MAPK phosphorylation, NF-κB activation, proMMP-2 expression and activation, and also the cell proliferation. U46619 causes an increase in the activation of sphingomyelinase (SMase) and sphingosine kinase (SPHK) and also increase sphingosine 1 phosphate (S1P) level. U46619 also induces phosphorylation of ERK1/2, which phosphorylates SPHK leading to an increase in S1P level. Both pharmacological and genetic inhibitors of SMase and SPHK markedly inhibit U46619-induced cell proliferation. Additionally, pharmacological and genetic inhibitors of MMP-2 markedly abrogate U46619-induced SMase activity and S1P level. EGCG markedly inhibit U46619-induced SMase activity, ERK1/2 and SPHK phosphorylation and S1P level in the cells. Overall, Sphingomyeline-Ceramide-Sphingosine-1-phosphate (Spm-Cer-S1P) signalling axis plays an important role in MMP-2 mediated U46619-induced proliferation of PASMCs. Importantly, EGCG inhibits U46619 induced increase in MMP-2 activation by modulating p(38)MAPK-NFκB pathway and subsequently prevents the cell proliferation. Copyright © 2015 John Wiley & Sons, Ltd.

Marking nut anaphylaxis

PubMed Central

Kral, Anita Christine; Hayball, John; Smith, William B

2016-01-01

Marking nut Semecarpus anacardium, so-called because it contains a pigment that has been used in the past to mark fabrics, is a known cause of contact hypersensitivity. It may be ingested as an ingredient of some traditional Hindi foods. We describe the first reported case of anaphylaxis to marking nut. PMID:27489793

Effects of sympathetic stimulation on cerebral and ocular blood flow. Modification by hypertension, hypercapnia, acetazolamide, PGI2 and papaverine.

PubMed

Beausang-Linder, M

1982-02-01

The effect of unilateral, electrical stimulation of the cervical sympathetic chain in rabbits anesthetized with pentobarbital sodium and vasodilated by hypercapnia, acetazolamide, papaverine or PGI2 was investigated to determine to what extent the sympathetic nerves to the brain and the eye cause vasoconstriction and prevent overperfusion in previously vasodilated animals. Evans blue was given as a tracer for protein leakage. Blood flow determinations were made with the labelled microsphere method during normotension and acute arterial hypertension. Hypertension was induced by ligation of the thoracic aorta and in some animals metaraminol or angiotensin was also used. Acetazolamide caused a two to threefold increase in cerebral blood flow (CBF) and hypercapnia resulted in a fivefold increase. CBF was not markedly affected by papaverine or PGI2. In the choroid plexus, the ciliary body and choroid, papaverine and hypercapnia caused significant blood flow increases on the control side. Sympathetic stimulation induced a 12% blood flow reduction in the brain in normotensive, hypercapnic animals. Marked effects of sympathetic stimulation at normotension were obtained under all conditions in the eye. In the hypertensive state the CBF reduction during sympathetic stimulation was moderate, but highly significant in hypercapnic or papaverine-treated animals as well as in controls. Leakage of Evans blue was more frequently seen on the nonstimulated side of the brain. In the eye there was leakage only on the control side except in PGI2-treated animals where 2 rabbits had bilateral leakage. The effect of sympathetic stimulation on the blood flow in the cerebrum and cerebellum in vasodilated animals seems to be small or absent if the blood pressure is normal. In the eye pronounced vasoconstriction occurs under these conditions. In acute arterial hypertension sympathetic stimulation protects both the cerebral and ocular barriers even under conditions of marked vasodilation.

[Diagnosis and Treatment of Peptic Ulcer Disease: Present and Future Perspective].

PubMed

Kim, Byung Wook

2016-06-25

Peptic ulcer disease is one of the most commonly encountered diseases in gastroenterology clinics. After the discovery of Helicobacter pylori by Warren and Marshall, it has been identified as the most important cause of peptic ulcer. Eradication of H. pylori markedly reduces the post-treatment recurrence rate of peptic ulcer. However, as human populations age, the incidence of cardiovascular and musculoskeletal diseases increases and consequent use of aspirin and non-steroidal anti-in-flammatory drugs increases. Thus causes and presenting patterns of peptic ulcer have changed. In this review, I describe new diagnostic and therapeutic strategies for peptic ulcer disease and explore future perspectives.

The history of dengue outbreaks in the Americas.

PubMed

Brathwaite Dick, Olivia; San Martín, José L; Montoya, Romeo H; del Diego, Jorge; Zambrano, Betzana; Dayan, Gustavo H

2012-10-01

Dengue is a viral disease usually transmitted by Aedes aegypti mosquitoes. Dengue outbreaks in the Americas reported in medical literature and to the Pan American Health Organization are described. The outbreak history from 1600 to 2010 was categorized into four phases: Introduction of dengue in the Americas (1600-1946); Continental plan for the eradication of the Ae. aegypti (1947-1970) marked by a successful eradication of the mosquito in 18 continental countries by 1962; Ae. aegypti reinfestation (1971-1999) caused by the failure of the mosquito eradication program; Increased dispersion of Ae. aegypti and dengue virus circulation (2000-2010) characterized by a marked increase in the number of outbreaks. During 2010 > 1.7 million dengue cases were reported, with 50,235 severe cases and 1,185 deaths. A dramatic increase in the number of outbreaks has been reported in recent years. Urgent global action is needed to avoid further disease spread.

The History of Dengue Outbreaks in the Americas

PubMed Central

Brathwaite Dick, Olivia; San Martín, José L.; Montoya, Romeo H.; del Diego, Jorge; Zambrano, Betzana; Dayan, Gustavo H.

2012-01-01

Dengue is a viral disease usually transmitted by Aedes aegypti mosquitoes. Dengue outbreaks in the Americas reported in medical literature and to the Pan American Health Organization are described. The outbreak history from 1600 to 2010 was categorized into four phases: Introduction of dengue in the Americas (1600–1946); Continental plan for the eradication of the Ae. aegypti (1947–1970) marked by a successful eradication of the mosquito in 18 continental countries by 1962; Ae. aegypti reinfestation (1971–1999) caused by the failure of the mosquito eradication program; Increased dispersion of Ae. aegypti and dengue virus circulation (2000–2010) characterized by a marked increase in the number of outbreaks. During 2010 > 1.7 million dengue cases were reported, with 50,235 severe cases and 1,185 deaths. A dramatic increase in the number of outbreaks has been reported in recent years. Urgent global action is needed to avoid further disease spread. PMID:23042846

Experience of wrong site surgery and surgical marking practices among clinicians in the UK

PubMed Central

Giles, Sally J; Rhodes, Penny; Clements, Gill; Cook, Gary A; Hayton, Ruth; Maxwell, Melanie J; Sheldon, Trevor A; Wright, John

2006-01-01

Background Little is known about the incidence of “wrong site surgery”, but the consequences of this type of medical error can be severe. Guidance from both the USA and more recently the UK has highlighted the importance of preventing error by marking patients before surgery. Objective To investigate the experiences of wrong site surgery and current marking practices among clinicians in the UK before the release of a national Correct Site Surgery Alert. Methods 38 telephone or face‐to‐face interviews were conducted with consultant surgeons in ophthalmology, orthopaedics and urology in 14 National Health Service hospitals in the UK. The interviews were coded and analysed thematically using the software package QSR Nud*ist 6. Results Most surgeons had experience of wrong site surgery, but there was no clear pattern of underlying causes. Marking practices varied considerably. Surgeons were divided on the value of marking and varied in their practices. Orthopaedic surgeons reported that they marked before surgery; however, some urologists and ophthalmologists reported that they did not. There seemed to be no formal hospital policies in place specifically relating to wrong site surgery, and there were problems associated with implementing a system of marking in some cases. The methods used to mark patients also varied. Some surgeons believed that marking was a limited method of preventing wrong site surgery and may even increase the risk of wrong site surgery. Conclusion Marking practices are variable and marking is not always used. Introducing standard guidance on marking may reduce the overall risk of wrong site surgery, especially as clinicians work at different hospital sites. However, the more specific needs of people and specialties must also be considered. PMID:17074875

Trends in mortality risk by education level and cause of death among US White women from 1986 to 2006.

PubMed

Montez, Jennifer Karas; Zajacova, Anna

2013-03-01

To elucidate why the inverse association between education level and mortality risk (the gradient) has increased markedly among White women since the mid-1980s, we identified causes of death for which the gradient increased. We used data from the 1986 to 2006 National Health Interview Survey Linked Mortality File on non-Hispanic White women aged 45 to 84 years (n = 230 692). We examined trends in the gradient by cause of death across 4 time periods and 4 education levels using age-standardized death rates. During 1986 to 2002, the growing gradient for all-cause mortality reflected increasing mortality among low-educated women and declining mortality among college-educated women; during 2003 to 2006 it mainly reflected declining mortality among college-educated women. The gradient increased for heart disease, lung cancer, chronic lower respiratory disease, cerebrovascular disease, diabetes, and Alzheimer's disease. Lung cancer and chronic lower respiratory disease explained 47% of the overall increase. Mortality disparities among White women widened across 1986 to 2006 partially because of causes of death for which smoking is a major risk factor. A comprehensive policy framework should address the social conditions that influence smoking among disadvantaged women.

Participation of the hypophyseal-adrenal cortex system in thrombin clearance during immobilization stress

NASA Technical Reports Server (NTRS)

Kudryashov, B. A.; Uljanov, A. M.; Shapiro, F. B.; Bazazyan, G. G.

1981-01-01

Thrombin marked with I-131 resulted in a considerable increase of the thrombined clearance rate in healthy male rats during stress caused by an immobilization lasting 30 minutes, and in an increase of thrombin clearance occurred by a combination of immobilization and administration of adrenocorticotropin (ACTH). Contrary to ACTH, the thrombin clearance is not stimulated in healthy animals by hydrocortisone. The results of the examination are presented.

Isotopic evidence bearing on Late Triassic extinction events, Queen Charlotte Islands, British Columbia, and implications for the duration and cause of the Triassic/Jurassic mass extinction

USGS Publications Warehouse

Ward, P.D.; Garrison, G.H.; Haggart, J.W.; Kring, D.A.; Beattie, M.J.

2004-01-01

Stable isotope analyses of Late Triassic to earliest Jurassic strata from Kennecott Point in the Queen Charlotte Islands, British Columbia, Canada shows the presence of two distinct and different organic carbon isotope anomalies at the Norian/Rhaetian and Rhaetian/Hettangian (=Triassic/Jurassic) stage boundaries. At the older of these boundaries, which is marked by the disappearance of the bivalve Monotis, the isotope record shows a series of short-lived positive excursions toward heavier values. Strata approaching this boundary show evidence of increasing anoxia. At the higher boundary, marked by the disappearance of the last remaining Triassic ammonites and over 50 species of radiolarians, the isotopic pattern consists of a series of short duration negative anomalies. The two events, separated by the duration of the Rhaetian age, comprise the end-Triassic mass extinction. While there is no definitive evidence as to cause, the isotopic record does not appear similar to that of the impact-caused Cretaceous/Tertiary boundary extinction. ?? 2004 Published by Elsevier B.V.

Influence of Processing in the Solid State Morphology of ABPBI/PBT polymeric Composite Films: X-Ray Studies

DTIC Science & Technology

1982-11-01

ratio is substantially superior to that of steel. Examples of HSHM fibers are: Kevlar , Poly(p-Benzamide), and Poly(p- phenylene Benzobisthiazole). The...is amorphous, but pressure treatment with phenol at 290-3050C for two hours causes it to crystallize. A marked increase in crystallinity of poly(p

A Chemical-Medical Mystery: Gold Jewelry and Black Marks on Skin

NASA Astrophysics Data System (ADS)

Kebbekus, Barbara B.

2000-10-01

Gold jewelry at times makes a black mark or smudge on skin. This may be caused by abrasive powders on the skin (e.g. zinc oxide) but the phenomenon may also be caused by other skin conditions, possibly the presence of chloride ion, acidity, or sulfur-containing amino acids. Some anecdotal evidence is published, but properly designed studies to clarify the actual causes are not available.

Effect of dietary fructose on portal and systemic serum fructose levels in rats and in KHK−/− and GLUT5−/− mice

PubMed Central

Patel, Chirag; Sugimoto, Keiichiro; Douard, Veronique; Shah, Ami; Inui, Hiroshi; Yamanouchi, Toshikazu

2015-01-01

Elevated blood fructose concentrations constitute the basis for organ dysfunction in fructose-induced metabolic syndrome. We hypothesized that diet-induced changes in blood fructose concentrations are regulated by ketohexokinase (KHK) and the fructose transporter GLUT5. Portal and systemic fructose concentrations determined by HPLC in wild-type mice fed for 7 days 0% free fructose were <0.07 mM, were independent of time after feeding, were similar to those of GLUT5−/−, and did not lead to hyperglycemia. Postprandial fructose levels, however, increased markedly in those fed isocaloric 20% fructose, causing significant hyperglycemia. Deletion of KHK prevented fructose-induced hyperglycemia, but caused dramatic hyperfructosemia (>1 mM) with reversed portal to systemic gradients. Systemic fructose in wild-type and KHK−/− mice changed by 0.34 and 1.8 mM, respectively, for every millimolar increase in portal fructose concentration. Systemic glucose varied strongly with systemic, but not portal, fructose levels in wild-type, and was independent of systemic and portal fructose in KHK−/−, mice. With ad libitum feeding for 12 wk, fructose-induced hyperglycemia in wild-type, but not hyperfructosemia in KHK−/− mice, increased HbA1c concentrations. Increasing dietary fructose to 40% intensified the hyperfructosemia of KHK−/− and the fructose-induced hyperglycemia of wild-type mice. Fructose perfusion or feeding in rats also caused duration- and dose-dependent hyperfructosemia and hyperglycemia. Significant levels of blood fructose are maintained independent of dietary fructose, KHK, and GLUT5, probably by endogenous synthesis of fructose. KHK prevents hyperfructosemia and fructose-induced hyperglycemia that would markedly increase HbA1c levels. These findings explain the hyperfructosemia of human hereditary fructosuria as well as the hyperglycemia of fructose-induced metabolic syndrome. PMID:26316589

Nanosecond pulsed electric field (nsPEF) enhance cytotoxicity of cisplatin to hepatocellular cells by microdomain disruption on plasma membrane.

PubMed

Yin, Shengyong; Chen, Xinhua; Xie, Haiyang; Zhou, Lin; Guo, Danjing; Xu, Yuning; Wu, Liming; Zheng, Shusen

2016-08-15

Previous studies showed nanosecond pulsed electric field (nsPEF) can ablate solid tumors including hepatocellular carcinoma (HCC) but its effect on cell membrane is not fully understood. We hypothesized nsPEF disrupt the microdomains on outer-cellular membrane with direct mechanical force and as a result the plasma membrane permeability increases to facilitate the small molecule intake. Three HCC cells were pulsed one pulse per minute, an interval longer than nanopore resealing time. The cationized ferritin was used to mark up the electronegative microdomains, propidium iodide (PI) for membrane permeabilization, energy dispersive X-ray spectroscopy (EDS) for the negative cell surface charge and cisplatin for inner-cellular cytotoxicity. We demonstrated that the ferritin marked-microdomain and negative cell surface charge were disrupted by nsPEF caused-mechanical force. The cell uptake of propidium and cytotoxicity of DNA-targeted cisplatin increased with a dose effect. Cisplatin gains its maximum inner-cellular cytotoxicity when combining with nsPEF stimulation. We conclude that nsPEF disrupt the microdomains on the outer cellular membrane directly and increase the membrane permeabilization for PI and cisplatin. The microdomain disruption and membrane infiltration changes are caused by the mechanical force from the changes of negative cell surface charge. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of Absence of Developing Grain on Carbohydrate Content and Senescence of Maize Leaves

PubMed Central

Allison, J. C. S.; Weinmann, H.

1970-01-01

In maize (Zea mays L.) grown under normal conditions in Rhodesia, prevention of pollination or removal of the ears after flowering caused premature senescence of the leaves above the ear, preceded by the appearance of a purplish red color. In plants from which the ears had been removed the concentration of sugars and starch increased markedly in both upper and lower leaves, the increase being greater in the upper leaves. PMID:16657481

High-Glucose or -Fructose Diet Cause Changes of the Gut Microbiota and Metabolic Disorders in Mice without Body Weight Change.

PubMed

Do, Moon Ho; Lee, Eunjung; Oh, Mi-Jin; Kim, Yoonsook; Park, Ho-Young

2018-06-13

High fat diet-induced changes in gut microbiota have been linked to intestinal permeability and metabolic endotoxemia, which is related to metabolic disorders. However, the influence of a high-glucose (HGD) or high-fructose (HFrD) diet on gut microbiota is largely unknown. We performed changes of gut microbiota in HGD- or HFrD-fed C57BL/6J mice by 16S rRNA analysis. Gut microbiota-derived endotoxin-induced metabolic disorders were evaluated by glucose and insulin tolerance test, gut permeability, Western blot and histological analysis. We found that the HGD and HFrD groups had comparatively higher blood glucose and endotoxin levels, fat mass, dyslipidemia, and glucose intolerance without changes in bodyweight. The HGD- and HFrD-fed mice lost gut microbial diversity, characterized by a lower proportion of Bacteroidetes and a markedly increased proportion of Proteobacteria. Moreover, the HGD and HFrD groups had increased gut permeability due to alterations to the tight junction proteins caused by gut inflammation. Hepatic inflammation and lipid accumulation were also markedly increased in the HGD and HFrD groups. High levels of glucose or fructose in the diet regulate the gut microbiota and increase intestinal permeability, which precedes the development of metabolic endotoxemia, inflammation, and lipid accumulation, ultimately leading to hepatic steatosis and normal-weight obesity.

Diploma Attainment among Teen Mothers. Fact Sheet. Publication #2010-01

ERIC Educational Resources Information Center

Perper, Kate; Peterson, Kristen; Manlove, Jennifer

2010-01-01

Recently released government data show that in 2006, the U.S. teen birth rate began to increase, marking the end of a 14-year period of decline. More specifically, these data show that between 2005 and 2007, the teen birth rate climbed five percent. This trend reversal is a cause for concern, given the negative consequences of teen childbearing…

Effects of defoliation and drought on root food reserves in sugar maple seedlings

Treesearch

Johnson Parker; Johnson Parker

1970-01-01

The artificial defoliation of sugar maple (Acer. saccharum Marsh.) can cause a marked decline in root food reserves, especially starch, and an increase in the levels of the reducing sugars, fructose and glucose. Defoliation can also bring on the dieback-decline syndrome in sugar maples (Parker and Houston 1968). Two experiments designed to examine this question were...

Influence of cadmium stress and arbuscular mycorrhizal fungi on nodule senescence in Cajanus cajan (L.) Millsp.

PubMed

Garg, Neera; Bhandari, Purnima

2012-01-01

Cadmium (Cd) causes oxidative damage and affects nodulation and nitrogen fixation process of legumes. Arbuscular mycorrhizal (AM) fungi have been demonstrated to alleviate heavy metal stress of plants. The present study was conducted to assess role of AM in alleviating negative effects of Cd on nodule senescence in Cajanus cajan genotypes differing in their metal tolerance. Fifteen day-old plants were subjected to Cd treatments--25 mg and 50 mg Cd per kg dry soil and were grown with and without Glomus mosseae. Cd treatments led to a decline in mycorrhizal infection (MI), nodule number and dry weights which was accompanied by reductions in leghemoglobin content, nitrogenase activity, organic acid contents. Cd supply caused a marked decrease in nitrogen (N), phosphorus (P), and iron (Fe) contents. Conversely, Cd increased membrane permeability, thiobarbituric acid reactive substances (TBARS), hydrogen peroxide (H2O2), and Cd contents in nodules. AM inoculations were beneficial in reducing the above mentioned harmful effects of Cd and significantly improved nodule functioning. Activities of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) increased markedly in nodules of mycorrhizal-stressed plants. The negative effects of Cd were genotype and concentration dependent.

A demonstration of athermal effects of continuous microwave irradiation on the growth and antibiotic sensitivity of Pseudomonas aeruginosa PAO1.

PubMed

Nakouti, Ismini; Hobbs, Glyn; Teethaisong, Yothin; Phipps, David

2017-01-01

Stress, caused by exposure to microwaves (2.45 GHz) at constant temperature (37 ± 0.5°C), alters the growth profile of Pseudomonas aeruginosa PAO1. In the absence of microwave treatment a simple, highly reproducible growth curve was observed over 24 h or more. Microwave treatment caused no reduction in growth during the first 6 h, but at a later stage (>12 h) the growth was markedly different to the controls. Secondary growth, typical of the presence of persisters clearly became apparent, as judged by both the dissolved oxygen and the cell density profiles. These treated cells showed distinct morphological changes, but on regrowth these cells reverted to normal. The microwave induced persisters were subject to antibiotic challenge (tobramycin) and showed increased sensitivity when compared to the unstressed planktonic cells. This is in marked contrast to antibiotic induced persisters which show increased resistance. This provides evidence for both a nonthermal effect of microwaves and a previously undescribed route to a novel form of antibiotic susceptible persister cells. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:37-44, 2017. © 2016 American Institute of Chemical Engineers.

Evaluation and differential diagnosis of marked, persistent eosinophilia

PubMed Central

Mejia, Rojelio; Nutman, Thomas B.

2012-01-01

High grade eosinophilia in patients can be a diagnostic dilemma, as the etiologies are extensive and varied. Hypereosinophilic syndromes (HES) are a group of heterogeneous disorders, many of which remain ill-defined. By definition, HES must be distinguished from other disorders with persistently elevated eosinophilia with a defined cause. Although marked eosinophilia worldwide is most commonly caused by helminth (worm) infections, non-infectious causes must be sought including drug reactions, malignancies, and immunologic, inflammatory and allergic diseases. PMID:22449625

[Cyclic fatigue of Vita mark II machinable ceramics under Hertzian's contact].

PubMed

Liu, Wei-Cai; Zhang, Zhi-Shen; Huang, Cheng-Min; Chao, Yong-Lie; Wan, Qian-Bing

2006-08-01

To investigate the cyclic fatigue modes of Vita mark II machinable ceramics under Hertzian's contact. Hertzian's contact technique (WC spheres r = 3.18 mm) was used to investigate the cyclic fatigue of Vita mark II machinable ceramic. All specimens were fatigued by cyclic loading in moist environment, furthermore, surviving strength was examined by three point test and morphology damage observation. In homogeneous Vita mark II machinable ceramics, two fatigue damage modes existed after cyclic loading with spheres under moist environment, including conventional tensile-driven cone cracking (brittle mode) and shear-driven microdamage accumulation (quasi-plastic mode). The latter generated radial cracks and deeply penetrating secondary cone crack. Initial strength degradation were caused by the cone cracks, subsequent and much more deleterious loss was caused by radial cracks. Cyclic fatigue modes of Vita mark II machinable ceramics includes brittle and quasi-plastic mode.

Design and Fabrication of Automatic Glass Cutting Machine

NASA Astrophysics Data System (ADS)

Veena, T. R.; Kadadevaramath, R. S.; Nagaraj, P. M.; Madhusudhan, S. V.

2016-09-01

This paper deals with the design and fabrication of the automatic glass or mirror cutting machine. In order to increase the accuracy of cut and production rate; and decrease the production time and accidents caused due to manual cutting of mirror or glass, this project aims at development of an automatic machine which uses a programmable logic controller (PLC) for controlling the movement of the conveyer and also to control the pneumatic circuit. In this machine, the work of the operator is to load and unload the mirror. The cutter used in this machine is carbide wheel with its cutting edge ground to a V-shaped profile. The PLC controls the pneumatic cylinder and intern actuates the cutter along the glass, a fracture layer is formed causing a mark to be formed below the fracture layer and a crack to be formed below the rib mark. The machine elements are designed using CATIA V5R20 and pneumatic circuit are designed using FESTO FLUID SIM software.

2, 4, 6-Trithiol-1, 3, 5-Triazine-Modified Gold Nanoparticles and Its Potential as Formalin Detector

NASA Astrophysics Data System (ADS)

Yulizar, Y.; Ariyanta, H. A.; Rakhmania, L.; Hafizah, M. A. E.

2018-04-01

Stabilized gold nanoparticles (AuNP) have been successfully prepared by a modification of ligand 2, 4, 6-trithiol-1, 3, 5-triazine (TT). TT has three thiol groups and nitrogen atoms on the aromatic ring that can interact and stabilize AuNP. TT modified AuNP (AuNP/TT) was characterized using UV-Vis spectrophotometer, particle size analyzer (PSA) and transmission electron microscopy (TEM). The characterization showed that AuNP/TT stable at a maximum wavelength (λmaks) of 537 nm with the particle diameter of 9.41 nm. The increased acidity (pH) causes the protonated thiol groups of TT marked with a visual change of colloidal AuNP/TT from purple to blue, causing AuNP and TT bonds weakened. In this study, the AuNP/TT was reacted with formalin. This interaction shows that AuNP/TT has a potential as an efficient detector of formalin, marked by changes in the diameter of the particle, colloidal color, and maximum wavelength shift.

Transient receptor potential ankyrin 1 mediates chronic pancreatitis pain in mice.

PubMed

Cattaruzza, Fiore; Johnson, Cali; Leggit, Alan; Grady, Eileen; Schenk, A Katrin; Cevikbas, Ferda; Cedron, Wendy; Bondada, Sandhya; Kirkwood, Rebekah; Malone, Brian; Steinhoff, Martin; Bunnett, Nigel; Kirkwood, Kimberly S

2013-06-01

Chronic pancreatitis (CP) is a devastating disease characterized by persistent and uncontrolled abdominal pain. Our lack of understanding is partially due to the lack of experimental models that mimic the human disease and also to the lack of validated behavioral measures of visceral pain. The ligand-gated cation channel transient receptor potential ankyrin 1 (TRPA1) mediates inflammation and pain in early experimental pancreatitis. It is unknown if TRPA1 causes fibrosis and sustained pancreatic pain. We induced CP by injecting the chemical agent trinitrobenzene sulfonic acid (TNBS), which causes severe acute pancreatitis, into the pancreatic duct of C57BL/6 trpa1(+/+) and trpa1(-/-) mice. Chronic inflammatory changes and pain behaviors were assessed after 2-3 wk. TNBS injection caused marked pancreatic fibrosis with increased collagen-staining intensity, atrophy, fatty replacement, monocyte infiltration, and pancreatic stellate cell activation, and these changes were reflected by increased histological damage scores. TNBS-injected animals showed mechanical hypersensitivity during von Frey filament probing of the abdomen, decreased daily voluntary wheel-running activity, and increased immobility scores during open-field testing. Pancreatic TNBS also reduced the threshold to hindpaw withdrawal to von Frey filament probing, suggesting central sensitization. Inflammatory changes and pain indexes were significantly reduced in trpa1(-/-) mice. In conclusion, we have characterized in mice a model of CP that resembles the human condition, with marked histological changes and behavioral measures of pain. We have demonstrated, using novel and objective pain measurements, that TRPA1 mediates inflammation and visceral hypersensitivity in CP and could be a therapeutic target for the treatment of sustained inflammatory abdominal pain.

Co-administration of pentoxifylline and thiopental causes death by acute pulmonary oedema in rats

PubMed Central

Pereda, J; Gómez-Cambronero, L; Alberola, A; Fabregat, G; Cerdá, M; Escobar, J; Sabater, L; García-de-la-Asuneión, J; Viña, J; Sastre, J

2006-01-01

Background and purpose: Pentoxifylline exhibits rheological properties that improve microvascular flow and it is widely used in vascular perfusion disorders. It also exhibits marked anti-inflammatory properties by inhibiting tumour necrosis factor α production. Thiopental is one of the most widely used drugs for rapid induction of anaesthesia. During experimental studies on the treatment of acute pancreatitis, we observed that when pentoxifylline was administered after anaesthesia with thiopental, most of the rats exhibited dyspnea, signs of pulmonary oedema and died. The aim of the work described here was to investigate the cause of the unexpected toxic effect of the combined treatment with thiopental and pentoxifylline. Experimental approach: Pulmonary vascular permeability and arterial blood gases were measured, and a histological analysis was performed. The possible role of haemodynamic changes in the formation of pulmonary oedema was also assessed. Key results: Co-administration of pentoxifylline and thiopental increased pulmonary vascular permeability and markedly decreased arterial pO2, with one third of rats suffering from hypoxemia. This combined treatment caused death by acute pulmonary oedema in 27% of normal rats and aggravated the respiratory insufficiency associated with acute pancreatitis in which the mortality rate increased to 60%. This pulmonary oedema was not mediated by cardiac failure or by pulmonary hypertension. Conclusions and Implications: Co-administration of pharmacological doses of pentoxifylline and thiopental caused pulmonary oedema and death in rats. Consequently, pentoxifylline should not be administered when anaesthesia is induced with thiopental to avoid any possible risk of acute pulmonary oedema and death in humans. PMID:16953192

Markedly severe dystonia in Japanese encephalitis.

PubMed

Kalita, J; Misra, U K

2000-11-01

Encephalitis has been reported to be a rare cause of severe dystonia. We describe five patients with markedly severe dystonia from Japanese encephalitis. These patients with markedly severe dystonia were seen during the past 8 years as a subgroup of 50 patients with Japanese encephalitis. The diagnosis of markedly severe dystonia was based on increasingly frequent episodes of generalized dystonia with bulbar, respiratory, or metabolic derangement or leading to exhaustion or pain. The diagnosis of JE was based on clinicoradiologic features and a fourfold increase of hemagglutination-inhibiting antibody titers in paired serum. The outcome of the patients was defined as a good, partial, or poor recovery on the basis of 1-year clinical status. All the patients were males, and their ages ranged from 6 to 19 years. Movement disorders appeared 1 to 3 weeks after the illness as the level of consciousness started improving. During the next 1 to 4 weeks, patients began to experience markedly severe dystonia. It was associated with marked axial dystonia resulting in opisthotonus and retrocollis in five patients, jaw-opening dystonia in two patients, teeth clenching in one patient, and oculogyric crisis and neck deviation in another patient. The attacks of markedly severe dystonia lasted for 2 to 30 minutes and occurred as many as 20 to 30 times daily. Other developments included fixed limb dystonia in one patient, severe spasticity and rigidity in five patients, and focal muscle wasting in one patient. These patients had only a modest improvement after treatment. Markedly severe dystonia abated by 2 to 6 months in all the patients who were followed up. Cranial magnetic resonance imaging showed bilateral thalamic involvement in all patients, brainstem involvement in three patients, and basal ganglia involvement in two patients. At the 3-month follow-up, all patients had a poor outcome. At 1 year, one patient had a complete recovery; one had a partial recovery; and two were bedridden. It can be concluded that markedly severe dystonia is an important and serious sequela of Japanese encephalitis and may occur as the result of thalamus, midbrain, or basal ganglia involvement in various combinations.

Long-term overexpression of human granulocyte colony-stimulating factor in transgenic mice: persistent neutrophilia with no increased mortality for more than one year.

PubMed

Serizawa, I; Amano, K; Ishii, H; Ichikawa, T; Kusaka, M; Taguchi, T; Kiyokawa, N; Fujimoto, J

2000-06-01

To investigate possible adverse consequences of persistent neutrophil overproduction, mice transgenic for human granulocyte colony-stimulating factor (hG-CSF) were studied for more than 1 year. They showed marked granulocytopoiesis and neutrophilia. Continuous medullary and extramedullary granulocytopoiesis resulted in marked changes in bone and liver. In the liver, haemorrhage and focal necrosis and a few haemangiosarcomas were present, presumably caused by the destructive granulocytopoiesis. Despite the high incidence of lung infiltration by mature neutrophils, lung lesions rarely appeared. Although there was a persistent increase in neutrophils, mortality of the mice did not differ from that of non-transgenic littermates at least within 1 year after birth. Factors other than overproduction of G-CSF and extensive neutrophilia could be required for the development of neutrophil-mediated acute and chronic tissue damage. Copyright 2000 Academic Press.

Hematological parameters of Ameiva ameiva (Reptilia: Teiidae) naturally infected with hemogregarine: confirmation of monocytosis.

PubMed

Bonadiman, Sergio F; Miranda, Farlen J B; Ribeiro, Maria Lucia S; Rabelo, Guilherme; Lainson, Ralph; Silva, Edilene O; DaMatta, Renato A

2010-07-15

Little is known on how hematozoan infection changes reptile hematology. The lizard Ameiva ameiva is widely distributed in the Americas and is infected by hematozoan parasites. Previous studies on this lizard have shown that the parasite of monocytes causes a variety of ultrastructural changes in infected host cells. The present study reports that this infection does not cause any change to the erythrocytic values. However, a marked increase in the number of leukocytes (especially monocytes) was detected. This indicates that the hemogregarine not only modulates the infected monocyte, but also increases the blood pool of this leukocyte. A Plasmodium sp was also found infecting erythrocytes of one lizard. Copyright (c) 2010 Elsevier B.V. All rights reserved.

A case of unilateral nephrectomy performed for autosomal dominant polycystic kidney disease with marked unilateral enlargement.

PubMed

Makabe, Shiho; Kataoka, Hiroshi; Kondo, Tsunenori; Tanabe, Kazunari; Tsuchiya, Ken; Nitta, Kosaku; Mochizuki, Toshio

2018-05-01

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the occurrence of multiple cysts that increase the size of both kidneys, progressively reducing kidney function. Usually the cysts occur bilaterally, and there is no difference in the degree of cyst enlargement between the left and right. Here, we report a case of ADPKD in which kidney size increased markedly on the left side and was accompanied by severe abdominal distension and discomfort. Renal dynamic scintigraphy revealed a severe reduction in function of the left kidney compared with the right. Open left nephrectomy was performed. No change in renal function was observed postoperatively [preoperative estimated glomerular filtration rate (eGFR): 57.6 mL/min/1.73 m 2 , 3-month postoperative eGFR: 56.4 mL/min/1.73 m 2 ], and the abdominal symptoms subsided. When one kidney is markedly larger than the other, the cause and status of the laterality should be evaluated by using renal dynamic scintigraphy in addition to other examinations such as computed tomography or magnetic resonance imaging. Unilateral nephrectomy should be considered as a potential treatment.

Functional changes in cerebral 5-hydroxytryptamine metabolism in the mouse induced by anticonvulsant drugs.

PubMed Central

Chadwick, D; Gorrod, J W; Jenner, P; Marsden, C D; Reynolds, E H

1978-01-01

1 Acute administration of clonazepam, diazepam, and diphenylhydantoin to mice elevated cerebral 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA); chronic administration had less effect. 2 Acute administration of clonazepam and diazepam but not diphenylhydantoin raised cerebral trytophan levels; chronic administration of clonazepam caused a smaller elevation of cerebral tryptophan but chronic administration of diazepam still caused a large rise in cerebral tryptophan. 3 Neither clonazepam nor diazepam caused induction of drug metabolizing enzymes on chronic administration but diphenylhydantoin had a marked effect. 4 These data suggest that the altered 5-HT metabolism caused by these compounds is unrelated to a common action on tryptophan levels, and that the reduced effect of clonazepam and diazepam on chronic administration cannot be attributed to increased metabolism of these compounds. 5 Clonazepam induced abnormal head movements in mice in a dose-dependent manner. Pretreatment of animals with tranylcypromine increased the intensity of movement, although pargyline was without effect. Similar effects were observed with diazepam and diphenylhydantoin, suggesting that the increase in cerebral 5-HT caused by these compounds is of functional significance in stimulating 5-HT receptors. PMID:620092

Are deep-sea ecosystems surrounding Madagascar threatened by land-use or climate change?

NASA Astrophysics Data System (ADS)

Fontanier, Christophe; Mamo, Briony; Toucanne, Samuel; Bayon, Germain; Schmidt, Sabine; Deflandre, Bruno; Dennielou, Bernard; Jouet, Gwenael; Garnier, Eline; Sakai, Saburo; Lamas, Ruth Martinez; Duros, Pauline; Toyofuku, Takashi; Salé, Aurélien; Belleney, Déborah; Bichon, Sabrina; Boissier, Audrey; Chéron, Sandrine; Pitel, Mathilde; Roubi, Angélique; Rovere, Mickaël; Grémare, Antoine; Dupré, Stéphanie; Jorry, Stéphan J.

2018-01-01

In this short communication, we present a multidisciplinary study of sedimentary records collected from a deep-sea interfluve proximal to the mouths of major northwestern Madagascan rivers. For the last 60 years, the seafloor has been repeatedly disturbed by the deposition of organic rich, tropical, terrestrial sediments causing marked reductions in benthic biodiversity. Increased soil erosion due to local land-use, deforestation and intensifying tropical cyclones are potential causes for this sedimentary budget and biodiversity shift. Our marine sedimentary records indicate that until now, these conditions have not occurred within the region for at least 20,000 years.

Mutational Signature Mark Cancer’s Smoking Gun

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

Alexandrov, Ludmil

A broad computational study of cancer genome sequences by Los Alamos National Laboratory with the UK’s Wellcome Trust Sanger Institute and other collaborators identifies telltale mutational signatures associated with smoking tobacco. The research demonstrates, for the first time, that smoking increases cancer risk by causing somatic mutations in tissues directly and indirectly exposed to tobacco smoke. The international study was published in the November 4 issue of Science. The analysis shows that tobacco smoking causes mutations leading to cancer by multiple distinct mechanisms, including by damaging DNA in organs and by speeding up a mutational cellular clock.

Mutational Signature Mark Cancer’s Smoking Gun

ScienceCinema

Alexandrov, Ludmil

2018-06-13

A broad computational study of cancer genome sequences by Los Alamos National Laboratory with the UK’s Wellcome Trust Sanger Institute and other collaborators identifies telltale mutational signatures associated with smoking tobacco. The research demonstrates, for the first time, that smoking increases cancer risk by causing somatic mutations in tissues directly and indirectly exposed to tobacco smoke. The international study was published in the November 4 issue of Science. The analysis shows that tobacco smoking causes mutations leading to cancer by multiple distinct mechanisms, including by damaging DNA in organs and by speeding up a mutational cellular clock.

How Social Preferences Shape Incentives in (Experimental) Markets for Credence Goods.

PubMed

Kerschbamer, Rudolf; Sutter, Matthias; Dulleck, Uwe

2017-03-01

Credence goods markets suffer from inefficiencies caused by superior information of sellers about the surplus-maximising quality. While standard theory predicts that equal mark-up prices solve the credence goods problem if customers can verify the quality received, experimental evidence indicates the opposite. We identify a lack of robustness with respect to heterogeneity in social preferences as a possible cause of this and conduct new experiments that allow for parsimonious identification of sellers' social preference types. Our results confirm the assumed heterogeneity in social preferences and provide strong support for our explanation of the failure of verifiability to increase efficiency.

Diet-induced obesity mediated by the JNK/DIO2 signal transduction pathway

PubMed Central

Vernia, Santiago; Cavanagh-Kyros, Julie; Barrett, Tamera; Jung, Dae Young; Kim, Jason K.; Davis, Roger J.

2013-01-01

The cJun N-terminal kinase (JNK) signaling pathway is a key mediator of metabolic stress responses caused by consuming a high-fat diet, including the development of obesity. To test the role of JNK, we examined diet-induced obesity in mice with targeted ablation of Jnk genes in the anterior pituitary gland. These mice exhibited an increase in the pituitary expression of thyroid-stimulating hormone (TSH), an increase in the blood concentration of thyroid hormone (T4), increased energy expenditure, and markedly reduced obesity compared with control mice. The increased amount of pituitary TSH was caused by reduced expression of type 2 iodothyronine deiodinase (Dio2), a gene that is required for T4-mediated negative feedback regulation of TSH expression. These data establish a molecular mechanism that accounts for the regulation of energy expenditure and the development of obesity by the JNK signaling pathway. PMID:24186979

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

A syndrome of multiorgan hyperplasia with features of gigantism, tumorigenesis, and female sterility in p27(Kip1)-deficient mice.

PubMed

Fero, M L; Rivkin, M; Tasch, M; Porter, P; Carow, C E; Firpo, E; Polyak, K; Tsai, L H; Broudy, V; Perlmutter, R M; Kaushansky, K; Roberts, J M

1996-05-31

Targeted disruption of the murine p27(Kip1) gene caused a gene dose-dependent increase in animal size without other gross morphologic abnormalities. All tissues were enlarged and contained more cells, although endocrine abnormalities were not evident. Thymic hyperplasia was associated with increased T lymphocyte proliferation, and T cells showed enhanced IL-2 responsiveness in vitro. Thus, p27 deficiency may cause a cell-autonomous defect resulting in enhanced proliferation in response to mitogens. In the spleen, the absence of p27 selectively enhanced proliferation of hematopoietic progenitor cells. p27 deletion, like deletion of the Rb gene, uniquely caused neoplastic growth of the pituitary pars intermedia, suggesting that p27 and Rb function in the same regulatory pathway. The absence of p27 also caused an ovulatory defect and female sterility. Maturation of secondary ovarian follicles into corpora lutea, which express high levels of p27, was markedly impaired.

[Fungal population structure and its biological effect in rhizosphere soil of continuously cropped potato].

PubMed

Meng, Pin-Pin; Liu, Xing; Qiu, Hui-Zhen; Zhang, Wen-Ming; Zhang, Chun-Hong; Wang, Di; Zhang, Jun-Lian; Shen, Qi-Rong

2012-11-01

Continuous cropping obstacle is one of the main restriction factors in potato industry. In order to explore the mechanisms of potato's continuous cropping obstacle and to reduce the impact on potato's tuber yield, a field experiment combined with PCR-DGGE molecular fingerprinting was conducted to investigate the fungal population structure and its biological effect in rhizosphere soil of continuously cropped potato. With the increasing year of potato' s continuous cropping, the numbers of visible bands in rhizosphere fungal DGGE profiles increased obviously. As compared with that of CK (rotation cropping), the operational taxonomic unit (OTU) in treatments of one to five years continuous cropping was increased by 38.5%, 38.5%, 30.8%, 46.2%, and 76.9% respectively, indicating that potato's continuous cropping caused an obvious increase in the individual numbers of dominant fungal populations in rhizosphere soil. Also with the increasing year of potato's continuous cropping, the similarity of the fungal population structure among the treatments had a gradual decrease. The sequencing of the fungal DGGE bands showed that with the increasing year of continuous cropping, the numbers of the potato's rhizosphere soil-borne pathogens Fusarium oxysporum and F. solani increased obviously, while the number of Chaetomium globosum, as a biocontrol species, had a marked decrease in the fifth year of continuous cropping. It was suggested that potato' s continuous cropping caused the pathogen fungal populations become the dominant microbial populations in rhizosphere soil, and the rhizosphere micro-ecological environment deteriorated, which in turn affected the root system, making the root vigor and its absorption area reduced, and ultimately, the tuber yield decreased markedly.

[Three cases of the malignant esophageal stenosis successfully treated with the Niti-S™ esophageal stent].

PubMed

Isohata, Noriyuki; Naritaka, Yoshihiko; Asaka, Shinichi; Shimakawa, Takeshi; Miyaki, Akira; Yamaguchi, Kentaro; Murayama, Minoru; Katsube, Takao; Ogawa, Kenji

2011-11-01

We herein report three cases of the malignant esophageal stenosis successfully treated with the Niti-S™ esophageal stent. CASE 1: The hilar lung cancer and its mediastinal lymph node metastasis pressed the esophagus extramurally and caused the marked stenosis. CASE 2: A metastatic lymph node along the left laryngeal nerve caused the stenosis of the trachea. A primary esophageal lesion located at the middle thoracic esophagus also caused the marked stenosis. At first, tracheal stent was placed because of dyspnea, and two weeks later, we placed an esophageal stent. Case 3: Esophageal cancer at lower thoracic esophagus after definitive radiation therapy caused the marked stenosis. Because of the stenosis of esophago-gastric junction( EGJ), we used an esophageal stent with a long cover in order to prevent a reflux into the esophagus. This new Niti-STM esophageal stent was easy to place at the stenosis without difficulty using a conventional device. The symptom was improved immediately for each case. We hope this new device will be used widely.

Chronic intermittent hypoxia and acetaminophen induce synergistic liver injury in mice.

PubMed

Savransky, Vladimir; Reinke, Christian; Jun, Jonathan; Bevans-Fonti, Shannon; Nanayakkara, Ashika; Li, Jianguo; Myers, Allen C; Torbenson, Michael S; Polotsky, Vsevolod Y

2009-02-01

Obstructive sleep apnoea (OSA) leads to chronic intermittent hypoxia (CIH) during sleep. Obstructive sleep apnoea has been associated with liver injury. Acetaminophen (APAP; known as paracetamol outside the USA) is one of the most commonly used drugs which has known hepatotoxicity. The goal of the present study was to examine whether CIH increases liver injury, hepatic oxidative stress and inflammation induced by chronic APAP treatment. Adult C57BL/6J mice were exposed to CIH or intermittent air (IA) for 4 weeks. Mice in both groups were treated with intraperitoneal injections of either APAP (200 mg kg(-1)) or normal saline daily. A combination of CIH and APAP caused liver injury, with marked increases in serum alanine aminotransferase, aspartate aminotransferase (AST), gamma-glutamyl transferase and total bilirubin levels, whereas CIH alone induced only elevation in serum AST levels. Acetaminophen alone did not affect serum levels of liver enzymes. Histopathology revealed hepatic necrosis and increased apoptosis in mice exposed to CIH and APAP, whereas the liver remained intact in all other groups. Mice exposed to CIH and APAP exhibited decreased hepatic glutathione in conjunction with a fivefold increase in nitrotyrosine levels, suggesting formation of toxic peroxynitrite in hepatocytes. Acetaminophen or CIH alone had no effect on either glutathione or nitrotyrosine. A combination of CIH and APAP caused marked increases in pro-inflammatory chemokines, monocyte chemoattractant protein-1 and macrophage inflammatory protein-2, which were not observed in mice exposed to CIH or APAP alone. We conclude that CIH and chronic APAP treatment lead to synergistic liver injury, which may have clinical implications for patients with OSA.

Chronic Intermittent Hypoxia and Acetaminophen Induce Synergistic Liver Injury

PubMed Central

Savransky, Vladimir; Reinke, Christian; Jun, Jonathan; Bevans-Fonti, Shannon; Nanayakkara, Ashika; Li, Jianguo; Myers, Allen C.; Torbenson, Michael S.; Polotsky, Vsevolod Y.

2010-01-01

Obstructive sleep apnea (OSA) leads to chronic intermittent hypoxia (CIH) during sleep. OSA has been associated with liver injury. Acetaminophen (APAP) is one of the most commonly used drugs, which has known hepatotoxicity. The goal of the present study was to examine whether CIH increases liver injury, hepatic oxidative stress and inflammation induced by chronic APAP treatment. C57BL/6J mice were exposed to CIH or intermittent air (IA) for 4 weeks. Mice in both groups were treated with intraperitoneal injections of either APAP (200 mg/kg) or normal saline daily. A combination of CIH and APAP caused liver injury with marked increases in serum alanine aminotransferase, aspartate aminotransferase (AST), gamma glutamyl transferase and total bilirubin levels, whereas CIH alone induced only elevation in serum AST levels. APAP alone did not affect serum levels of liver enzymes. Histopathology revealed hepatic necrosis and increased apoptosis in mice exposed to CIH and APAP, whereas the liver remained intact in all other groups. Mice exposed to CIH and APAP exhibited decreased hepatic glutathione in conjunction with a five-fold increase in nitrotyrosine levels, suggesting formation of toxic peroxynitrite in hepatocytes. APAP or CIH alone had no effect on either glutathione or nitrotyrosine. A combination of CIH and APAP caused marked increases in pro-inflammatory chemokines, monocyte chemoattractant protein-1 and macrophage inflammatory protein-2, which were not observed in mice exposed to CIH or APAP alone. We conclude that CIH and chronic APAP treatment lead to synergistic liver injury, which may have clinical implications for patients with OSA. PMID:19028810

Studies of the hormonal control of postnatal testicular descent in the rat.

PubMed

Spencer, J R; Vaughan, E D; Imperato-McGinley, J

1993-03-01

Dihydrotestosterone is believed to control the transinguinal phase of testicular descent based on hormonal manipulation studies performed in postnatal rats. In the present study, these hormonal manipulation experiments were repeated, and the results were compared with those obtained using the antiandrogens flutamide and cyproterone acetate. 17 beta-estradiol completely blocked testicular descent, but testosterone and dihydrotestosterone were equally effective in reversing this inhibition. Neither flutamide nor cyproterone acetate prevented testicular descent in postnatal rats despite marked peripheral antiandrogenic action. Further analysis of the data revealed a correlation between testicular size and descent. Androgen receptor blockade did not produce a marked reduction in testicular size and consequently did not prevent testicular descent, whereas estradiol alone caused marked testicular atrophy and testicular maldescent. Reduction of the estradiol dosage or concomitant administration of androgens or human chorionic gonadotropin resulted in both increased testicular size and degree of descent. These data suggest that growth of the neonatal rat testis may contribute to its passage into the scrotum.

Traumatic brain injury in the Netherlands, trends in emergency department visits, hospitalization and mortality between 1998 and 2012.

PubMed

Van den Brand, Crispijn L; Karger, Lennard B; Nijman, Susanne T M; Hunink, Myriam G M; Patka, Peter; Jellema, Korné

2017-03-06

Traumatic brain injury (TBI) is a major cause of morbidity and mortality worldwide. The effects of epidemiological changes such as ageing of the population and increased traffic safety on the incidence of TBI are unknown. The objective of this study was to evaluate trends in TBI-related emergency department (ED) visits, hospitalization and mortality in the Netherlands between 1998 and 2012. This was a retrospective observational, longitudinal study. The main outcome measures were TBI-related ED visits, hospitalization and mortality. Between 1998 and 2012, there were 500 000 TBI-related ED visits in the Netherlands. In the same period, there were 222 000 TBI-related admissions and 17 000 TBI-related deaths. During this period, there was a 75% increase in ED visits for TBI and a 95% increase for TBI-related hospitalization; overall mortality because of TBI did not change significantly. Despite the overall increase in TBI-related ED visits, this increase was not evenly distributed among age groups or trauma mechanisms. In patients younger than 65 years, a declining trend in ED visits for TBI caused by road traffic accidents was observed. Among patients 65 years or older, ED visits for TBI caused by a fall increased markedly. TBI-related mortality shifted from mainly young (67%) and middle-aged individuals (<65 years) to mainly elderly (63%) individuals (≥65 years) between 1998 and 2012. The conclusions of this study did not change when adjusting for changes in age, sex and overall population growth. The incidence of TBI-related ED visits and hospitalization increased markedly between 1998 and 2012 in the Netherlands. TBI-related mortality occurred at an older age. These observations are probably the result of a change in aetiology of TBI, specifically a decrease in traffic accidents and an increase in falls in the ageing population. This hypothesis is supported by our data. However, ageing of the population is not the only cause of the changes observed; the observed changes remained significant when correcting for age and sex. The higher incidence of TBI with a relatively stable mortality rate highlights the importance of clinical decision rules to identify patients with a high risk of poor outcome after TBI.

Residual contamination and corrosion on electrochemically marked uranium

NASA Astrophysics Data System (ADS)

Seals, R. D.; Bullock, J. S.; Cristy, S. S.; Bennett, R. K.

Residual contamination and potential corrosion problems on uranium parts electrochemically marked with PHB-1 and PHB-1E electroetchants have been investigated using ion microprobe mass analysis (IMMA), scanning electron microscopy (SEM), and light microscopy (LM). The effectiveness of various solvent-cleaning sequences and the influence of the use of an abrasive cleaner were evaluated. The corrosion depths and chlorine distributions resulting from the electroetching process were determined. To meet the objective, the surfaces of uranium coupons, which had been processed according to production procedures for parts, i.e., machining, cleaning, marking, inspecting and coating with Shell Vitrea-29® oil, were studied. The greater surface wetting capability of the PHB-1E electroetchant solution relative to PHB-1 resulted in less localized corrosion at the point of attack which provided a more legible mark. Components of the electroetchants (aluminum, potassium and chromium) were found in the marked areas of both types of electroetched samples. Chromium, resulting from the corrosion inhibitor in the electroetchants, was found in the etched areas as well as on the coupon away from the electroetched areas. Depth profile data indicated that the major etching action (marking thickness) of the electroetchants penetrated to a depth of approximately 200 nm. Trace amounts of chlorine were present primarily within the first 65 nm of the marked surface. Comparison of the solvent rinsing sequences revealed that the most effective cleaning process included a degreaser, such as perchloroethylene, followed by a polar solvent, such as alcohol. Evaluation of the use of an abrasive cleaner on the electroetched areas indicates that this process removed residual contaminants, increased mark legibility and did not introduce significant residuals from the abrading material or cause significant surface damage.

Pulmonary infection of cystic fibrosis mice with Staphylococcus aureus requires expression of α-toxin.

PubMed

Keitsch, Simone; Riethmüller, Joachim; Soddemann, Matthias; Sehl, Carolin; Wilker, Barbara; Edwards, Michael J; Caldwell, Charles C; Fraunholz, Martin; Gulbins, Erich; Becker, Katrin Anne

2018-05-01

Pulmonary infections of cystic fibrosis (CF) patients with Staphylococcus aureus (S. aureus) occur very early in the disease. The molecular details that cause infection-susceptibility of CF patients to and mediate infection with S. aureus are poorly characterized. Therefore, we aimed to identify the role of α-toxin, a major S. aureus toxin, for pulmonary infection of CF mice. Infection with S. aureus JE2 resulted in severe pneumonia in CF mice, while wildtype mice were almost unaffected. Deficiency of α-toxin in JE2-Δhla reduced the pathogenicity of S. aureus in CF mice. However, CF mice were still more susceptible to the mutant S. aureus strain than wildtype mice. The S. aureus JE2 induced a marked increase of ceramide and a downregulation of sphingosine and acid ceramidase expression in bronchi of CF mice. Deletion of α-toxin reduced these changes after infection of CF mice. Similar changes were observed in wildtype mice, but at much lower levels. Our data indicate that expression of α-toxin is a major factor causing S. aureus infections in CF mice. Wildtype S. aureus induces a marked increase of ceramide and a reduction of sphingosine and acid ceramidase expression in bronchial epithelial cells of wildtype and CF mice, changes that determine infection susceptibility.

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.

The frequency and extent of sub-ice phytoplankton blooms in the Arctic Ocean

PubMed Central

Horvat, Christopher; Jones, David Rees; Iams, Sarah; Schroeder, David; Flocco, Daniela; Feltham, Daniel

2017-01-01

In July 2011, the observation of a massive phytoplankton bloom underneath a sea ice–covered region of the Chukchi Sea shifted the scientific consensus that regions of the Arctic Ocean covered by sea ice were inhospitable to photosynthetic life. Although the impact of widespread phytoplankton blooms under sea ice on Arctic Ocean ecology and carbon fixation is potentially marked, the prevalence of these events in the modern Arctic and in the recent past is, to date, unknown. We investigate the timing, frequency, and evolution of these events over the past 30 years. Although sea ice strongly attenuates solar radiation, it has thinned significantly over the past 30 years. The thinner summertime Arctic sea ice is increasingly covered in melt ponds, which permit more light penetration than bare or snow-covered ice. Our model results indicate that the recent thinning of Arctic sea ice is the main cause of a marked increase in the prevalence of light conditions conducive to sub-ice blooms. We find that as little as 20 years ago, the conditions required for sub-ice blooms may have been uncommon, but their frequency has increased to the point that nearly 30% of the ice-covered Arctic Ocean in July permits sub-ice blooms. Recent climate change may have markedly altered the ecology of the Arctic Ocean. PMID:28435859

Impact of Saharan dust particles on hospital admissions in Madrid (Spain).

PubMed

Reyes, María; Díaz, Julio; Tobias, Aurelio; Montero, Juan Carlos; Linares, Cristina

2014-01-01

Saharan dust intrusions make a major contribution to levels of particulate matter (PM) present in the atmosphere of large cities. We analysed the impact of different PM fractions during periods with and without Saharan dust intrusions, using time-series analysis with Poisson regression models, based on: concentrations of coarse PM (PM10 and PM10-2.5) and fine PM (PM2.5); and daily all-, circulatory- and respiratory-cause hospital admissions. While periods without Saharan dust intrusions were marked by a statistically significant association between daily mean PM2.5 concentrations and all- and circulatory-cause hospital admissions, periods with such intrusions saw a significant increase in respiratory-cause admissions associated with fractions corresponding to PM10 and PM10-2.5.

[Neutropenia in dogs: etiology and prognostic factors].

PubMed

Cook, Andrea M; Bauer, Natali; Neiger, Reto; Peppler, Christine; Moritz, Andreas

2016-10-12

The aim of this retrospective study was to evaluate frequency, prognostic factors, and differences for various etiologies of neutropenia in dogs. A total of 391 dogs with neutrophil counts < 2.78 x 10 9 /l (January 2008 to December 2012) were included and, depending on the etiology of neutropenia, assigned to seven diagnostic groups: nonbacterial infectious disease, increased demand due to marked inflammation, drug-associated, bone-marrow diseases, immune-mediated, physiologic, miscellaneous. Absolute neutrophil counts, evidence of neutrophil toxicity or left shift, case history, rectal temperature, hospitalization, and survival were compared among groups. Increased demand due to marked inflammation (90/391, 23%) and nonbacterial infectious disease (70/391, 18%) were the most common causes for neutropenia, followed by drug-associated neutropenia (43/391, 11%) and bone-marrow disease (32/391, 8%). Immune-mediated and physiologic neutropenia (both 16/391, 4%) were uncommon. Almost one third (124/391, 32%) of dogs were assigned to the miscellaneous group. Absolute neutrophil counts were significantly higher (p < 0.01) in dogs of the physiologic and miscellaneous groups than in the other groups. Dogs with immune-mediated neutropenia or nonbacterial infectious disease displayed significantly lower absolute neutrophil counts than dogs with neutropenia due to an increased demand (p < 0.001) and were most commonly referred with a history of fever (11/16, 69%) or gastrointestinal signs (52/70, 74%), respectively. Neutrophil toxicity and left shift were most commonly associated with an increased demand due to marked inflammation (60/90 and 25/90, 67% and 28%, respectively) and the mortality rate was highest in this group (32/90, 36%). Neutrophil toxicity and left shift are associated with an increased demand due to marked inflammation and may indicate a poor prognosis. The lower the absolute neutrophil count, the greater the probability of an immune-mediated neutropenia. Neutropenia should be assessed in context with case history, clinical examination, and neutrophil morphology.

Measurement of endogenous noradrenaline release in the rat cerebral cortex in vivo by transcortical dialysis: effects of drugs affecting noradrenergic transmission.

PubMed

L'Heureux, R; Dennis, T; Curet, O; Scatton, B

1986-06-01

The release of endogenous noradrenaline was measured in the cerebral cortex of the halothane-anesthetized rat by using the technique of brain dialysis coupled to a radioenzymatic assay. A thin dialysis tube was inserted transversally in the cerebral cortex (transcortical dialysis) and perfused with Ringer medium (2 microliter min-1). Under basal conditions, the cortical output of noradrenaline was stable over a period of at least 6 h and amounted to 8.7 pg/20 min (not corrected for recovery). Histological control of the perfused area revealed very little damage and normal morphology in the vicinity of the dialysis tube. Omission of calcium from the perfusion medium caused a marked drop in cortical noradrenaline output. Bilateral electrical stimulation (for 10 min) of the ascending noradrenergic pathways in the medial forebrain bundle caused a frequency-dependent increase in cortical noradrenaline output over the range 5-20 Hz. Stimulation at a higher frequency (50 Hz) resulted in a levelling off of the increase in cortical noradrenaline release. Systemic administration of the dopamine-beta-hydroxylase inhibitor bis-(4-methyl-1-homopiperazinylthiocarbonyl) disulfide (FLA 63) (25 mg/kg i.p.) markedly reduced, whereas injection of the monoamine oxidase inhibitor pargyline (75 mg/kg i.p.) resulted in a progressive increase in, cortical noradrenaline output. d-Amphetamine (2 mg/kg i.p.) provoked a sharp increase in cortical noradrenaline release (+450% over basal values within 40 min). Desmethylimipramine (10 mg/kg i.p.) produced a twofold increase of cortical noradrenaline release. Finally, idazoxan (20 mg/kg i.p.) and clonidine (0.3 mg/kg i.p.), respectively, increased and decreased the release of noradrenaline from the cerebral cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Marking small hive beetles with thoracic notching: Effects on longevity, flight ability and fecundity.

USDA-ARS?s Scientific Manuscript database

We tested two marking techniques for adult small hive beetles (SHB): dusting and thoracic notching. The use of blue and red chalk dusts to mark beetles was not persistent and caused early death of SHB with an average survival of 52.6 ± 23.8 and 13.9 ± 7.3 days, respectively. In contrast, notched bee...

The Effects of Laser Marking and Symbol Etching on the Fatigue Life of Medical Devices.

PubMed

Ogrodnik, P J; Moorcroft, C I; Wardle, P

2013-01-01

This paper examines the question;" does permanent laser marking affect the mechanical performance of a metallic medical component?" The literature review revealed the surprising fact that very little has been presented or studied even though intuition suggests that its effect could be detrimental to a component's fatigue life. A brief investigation of laser marking suggests that defects greater than 25 μm are possible. A theoretical investigation further suggests that this is unlikely to cause issues with relation to fast fracture but is highly likely to cause fatigue life issues. An experimental investigation confirmed that laser marking reduced the fatigue life of a component. This combination of lines of evidence suggests, strongly, that positioning of laser marking is highly critical and should not be left to chance. It is further suggested that medical device designers, especially those related to orthopaedic implants, should consider the position of laser marking in the design process. They should ensure that it is in an area of low stress amplitude. They should also ensure that they investigate worst-case scenarios when considering the stress environment; this, however, may not be straightforward.

The Effects of Laser Marking and Symbol Etching on the Fatigue Life of Medical Devices

PubMed Central

Ogrodnik, P. J.; Moorcroft, C. I.; Wardle, P.

2013-01-01

This paper examines the question;“ does permanent laser marking affect the mechanical performance of a metallic medical component?” The literature review revealed the surprising fact that very little has been presented or studied even though intuition suggests that its effect could be detrimental to a component's fatigue life. A brief investigation of laser marking suggests that defects greater than 25 μm are possible. A theoretical investigation further suggests that this is unlikely to cause issues with relation to fast fracture but is highly likely to cause fatigue life issues. An experimental investigation confirmed that laser marking reduced the fatigue life of a component. This combination of lines of evidence suggests, strongly, that positioning of laser marking is highly critical and should not be left to chance. It is further suggested that medical device designers, especially those related to orthopaedic implants, should consider the position of laser marking in the design process. They should ensure that it is in an area of low stress amplitude. They should also ensure that they investigate worst-case scenarios when considering the stress environment; this, however, may not be straightforward. PMID:27006919

Salinization owing to evaporation from bare-soil surfaces and its influences on the evaporation

NASA Astrophysics Data System (ADS)

Shimojimaa, Eiichi; Yoshioka, Ryuma; Tamagawa, Ichiro

1996-04-01

To investigate the relationship between evaporation and salinization, the surfaces of three columns of uniform porous materials, desert dune sand, silica sand and glass beads, respectively, were exposed to a temperature-, humidity- and/or wind-speed-controlled ambient atmosphere. For the dune sand, chemicals such as Na +, Ca 2+, Cl - and SO 42-, dissolved mainly from CaSO 4, Na 2SO 4, CaCO 3 and NaC1 in the sand particles, caused marked salinization near the top surface. Slow dissolution of Na 2SO 4 and CaSO 4 influenced the development of concentration profiles for SO 42- and Na + markedly for months after the beginning of the experiment, while the profile of Cl - was not affected directly, because dissolution of NaCl was rapid. Concentration profiles of Cl - for the glass beads and for the silica sand columns filled with a high concentration of NaCI solution of (10 4 mg1 -1 for Cl -), were analysed similarly. Experimental results suggested that the vapour flux in a dry soil became larger because of the increase in the gradient of the vapour density caused by greater chemical enrichment near the top surface compared with that at the evaporation surface. The vapour flux also became smaller as the gradient of the vapour density decreased, owing to the markedly enriched evaporation surface. In the experiment with glass beads, filled with the NaCl solution, solute crystallization (4-10 mm thick) was observed. For the dune sand, only when a turbulent airflow was applied did a crust (a few millimetres in thickness) form entirely on the top surface. Such deposition led to a reduction in the flux of water vapour as the permeable cross-sectional area decreased. The resistance to transfer increased three to ten times for the glass beads but only by 30% for the dune sand. The lower increase for the dune sand may be due to penetration of the applied airflow into cracks in the crust.

Ischemic syndromes causing dizziness and vertigo.

PubMed

Choi, K-D; Lee, H; Kim, J-S

2016-01-01

Dizziness/vertigo and imbalance are the most common symptoms of vertebrobasilar ischemia. Even though dizziness/vertigo usually accompanies other neurologic symptoms and signs in cerebrovascular disorders, a diagnosis of isolated vascular vertigo is increasing markedly by virtue of recent developments in clinical neurotology and neuroimaging. It is important to differentiate isolated vertigo of a vascular cause from more benign disorders involving the inner ear, since therapeutic strategies and prognosis differ between these two conditions. Over the last decade, we have achieved a marked development in the understanding and diagnosis of vascular dizziness/vertigo. Introduction of diffusion-weighted magnetic resonance imaging (MRI) has greatly enhanced detection of infarctions in patients with vascular dizziness/vertigo, especially in the posterior-circulation territories. However, well-organized bedside neurotologic evaluation is even more sensitive than MRI in detecting acute infarction as a cause of spontaneous prolonged vertigo. Furthermore, detailed evaluation of strategic infarctions has elucidated the function of various vestibular structures of the brainstem and cerebellum. In contrast, diagnosis of isolated labyrinthine infarction still remains a challenge. This diagnostic difficulty also applies to isolated transient dizziness/vertigo of vascular origin. Regarding the common nonlacunar mechanisms in the acute vestibular syndrome from small infarctions, individual strategies may be indicated to prevent recurrences of stroke in patients with vascular vertigo. © 2016 Elsevier B.V. All rights reserved.

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

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

PubMed

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

2008-06-01

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

Thermal and hydrologic responses to climate change predict marked alterations in boreal stream invertebrate assemblages.

PubMed

Mustonen, Kaisa-Riikka; Mykrä, Heikki; Marttila, Hannu; Sarremejane, Romain; Veijalainen, Noora; Sippel, Kalle; Muotka, Timo; Hawkins, Charles P

2018-06-01

Air temperature at the northernmost latitudes is predicted to increase steeply and precipitation to become more variable by the end of the 21st century, resulting in altered thermal and hydrological regimes. We applied five climate scenarios to predict the future (2070-2100) benthic macroinvertebrate assemblages at 239 near-pristine sites across Finland (ca. 1200 km latitudinal span). We used a multitaxon distribution model with air temperature and modeled daily flow as predictors. As expected, projected air temperature increased the most in northernmost Finland. Predicted taxonomic richness also increased the most in northern Finland, congruent with the predicted northwards shift of many species' distributions. Compositional changes were predicted to be high even without changes in richness, suggesting that species replacement may be the main mechanism causing climate-induced changes in macroinvertebrate assemblages. Northern streams were predicted to lose much of the seasonality of their flow regimes, causing potentially marked changes in stream benthic assemblages. Sites with the highest loss of seasonality were predicted to support future assemblages that deviate most in compositional similarity from the present-day assemblages. Macroinvertebrate assemblages were also predicted to change more in headwaters than in larger streams, as headwaters were particularly sensitive to changes in flow patterns. Our results emphasize the importance of focusing protection and mitigation on headwater streams with high-flow seasonality because of their vulnerability to climate change. © 2018 John Wiley & Sons Ltd.

Responses of In vitro-Grown Plantlets (Vitis vinifera) to Grapevine leafroll-Associated Virus-3 and PEG-Induced Drought Stress.

PubMed

Cui, Zhen-Hua; Bi, Wen-Lu; Hao, Xin-Yi; Xu, Yan; Li, Peng-Min; Walker, M Andrew; Wang, Qiao-Chun

2016-01-01

Stresses caused by viral diseases and drought have long threatened sustainable production of grapevine. These two stresses frequently occur simultaneously in many of grapevine growing regions of the world. We studied responses of in vitro-grown plantlets (Vitis vinifera) to Grapevine leafroll associated virus-3 (GLRaV-3) and PEG-induced drought stress. Results showed that stress induced by either virus infection or drought had negative effects on vegetative growth, caused significant decreases and increases in total soluble protein and free proline, respectively, induced obvious cell membrane damage and cell death, and markedly increased accumulations of [Formula: see text] and H2O2. Co-stress by virus and drought had much severer effects than single stress on the said parameters. Virus infection alone did not cause significant alternations in activities of POD, ROS, and SOD, and contents of MDA, which, however, markedly increased in the plantlets when grown under single drought stress and co-stress by the virus and drought. Levels of ABA increased, while those of IAA decreased in the plantlets stressed by virus infection or drought. Simultaneous stresses by the virus and drought had co-effects on the levels of ABA and IAA. Up-regulation of expressions of ABA biosynthesis genes and down-regulation of expressions of IAA biosynthesis genes were responsible for the alternations of ABA and IAA levels induced by either the virus infection or drought stress and co-stress by them. Experimental strategies established in the present study using in vitro system facilitate investigations on 'pure' biotic and abiotic stress on plants. The results obtained here provide new insights into adverse effects of stress induced by virus and drought, in single and particularly their combination, on plants, and allow us to re-orientate agricultural managements toward sustainable development of the agriculture.

[Causes, diagnosis, and animal behavioural therapy of feline house soiling].

PubMed

Kuhne, F

2015-01-01

Feline house soiling, i. e. urinating or defecating outside the litterbox, is the most common behavioural problem for which cat owners seek assistance from veterinarians. The reasons for feline house soiling are inappropriate toileting or urine marking. To identify the initiating cause(s) and maintaining factors, a comprehensive behavioural history is required. Urine marking may be caused by anxiety-evoking stuations or arousing events, whereas inappropriate toileting is mainly due to factors related to the litterbox. The treatment plan should initially focus on the pet's well-being. Therefore, it is important to improve the litterbox management to curtail the problem. The main approaches to resolve feline house soiling involve avoiding the cat's exposure to triggering stimuli, re-establishing regular litterbox use, and behavioural modification.

What is the cause of benign transient hyperphosphatasemia? A study of 35 cases.

PubMed

Crofton, P M

1988-02-01

In a study of 35 children with benign transient hyperphosphatasemia, I found a marked seasonal clustering of cases after the summer months. Furthermore, plasma 25-hydroxyvitamin D concentrations were almost twice those of controls matched for age and time of year. Many children had evidence of weight loss and one had idiopathic hypercalcemia of infancy. Activities both of liver and bone isoenzymes of alkaline phosphatase (EC 3.1.3.1) in plasma were increased. The liver and (to a lesser extent) bone isoenzymes had enhanced electrophoretic mobility, and both showed increased binding to wheat-germ lectin by affinity electrophoresis. For the liver (and probably also the bone) isoenzyme, these changes were due to an increased content of sialic acid. A possible etiology for the condition is proposed involving (a) increased synthesis of alkaline phosphatase, mediated by vitamin D metabolites, and (b) decreased hepatic clearance caused by the high sialic acid content and exacerbated in some cases by the effects of some drugs on the liver.

Effects of n-acetylcysteine in a rat model of ischemia and reperfusion injury.

PubMed

Cuzzocrea, S; Mazzon, E; Costantino, G; Serraino, I; De Sarro, A; Caputi, A P

2000-08-18

Splanchnic artery occlusion shock (SAO) causes an enhanced formation of reactive oxygen species (ROS), which contribute to the pathophysiology of shock. Here we have investigated the effects of n-acetylcysteine (NAC), a free radical scavenger, in rats subjected to SAO shock. Treatment of rats with NAC (applied at 20 mg/kg, 5 min prior to reperfusion, followed by an infusion of 20 mg/kg/h) attenuated the mean arterial blood and the migration of polymorphonuclear cells (PMNs) caused by SAO-shock. NAC also attenuated the ileum injury (histology) as well as the increase in the tissue levels of myeloperoxidase (MPO) and malondialdehyde (MDA) caused by SAO shock in the ileum. There was a marked increase in the oxidation of dihydrorhodamine 123 to rhodamine in the plasma of the SAO-shocked rats after reperfusion. Immunohistochemical analysis for nitrotyrosine and for poly(ADP-ribose) synthetase (PARS) revealed a positive staining in ileum from SAO-shocked rats. The degree of staining for nitrotyrosine and PARS were markedly reduced in tissue sections obtained from SAO-shocked rats which had received NAC. Reperfused ileum tissue sections from SAO-shocked rats showed positive staining for P-selectin, which was mainly localised in the vascular endothelial cells. Ileum tissue section obtained from SAO-shocked rats with anti-intercellular adhesion molecule (ICAM-1) antibody showed a diffuse staining. NAC treatment markedly reduced the intensity and degree of P-selectin and ICAM-1 in tissue section from SAO-shocked rats. In addition, in ex vivo studies in aortic rings from shocked rats, we found reduced contractions to noradrenaline and reduced responsiveness to a relaxant effect to acetylcholine (vascular hyporeactivity and endothelial dysfunction, respectively). NAC treatment improved contractile responsiveness to noradrenaline, enhanced the endothelium-dependent relaxations and significantly improved survival. Taken together, our results clearly demonstrate that NAC treatment exert a protective effect and part of this effect may be due to inhibition of the expression of adhesion molecule and peroxynitrite-related pathways and subsequent reduction of neutrophil-mediated cellular injury.

The increasing hospital disease burden of haemochromatosis in England.

PubMed

Cowan, M L; Westlake, S; Thomson, S J; Rahman, T M; Majeed, A; Maxwell, J D; Kang, J-Y

2010-01-15

Hereditary haemochromatosis is a preventable cause of liver disease with an increasing disease burden. To investigate time trends for hospital admission ascribed to haemochromatosis in England during the period from 1989/1990 to 2002/2003 and mortality from 1979 to 2005. Hospital admission data, relating to both in-patients and day-cases, were obtained from the Hospital Episodes Statistics service. Mortality rates for England and Wales were provided by the Office for National Statistics. Haemochromatosis is an uncommon cause for hospital admission. Age-standardized in-patient admission rates increased over the study period by 269% in men and by 290% in women: (from 0.64 to 2.36 and from 0.21 to 0.81 per year per 100 000). The increase in age-standardized day-case admission rates was even higher (men: from 2.78 to 34.9 per year per 100 000, 1155%; women: from 0.58 to 11.67 per year per 100 000, 1924%). Haemochromatosis was recorded as an uncommon cause of death. Hospital in-patient and day case admissions for haemochromatosis increased markedly over the study period while mortality remained low. Both admission rates and mortality were higher in men than in women. The increase in admission rate may reflect improved recognition and diagnosis of iron overload disorders following identification of the HFE gene.

Ectopic recombination between Ty elements in Saccharomyces cerevisiae is not induced by DNA damage.

PubMed

Parket, A; Kupiec, M

1992-10-01

Mitotic recombination is increased when cells are treated with a variety of physical and chemical agents that cause damage to their DNA. We show here, using Saccharomyces cerevisiae strains that carry marked Ty elements, that recombination between members of this family of retrotransposons is not increased by UV irradiation or by treatment with the radiomimetic drug methyl methanesulfonate. Both ectopic recombination and mutation events were elevated by these agents for non-Ty sequences in the same strain. We discuss possible mechanisms that can prevent the induction of recombination between Ty elements.

The mitochondria-targeted antioxidant MitoQ attenuates liver fibrosis in mice.

PubMed

Rehman, Hasibur; Liu, Qinlong; Krishnasamy, Yasodha; Shi, Zengdun; Ramshesh, Venkat K; Haque, Khujista; Schnellmann, Rick G; Murphy, Michael P; Lemasters, John J; Rockey, Don C; Zhong, Zhi

2016-01-01

Oxidative stress plays an essential role in liver fibrosis. This study investigated whether MitoQ, an orally active mitochondrial antioxidant, decreases liver fibrosis. Mice were injected with corn oil or carbon tetrachloride (CCl4, 1:3 dilution in corn oil; 1 µl/g, ip) once every 3 days for up to 6 weeks. 4-Hydroxynonenal adducts increased markedly after CCl4 treatment, indicating oxidative stress. MitoQ attenuated oxidative stress after CCl4. Collagen 1α1 mRNA and hydroxyproline increased markedly after CCl4 treatment, indicating increased collagen formation and deposition. CCl4 caused overt pericentral fibrosis as revealed by both the sirius red staining and second harmonic generation microscopy. MitoQ blunted fibrosis after CCl4. Profibrotic transforming growth factor-β1 (TGF-β1) mRNA and expression of smooth muscle α-actin, an indicator of hepatic stellate cell (HSC) activation, increased markedly after CCl4 treatment. Smad 2/3, the major mediator of TGF-β fibrogenic effects, was also activated after CCl4 treatment. MitoQ blunted HSC activation, TGF-β expression, and Smad2/3 activation after CCl4 treatment. MitoQ also decreased necrosis, apoptosis and inflammation after CCl4 treatment. In cultured HSCs, MitoQ decreased oxidative stress, inhibited HSC activation, TGF-β1 expression, Smad2/3 activation, and extracellular signal-regulated protein kinase activation. Taken together, these data indicate that mitochondrial reactive oxygen species play an important role in liver fibrosis and that mitochondria-targeted antioxidants are promising potential therapies for prevention and treatment of liver fibrosis.

The mitochondria-targeted antioxidant MitoQ attenuates liver fibrosis in mice

PubMed Central

Rehman, Hasibur; Liu, Qinlong; Krishnasamy, Yasodha; Shi, Zengdun; Ramshesh, Venkat K; Haque, Khujista; Schnellmann, Rick G; Murphy, Michael P; Lemasters, John J; Rockey, Don C; Zhong, Zhi

2016-01-01

Oxidative stress plays an essential role in liver fibrosis. This study investigated whether MitoQ, an orally active mitochondrial antioxidant, decreases liver fibrosis. Mice were injected with corn oil or carbon tetrachloride (CCl4, 1:3 dilution in corn oil; 1 µl/g, ip) once every 3 days for up to 6 weeks. 4-Hydroxynonenal adducts increased markedly after CCl4 treatment, indicating oxidative stress. MitoQ attenuated oxidative stress after CCl4. Collagen 1α1 mRNA and hydroxyproline increased markedly after CCl4 treatment, indicating increased collagen formation and deposition. CCl4 caused overt pericentral fibrosis as revealed by both the sirius red staining and second harmonic generation microscopy. MitoQ blunted fibrosis after CCl4. Profibrotic transforming growth factor-β1 (TGF-β1) mRNA and expression of smooth muscle α-actin, an indicator of hepatic stellate cell (HSC) activation, increased markedly after CCl4 treatment. Smad 2/3, the major mediator of TGF-β fibrogenic effects, was also activated after CCl4 treatment. MitoQ blunted HSC activation, TGF-β expression, and Smad2/3 activation after CCl4 treatment. MitoQ also decreased necrosis, apoptosis and inflammation after CCl4 treatment. In cultured HSCs, MitoQ decreased oxidative stress, inhibited HSC activation, TGF-β1 expression, Smad2/3 activation, and extracellular signal-regulated protein kinase activation. Taken together, these data indicate that mitochondrial reactive oxygen species play an important role in liver fibrosis and that mitochondria-targeted antioxidants are promising potential therapies for prevention and treatment of liver fibrosis. PMID:27186319

Nepheline rock dust pneumoconiosis. A report of 2 cases

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

Olscamp, G.; Herman, S.J.; Weisbrod, G.L.

1982-01-01

Two cases of nepheline rock dust pneumoconiosis are presented. Radiologically, this is seen as a diffuse increase in interstitial lung markings, lymphadenopathy, air-space disease, and atelectasis secondary to extrinsic compression by enlarged hilar lymph nodes. Major differential diagnoses include carcinoma of the lung, sarcoidosis, and interstitial lung disease caused by other inorganic dusts. Nepheline rock dust pneumoconiosis should be considered when the above radiological changes are observed and an occupational exposure to inorganic dust is documented.

Nepheline rock dust pneumoconiosis: a report of 2 cases

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

Olscamp, G.; Herman, S.J.; Weisbrod, G.L.

1982-01-01

Two cases of nepheline rock dust pneumoconiosis are presented. Radiologically, this is seen as a diffuse increase in interstitial lung markings, lymphadenopathy air-space disease, and atelectasis secondary to extrinsic compression by enlarged hilar lymph nodes. Major differential diagnoses include carcinoma of the lung, sarcoidosis, and interstitial lung disease caused by other inorganic dusts. Nepheline rock dust pneumoconiosis should be considered when the above radiological changes are observed and an occupational exposure to inorganic dust is documented.

Assessment of surface relief and short cracks under cyclic creep in a type 316LN austenitic stainless steel

NASA Astrophysics Data System (ADS)

Sarkar, Aritra; Nagesha, A.; Parameswaran, P.; Sandhya, R.; Laha, K.

2015-12-01

Formation of surface relief and short cracks under cyclic creep (stress-controlled fatigue) in type 316LN stainless steel was studied at temperatures ranging from ambient to 923 K using scanning electron microscopy technique. The surface topography and crack distribution behaviour under cyclic creep were found to be strong functions of testing temperature due to the difference in strain accumulation. At 823 K, surface relief mainly consisted of fine slip markings due to negligible accumulation of strain as a consequence of dynamic strain ageing (DSA) which led to an increase in the cyclic life. Persistent slip markings (PSM) with distinct extrusions containing minute cracks were seen to prevail in the temperature range 873-923 K, indicating a higher slip activity causing higher strain accumulation in the absence of DSA. Besides, a large number of secondary cracks (both transgranular and intergranular) which were partially accentuated by severe oxidation, were observed. Extensive cavitation-induced grain boundary cracking took place at 923 K, which coalesced with PSM-induced transgranular cracks resulting in failure dominated by creep that in turn led to a drastic reduction in cyclic life. Investigations on the influence of stress rate were also carried out which underlined the presence of DSA at 823 K. At 923 K, lowering the stress rate caused further strengthening of the contribution from creep damage marked by a shift in the damage mechanism from cyclic slip to diffusion.

Investigation of Meniscus Region Behavior and Oscillation Mark Formation in Steel Continuous Casting Using a Transient Thermo-Fluid Model

NASA Astrophysics Data System (ADS)

Blaes, Carly

In the continuous casting of steel, many complex phenomena in the meniscus region of the mold are responsible for the formation of oscillation marks. Oscillation marks are depressions found around the perimeter of continuously cast steel slabs, which if too large can lead to cracking in steel slabs. Therefore, knowledge on how to minimize the size of oscillation marks is very valuable. A computational model was created of the meniscus region, which includes transient multiphase fluid flow of slag and steel, with low-Reynolds turbulence, heat transfer in the mold, slag, and steel, steel shell solidification, mold oscillation, and temperature-dependent properties. This model was first validated using previous experimental and plant data. The model was then used to study the impact of varying casting parameters, including oscillation frequency, stroke, modification ratio, casting speed, molten steel level fluctuations, and temperature-dependent slag properties and surface tension on the oscillation mark shape, and other aspects of thermal-flow behavior during each oscillation cycle, including heat flux profile, slag consumption and mold friction. The first half of oscillation marks were formed during negative strip time as the slag rim pushed molten steel away from the mold wall and that the second half of oscillation marks were formed during positive strip time as the molten steel is drawn near the mold wall due to the upstroke of the mold. Oscillation mark depth was found to decrease with increasing frequency, modification ratio, casting speed, and slag viscosity, while oscillation mark depth was found to increase with increasing stroke. Oscillation mark width was only found to increase due to increases in pitch, which can be contributed to decreasing frequency or increasing casting speed. While many observations were made in this study, in general, oscillation mark depth and total slag consumption increase with increasing negative strip time, while the average heat flux and average mold friction decrease with increasing negative strip time.

7 CFR 52.806 - Color.

Code of Federal Regulations, 2013 CFR

2013-01-01

... AND THE EGG PRODUCTS INSPECTION ACT PROCESSED FRUITS AND VEGETABLES, PROCESSED PRODUCTS THEREOF, AND... uniform in that the number of cherries that vary markedly from this color due to oxidation, improper... cherries that vary markedly from this color due to oxidation, improper processing, or other causes, or that...

7 CFR 52.806 - Color.

Code of Federal Regulations, 2014 CFR

2014-01-01

... AND THE EGG PRODUCTS INSPECTION ACT PROCESSED FRUITS AND VEGETABLES, PROCESSED PRODUCTS THEREOF, AND... uniform in that the number of cherries that vary markedly from this color due to oxidation, improper... cherries that vary markedly from this color due to oxidation, improper processing, or other causes, or that...

Effect of arachidonic acid metabolites on thymocyte proliferation.

PubMed

Delebassée, S; Gualde, N

1988-01-01

The influences of prostaglandin E2 (PGE2), 15-hydroxyeicosatetraenoic acid (15-HETE) and leukotrienes (LT) on the proliferative response of mature (PNA-) and immature (PNA+) mouse thymocytes was investigated. Both PNA+ and PNA- thymocytes proliferated when cultured with concanavalin A plus interleukin-2. PGE2 in concentrations of 10(-6) to 10(-9) M caused significant inhibition of proliferation of both PNA+ and PNA- thymocytes in these cultures. In contrast, the lipoxygenase products 15-HETE, LTB4, LTC4 and LTD4 caused marked increases in proliferation of PNA+ thymocytes while having no effect on PNA- cells. Therefore, the effect of leukotrienes on thymocyte proliferation depends upon the level of cell maturation and mainly affects immature PNA+ thymocytes.

Aspects of the pharmacology of a new anthelmintic

PubMed Central

Aubry, M. L.; Cowell, Pauline; Davey, M. J.; Shevde, S.

1970-01-01

1. The pharmacological properties of an anthelmintic, pyrantel, and some of its analogues have been described and compared with piperazine in a variety of vertebrate and helminth preparations. 2. Pyrantel and its analogues in common with nicotine and decamethonium cause spastic paralysis in chicks and contracture of the chick semispinalis and toad rectus abdominis muscles. 3. In the soleus and anterior tibialis muscles of the cat, pyrantel in large amounts caused a short-lived neuromuscular block that was preceded by initial depolarization. 4. In preparations from cat and rat, pyrantel showed properties common to both competitive and depolarizing neuromuscular blocking drugs. 5. Pyrantel blocked the contracture evoked by transmural stimulation and caused a marked contracture of the worm. Piperazine caused a gradually developing reduction in the responses to transmural stimulation and no contracture. 6. Pyrantel and its analogues caused a slowly developing contracture of strip preparations of Ascaris, being more than 100 times more active than acetylcholine in this respect. Piperazine caused a relaxation of Ascaris strip preparations and in common with (+)-tubocurarine blocked the responses to acetylcholine and pyrantel analogues on this preparation. 7. Pyrantel caused depolarization and increased spike discharge frequency in single muscle cells of Ascaris, these changes being accompanied by increase in tension. Piperazine, on the other hand, caused hyperpolarization and reduction in spike discharge frequency and relaxation, and antagonized the effects of pyrantel. PMID:5417856

Rotary Valve FY 2016 Highlights

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

Fitsos, P.

The fiscal year started with the Rotary Valve (RV) being reassembled after having crashed in June of 2015. The crash occurred when the RV inner surface contacted the housing. The cause of the crash was never confirmed. No particles were found in the 2.5 thousandths of an inch gap and the filters the helium gas passed through were all clean. There were marks on the bearings that looked like electrostatic discharge as shown below in Figure 1. These marks hadn’t been seen before and there were similar discharge marks on some of the ball bearings. Examples of this were foundmore » in a literature search of bearing failures. This leads to a possible cause due to this arcing affecting the rotational accuracy of the bearings driving the RV into the housing.« less

Hyperthyroidism caused by a pituitary thyrotrophin-secreting tumour with excessive secretion of thyrotrophin-releasing hormone and subsequently followed by Graves' disease in a middle-aged woman.

PubMed

Kamoi, K; Mitsuma, T; Sato, H; Yokoyama, M; Washiyama, K; Tanaka, R; Arai, O; Takasu, N; Yamada, T

1985-11-01

A 46-year-old woman had signs of thyrotoxicosis and galactorrhoea. Serum immunoreactive TSH and its alpha-subunit increased in the presence of high serum triiodothyronine (T3), thyroxine (T4), and free T4 concentrations, whereas beta-subunit TSH was undetectable. Exogenous TRH failed to increase serum TSH. Serum TSH was markedly suppressed by glucocorticoid, but was increased by antithyroid drug. L-Dopa or bromocriptine partially suppressed, but nomifensine had no influence on serum TSH. Serum prolactin (Prl) was above normal and markedly increased by TRH, but depressed by bromocriptine and not suppressed by nomifensine. Plasma TRH was normal in the hyperthyroid state, but was increased by glucocorticoid and antithyroid drug. Excess thyroid hormone depressed plasma TRH concentrations. Basal serum GH levels were constantly low. Transsphenoidal removal of the tumour normalized serum hormones (T3, T4 free T4, TSH, alpha-subunit and Prl), and eradicated the clinical signs of hyperthyroidism and galactorrhoea. Histological study of the tumour tissue demonstrated both thyrotrophes and somatotrophes. A reciprocal relationship between serum TSH and T4 concentrations shifted to a higher level before but was normalized after removal of the tumour. Ten months later, the clinical signs of thyrotoxicosis and the increase in serum thyroid hormone recurred without a concomitant increase in serum TSH and its alpha-subunit. Thyroidal auto-antibodies were slightly positive, but thyrotrophin-binding inhibitor immunoglobulin (TBII) was negative. Administration of antithyroid drug produced a euthyroid state, but 3 years later, discontinuation of the treatment resulted in recurrent hyperthyroidism without suppressed plasma TRH and with no evidence of regrowth of the pituitary tumour. It is suggested that the patient initially had hyperthyroidism owing to excessive TSH secretion from the tumour caused by abnormal TRH secretion, and subsequently had hyperthyroidism owing to Graves' disease.

Elimination of Dual Slope from the Coffin Manson Relationship of Low-Cycle Fatigue in the Titanium Alloy Timetal 834, by Cold Rolling

NASA Astrophysics Data System (ADS)

Sai Srinadh, K. V.; Singh, Vakil

2007-08-01

Cold rolling of the titanium alloy Timetal 834 was found to cause marked enhancement in low-cycle fatigue (LCF) life at low strain amplitude and to eliminate bilinear behavior from the Coffin Manson (C-M) relationship. It was due to work hardening of surface grains of soft orientation and consequent increase in resistance of the material against crack initiation. The observed effect was not associated with texture.

Comparison of propranolol and metoprolol in the management of hyperthyroidism.

PubMed

Murchison, L E; How, J; Bewsher, P D

1979-12-01

1 Propranolol and metoprolol were both effective in controlling the symptoms and signs of hyperthyroidism. 2 Propranolol caused a highly significant increase in serum reverse T3 concentrations with lesser changes in other serum thyroid hormone levels, whereas metoprolol did not have this effect. 3 Steady-state plasma propranolol and metoprolol levels showed marked inter-individual variation. Metoprolol concentrations showed relatively little intra-individual variability, and could be related to the clinical efficacy of the drug, whereas no such relationship was demonstrated for propranolol.

Breast Tumor pH: Design, Evaluation, and Application of Novel Reporter Molecules

DTIC Science & Technology

2001-10-01

DM, Burton DJ. J. Am Chem Soc. 1986, 108, 832. 8. Urata , H, Fuchikami T. Tet. Letters 1991,91. 9. Mehta, VD, Kulkarni PV, Mason RP, et al. 6...substitution reaction on an aryl iodide with trifluoromethyl copper ("CuCF3") [7]. Urata [8] described a convenient method for the in situ generation of...the stronger electron-withdrawing nature of the CF3 group causes this marked increase in acidity, which makes 6-CF3POL a better probe for

Cannabinoid hyperemesis and compulsive bathing: a case series and paradoxical pathophysiological explanation.

PubMed

Patterson, Dale A; Smith, Emmaleigh; Monahan, Mark; Medvecz, Andrew; Hagerty, Beth; Krijger, Lisa; Chauhan, Aakash; Walsh, Mark

2010-01-01

Cannabinoid hyperemesis is a syndrome characterized by severe nausea and hyperemesis associated with chronic marijuana abuse and marked by compulsive bathing habits, which temporarily alleviate symptoms. We describe the syndrome in 4 adult patients for whom extensive gastrointestinal evaluations failed to identify another clear cause. Cessation of marijuana use resulted in the alleviation of their symptoms. Because recreational and medical use of marijuana is increasing in the United States, this condition should be considered in many patients who present with cyclical vomiting.

Oxidation of cholesterol moiety of low density lipoprotein in the presence of human endothelial cells or Cu+2 ions: identification of major products and their effects.

PubMed

Bhadra, S; Arshad, M A; Rymaszewski, Z; Norman, E; Wherley, R; Subbiah, M T

1991-04-15

Oxidation of lipoproteins is believed to play a key role in atherogenesis. In this study, low density lipoproteins (LDL) was subjected to oxidation in the presence of either human umbilical vein endothelial cells or with Cu+2 ions and the major oxides formed were identified. While cholesterol-alpha-epoxide (C-alpha EP) was the major product of cholesterol peroxidation in the presence of endothelial cells, cholest-3,5-dien-7-one (CD) predominated in the presence of Cu+2 ion. Both steroids were identified by gas chromatography/mass spectrometry. HDL cholesterol was resistant to oxidation. When tested on human skin fibroblasts in culture C-alpha EP (10 micrograms/ml) caused marked stimulation of 14C-oleate incorporation into cholesterol esters, while CD stimulated cholesterol esterification only mildly. These studies show that a) C-alpha EP is the major peroxidation product of LDL cholesterol moiety in the presence of endothelial cells and b) it causes marked stimulation of cholesterol esterification in cells. C-alpha EP may play a key role in increasing cholesterol esterification noted in atherogenesis.

Inhibition of protein synthesis by N-methyl-N-nitrosourea in vivo

PubMed Central

Kleihues, P.; Magee, P. N.

1973-01-01

1. The intraperitoneal injection of N-methyl-N-nitrosourea (100mg/kg) caused a partial inhibition of protein synthesis in several organs of the rat, the maximum effect occurring after 2–3h. 2. In the liver the inhibition of protein synthesis was paralleled by a marked disaggregation of polyribosomes and an increase in ribosome monomers and ribosomal subunits. No significant breakdown of polyribosomes was found in adult rat brains although N-methyl-N-nitrosourea inhibited cerebral and hepatic protein synthesis to a similar extent. In weanling rats N-methyl-N-nitrosourea caused a shift in the cerebral polyribosome profile similar to but less marked than that in rat liver. 3. Reaction of polyribosomal RNA with N-[14C]methyl-N-nitrosourea in vitro did not lead to a disaggregation of polyribosomes although the amounts of 7-methylguanine produced were up to twenty times higher than those found after administration of sublethal doses in vivo. 4. It was concluded that changes in the polyribosome profile induced by N-methyl-N-nitrosourea may reflect the mechanism of inhibition of protein synthesis rather than being a direct consequence of the methylation of polyribosomal mRNA. PMID:4774397

Pegvisomant treatment in gigantism caused by a growth hormone-secreting giant pituitary adenoma.

PubMed

Müssig, K; Gallwitz, B; Honegger, J; Strasburger, C J; Bidlingmaier, M; Machicao, F; Bornemann, A; Ranke, M B; Häring, H-U; Petersenn, S

2007-03-01

Gigantism is rare with the majority of cases caused by a growth hormone (GH)-secreting pituitary adenoma. Treatment options for GH-secreting pituitary adenomas have been widened with the availability of long-acting dopamine agonists, depot preparations of somatostatin analogues, and recently the GH receptor antagonist pegvisomant. A 23-year-old male patient presented with continuous increase in height during the past 6 years due to a GH-secreting giant pituitary adenoma. Because of major intracranial extension and failure of octreotide treatment to shrink the tumour, the tumour was partially resected by a trans-frontal surgical approach. At immunohistochemistry, the tumour showed a marked expression of GH and a sparsely focal expression of prolactin. Somatostatin receptors (sst) 1-5 were not detected. Tumour tissue weakly expressed dopamine receptor type 2. The Gs alpha subunit was intact. Conversion from somatostatin analogue to pegvisomant normalized insulin-like-growth-factor-I (IGF-I) levels and markedly improved glucose tolerance. Pegvisomant is a potent treatment option in patients with pituitary gigantism. In patients who do not respond to somatostatin analogues, knowledge of the SST receptor status may shorten the time to initiation of pegvisomant treatment.

Role of nitric oxide and septide-insensitive NK1 receptors in bronchoconstriction induced by aerosolised neurokinin A in guinea-pigs

PubMed Central

Ricciardolo, Fabio L M; Trevisani, Marcello; Geppetti, Pierangelo; Nadel, Jay A; Amadesi, Silvia; Bertrand, Claude

2000-01-01

The tachykinin, neurokinin A (NKA), contracts guinea-pig airways both in vitro and in vivo, preferentially activating smooth muscle NK2 receptors, although smooth muscle NK1 receptors may also contribute. In vitro evidence suggests that NKA activates epithelial NK1 receptors, inducing the release of nitric oxide (NO) and subsequent smooth muscle relaxation. A number of selective NK1 receptor agonists have been reported to activate both smooth muscle and epithelial NK1 receptors, however septide appears only to activate smooth muscle NK1 receptors. The aim of the present study was to investigate whether NKA-induced bronchoconstriction in guinea-pigs in vivo may be limited by NO release via NK1 receptor activation, and whether selective NK1 receptor agonists may activate this mechanism differently. Aerosolized NKA caused an increase in total pulmonary resistance (RL) that was markedly reduced by the NK2 receptor antagonist, SR 48968, and abolished by the combination of SR 48968 and the NK1 receptor antagonist, CP-99,994. The increase in RL evoked by NKA was potentiated by pretreatment with the NO synthase (NOs) inhibitor, L-NAME, but not by the inactive enantiomer D-NAME. Potentiation by L-NAME of NKA-induced increase in RL was reversed by L-Arginine, but not by D-Arginine. Pretreatment with L-NAME did not affect the increase in RL induced by the selective NK2 receptor agonist, [β-Ala8]NKA(4-10), and by the selective NK1 receptor agonist, septide, whereas it markedly potentiated the increase in RL caused by a different NK1 selective agonist, [Sar9,Met(O2)11]SP. Dose-response curves showed that septide was a more potent bronchoconstrictor than [Sar9,Met(O2)11]SP to cause bronchoconstriction. Pretreatment with the NK1 receptor antagonist, CP-96,994, abolished the ability of L-NAME to increase bronchoconstriction to aerosolized NKA. Bronchoconstriction to aerosolized NKA was increased by L-NAME, after pretreatment with the NK3 receptor antagonist, SR 142801. The present study shows that in vivo bronchoconstriction in response to the aerosolized naturally occurring tachykinin, NKA, is limited by its own ability to release relaxant NO via NK1 receptor activation. This receptor is apparently insensitive to septide, thus justifying, at least in part, the high potency of septide to cause bronchoconstriction in guinea-pigs. PMID:10696090

Role of nitric oxide and septide-insensitive NK(1) receptors in bronchoconstriction induced by aerosolised neurokinin A in guinea-pigs.

PubMed

Ricciardolo, F L; Trevisani, M; Geppetti, P; Nadel, J A; Amadesi, S; Bertrand, C

2000-03-01

The tachykinin, neurokinin A (NKA), contracts guinea-pig airways both in vitro and in vivo, preferentially activating smooth muscle NK(2) receptors, although smooth muscle NK(1) receptors may also contribute. In vitro evidence suggests that NKA activates epithelial NK(1) receptors, inducing the release of nitric oxide (NO) and subsequent smooth muscle relaxation. A number of selective NK(1) receptor agonists have been reported to activate both smooth muscle and epithelial NK(1) receptors, however septide appears only to activate smooth muscle NK(1) receptors. The aim of the present study was to investigate whether NKA-induced bronchoconstriction in guinea-pigs in vivo may be limited by NO release via NK(1) receptor activation, and whether selective NK(1) receptor agonists may activate this mechanism differently. Aerosolized NKA caused an increase in total pulmonary resistance (RL) that was markedly reduced by the NK(2) receptor antagonist, SR 48968, and abolished by the combination of SR 48968 and the NK(1) receptor antagonist, CP-99, 994. The increase in RL evoked by NKA was potentiated by pretreatment with the NO synthase (NOs) inhibitor, L-NAME, but not by the inactive enantiomer D-NAME. Potentiation by L-NAME of NKA-induced increase in RL was reversed by L-Arginine, but not by D-Arginine. Pretreatment with L-NAME did not affect the increase in RL induced by the selective NK(2) receptor agonist, [beta-Ala(8)]NKA(4-10), and by the selective NK(1) receptor agonist, septide, whereas it markedly potentiated the increase in RL caused by a different NK(1) selective agonist, [Sar(9),Met(O(2))(11)]SP. Dose-response curves showed that septide was a more potent bronchoconstrictor than [Sar(9),Met(O(2))(11)]SP to cause bronchoconstriction. Pretreatment with the NK(1) receptor antagonist, CP-96,994, abolished the ability of L-NAME to increase bronchoconstriction to aerosolized NKA. Bronchoconstriction to aerosolized NKA was increased by L-NAME, after pretreatment with the NK(3) receptor antagonist, SR 142801. The present study shows that in vivo bronchoconstriction in response to the aerosolized naturally occurring tachykinin, NKA, is limited by its own ability to release relaxant NO via NK(1) receptor activation. This receptor is apparently insensitive to septide, thus justifying, at least in part, the high potency of septide to cause bronchoconstriction in guinea-pigs.

Lake sediment records on climate change and human activities in the Xingyun Lake catchment, SW China.

PubMed

Zhang, Wenxiang; Ming, Qingzhong; Shi, Zhengtao; Chen, Guangjie; Niu, Jie; Lei, Guoliang; Chang, Fengqin; Zhang, Hucai

2014-01-01

Sediments from Xinyun Lake in central Yunnan, southwest China, provide a record of environmental history since the Holocene. With the application of multi-proxy indicators (total organic carbon (TOC), total nitrogen (TN), δ13C and δ15N isotopes, C/N ratio, grain size, magnetic susceptibility (MS) and CaCO3 content), as well as accelerator mass spectrometry (AMS) 14C datings, four major climatic stages during the Holocene have been identified in Xingyun's catchment. A marked increase in lacustrine palaeoproductivity occurred from 11.06 to 9.98 cal. ka BP, which likely resulted from an enhanced Asian southwest monsoon and warm-humid climate. Between 9.98 and 5.93 cal. ka BP, a gradually increased lake level might have reached the optimum water depth, causing a marked decline in coverage by aquatic plants and lake productivity of the lake. This was caused by strong Asian southwest monsoon, and coincided with the global Holocene Optimum. During the period of 5.60-1.35 cal. ka BP, it resulted in a warm and dry climate at this stage, which is comparable to the aridification of India during the mid- and late Holocene. The intensifying human activity and land-use in the lake catchment since the early Tang Dynasty (∼1.35 cal. ka BP) were associated with the ancient Dian culture within Xingyun's catchment. The extensive deforestation and development of agriculture in the lake catchment caused heavy soil loss. Our study clearly shows that long-term human activities and land-use change have strongly impacted the evolution of the lake environment and therefore modulated the sediment records of the regional climate in central Yunnan for more than one thousand years.

Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome.

PubMed

Sousa, Sérgio B; Jenkins, Dagan; Chanudet, Estelle; Tasseva, Guergana; Ishida, Miho; Anderson, Glenn; Docker, James; Ryten, Mina; Sa, Joaquim; Saraiva, Jorge M; Barnicoat, Angela; Scott, Richard; Calder, Alistair; Wattanasirichaigoon, Duangrurdee; Chrzanowska, Krystyna; Simandlová, Martina; Van Maldergem, Lionel; Stanier, Philip; Beales, Philip L; Vance, Jean E; Moore, Gudrun E

2014-01-01

Lenz-Majewski syndrome (LMS) is a syndrome of intellectual disability and multiple congenital anomalies that features generalized craniotubular hyperostosis. By using whole-exome sequencing and selecting variants consistent with the predicted dominant de novo etiology of LMS, we identified causative heterozygous missense mutations in PTDSS1, which encodes phosphatidylserine synthase 1 (PSS1). PSS1 is one of two enzymes involved in the production of phosphatidylserine. Phosphatidylserine synthesis was increased in intact fibroblasts from affected individuals, and end-product inhibition of PSS1 by phosphatidylserine was markedly reduced. Therefore, these mutations cause a gain-of-function effect associated with regulatory dysfunction of PSS1. We have identified LMS as the first human disease, to our knowledge, caused by disrupted phosphatidylserine metabolism. Our results point to an unexplored link between phosphatidylserine synthesis and bone metabolism.

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

Effects of experimental exposure to triethylamine on vision and the eye

PubMed Central

Jarvinen, P.; Engstrom, K.; Riihimaki, V.; Ruusuvaara, P.; Setala, K.

1999-01-01

OBJECTIVES: To determine the effect of triethylamine (TEA) on the cornea and to evaluate the cause of blurred vision. To find the lowest observed effect concentration of exposure to TEA. METHODS: Four people were exposed to TEA for 4 hours at concentrations of 40.6, 6.5, and 3.0 mg/m3. Before and after every exposure, symptoms and ocular microscopy findings were recorded. Binocular visual acuity and contrast sensitivity at 2.5% contrast were also measured. Also, before and after the 40.6 mg/m3 exposure, corneal thickness was measured and ocular dimensions were recorded by ultrasonography, endothelial cells of the cornea were analysed, and serum and lacrimal specimens were collected for the analysis of TEA. RESULTS: After exposure to 40.6 mg/m3 TEA there was a marked oedema in the corneal epithelium and subepithelial microcysts. However, corneal thickness increased only minimally because of the epithelial oedema. The lacrimal concentrations of TEA were, on average (range) 41 (18-83) times higher than the serum TEA concentrations. The vision was blurred in all subjects and visual acuity and contrast sensitivity had decreased in three of the four subjects. After exposure to TEA at 6.5 mg/m3 two subjects experienced symptoms, and contrast sensitivity had decreased in three of the four subjects. There were no symptoms or decreases in contrast sensitivity after exposure to a TEA concentration of 3.0 mg/m3. CONCLUSIONS: TEA caused a marked oedema and microcysts in corneal epithelium but only minor increases in corneal thickness. The effects may be mediated by the lacrimal fluid owing to its high TEA concentration. Four hour exposure to a TEA concentration of 3.0 mg/m3 seemed to cause no effects, whereas exposure to 6.5 mg/m3 for the same period caused blurred vision and a decrease in contrast sensitivity.   PMID:10341738

Natural biopolymer-based nanocomposite films for packaging applications.

PubMed

Rhim, Jong-Whan; Ng, Perry K W

2007-01-01

Concerns on environmental waste problems caused by non-biodegradable petrochemical-based plastic packaging materials as well as the consumer's demand for high quality food products has caused an increasing interest in developing biodegradable packaging materials using annually renewable natural biopolymers such as polysaccharides and proteins. Inherent shortcomings of natural polymer-based packaging materials such as low mechanical properties and low water resistance can be recovered by applying a nanocomposite technology. Polymer nanocomposites, especially natural biopolymer-layered silicate nanocomposites, exhibit markedly improved packaging properties due to their nanometer size dispersion. These improvements include increased modulus and strength, decreased gas permeability, and increased water resistance. Additionally, biologically active ingredients can be added to impart the desired functional properties to the resulting packaging materials. Consequently, natural biopolymer-based nanocomposite packaging materials with bio-functional properties have a huge potential for application in the active food packaging industry. In this review, recent advances in the preparation of natural biopolymer-based films and their nanocomposites, and their potential use in packaging applications are addressed.

In vivo effects of 17-β-estradiol on plasma immunoglobulin levels and leukocyte density in zebrafish Danio rerio

NASA Astrophysics Data System (ADS)

Li, Lei; Zhang, Shicui; Tong, Zhou; Liu, Jia

2010-05-01

Estradiol, or 17-β-estradiol (E2), the most potent naturally occurring estrogen, is involved in the hormone-immune system interaction in both mammals and fish. However, in vivo studies are largely limited, and little is known about whether E2 exerts similar effects on both female and male zebrafish ( Danio rerio). Here, we show exposure of both sexes of D. rerio to 20 nmol/L E2 resulted in a significant increase in Vg1 expression, but caused little damage to the hepatocytes, suggesting that this is the optimum E2 concentration. Also, exposure to 20 nmol/L E2 for 20 days caused a marked increase in plasma IgM levels, but had little influence on the peripheral leukocyte density, providing the first evidence of a hormone-immune system interaction in this species.

Essential role of carbonic anhydrase XII in secretory gland fluid and HCO3 (-) secretion revealed by disease causing human mutation.

PubMed

Hong, Jeong Hee; Muhammad, Emad; Zheng, Changyu; Hershkovitz, Eli; Alkrinawi, Soliman; Loewenthal, Neta; Parvari, Ruti; Muallem, Shmuel

2015-12-15

Fluid and HCO3 (-) secretion is essential for all epithelia; aberrant secretion is associated with several diseases. Carbonic anhydrase XII (CA12) is the key carbonic anhydrase in epithelial fluid and HCO3 (-) secretion and works by activating the ductal Cl(-) -HCO3 (-) exchanger AE2. Delivery of CA12 to salivary glands increases salivation in mice and of the human mutation CA12(E143K) markedly inhibits it. The human mutation CA12(E143K) causes disease due to aberrant CA12 glycosylation, and misfolding resulting in loss of AE2 activity. Aberrant epithelial fluid and HCO3 (-) secretion is associated with many diseases. The activity of HCO3 (-) transporters depends of HCO3 (-) availability that is determined by carbonic anhydrases (CAs). Which CAs are essential for epithelial function is unknown. CA12 stands out since the CA12(E143K) mutation causes salt wasting in sweat and dehydration in humans. Here, we report that expression of CA12 and of CA12(E143K) in mice salivary glands respectively increased and prominently inhibited ductal fluid secretion and salivation in vivo. CA12 markedly increases the activity and is the major HCO3 (-) supplier of ductal Cl(-) -HCO3 (-) exchanger AE2, but not of NBCe1-B. The E143K mutation alters CA12 glycosylation at N28 and N80, resulting in retention of the basolateral CA12 in the ER. Knockdown of AE2 and of CA12 inhibited pancreatic and salivary gland ductal AE2 activity and fluid secretion. Accordingly, patients homozygous for the CA12(E143K) mutation have a dry mouth, dry tongue phenotype. These findings reveal an unsuspected prominent role of CA12 in epithelial function, explain the disease and call for caution in the use of CA12 inhibitors in cancer treatment. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

S-Glutathionylation of troponin I (fast) increases contractile apparatus Ca2+ sensitivity in fast-twitch muscle fibres of rats and humans

PubMed Central

Mollica, J P; Dutka, T L; Merry, T L; Lamboley, C R; McConell, G K; McKenna, M J; Murphy, R M; Lamb, G D

2012-01-01

Oxidation can decrease or increase the Ca2+ sensitivity of the contractile apparatus in rodent fast-twitch (type II) skeletal muscle fibres, but the reactions and molecular targets involved are unknown. This study examined whether increased Ca2+ sensitivity is due to S-glutathionylation of particular cysteine residues. Skinned muscle fibres were directly activated in heavily buffered Ca2+ solutions to assess contractile apparatus Ca2+ sensitivity. Rat type II fibres were subjected to S-glutathionylation by successive treatments with 2,2′-dithiodipyridine (DTDP) and glutathione (GSH), and displayed a maximal increase in pCa50 (−log10µCa2+½ at half-maximal force) of ∼0.24 pCa units, with little or no effect on maximum force or Hill coefficient. Partial similar effect was produced by exposure to oxidized gluthathione (GSSG, 10 mm) for 10 min at pH 7.1, and near-maximal effect by GSSG treatment at pH 8.5. None of these treatments significantly altered Ca2+ sensitivity in rat type I fibres. Western blotting showed that both the DTDP–GSH and GSSG–pH 8.5 treatments caused marked S-glutathionylation of the fast troponin I isoform (TnIf) present in type II fibres, but not of troponin C (TnC) or myosin light chain 2. Both the increased Ca2+ sensitivity and glutathionylation of TnIf were blocked by N-ethylmaleimide (NEM). S-Nitrosoglutathione (GSNO) also increased Ca2+ sensitivity, but only in conditions where it caused S-glutathionylation of TnIf. In human type II fibres from vastus lateralis muscle, DTDP–GSH treatment also caused similar increased Ca2+ sensitivity and S-glutathionylation of TnIf. When the slow isoform of TnI in type I fibres of rat was partially substituted (∼30%) with TnIf, DTDP–GSH treatment caused a significant increase in Ca2+ sensitivity (∼0.08 pCa units). TnIf in type II fibres from toad and chicken muscle lack Cys133 present in mammalian TnIf, and such fibres showed no change in Ca2+ sensitivity with DTDP–GSH nor any S-glutathionylation of TnIf (latter examined only in toad). Following 40 min of cycling exercise in human subjects (at ∼60% peak oxygen consumption), TnIf in vastus lateralis muscle displayed a marked increase in S-glutathionylation (∼4-fold). These findings show that S-glutathionylation of TnIf, most probably at Cys133, increases the Ca2+ sensitivity of the contractile apparatus, and that this occurs in exercising humans, with likely beneficial effects on performance. PMID:22250211

S-glutathionylation of troponin I (fast) increases contractile apparatus Ca2+ sensitivity in fast-twitch muscle fibres of rats and humans.

PubMed

Mollica, J P; Dutka, T L; Merry, T L; Lamboley, C R; McConell, G K; McKenna, M J; Murphy, R M; Lamb, G D

2012-03-15

Oxidation can decrease or increase the Ca2+ sensitivity of the contractile apparatus in rodent fast-twitch (type II) skeletal muscle fibres, but the reactions and molecular targets involved are unknown. This study examined whether increased Ca2+ sensitivity is due to S-glutathionylation of particular cysteine residues. Skinned muscle fibres were directly activated in heavily buffered Ca2+ solutions to assess contractile apparatus Ca2+ sensitivity. Rat type II fibres were subjected to S-glutathionylation by successive treatments with 2,2′-dithiodipyridine (DTDP) and glutathione (GSH), and displayed a maximal increase in pCa50 (−log10 [Ca2+] at half-maximal force) of ∼0.24 pCa units, with little or no effect on maximum force or Hill coefficient. Partial similar effect was produced by exposure to oxidized gluthathione (GSSG, 10 mM) for 10 min at pH 7.1, and near-maximal effect by GSSG treatment at pH 8.5. None of these treatments significantly altered Ca2+ sensitivity in rat type I fibres. Western blotting showed that both the DTDP–GSH and GSSG–pH 8.5 treatments caused marked S-glutathionylation of the fast troponin I isoform (TnI(f)) present in type II fibres, but not of troponin C (TnC) or myosin light chain 2. Both the increased Ca2+ sensitivity and glutathionylation of TnI(f) were blocked by N-ethylmaleimide (NEM). S-nitrosoglutathione (GSNO) also increased Ca2+ sensitivity, but only in conditions where it caused S-glutathionylation of TnI(f). In human type II fibres from vastus lateralis muscle, DTDP–GSH treatment also caused similar increased Ca2+ sensitivity and S-glutathionylation of TnI(f). When the slow isoform of TnI in type I fibres of rat was partially substituted (∼30%) with TnI(f), DTDP–GSH treatment caused a significant increase in Ca2+ sensitivity (∼0.08 pCa units). TnIf in type II fibres from toad and chicken muscle lack Cys133 present in mammalian TnIf, and such fibres showed no change in Ca2+ sensitivity with DTDP–GSH nor any S-glutathionylation of TnI(f) (latter examined only in toad). Following 40 min of cycling exercise in human subjects (at ∼60% peak oxygen consumption), TnI(f) in vastus lateralis muscle displayed a marked increase in S-glutathionylation (∼4-fold). These findings show that S-glutathionylation of TnI(f), most probably at Cys133, increases the Ca2+ sensitivity of the contractile apparatus, and that this occurs in exercising humans, with likely beneficial effects on performance.

Obesity-driven disruption of haematopoiesis and the bone marrow niche.

PubMed

Adler, Benjamin J; Kaushansky, Kenneth; Rubin, Clinton T

2014-12-01

Obesity markedly increases susceptibility to a range of diseases and simultaneously undermines the viability and fate selection of haematopoietic stem cells (HSCs), and thus the kinetics of leukocyte production that is critical to innate and adaptive immunity. Considering that blood cell production and the differentiation of HSCs and their progeny is orchestrated, in part, by complex interacting signals emanating from the bone marrow microenvironment, it is not surprising that conditions that disturb bone marrow structure inevitably disrupt both the numbers and lineage-fates of these key blood cell progenitors. In addition to the increased adipose burden in visceral and subcutaneous compartments, obesity causes a marked increase in the size and number of adipocytes encroaching into the bone marrow space, almost certainly disturbing HSC interactions with neighbouring cells, which include osteoblasts, osteoclasts, mesenchymal cells and endothelial cells. As the global obesity pandemic grows, the short-term and long-term consequences of increased bone marrow adiposity on HSC lineage selection and immune function remain uncertain. This Review discusses the differentiation and function of haematopoietic cell populations, the principal physicochemical components of the bone marrow niche, and how this environment influences HSCs and haematopoiesis in general. The effect of adipocytes and adiposity on HSC and progenitor cell populations is also discussed, with the goal of understanding how obesity might compromise the core haematopoietic system.

Modification of kindled amygdaloid seizures by opiate agonists and antagonists.

PubMed

Albertson, T E; Joy, R M; Stark, L G

1984-03-01

The effects of 19 opiate agonists and antagonists on kindled amygdaloid seizures in the rat were studied. The mu agonists tended to reduce the length of elicited afterdischarges and behavioral ranks, while markedly increasing postictal electroencephalogram spikes and behavioral arrest time. These effects were reversed by naloxone. The kappa agonists reduced behavioral rank and variably reduced afterdischarge length with a concomitant lengthening of postictal behavioral arrest time and number of electroencephalogram spikes. The putative sigma agonist, SKF 10,047, reduced afterdischarge durations only at the higher doses tested. The decreases found after the sigma agonists in postictal electroencephalogram spiking and time of behavioral arrest were not reversed by naloxone. Only the lower doses of normeperidine were found to decrease seizure thresholds. The mixed agonist/antagonists (MAA) cyclazocine and cyclorphan markedly increased seizure threshold and reduced afterdischarge duration and behavioral rank. Only the MAA pentazocine tended to increase threshold but not suprathreshold afterdischarge durations. The order of ability to modify the ictal events was MAA (selected) greater than kappa agonists greater than mu agonists greater than sigma agonists. The increase in postictal events (behavior arrest and spikes) was caused most effectively by pretreatment with mu agonist greater than kappa agonist greater than selected MAA greater than sigma agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

X-chromosomal inactivation directly influences the phenotypic manifestation of X-linked protoporphyria

PubMed Central

Brancaleoni, V.; Balwani, M.; Granata, F.; Graziadei, G.; Missineo, P.; Fiorentino, V.; Fustinoni, S.; Cappellini, M.D.; Naik, H.; Desnick, R.J.; Di Pierro, E.

2015-01-01

X-linked protoporphyria (XLP), a rare erythropoietic porphyria, results from terminal exon gain-of-function mutations in the ALAS2 gene causing increased ALAS2 activity and markedly increased erythrocyte protoporphyrin levels. Patients present with severe cutaneous photosensitivity and may develop liver dysfunction. XLP was originally reported as X-linked dominant with 100% penetrance in males and females. We characterized 11 heterozygous females from six unrelated XLP families and show markedly varying phenotypic and biochemical heterogeneity, reflecting the degree of X-chromsomal inactivation of the mutant gene. ALAS2 sequencing identified the specific mutation and confirmed heterozygosity among the females. Clinical history, plasma and erythrocyte protoporphyrin levels were determined. Methylation assays of the androgen receptor and zinc-finger MYM type 3 short tandem repeat polymorphisms estimated each heterozygotes X-chromosomal inactivation pattern. Heterozygotes with equal or increased skewing, favoring expression of the wild-type allele had no clinical symptoms and only slightly increased erythrocyte protoporphyrin concentrations and/or frequency of protoporphyrin-containing peripheral blood fluorocytes. When the wild-type allele was preferentially inactivated, heterozygous females manifested the disease phenotype and had both higher erythrocyte protoporphyrin levels and circulating fluorocytes. These findings confirm that the previous dominant classification of XLP is inappropriate and genetically misleading, as the disorder is more appropriately designated XLP. PMID:25615817

GNPAT p.D519G is independently associated with markedly increased iron stores in HFE p.C282Y homozygotes.

PubMed

Barton, James C; Chen, Wen-Pin; Emond, Mary J; Phatak, Pradyumna D; Subramaniam, V Nathan; Adams, Paul C; Gurrin, Lyle C; Anderson, Gregory J; Ramm, Grant A; Powell, Lawrie W; Allen, Katrina J; Phillips, John D; Parker, Charles J; McLaren, Gordon D; McLaren, Christine E

2017-03-01

GNPAT p.D519G positivity is significantly increased in HFE p.C282Y homozygotes with markedly increased iron stores. We sought to determine associations of p.D519G and iron-related variables with iron stores in p.C282Y homozygotes. We defined markedly increased iron stores as serum ferritin >2247pmol/L (>1000μg/L) and either hepatic iron >236μmol/g dry weight or iron >10g by induction phlebotomy (men and women). We defined normal or mildly elevated iron stores as serum ferritin <674.1pmol/L (<300μg/L) or either age≥40y with iron ≤2.5g iron by induction phlebotomy or age≥50y with ≤3.0g iron by induction phlebotomy (men only). We compared participant subgroups using univariate methods. Using multivariable logistic regression, we evaluated associations of markedly increased iron stores with these variables: age; iron supplement use (dichotomous); whole blood units donated; erythrocyte units received as transfusion; daily alcohol consumption, g; and p.D519G positivity (heterozygosity or homozygosity). The mean age of 56 participants (94.6% men) was 55±10 (SD) y; 41 had markedly increased iron stores. Prevalences of swollen/tender 2nd/3rd metacarpophalangeal joints and elevated aspartate or alanine aminotransferase were significantly greater in participants with markedly increased iron stores. Only participants with markedly increased iron stores had cirrhosis. In multivariable analyses, p.D519G positivity was the only exposure variable significantly associated with markedly increased iron stores (odds ratio 9.9, 95% CI [1.6, 60.3], p=0.0126). GNPAT p.D519G is strongly associated with markedly increased iron stores in p.C282Y homozygotes after correction for age, iron-related variables, and alcohol consumption. Copyright © 2016 Elsevier Inc. All rights reserved.

Early life nutrition, epigenetics and programming of later life disease.

PubMed

Vickers, Mark H

2014-06-02

The global pandemic of obesity and type 2 diabetes is often causally linked to marked changes in diet and lifestyle; namely marked increases in dietary intakes of high energy diets and concomitant reductions in physical activity levels. However, less attention has been paid to the role of developmental plasticity and alterations in phenotypic outcomes resulting from altered environmental conditions during the early life period. Human and experimental animal studies have highlighted the link between alterations in the early life environment and increased risk of obesity and metabolic disorders in later life. This link is conceptualised as the developmental programming hypothesis whereby environmental influences during critical periods of developmental plasticity can elicit lifelong effects on the health and well-being of the offspring. In particular, the nutritional environment in which the fetus or infant develops influences the risk of metabolic disorders in offspring. The late onset of such diseases in response to earlier transient experiences has led to the suggestion that developmental programming may have an epigenetic component, as epigenetic marks such as DNA methylation or histone tail modifications could provide a persistent memory of earlier nutritional states. Moreover, evidence exists, at least from animal models, that such epigenetic programming should be viewed as a transgenerational phenomenon. However, the mechanisms by which early environmental insults can have long-term effects on offspring are relatively unclear. Thus far, these mechanisms include permanent structural changes to the organ caused by suboptimal levels of an important factor during a critical developmental period, changes in gene expression caused by epigenetic modifications (including DNA methylation, histone modification, and microRNA) and permanent changes in cellular ageing. A better understanding of the epigenetic basis of developmental programming and how these effects may be transmitted across generations is essential for the implementation of initiatives aimed at curbing the current obesity and diabetes crisis.

In vivo selection of hematopoietic progenitor cells and temozolomide dose intensification in rhesus macaques through lentiviral transduction with a drug resistance gene

PubMed Central

Larochelle, Andre; Choi, Uimook; Shou, Yan; Naumann, Nora; Loktionova, Natalia A.; Clevenger, Joshua R.; Krouse, Allen; Metzger, Mark; Donahue, Robert E.; Kang, Elizabeth; Stewart, Clinton; Persons, Derek; Malech, Harry L.; Dunbar, Cynthia E.; Sorrentino, Brian P.

2009-01-01

Major limitations to gene therapy using HSCs are low gene transfer efficiency and the inability of most therapeutic genes to confer a selective advantage on the gene-corrected cells. One approach to enrich for gene-modified cells in vivo is to include in the retroviral vector a drug resistance gene, such as the P140K mutant of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT*). We transplanted 5 rhesus macaques with CD34+ cells transduced with lentiviral vectors encoding MGMT* and a fluorescent marker, with or without homeobox B4 (HOXB4), a potent stem cell self-renewal gene. Transgene expression and common integration sites in lymphoid and myeloid lineages several months after transplantation confirmed transduction of long-term repopulating HSCs. However, all animals showed only a transient increase in gene-marked lymphoid and myeloid cells after O6-benzylguanine (BG) and temozolomide (TMZ) administration. In 1 animal, cells transduced with MGMT* lentiviral vectors were protected and expanded after multiple courses of BG/TMZ, providing a substantial increase in the maximum tolerated dose of TMZ. Additional cycles of chemotherapy using 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) resulted in similar increases in gene marking levels, but caused high levels of nonhematopoietic toxicity. Inclusion of HOXB4 in the MGMT* vectors resulted in no substantial increase in gene marking or HSC amplification after chemotherapy treatment. Our data therefore suggest that lentivirally mediated gene transfer in transplanted HSCs can provide in vivo chemoprotection of progenitor cells, although selection of long-term repopulating HSCs was not seen. PMID:19509470

Accumulation of hydroxyproline-rich glycoprotein mRNAs in response to fungal elicitor and infection.

PubMed

Showalter, A M; Bell, J N; Cramer, C L; Bailey, J A; Varner, J E; Lamb, C J

1985-10-01

Hydroxyproline-rich glycoproteins (HRGPs) are important structural components of plant cell walls and also accumulate in response to infection as an apparent defense mechanism. Accumulation of HRGP mRNA in biologically stressed bean (Phaseolus vulgaris L.) cells was monitored by blot hybridization with (32)P-labeled tomato genomic HRGP sequences. Elicitor treatment of suspension-cultured cells caused a marked increase in hybridizable HRGP mRNA. The response was less rapid but more prolonged than that observed for mRNAs encoding enzymes of phytoalexin biosynthesis. HRGP mRNA also accumulated during race:cultivar-specific interactions between bean hypocotyls and the partially biotrophic fungus Colletotrichum lindemuthianum, the causal agent of anthracnose. In an incompatible interaction (host resistant) there was an early increase in HRGP mRNA correlated with expression of hypersensitive resistance; whereas, in a compatible interaction (host susceptible), marked accumulation of HRGP mRNA occurred as a delayed response at the onset of lesion formation. In both interactions, mRNA accumulation was observed in uninfected cells distant from the site of fungal inoculation, indicating intercellular transmission of an elicitation signal.

[Hypernatremia caused by treatment with GHB obtained via a doctor's prescription].

PubMed

Rood, I M; Seijger, C G W; van Waarde, J A; de Maat, M M R; Verhave, J C; Blans, M J

In the last few years, gamma hydroxybutyric acid (GHB) has been used increasingly as a party drug; this has led to a marked increase in the number of requests for professional help with the treatment of GHB addiction. Pharmaceutical GHB (sodium oxybate, the sodium-salt of GHB), registered for cataplexia in narcolepsy patients, is used off-label to treat the withdrawal symptoms associated with GHB addiction. Pharmaceutical GHB has a high sodium load. In this report we present the cases of two patients who developed symptomatic hypernatremia following treatment with pharmaceutical GHB and who thereafter needed intensive care for the severe withdrawal symptoms that they experienced.

The interplay of attention economics and computer-aided detection marks in screening mammography

NASA Astrophysics Data System (ADS)

Schwartz, Tayler M.; Sridharan, Radhika; Wei, Wei; Lukyanchenko, Olga; Geiser, William; Whitman, Gary J.; Haygood, Tamara Miner

2016-03-01

Introduction: According to attention economists, overabundant information leads to decreased attention for individual pieces of information. Computer-aided detection (CAD) alerts radiologists to findings potentially associated with breast cancer but is notorious for creating an abundance of false-positive marks. We suspected that increased CAD marks do not lengthen mammogram interpretation time, as radiologists will selectively disregard these marks when present in larger numbers. We explore the relevance of attention economics in mammography by examining how the number of CAD marks affects interpretation time. Methods: We performed a retrospective review of bilateral digital screening mammograms obtained between January 1, 2011 and February 28, 2014, using only weekend interpretations to decrease distractions and the likelihood of trainee participation. We stratified data according to reader and used ANOVA to assess the relationship between number of CAD marks and interpretation time. Results: Ten radiologists, with median experience after residency of 12.5 years (range 6 to 24,) interpreted 1849 mammograms. When accounting for number of images, Breast Imaging Reporting and Data System category, and breast density, increasing numbers of CAD marks was correlated with longer interpretation time only for the three radiologists with the fewest years of experience (median 7 years.) Conclusion: For the 7 most experienced readers, increasing CAD marks did not lengthen interpretation time. We surmise that as CAD marks increase, the attention given to individual marks decreases. Experienced radiologists may rapidly dismiss larger numbers of CAD marks as false-positive, having learned that devoting extra attention to such marks does not improve clinical detection.

Visual detection of gas shows from coal core and cuttings using liquid leak detector

USGS Publications Warehouse

Barker, C.E.

2006-01-01

Portions of core or cutting samples that have active gas shows can be identified by applying a liquid leak detector to the core surface. Although these gas shows can be caused by manmade changes to the coals' internal structure and surface of the core during the coring process, in many cases, the marked gas shows overlie changes in maceral composition, subtle fractures or coal, coal structure and so forth that seemingly are places where natural primary permeability is higher and gas shows would be favored. Given the limited time available for core description before a core is closed in a canister, using the liquid leak detector method to mark gas shows enhances core description by providing a photographic record of places of apparently increased gas flow likely related to enhanced coal permeability that cannot be easily detected otherwise.

Protective Effect of a Synbiotic against Multidrug-Resistant Acinetobacter baumannii in a Murine Infection Model

PubMed Central

Takahashi, Akira; Yuki, Norikatsu; Kaji, Rumi; Takahashi, Takuya; Nomoto, Koji

2016-01-01

This study investigated the ability of the probiotic Bifidobacterium breve strain Yakult (BbY) to protect against infection, as well as the potentiation of BbY activity by the synbiotic combination of BbY and prebiotic galactooligosaccharides (GOS). The study employed a mouse model of lethal intestinal multidrug-resistant Acinetobacter baumannii (MDRAb) infection. The endogenous intestinal microbiota was disrupted by the administration of multiple antibiotics, causing the loss of endogenous Bifidobacterium. Oral infection of these mice with MDRAb resulted in marked growth of this organism. Additional treatment of the infected mice with a sublethal dose of 5-fluorouracil (5-FU) induced systemic invasion by MDRAb and subsequent animal death. The continuous oral administration of BbY increased the survival rate and inhibited the intestinal growth and invasion by MDRAb in the infection model. Disruptions of the intestinal environment and barrier function in the infected mice were attenuated by BbY. Protection against the MDRAb infection was markedly potentiated by a synbiotic combination of BbY and GOS, although GOS by itself did not provide protection. Negative correlations were observed between intestinal MDRAb and BbY counts or acetic acid levels; positive correlations were observed between acetic acid levels and intestinal epithelium expression of tight-junction-related genes. These results demonstrated that the probiotic and synbiotic markedly potentiated protection against fatal intestinal infection caused by a multidrug-resistant bacterium. Probiotics and synbiotics are presumed to provide protection by compensation for the disrupted indigenous populations, thereby maintaining the intestinal environments and barrier functions otherwise targeted during opportunistic infection by MDRAb. PMID:26953197

Local Acetaldehyde—An Essential Role in Alcohol-Related Upper Gastrointestinal Tract Carcinogenesis

PubMed Central

Salaspuro, Mikko

2018-01-01

The resident microbiome plays a key role in exposure of the upper gastrointestinal (GI) tract mucosa to acetaldehyde (ACH), a carcinogenic metabolite of ethanol. Poor oral health is a significant risk factor for oral and esophageal carcinogenesis and is characterized by a dysbiotic microbiome. Dysbiosis leads to increased growth of opportunistic pathogens (such as Candida yeasts) and may cause an up to 100% increase in the local ACH production, which is further modified by organ-specific expression and gene polymorphisms of ethanol-metabolizing and ACH-metabolizing enzymes. A point mutation in the aldehyde dehydrogenase 2 gene has randomized millions of alcohol consumers to markedly increased local ACH exposure via saliva and gastric juice, which is associated with a manifold risk for upper GI tract cancers. This human cancer model proves conclusively the causal relationship between ACH and upper GI tract carcinogenesis and provides novel possibilities for the quantitative assessment of ACH carcinogenicity in the human oropharynx. ACH formed from ethanol present in “non-alcoholic” beverages, fermented food, or added during food preparation forms a significant epidemiologic bias in cancer epidemiology. The same also concerns “free” ACH present in mutagenic concentrations in multiple beverages and foodstuffs. Local exposure to ACH is cumulative and can be reduced markedly both at the population and individual level. At best, a person would never consume tobacco, alcohol, or both. However, even smoking cessation and moderation of alcohol consumption are associated with a marked decrease in local ACH exposure and cancer risk, especially among established risk groups. PMID:29303995

Evidence that dorsally mounted satellite transmitters affect migration chronology of Northern Pintails

USGS Publications Warehouse

Hupp, Jerry W.; Kharitonov, Sergei; Yamaguchi, Noriyuki M.; Ozaki, K.; Flint, Paul L.; Pearce, John M.; Tokita, Ken-ichi; Shimada, Tetsuo; Higuchi, Hiroyoshi

2015-01-01

We compared migration movements and chronology between Northern Pintails (Anas acuta) marked with dorsally mounted satellite transmitters and pintails marked only with tarsus rings. During weekly intervals of spring and autumn migration between their wintering area in Japan and nesting areas in Russia, the mean distance that ringed pintails had migrated was up to 1000 km farther than the mean distance radiomarked pintails migrated. Radiomarked pintails were detected at spring migration sites on average 9.9 days (90 % CI 8.0, 11.8) later than ringed pintails that were recovered within 50 km. Although ringed and radiomarked pintails departed from Japan on similar dates, the disparity in detection of radiomarked versus ringed pintails at shared sites increased 7.7 days (90 % CI 5.2, 10.2) for each 1000 km increase in distance from Japan. Thus, pintails marked with satellite transmitters arrived at nesting areas that were 2500 km from Japan on average 19 days later than ringed birds. Radiomarked pintails were detected at autumn migration stopovers on average 13.1 days (90 % CI 9.8, 16.4) later than ringed birds that were recovered within 50 km. We hypothesize that dorsal attachment of 12–20 g satellite transmitters to Northern Pintails increased the energetic cost of flight, which resulted in more rapid depletion of energetic reserves and shortened the distance pintails could fly without refueling. Radiomarked pintails may have used more stopovers or spent longer periods at stopovers. causing their migration schedule to diverge from ringed pintails. We urge further evaluation of the effects of dorsally mounted transmitters on migration chronology of waterfowl.

Regulation of virulence by a two-component system in group B streptococcus.

PubMed

Jiang, Sheng-Mei; Cieslewicz, Michael J; Kasper, Dennis L; Wessels, Michael R

2005-02-01

Group B Streptococcus (GBS) is frequently carried in the gastrointestinal or genitourinary tract as a commensal organism, yet it has the potential to cause life-threatening infection in newborn infants, pregnant women, and individuals with chronic illness. Regulation of virulence factor expression may affect whether GBS behaves as an asymptomatic colonizer or an invasive pathogen, but little is known about how such factors are controlled in GBS. We now report the characterization of a GBS locus that encodes a two-component regulatory system similar to CsrRS (or CovRS) in Streptococcus pyogenes. Inactivation of csrR, encoding the putative response regulator, in two unrelated wild-type strains of GBS resulted in a marked increase in production of beta-hemolysin/cytolysin and a striking decrease in production of CAMP factor, an unrelated cytolytic toxin. Quantitative RNA hybridization experiments revealed that these two phenotypes were associated with a marked increase and decrease in expression of the corresponding genes, cylE and cfb, respectively. The CsrR mutant strains also displayed increased expression of scpB encoding C5a peptidase. Similar, but less marked, changes in gene expression were observed in CsrS (putative sensor component) mutants, evidence that CsrR and CsrS constitute a functional two-component system. Experimental infection studies in mice demonstrated reduced virulence of both CsrR and CsrS mutant strains relative to the wild type. Together, these results indicate that CsrRS regulates expression of multiple GBS virulence determinants and is likely to play an important role in GBS pathogenesis.

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.

Midwifery students experience of teamwork projects involving mark-related peer feedback.

PubMed

Hastie, Carolyn R; Fahy, Kathleen M; Parratt, Jenny A; Grace, Sandra

2016-06-01

Lack of teamwork skills among health care professionals endangers patients and enables workplace bullying. Individual teamwork skills are increasingly being assessed in the undergraduate health courses but rarely defined, made explicit or taught. To remedy these deficiencies we introduced a longitudinal educational strategy across all three years of the Bachelor of Midwifery program. To report on students' experiences of engaging in team based assignments which involved mark-related peer feedback. Stories of midwifery students' experiences were collected from 17 participants across the three years of the degree. These were transcribed and analysed thematically and interpreted using feminist collaborative conversations. Most participants reported being in well-functioning teams and enjoyed the experience; they spoke of 'we' and said 'Everyone was on Board'. Students in poorly functioning teams spoke of 'I' and 'they'. These students complained about the poor performance of others but they didn't speak up because they 'didn't want to make waves' and they didn't have the skills to be able to confidently manage conflict. All participants agreed 'Peer-related marks cause mayhem'. Teamwork skills should be specifically taught and assessed. These skills take time to develop. Students, therefore, should be engaged in a teamwork assignment in each semester of the entire program. Peer feedback should be moderated by the teacher and not directly related to marks. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Respiratory Viral Infection in Neonatal Piglets Causes Marked Microglia Activation in the Hippocampus and Deficits in Spatial Learning

PubMed Central

Elmore, Monica R. P.; Burton, Michael D.; Conrad, Matthew S.; Rytych, Jennifer L.; Van Alstine, William G.

2014-01-01

Environmental insults during sensitive periods can affect hippocampal development and function, but little is known about peripheral infection, especially in humans and other animals whose brain is gyrencephalic and experiences major perinatal growth. Using a piglet model, the present study showed that inoculation on postnatal day 7 with the porcine reproductive and respiratory syndrome virus (PRRSV) caused microglial activation within the hippocampus with 82% and 43% of isolated microglia being MHC II+ 13 and 20 d after inoculation, respectively. In control piglets, <5% of microglia isolated from the hippocampus were MHC II+. PRRSV piglets were febrile (p < 0.0001), anorectic (p < 0.0001), and weighed less at the end of the study (p = 0.002) compared with control piglets. Increased inflammatory gene expression (e.g., IL-1β, IL-6, TNF-α, and IFN-γ) was seen across multiple brain regions, including the hippocampus, whereas reductions in CD200, NGF, and MBP were evident. In a test of spatial learning, PRRSV piglets took longer to acquire the task, had a longer latency to choice, and had a higher total distance moved. Overall, these data demonstrate that viral respiratory infection is associated with a marked increase in activated microglia in the hippocampus, neuroinflammation, and impaired performance in a spatial cognitive task. As respiratory infections are common in human neonates and infants, approaches to regulate microglial cell activity are likely to be important. PMID:24501353

Hereditary internal anal sphincter myopathy causing proctalgia fugax and constipation. A newly identified condition.

PubMed

Kamm, M A; Hoyle, C H; Burleigh, D E; Law, P J; Swash, M; Martin, J E; Nicholls, R J; Northover, J M

1991-03-01

A newly identified myopathy of the internal anal sphincter is described. In the affected family, at least one member from each of five generations had severe proctalgia fugax; onset was usually in the third to fifth decades of life. Three members of the family have been studied in detail. Each had severe pain intermittently during the day and hourly during the night. Constipation was an associated symptom, in particular difficulty with rectal evacuation. Clinically the internal anal sphincter was thickened and of decreased compliance. The maximum anal canal pressure was usually increased with marked ultraslow wave activity. Anal endosonography confirmed a grossly thickened internal anal sphincter. Two patients were treated by internal anal sphincter strip myectomy; one showed marked improvement and one was relieved of the constipation but had only slight improvement of the pain. The hypertrophied muscle in two of the patients showed unique myopathic changes, consisting of vacuolar changes with periodic acid-Schiff-positive polyglycosan bodies in the smooth muscle fibers and increased endomysial fibrosis. In vitro organ-bath studies showed insensitivity of the muscle to noradrenaline, isoprenaline, carbachol, dimethylpiperazinium, and electrical-field stimulation. Immunohistochemical studies for substance P, calcitonin gene-related peptide, galanin, neuropeptide Y, and vasoactive intestinal peptide showed staining in a similar distribution to that in control tissue. A specific autosomal-dominant inherited myopathy of the internal anal sphincter that causes anal pain and constipation has been identified and characterized.

Pulmonary blood flow and pulmonary hypertension: Is the pulmonary circulation flowophobic or flowophilic?

PubMed Central

Kulik, Thomas J.

2012-01-01

Increased pulmonary blood flow (PBF) is widely thought to provoke pulmonary vascular obstructive disease (PVO), but the impact of wall shear stress in the lung is actually poorly defined. We examined information from patients having cardiac lesions which impact the pulmonary circulation in distinct ways, as well as experimental studies, asking how altered hemodynamics impact the risk of developing PVO. Our results are as follows: (1) with atrial septal defect (ASD; increased PBF but low PAP), shear stress may be increased but there is little tendency to develop PVO; (2) with normal PBF but increased pulmonary vascular resistance (PVR; mitral valve disease) shear stress may also be increased but risk of PVO still low; (3) with high PVR and PBF (e.g., large ventricular septal defect), wall shear stress is markedly increased and the likelihood of developing PVO is much higher than with high PBF or PAP only; and (4) with ASD, experimental and clinical observations suggest that increased PBF plus another stimulus (e.g., endothelial inflammation) may be required for PVO. We conclude that modestly increased wall shear stress (e.g., ASD) infrequently provokes PVO, and likely requires other factors to be harmful. Likewise, increased PAP seldom causes PVO. Markedly increased wall shear stress may greatly increase the likelihood of PVO, but we cannot discriminate its effect from the combined effects of increased PAP and PBF. Finally, the age of onset of increased PAP may critically impact the risk of PVO. Some implications of these observations for future investigations are discussed. PMID:23130101

Injury of cortical neurons is caused by the advanced glycation end products-mediated pathway☆

PubMed Central

Xing, Ying; Zhang, Xu; Song, Xiangfu; Lv, Zhongwen; Hou, Lingling; Li, Fei

2013-01-01

Advanced glycation end products lead to cell apoptosis, and cause cell death by increasing endoplasmic reticulum stress. Advanced glycation end products alone may also directly cause damage to tissues and cells, but the precise mechanism remains unknown. This study used primary cultures of rat cerebral cortex neurons, and treated cells with different concentrations of glycation end products (50, 100, 200, 400 mg/L), and with an antibody for the receptor of advanced glycation end products before and after treatment with advanced glycation end products. The results showed that with increasing concentrations of glycation end products, free radical content increased in neurons, and the number of apoptotic cells increased in a dose-dependent manner. Before and after treatment of advanced glycation end products, the addition of the antibody against advanced glycation end-products markedly reduced hydroxyl free radicals, malondialdehyde levels, and inhibited cell apoptosis. This result indicated that the antibody for receptor of advanced glycation end-products in neurons from the rat cerebral cortex can reduce glycation end product-induced oxidative stress damage by suppressing glycation end product receptors. Overall, our study confirms that the advanced glycation end products-advanced glycation end products receptor pathway may be the main signaling pathway leading to neuronal damage. PMID:25206382

Perioperative ultrasound-guided wire marking of calcific deposits in calcifying tendinitis of the rotator cuff.

PubMed

Sigg, Andreas; Draws, Detlev; Stamm, Axel; Pfeiffer, Michael

2011-03-01

The identification of a calcific deposit in the rotator cuff can often cause difficulties. A new technique is described to identify the calcific deposit perioperatively with a ultrasound-guided wire. The technique allows a safe direct marking of calcific deposits making the procedure faster especially in difficult cases.

Physicochemical properties of foal meat as affected by cooking methods.

PubMed

Lorenzo, José M; Cittadini, Aurora; Munekata, Paulo E; Domínguez, Rubén

2015-10-01

The present study deals with the effect of four different cooking techniques (roasting, grilling, microwave baking and frying with olive oil) on physicochemical parameters (cooking loss, WHC, texture and colour) and lipid oxidation (by TBARS measurement) of foal meat. Thermal treatments induced water loss (P<0.001), being lower in foal steaks cooked in the grill (25.8%) and higher in foal samples cooked in the microwave (39.5%). As it was expected, all the cooking methods increased TBARS index, since high temperature during cooking seems to cause an increase of the lipid oxidation in foal steaks. Statistical analysis displayed that WHC was affected (P<0.001) by thermal treatment, since the smallest WHC values were observed in samples from microwave treatment. Thermal treatment also caused a significant (P<0.001) increase in the force needed to cut the foal steaks. Regarding colour parameter, cooking led to an increase of L*-value (lightness) and b*-value (yellowness), while a*-value (redness) markedly decreased in all samples. Copyright © 2015 Elsevier Ltd. All rights reserved.

Characteristics of Dysphagia in Infants with Microcephaly Caused by Congenital Zika Virus Infection, Brazil, 2015.

PubMed

Leal, Mariana C; van der Linden, Vanessa; Bezerra, Thiago P; de Valois, Luciana; Borges, Adriana C G; Antunes, Margarida M C; Brandt, Kátia G; Moura, Catharina X; Rodrigues, Laura C; Ximenes, Coeli R

2017-08-01

We summarize the characteristics of dysphagia in 9 infants in Brazil with microcephaly caused by congenital Zika virus infection. The Schedule for Oral Motor Assessment, fiberoptic endoscopic evaluation of swallowing, and the videofluoroscopic swallowing study were used as noninstrumental and instrumental assessments. All infants had a degree of neurologic damage and showed abnormalities in the oral phase. Of the 9 infants, 8 lacked oral and upper respiratory tract sensitivity, leading to delays in initiation of the pharyngeal phase of swallowing. Those delays, combined with marked oral dysfunction, increased the risk for aspiration of food, particularly liquid foods. Dysphagia resulting from congenital Zika virus syndrome microcephaly can develop in infants >3 months of age and is severe.

Characteristics of Dysphagia in Infants with Microcephaly Caused by Congenital Zika Virus Infection, Brazil, 2015

PubMed Central

van der Linden, Vanessa; Bezerra, Thiago P.; de Valois, Luciana; Borges, Adriana C.G.; Antunes, Margarida M.C.; Brandt, Kátia G.; Moura, Catharina X.; Rodrigues, Laura C.; Ximenes, Coeli R.

2017-01-01

We summarize the characteristics of dysphagia in 9 infants in Brazil with microcephaly caused by congenital Zika virus infection. The Schedule for Oral Motor Assessment, fiberoptic endoscopic evaluation of swallowing, and the videofluoroscopic swallowing study were used as noninstrumental and instrumental assessments. All infants had a degree of neurologic damage and showed abnormalities in the oral phase. Of the 9 infants, 8 lacked oral and upper respiratory tract sensitivity, leading to delays in initiation of the pharyngeal phase of swallowing. Those delays, combined with marked oral dysfunction, increased the risk for aspiration of food, particularly liquid foods. Dysphagia resulting from congenital Zika virus syndrome microcephaly can develop in infants >3 months of age and is severe. PMID:28604336

Interpretation of snow-climate feedback as produced by 17 general circulation models

NASA Technical Reports Server (NTRS)

Cess, R. D.; Zhang, M.-H.; Potter, G. L.; Blanchet, J.-P.; Chalita, S.; Colman, R.; Dazlich, D. A.; Del Genio, A. D.; Lacis, A. A.; Dymnikov, V.

1991-01-01

Snow feedback is expected to amplify global warming caused by increasing concentrations of atmospheric greenhouse gases. The conventional explanation is that a warmer earth will have less snow cover, resulting in a darker planet that absorbs more solar radiation. An intercomparison of 17 general circulation models, for which perturbations of sea surface temperature were used as a surrogate climate change, suggests that this explanation is overly simplistic. The results instead indicate that additional amplification or moderation may be caused both by cloud interactions and longwave radiation. One measure of this net effect of snow feedback was found to differ markedly among the 17 climate models, ranging from weak negative feedback in some models to strong positive feedback in others.

Insulin autoimmune syndrome caused by an adhesive skin patch containing loxoprofen-sodium.

PubMed

Okazaki-Sakai, Satoko; Yoshimoto, Sachiko; Yagi, Kunimasa; Wakasugi, Takanobu; Takeda, Yoshiyu; Yamagishi, Masakazu

2013-01-01

A 62-year-old woman complained of repeated hypoglycemic events. A 75 g oral glucose tolerance test (75 gOGTT) showed a marked increase in the plasma insulin level and impaired glucose tolerance. The patient exhibited a high titer of plasma anti-insulin autoantibodies. Her diagnosis was insulin autoimmune syndrome (IAS). Following the cessation of loxoprofen-sodium (LOXs), she experienced no further hypoglycemic episodes. However, the hypoglycemic attacks recurred following the accidental readministration of LOXs in an adhesive skin patch. Considering the changes in the titer of anti-insulin autoantibodies, the repeated 75 gOGTT and the repeated Scatchard analysis, we determined LOXs to be the cause of the IAS and evaluated the characteristics of the autoantibodies.

Triglyceride Treatment in the Age of Cholesterol Reduction

PubMed Central

Agrawal, Nidhi; Corradi, Patricia Freitas; Gumaste, Namrata; Goldberg, Ira J.

2017-01-01

Cholesterol reduction has markedly reduced major cardiovascular disease (CVD) events and shown regression of atherosclerosis in some studies. However, CVD has for decades also been associated with increased levels of circulating triglyceride (TG)-rich lipoproteins. Whether this is due to a direct toxic effect of these lipoproteins on arteries or whether this is merely an association is unresolved. More recent genetic analyses have linked genes that modulate TG metabolism with CVD. Moreover, analyses of subgroups of hypertriglyceridemic (HTG) subjects in clinical trials using fibric acid drugs have been interpreted as evidence that TG reduction reduces CVD events. This review will focus on how HTG might cause CVD, whether TG reduction makes a difference, what pathophysiological defects cause HTG, and what options are available for treatment. PMID:27544319

Sea lamprey (Petromyzon marinus) parasite-host interactions in the Great Lakes

USGS Publications Warehouse

Bence, James R.; Bergstedt, Roger A.; Christie, Gavin C.; Cochran, Phillip A.; Ebener, Mark P.; Koonce, Joseph F.; Rutter, Michael A.; Swink, William D.

2003-01-01

Prediction of how host mortality responds to efforts to control sea lampreys (Petromyzon marinus) is central to the integrated management strategy for sea lamprey (IMSL) in the Great Lakes. A parasite-host submodel is used as part of this strategy, and this includes a type-2 multi-species functional response, a developmental response, but no numerical response. General patterns of host species and size selection are consistent with the model assumptions, but some observations appear to diverge. For example, some patterns in sea lamprey marking on hosts suggest increases in selectivity for less preferred hosts and lower host survival when preferred hosts are scarce. Nevertheless, many of the IMSL assumptions may be adequate under conditions targeted by fish community objectives. Of great concern is the possibility that the survival of young parasites (parasitic-phase sea lampreys) varies substantially among lakes or over time. Joint analysis of abundance estimates for parasites being produced in streams and returning spawners could address this. Data on sea lamprey marks is a critical source of information on sea lamprey activity and potential effects. Theory connecting observed marks to sea lamprey feeding activity and host mortality is reviewed. Uncertainties regarding healing and attachment times, the probability of hosts surviving attacks, and problems in consistent classification of marks have led to widely divergent estimates of damages caused by sea lamprey. Laboratory and field studies are recommended to provide a firmer linkage between host blood loss, host mortality, and observed marks on surviving hosts, so as to improve estimates of damage.

[A homicidal strangulation by ligature, disguised as a suicidal hanging].

PubMed

Ueno, Y; Fukunaga, T; Nakagawa, K; Imabayashi, T; Fujiwara, S; Adachi, J; Mizoi, Y

1989-02-01

A naked 38-year-old woman was found dead, lying beside a bed in a guest room of a hotel. A cotton cord was looped around her neck, with one end tied to a bedpost. Thus it seemed that she had hanged herself in a lying position. Yet, certain suspicious factors gave rise to doubts. The hair and a necklace were intertwined with the cord and a man that had been staying in the same room had fled. On the postmortem examination, marked congestion and many petechial haemorrhages were seen in the face and the upper area of the neck, also in conjunctiva. A light-brown and highly dry ligature mark, about one centimeter in width, was found on the neck. The mark, crossing the front of the neck, was clearly evident from the back to the right side of the neck. The lower borders of the congestion and petechial haemorrhages in the face and neck were located 1 or 2 centimeters above the ligature mark. On the left side of the neck, another pale ligature mark with slight subcutaneous haemorrhages was seen between the dry mark and the lower border of the congested part of the neck. A similar ligature mark also was found on the back of the neck. On internal examination, congestion of the cervical lymph nodes and haemorrhages in the cervical muscles were recognized in the areas of the cutaneous congestion. These findings supported suspicions that the dry ligature mark had been caused by hanging after her death, and that the light ligature mark with slight subcutaneous haemorrhages on the left side and back of the neck had been caused by strangulation, which had brought on the victim's death. Therefore, it was decided that her death had been disguised as a suicidal hanging, after she had been strangled by ligature. A week later, her former husband was arrested and confessed his crime.

A mechanism by which dietary trans fats cause atherosclerosis.

PubMed

Chen, Chun-Lin; Tetri, Laura H; Neuschwander-Tetri, Brent A; Huang, Shuan Shian; Huang, Jung San

2011-07-01

Dietary trans fats (TFs) have been causally linked to atherosclerosis, but the mechanism by which they cause the disease remains elusive. Suppressed transforming growth factor (TGF)-β responsiveness in aortic endothelium has been shown to play an important role in the pathogenesis of atherosclerosis in animals with hypercholesterolemia. We investigated the effects of a high TF diet on TGF-β responsiveness in aortic endothelium and integration of cholesterol in tissues. Here, we show that normal mice fed a high TF diet for 24 weeks exhibit atherosclerotic lesions and suppressed TGF-β responsiveness in aortic endothelium. The suppressed TGF-β responsiveness is evidenced by markedly reduced expression of TGF-β type I and II receptors and profoundly decreased levels of phosphorylated Smad2, an important TGF-β response indicator, in aortic endothelium. These mice exhibit greatly increased integration of cholesterol into tissue plasma membranes. These results suggest that dietary TFs cause atherosclerosis, at least in part, by suppressing TGF-β responsiveness. This effect is presumably mediated by the increased deposition of cholesterol into cellular plasma membranes in vascular tissue, as in hypercholesterolemia. Copyright © 2011 Elsevier Inc. All rights reserved.

Pathophysiological responses to meals in the Zollinger-Ellison syndrome: I. Paradoxical postprandial inhibition of gastric secretion.

PubMed Central

Malagelada, J R

1978-01-01

The gastric acid, pepsin, and secretory volume output in response to a mixed meal were measured in six patients with Zollinger-Ellison syndrome caused by a gastrin-producing tumour proved subsequently at surgery. The patients were all normocalcaemic, and none had previous abdominal surgery. In four of the six patients, ingestion of the meal markedly inhibited the gastric secretory output, which decreased to below fasting levels, returning later to basal values. In two other patients, whose fasting acid output was considerably lower, the secretory output increased after the meal, but some inhibiton of gastric secretion was also apparent for variable intervals of time. The serum gastrin concentration in all patients remained essentially unchanged or increased after the meal. Two patients were restudied after successful removal of the duodenal gastrin-producing tumour, and in each the normal gastric secretory and gastrin-releasing responses were completely restored. Our studies suggest that, in patients with the Zollinger-Ellison syndrome caused by a gastrinoma, physiological regulatory mechanisms triggered by food reduce the continuous stimulation of gastric secretion caused by their tumoural hypergastrinaemia. PMID:25828

Pathophysiological responses to meals in the Zollinger-Ellison syndrome: I. Paradoxical postprandial inhibition of gastric secretion.

PubMed

Malagelada, J R

1978-04-01

The gastric acid, pepsin, and secretory volume output in response to a mixed meal were measured in six patients with Zollinger-Ellison syndrome caused by a gastrin-producing tumour proved subsequently at surgery. The patients were all normocalcaemic, and none had previous abdominal surgery. In four of the six patients, ingestion of the meal markedly inhibited the gastric secretory output, which decreased to below fasting levels, returning later to basal values. In two other patients, whose fasting acid output was considerably lower, the secretory output increased after the meal, but some inhibiton of gastric secretion was also apparent for variable intervals of time. The serum gastrin concentration in all patients remained essentially unchanged or increased after the meal. Two patients were restudied after successful removal of the duodenal gastrin-producing tumour, and in each the normal gastric secretory and gastrin-releasing responses were completely restored. Our studies suggest that, in patients with the Zollinger-Ellison syndrome caused by a gastrinoma, physiological regulatory mechanisms triggered by food reduce the continuous stimulation of gastric secretion caused by their tumoural hypergastrinaemia.

A contemporary decennial global sample of changing agricultural field sizes

NASA Astrophysics Data System (ADS)

White, E.; Roy, D. P.

2011-12-01

In the last several hundred years agriculture has caused significant human induced Land Cover Land Use Change (LCLUC) with dramatic cropland expansion and a marked increase in agricultural productivity. The size of agricultural fields is a fundamental description of rural landscapes and provides an insight into the drivers of rural LCLUC. Increasing field sizes cause a subsequent decrease in the number of fields and therefore decreased landscape spatial complexity with impacts on biodiversity, habitat, soil erosion, plant-pollinator interactions, diffusion of disease pathogens and pests, and loss or degradation in buffers to nutrient, herbicide and pesticide flows. In this study, globally distributed locations with significant contemporary field size change were selected guided by a global map of agricultural yield and literature review and were selected to be representative of different driving forces of field size change (associated with technological innovation, socio-economic conditions, government policy, historic patterns of land cover land use, and environmental setting). Seasonal Landsat data acquired on a decadal basis (for 1980, 1990, 2000 and 2010) were used to extract field boundaries and the temporal changes in field size quantified and their causes discussed.

Autoimmune pernicious anaemia as a cause of collapse, heart failure and marked panyctopaenia in a young patient.

PubMed

Carey, Justin; Hack, Ebru

2012-05-08

A 35-year-old woman with a history of vitiligo, hypothyroidism and amenorrhoea presented with collapse and clinical features of cardiac failure. Laboratory investigations revealed pancytopaenia, the cause of which was found to be vitamin B12 deficiency due to pernicious anaemia. Treatment with intramuscular hydroxycobalamin was commenced and the patient improved steadily with concomitant improvement in her haematological indices. Clinical features of pernicious anaemia which can include marked pancytopaenia, diagnostic approach, associated conditions and approach to treatment are discussed. The importance of surveillance for gastrointestinal malignancy is emphasised.

Autoimmune pernicious anaemia as a cause of collapse, heart failure and marked panyctopaenia in a young patient

PubMed Central

Carey, Justin; Hack, Ebru

2012-01-01

A 35-year-old woman with a history of vitiligo, hypothyroidism and amenorrhoea presented with collapse and clinical features of cardiac failure. Laboratory investigations revealed pancytopaenia, the cause of which was found to be vitamin B12 deficiency due to pernicious anaemia. Treatment with intramuscular hydroxycobalamin was commenced and the patient improved steadily with concomitant improvement in her haematological indices. Clinical features of pernicious anaemia which can include marked pancytopaenia, diagnostic approach, associated conditions and approach to treatment are discussed. The importance of surveillance for gastrointestinal malignancy is emphasised. PMID:22605831

[Analysis of public quality reports for home care and long-term care with respect to their usefulness for the customer].

PubMed

Sünderkamp, Susanne; Weiß, Christian; Rothgang, Heinz

2014-10-01

Public quality reports, based on new legislative regulations of 2008, were supposed to offer potential customers the possibility to make a well-informed choice of a care provider. This empirical study on marks for long-term care is based on the public quality reports of the Medical Service of the Health Insurance Companies (MDK), of 11 884 home care services and 10 310 nursing homes, which corresponds to a comprehensive survey of almost all care providers in Germany. Descriptive statistical methods and discussion of the results concerning the customer benefit. The analysis of transparency reports reveals a limited value for customers, which is particularly caused by very good quality results with low scattering. In addition, a high amount of missing data - especially in the area of home care providers - leads to a growing influence of service criteria on the final grade. Though deficits in nursing might be compensated by good marks in service criteria, it rarely occurs. At present, a more detailed look at risk criteria hardly improves the customer benefit. The marks for nursing need to be improved to increase their informative value for the customer.

Acute Ozone-Induced Pulmonary and Systemic Metabolic ...

EPA Pesticide Factsheets

Acute ozone exposure increases circulating stress hormones and induces metabolic alterations in animals and humans. We hypothesized that the increase of adrenal-derived stress hormones is necessary for both ozone-induced metabolic effects and lung injury. Male Wistar-Kyoto rats underwent adrenal demedullation (DEMED), total bilateral adrenalectomy (ADREX), or sham surgery (SHAM). After a 4 day recovery, rats were exposed to air or ozone (1ppm), 4h/day for 1 or 2 days. Circulating adrenaline levels dropped to nearly zero in DEMED and ADREX rats relative to air-exposed SHAM. Corticosterone levels tended to be low in DEMED rats and dropped to nearly zero in ADREX rats. Adrenalectomy in air-exposed rats caused modest changes in metabolites and lung toxicity parameters. Ozone-induced hyperglycemia and glucose intolerance were markedly attenuated in DEMED rats with nearly complete reversal in ADREX rats. Ozone increased circulating epinephrine and corticosterone in SHAM but not in DEMED or ADREX rats. Free fatty acids (p=0.15) and branched-chain amino acids increased after ozone exposure in SHAM but not in DEMED or ADREX rats. Lung minute volume was not affected by surgery or ozone but ozone-induced labored breathing was less pronounced in ADREX rats. Ozone-induced increases in lung protein leakage and neutrophilic inflammation were markedly reduced in DEMED and ADREX rats (ADREX>DMED). Ozone-mediated decreases in circulating white blood cells in SHAM were not obser

Acute Ozone-Induced Pulmonary and Systemic Metabolic ...

EPA Pesticide Factsheets

Acute ozone exposure increases circulating stress hormones and induces peripheral metabolic alterations in animals and humans. We hypothesized that the increase of adrenal-derived stress hormones is necessary for ozone-induced systemic metabolic effects and lung injury. Male Wistar-Kyoto rats (12 week-old) underwent total bilateral adrenalectomy (ADREX), adrenal demedullation (DEMED) or sham surgery (SHEM). After 4 day recovery, rats were exposed to air or ozone (1ppm), 4h/day for 1 or 2 days. Circulating adrenaline levels dropped to nearly zero in DEMED and ADREX rats relative to air-exposed SHAM. Corticosterone levels tended to be low in DEMED rats and dropped to nearly zero in ADREX rats. Adrenalectomy in air-exposed rats caused modest changes in metabolites and lung toxicity parameters. Ozone-induced hyperglycemia and glucose intolerance were markedly attenuated in DEMED with nearly complete reversal in ADREX rats. Ozone increased circulating epinephrine and corticosterone in SHAM but not in DEMED or ADREX rats. Free fatty acids and branched-chain amino acids tended to increase after ozone exposure in SHAM but not in DEMED or ADREX rats. Lung minute volume was not affected by surgery or ozone but ozone-induced labored breathing was less pronounced in ADREX rats. Ozone-induced increases in lung protein leakage and neutrophilic inflammation were markedly reduced in DEMED and ADREX rats (ADREX>DMED). Ozone-mediated decrease in circulating WBC in SHAM was not

[Werkgartner's muzzle imprint mark--a literature study].

PubMed

Geserick, Gunther; Vendura, Klaus; Wirth, Ingo

2009-01-01

Since Werkgartner described and correctly interpreted the muzzle imprint mark around the gunshot entrance wound in 1922, this finding has been generally accepted as a sign of a contact shot. In further studies, it could finally be clarified that the muzzle imprint mark is caused by the expansive power of the powder gases with pressure on and abrasion of the skin at the muzzle (weapon imprint). Its shape depends on the firearm, the ammunition and the anatomical conditions, but does not require a bullet. Examinations under a magnifying glass microscope and histological investigations can complete the macroscopic findings. Occasionally, the muzzle imprint mark requires a certain "drying period" in order to become clearly visible. In rare cases, muzzle imprint marks also form on textiles perforated by the projectile. Characteristically shaped muzzled imprint marks can provide clues to the type of the firearm and its position at the time of discharge.

The Effect of Artificial Aging on the Tensile Properties of Alclad 24S-T and 24S-T Aluminum Alloy

NASA Technical Reports Server (NTRS)

Kotanchik, Joseph N.; Woods, Walter; Zender, George W.

1943-01-01

An experimental study was made to determine the effect of artificial aging on the tensile properties of alclad 24S-T and 24S-T aluminum-alloy sheet material. The results of the tests show that certain combinations of aging time and temperature cause a marked increase in the yield strength and a small increase in the ultimate strength; these increases are accompanied by a very large decrease in elongation. A curve is presented that shows the maximum yield strengths that can be obtained by aging this material at various combinations of time and temperature. The higher values of yield stress are obtained in material aged at relatively longer times and lower temperatures.

Structural mass irregularities and fiber volume influence on morphology and mechanical properties of unsaturated polyester resin in matrix composites

PubMed Central

Ahmed, Khalil; Nasir, Muhammad; Fatima, Nasreen; Khan, Khalid M.; Zahra, Durey N.

2014-01-01

This paper presents the comparative results of a current study on unsaturated polyester resin (UPR) matrix composites processed by filament winding method, with cotton spun yarn of different mass irregularities and two different volume fractions. Physical and mechanical properties were measured, namely ultimate stress, stiffness, elongation%. The mechanical properties of the composites increased significantly with the increase in the fiber volume fraction in agreement with the Counto model. Mass irregularities in the yarn structure were quantitatively measured and visualized by scanning electron microscopy (SEM). Mass irregularities cause marked decrease in relative strength about 25% and 33% which increases with fiber volume fraction. Ultimate stress and stiffness increases with fiber volume fraction and is always higher for yarn with less mass irregularities. PMID:26644920

Dissimilarities between methylene blue and cyanide on relaxation and cyclic GMP formation in endothelium-intact intrapulmonary artery caused by nitrogen oxide-containing vasodilators and acetylcholine

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

Ignarro, L.J.; Harbison, R.G.; Wood, K.S.

1986-01-01

The objective of the present study was to ascertain whether cyanide shares the properties of methylene blue as a selective inhibitor of vascular smooth muscle relaxation elicited by agents that stimulate the formation of cyclic GMP. Experiments were performed with endothelium-intact rings prepared from bovine intrapulmonary artery. Methylene blue, a good inhibitor of soluble guanylate cyclase, antagonized both arterial relaxation and cyclic GMP accumulation in response to sodium nitroprusside, glyceryl trinitrate, S-nitroso-N-acetylpenicillamine and acetylcholine. In contrast, cyanide inhibited only the responses to sodium nitroprusside. Increasing concentrations of methylene blue depressed resting arterial levels of cyclic GMP and caused slowly developingmore » but marked contractions whereas cyanide was without effect. Contractile responses to phenylephrine, potassium and U46619 were potentiated by methylene blue but not by cyanide. Preincubation of dilute solutions of cyanide containing sodium nitroprusside in oxygenated Krebs' buffer at 37 degrees C for 15 min before addition to bath chambers depressed relaxation and cyclic GMP accumulation caused by sodium nitroprusside markedly. Similar treatment of glyceryl trinitrate, however, failed to alter its effects in arterial rings. A chemical inactivation of sodium nitroprusside by cyanide appears to account for the specific inhibitory action of cyanide on arterial responses to sodium nitroprusside. This study indicates clearly that cyanide does not share the properties of methylene blue as an inhibitor of arterial relaxation elicited by vasodilators that stimulate cyclic GMP formation.« less

Modulation of actin dynamics as potential macrophage subtype-targeting anti-tumour strategy.

PubMed

Pergola, Carlo; Schubert, Katrin; Pace, Simona; Ziereisen, Jana; Nikels, Felix; Scherer, Olga; Hüttel, Stephan; Zahler, Stefan; Vollmar, Angelika M; Weinigel, Christina; Rummler, Silke; Müller, Rolf; Raasch, Martin; Mosig, Alexander; Koeberle, Andreas; Werz, Oliver

2017-01-30

Tumour-associated macrophages mainly comprise immunosuppressive M2 phenotypes that promote tumour progression besides anti-tumoural M1 subsets. Selective depletion or reprogramming of M2 may represent an innovative anti-cancer strategy. The actin cytoskeleton is central for cellular homeostasis and is targeted for anti-cancer chemotherapy. Here, we show that targeting G-actin nucleation using chondramide A (ChA) predominantly depletes human M2 while promoting the tumour-suppressive M1 phenotype. ChA reduced the viability of M2, with minor effects on M1, but increased tumour necrosis factor (TNF)α release from M1. Interestingly, ChA caused rapid disruption of dynamic F-actin filaments and polymerization of G-actin, followed by reduction of cell size, binucleation and cell division, without cellular collapse. In M1, but not in M2, ChA caused marked activation of SAPK/JNK and NFκB, with slight or no effects on Akt, STAT-1/-3, ERK-1/2, and p38 MAPK, seemingly accounting for the better survival of M1 and TNFα secretion. In a microfluidically-supported human tumour biochip model, circulating ChA-treated M1 markedly reduced tumour cell viability through enhanced release of TNFα. Together, ChA may cause an anti-tumoural microenvironment by depletion of M2 and activation of M1, suggesting induction of G-actin nucleation as potential strategy to target tumour-associated macrophages in addition to neoplastic cells.

Modulation of actin dynamics as potential macrophage subtype-targeting anti-tumour strategy

PubMed Central

Pergola, Carlo; Schubert, Katrin; Pace, Simona; Ziereisen, Jana; Nikels, Felix; Scherer, Olga; Hüttel, Stephan; Zahler, Stefan; Vollmar, Angelika M.; Weinigel, Christina; Rummler, Silke; Müller, Rolf; Raasch, Martin; Mosig, Alexander; Koeberle, Andreas; Werz, Oliver

2017-01-01

Tumour-associated macrophages mainly comprise immunosuppressive M2 phenotypes that promote tumour progression besides anti-tumoural M1 subsets. Selective depletion or reprogramming of M2 may represent an innovative anti-cancer strategy. The actin cytoskeleton is central for cellular homeostasis and is targeted for anti-cancer chemotherapy. Here, we show that targeting G-actin nucleation using chondramide A (ChA) predominantly depletes human M2 while promoting the tumour-suppressive M1 phenotype. ChA reduced the viability of M2, with minor effects on M1, but increased tumour necrosis factor (TNF)α release from M1. Interestingly, ChA caused rapid disruption of dynamic F-actin filaments and polymerization of G-actin, followed by reduction of cell size, binucleation and cell division, without cellular collapse. In M1, but not in M2, ChA caused marked activation of SAPK/JNK and NFκB, with slight or no effects on Akt, STAT-1/-3, ERK-1/2, and p38 MAPK, seemingly accounting for the better survival of M1 and TNFα secretion. In a microfluidically-supported human tumour biochip model, circulating ChA-treated M1 markedly reduced tumour cell viability through enhanced release of TNFα. Together, ChA may cause an anti-tumoural microenvironment by depletion of M2 and activation of M1, suggesting induction of G-actin nucleation as potential strategy to target tumour-associated macrophages in addition to neoplastic cells. PMID:28134280

Female-specific down-regulation of tissue-PMN drives impaired Treg and amplified effector T cell responses in autoimmune dry eye disease1

PubMed Central

Gao, Yuan; Min, Kyungji; Zhang, Yibing; Su, John; Greenwood, Matthew; Gronert, Karsten

2015-01-01

Immune-driven dry eye disease primarily affects women; the cause for this sex-specific prevalence is unknown. PMN have distinct phenotypes that drive inflammation but also regulate lymphocytes and are the rate-limiting cell for generating anti-inflammatory lipoxin A4 (LXA4). Estrogen regulates the LXA4 circuit to induce delayed female-specific wound healing in the cornea. However, the role of PMN in dry eye disease remains unexplored. We discovered a LXA4-producing tissue-PMN population in the corneal limbus, lacrimal glands and cervical lymph nodes of healthy male and female mice. These tissue-PMN, unlike inflammatory-PMN, expressed a highly amplified LXA4 circuit and were sex-specifically regulated during immune-driven dry eye disease. Desiccating stress in females, unlike in males, triggered a remarkable decrease in lymph node PMN and LXA4 formation that remained depressed during dry eye disease. Depressed lymph node PMN and LXA4 in females correlated with an increase in T effector cells (TH1 and TH17), a decrease in regulatory T cells (Treg) and increased dry eye pathogenesis. Antibody depletion of tissue-PMN abrogated LXA4 formation in lymph nodes, caused a marked increase in TH1 and TH17 and decrease in Treg cells. To establish an immune regulatory role for PMN-derived LXA4 in dry eye females were treated with LXA4. LXA4 treatment markedly inhibited TH1 and TH17 and amplified Treg cells in draining lymph nodes, while reducing dry eye pathogenesis. These results identify female-specific regulation of LXA4-producing tissue-PMN as a potential key factor in aberrant T effector cell activation and initiation of immune-driven dry eye disease. PMID:26324767

Distinct effects of ovarian transplantation and exogenous 17 beta-oestradiol on cancellous bone of osteopenic ovariectomized rats.

PubMed

Gallagher, A C; Chambers, T J; Tobias, J H

1995-10-01

Although 17 beta-oestradiol (E2) is known to prevent bone loss, prolonged administration of E2 is unable to reverse this in female rats rendered osteopenic by ovariectomy. To determine whether this reflects a failure to replace other components of ovarian function involved in bone metabolism, we compared the effects of administering E2 to osteopenic ovariectomized (ovx) rats with those of ovarian transplantation. Ovariectomy was performed in female rats. After 13 weeks, by which time marked bone loss had occurred, one group of ovx animals received ovaries from donor rats, and, after a delay of 2 weeks to allow oestrus cycles to return, a further group received E2 5 micrograms.kg-1.day-1 for 9 weeks. The dose of E2 was chosen as that which in preliminary studies restored mean serum E2 levels to that of intact female rats. The study was terminated 24 weeks after ovariectomy. Both E2 and ovarian transplantation largely restored indices of oestrogenic exposure in ovx rats to those of sham-ovx animals. Animals receiving ovarian transplants also showed a small increase in serum progesterone and full restoration of serum testosterone. However, while ovarian transplantation also returned indices of cancellous bone metabolism to those of sham-ovx animals, there was little increase in bone volume. Interestingly, exogenous E2 caused a greater increase in cancellous bone volume than ovarian transplantation but also caused more marked suppression of bone formation, as assessed at the end of the study. In conclusion, exogenous E2 and ovarian transplantation exerted distinct effects on skeletal metabolism in osteopenic ovx rats, although the basis for this difference is currently unclear.

An exogenous hydrogen sulphide donor, NaHS, inhibits the apoptosis signaling pathway to exert cardio-protective effects in a rat hemorrhagic shock model.

PubMed

Xu, Yanjie; Dai, Xiongwei; Zhu, Danxia; Xu, Xiaoli; Gao, Cao; Wu, Changping

2015-01-01

Hydrogen sulfide (H2S) has been reported to be interwined in multiple systems, specifically in the cardiovascular system. However, the mechanisms underlying remain controversial. In the present study, we assessed the cardio-protective effects of H2S in the rat hemorrhagic shock model. Hemorrhagic shock was induced in adult male Sprague-Dawley rats by drawing blood from the femoral artery to maintain the mean arterial pressure at 35-40 mmHg for 1.5 h. The rats were assigned to four groups and the H2S donor, NaHS (28 μmol/kg, i.p.), was injected before the resuscitation in certain groups. After resuscitation the animals were observed and then killed to harvest the hearts. The morphological investigation and ultrastructural analyses were done and apoptotic cells were detected. The levels of relevant proteins were examined using Western blotting and immunohistochemical analyses. Resuscitated hemorrhagic shock induced heart injury and significantly increased the levels of serum myocardial enzymes, creatine kinase (CK) and lactate dehydrogenase (LDH) levels. Furthermore, it caused marked increase of apoptotic cells in heart tissue. Moreover, the expression of death receptor Fas and Fas-ligand, as well as the expression of apoptosis-relevant proteins active-caspase 3 and active-caspase 8 were markedly increased. Administration of NaHS significantly ameliorated hemorrhagic shock caused hemodynamic deterioration, decreased myocardial enzymes elevation, protected myocardial ultrastructure, and inhibited the expression of apoptosis-relevant proteins. It suggested that H2S might exert its cardio-protective roles via both the extrinsic Fas/FasL/caspase-8/caspase-3 pathway and the intrinsic mitochondria-involved pathways.

Minnesota Local Agency Pavement Marking : Mining Existing Data

DOT National Transportation Integrated Search

2017-11-01

Pavement marking is important for safety. Maximizing pavement marking performance in terms of increased retroreflectivity, within limited budget constraints, allows agencies to make better decisions toward providing more effective pavement marking pe...

[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.

Familial Gastric Cancers.

PubMed

Setia, Namrata; Clark, Jeffrey W; Duda, Dan G; Hong, Theodore S; Kwak, Eunice L; Mullen, John T; Lauwers, Gregory Y

2015-12-01

Although the majority of gastric carcinomas are sporadic, approximately 10% show familial aggregation, and a hereditary cause is determined in 1%-3% cases. Of these, hereditary diffuse gastric cancer is the most recognized predisposition syndrome. Although rare, the less commonly known syndromes also confer a markedly increased risk for development of gastric cancer. Identification and characterization of these syndromes require a multidisciplinary effort involving oncologists, surgeons, genetic counselors, biologists, and pathologists. This article reviews the molecular genetics, clinical and pathologic features, surveillance guidelines, and preventive measures of common and less common hereditary gastric cancer predisposition syndromes. ©AlphaMed Press.

Infrared site testing of Mt. Lemmon and Catalina Observatory

NASA Technical Reports Server (NTRS)

Kuiper, G. P.

1973-01-01

The operation and problems involved with two sky noise meters installed in the Catalina Mountains near Tucson, Arizona are discussed. The instruments were installed at two different locations on Mt. Lemon. It was found that when photometric conditions prevailed, a positive correlation existed between the outputs of the two instruments. In particular, the strongdiurnal effect, in which the sky noise increases abruptly at sunrise and falls markedly after sunset, was reproduced by both instruments. Discrepancies in data recorded by the two instruments are analyzed and possible causes for the discrepancies are proposed.

Comparison of propranolol and metoprolol in the management of hyperthyroidism.

PubMed Central

Murchison, L E; How, J; Bewsher, P D

1979-01-01

1 Propranolol and metoprolol were both effective in controlling the symptoms and signs of hyperthyroidism. 2 Propranolol caused a highly significant increase in serum reverse T3 concentrations with lesser changes in other serum thyroid hormone levels, whereas metoprolol did not have this effect. 3 Steady-state plasma propranolol and metoprolol levels showed marked inter-individual variation. Metoprolol concentrations showed relatively little intra-individual variability, and could be related to the clinical efficacy of the drug, whereas no such relationship was demonstrated for propranolol. PMID:391258

Prevention of Infectious Complications in Patients With Chronic Granulomatous Disease.

PubMed

Slack, Maria A; Thomsen, Isaac P

2018-05-09

Chronic granulomatous disease (CGD) is a primary immunodeficiency that confers a markedly increased risk of bacterial and fungal infections caused by certain opportunistic pathogens. Current evidence supports the use of prophylactic antibacterial, antifungal, and immunomodulatory therapies designed to prevent serious or life-threatening infections in patients with CGD. In this review, we discuss current strategies for the prevention of infections in children and adults with CGD and the evidence that supports those strategies. In addition, we address current challenges and opportunities for future research in this important area.

Recapture Heterogeneity in Cliff Swallows: Increased Exposure to Mist Nets Leads to Net Avoidance

PubMed Central

Roche, Erin A.; Brown, Charles R.; Brown, Mary Bomberger; Lear, Kristen M.

2013-01-01

Ecologists often use mark-recapture to estimate demographic variables such as abundance, growth rate, or survival for samples of wild animal populations. A common assumption underlying mark-recapture is that all animals have an equal probability of detection, and failure to meet or correct for this assumption–as when certain members of the population are either easier or more difficult to capture than other animals–can lead to biased and inaccurate demographic estimates. We built within-year and among-years Cormack-Jolly-Seber recaptures-only models to identify causes of capture heterogeneity for a population of colonially nesting cliff swallows (Petrochelidon pyrrhonota) caught using mist-netting as a part of a 20-year mark-recapture study in southwestern Nebraska, U.S.A. Daily detection of cliff swallows caught in stationary mist nets at their colony sites declined as the birds got older and as the frequency of netting at a site within a season increased. Experienced birds’ avoidance of the net could be countered by sudden disturbances that startled them into a net, such as when we dropped a net over the side of a bridge or flushed nesting cliff swallows into a stationary net positioned at a colony entrance. Our results support the widely held, but seldom tested, belief that birds learn to avoid stationary mist nets over time, but also show that modifications of traditional field methods can reduce this source of recapture heterogeneity. PMID:23472138

Influence of the axial rotation angle on tool mark striations.

PubMed

Garcia, Derrel Louis; Pieterman, René; Baiker, Martin

2017-10-01

A tool's axial rotation influences the geometric properties of a tool mark. The larger the axial rotation angle, the larger the compression of structural details like striations. This complicates comparing tool marks at different axial rotations. Using chisels, tool marks were made from 0° to 75° axial rotation and compared using an automated approach Baiker et al. [10]. In addition, a 3D topographic surface of a chisel was obtained to generate virtual tool marks and to test whether the axial rotation angle of a mark could be predicted. After examination of the tool mark and chisel data-sets it was observed that marks lose information with increasing rotation due to the change in relative distance between geometrical details on the tool and the disappearance of smaller details. The similarity and repeatability were high for comparisons between marks with no difference in axial rotation, but decreasing with increased rotation angle from 0° to 75°. With an increasing difference in the rotation angles, the tool marks had to be corrected to account for the different compression factors between them. For compression up to 7.5%, this was obtained automatically by the tool mark alignment method. For larger compression, manually re-sizing the marks to the uncompressed widths at 0° rotation before the alignment was found suitable for successfully comparing even large differences in axial rotation. The similarity and repeatability were decreasing however, with increasing degree of re-sizing. The quality was assessed by determining the similarity at different detail levels within a tool mark. With an axial rotation up to 75°, tool marks were found to reliably represent structural details down to 100μm. The similarity of structural details below 100μm was dependent on the angle, with the highest similarity at small rotation angles and the lowest similarity at large rotation angles. Filtering to remove the details below 100μm lead to consistently higher similarity between tool marks at all angles and allowed for a comparison of marks up to 75° axial rotation. Finally, generated virtual tool mark profiles with an axial rotation were compared to experimental tool marks. The similarity between virtual and experimental tool marks remained high up to 60° rotation after which it decreased due to the loss in quality in both marks. Predicting the rotation angle is possible under certain conditions up to 45° rotation with an accuracy of 2.667±0.577° rotation. Copyright © 2017 Elsevier B.V. All rights reserved.

Causes of death among persons with multiple sclerosis.

PubMed

Cutter, Gary R; Zimmerman, Jeffrey; Salter, Amber R; Knappertz, Volker; Suarez, Gustavo; Waterbor, John; Howard, Virginia J; Ann Marrie, Ruth

2015-09-01

Multiple Sclerosis (MS) is a leading cause of disability among young Americans. Reports suggest that life expectancy (i.e., average age at death) remains reduced as compared to the general population, but underlying causes of death (UCOD) are less well-characterized. To describe the cause-specific mortality among participants enrolled in the North American Research Committee on Multiple Sclerosis (NARCOMS) registry and to compare the profile of these causes by age, sex, race and disability status at entry into NARCOMS, with U.S. mortality data. The underlying cause of death (UCOD), any mention cause of death and proportionate mortality were compared among U.S. NARCOMS participants by age, sex, race and disability status. Of the 32,445 participants to be considered for this study, 2,927 had died. Compared to survivors, decedents were older at enrollment and MS diagnosis, more likely to be male, and had less education. UCOD differed markedly by age group. In both sexes, MS as the UCOD was proportionately lower by 20% or more in those aged 25-39 compared to those aged 75 or older. Cancer and cardiovascular causes were more frequent as causes of death with increasing age, but were less than expected at older ages. The effect of disability on mortality was roughly equivalent to the effect of aging on mortality. Among NARCOMS participants older age at enrollment, male sex and greater disability were associated with increased mortality risk. This cohort of MS subjects had a lower proportionate mortality from cardiovascular disease and cancer compared to the U.S. population. Copyright © 2015 Elsevier B.V. All rights reserved.

A comparison of 2 techniques for estimating deer density

USGS Publications Warehouse

Storm, G.L.; Cottam, D.F.; Yahner, R.H.; Nichols, J.D.

1977-01-01

We applied mark-resight and area-conversion methods to estimate deer abundance at a 2,862-ha area in and surrounding the Gettysburg National Military Park and Eisenhower National Historic Site during 1987-1991. One observer in each of 11 compartments counted marked and unmarked deer during 65-75 minutes at dusk during 3 counts in each of April and November. Use of radio-collars and vinyl collars provided a complete inventory of marked deer in the population prior to the counts. We sighted 54% of the marked deer during April 1987 and 1988, and 43% of the marked deer during November 1987 and 1988. Mean number of deer counted increased from 427 in April 1987 to 582 in April 1991, and increased from 467 in November 1987 to 662 in November 1990. Herd size during April, based on the mark-resight method, increased from approximately 700-1,400 from 1987-1991, whereas the estimates for November indicated an increase from 983 for 1987 to 1,592 for 1990. Given the large proportion of open area and the extensive road system throughout the study area, we concluded that the sighting probability for marked and unmarked deer was fairly similar. We believe that the mark-resight method was better suited to our study than the area-conversion method because deer were not evenly distributed between areas suitable and unsuitable for sighting within open and forested areas. The assumption of equal distribution is required by the area-conversion method. Deer marked for the mark-resight method also helped reduce double counting during the dusk surveys.

[MRT of the liver in Wilson's disease].

PubMed

Vogl, T J; Steiner, S; Hammerstingl, R; Schwarz, S; Kraft, E; Weinzierl, M; Felix, R

1994-01-01

To show that Wilson's disease is one likely cause of multiple low-intensity nodules of the liver we obtained MR images in 16 patients with clinically and histopathologically confirmed Wilson's disease. Corresponding to morphological changes MRI enabled the subdivision of the patients into two groups. Using a T2-weighted spin-echo sequence (TR/TE = 2000/45-90) liver parenchyma showed multiple tiny low-intensity-nodules surrounded by high-intensity septa in 10 out of 16 patients. 5 patients had also low-intensity nodules in T1-weighted images (TR/TE = 600/20). In patients of this group histopathology revealed liver cirrhosis (n = 7) and fibrosis (n = 2). Common feature of this patient group was marked inflammatory cell infiltration into fibrous septa, increase of copper concentration in liver parenchyma and distinct pathological changes of laboratory data. In the remaining 6 patients no pathological change of liver morphology was demonstrated by MRI corresponding to slight histopathological changes of parenchyma and normal laboratory data. As low-intensity nodules surrounded by high intensity septa can be demonstrated in patients with marked inflammatory infiltration of liver parenchyma MRI may help to define Wilson patients with poorer prognosis. In patients with low-intensity nodules of the liver and unknown cause of liver cirrhosis laboratory data and histopathology should be checked when searching for disorders of copper metabolism.

The action of chlorphenesin carbamate on the frog spinal cord.

PubMed

Aihara, H; Kurachi, M; Nakane, S; Sasajima, M; Ohzeki, M

1980-02-01

Studies were carried out to elucidate the mechanism of action of chlorphenesin carbamate (CPC) and to compare the effect of the drug with that of mephenesin on the isolated bullfrog spinal cord. Ventral and dorsal root potentials were recorded by means of the sucrose-gap method. CPC caused marked hyperpolarizations and depressed spontaneous activities in both of the primary afferent terminals (PAT) and motoneurons (MN). These hyperpolarizations were observed even in high-Mg2+ and Ca2+-free Ringer's solution, suggesting that CPC has direct actions on PAT and MN. Various reflex potentials (dorsal and ventral root potentials elicited by stimulating dorsal and ventral root, respectively) tended to be depressed by CPC as well as by mephenesin. Excitatory amino acids (L-aspartic acid and L-glutamic acid) caused marked depolarizations in PAT and MN, and increased the firing rate in MN. CPC did not modify the depolarization but abolished the motoneuron firing induced by these amino acids. However, mephenesin reduced both the depolarization and the motoneuron firing. The dorsal and ventral root potentials evoked by tetanic stimulation (40 Hz) of the dorsal root were depressed by the drugs. These results indicate that CPC has an apparent depressing action on the spinal neuron, and this action may be ascribed to the slight hyperpolarization and/or the prolongation of refractory period.

Beneficial effects of coconut water feeding on lipid metabolism in cholesterol-fed rats.

PubMed

Sandhya, V G; Rajamohan, T

2006-01-01

The purpose of this study was to determine the effect of coconut water feeding in cholesterol-fed rats. Male albino rats were fed tender coconut water and mature coconut water at a dose level of 4 mL/100 g of body weight. Cholesterol feeding caused a marked increase in total cholesterol, very low-density lipoprotein (VLDL) + low-density lipoprotein (LDL) cholesterol, and triglycerides in serum. Administration of coconut water counteracts the increase in total cholesterol, VLDL + LDL cholesterol, and triglycerides, while high-density lipoprotein cholesterol was higher. Lipid levels in the tissues viz. liver, heart, kidney, and aorta were markedly decreased in cholesterol-fed rats supplemented with coconut water. Feeding coconut water resulted in increased activities of 3-hydroxy-3-methylglutaryl-CoA reductase in liver, lipoprotein lipase in heart and adipose tissue, and plasma lecithin:cholesterol acyl transferase, while lipogenic enzymes showed decreased activities. An increased rate of cholesterol conversion to bile acid and an increased excretion of bile acids and neutral sterols were observed in rats fed coconut water. Histopathological studies of liver and aorta revealed much less fatty accumulation in these tissues in cholesterol-fed rats supplemented with coconut water. Feeding coconut water resulted in increased plasma L-arginine content, urinary nitrite level, and nitric oxide synthase activity. These results indicate that both tender and mature coconut water has beneficial effects on serum and tissue lipid parameters in rats fed cholesterol-containing diet.

Melanism in Panthea furcilla (packard) (lepidoptera, noctuidae): field studies in central Massachusetts

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

Jones, T.K.

1977-01-01

Field studies were undertaken to determine the nature and extent of melanism in two populations of the cryptic moth, Panthea furcilla. Melanic frequencies significantly increased over a three year period in both populations of P. furcilla sampled. Predation experiments showed that melanics suffer less predation than typicals. However, life expectancies for typical and melanic morphs were nearly equal as computed from mark-release-recapture data. Accordingly it is suggested that one advantage melanics enjoy is their greater vigor prior to the imaginal stage. Acid-rainfall, as a Northeast regional problem, is advanced as a possible cause for the increase in melanic frequencies. 22more » references, 9 tables.« less

Gastrointestinal involvement in systemic mastocytosis.

PubMed Central

Ammann, R W; Vetter, D; Deyhle, P; Tschen, H; Sulser, H; Schmid, M

1976-01-01

Four consecutive patients with systemic mastocytosis were studied. One patient had a malabsorption syndrome with only minor histological changes of the intestinal mucosa. Another patient with ulcer diathesis had a gastric secretory pattern resembling Zollinger-Ellison syndrome. Serum gastrin and histamine levels were consistently normal in all patients. Endoscopy of stomach and colon disclosed urticaria-like papulae either spontaneously or after topical provocation in all patients. No increase of mast cells was found in multiple mucosal biopsies. A markedly increased gastric tissue content of histamine was found, however, in the three patients studied. The findings suggest that urticaria-like lesions associated with a high tissue content of histamine may be more important that hyperhistaminaemia in causing the various gastrointestinal symptoms. PMID:1261881

[Mortality from violent causes in the Americas].

PubMed

Yunes, J

1993-04-01

With a view to assembling information to aid in decision-making with regard to prevention policies, a study of mortality from violent causes and its trends in the countries of the Americas was carried out. The study focused on persons under 24 years of age and utilized information from 1980 and 1986 taken from the data base of the Pan American Health Organization. The causes of death were grouped in accordance with the International Classification of Diseases, Ninth Revision. Accidental deaths were separated from intentional deaths by means of the following classification: traffic accidents, other accidents, homicides, suicides, and "unknown causes." The information on violent deaths was compared with information on deaths from infectious diseases during the same period. The results indicate that in 1986, 517,465 deaths from violent causes were recorded in the 28 countries of the Region. Violent deaths as a proportion of total deaths ranged from 3.7% in Jamaica to 26.8% in El Salvador. It was observed that between 1980 and 1986 traffic accidents and "other accidents" tended to diminish but there was a moderate increase in suicides. Homicide rates varied markedly between the countries. In the under-1 and 1-4 year age groups, the highest rates corresponded to "other accidents," except in Chile, where among children aged 1-4 the largest proportion of deaths were attributed to "unknown causes." Comparative analysis of deaths from violent causes and from infectious diseases in the population aged 0-24 years showed that the former increase whereas the latter decrease as age increases. The study pointed up the need to promote further research on these phenomena in order to develop appropriate prevention strategies.

Effect of Slag-Steel Reaction on the Initial Solidification of Molten Steel during Continuous Casting

NASA Astrophysics Data System (ADS)

Wang, Wanlin; Lou, Zhican; Zhang, Haihui

2018-03-01

With the mold simulator technique, the effect of slag-steel reaction on the initial shell solidification as well as the heat transfer and lubrication behavior of the infiltrated mold/shell slag film was studied in this article. The results showed that the Al2O3 content, the CaO/SiO2 ratio, and the viscosity of mold flux were increased with the progress of the slag-steel reaction during casting. The slag-steel reaction has two major effects on the initial shell solidification: one is increasing the mold heat flux and shell thickness by the decrease of slag film thickness. The other is the reduction of mold heat flux by the increase of crystal fraction in slag film. Mold flux with a lower basicity, viscosity, and crystallization temperature would result in a larger liquid slag consumption and the uneven infiltration of slag into the mold and shell gap that eventually leads to the irregular solidification of initial shell with a poor surface quality, such as slag entrapment and depressions as well as glaciation marks. Conversely, mold flux with a higher viscosity, basicity, and crystallization temperature would result in a smaller liquid slag consumption, which would cause the poor mold lubrication, the longitudinal shell surface defects, and drag marks.

Oxidative stress response of the black tiger shrimp Penaeus monodon to Vibrio parahaemolyticus challenge.

PubMed

Duan, Yafei; Zhang, Jiasong; Dong, Hongbiao; Wang, Yun; Liu, Qingsong; Li, Hua

2015-10-01

Vibrio parahaemolyticus is a virulent pathogen that affects shrimp aquaculture. Reactive oxygen species are produced by the immune system that defends the host against foreign microorganisms. In the present study, the oxidative stress response in hepatopancreas and gills of Penaeus monodon to V. parahaemolyticus challenge were studied, such as respiratory burst, ROS production (·O2(-) and ·OH), activities of antioxidant enzymes (CAT, GPx, SOD, POD and GST) and oxidative damage to lipid and protein (indexed by contents of MDA). Compared with the control group, after V. parahaemolyticus challenge, respiratory burst and ROS production were up-regulated significantly. GPx and POD activity increased significantly in hepatopancreas and gills of the shrimps at 12 h, but CAT activity decreased markedly at 12 h and 24 h. SOD and GST activity in hepatopancreas of the shrimps increased significantly at 1.5 h, but decreased markedly at 12 h-48 h. MDA content increased significantly after 6 h-24 h challenge. HE staining showed that V. parahaemolyticus challenge induced damage symptoms in hepatopancreas of P. monodon. Our study revealed that V. parahaemolyticus influenced the antioxidative status and caused oxidative stress and tissue damage via confusion of antioxidant enzymes in P. monodon. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of Slag-Steel Reaction on the Initial Solidification of Molten Steel during Continuous Casting

NASA Astrophysics Data System (ADS)

Wang, Wanlin; Lou, Zhican; Zhang, Haihui

2018-06-01

With the mold simulator technique, the effect of slag-steel reaction on the initial shell solidification as well as the heat transfer and lubrication behavior of the infiltrated mold/shell slag film was studied in this article. The results showed that the Al2O3 content, the CaO/SiO2 ratio, and the viscosity of mold flux were increased with the progress of the slag-steel reaction during casting. The slag-steel reaction has two major effects on the initial shell solidification: one is increasing the mold heat flux and shell thickness by the decrease of slag film thickness. The other is the reduction of mold heat flux by the increase of crystal fraction in slag film. Mold flux with a lower basicity, viscosity, and crystallization temperature would result in a larger liquid slag consumption and the uneven infiltration of slag into the mold and shell gap that eventually leads to the irregular solidification of initial shell with a poor surface quality, such as slag entrapment and depressions as well as glaciation marks. Conversely, mold flux with a higher viscosity, basicity, and crystallization temperature would result in a smaller liquid slag consumption, which would cause the poor mold lubrication, the longitudinal shell surface defects, and drag marks.

Classifying sea lamprey marks on Great Lakes lake trout: observer agreement, evidence on healing times between classes and recommendations for reporting of marking statistics

USGS Publications Warehouse

Ebener, Mark P.; Bence, James R.; Bergstedt, Roger A.; Mullet, Katherine M.

2003-01-01

In 1997 and 1998 two workshops were held to evaluate how consistent observers were at classifying sea lamprey (Petromyzon marinus) marks on Great Lakes lake trout (Salvelinus namaycush) as described in the King classification system. Two trials were held at each workshop, with group discussion between trials. Variation in counting and classifying marks was considerable, such that reporting rates for A1–A3 marks varied two to three-fold among observers of the same lake trout. Observer variation was greater for classification of healing or healed marks than for fresh marks. The workshops highlighted, as causes for inconsistent mark classification, both departures from the accepted protocol for classifying marks by some agencies, and differences in how sliding and multiple marks were interpreted. Group discussions led to greater agreement in classifying marks. We recommend ways to improve the reliability of marking statistics, including the use of a dichotomous key to classify marks. Laboratory data show that healing times of marks on lake trout were much longer at 4°C and 1°C than at 10°C and varied greatly among individuals. Reported A1–A3 and B1–B3 marks observed in late summer and fall collections likely result from a mixture of attacks by two year classes of sea lamprey. It is likely that a substantial but highly uncertain proportion of attacks that occur in late summer and fall lead to marks that are classified as A1–A3 the next spring. We recommend additional research on mark stage duration.

Cancer control and prevention: nutrition and epigenetics.

PubMed

Verma, Mukesh

2013-07-01

To evaluate recent developments in nutritional epigenomics and related challenges, opportunities, and implications for cancer control and prevention. Cancer is one of the leading causes of death worldwide, and understanding the factors that contribute to cancer development may facilitate the development of strategies for cancer prevention and control. Cancer development involves genetic and epigenetic alterations. Genetic marks are permanent, whereas epigenetic marks are dynamic, change with age, and are influenced by the external environment. Thus, epigenetics provides a link between the environment, diet, and cancer development. Proper food selection is imperative for better health and to avoid cancer and other diseases. Nutrients either contribute directly to cancer prevention or support the repair of genomic and epigenomic damage caused by exposure to cancer-causing agents such as toxins, free radicals, radiation, and infectious agents. Nutritional epigenomics provides an opportunity for cancer prevention because selected nutrients have the potential to reverse cancer-associated epigenetic marks in different tumor types. A number of natural foods and their bioactive components have been shown to have methylation-inhibitory and deacetylation-inhibitory properties. Natural foods and bioactive food components have characteristics and functions that are similar to epigenetic inhibitors and therefore have potential in cancer control and prevention.

The influence of social and endocrine factors on urine-marking by captive wolves (Canis lupus)

USGS Publications Warehouse

Asa, C.S.; Mech, L.D.; Seal, U.S.; Plotka, E.D.

1990-01-01

Although serum hormones varied seasonally in all adult animals, only dominant male and female wolves urine-marked. Serum testosterone and urine-marking rates, which increased during the fall/winter breeding season, were positively correlated in both male and female dominant wolves. Estradiol, which increased in conjunction with proestrus and estrus, was not correlated with female urine-marking. These findings suggest that hormonal influence on urine-marking in the wolf is modulated by social factors and contrast with those for both domestic dogs and coyotes, two other members of the genus Canis.

Spatial dynamics of the invasive defoliator amber-marked birch leafminer across the Anchorage landscape

Treesearch

J.E. Lundquist; R.M. Reich; M. Tuffly

2012-01-01

The amber-marked birch leafminer has caused severe infestations of birch species in Anchorage, AK, since 2002. Its spatial distribution has been monitored since 2006 and summarized using interpolated surfaces based on simple kriging. In this study, we developed methods of assessing and describing spatial distribution of the leafminer as they vary from year to year, and...

Evaluation of Dowfrost(TM) HD as a Thermal Control Fluid for Constellation Vehicles

NASA Technical Reports Server (NTRS)

Lee, Steve

2009-01-01

A test was conducted from November 2008 to January 2009 to help determine the compatibility of an inhibited propylene glycol/water solution with planned Constellation vehicles. Dowfrost(TradeMark) HD was selected as the baseline for Orion, as well as other Constellation systems. Therefore, the same Dowfrost(TradeMark) HD/Water solution planned for Orion was chosen for this test. The fluid was subjected to a thermal fluid loop that had flightlike properties, as compared to Orion. The fluid loop had similar wetted materials, temperatures, flow rates, and aluminum wetted surface area to fluid volume ratio. The test was designed to last for 10 years, the life expectancy of the lunar habitat. However, the test lasted less than two months. System filters became clogged with precipitate, rendering the fluid system inoperable. Upon examination of the precipitate, it was determined that the precipitate composition contained aluminum, which could have only come from materials in the test stand, as aluminum is not part of the Dowfrost(TradeMark HD composition. Also, the fluid pH was determined to have increased from 10.1, at the first test sample, to 12.2, at the completion of the test. This high of a pH is corrosive to aluminum and was certainly a contributing factor to the development of precipitate. Chemical analyses and bench-top tests are currently ongoing to determine the underlying cause for this rapid degradation of the fluid. Hamilton Sundstrand, the contractor developing the Orion thermal fluid loop, is performing a parallel effort to not only understand the cause of fluid degradation in the test, but also to investigate solutions to avoid this problem in the Orion s thermal control system. JSC also consulted with the Hamilton Sundstrand team in the development of this test and the subsequent analysis.

A Brief Study on Toxic Combustion Products of the Polymers Used in High-Pressure Oxygen Systems

NASA Technical Reports Server (NTRS)

Hshieh, Fu-Yu; Beeson, Harold D.

2005-01-01

One likely cause of polymer ignition in a high-pressure oxygen system is the adiabatic-compression heating of polymers caused by pneumatic impact. Oxidative pyrolysis or combustion of polymers in a high-pressure oxygen system could generate toxic gases. This paper investigates the feasibility of using the NASA pneumatic-impact system to conduct adiabatic-compression combustion tests and determines the toxic combustion products produced from the burning of five selected polymers. Five polymers commonly used in high-pressure oxygen systems, Zytel(Registered TradeMark) 42 (Nylon 6/6), Buna N (nitrile rubber), Witon(Registered TradeMark) A (copolymer of vinylidene fluoride and hexafluoropropylene), Neoflon(Registered TradeMark) (polychlorotrifluoroethylene), and Teflon(Registered TradeMark) (polytetrafluoroethylene), were tested in the NASA pneumatic-impact test system at 17.2-MPa oxygen pressure. The polymers were ignited and burned; combustion products were collected in a stainless-steel sample bottle and analyzed using various methods. The results show that the NASA pneumatic-impact system is an appropriate test system to conduct adiabatic-compression combustion tests and to collect combustion products for further chemical analysis. The composition of the combustion product gas generated from burning the five selected polymers are presented and discussed.

Resurrecting the intestinal microbiota to combat antibiotic-resistant pathogens

PubMed Central

Pamer, Eric G.

2016-01-01

The intestinal microbiota, which is composed of diverse populations of commensal bacterial species, provides resistance against colonization and invasion by pathogens. Antibiotic treatment can damage the intestinal microbiota and, paradoxically, increase susceptibility to infections. Reestablishing microbiota-mediated colonization resistance after antibiotic treatment could markedly reduce infections, particularly those caused by antibiotic-resistant bacteria. Ongoing studies are identifying commensal bacterial species that can be developed into next-generation probiotics to reestablish or enhance colonization resistance. These live medicines are at various stages of discovery, testing, and production and are being subjected to existing regulatory gauntlets for eventual introduction into clinical practice. The development of next-generation probiotics to reestablish colonization resistance and eliminate potential pathogens from the gut is warranted and will reduce health care–associated infections caused by highly antibiotic-resistant bacteria. PMID:27126035

Sidescan-sonar mapping of benthic trawl marks on the shelf and slope off Eureka, California

USGS Publications Warehouse

Friedlander, A.M.; Boehlert, G.W.; Field, M.E.; Mason, J.E.; Gardner, J.V.; Dartnell, P.

1999-01-01

The abundance and orientation of trawl marks was quantified over an extensive portion (>2700 km2) of the Eureka, California, outer shelf and slope, an important commercial bottom trawling ground for such high-value species as rockfish, sole, and sablefish. Fishing logbook data indicate that the entire reporting area was trawled about one and a half times on an average annual basis and that some areas were trawled over three times annually. High-resolution sidescan-sonar images of the study area revealed deep gouges on the seafloor, caused by heavy steel trawl doors that act to weigh down and spread open the bottom trawls. These trawl marks are commonly oriented parallel to bathymetric contours and many could be traced for several kilometers. Trawl marks showed a quadratic relationship in relation to water depth, with the greatest number of trawl marks observed at ~400 m. There was a significant positive correlation between the number of trawl marks observed on the sidescan images and the number of annual trawl hours logged within reporting areas. This finding indicates that acoustic remote sensing is a promising independent approach to evaluate fishing effort on a scale consistent with commercial fishing activities. Bottom trawling gear is known to modify seafloor habitats by altering benthic habitat complexity and by removing or damaging infauna and sessile organisms. Identifying the extent of trawling in these areas may help determine the effects of this type of fishing gear on the benthos and develop indices of habitat disturbance caused by fishing activities.

Strong Inverse Correlation Between MicroRNA-125b and Human Papillomavirus DNA in Productive Infection

PubMed Central

Nuovo, Gerard J.; Wu, Xin; Volinia, Stefano; Yan, Fengting; di Leva, Gianpiero; Chin, Nena; Nicol, Alcina F.; Jiang, Jinmai; Otterson, Gregory; Schmittgen, Thomas D.; Croce, Carlo

2014-01-01

Infection by the human papillomavirus (HPV) is a cause of cervical intraepithelial neoplasia (CIN) and cancer. microRNA (miRNA) in situ analysis of the transformation zone epithelia, the site of initial cervical HPV infection, showed that miRNAs let-7c, — 99a, 26a, and 125b were the most abundantly expressed. In situ testing of CIN 1 showed a dramatic reduction in miR-125b expression in the koilocytes, the cytologic marker of productive HPV infection. A marked reduction in miR-125b was likewise observed in the HPV-infected cells of the condyloma acuminatum, verruca vulgaris, and epidermodysplasia verruciformis. Reverse transcriptase in situ polymerase chain reaction (PCR) showed that the pre-miRNA 125b was present in the koilocyte, suggesting direct inactivation of the mature miRNA. HEK cells transfected with only the antimiR-125b showed perinuclear halos equivalent to HPV-infected koilocytes. NIH 3T3 cells transfected with the HPV 16 full-length genome and mimetic miR-125b showed a marked reduction in viral DNA and protein synthesis by quantitative PCR and in situ-based analyses, respectively (P=0.002). Alternatively, cotransfection with anti-miR-125b and HPV 16 markedly increased HPV DNA (P=0.002). Sequence analyses showed strong homology between L2 of different HPV genotypes and miR-125b. Transfection with HPV 16 L2 resulted in a marked reduction in miR-125b levels in the NIH 3T3 cells. HPV L2-induced inactivation of miR-125b is associated with the classic cytologic changes of the koilocyte, and the exogenous application of mimetic miR-125b markedly inhibits HPV DNA synthesis. PMID:20736742

Strong inverse correlation between microRNA-125b and human papillomavirus DNA in productive infection.

PubMed

Nuovo, Gerard J; Wu, Xin; Volinia, Stefano; Yan, Fengting; di Leva, Gianpiero; Chin, Nena; Nicol, Alcina F; Jiang, Jinmai; Otterson, Gregory; Schmittgen, Thomas D; Croce, Carlo

2010-09-01

Infection by the human papillomavirus (HPV) is a cause of cervical intraepithelial neoplasia (CIN) and cancer. microRNA (miRNA) in situ analysis of the transformation zone epithelia, the site of initial cervical HPV infection, showed that miRNAs let-7c, -99a, 26a, and 125b were the most abundantly expressed. In situ testing of CIN 1 showed a dramatic reduction in miR-125b expression in the koilocytes, the cytologic marker of productive HPV infection. A marked reduction in miR-125b was likewise observed in the HPV-infected cells of the condyloma acuminatum, verruca vulgaris, and epidermodysplasia verruciformis. Reverse transcriptase in situ polymerase chain reaction (PCR) showed that the pre-miRNA 125b was present in the koilocyte, suggesting direct inactivation of the mature miRNA. HEK cells transfected with only the antimiR-125b showed perinuclear halos equivalent to HPV-infected koilocytes. NIH 3T3 cells transfected with the HPV 16 full-length genome and mimetic miR-125b showed a marked reduction in viral DNA and protein synthesis by quantitative PCR and in situ-based analyses, respectively (P=0.002). Alternatively, cotransfection with anti-miR-125b and HPV 16 markedly increased HPV DNA (P=0.002). Sequence analyses showed strong homology between L2 of different HPV genotypes and miR-125b. Transfection with HPV 16 L2 resulted in a marked reduction in miR-125b levels in the NIH 3T3 cells. HPV L2-induced inactivation of miR-125b is associated with the classic cytologic changes of the koilocyte, and the exogenous application of mimetic miR-125b markedly inhibits HPV DNA synthesis.

Isolation of Trichophyton violaceum and Trichophyton soudanense in Baltimore, Maryland▿

PubMed Central

Magill, Shelley S.; Manfredi, Liliana; Swiderski, Andrew; Cohen, Bernard; Merz, William G.

2007-01-01

Tinea capitis is of public health importance because of its transmissibility. Trichophyton violaceum and Trichophyton soudanense, which are common causes of tinea capitis in parts of Africa and West Asia, have only rarely been reported to cause dermatophytoses in the United States. We identified 24 patients with 25 positive cultures for T. violaceum or T. soudanense that were processed in a single hospital laboratory in Baltimore, Maryland, between 1 January 2000 and 30 June 2006. Most patients for whom clinical information was available had tinea capitis. There was a marked increase in the isolation of these organisms between the period from 2000 to 2002 and the period from 2003 to 2006, possibly associated with changes in immigration to the Baltimore metropolitan area. The changing epidemiology of this transmissible fungal infection not only is of public health interest as an example of the introduction of a “new” pathogen to an area where it traditionally was not endemic but also is of clinical and microbiological importance given reports suggesting an increasing incidence of tinea capitis in some areas and increasing clinical failure rates of current therapies. PMID:17151204

Comparison of microbiological loads and physicochemical properties of raw milk treated with single-/multiple-cycle high hydrostatic pressure and ultraviolet-C light

NASA Astrophysics Data System (ADS)

Hu, Guanglan; Zheng, Yuanrong; Wang, Danfeng; Zha, Baoping; Liu, Zhenmin; Deng, Yun

2015-07-01

The effects of ultraviolet-C radiation (UV-C, 11.8 W/m2), single-cycle and multiple-cycle high hydrostatic pressure (HHP at 200, 400 or 600 MPa) on microbial load and physicochemical quality of raw milk were evaluated. Reductions of aerobic plate count (APC) and coliform count (CC) by HHP were more than 99.9% and 98.7%, respectively. Inactivation efficiency of microorganisms increased with pressure level. At the same pressure level, two-cycle treatments caused lower APC, but did not show CC differences compared with single-cycle treatments. Reductions of APC and CC by UV-C were somewhere between 200 MPa and 400/600 MPa. Both HHP and UV-C significantly decreased lightness and increased pH, but did not change soluble solids content and thiobarbituric acid-reactive substances' values. Two 2.5 min cycles of HHP at 600 MPa caused minimum APC and CC, and maximum conductivity. Compared with HHP, UV-C markedly increased protein oxidation and reduced darkening.

Oxidized CaMKII causes cardiac sinus node dysfunction in mice

PubMed Central

Swaminathan, Paari Dominic; Purohit, Anil; Soni, Siddarth; Voigt, Niels; Singh, Madhu V.; Glukhov, Alexey V.; Gao, Zhan; He, B. Julie; Luczak, Elizabeth D.; Joiner, Mei-ling A.; Kutschke, William; Yang, Jinying; Donahue, J. Kevin; Weiss, Robert M.; Grumbach, Isabella M.; Ogawa, Masahiro; Chen, Peng-Sheng; Efimov, Igor; Dobrev, Dobromir; Mohler, Peter J.; Hund, Thomas J.; Anderson, Mark E.

2011-01-01

Sinus node dysfunction (SND) is a major public health problem that is associated with sudden cardiac death and requires surgical implantation of artificial pacemakers. However, little is known about the molecular and cellular mechanisms that cause SND. Most SND occurs in the setting of heart failure and hypertension, conditions that are marked by elevated circulating angiotensin II (Ang II) and increased oxidant stress. Here, we show that oxidized calmodulin kinase II (ox-CaMKII) is a biomarker for SND in patients and dogs and a disease determinant in mice. In wild-type mice, Ang II infusion caused sinoatrial nodal (SAN) cell oxidation by activating NADPH oxidase, leading to increased ox-CaMKII, SAN cell apoptosis, and SND. p47–/– mice lacking functional NADPH oxidase and mice with myocardial or SAN-targeted CaMKII inhibition were highly resistant to SAN apoptosis and SND, suggesting that ox-CaMKII–triggered SAN cell death contributed to SND. We developed a computational model of the sinoatrial node that showed that a loss of SAN cells below a critical threshold caused SND by preventing normal impulse formation and propagation. These data provide novel molecular and mechanistic information to understand SND and suggest that targeted CaMKII inhibition may be useful for preventing SND in high-risk patients. PMID:21785215

7 CFR 52.806 - Color.

Code of Federal Regulations, 2012 CFR

2012-01-01

... PROCESSED FRUITS AND VEGETABLES, PROCESSED PRODUCTS THEREOF, AND CERTAIN OTHER PROCESSED FOOD PRODUCTS 1... cherries that vary markedly from this color due to oxidation, improper processing, or other causes, or that... to oxidation, improper processing, or other causes, or that are undercolored, does not exceed the...

7 CFR 52.806 - Color.

Code of Federal Regulations, 2011 CFR

2011-01-01

... PROCESSED FRUITS AND VEGETABLES, PROCESSED PRODUCTS THEREOF, AND CERTAIN OTHER PROCESSED FOOD PRODUCTS 1... cherries that vary markedly from this color due to oxidation, improper processing, or other causes, or that... to oxidation, improper processing, or other causes, or that are undercolored, does not exceed the...

Expression of intra- and extracellular granzymes in patients with typhoid fever.

PubMed

de Jong, Hanna K; Garcia-Laorden, Maria Isabel; Hoogendijk, Arie J; Parry, Christopher M; Maude, Rapeephan R; Dondorp, Arjen M; Faiz, Mohammed Abul; van der Poll, Tom; Wiersinga, Willem Joost

2017-07-01

Typhoid fever, caused by the intracellular pathogen Salmonella (S.) enterica serovar Typhi, remains a major cause of morbidity and mortality worldwide. Granzymes are serine proteases promoting cytotoxic lymphocytes mediated eradication of intracellular pathogens via the induction of cell death and which can also play a role in inflammation. We aimed to characterize the expression of extracellular and intracellular granzymes in patients with typhoid fever and whether the extracellular levels of granzyme correlated with IFN-γ release. We analyzed soluble protein levels of extracellular granzyme A and B in healthy volunteers and patients with confirmed S. Typhi infection on admission and day of discharge, and investigated whether this correlated with interferon (IFN)-γ release, a cytokine significantly expressed in typhoid fever. The intracellular expression of granzyme A, B and K in subsets of lymphocytic cells was determined using flow cytometry. Patients demonstrated a marked increase of extracellular granzyme A and B in acute phase plasma and a correlation of both granzymes with IFN-γ release. In patients, lower plasma levels of granzyme B, but not granzyme A, were found at day of discharge compared to admission, indicating an association of granzyme B with stage of disease. Peripheral blood mononuclear cells of typhoid fever patients had a higher percentage of lymphocytic cells expressing intracellular granzyme A and granzyme B, but not granzyme K, compared to controls. The marked increase observed in extra- and intracellular levels of granzyme expression in patients with typhoid fever, and the correlation with stage of disease, suggests a role for granzymes in the host response to this disease.

Expression of intra- and extracellular granzymes in patients with typhoid fever

PubMed Central

Garcia-Laorden, Maria Isabel; Hoogendijk, Arie J.; Parry, Christopher M.; Maude, Rapeephan R.; Dondorp, Arjen M.; Faiz, Mohammed Abul; van der Poll, Tom; Wiersinga, Willem Joost

2017-01-01

Background Typhoid fever, caused by the intracellular pathogen Salmonella (S.) enterica serovar Typhi, remains a major cause of morbidity and mortality worldwide. Granzymes are serine proteases promoting cytotoxic lymphocytes mediated eradication of intracellular pathogens via the induction of cell death and which can also play a role in inflammation. We aimed to characterize the expression of extracellular and intracellular granzymes in patients with typhoid fever and whether the extracellular levels of granzyme correlated with IFN-γ release. Methods and principal findings We analyzed soluble protein levels of extracellular granzyme A and B in healthy volunteers and patients with confirmed S. Typhi infection on admission and day of discharge, and investigated whether this correlated with interferon (IFN)-γ release, a cytokine significantly expressed in typhoid fever. The intracellular expression of granzyme A, B and K in subsets of lymphocytic cells was determined using flow cytometry. Patients demonstrated a marked increase of extracellular granzyme A and B in acute phase plasma and a correlation of both granzymes with IFN-γ release. In patients, lower plasma levels of granzyme B, but not granzyme A, were found at day of discharge compared to admission, indicating an association of granzyme B with stage of disease. Peripheral blood mononuclear cells of typhoid fever patients had a higher percentage of lymphocytic cells expressing intracellular granzyme A and granzyme B, but not granzyme K, compared to controls. Conclusion The marked increase observed in extra- and intracellular levels of granzyme expression in patients with typhoid fever, and the correlation with stage of disease, suggests a role for granzymes in the host response to this disease. PMID:28749963

Fifty Years of Progress in Water Relations Research

PubMed Central

Kramer, Paul J.

1974-01-01

Many of the basic concepts dealing with soil and plant water relationships were in existence 50 years ago, but were inadequately presented in the textbooks of that time. There has been a marked increase in the amount of work done in this field during recent decades, but much of it involves advances in understanding the concepts already in existence. Three of the most important advances in the field of water relations are: (a) acceptance of the term, water potential, to describe the free energy status of water in soil and plants; (b) marked improvement in methods of measuring water potential and stomatal resistance; and (c) use of the concept of water flow in the soil-plant system as analogous to flow of electricity in a conducting system. A number of interesting and important problems remain to be studied. Of these, probably the most important is to learn why mild water stress of less than - 10 bars can affect various enzyme-mediated metabolic processes. Plant scientists in applied fields also need to learn more about the causes of differences in ability to tolerate drought among plants of various kinds. There is uncertainty concerning the relative magnitude of the resistances to water flow in various parts of the soil-plant system and concerning the causes of the apparent changes in resistance to water flow with increase in rate and with time of day. More information also is needed concerning the role of growth regulators synthesized in roots and the importance of the older, suberized roots in the absorption of water and mineral nutrients. PMID:16658910

Site fidelity by bees drives pollination facilitation in sequentially blooming plant species.

PubMed

Ogilvie, Jane E; Thomson, James D

2016-06-01

Plant species can influence the pollination and reproductive success of coflowering neighbors that share pollinators. Because some individual pollinators habitually forage in particular areas, it is also possible that plant species could influence the pollination of neighbors that bloom later. When flowers of a preferred forage plant decline in an area, site-fidelity may cause individual flower feeders to stay in an area and switch plant species rather than search for preferred plants in a new location. A newly blooming plant species may quickly inherit a set of visitors from a prior plant species, and therefore experience higher pollination success than it would in an area where the first species never bloomed. To test this, we manipulated the placement and timing of two plant species, Delphinium barbeyi and later-blooming Gentiana parryi. We recorded the responses of individually marked bumble bee pollinators. About 63% of marked individuals returned repeatedly to the same areas to forage on Delphinium. When Delphinium was experimentally taken out of bloom, most of those site-faithful individuals (78%) stayed and switched to Gentiana. Consequently, Gentiana flowers received more visits in areas where Delphinium had previously flowered, compared to areas where Delphinium was still flowering or never occurred. Gentiana stigmas received more pollen in areas where Delphinium disappeared than where it never bloomed, indicating that Delphinium increases the pollination of Gentiana when they are separated in time. Overall, we show that individual bumble bees are often site-faithful, causing one plant species to increase the pollination of another even when separated in time, which is a novel mechanism of pollination facilitation.

Recognition in context: Implications for trade mark law.

PubMed

Humphreys, Michael S; McFarlane, Kimberley A; Burt, Jennifer S; Kelly, Sarah J; Weatherall, Kimberlee G; Burrell, Robert G

2017-10-01

Context effects in recognition have played a major role in evaluating theories of recognition. Understanding how context impacts recognition is also important for making sound trade mark law. Consumers attempting to discriminate between the brand they are looking for and a look-alike product often have to differentiate products which share a great deal of common context: positioning on the supermarket shelf, the type of store, aspects of the packaging, or brand claims. Trade mark and related laws aim to protect brands and reduce consumer confusion, but courts assessing allegations of trade mark infringement often lack careful empirical evidence concerning the impact of brand and context similarity, and, in the absence of such evidence, make assumptions about how consumers respond to brands that downplay the importance of context and focus on the similarity of registered marks. The experiments reported in this paper aimed to test certain common assumptions in trade mark law, providing evidence that shared context can cause mistakes even where brand similarity is low.

A Morphological and Morphometric Study of Bite Marks Caused by Mice (Mus Musculus) on Different Baits for Forensic Purposes.

PubMed

Toledo, Víctor A; Fonseca, Gabriel M; González, Paula A; Ibarra, Luis; Torres, Francisco J; Sáez, Pedro L

2017-03-01

In animal bites, the dental attributes can be fundamental in identifying the marks made by various species on different matrices. Although rodent bite marks have been studied in the context of postmortem interference, little research has used different baits to analyze these marks linking not only specific behavior patterns but also the possibility of structural damage. Twenty mice (Mus musculus) were exposed to different baits to study their bite marks in a controlled model. The known pattern of parallel and multiple grooves has been seen in all baits, but polyvinyl chloride and fiber-optic cable were significantly different between each other and the other baits. Some baits showed patterns of anchorage of the upper incisors and space between the lower incisors when gnawing. This technical note represents a novel model of analysis where veterinarians and/or dentists may be asked to give an opinion on alleged animal bite marks. © 2016 American Academy of Forensic Sciences.

Distinct gene expression profiles characterize the histopathological stages of disease in Helicobacter-induced mucosa-associated lymphoid tissue lymphoma

PubMed Central

Mueller, Anne; O'Rourke, Jani; Grimm, Jan; Guillemin, Karen; Dixon, Michael F.; Lee, Adrian; Falkow, Stanley

2003-01-01

Long-term colonization of humans with Helicobacter pylori can cause the development of gastric B cell mucosa-associated lymphoid tissue lymphoma, yet little is known about the sequence of molecular steps that accompany disease progression. We used microarray analysis and laser microdissection to identify gene expression profiles characteristic and predictive of the various histopathological stages in a mouse model of the disease. The initial step in lymphoma development is marked by infiltration of reactive lymphocytes into the stomach and the launching of a mucosal immune response. Our analysis uncovered molecular markers of both of these processes, including genes coding for the immunoglobulins and the small proline-rich protein Sprr 2A. The subsequent step is characterized histologically by the antigen-driven proliferation and aggregation of B cells and the gradual appearance of lymphoepithelial lesions. In tissues of this stage, we observed increased expression of genes previously associated with malignancy, including the laminin receptor-1 and the multidrug-resistance channel MDR-1. Finally, we found that the transition to destructive lymphoepithelial lesions and malignant lymphoma is marked by an increase in transcription of a single gene encoding calgranulin A/Mrp-8. PMID:12552104

The effect of x rays, DTPA, and aspirin on the absorption of plutonium from the gastrointestinal tract of rats

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

Sullivan, M.F.; Gorham, L.S.; Miller, B.M.

To measure the effect of radiation on plutonium transport, rats that were exposed to 250-kVp X rays were given /sup 238/Pu 3 days afterwards by either gavage or injection into a ligated segment of the duodenum. In a second group of experiments, rats were either injected intraduodenally with /sup 238/Pu-DTPA or administered the chelate intravenously and the /sup 238/Pu by gavage. In a third experiment, rats that had been gavaged with 200 or 400 mg/kg/day of aspirin for 2 days were injected intragastrically with /sup 238/Pu nitrate. Results of the first experiment showed a dose-dependent increase in /sup 238/Pu absorptionmore » between 800 and 1500 rad of lower-body X irradiation. Intravenous or intraduodenal injections of DTPA caused a marked increase in /sup 238/Pu absorption but resulted in decreased plutonium deposition in the skeleton and liver. Retention of /sup 238/Pu in the skeleton of rats given aspirin was double that of controls, but the effect on plutonium absorption was less marked than that of DTPA.« less

Changing arctic ecosystems—What is causing the rapid increase of snow geese in northern Alaska?

USGS Publications Warehouse

Hupp, Jerry W.; Ward, David H.; Whalen, Mary E.; Pearce, John M.

2015-09-10

Through the Changing Arctic Ecosystems (CAE) initiative, the U.S. Geological Survey (USGS) informs key resource management decisions for Arctic Alaska by providing scientific information on current and future ecosystem response to a warming climate. The Arctic Coastal Plain (ACP) of northern Alaska is a key study area within the USGS CAE initiative. This region has experienced a warming trend over the past decades, leading to decreased sea ice, permafrost thaw, and an advancement of spring phenology. The number of birds on the ACP also is changing, marked by increased populations of the four species of geese that nest in the region. The Snow Goose (Chen caerulescens) is the most rapidly increasing of these species. USGS CAE research is quantifying these changes and their implications for management agencies.

Working Memory Capacity as a Dynamic Process

PubMed Central

Simmering, Vanessa R.; Perone, Sammy

2013-01-01

A well-known characteristic of working memory (WM) is its limited capacity. The source of such limitations, however, is a continued point of debate. Developmental research is positioned to address this debate by jointly identifying the source(s) of limitations and the mechanism(s) underlying capacity increases. Here we provide a cross-domain survey of studies and theories of WM capacity development, which reveals a complex picture: dozens of studies from 50 papers show nearly universal increases in capacity estimates with age, but marked variation across studies, tasks, and domains. We argue that the full pattern of performance cannot be captured through traditional approaches emphasizing single causes, or even multiple separable causes, underlying capacity development. Rather, we consider WM capacity as a dynamic process that emerges from a unified cognitive system flexibly adapting to the context and demands of each task. We conclude by enumerating specific challenges for researchers and theorists that will need to be met in order to move our understanding forward. PMID:23335902

Adaptation options for wheat in Europe will be limited by increased adverse weather events under climate change.

PubMed

Trnka, Miroslav; Hlavinka, Petr; Semenov, Mikhail A

2015-11-06

Ways of increasing the production of wheat, the most widely grown cereal crop, will need to be found to meet the increasing demand caused by human population growth in the coming decades. This increase must occur despite the decrease in yield gains now being reported in some regions, increased price volatility and the expected increase in the frequency of adverse weather events that can reduce yields. However, if and how the frequency of adverse weather events will change over Europe, the most important wheat-growing area, has not yet been analysed. Here, we show that the accumulated probability of 11 adverse weather events with the potential to significantly reduce yield will increase markedly across all of Europe. We found that by the end of the century, the exposure of the key European wheat-growing areas, where most wheat production is currently concentrated, may increase more than twofold. However, if we consider the entire arable land area of Europe, a greater than threefold increase in risk was predicted. Therefore, shifting wheat production to new producing regions to reduce the risk might not be possible as the risk of adverse events beyond the key wheat-growing areas increases even more. Furthermore, we found a marked increase in wheat exposure to high temperatures, severe droughts and field inaccessibility compared with other types of adverse events. Our results also showed the limitations of some of the presently debated adaptation options and demonstrated the need for development of region-specific strategies. Other regions of the world could be affected by adverse weather events in the future in a way different from that considered here for Europe. This observation emphasizes the importance of conducting similar analyses for other major wheat regions. © 2015 The Authors.

Adaptation options for wheat in Europe will be limited by increased adverse weather events under climate change

PubMed Central

Trnka, Miroslav; Hlavinka, Petr; Semenov, Mikhail A.

2015-01-01

Ways of increasing the production of wheat, the most widely grown cereal crop, will need to be found to meet the increasing demand caused by human population growth in the coming decades. This increase must occur despite the decrease in yield gains now being reported in some regions, increased price volatility and the expected increase in the frequency of adverse weather events that can reduce yields. However, if and how the frequency of adverse weather events will change over Europe, the most important wheat-growing area, has not yet been analysed. Here, we show that the accumulated probability of 11 adverse weather events with the potential to significantly reduce yield will increase markedly across all of Europe. We found that by the end of the century, the exposure of the key European wheat-growing areas, where most wheat production is currently concentrated, may increase more than twofold. However, if we consider the entire arable land area of Europe, a greater than threefold increase in risk was predicted. Therefore, shifting wheat production to new producing regions to reduce the risk might not be possible as the risk of adverse events beyond the key wheat-growing areas increases even more. Furthermore, we found a marked increase in wheat exposure to high temperatures, severe droughts and field inaccessibility compared with other types of adverse events. Our results also showed the limitations of some of the presently debated adaptation options and demonstrated the need for development of region-specific strategies. Other regions of the world could be affected by adverse weather events in the future in a way different from that considered here for Europe. This observation emphasizes the importance of conducting similar analyses for other major wheat regions. PMID:26577595

Mortality in patients with diabetes mellitus and Addison's disease: a nationwide, matched, observational cohort study.

PubMed

Chantzichristos, Dimitrios; Persson, Anders; Eliasson, Björn; Miftaraj, Mervete; Franzén, Stefan; Bergthorsdottir, Ragnhildur; Gudbjörnsdottir, Soffia; Svensson, Ann-Marie; Johannsson, Gudmundur

2017-01-01

Our hypothesis was that patients with diabetes mellitus obtain an additional risk of death if they develop Addison's disease (AD). Nationwide, matched, observational cohort study cross-referencing the Swedish National Diabetes Register with Inpatient, Cancer and Cause of Death Registers in patients with diabetes (type 1 and 2) and AD and matched controls with diabetes. Clinical characteristics at baseline, overall, and cause-specific mortality were assessed. The relative risk of death was assessed using a Cox proportional hazards regression model. Between January 1996 and December 2012, 226 patients with diabetes and AD were identified and matched with 1129 controls with diabetes. Median (interquartile range) follow-up was 5.9 (2.7-8.6) years. When patients with diabetes were diagnosed with AD, they had an increased frequency of diabetes complications, but both medical history of cancer and coronary heart disease did not differ compared with controls. Sixty-four of the 226 patients with diabetes and AD (28%) died, while 112 of the 1129 controls (10%) died. The estimated relative risk increase (hazard ratio) in overall mortality in the diabetes and AD group was 3.89 (95% confidence interval 2.84-5.32) compared with controls with diabetes. The most common cause of death was cardiovascular in both groups, but patients with diabetes and AD showed an increased death rate from diabetes complications, infectious diseases and unknown causes. Patients with the rare combination of diabetes and AD showed a markedly increased mortality and died more frequently from infections and unknown causes than patients with diabetes alone. Improved strategy for the management of this combination of metabolic disorders is needed. © 2017 European Society of Endocrinology.

Cultural and Species Differences in Gazing Patterns for Marked and Decorated Objects: A Comparative Eye-Tracking Study

PubMed Central

Mühlenbeck, Cordelia; Jacobsen, Thomas; Pritsch, Carla; Liebal, Katja

2017-01-01

Objects from the Middle Paleolithic period colored with ochre and marked with incisions represent the beginning of non-utilitarian object manipulation in different species of the Homo genus. To investigate the visual effects caused by these markings, we compared humans who have different cultural backgrounds (Namibian hunter–gatherers and German city dwellers) to one species of non-human great apes (orangutans) with respect to their perceptions of markings on objects. We used eye-tracking to analyze their fixation patterns and the durations of their fixations on marked and unmarked stones and sticks. In an additional test, humans evaluated the objects regarding their aesthetic preferences. Our hypotheses were that colorful markings help an individual to structure the surrounding world by making certain features of the environment salient, and that aesthetic appreciation should be associated with this structuring. Our results showed that humans fixated on the marked objects longer and used them in the structural processing of the objects and their background, but did not consistently report finding them more beautiful. Orangutans, in contrast, did not distinguish between object and background in their visual processing and did not clearly fixate longer on the markings. Our results suggest that marking behavior is characteristic for humans and evolved as an attention-directing rather than aesthetic benefit. PMID:28167923

Character-marked furniture: potential for lumber yield increase in rip-first rough mills

Treesearch

Urs Buehlmann; Janice K. Wiedenbeck; D. Earl Kline; D. Earl Kline

1998-01-01

The inclusion of character marks in furniture parts increases part yield at least as much as previously estimated by industrial practitioners and scientists specializing in yield efficiency. However, character-marked furniture is uncommon in the more popular North American furniture species and designs. Opportunities for extending the hardwood resource associated with...

Character-marked furniture: potential for lumber yield increase in crosscut-first rough mills

Treesearch

Urs Buehlmann; Janice K. Wiedenbeck; E. Earl Kline; E. Earl Kline

1999-01-01

Including character marks in dimension parts of the furniture, cabinet, and dimension industries offers an opportunity to increase lumber yield substantially. However, little quantitative knowledge exists as to how the incorporation of character marks in parts influences yield when processing lumber in a crosscut-first rough mill. Using computer simulation, this study...

Dietary Choline Deficiency causes DNA Strand Breaks and Alters Epigenetic Marks on DNA and Histones

PubMed Central

Zeisel, Steven H.

2011-01-01

Dietary choline is an important modulator of gene expression (via epigenetic marks) and of DNA integrity. Choline was discovered to be an essential nutrient for some humans approximately one decade ago. This requirement is diminished in young women because estrogen drives endogenous synthesis of phosphatidylcholine, from which choline can be derived. Almost half of women have a single nucleotide polymorphism that abrogates estrogen-induction of endogenous synthesis, and these women require dietary choline just as do men. In the US, dietary intake of choline is marginal. Choline deficiency in people is associated with liver and muscle dysfunction and damage, with apoptosis, and with increased DNA strand breaks. Several mechanisms explain these modifications to DNA. Choline deficiency increases leakage of reactive oxygen species from mitochondria consequent to altered mitochondrial membrane composition and enhanced fatty acid oxidation. Choline deficiency impairs folate metabolism, resulting in decreased thymidylate synthesis and increased uracil misincorporation into DNA, with strand breaks resulting during error-prone repair attempts. Choline deficiency alters DNA methylation, which alters gene expression for critical genes involved in DNA mismatch repair, resulting in increased mutation rates. Any dietary deficiency which increases mutation rates should be associated with increased risk of cancers, and this is the case for choline deficiency. In rodent models, diets low in choline and methyl-groups result in spontaneous hepatocarcinomas. In human epidemiological studies, there are interesting data that suggest that this also may be the case for humans, especially those with SNPs that increase the dietary requirement for choline. PMID:22041500

Dietary choline deficiency causes DNA strand breaks and alters epigenetic marks on DNA and histones.

PubMed

Zeisel, Steven H

2012-05-01

Dietary choline is an important modulator of gene expression (via epigenetic marks) and of DNA integrity. Choline was discovered to be an essential nutrient for some humans approximately one decade ago. This requirement is diminished in young women because estrogen drives endogenous synthesis of phosphatidylcholine, from which choline can be derived. Almost half of women have a single nucleotide polymorphism that abrogates estrogen-induction of endogenous synthesis, and these women require dietary choline just as do men. In the US, dietary intake of choline is marginal. Choline deficiency in people is associated with liver and muscle dysfunction and damage, with apoptosis, and with increased DNA strand breaks. Several mechanisms explain these modifications to DNA. Choline deficiency increases leakage of reactive oxygen species from mitochondria consequent to altered mitochondrial membrane composition and enhanced fatty acid oxidation. Choline deficiency impairs folate metabolism, resulting in decreased thymidylate synthesis and increased uracil misincorporation into DNA, with strand breaks resulting during error-prone repair attempts. Choline deficiency alters DNA methylation, which alters gene expression for critical genes involved in DNA mismatch repair, resulting in increased mutation rates. Any dietary deficiency which increases mutation rates should be associated with increased risk of cancers, and this is the case for choline deficiency. In rodent models, diets low in choline and methyl-groups result in spontaneous hepatocarcinomas. In human epidemiological studies, there are interesting data that suggest that this also may be the case for humans, especially those with SNPs that increase the dietary requirement for choline. Copyright © 2011 Elsevier B.V. All rights reserved.

Numerical Studies of Three-dimensional Breakdown in Trailing Vortex Wakes

NASA Technical Reports Server (NTRS)

Evans, P. F.; Hackett, J. E.

1976-01-01

Finite element, three dimensional relaxation methods are used to calculate the development of vortex wakes behind aircraft for a considerable downstream distance. The inclusion of a self-induction term in the solution, dependent upon local curvature and vortex core radius, permits calculation of finite lifetimes for systems for which infinite life would be predicted two dimensionally. The associated computer program is described together with single-pair, twin-pair, and multiple-pair studies carried out using it. It is found, in single-pair studies, that there is a lower limit to the wavelengths at which the Crow-type of instability can occur. Below this limit, self-induction effects cause the plane of the disturbance waves to rotate counter to the vortex direction. Self induction in two dimensionally generated twin spiral waves causes an increase in axial length which becomes more marked with decreasing initial wavelength. The time taken for vortex convergence toward the center plane is correspondingly increased. The limited parametric twin-pair study performed suggests that time-to-converge increases with increasing flap span. Limited studies of Boeing 747 configurations show correct qualitative response to removal of the outer flap and to gear deployment, as compared with wind tunnel and flight test experience.

Off-target effects of sulforaphane include the derepression of long terminal repeats through histone acetylation events.

PubMed

Baier, Scott R; Zbasnik, Richard; Schlegel, Vicki; Zempleni, Janos

2014-06-01

Sulforaphane is a naturally occurring isothiocyanate in cruciferous vegetables. Sulforaphane inhibits histone deacetylases, leading to the transcriptional activation of genes including tumor suppressor genes. The compound has attracted considerable attention in the chemoprevention of prostate cancer. Here we tested the hypothesis that sulforaphane is not specific for tumor suppressor genes but also activates loci such as long terminal repeats (LTRs), which might impair genome stability. Studies were conducted using chemically pure sulforaphane in primary human IMR-90 fibroblasts and in broccoli sprout feeding studies in healthy adults. Sulforaphane (2.0 μM) caused an increase in LTR transcriptional activity in cultured cells. Consumption of broccoli sprouts (34, 68 or 102 g) by human volunteers caused a dose dependent elevation in LTR mRNA in circulating leukocytes, peaking at more than a 10-fold increase. This increase in transcript levels was associated with an increase in histone H3 K9 acetylation marks in LTR 15 in peripheral blood mononuclear cells from subjects consuming sprouts. Collectively, this study suggests that sulforaphane has off-target effects that warrant further investigation when recommending high levels of sulforaphane intake, despite its promising activities in chemoprevention. Copyright © 2014 Elsevier Inc. All rights reserved.

Humans Have Already Increased the Risk of Basin-wide Disruptions to Pacific Rainfall, and the Risk Increases Even If Global Warming is Restricted to the 2oC Paris Target

NASA Astrophysics Data System (ADS)

Power, S.; Delage, F.; Chung, C.; Ye, H.; Murphy, B.

2017-12-01

The El Nino-Southern Oscillation causes major, intermittent disruptions to rainfall patterns and intensity over the Pacific Ocean lasting up to approximately one year. These disruptions have major impacts on severe weather, agricultural production, ecosystems, streamflow, and disease within and adjacent to the Pacific, and in many countries beyond. The frequency with which major disruptions to Pacific rainfall occur has been projected to increase over the 21st century, in response to global warming caused by large 21st century greenhouse gas emissions. Here we use the latest generation of climate models to show that the risk of disruption has already increased, and that humans may have contributed to the severity of the 1982/83 and 1997/98 events. We also demonstrate - for the first time - that although marked and sustained reductions in 21st century anthropogenic greenhouse gas emissions can greatly moderate the likelihood of major disruption, elevated risk of occurrence appears locked in now, and for at least the remainder of the 21st century. DOI: 10.1038/ncomms14368

Benzo[a]pyrene exposure increases toxic biomarkers and morphological disorders in mouse cervix.

PubMed

Gao, Meili; Li, Yongfei; Sun, Ying; Shah, Walayat; Yang, Shuiyun; Wang, Yili; Long, Jiangang

2011-11-01

Benzo[a]pyrene (BaP) is a representative compound of polycyclic aromatic hydrocarbons exerting cytotoxicity and genotoxicity in the human liver, lung, stomach and skin. However, the toxic effect of BaP on cervical tissue remains unclear. This study was carried out to investigate the toxic effects of BaP on the cervix of ICR mice. Female mice were treated with BaP by intraperitoneal injection and oral gavage at a dose of 2.5, 5 and 10 mg/kg body-weight, twice a week for 14 weeks. BaP treatment caused a significant increase in the levels of MDA and IL-6 with significantly increased activity of CYP1A1, creatine kinase and aspartate aminotransferase (AST) and decreased activity of glutathione-S-transferase in the cervix and liver. The relative cervix weight was markedly reduced in the intraperitoneal BaP injection groups, whereas only a slight reduction was observed in the oral gavage groups. The increase in weight decreased with increasing BaP dose. Moreover, BaP treatment induced significant pathomorphological changes in the cervical tissue and increased the mortality of the mice. Taken together, these results suggest that BaP causes a certain toxic effect on cervical tissue. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

Immunomodulators targeting MARCO expression improve resistance to postinfluenza bacterial pneumonia.

PubMed

Wu, Muzo; Gibbons, John G; DeLoid, Glen M; Bedugnis, Alice S; Thimmulappa, Rajesh K; Biswal, Shyam; Kobzik, Lester

2017-07-01

Downregulation of the alveolar macrophage (AM) receptor with collagenous structure (MARCO) leads to susceptibility to postinfluenza bacterial pneumonia, a major cause of morbidity and mortality. We sought to determine whether immunomodulation of MARCO could improve host defense and resistance to secondary bacterial pneumonia. RNAseq analysis identified a striking increase in MARCO expression between days 9 and 11 after influenza infection and indicated important roles for Akt and Nrf2 in MARCO recovery. In vitro, primary human AM-like monocyte-derived macrophages (AM-MDMs) and THP-1 macrophages were treated with IFNγ to model influenza effects. Activators of Nrf2 (sulforaphane) or Akt (SC79) caused increased MARCO expression and a MARCO-dependent improvement in phagocytosis in IFNγ-treated cells and improved survival in mice with postinfluenza pneumococcal pneumonia. Transcription factor analysis also indicated a role for transcription factor E-box (TFEB) in MARCO recovery. Overexpression of TFEB in THP-1 cells led to marked increases in MARCO. The ability of Akt activation to increase MARCO expression in IFNγ-treated AM-MDMs was abrogated in TFEB-knockdown cells, indicating Akt increases MARCO expression through TFEB. Increasing MARCO expression by targeting Nrf2 signaling or the Akt-TFEB-MARCO pathway are promising strategies to improve bacterial clearance and survival in postinfluenza bacterial pneumonia. Copyright © 2017 the American Physiological Society.

Increased prevalence of group A streptococcus isolates in streptococcal toxic shock syndrome cases in Japan from 2010 to 2012.

PubMed

Ikebe, T; Tominaga, K; Shima, T; Okuno, R; Kubota, H; Ogata, K; Chiba, K; Katsukawa, C; Ohya, H; Tada, Y; Okabe, N; Watanabe, H; Ogawa, M; Ohnishi, M

2015-03-01

Streptococcal toxic shock syndrome (STSS) is a severe invasive infection characterized by the sudden onset of shock, multi-organ failure, and high mortality. In Japan, appropriate notification measures based on the Infectious Disease Control law are mandatory for cases of STSS caused by β-haemolytic streptococcus. STSS is mainly caused by group A streptococcus (GAS). Although an average of 60-70 cases of GAS-induced STSS are reported annually, 143 cases were recorded in 2011. To determine the reason behind this marked increase, we characterized the emm genotype of 249 GAS isolates from STSS patients in Japan from 2010 to 2012 and performed antimicrobial susceptibility testing. The predominant genotype was found to be emm1, followed by emm89, emm12, emm28, emm3, and emm90. These six genotypes constituted more than 90% of the STSS isolates. The number of emm1, emm89, emm12, and emm28 isolates increased concomitantly with the increase in the total number of STSS cases. In particular, the number of mefA-positive emm1 isolates has escalated since 2011. Thus, the increase in the incidence of STSS can be attributed to an increase in the number of cases associated with specific genotypes.

Effects of erbium-and chromium-doped yttrium scandium gallium garnet and diode lasers on the surfaces of restorative dental materials: a scanning electron microscope study.

PubMed

Hatipoglu, M; Barutcigil, C

2015-01-01

The aim of this study is to evaluate the potential effects of laser irradiation, which is commonly performed in periodontal surgery, on the surfaces of restorative materials. Five different restorative dental materials were used in this study, as follows: (1) Resin composite, (2) poly acid-modified resin composite (compomer), (3) conventional glass ionomer cement (GIC), (4) resin-modified glass ionomer cement (RMGIC), and (5) amalgam. Four cylindrical samples (8 mm diameter, 2 mm height) were prepared for each restorative material. In addition, four freshly extracted, sound human incisors teeth were selected. Two different laser systems commonly used in periodontal surgery were examined in this study: A 810 nm diode laser at a setting of 1 W with continuous-phase laser irradiation for 10 s, and an erbium-and chromium-doped yttrium scandium gallium garnet (Er, Cr: YSGG) laser at settings of 2.5 W, 3.25 W, and 4 W with 25 Hz laser irradiation for 10 s. Scanning electron microscopy (SEM) analysis was performed to evaluate the morphology and surface deformation of the restorative materials and tooth surfaces. According to the SEM images, the Er, Cr: YSGG laser causes irradiation markings that appear as demineralized surfaces on tooth samples. The Er, Cr: YSGG laser also caused deep defects on composite, compomer, and RMGIC surfaces because of its high power, and the ablation was deeper for these samples. High-magnification SEM images of GIC samples showed the melting and combustion effects of the Er, Cr: YSGG laser, which increased as the laser power was increased. In amalgam samples, neither laser left significant harmful effects at the lowest power setting. The diode laser did cause irradiation markings, but they were insignificant compared with those left by the Er, Cr: YSGG laser on the surfaces of the different materials and teeth. Within the limitations of this study, it can be concluded that Er, Cr: YSGG laser irradiation could cause distortions of the surfaces of restorative materials. Diode lasers can be preferred for periodontal surgery.

Variability of intensity ratios of H to He and He to ions with Z not smaller than 3 in solar energetic particle events

NASA Technical Reports Server (NTRS)

Van Allen, J. A.; Venkatarangan, P.; Venkatesan, D.

1974-01-01

Data from the solid-state detector on Explorer 35 are applied to a study of two intensity ratios in the sub-MeV per nucleon specific kinetic energy range for several energetic particle events. It is found that the intensity ratios vary markedly from event to event, particularly during the time history of the individual events. This implies that the ratios have no simple relationship to 'solar abundances' in the usual sense of the term. The pattern of the variability of each ratio is established; the ratio of He to ions with Z not smaller than 3 starts with a low value and increases as the event proceeds. The H/He ratio exhibits a qualitatively similar time history with marked relative enhancement of He early in an event. Differential diffusion of the various ionic species with differing magnetic rigidities is seen to be the dominant physical cause for the variabilities observed.

Cell lineage analysis in human brain using endogenous retroelements

PubMed Central

Evrony, Gilad D.; Lee, Eunjung; Mehta, Bhaven K.; Benjamini, Yuval; Johnson, Robert M.; Cai, Xuyu; Yang, Lixing; Haseley, Psalm; Lehmann, Hillel S.; Park, Peter J.; Walsh, Christopher A.

2015-01-01

Summary Somatic mutations occur during brain development and are increasingly implicated as a cause of neurogenetic disease. However, the patterns in which somatic mutations distribute in the human brain are unknown. We used high-coverage whole-genome sequencing of single neurons from a normal individual to identify spontaneous somatic mutations as clonal marks to track cell lineages in human brain. Somatic mutation analyses in >30 locations throughout the nervous system identified multiple lineages and sub-lineages of cells marked by different LINE-1 (L1) retrotransposition events and subsequent mutation of poly-A microsatellites within L1. One clone contained thousands of cells limited to the left middle frontal gyrus, whereas a second distinct clone contained millions of cells distributed over the entire left hemisphere. These patterns mirror known somatic mutation disorders of brain development, and suggest that focally distributed mutations are also prevalent in normal brains. Single-cell analysis of somatic mutation enables tracing of cell lineage clones in human brain. PMID:25569347

Alkaptonuria and Pompe disease in one patient: metabolic and molecular analysis.

PubMed

Zouheir Habbal, Mohammad; Bou Assi, Tarek; Mansour, Hicham

2013-04-29

Pompe disease is characterised by deficiency of acid α-glucosidase that results in abnormal glycogen deposition in the muscles. Alkaptonuria is caused by a defect in the enzyme homogentisate 1,2-dioxygenase with subsequent accumulation of homogentisic acid. We report the case of a 6-year-old boy diagnosed with Pompe disease and alkaptonuria. Urine organic acids and α-glucosidase were measured. Homogentisate 1,2-dioxygenase (HGO) and acid alpha-glucosidase (GAA) genes were sequenced by Sanger DNA sequencing. The level of α-glucosidase in white blood cells was markedly decreased (4 nm/mg) while the level of homogentisic acid was markedly increased (15 027 mmol/mol creatine). GAA sequencing detected two heterozygous GAA mutations (C.670C>T and C.1064T>C) while HGO sequencing revealed three polymorphisms in exons 4, 5 and 6, respectively. To the best of our knowledge, this is the first reported instance of Pompe disease and alkaptonuria occurring in the same individual.

Alkaptonuria and pompe disease in one patient: metabolic and molecular analysis

PubMed Central

Habbal, Mohammad Zouheir; Bou Assi, Tarek; Mansour, Hicham

2013-01-01

Pompe disease is characterised by deficiency of acid α-glucosidase that results in abnormal glycogen deposition in the muscles. Alkaptonuria is caused by a defect in the enzyme homogentisate 1,2-dioxygenase with subsequent accumulation of homogentisic acid. We report the case of a 6-year-old boy diagnosed with Pompe disease and alkaptonuria. Urine organic acids and α-glucosidase were measured. Homogentisate 1,2-dioxygenase (HGO) and acid alpha-glucosidase (GAA) genes were sequenced by Sanger DNA sequencing. The level of α-glucosidase in white blood cells was markedly decreased (4 nm/mg) while the level of homogentisic acid was markedly increased (15 027 mmol/mol creatine). GAA sequencing detected two heterozygous GAA mutations (C.670C>T and C.1064T>C) while HGO sequencing revealed three polymorphisms in exons 4, 5 and 6, respectively. To the best of our knowledge, this is the first reported instance of Pompe disease and alkaptonuria occurring in the same individual. PMID:23632174

The epigenomic interface between genome and environment in common complex diseases.

PubMed

Bell, Christopher G; Beck, Stephan

2010-12-01

The epigenome plays the pivotal role as interface between genome and environment. True genome-wide assessments of epigenetic marks, such as DNA methylation (methylomes) or chromatin modifications (chromatinomes), are now possible, either through high-throughput arrays or increasingly by second-generation DNA sequencing methods. The ability to collect these data at this level of resolution enables us to begin to be able to propose detailed questions, and interrogate this information, with regards to changes that occur due to development, lineage and tissue-specificity, and significantly those caused by environmental influence, such as ageing, stress, diet, hormones or toxins. Common complex traits are under variable levels of genetic influence and additionally epigenetic effect. The detection of pathological epigenetic alterations will reveal additional insights into their aetiology and how possible environmental modulation of this mechanism may occur. Due to the reversibility of these marks, the potential for sequence-specific targeted therapeutics exists. This review surveys recent epigenomic advances and their current and prospective application to the study of common diseases.

Environmental zinc and cadmium pollution associated with generalized osteochondrosis, osteoporosis, and nephrocalcinosis in horses

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

Gunson, D.E.; Kowalczyk, D.F.; Shoop, C.R.

1982-02-01

Several suspect causes of chronic zinc/cadmium toxicosis in horses near a zinc smelter were investigated following observations of lameness, swollen joints, and unthriftiness, particularly in foals. Two foals born and raised near the smelter were lame and had joint swellings that were attributable to severe generalized osteochondrosis. Zinc and cadmium concentrations were markedly increased in the pancreas, liver, and kidney. The serum of 1 foal, zinc and potassium concentrations were high, whereas calcium and magnesium concentrations were low. Marked nephrocalcinosis and osteoporosis were observed in this foal. Nephrocalcinosis also was observed in his dam, who died of a punctured lungmore » following rib fractures, though there was no history of trauma. The joint cartilage lesions were similar to those induced experimentally in animals fed high-zinc diets and may have been the result of zin-induced abnormality of copper metabolism. The osteoporosis and nephrocalcinosis were consistent with chronic cadmium toxicosis.« less

Place of Death in Patients with Lung Cancer: A Retrospective Cohort Study from 2004-2013.

PubMed

O'Dowd, Emma L; McKeever, Tricia M; Baldwin, David R; Hubbard, Richard B

2016-01-01

Many patients with cancer die in an acute hospital bed, which has been frequently identified as the least preferred location, with psychological and financial implications. This study looks at place and cause of death in patients with lung cancer and identifies which factors are associated with dying in an acute hospital bed versus at home. We used the National Lung Cancer Audit linked to Hospital Episode Statistics and Office for National Statistics data to determine cause and place of death in those with lung cancer; both overall and by cancer Network. We used multivariate logistic regression to compare features of those who died in an acute hospital versus those who died at home. Of 143627 patients identified 40% (57678) died in an acute hospital, 29% (41957) died at home and 17% (24108) died in a hospice. Individual factors associated with death in an acute hospital bed compared to home were male sex, increasing age, poor performance status, social deprivation and diagnosis via an emergency route. There was marked variation between cancer Networks in place of death. The proportion of patients dying in an acute hospital ranged from 28% to 48%, with variation most notable in provision of hospice care (9% versus 33%). Cause of death in the majority was lung cancer (86%), with other malignancies, chronic obstructive pulmonary disease (COPD) and ischaemic heart disease (IHD) comprising 9% collectively. A substantial proportion of patients with lung cancer die in acute hospital beds and this is more likely with increasing age, male sex, social deprivation and in those with poor performance status. There is marked variation between Networks, suggesting a need to improve end-of-life planning in those at greatest risk, and to review the allocation of resources to provide more hospice beds, enhanced community support and ensure equal access.

Feedback from Arctic charr: Feed flavour stimulation and re-feeding after feed deprivation stimulate genes encoding both orexigenic and anorexigenic neuropeptides.

PubMed

Striberny, Anja; Jørgensen, Even H

2017-05-15

Despite vast research attention, the knowledge about central mechanisms of appetite regulation in teleost remains inconclusive. A common strategy in studies on appetite regulating mechanisms is to measure the response to feed restriction or - deprivation, but responses vary between fish species and between experiments, and are also likely dependent on the degree of energy perturbation. The anadromous Arctic charr is an interesting model for studying appetite regulation as its feeding cycle comprises months of winter anorexia, and hyperphagia during summer. Here we studied how the gene expression of putative hypothalamic appetite regulators were affected by two days, one week and one month feed deprivation during summer, and subsequent re-feeding and exposure to feed flavour. Short-term feed deprivation caused only a minor reduction in condition factor and had no effect on hypothalamic gene expression. Long-term feed-deprivation caused a marked reduction in weight and condition factor which contrasted the increase in weight and condition factor seen in ad libitum fed controls. A marked energy perturbation by feed deprivation was also indicated by a lower hypothalamic expression of the genes encoding insulin-like growth factor 1 (IGF1) and IGF1 binding protein 5 in the feed deprived charr compared to fed controls. Surprisingly, long-term feed deprivation and energy perturbation did not induce changes in hypothalamic appetite regulators. Unexpectedly, re-feeding and exposure to feed flavour caused an increase in the expression of the genes encoding the orexigenic agouti-related peptide and the anorexigenic melanocortin receptor 4 and cocaine- and amphetamine-regulated transcript. Our study gives strong evidence for a role of these in appetite regulation in Arctic charr, but their mechanisms of action remain unknown. We suggest that changes in gene expression are more likely to be registered during transition phases, e.g. from fasting to feeding and upon stimulatory inputs such as feed flavour. Copyright © 2017 Elsevier Inc. All rights reserved.

Cocklebur (Xanthium strumarium, L. var. strumarium) intoxication in swine: review and redefinition of the toxic principle.

PubMed

Stuart, B P; Cole, R J; Gosser, H S

1981-05-01

Cocklebur (Xanthium strumarium) fed to feeder pigs was associated with acute to subacute hepatotoxicosis. Cotyledonary seedings fed at 0.75% to 3% of body weight or ground bur fed at 20% to 30% of the ration caused acute depression, convulsions, and death. Principle gross lesions were marked serofibrinous ascites, edema of the gallbladder wall, and lobular accentuation of the liver. Acute to subacute centrilobular hepatic necrosis was present microscopically. The previously reported toxic principle, hydroquinone, was not recovered from the plant or bur of X. strumarium. Authentic hydroquinone administered orally failed to produce lesions typical of cocklebur intoxication but did produce marked hyperglycemia. Carboxyatractyloside recovered from the aqueous extract of X. strumarium and authentic carboxyatractyloside, when fed to pigs, caused signs and lesions typical of cocklebur intoxication. Marked hypoglycemia and elevated serum glutamic oxaloacetic transaminase and serum isocitric dehydrogenase concentrations occurred in pigs with acute hepatic necrosis that had received either cocklebur seedlings, ground bur or carboxyatractyloside.

Multiple proximate and ultimate causes of natal dispersal in white-tailed deer

USGS Publications Warehouse

Long, E.S.; Diefenbach, D.R.; Rosenberry, C.S.; Wallingford, B.D.

2008-01-01

Proximate and ultimate causes of dispersal in vertebrates vary, and relative importance of these causes is poorly understood. Among populations, inter- and intrasexual social cues for dispersal are thought to reduce inbreeding and local mate competition, respectively, and specific emigration cue may affect dispersal distance, such that inbreeding avoidance dispersal tends to be farther than dispersal to reduce local competition. To investigate potential occurrence of multiple proximate and ultimate causes of dispersal within populations, we radio-marked 363 juvenile male white-tailed deer (Odocoileus virginianus) in 2 study areas in Pennsylvania. Natal dispersal probability and distance were monitored over a 3-year period when large-scale management changes reduced density of adult females and increased density of adult males. Most dispersal (95-97%) occurred during two 12-week periods: spring, when yearling males still closely associate with related females, and prior to fall breeding season, when yearling males closely associate with other breeding-age males. Following changes to sex and age structure that reduced potential for inbreeding and increased potential for mate competition, annual dispersal probability did not change; however, probability of spring dispersal decreased, whereas probability of fall dispersal increased. Spring dispersal distances were greater than fall dispersal distances, suggesting that adaptive inbreeding avoidance dispersal requires greater distance than mate competition dispersal where opposite-sex relatives are philopatric and populations are not patchily distributed. Both inbreeding avoidance and mate competition are important ultimate causes of dispersal of white-tailed deer, but ultimate motivations for dispersal are proximately cued by different social mechanisms and elicit different responses in dispersers.

Public health impact of androgens.

PubMed

Kanayama, Gen; Kaufman, Marc J; Pope, Harrison G

2018-06-01

To summarize recent findings regarding the public health impact of androgen abuse. Abuse of androgens (also called 'anabolic-androgenic steroids') has grown into a major worldwide substance abuse problem involving tens of millions of individuals, of whom about 98% are men. Most androgen abusers are still under age 50 today, and thus, the long-term effects of these drugs are only beginning to be understood. Recent studies confirm that long-term supraphysiologic androgen exposure produces cardiovascular toxicity, characterized especially by cardiomyopathy and atherosclerotic disease. Withdrawal from androgens after long-term use may produce prolonged and sometimes irreversible hypogonadism in men. Supraphysiologic androgen levels may sometimes cause irritability, aggressiveness, and violence, whereas androgen withdrawal may cause depression. However, these psychiatric effects are idiosyncratic, affecting only a minority of users. Emerging evidence now also suggests that long-term androgen exposure may cause neurotoxicity, raising the possibility that aging androgen abusers may be at increased risk for dementia. Several recent studies have also described androgen-induced hepatotoxicity, nephrotoxicity, and adverse musculoskeletal effects. Recent studies have demonstrated marked adverse effects of long-term androgen abuse. As increasing numbers of androgen abusers reach middle age, these effects will likely represent an emerging public health problem.

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

Otolith marking of juvenile shortnose gar by immersion in oxytetracycline

USGS Publications Warehouse

Snow, Richard A.; Long, James M.

2017-01-01

Oxytetracycline (OTC) has been used to mark a variety of fish species at multiple developmental stages; however, there is little information on batch-marking Lepisosteidae. Juvenile Shortnose Gar Lepisosteus platostomus (53 ± 3 mm TL) were seined from an Oklahoma State University research pond and transported to the Oklahoma Fishery Research Lab. Juvenile Shortnose Gar were exposed to a range of OTC concentrations—0, 500, 600, and 700 mg/L—for 4, 5, or 6 h. Lapillus and sagitta otoliths were examined 14 d postexposure for mark presence and evaluation using fluorescent microscopy. Overall, 93.3% of otoliths exposed to OTC exhibited a mark. Concentration of OTC affected the mean mark quality, whereas duration and otolith type examined did not. However, as concentration increased, so did mortality, suggesting a balance is needed to achieve marking goals. Based on our findings, batch marking of Shortnose Gar can be successful at OTC concentrations from 500 to 700 mg/L for 4–6 h, although mark quality may vary and mortality rates increase at the higher concentrations and longer durations.

[Vasovagal syncope as a cause of serious body injury - two case reports].

PubMed

Gajek, Jacek; Zyśko, Dorota

2003-04-01

Vasovagal syncope is a reflex reaction, leading to marked hypotension and/or bradycardia with transient loss of consciousness and the postural muscle tone. The recovery is spontaneous and usually rapid. Serious body injuries caused by fainting are rare. We present two patients with vasovagal syncope which caused serious injury. Different therapeutic options, including pacemaker implantation, are discussed.

Potentiation by cholinesterase inhibitors of cholinergic activity in rat isolated stomach and colon.

PubMed

Jarvie, Emma M; Cellek, Selim; Sanger, Gareth J

2008-01-01

Acetylcholinesterase (AChE) inhibitors stimulate gastrointestinal (GI) motility and are potential treatments of conditions associated with inadequate GI motility. The ability of itopride to facilitate neuronally (predominantly cholinergic) mediated contractions of rat isolated stomach, evoked by electrical field stimulation (EFS), has been compared with other cholinesterase inhibitors and with tegaserod, a clinically effective prokinetic and non-selective 5-HT(4) receptor agonist which also facilitates GI cholinergic function. Neostigmine greatly increased EFS-evoked contractions over a narrow concentration range (0.01-1 microM; 754+/-337% facilitation at 1 microM); higher concentrations (1, 3 microM) also increased muscle tension. Donepezil increased EFS-evoked contractions gradually over the full range of concentrations (0.01-10 microM; maximum increase 516+/-20% at 10 microM). Itopride increased the contractions even more gradually, rising to 188+/-84% at 10 microM. The butyrylcholinesterase inhibitor iso-OMPA 0.01-10 microM also increased EFS-evoked contractions, to a maximum of 36+/-5.0% at 10 microM, similar to that caused by tegaserod (35+/-5.2% increase at 1 microM). The effects of tegaserod, but not itopride were inhibited by the 5-HT(4) receptor antagonist SB-204070A 0.3 microM. In rat isolated colon, neostigmine was again the most efficacious, causing a defined maximum increase in EFS-evoked contractions (343+/-82% at 10 microM), without changing muscle tension. Maximum increases caused by donepezil and itopride were, respectively, 57.6+/-20 and 43+/-15% at 10 microM. These data indicate that the abilities of different AChE inhibitors to increase GI cholinergic activity differ markedly. Understanding the reasons is essential if AChE inhibitors are to be optimally developed as GI prokinetics.

Microscopic analysis and simulation of check-mark stain on the galvanized steel strip

NASA Astrophysics Data System (ADS)

So, Hongyun; Yoon, Hyun Gi; Chung, Myung Kyoon

2010-11-01

When galvanized steel strip is produced through a continuous hot-dip galvanizing process, the thickness of adhered zinc film is controlled by plane impinging air gas jet referred to as "air-knife system". In such a gas-jet wiping process, stain of check-mark or sag line shape frequently appears. The check-mark defect is caused by non-uniform zinc coating and the oblique patterns such as "W", "V" or "X" on the coated surface. The present paper presents a cause and analysis of the check-mark formation and a numerical simulation of sag lines by using the numerical data produced by Large Eddy Simulation (LES) of the three-dimensional compressible turbulent flow field around the air-knife system. It was found that there is alternating plane-wise vortices near the impinging stagnation region and such alternating vortices move almost periodically to the right and to the left sides on the stagnation line due to the jet flow instability. Meanwhile, in order to simulate the check-mark formation, a novel perturbation model has been developed to predict the variation of coating thickness along the transverse direction. Finally, the three-dimensional zinc coating surface was obtained by the present perturbation model. It was found that the sag line formation is determined by the combination of the instantaneous coating thickness distribution along the transverse direction near the stagnation line and the feed speed of the steel strip.

PULMONARY AND CARDIAC GENE EXPRESSION FOLLOWING ACUTE ULTRAFINE CARBON PARTICLE INHALATION IN HYPERTENSIVE RATS

EPA Science Inventory

Inhalation of ultrafine carbon particles (ufCP) causes cardiac physiological changes without marked pulmonary injury or inflammation. We hypothesized that acute ufCP exposure of 13 months old Spontaneously Hypertensive (SH) rats will cause differential effects on the lung and hea...

Bayesian Analysis of Silica Exposure and Lung Cancer Using Human and Animal Studies.

PubMed

Bartell, Scott M; Hamra, Ghassan Badri; Steenland, Kyle

2017-03-01

Bayesian methods can be used to incorporate external information into epidemiologic exposure-response analyses of silica and lung cancer. We used data from a pooled mortality analysis of silica and lung cancer (n = 65,980), using untransformed and log-transformed cumulative exposure. Animal data came from chronic silica inhalation studies using rats. We conducted Bayesian analyses with informative priors based on the animal data and different cross-species extrapolation factors. We also conducted analyses with exposure measurement error corrections in the absence of a gold standard, assuming Berkson-type error that increased with increasing exposure. The pooled animal data exposure-response coefficient was markedly higher (log exposure) or lower (untransformed exposure) than the coefficient for the pooled human data. With 10-fold uncertainty, the animal prior had little effect on results for pooled analyses and only modest effects in some individual studies. One-fold uncertainty produced markedly different results for both pooled and individual studies. Measurement error correction had little effect in pooled analyses using log exposure. Using untransformed exposure, measurement error correction caused a 5% decrease in the exposure-response coefficient for the pooled analysis and marked changes in some individual studies. The animal prior had more impact for smaller human studies and for one-fold versus three- or 10-fold uncertainty. Adjustment for Berkson error using Bayesian methods had little effect on the exposure-response coefficient when exposure was log transformed or when the sample size was large. See video abstract at, http://links.lww.com/EDE/B160.

GHRH excess and blockade in X-LAG syndrome.

PubMed

Daly, Adrian F; Lysy, Philippe A; Desfilles, Céline; Rostomyan, Liliya; Mohamed, Amira; Caberg, Jean-Hubert; Raverot, Veronique; Castermans, Emilie; Marbaix, Etienne; Maiter, Dominique; Brunelle, Chloe; Trivellin, Giampaolo; Stratakis, Constantine A; Bours, Vincent; Raftopoulos, Christian; Beauloye, Veronique; Barlier, Anne; Beckers, Albert

2016-03-01

X-linked acrogigantism (X-LAG) syndrome is a newly described form of inheritable pituitary gigantism that begins in early childhood and is usually associated with markedly elevated GH and prolactin secretion by mixed pituitary adenomas/hyperplasia. Microduplications on chromosome Xq26.3 including the GPR101 gene cause X-LAG syndrome. In individual cases random GHRH levels have been elevated. We performed a series of hormonal profiles in a young female sporadic X-LAG syndrome patient and subsequently undertook in vitro studies of primary pituitary tumor culture following neurosurgical resection. The patient demonstrated consistently elevated circulating GHRH levels throughout preoperative testing, which was accompanied by marked GH and prolactin hypersecretion; GH demonstrated a paradoxical increase following TRH administration. In vitro, the pituitary cells showed baseline GH and prolactin release that was further stimulated by GHRH administration. Co-incubation with GHRH and the GHRH receptor antagonist, acetyl-(d-Arg(2))-GHRH (1-29) amide, blocked the GHRH-induced GH stimulation; the GHRH receptor antagonist alone significantly reduced GH release. Pasireotide, but not octreotide, inhibited GH secretion. A ghrelin receptor agonist and an inverse agonist led to modest, statistically significant increases and decreases in GH secretion, respectively. GHRH hypersecretion can accompany the pituitary abnormalities seen in X-LAG syndrome. These data suggest that the pathology of X-LAG syndrome may include hypothalamic dysregulation of GHRH secretion, which is in keeping with localization of GPR101 in the hypothalamus. Therapeutic blockade of GHRH secretion could represent a way to target the marked hormonal hypersecretion and overgrowth that characterizes X-LAG syndrome. © 2016 Society for Endocrinology.

Forster's tern chick survival in response to a managed relocation of predatory California gulls

USGS Publications Warehouse

Ackerman, Joshua T.; Herzog, Mark P.; Hartman, C. Alex; Herring, Garth

2014-01-01

Gull populations can severely limit the productivity of waterbirds. Relocating gull colonies may reduce their effects on nearby breeding waterbirds, but there are few examples of this management strategy. We examined gull predation and survival of Forster's tern (Sterna forsteri) chicks before (2010) and after (2011) the managed relocation of the largest California gull (Larus californicus) colony (24,000 adults) in San Francisco Bay, California. Overall, survival of radio-marked Forster's tern chicks from hatching to fledging was 0.22 ± 0.03 (mean ± SE), and daily survival rates increased with age. Gulls were the predominant predator of tern chicks, potentially causing 54% of chick deaths. Prior to the gull colony relocation, 56% of radio-marked and 20% of banded tern chicks from the nearest tern colony were recovered dead in the gull colony, compared to only 15% of radio-marked and 4% of banded chicks recovered dead from all other tern colonies. The managed relocation of the gull colony substantially increased tern chick survival (by 900%) in the nearby (3.8 km) reference tern colony (0.29 ± 0.10 in 2010 and 0.25 ± 0.09 in 2011). Among 19 tern nesting islands, fledging success was higher when gull abundance was lower at nearby colonies and when gull colonies were farther from the tern colony. Our results indicate that the managed relocation of gull colonies away from preferred nesting areas of sensitive waterbirds can improve local reproductive success, but this conservation strategy may shift gull predation pressure to other areas or species.

Comparison of the effects of single and daily repeated immobilization stress on resting activity and heterotypic sensitization of the hypothalamic-pituitary-adrenal axis.

PubMed

Daviu, Núria; Rabasa, Cristina; Nadal, Roser; Armario, Antonio

2014-03-01

Acute exposure to severe stressors causes marked activation of the hypothalamic-pituitary-adrenal (HPA) axis that is reflected on the day after higher resting levels of HPA hormones and sensitization of the HPA response to novel (heterotypic) stressors. However, whether a single exposure to a severe stressor or daily repeated exposure to the same (homotypic) stressor modifies these responses to the same extent has not been studied. In this experiment, we studied this issue in adult male Sprague-Dawley rats daily exposed for seven days to a severe stressor such as immobilization on boards (IMO). A first exposure to 1 h IMO resulted in a marked activation of the HPA axis as reflected in plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone, and such activation was significantly reduced after the seventh IMO. On the day after the first IMO, higher resting levels of ACTH and corticosterone and sensitization of their responses to a short exposure to an open-field (OF) were observed, together with a marked hypoactivity in this environment. Repeated exposure to IMO partially reduced hypoactivity, the increase in resting levels of HPA hormones and the ACTH responsiveness to the OF on the day after the last exposure to IMO. In contrast, corticosterone response was gradually increased, suggesting partial dissociation from ACTH. These results indicate that daily repeated exposure to the same stressor partially reduced the HPA response to the homotypic stressor as well as the sensitization of HPA axis activity observed the day after chronic stress cessation.

Resolution of renal adenocarcinoma-induced secondary inappropriate polycythaemia after nephrectomy in two cats.

PubMed

Klainbart, Sigal; Segev, Gilad; Loeb, Emmanuel; Melamed, Dana; Aroch, Itamar

2008-07-01

Two cases of secondary, inappropriate polycythaemia caused by renal adenocarcinoma in domestic shorthair cats, are described. The cats were 9 and 12 years old and both were presented because of generalised seizures presumably due to hyperviscosity. Both cats had a markedly increased haematocrit (0.770 and 0.632 l/l) and thrombocytosis (744 x 10(9)/l and 926 x 10(9)/l). An abdominal ultrasound revealed a mass in the cranial pole of one kidney in both cats. Serum erythropoietin (EPO) concentration was within the reference interval (RI) in both cats but was inappropriately high considering the markedly increased haematocrit. The cats were initially stabilised and managed by multiple phlebotomies and intravenous fluid therapy and underwent nephrectomy of the affected kidney later on. Both the polycythaemia and thrombocytosis resolved following surgery. Postoperative serum EPO concentration, measured in one cat, decreased markedly. Histopathology of the affected kidneys confirmed a diagnosis of renal adenocarcinoma. Both cats were stable for an 8-month follow-up period; however, one cat had developed a stable chronic kidney disease (CKD), while the other was represented 8 months postoperatively due to dyspnoea, and had radiographic evidence of lung metastasis, presumably because of the spread of the original renal tumour and was euthanased. Initial stabilisation of polycythaemic cats should include multiple phlebotomies. Nephrectomy should be considered in cats with secondary, inappropriate, renal adenocarcinoma-related polycythaemia when only one kidney is affected by the tumour, and provided that the other kidney's function is satisfactory. Nephrectomy should be expected to resolve the polycythaemia and lead to normalisation of serum EPO concentration.

Snake fungal disease: An emerging threat to wild snakes

USGS Publications Warehouse

Lorch, Jeffrey M.; Knowles, Susan N.; Lankton, Julia S.; Michell, Kathy; Edwards, Jaime L.; Kapfer, Joshua M.; Staffen, Richard A.; Wild, Erik R.; Schmidt, Katie Z.; Ballmann, Anne; Blodgett, Doug; Farrell, Terence M.; Glorioso, Brad M.; Last, Lisa A.; Price, Steven J.; Schuler, Krysten L.; Smith, Christopher; Wellehan, James F. X.; Blehert, David S.

2016-01-01

Since 2006, there has been a marked increase in the number of reports of severe and often fatal fungal skin infections in wild snakes in the eastern USA. The emerging condition, referred to as snake fungal disease (SFD), was initially documented in rattlesnakes, where the infections were believed to pose a risk to the viability of affected populations. The disease is caused byOphidiomyces ophiodiicola, a fungus recently split from a complex of fungi long referred to as the Chrysosporium anamorph of Nannizziopsis vriesii (CANV). Here we review the current state of knowledge about O. ophiodiicola and SFD. In addition, we provide original findings which demonstrate that O. ophiodiicola is widely distributed in eastern North America, has a broad host range, is the predominant cause of fungal skin infections in wild snakes and often causes mild infections in snakes emerging from hibernation. This new information, together with what is already available in the scientific literature, advances our knowledge of the cause, pathogenesis and ecology of SFD. However, additional research is necessary to elucidate the factors driving the emergence of this disease and develop strategies to mitigate its impacts.

Subsidence of Surtsey volcano, 1967-1991

USGS Publications Warehouse

Moore, J.G.; Jakobsson, S.; Holmjarn, J.

1992-01-01

The Surtsey marine volcano was built on the southern insular shelf of Iceland, along the seaward extension of the east volcanic zone, during episodic explosive and effusive activity from 1963 to 1967. A 1600-m-long, east-west line of 42 bench marks was established across the island shortly after volcanic activity stopped. From 1967 to 1991 a series of leveling surveys measured the relative elevation of the original bench marks, as well as additional bench marks installed in 1979, 1982 and 1985. Concurrent measurements were made of water levels in a pit dug on the north coast, in a drill hole, and along the coastline exposed to the open ocean. These surveys indicate that the dominant vertical movement of Surtsey is a general subsidence of about 1.1??0.3 m during the 24-year period of observations. The rate of subsidence decreased from 15-20 cm/year for 1967-1968 to 1-2 cm/year in 1991. Greatest subsidence is centered about the eastern vent area. Through 1970, subsidence was locally greatest where the lava plain is thinnest, adjacent to the flanks of the eastern tephra cone. From 1982 onward, the region closest to the hydrothermal zone, which is best developed in the vicinity of the eastern vent, began showing less subsidence relative to the rest of the surveyed bench marks. The general subsidence of the island probably results from compaction of the volcanic material comprising Surtsey, compaction of the sea-floor sediments underlying the island, and possibly downwarping of the lithosphere due to the laod of Surtsey. The more localized early downwarping near the eastern tephra cone is apparently due to greater compaction of tephra relative to lava. The later diminished local subsidence near the hydrothermal zone is probably due to a minor volume increase caused by hydrous alteration of glassy tephra. However, this volume increase is concentrated at depth beneath the bottom of the 176-m-deep cased drillhole. ?? 1992 Springer-Verlag.

Effects of pediatric first aid training on preschool teachers: a longitudinal cohort study in China.

PubMed

Li, Feng; Sheng, Xiaoyang; Zhang, Jinsong; Jiang, Fan; Shen, Xiaoming

2014-08-24

Unintentional injuries are a major cause of death among children. Data suggest that the retention of knowledge and skills about first aid declined over time. The purpose of this study was to assess the effects of pediatric first aid training among teachers. A stratified random sampling method was used to select 1,067 teachers. The selected trainees received pediatric first aid training. Follow-up assessments were conducted 6 months, 9 months and 4 years following the training. A standardized collection of demographics was performed, and participants were given a questionnaire to indicate knowledge of and emotions about first aid. In the pretest, 1067 people responded with a mean of 21.0 correct answers to 37 questions, whereas in the post-test period, the mean score increased to 32.2 correct answers of 37 questions (P <0.001). There was a decrease in scores from post-test to 6 months, 9 months and 4 years after the training. However, the mean at the 6-month, 9-month and 4-year marks were higher than the pretest mean (P < 0.001). A total of 82.8% of the participants achieved a pass mark of 80% or above; 42.8% of participants achieved the pass mark at 6 months, 41.7% at 9 months and 11.7% at 4 years (compared with pre-test, P < 0.001). The mean score of the subjects' emotions in the post-test period increased to 81 (P < 0.001). The mean scores of emotions at 9 months or 4 years were higher than the pretest mean (P < 0.001). At the 4-year mark, the majority of preschool staff (>70%) had administered correct first aid for injuries. This study demonstrated that the acquisition of knowledge, both short and long term, significantly improves. Despite appreciable decreases in knowledge long term, knowledge retention was modest but stable.

Epidemic 2014 enterovirus D68 cross-reacts with human rhinovirus on a respiratory molecular diagnostic platform.

PubMed

McAllister, Shane C; Schleiss, Mark R; Arbefeville, Sophie; Steiner, Marie E; Hanson, Ryan S; Pollock, Catherine; Ferrieri, Patricia

2015-01-01

Enterovirus D68 (EV-D68) is an emerging virus known to cause sporadic disease and occasional epidemics of severe lower respiratory tract infection. However, the true prevalence of infection with EV-D68 is unknown, due in part to the lack of a rapid and specific nucleic acid amplification test as well as the infrequency with which respiratory samples are analyzed by enterovirus surveillance programs. During the 2014 EV-D68 epidemic in the United States, we noted an increased frequency of "low-positive" results for human rhinovirus (HRV) detected in respiratory tract samples using the GenMark Diagnostics eSensor respiratory viral panel, a multiplex PCR assay able to detect 14 known respiratory viruses but not enteroviruses. We simultaneously noted markedly increased admissions to our Pediatric Intensive Care Unit for severe lower respiratory tract infections in patients both with and without a history of reactive airway disease. Accordingly, we hypothesized that these "low-positive" RVP results were due to EV-D68 rather than rhinovirus infection. Sequencing of the picornavirus 5' untranslated region (5'-UTR) of 49 samples positive for HRV by the GenMark RVP revealed that 33 (67.3%) were in fact EV-D68. Notably, the mean intensity of the HRV RVP result was significantly lower in the sequence-identified EV-D68 samples (20.3 nA) compared to HRV (129.7 nA). Using a cut-off of 40 nA for the differentiation of EV-D68 from HRV resulted in 94% sensitivity and 88% specificity. The robust diagnostic characteristics of our data suggest that the cross-reactivity of EV-D68 and HRV on the GenMark Diagnostics eSensor RVP platform may be an important factor to consider in making accurate molecular diagnosis of EV-D68 at institutions utilizing this system or other molecular respiratory platforms that may also cross-react.

Enhancement of cytogenetic damage and of antineoplastic effect by caffeine in Ehrlich ascites tumor cells treated with cyclophosphamide in vivo.

PubMed

Mourelatos, D; Dozi-Vassiliades, J; Kotsis, A; Gourtsas, C

1988-03-01

Enhanced cytogenetic damage by cyclophosphamide (CP) was observed when Ehrlich ascites tumor cells were exposed in vivo to nontoxic concentrations of caffeine. One h before i.p. injection of 5-bromodeoxyuridine adsorbed to activated charcoal Ehrlich ascites tumor-bearing mice treated i.p. with CP appear to have a dose-dependent increase in sister chromatid exchange rates and cell division delays. Caffeine increased the survival time of the Ehrlich ascites tumor-bearing mice treated with CP and markedly reduced the ascitic volume. Therefore, the in vivo antitumor effect by CP in conjunction with caffeine appears to correlate well with the in vivo synergistic effect on cytogenetic damage caused by the combined CP plus caffeine treatment.

Inability to produce a model of dialysis encephalopathy in the rat by aluminum administration.

PubMed

Perry, T L; Yong, V W; Godolphin, W J; Sutter, M; Hansen, S; Kish, S J; Foulks, J G; Ito, M

1987-04-01

We attempted to produce a rat model of brain aluminum toxicity in order to explore whether or not aluminum accumulation produces the neurochemical changes observed in brains of patients who die with dialysis encephalopathy. Daily subcutaneous injection of Al(OH)3 caused marked elevation of serum aluminum concentrations, but did not increase brain aluminum contents, either in rats with normal renal function, or in rats with unilateral or 5/6 nephrectomies. LiCl pretreatment, which has been reported to cause irreversible renal failure, did not impair renal function nor aid in achieving elevated brain aluminum contents. No reductions in brain contents of gamma-aminobutyric acid (GABA) or in glutamic acid decarboxylase (GAD, E.C.4.1.1.15) and choline acetyltransferase (ChAT, E.C.2.3.1.6) activities were observed in aluminum-treated rats. We conclude that the rat is not a suitable laboratory animal to explore the role of aluminum toxicity in causing the GABA and ChAT deficits present in brains of hemodialyzed human patients.

Tumour-associated osteomalacia and hypoglycaemia in a patient with prostate cancer: is Klotho involved?

PubMed

Latifyan, Sofiya Bedo; Vanhaeverbeek, Michel; Klastersky, Jean

2014-11-17

Tumour-associated osteomalacia is a paraneoplastic syndrome caused by renal phosphate wasting, leading to severe hypophosphataemia. Excess of circulating fibroblast growth factor 23 (FGF23) is the likely cause, acting via the FGF23/α-Klotho coreceptor, a critical regulator of phosphate metabolism. The other possible effects of that complex in humans are still under investigation. We present a case of an 84-year-old Belgian man, presenting prostate cancer with bone metastases. From June 2010 to March 2013, he presented three episodes of disease progression. From January 2012, the patient developed a progressively marked dorsal kyphosis with significant hypophosphataemia. The calculated TRP (tubular reabsorption of phosphate) was decreased and the FGF23 increased. Mid-March 2013, the patient died after a profound unconsciousness due to hypoglycaemia with hypothermia. We hypothesised that the two paraneoplastic manifestations of this patient (tumour-associated osteomalacia and refractory hypoglycaemia) were due to one cause chain with two main nodes-FGF23 and its coreceptor Klotho.. 2014 BMJ Publishing Group Ltd.

Stroke in Latin America: Burden of Disease and Opportunities for Prevention.

PubMed

Avezum, Álvaro; Costa-Filho, Francisco F; Pieri, Alexandre; Martins, Sheila O; Marin-Neto, José A

2015-12-01

The epidemiological transition in Latin America toward older urban dwelling adults has led to the rise in cardiovascular risk factors and an increase in morbidity and mortality rates related to both stroke and myocardial infarction. As a result, there is an immediate need for effective actions resulting in better detection and control of cardiovascular risk factors that will ultimately reduce cardiovascular disease burden. Data from case-control studies have identified the following risk factors associated with stroke: hypertension; smoking; abdominal obesity; diet; physical activity; diabetes; alcohol intake; psychosocial factors; cardiac causes; and dyslipidemia. In addition to its high mortality, patients who survive after a stroke present quite frequently with marked physical and functional disability. Because stroke is the leading cause of death in most Latin American countries and also because it is a clearly preventable cause of death and disability, simple, affordable, and efficient strategies must be urgently implemented in Latin America. Copyright © 2015 World Heart Federation (Geneva). Published by Elsevier B.V. All rights reserved.

The PPARβ/δ activator GW501516 prevents the down-regulation of AMPK caused by a high-fat diet in liver and amplifies the PGC-1α-Lipin 1-PPARα pathway leading to increased fatty acid oxidation.

PubMed

Barroso, Emma; Rodríguez-Calvo, Ricardo; Serrano-Marco, Lucía; Astudillo, Alma M; Balsinde, Jesús; Palomer, Xavier; Vázquez-Carrera, Manuel

2011-05-01

Metabolic syndrome-associated dyslipidemia is mainly initiated by hepatic overproduction of the plasma lipoproteins carrying triglycerides. Here we examined the effects of the peroxisome proliferator-activated receptors (PPAR)-β/δ activator GW501516 on high-fat diet (HFD)-induced hypertriglyceridemia and hepatic fatty acid oxidation. Exposure to the HFD caused hypertriglyceridemia that was accompanied by reduced hepatic mRNA levels of PPAR-γ coactivator 1 (PGC-1)-α and lipin 1, and these effects were prevented by GW501516 treatment. GW501516 treatment also increased nuclear lipin 1 protein levels, leading to amplification in the PGC-1α-PPARα signaling system, as demonstrated by the increase in PPARα levels and PPARα-DNA binding activity and the increased expression of PPARα-target genes involved in fatty acid oxidation. These effects of GW501516 were accompanied by an increase in plasma β-hydroxybutyrate levels, demonstrating enhanced hepatic fatty acid oxidation. Moreover, GW501516 increased the levels of the hepatic endogenous ligand for PPARα, 16:0/18:1-phosphatidilcholine and markedly enhanced the expression of the hepatic Vldl receptor. Interestingly, GW501516 prevented the reduction in AMP-activated protein kinase (AMPK) phosphorylation and the increase in phosphorylated levels of ERK1/2 caused by HFD. In addition, our data indicate that the activation of AMPK after GW501516 treatment in mice fed HFD might be the result of an increase in the AMP to ATP ratio in hepatocytes. These findings indicate that the hypotriglyceridemic effect of GW501516 in HFD-fed mice is accompanied by an increase in phospho-AMPK levels and the amplification of the PGC-1α-lipin 1-PPARα pathway.

Tailoring nanoscopic confines to maximize catalytic activity of hydronium ions

NASA Astrophysics Data System (ADS)

Shi, Hui; Eckstein, Sebastian; Vjunov, Aleksei; Camaioni, Donald M.; Lercher, Johannes A.

2017-05-01

Acid catalysis by hydronium ions is ubiquitous in aqueous-phase organic reactions. Here we show that hydronium ion catalysis, exemplified by intramolecular dehydration of cyclohexanol, is markedly influenced by steric constraints, yielding turnover rates that increase by up to two orders of magnitude in tight confines relative to an aqueous solution of a Brønsted acid. The higher activities in zeolites BEA and FAU than in water are caused by more positive activation entropies that more than offset higher activation enthalpies. The higher activity in zeolite MFI with pores smaller than BEA and FAU is caused by a lower activation enthalpy in the tighter confines that more than offsets a less positive activation entropy. Molecularly sized pores significantly enhance the association between hydronium ions and alcohols in a steric environment resembling the constraints in pockets of enzymes stabilizing active sites.

Enterococcal Endocarditis: Can We Win the War?

PubMed Central

Munita, Jose M.

2015-01-01

Treatment of enterococcal infections has long been recognized as an important clinical challenge, particularly in the setting of infective endocarditis (IE). Furthermore, the increase prevalence of isolates exhibiting multidrug resistance (MDR) to traditional anti-enterococcal antibiotics such as ampicillin, vancomycin and aminoglycosides (high-level resistance) poses immense therapeutic dilemmas in hospitals around the world. Unlike IE caused by most isolates of Enterococcus faecalis, which still retain susceptibility to ampicillin and vancomycin, the emergence and dissemination of a hospital-associated genetic clade of multidrug resistant Enterococcus faecium, markedly limits the therapeutic options. The best treatment of IE MDR enterococcal endocarditis is unknown and the paucity of antibiotics with bactericidal activity against these organisms is a cause of serious concern. Although it appears that we are winning the war against E. faecalis, the battle rages on against isolates of multidrug-resistant E. faecium. PMID:22661339

Common Risk Factors for Urinary House Soiling (Periuria) in Cats and Its Differentiation: The Sensitivity and Specificity of Common Diagnostic Signs

PubMed Central

Barcelos, Ana Maria; McPeake, Kevin; Affenzeller, Nadja; Mills, Daniel Simon

2018-01-01

Urinary house soiling (periuria) in the home is a common but serious behaviour problem in cats. Although many specific risk factors and triggers have been postulated, their importance is largely unknown. This study assessed: (1) the significance of purported risk factors for periuria as well as specifically marking and latrine behaviour in the home; (2) the specificity and sensitivity of signs commonly used to differentiate latrine and marking behaviour. Owner responses to an internet survey (n = 245) were classified into three groups: control, marking and latrine behaviour, along with 41 potential risk factors and 15 predictors used to diagnose marking and latrine problems. Univariate statistical analyses and non-parametric tests of association were used to determine simple associations. In addition the sensitivity and specificity of four cardinal signs (posture to urinate, attempt to cover soiled area, surface chosen and volume of urine deposited) were calculated. Significant potential risk factors were: age (marking cats were older than the other two groups); multi-cat household (increased risk of marking and latrine behaviours); free outside access and cat flaps in the house (higher frequency of marking); outside access in general (lower prevalence of latrine behaviour); defecation outside the litter box (higher frequency of latrine behaviour); a heavy dependence by the cat on its owner (lower frequency of latrine behaviour) and a relaxed personality (lower risk of marking behaviour). Litterbox attributes and disease related factors were not significant. Individual cardinal signs were generally not good predictors of diagnosis. This study challenges the poor quality of evidence that has underpinned some of the hypotheses concerning the causes of periuria in cats. The results, in particular, highlight the general importance of the social environment, with the presence of other cats in the household, the cat-owner bond and personality related factors, alongside factors like the use of a cat flap which might also alter the social environment, all implicated as significant risk factors. While the physical environment may be important in specific cases, it seems this is less important as a general risk factor. The findings quantify the risk of misdiagnosis if a single sign is considered sufficient for diagnosis. PMID:29892606

[Accidents by external causes in adolescents: care in sentinel urgency and emergency services in the Brazilian State Capitals--2009].

PubMed

Malta, Deborah Carvalho; Mascarenhas, Márcio Dênis Medeiros; Bernal, Regina Tomie Ivata; Andrade, Silvania Suely Caribé de Araújo; das Neves, Alice Cristina Medeiros; de Melo, Elza Machado; da Silva Junior, Jarbas Barbosa

2012-09-01

Adolescents are seeking new references and experiences, which may involve attitudes of risk and exposure to accidents and violence from external causes. These events constitute a serious Public Health problem. The scope of this study was to analyze the occurrence of accidents by external causes in adolescents from 10 to 19 years of age attended at sentinel urgency and emergency services in Brazil. Data from the 2009 Surveillance System for Violence and Accidents (VIVA 2009) was analyzed in 74 emergency units in 23 state capitals and the Federal District. The findings revealed that 6,434 adolescents (89.8%) were victims of accidents and 730 (10.2 %) were victims of violence. The main causes of the accidents were falls and traffic accidents, and assaults were predominant in violence. For both accidents and violence, non-white male adolescents were predominant and the events occurred most frequently on the public highways. A marked increase was detected, with hospitalization of victims of violence between 15 and 19 years of age. Understanding the epidemiological reality of external causes among adolescents represents an important tool for health prevention and promotion policies and the culture of peace seeking to reduce morbidity and mortality.

The mitochondrial transporter ABC-me (ABCB10), a downstream target of GATA-1, is essential for erythropoiesis in vivo.

PubMed

Hyde, B B; Liesa, M; Elorza, A A; Qiu, W; Haigh, S E; Richey, L; Mikkola, H K; Schlaeger, T M; Shirihai, O S

2012-07-01

The mitochondrial transporter ATP binding cassette mitochondrial erythroid (ABC-me/ABCB10) is highly induced during erythroid differentiation by GATA-1 and its overexpression increases hemoglobin production rates in vitro. However, the role of ABC-me in erythropoiesis in vivo is unknown. Here we report for the first time that erythrocyte development in mice requires ABC-me. ABC-me-/- mice die at day 12.5 of gestation, showing nearly complete eradication of primitive erythropoiesis and lack of hemoglobinized cells at day 10.5. ABC-me-/- erythroid cells fail to differentiate because they exhibit a marked increase in apoptosis, both in vivo and ex vivo. Erythroid precursors are particularly sensitive to oxidative stress and ABC-me in the heart and its yeast ortholog multidrug resistance-like 1 have been shown to protect against oxidative stress. Thus, we hypothesized that increased apoptosis in ABC-me-/- erythroid precursors was caused by oxidative stress. Within this context, ABC-me deletion causes an increase in mitochondrial superoxide production and protein carbonylation in erythroid precursors. Furthermore, treatment of ABC-me-/- erythroid progenitors with the mitochondrial antioxidant MnTBAP (superoxide dismutase 2 mimetic) supports survival, ex vivo differentiation and increased hemoglobin production. Altogether, our findings demonstrate that ABC-me is essential for erythropoiesis in vivo.

Gain-of-function mutations of Ptpn11 (Shp2) cause aberrant mitosis and increase susceptibility to DNA damage-induced malignancies

PubMed Central

Liu, Xia; Zheng, Hong; Li, Xiaobo; Wang, Siying; Meyerson, Howard J.; Yang, Wentian; Neel, Benjamin G.; Qu, Cheng-Kui

2016-01-01

Gain-of-function (GOF) mutations of protein tyrosine phosphatase nonreceptor type 11 Ptpn11 (Shp2), a protein tyrosine phosphatase implicated in multiple cell signaling pathways, are associated with childhood leukemias and solid tumors. The underlying mechanisms are not fully understood. Here, we report that Ptpn11 GOF mutations disturb mitosis and cytokinesis, causing chromosomal instability and greatly increased susceptibility to DNA damage-induced malignancies. We find that Shp2 is distributed to the kinetochore, centrosome, spindle midzone, and midbody, all of which are known to play critical roles in chromosome segregation and cytokinesis. Mouse embryonic fibroblasts with Ptpn11 GOF mutations show a compromised mitotic checkpoint. Centrosome amplification and aberrant mitosis with misaligned or lagging chromosomes are significantly increased in Ptpn11-mutated mouse and patient cells. Abnormal cytokinesis is also markedly increased in these cells. Further mechanistic analyses reveal that GOF mutant Shp2 hyperactivates the Polo-like kinase 1 (Plk1) kinase by enhancing c-Src kinase-mediated tyrosine phosphorylation of Plk1. This study provides novel insights into the tumorigenesis associated with Ptpn11 GOF mutations and cautions that DNA-damaging treatments in Noonan syndrome patients with germ-line Ptpn11 GOF mutations could increase the risk of therapy-induced malignancies. PMID:26755576

Aldosterone regulation of sodium and potassium transport in the cortical collecting duct.

PubMed

O'Neil, R G

1990-07-01

The aldosterone-induced up-regulation of Na absorption and K secretion in the CCD is complex and involves the regulation of numerous transport proteins. Some aspects of the response may be species dependent. For example, stimulation of Na and K transport in the rabbit CCD involves a marked up-regulation in the apical cell membrane Na and K conductances, the basolateral cell membrane K conductance, and the basolateral membrane NaK-ATPase activity. In the rat CCD, aldosterone causes a similar up-regulation in the NaK-ATPase and the apical membrane Na conductance, but supposedly has little influence on the apical and basolateral membrane K conductances as evaluated by indirect methods. Furthermore, the marked hyperpolarization of the basolateral membrane with long-term aldosterone treatment in the rabbit CCD is blunted or absent in the rat CCD. Other differences between the CCD of these two species have been outlined. Nonetheless, the basic responses of the CCDs from the two species show similar trends. The actions of aldosterone in the CCD principal cell are summarized in Figure 5. The initial steps have been described previously. Aldosterone (A) diffuse across the cell membrane and binds to a cytoplasmic receptor (R). The receptor complex moves into the nucleus and binds to an acceptor site on chromatin, initiating transcription and the subsequent synthesis of a myriad of new proteins referred to as aldosterone-induced proteins (AIP). The initial observed action of aldosterone is an upregulation of the apical membrane Na conductance during the early phase, which occurs within 1 to 2 hours. The increase in Na conductance likely reflects activation of preexisting latent Na channels and not synthesis of new channels, although activation does require protein synthesis. The increased Na influx during the early phase presents a larger Na load to the Na pump, which is likely reflected as a modest transient increase in intracellular Na activity. Based on kinetic considerations alone, this should cause an increased transport turnover of the pump with a greater Na extrusion rate and K uptake rate. The stimulated Na influx also causes a modest depolarization of the apical membrane during the early phase, which when combined with the increased K uptake via the pump and an apparent modest elevation in the intracellular K activity, results in a more favorable gradient for K secretion (increased driving force) into the tubule lumen.(ABSTRACT TRUNCATED AT 400 WORDS)

Further evidence of the effects of global warming on lichens, particularly those with Trentepohlia phycobionts.

PubMed

Aptroot, A; van Herk, C M

2007-03-01

Increasing evidence suggests that lichens are responding to climate change in Western Europe. More epiphytic species appear to be increasing, rather than declining, as a result of global warming. Many terricolous species, in contrast, are declining. Changes to epiphytic floras are markedly more rapid in formerly heavily polluted, generally built-up or open rural areas, as compared to forested regions. Both the distribution (southern) and ecology (warmth-loving) of the newly established or increasing species seem to be determined by global warming. Epiphytic temperate to boreo-montane species appear to be relatively unaffected. Vacant niches caused by other environmental changes are showing the most pronounced effects of global warming. Species most rapidly increasing in forests, although taxonomically unrelated, all contain Trentepohlia as phycobiont in addition to having a southern distribution. This suggests that in this habitat, Trentepohlia algae, rather than the different lichen symbioses, are affected by global warming.

RLIP76 Protein Knockdown Attenuates Obesity Due to a High-fat Diet*

PubMed Central

Singhal, Sharad S.; Figarola, James; Singhal, Jyotsana; Reddy, Marpadga A.; Liu, Xueli; Berz, David; Natarajan, Rama; Awasthi, Sanjay

2013-01-01

Feeding a Western high-fat diet (HFD) to C57BL/6 mice induces obesity, associated with a chronic inflammatory state, lipid transport, and metabolic derangements, and organ system effects that particularly prominent in the kidneys. Here, we report that RLIP76 homozygous knock-out (RLIP76−/−) mice are highly resistant to obesity as well as these other features of metabolic syndrome caused by HFD. The normal increase in pro-inflammatory and fibrotic markers associated with HFD induced obesity in wild-type C57B mice was broadly and nearly completely abrogated in RLIP76−/− mice. This is a particularly striking finding because chemical markers of oxidative stress including lipid hydroperoxides and alkenals were significantly higher in RLIP76−/− mice. Whereas HFD caused marked suppression of AMPK in wild-type C57B mice, RLIP76−/− mice had baseline activation of AMP-activated protein kinase, which was not further affected by HFD. The baseline renal function was reduced in RLIP76−/− mice as compared with wild-type, but was unaffected by HFD, in marked contrast to severe renal impairment and glomerulopathy in the wild-type mice given HFD. Our findings confirm a fundamental role of RLIP76 in regulating the function of obesity-promoting pro-inflammatory cytokines, and provide a novel mechanism for targeted therapy of obesity and metabolic syndrome. PMID:23821548

Loss of Canonical Smad4 Signaling Promotes KRAS Driven Malignant Transformation of Human Pancreatic Duct Epithelial Cells and Metastasis

PubMed Central

Leung, Lisa; Radulovich, Nikolina; Zhu, Chang-Qi; Wang, Dennis; To, Christine; Ibrahimov, Emin; Tsao, Ming-Sound

2013-01-01

Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of cancer death in North America. Activating KRAS mutations and Smad4 loss occur in approximately 90% and 55% of PDAC, respectively. While their roles in the early stages of PDAC development have been confirmed in genetically modified mouse models, their roles in the multistep malignant transformation of human pancreatic duct cells have not been directly demonstrated. Here, we report that Smad4 represents a barrier in KRAS-mediated malignant transformation of the near normal immortalized human pancreatic duct epithelial (HPDE) cell line model. Marked Smad4 downregulation by shRNA in KRAS G12V expressing HPDE cells failed to cause tumorigenic transformation. However, KRAS-mediated malignant transformation occurred in a new HPDE-TGF-β resistant (TβR) cell line that completely lacks Smad4 protein expression and is resistant to the mito-inhibitory activity of TGF-β. This transformation resulted in tumor formation and development of metastatic phenotype when the cells were implanted orthotopically into the mouse pancreas. Smad4 restoration re-established TGF-β sensitivity, markedly increased tumor latency by promoting apoptosis, and decreased metastatic potential. These results directly establish the critical combination of the KRAS oncogene and complete Smad4 inactivation in the multi-stage malignant transformation and metastatic progression of normal human HPDE cells. PMID:24386371

Hypoglycemia, hepatic dysfunction, muscle weakness, cardiomyopathy, free carnitine deficiency and long-chain acylcarnitine excess responsive to medium chain triglyceride diet.

PubMed

Glasgow, A M; Engel, A G; Bier, D M; Perry, L W; Dickie, M; Todaro, J; Brown, B I; Utter, M F

1983-05-01

Fraternal twins who had fasting hypoglycemia, hypoketonemia, muscle weakness, and hepatic dysfunction are reported. The hepatic dysfunction occurred only during periods of caloric deprivation. The surviving patient developed a cardiomyopathy. In this sibling, muscle weakness and cardiomyopathy were markedly improved by a diet high in medium chain triglycerides. There was a marked deficiency of muscle total carnitine and a mild deficiency of hepatic total carnitine. Unlike patients with systemic carnitine deficiency, serum and muscle long-chain acylcarnitine were elevated and renal reabsorption of carnitine was normal. It was postulated that the defect in long-chain fatty acid oxidation in this disorder is caused by an abnormality in the mitochondrial acylcarnitine transport. Detailed studies of the cause of the hypoglycemia revealed that insulin, growth hormone, cortisol, and glucagon secretion were appropriate and that it is unlikely that there was a major deficiency of a glycolytic or gluconeogenic enzyme. Glucose production and alanine conversion to glucose were in the low normal range when compared to normal children in the postabsorptive state. The hypoglycemia in our patients was probably due to a modest increase in glucose consumption, secondary to the decreased oxidation of fatty acids and ketones, alternate fuels which spare glucose utilization, plus a modest decrease in hepatic glucose production secondary to decreased available hepatic energy substrates.

Effect of Inflammatory and Noninflammatory Stress on Beta-Hydroxybutyrate and Free Fatty Acids in Rat Blood.

DTIC Science & Technology

fasting plus screen-restraint and fasting plus femoral fracture. Inflammatory stresses caused a marked inhibition of the normal fasting-induced ketosis ...and a reduction in the level of circulating free fatty acids. Noninflammatory stresses caused no inhibition of the normal fasting-induced ketosis but did cause a reduction in the level of circulating free fatty acids. (Author)

Effect of reclaimed water effluent on bacterial community structure in the Typha angustifolia L. rhizosphere soil of urbanized riverside wetland, China.

PubMed

Huang, Xingru; Xiong, Wei; Liu, Wei; Guo, Xiaoyu

2017-05-01

In order to evaluate the impact of reclaimed water on the ecology of bacterial communities in the Typha angustifolia L. rhizosphere soil, bacterial community structure was investigated using a combination of terminal restriction fragment length polymorphism and 16S rRNA gene clone library. The results revealed significant spatial variation of bacterial communities along the river from upstream and downstream. For example, a higher relative abundance of γ-Proteobacteria, Firmicutes, Chloroflexi and a lower proportion of β-Proteobacteria and ε-Proteobacteria was detected at the downstream site compared to the upstream site. Additionally, with an increase of the reclaimed water interference intensity, the rhizosphere bacterial community showed a decrease in taxon richness, evenness and diversity. The relative abundance of bacteria closely related to the resistant of heavy-metal was markedly increased, while the bacteria related for carbon/nitrogen/phosphorus/sulfur cycling wasn't strikingly changed. Besides that, the pathogenic bacteria markedly increased in the downstream rhizosphere soil since reclaimed water supplement, while the possible plant growth-promoting rhizobacteria obviously reduced in the downstream sediment. Together these data suggest cause and effect between reclaimed water input into the wetland, shift in bacterial communities through habitat change, and alteration of capacity for biogeochemical cycling of contaminants. Copyright © 2016. Published by Elsevier B.V.

Metabolomic profiling of brain tissues of mice chronically exposed to heroin.

PubMed

Li, Ren-Shi; Takeda, Tomoki; Ohshima, Takashi; Yamada, Hideyuki; Ishii, Yuji

2017-02-01

The chronic neurotoxicity of heroin on the nervous system is poorly understood. To address this issue, we comprehensively assessed the alteration of brain metabolomics caused by chronic heroin exposure and the withdrawal of heroin. Male C57BL/6J mice (n = 10) were given heroin (15 μmol/kg, i.p., twice a day) for 12 days while the withdrawal group received saline-treatment instead of heroin for the last two days. The control group received saline. We developed an UPLC-TOF/MS-based metabolomic approach to analyze the metabolites and carry out a metabolic pathway analysis in the brain. The major metabolites contributing to the discrimination were identified as amino acids, tricarboxylic-acid cycle intermediates, neurotransmitters, nucleotides and other compounds. A marked reduction in histidine and a slight but significant increase in phenylalanine and tryptophan were observed after heroin was withdrawn while the increased level of catecholamines was restored to baseline. Interestingly, N-acetylserotonin - a precursor of melatonin - was increased with the withdrawal of heroin while melatonin was markedly reduced along with the sub-chronic exposure to heroin. This shows that heroin disrupts not only the energy metabolism but also the biosynthesis of both catecholamines and melatonin in the mouse brain. Therefore, these substances are candidate biomarkers for chronic heroin-abuse. Copyright © 2016 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

The zinc ionophore clioquinol reverses autophagy arrest in chloroquine-treated ARPE-19 cells and in APP/mutant presenilin-1-transfected Chinese hamster ovary cells.

PubMed

Seo, Bo-Ra; Lee, Sook-Jeong; Cho, Kyung Sook; Yoon, Young Hee; Koh, Jae-Young

2015-12-01

Arrested autophagy may contribute to the pathogenesis of Alzheimer's disease. Because we found that chloroquine (CQ) causes arrested autophagy but clioquinol (ClioQ), a zinc ionophore, activates autophagic flux, in the present study, we examined whether ClioQ can overcome arrested autophagy induced by CQ or mutant presenilin-1 (mPS1). CQ induced vacuole formation and cell death in adult retinal pigment epithelial (ARPE-19) cells, but co-treatment with ClioQ attenuated CQ-associated toxicity in a zinc-dependent manner. Increases in lysosome dilation and blockage of autophagic flux by CQ were also markedly attenuated by ClioQ treatment. Interestingly, CQ increased lysosomal pH in amyloid precursor protein (APP)/mPS1-expressing Chinese hamster ovary 7WΔE9 (CHO-7WΔE9) cell line, and ClioQ partially re-acidified lysosomes. Furthermore, accumulation of amyloid-β (Aβ) oligomers in CHO-7WΔE9 cells was markedly attenuated by ClioQ. Moreover, intracellular accumulation of exogenously applied fluorescein isothiocyanate-conjugated Aβ(1-42) was also increased by CQ but was returned to control levels by ClioQ. These results suggest that modulation of lysosomal functions by manipulating lysosomal zinc levels may be a useful strategy for clearing intracellular Aβ oligomers. Copyright © 2015 Elsevier Inc. All rights reserved.

Partial lesion of the serotonergic system by a single dose of MDMA results in behavioural disinhibition and enhances acute MDMA-induced social behaviour on the social interaction test.

PubMed

Ando, Romeo D; Benko, Anita; Ferrington, Linda; Kirilly, Eszter; Kelly, Paul A T; Bagdy, Gyorgy

2006-06-01

The acute effects of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) on anxiety-related behaviours were studied using indices of social interaction in Dark Agouti (DA) both drug naive rats and those pretreated with MDMA (15 mg/kg i.p.) 3 weeks earlier. The functional neuroanatomy of these MDMA effects was visualised using 2-deoxyglucose imaging of local cerebral glucose use (LCMRglu), whilst MDMA-induced serotonergic neurotoxicity was measured by radioligand binding with [3H]paroxetine. Acute MDMA alone markedly decreased most typical elements of social interaction but increased adjacent lying, a behaviour that also contains social elements. In animals pre-exposed to MDMA, decreased [3H]paroxetine binding indicated serotonergic terminal depletion, and in these animals significant increases in locomotor activity, exploratory behaviour and aggressive behaviour were found. Both behavioural effects and also the metabolic activation induced by acute MDMA were potentiated in rats previously exposed to the drug. In conclusion, a single dose of MDMA caused marked changes in social behaviour acutely that might be interpreted either as a decrease or increase in anxiety. Three weeks after MDMA a behavioural disinhibition similar to psychomotor agitation, a symptom connected to depression or mania, and a sensitization to the acute effects of MDMA are apparent in both the behavioural and brain metabolic effects of the drug.

[The impaired glucose tolerance in the pathogenesis of dyslipidemia].

PubMed

Ikoue, I; Takahashi, K; Katayama, S

1996-10-01

It is well known that hyperlipidemia is often present in patient with impaired glucose tolerance, obesity and/or hypertension. All of these are risk factors for coronary artery disease (CAD). The coexistence of these risk factors markedly increase the likelihood of CAD. Recently, it has been reported that the impaired glucose tolerance and insulin resistence are associated with the increased proinsulin, which is linked to the risk of CAD. We review that the impaired glucose tolerance is an important factor causing dyslipidemia. The characteristic of dyslipidemia associated with the impaired glucose tolerance include hypertriglyceridemia, high level of VLDL and low level of HDL cholesterol. They also associate with accumulation of remnant lipoproteins and appearance of small dense LDL. In addition, we pointed out that the increased number of risk factors is associated with elevated insulin and proinsulin level.

Avian community response to small-scale habitat disturbance in Maine

USGS Publications Warehouse

Derleth, E.L.; McAuley, D.G.; Dwyer, T.J.

1989-01-01

The effects of small clearcuts (1 - 8 ha) on avian communities in the forest of eastern Maine were studied using point counts during spring 1978 - 1981. Surveys were conducted in uncut (control) and clear-cut (treatment) plots in three stand types: conifer, hardwood, and mixed growth. We used a mark-recapture model and its associated jackknife species richness estimator (N), as an indicator of avian community structure. Increases in estimated richness (N) and Shannon - Weaver diversity (H') were noted in the treated hardwood and mixed growth, but not in the conifer stands. Seventeen avian species increased in relative abundance, whereas two species declined. Stand treatment was associated with important changes in bird species composition. Increased habitat patchiness and the creation of forest edge are hypothesized as causes for the greater estimates of richness and diversity.

Effect of bombesin on serum immunoreactive trypsin in healthy subjects and in patients with chronic pancreatitis.

PubMed

Labò, G; Vezzadini, P; Gullo, L; Sternini, C; Bonora, G

1983-08-01

We studied the effect of bombesin (9 ng/kg X min for 30 min by intravenous infusion) on serum immunoreactive trypsin in healthy subjects and in chronic pancreatitis patients. Bombesin administration caused a marked and significant increase of serum immunoreactive trypsin concentration in healthy subjects. The increase occurred in the first 15 min after the beginning of bombesin infusion and persisted for the duration of the study (2 h). In patients with chronic pancreatitis, the increase was much less pronounced. In these patients, the integrated immunoreactive trypsin response to bombesin was significantly correlated with bicarbonate, lipase, and chymotrypsin outputs into the duodenum. The response of serum immunoreactive trypsin to bombesin stimulation seems to vary according to the degree of pancreatic exocrine dysfunction and to reflect the functional capacity of acinar cell mass.

Rhabdomyolysis and Artifactual Increase in Plasma Bicarbonate Concentration in an Amazon Parrot (Amazona species).

PubMed

Leissinger, Mary K; Johnson, James G; Tully, Thomas N; Gaunt, Stephen D

2017-09-01

A 7-year-old male Amazon parrot housed outdoors presented with acute collapse, marked lethargy, and open-mouth breathing. The patient had stiffness of the pectoral muscles, and petechiation and ecchymosis noted around the eyes and beneath the mandible. Laboratory data revealed markedly increased aspartate aminotransferase, creatine kinase, and lactate dehydrogenase activity consistent with rhabdomyolysis, as well as markedly increased plasma bicarbonate concentration. Marked clinical improvement and resolution of laboratory abnormalities occurred with fluid therapy, administration of a nonsteroidal anti-inflammatory medication, and husbandry modifications, including indoor housing and dietary alteration. A spurious increase in bicarbonate measurement as documented in equine and bovine cases of rhabdomyolysis also occurred in this avian patient and must be considered for accurate interpretation of acid-base status in exotic species presenting with consistent clinical signs.

Tree-Ring Dating of Extreme Lake Levels at the Subarctic?Boreal Interface

NASA Astrophysics Data System (ADS)

Bégin, Yves

2001-03-01

The dates of extreme water levels of two large lakes in northern Quebec have been recorded over the last century by ice scars on shoreline trees and sequences of reaction wood in shore trees tilted by wave erosion. Ice-scar chronologies indicate high water levels in spring, whereas tree-tilting by waves is caused by summer high waters. A major increase in both the amplitude and frequency of ice floods occurred in the 1930s. No such change was indicated by the tree-tilting chronologies, but wave erosion occurred in exceptionally rainy years. According to the modern record, spring lake-level rise is due to increased snowfalls since the 1930s. However, the absence of erosional marks in a large number of years since 1930 suggests a high frequency of low-water-level years resulting from dry conditions. Intercalary years with very large numbers of marked trees (e.g., 1935) indicate that the interannual range of summer lake levels has increased since the 1930s. Increased lake-flood frequency is postulated to be related to a slower expansion of arctic anticyclones, favoring the passage of cyclonic air masses over the area and resulting in abundant snowfall in early winter. Conditions in summer are due to the rate of weakening of the anticyclones controlling the position of the arctic front in summer. This position influences the path of the cyclonic air masses, which control summer precipitation and, consequently, summer lake levels in the area.

Dioxin-induced up-regulation of the active form of vitamin D is the main cause for its inhibitory action on osteoblast activities, leading to developmental bone toxicity

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

Nishimura, Noriko; Nishimura, Hisao; Ito, Tomohiro

2009-05-01

Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) is known to cause bone toxicity, particularly during animal development, although its action mechanism to cause this toxicity has yet to be elucidated. Mouse pups were exposed to TCDD via dam's milk that were administered orally with 15 {mu}g TCDD/kg b.w. on postnatal day 1. Here we report that TCDD causes up-regulation of vitamin D 1{alpha}-hydroxylase in kidney, resulting in a 2-fold increase in the active form of vitamin D, 1,25-dihydroxyvitamin D{sub 3}, in serum. This action of TCDD is not caused by changes in parathyroid hormone, a decrease in vitamin D degrading enzyme, vitamin D 24-hydroxylase,more » or alterations in serum Ca{sup 2+} concentration. Vitamin D is known to affect bone mineralization. Our data clearly show that TCDD-exposed mice exhibit a marked decrease in osteocalcin and collagen type 1 as well as alkaline phosphatase gene expression in tibia by postnatal day 21, which is accompanied with a mineralization defect in the tibia, lowered activity of osteoblastic bone formation, and an increase in fibroblastic growth factor-23, a sign of increased vitamin D effect. Despite these significant effects of TCDD on osteoblast activities, none of the markers of osteoclast activities was found to be affected. Histomorphometry confirmed that osteoblastic activity, but not bone resorption activity, was altered by TCDD. A prominent lesion commonly observed in these TCDD-treated mice was impaired bone mineralization that is characterized by an increased volume and thickness of osteoids lining both the endosteum of the cortical bone and trabeculae. Together, these data suggest that the impaired mineralization resulting from reduction of the osteoblastic activity, which is caused by TCDD-induced up-regulation of vitamin D, is responsible for its bone developmental toxicity.« less

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

PubMed

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

2016-12-01

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

Mechanism of action of additives in chemical vapor generation of hydrogen selenide: Iodide and thiocyanate

NASA Astrophysics Data System (ADS)

Pitzalis, Emanuela; Onor, Massimo; Spiniello, Roberto; Braz, Carlos Eduardo Mendes; D'Ulivo, Alessandro

2018-07-01

The chemical vapor generation of H2Se has been investigated in the presence and in the absence of either NaI or NaSCN as additives (0.5 mol L-1), in HClO4 media (0.1-5.0 mol L-1) and using a low concentration of NaBH4 (0.02 mol L-1). The enhancement of generation efficiency of H2Se produced by iodide and thiocyanate was measured by a continuous flow reaction system coupled with a miniature argon‑hydrogen diffusion flame and atomic absorption detection. The chemifold of the continuous flow reactor was designed in order to change the mixing sequence and the interaction time of the reagents. By this way it has been possible to evaluate the contribution of additive‑selenium and additive-borane species to the mechanism producing the increase of generation efficiency of H2Se. Both the iodide complexes of selenium and borane contribute to enhance generation efficiency of H2Se, whereas the thiocyanate complexes of selenium rather than thiocyanate-borane complexes play a major role in the enhancement of the efficiency. At elevated acidities (2 < [H+] < 5 mol L-1), only thiocyanate continues to maintain its properties to increase H2Se generation efficiency while iodide causes a marked signal depression unless its addition is performed after the starting of SeIV- [BH4-] reaction with an appropriate time delay. Both iodide and thiocyanate caused marked depression of H2Se generation when NaBH4 was replaced by the amine boranes, NH3-BH3 and tert-ButylNH2-BH3.

The crucial protective role of glutathione against tienilic acid hepatotoxicity in rats

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

Nishiya, Takayoshi; Mori, Kazuhiko; Hattori, Chiharu

2008-10-15

To investigate the hepatotoxic potential of tienilic acid in vivo, we administered a single oral dose of tienilic acid to Sprague-Dawley rats and performed general clinicopathological examinations and hepatic gene expression analysis using Affymetrix microarrays. No change in the serum transaminases was noted at up to 1000 mg/kg, although slight elevation of the serum bile acid and bilirubin, and very mild hepatotoxic changes in morphology were observed. In contrast to the marginal clinicopathological changes, marked upregulation of the genes involved in glutathione biosynthesis [glutathione synthetase and glutamate-cysteine ligase (Gcl)], oxidative stress response [heme oxygenase-1 and NAD(P)H dehydrogenase quinone 1] andmore » phase II drug metabolism (glutathione S-transferase and UDP glycosyltransferase 1A6) were noted after 3 or 6 h post-dosing. The hepatic reduced glutathione level decreased at 3-6 h, and then increased at 24 or 48 h, indicating that the upregulation of NF-E2-related factor 2 (Nrf2)-regulated gene and the late increase in hepatic glutathione are protective responses against the oxidative and/or electrophilic stresses caused by tienilic acid. In a subsequent experiment, tienilic acid in combination with L-buthionine-(S,R)-sulfoximine (BSO), an inhibitor of Gcl caused marked elevation of serum alanine aminotransferase (ALT) with extensive centrilobular hepatocyte necrosis, whereas BSO alone showed no hepatotoxicity. The elevation of ALT by this combination was observed at the same dose levels of tienilic acid as the upregulation of the Nrf2-regulated genes by tienilic acid alone. In conclusion, these results suggest that the impairment of glutathione biosynthesis may play a critical role in the development of tienilic acid hepatotoxicity through extensive oxidative and/or electrophilic stresses.« less

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

Carbohydrate Metabolism Is Perturbed in Peroxisome-deficient Hepatocytes Due to Mitochondrial Dysfunction, AMP-activated Protein Kinase (AMPK) Activation, and Peroxisome Proliferator-activated Receptor γ Coactivator 1α (PGC-1α) Suppression*

PubMed Central

Peeters, Annelies; Fraisl, Peter; van den Berg, Sjoerd; Ver Loren van Themaat, Emiel; Van Kampen, Antoine; Rider, Mark H.; Takemori, Hiroshi; van Dijk, Ko Willems; Van Veldhoven, Paul P.; Carmeliet, Peter; Baes, Myriam

2011-01-01

Hepatic peroxisomes are essential for lipid conversions that include the formation of mature conjugated bile acids, the degradation of branched chain fatty acids, and the synthesis of docosahexaenoic acid. Through unresolved mechanisms, deletion of functional peroxisomes from mouse hepatocytes (L-Pex5−/− mice) causes severe structural and functional abnormalities at the inner mitochondrial membrane. We now demonstrate that the peroxisomal and mitochondrial anomalies trigger energy deficits, as shown by increased AMP/ATP and decreased NAD+/NADH ratios. This causes suppression of gluconeogenesis and glycogen synthesis and up-regulation of glycolysis. As a consequence, L-Pex5−/− mice combust more carbohydrates resulting in lower body weights despite increased food intake. The perturbation of carbohydrate metabolism does not require a long term adaptation to the absence of functional peroxisomes as similar metabolic changes were also rapidly induced by acute elimination of Pex5 via adenoviral administration of Cre. Despite its marked activation, peroxisome proliferator-activated receptor α (PPARα) was not causally involved in these metabolic perturbations, because all abnormalities still manifested when peroxisomes were eliminated in a peroxisome proliferator-activated receptor α null background. Instead, AMP-activated kinase activation was responsible for the down-regulation of glycogen synthesis and induction of glycolysis. Remarkably, PGC-1α was suppressed despite AMP-activated kinase activation, a paradigm not previously reported, and they jointly contributed to impaired gluconeogenesis. In conclusion, lack of functional peroxisomes from hepatocytes results in marked disturbances of carbohydrate homeostasis, which are consistent with adaptations to an energy deficit. Because this is primarily due to impaired mitochondrial ATP production, these L-Pex5-deficient livers can also be considered as a model for secondary mitochondrial hepatopathies. PMID:22002056

The cytotoxic activity of miltefosine against Leishmania and macrophages is associated with dynamic changes in plasma membrane proteins.

PubMed

Fernandes, Kelly Souza; de Souza, Paulo Eduardo Narcizo; Dorta, Miriam Leandro; Alonso, Antonio

2017-01-01

In this study, we combined electron paramagnetic resonance (EPR) spectroscopy with an analysis of biophysical cellular parameters to study the mechanisms underlying the in vitro anti-leishmanial activity of miltefosine (MT). A thiol-specific spin label attached to membrane-bound proteins of Leishmania amazonensis and peritoneal macrophages indicated that MT may bind to plasma membrane proteins in large quantities via a detergent-like action and cause structural changes associated with a marked increase in dynamics and exposure to an aqueous environment. EPR spectra of a spin-labeled stearic acid indicated strong interactions between the probe and membrane proteins and a marked increase in the membrane fluidity of MT-treated cells. The cytotoxicity of MT was found to depend on the cell concentration used in the assay. This dependence was described by an equation involving the 50% inhibitory concentrations of MT in the aqueous medium (c w50 ) and the cell membrane (c m50 ) and the membrane-aqueous medium partition coefficient of MT (K). With a c w50 of 8.7μM, macrophages were less sensitive to MT than amastigotes and promastigotes of Leishmania, which had c w50 values of 2.4-3.1μM. The estimated c m50 of MT for Leishmania was 1.8M, which appears sufficient to cause ruptures or formation of pores in the plasma membrane. Additionally, we demonstrated that the changes in the plasma membrane detected by EPR spectroscopy occurred at cytotoxic concentrations of MT, as assessed through in vitro assays. Copyright © 2016 Elsevier B.V. All rights reserved.

Roles of oxygen radicals and elastase in citric acid-induced airway constriction of guinea-pigs

PubMed Central

Lai, Y -L; Chiou, W -Y; Lu, F J; Chiang, L Y

1999-01-01

Antioxidants attenuate noncholinergic airway constriction. To further investigate the relationship between tachykinin-mediated airway constriction and oxygen radicals, we explored citric acid-induced bronchial constriction in 48 young Hartley strain guinea-pigs, divided into six groups: control; citric acid; hexa(sulphobutyl)fullerenes+citric acid; hexa(sulphobutyl)fullerenes+phosphoramidon+citric acid; dimethylthiourea (DMTU)+citric acid; and DMTU+phosphoramidon+citric acid. Hexa(sulphobutyl)fullerenes and DMTU are scavengers of oxygen radicals while phosphoramidon is an inhibitor of the major degradation enzyme for tachykinins. Animals were anaesthetized, paralyzed, and artificially ventilated. Each animal was given 50 breaths of 4 ml saline or citric acid aerosol. We measured dynamic respiratory compliance (Crs), forced expiratory volume in 0.1 (FEV0.1), and maximal expiratory flow at 30% total lung capacity (V[dot above]max30) to evaluate the degree of airway constriction. Citric acid, but not saline, aerosol inhalation caused marked decreases in Crs, FEV0.1 and V[dot above]max30, indicating marked airway constriction. This constriction was significantly attenuated by either hexa(sulphobutyl)fullerenes or by DMTU. In addition, phosphoramidon significantly reversed the attenuating action of hexa(sulphobutyl)fullerenes, but not that of DMTU. Citric acid aerosol inhalation caused increases in both lucigenin- and t-butyl hydroperoxide-initiated chemiluminescence counts, indicating citric acid-induced increase in oxygen radicals and decrease in antioxidants in bronchoalveolar lavage fluid. These alterations were significantly suppressed by either hexa(sulphobutyl)fullerenes or DMTU. An elastase inhibitor eglin-c also significantly attenuated citric acid-induced airway constriction, indicating the contributing role of elastase in this type of constriction. We conclude that both oxygen radicals and elastase play an important role in tachykinin-mediated, citric acid-induced airway constriction. PMID:10188991

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.

Biomechanical and ultrastructural comparison of cryopreservation and a novel cellular extraction of porcine aortic valve leaflets.

PubMed

Courtman, D W; Pereira, C A; Omar, S; Langdon, S E; Lee, J M; Wilson, G J

1995-12-01

Heart valve substitutes of biological origin often fail by degenerative mechanisms. Many authors have hypothesized that mechanical fatigue and structural degradation are instrumental to in vivo failure. Since the properties of the structural matrix at implantation may predetermine failure, we have examined the ultrastructure, fracture, mechanics, and uniaxial high-strain-rate viscoelastic properties of: (1) fresh, (2) cryopreserved, and (3) cellular extracted porcine aortic valve leaflets. The cellular extraction process is being developed in order to reduce immunological attack and calcification. Cryopreservation causes cellular disruption and necrotic changes throughout the tissue, whereas extraction removes all cells and lipid membranes. Both processes leave an intact collagen and elastin structural matrix and preserve the high-strain-rate viscoelastic characteristics of the fresh leaflets. Extraction does cause a 20% reduction in the fracture tension and increases tissue extensibility, with the percent strain at fracture rising to 45.3 +/- 4 (mean +/- SEM) from 31.5 +/- 3 for fresh leaflets. However, extraction does preserve matrix structure and mechanics over the physiological loading range. Glutaraldehyde fixation produces increased extensibility, increased elastic behavior, and, when applied to extracted leaflets, it causes a marked drop in fracture tension, to 50% of that for fresh leaflets. The combination of extraction and fixation may lead to early degenerative failure. The cellular extraction technique alone may be a useful alternative to glutaraldehyde fixation in preparing bioprosthetic heart valves.

Addition of an organic amendment and/or residue mud to bauxite residue sand in order to improve its properties as a growth medium.

PubMed

Jones, B E H; Haynes, R J; Phillips, I R

2012-03-01

The effects of addition of carbonated residue mud (RMC) or seawater neutralized residue mud (RMS), at two rates, in the presence or absence of added green waste compost, on the chemical, physical and microbial properties of gypsum-treated bauxite residue sand were studied in a laboratory incubation study. The growth of two species commonly used in revegetation of residue sand (Lolium rigidum and Acacia saligna) in the treatments was then studied in a 18-week greenhouse study. Addition of green waste-based compost increased ammonium acetate-extractable (exchangeable) Mg, K and Na. Addition of residue mud at 5 and 10% w/w reduced exchangeable Ca but increased that of Mg and Na (and K for RMS). Concentrations of K, Na, Mg and level of EC in saturation paste extracts were increased by residue mud additions. Concentrations of cations in water extracts were considerably higher than those in saturation paste extracts but trends with treatment were broadly similar. Addition of both compost and residue mud caused a significant decrease in macroporosity with a concomitant increase in mesoporosity and microporosity, available water holding capacity and the quantity of water held at field capacity. Increasing rates of added residue mud reduced the percentage of sample present as discrete sand particles and increased that in aggregated form (particularly in the 1-2 and >10mm diameter ranges). Organic C content, C/N ratio, soluble organic C, microbial biomass C and basal respiration were increased by compost additions. Where compost was added, residue mud additions caused a substantial increase in microbial biomass and basal respiration. L. rigidum grew satisfactorily in all treatments although yields tended to be reduced by additions of mud (especially RMC) particularly in the absence of added compost. Growth of A. saligna was poor in sand alone and mud-amended sand and was greatly promoted by additions of compost. However, in the presence of compost, addition of carbonated mud had a marked depressive effect on both top and root growth. The significant positive effect of compost was attributed to substantial inputs of K and marked reductions in the Na/K ratio in soil solution while the depressive effect of RMC was attributed to its greater alkalinity and consequently higher concentrations of HCO(3)(-) in solution. Copyright © 2011 Elsevier Ltd. All rights reserved.

The Impact on Stakeholder Confidence of Increased Transparency in the Examination Assessment Process

ERIC Educational Resources Information Center

Bamber, Matthew

2015-01-01

A group of postgraduate accounting and finance students were asked to participate in a three-phase exercise: sit an unseen past examination question; mark a fully anonymised previous student solution (exemplar); and then mark their own work. The marking process was facilitated by explaining and discussing the marking guide, assessment systems and…

Evolving epidemiology of HIV-associated malignancies.

PubMed

Shiels, Meredith S; Engels, Eric A

2017-01-01

The purpose of this review is to describe the epidemiology of cancers that occur at an elevated rate among people with HIV infection in the current treatment era, including discussion of the cause of these cancers, as well as changes in cancer incidence and burden over time. Rates of Kaposi sarcoma, non-Hodgkin lymphoma and cervical cancer have declined sharply in developed countries during the highly active antiretroviral therapy era, but remain elevated 800-fold, 10-fold and four-fold, respectively, compared with the general population. Most studies have reported significant increases in liver cancer rates and decreases in lung cancer over time. Although some studies have reported significant increases in anal cancer rates and declines in Hodgkin lymphoma rates, others have shown stable incidence. Declining mortality among HIV-infected individuals has resulted in the growth and aging of the HIV-infected population, causing an increase in the number of non-AIDS-defining cancers diagnosed each year in HIV-infected people. The epidemiology of cancer among HIV-infected people has evolved since the beginning of the HIV epidemic with particularly marked changes since the introduction of modern treatment. Public health interventions aimed at prevention and early detection of cancer among HIV-infected people are needed.

Physiological and behavioural responses of young horses to hot iron branding and microchip implantation.

PubMed

Erber, R; Wulf, M; Becker-Birck, M; Kaps, S; Aurich, J E; Möstl, E; Aurich, C

2012-02-01

Branding is the traditional and well-established method used to mark horses, but recently microchip transponders for implantation have become available. In this study, behaviour, physiological stress variables and skin temperature in foals were determined in response to hot-iron branding (n=7) and microchip implantation (n=7). Salivary cortisol concentrations increased in response to branding (1.8 ± 0.2 ng/mL) and microchip implantation (1.4 ± 0.1ng/mL), but cortisol release over time did not differ. In response to both manipulations there was a transient increase in heart rate (P<0.001) and heart rate variability (P<0.01). Branding and microchip implantation induced a comparable aversive behaviour (branding, score 3.86 ± 0.85; microchip, score 4.00 ± 0.82). Both techniques thus caused similar physiological and behavioural changes indicative of stress. Acutely, implantation of a microchip was as stressful as branding in foals. Branding caused a necrotising skin burn lasting at least 7 days. Moreover branding, but not microchip implantation (P<0.001), was accompanied by a generalized increase in skin temperature which was comparable to low degree post-burn hypermetabolism in humans. Copyright © 2011 Elsevier Ltd. All rights reserved.

Half-century evidence from western Canada shows forest dynamics are primarily driven by competition followed by climate

PubMed Central

Zhang, Jian; Huang, Shongming; He, Fangliang

2015-01-01

Tree mortality, growth, and recruitment are essential components of forest dynamics and resiliency, for which there is great concern as climate change progresses at high latitudes. Tree mortality has been observed to increase over the past decades in many regions, but the causes of this increase are not well understood, and we know even less about long-term changes in growth and recruitment rates. Using a dataset of long-term (1958–2009) observations on 1,680 permanent sample plots from undisturbed natural forests in western Canada, we found that tree demographic rates have changed markedly over the last five decades. We observed a widespread, significant increase in tree mortality, a significant decrease in tree growth, and a similar but weaker trend of decreasing recruitment. However, these changes varied widely across tree size, forest age, ecozones, and species. We found that competition was the primary factor causing the long-term changes in tree mortality, growth, and recruitment. Regional climate had a weaker yet still significant effect on tree mortality, but little effect on tree growth and recruitment. This finding suggests that internal community-level processes—more so than external climatic factors—are driving forest dynamics. PMID:25775576

Half-century evidence from western Canada shows forest dynamics are primarily driven by competition followed by climate.

PubMed

Zhang, Jian; Huang, Shongming; He, Fangliang

2015-03-31

Tree mortality, growth, and recruitment are essential components of forest dynamics and resiliency, for which there is great concern as climate change progresses at high latitudes. Tree mortality has been observed to increase over the past decades in many regions, but the causes of this increase are not well understood, and we know even less about long-term changes in growth and recruitment rates. Using a dataset of long-term (1958-2009) observations on 1,680 permanent sample plots from undisturbed natural forests in western Canada, we found that tree demographic rates have changed markedly over the last five decades. We observed a widespread, significant increase in tree mortality, a significant decrease in tree growth, and a similar but weaker trend of decreasing recruitment. However, these changes varied widely across tree size, forest age, ecozones, and species. We found that competition was the primary factor causing the long-term changes in tree mortality, growth, and recruitment. Regional climate had a weaker yet still significant effect on tree mortality, but little effect on tree growth and recruitment. This finding suggests that internal community-level processes-more so than external climatic factors-are driving forest dynamics.

Earth fissures and localized differential subsidence

USGS Publications Warehouse

Holzer, Thomas L.; Pampeyan, Earl Haig

1979-01-01

Long tension cracks caused by declines of ground-water level at four sites in Arizona, California, and Nevada occur at points of maximum, convex-upward curvature in subsidence profiles based on relevelings of closely-spaced bench marks aligned perpendicular to the cracks. We conclude the cracks are caused by horizontal strains associated with the differential subsidence.

A Y-like social chromosome causes alternative colony organization in fire ants

USDA-ARS?s Scientific Manuscript database

Intraspecific variability in social organization is common, yet the underlying causes are rarely known1-3. In the fire ant Solenopsis invicta, the existence of two divergent forms of social organisation is under the control of a single Mendelian genomic element marked by two variants of an odorant b...

Photobleaching response of different sources of chromophoric dissolved organic matter exposed to natural solar radiation using absorption and excitation-emission matrix spectra.

PubMed

Zhang, Yunlin; Liu, Xiaohan; Osburn, Christopher L; Wang, Mingzhu; Qin, Boqiang; Zhou, Yongqiang

2013-01-01

CDOM biogeochemical cycle is driven by several physical and biological processes such as river input, biogeneration and photobleaching that act as primary sinks and sources of CDOM. Watershed-derived allochthonous (WDA) and phytoplankton-derived autochthonous (PDA) CDOM were exposed to 9 days of natural solar radiation to assess the photobleaching response of different CDOM sources, using absorption and fluorescence (excitation-emission matrix) spectroscopy. Our results showed a marked decrease in total dissolved nitrogen (TDN) concentration under natural sunlight exposure for both WDA and PDA CDOM, indicating photoproduction of ammonium from TDN. In contrast, photobleaching caused a marked increase in total dissolved phosphorus (TDP) concentration for both WDA and PDA CDOM. Thus TDN:TDP ratios decreased significantly both for WDA and PDA CDOM, which partially explained the seasonal dynamic of TDN:TDP ratio in Lake Taihu. Photobleaching rate of CDOM absorption a(254), was 0.032 m/MJ for WDA CDOM and 0.051 m/MJ for PDA CDOM from days 0-9, indicating that phototransformations were initially more rapid for the newly produced CDOM from phytoplankton than for the river CDOM. Extrapolation of these values to the field indicated that 3.9%-5.1% CDOM at the water surface was photobleached and mineralized every day in summer in Lake Taihu. Photobleaching caused the increase of spectral slope, spectral slope ratio and molecular size, indicating the CDOM mean molecular weight decrease which was favorable to further microbial degradation of mineralization. Three fluorescent components were validated in parallel factor analysis models calculated separately for WDA and PDA CDOM. Our study suggests that the humic-like fluorescence materials could be rapidly and easily photobleached for WDA and PDA CDOM, but the protein-like fluorescence materials was not photobleached and even increased from the transformation of the humic-like fluorescence substance to the protein-like fluorescence substance. Photobleaching was an important driver of CDOM and nutrients biogeochemistry in lake water.

Photobleaching Response of Different Sources of Chromophoric Dissolved Organic Matter Exposed to Natural Solar Radiation Using Absorption and Excitation–Emission Matrix Spectra

PubMed Central

Zhang, Yunlin; Liu, Xiaohan; Osburn, Christopher L.; Wang, Mingzhu; Qin, Boqiang; Zhou, Yongqiang

2013-01-01

CDOM biogeochemical cycle is driven by several physical and biological processes such as river input, biogeneration and photobleaching that act as primary sinks and sources of CDOM. Watershed-derived allochthonous (WDA) and phytoplankton-derived autochthonous (PDA) CDOM were exposed to 9 days of natural solar radiation to assess the photobleaching response of different CDOM sources, using absorption and fluorescence (excitation-emission matrix) spectroscopy. Our results showed a marked decrease in total dissolved nitrogen (TDN) concentration under natural sunlight exposure for both WDA and PDA CDOM, indicating photoproduction of ammonium from TDN. In contrast, photobleaching caused a marked increase in total dissolved phosphorus (TDP) concentration for both WDA and PDA CDOM. Thus TDN∶TDP ratios decreased significantly both for WDA and PDA CDOM, which partially explained the seasonal dynamic of TDN∶TDP ratio in Lake Taihu. Photobleaching rate of CDOM absorption a(254), was 0.032 m/MJ for WDA CDOM and 0.051 m/MJ for PDA CDOM from days 0–9, indicating that phototransformations were initially more rapid for the newly produced CDOM from phytoplankton than for the river CDOM. Extrapolation of these values to the field indicated that 3.9%–5.1% CDOM at the water surface was photobleached and mineralized every day in summer in Lake Taihu. Photobleaching caused the increase of spectral slope, spectral slope ratio and molecular size, indicating the CDOM mean molecular weight decrease which was favorable to further microbial degradation of mineralization. Three fluorescent components were validated in parallel factor analysis models calculated separately for WDA and PDA CDOM. Our study suggests that the humic-like fluorescence materials could be rapidly and easily photobleached for WDA and PDA CDOM, but the protein-like fluorescence materials was not photobleached and even increased from the transformation of the humic-like fluorescence substance to the protein-like fluorescence substance. Photobleaching was an important driver of CDOM and nutrients biogeochemistry in lake water. PMID:24204852

Synthesis of Creatine in X-irradiated Rats

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

Nerurkar, M. K.; Sahasrabudhe, M. B.

1960-01-01

BS>Synthesis and excretion of creatine and creatinine in total-body x- irradiated (600 n) rats were investigated. Irradiated rats exhibited a marked creatinuria, whereas creatinine excretion was only slightly increased in comparison to that of non-irradiated control animals. The increased creatine excretion after irradiation was ascribed to accelerated synthesis in the liver and greater release from the muscle. In vitro studies on the synthesis of creatine in liver homogenates revealed that the synthetic activity decreased immediately after irradiation but at later intervals showed a marked rise. The immediate fall in the creatine synthesis was not due to decreased availability of ATPmore » or glutathione. Administration of nicotinamide to animals, to inhibit the new creatine synthesis in the liver. indicated that although the creatine formation in the liver of x-irradiated rats was elevated. it could not account for more than a small fraction of the creatinuria observed. Most of the urinary creatine originated from the muscle, probably because of the impaired reconversion of creatine to phosphocreatine. Since the muscle ATP-creatine transphosphorylase activity was not affected by irradiation, it is suggested that the mobilization of muscle creatine to cause creatinuria is probably due to the diminution of glycolysis in the muscle of irradiated animals.« less

Renalase is a novel, soluble monoamine oxidase that regulates cardiac function and blood pressure

PubMed Central

Xu, Jianchao; Li, Guoyong; Wang, Peili; Velazquez, Heino; Yao, Xiaoqiang; Li, Yanyan; Wu, Yanling; Peixoto, Aldo; Crowley, Susan; Desir, Gary V.

2005-01-01

The kidney not only regulates fluid and electrolyte balance but also functions as an endocrine organ. For instance, it is the major source of circulating erythropoietin and renin. Despite currently available therapies, there is a marked increase in cardiovascular morbidity and mortality among patients suffering from end-stage renal disease. We hypothesized that the current understanding of the endocrine function of the kidney was incomplete and that the organ might secrete additional proteins with important biological roles. Here we report the identification of a novel flavin adenine dinucleotide–dependent amine oxidase (renalase) that is secreted into the blood by the kidney and metabolizes catecholamines in vitro (renalase metabolizes dopamine most efficiently, followed by epinephrine, and then norepinephrine). In humans, renalase gene expression is highest in the kidney but is also detectable in the heart, skeletal muscle, and the small intestine. The plasma concentration of renalase is markedly reduced in patients with end-stage renal disease, as compared with healthy subjects. Renalase infusion in rats caused a decrease in cardiac contractility, heart rate, and blood pressure and prevented a compensatory increase in peripheral vascular tone. These results identify renalase as what we believe to be a novel amine oxidase that is secreted by the kidney, circulates in blood, and modulates cardiac function and systemic blood pressure. PMID:15841207

Adolescent conduct problems and premature mortality: follow-up to age 65 years in a national birth cohort.

PubMed

Maughan, B; Stafford, M; Shah, I; Kuh, D

2014-04-01

Severe youth antisocial behaviour has been associated with increased risk of premature mortality in high-risk samples for many years, and some evidence now points to similar effects in representative samples. We set out to assess the prospective association between adolescent conduct problems and premature mortality in a population-based sample of men and women followed to the age of 65 years. A total of 4158 members of the Medical Research Council National Survey of Health and Development (the British 1946 birth cohort) were assessed for conduct problems at the ages of 13 and 15 years. Follow-up to the age of 65 years via the UK National Health Service Central Register provided data on date and cause of death. Dimensional measures of teacher-rated adolescent conduct problems were associated with increased hazards of death from cardiovascular disease by the age of 65 years in men [hazard ratio (HR) 1.17, 95% confidence interval (CI) 1.04-1.32], and of all-cause and cancer mortality by the age of 65 years in women (all-cause HR 1.16, 95% CI 1.07-1.25). Adjustment for childhood cognition and family social class did little to attenuate these risks. Adolescent conduct problems were not associated with increased risks of unnatural/substance-related deaths in men or women in this representative sample. Whereas previous studies of high-risk delinquent or offender samples have highlighted increased risks of unnatural and alcohol- or substance abuse-related deaths in early adulthood, we found marked differences in mortality risk from other causes emerging later in the life course among women as well as men.

Oxygen toxicity in the perfused rat liver and lung under hyperbaric conditions.

PubMed Central

Nishiki, K; Jamieson, D; Oshino, N; Chance, B

1976-01-01

1. In the lung and liver of tocopherol-deficient rats, the activities of glutathione peroxidase and glucose 6-phosphate dehydrogenase were increased substantially, suggesting an important role for both enzymes in protecting the organ against the deleterious effects of lipid peroxides. 2. Facilitation of the glutathione peroxidase reaction by infusing t-butyl hydroperoxide caused the oxidation of nicotinamide nucleotides and glutathione, resulting in a concomitant increase in the rate of release of oxidized glutathione into the perfusate. Thus the rate of production of lipid peroxide and H2O2 in the perfused organ could be compared by simultaneous measurement of the rate of glutathione release and the turnover number of the catalase reaction. 3. On hyperbaric oxygenation at 4 X 10(5)Pa, H2O2 production, estimated from the turnover of the catalase reaction, was increased slightly in the liver, and glutathione release was increased slightly, in both lung and liver. 4. Tocopherol deficiency caused a marked increase in lipid-peroxide formation as indicated by a corresponding increase in glutathione release under hyperbaric oxygenation, with a further enhancement when the tocopherol-deficient rats were also starved. 5. The study demonstrates that the primary response to hyperbaric oxygenation is an elevation of the rate of lipid peroxidation rather than of the rate of formation of H2O2 or superoxide. PMID:12754

Group in-course assessment promotes cooperative learning and increases performance.

PubMed

Pratten, Margaret K; Merrick, Deborah; Burr, Steven A

2014-01-01

The authors describe and evaluate a method to motivate medical students to maximize the effectiveness of dissection opportunities by using In-Course-Assessments (ICAs) to encourage teamwork. A student's final mark was derived by combining the group dissection mark, group mark for questions, and their individual question mark. An analysis of the impact of the ICA was performed by comparing end of module practical summative marks in student cohorts who had, or had not, participated in the ICAs. Summative marks were compared by two-way ANOVA followed by Dunnets test, or by repeated measures ANOVA, as appropriate. A cohort of medical students was selected that had experienced both practical classes without (year one) and with the new ICA structure (year two). Comparison of summative year one and year two marks illustrated an increased improvement in year two performance in this cohort. A significant increase was also noted when comparing this cohort with five preceding year two cohorts who had not experienced the ICAs (P <0.0001). To ensure that variation in the practical summative examination was not impacting on the data, a comparison was made between three cohorts who had performed the same summative examination. Results show that students who had undertook weekly ICAs showed significantly improved summative marks, compared with those who did not (P <0.0001). This approach to ICA promotes engagement with learning resources in an active, team-based, cooperative learning environment. © 2013 American Association of Anatomists.

An Industry-Scale Mass Marking Technique for Tracing Farmed Fish Escapees

PubMed Central

Warren-Myers, Fletcher; Dempster, Tim; Fjelldal, Per Gunnar; Hansen, Tom; Swearer, Stephen E.

2015-01-01

Farmed fish escape and enter the environment with subsequent effects on wild populations. Reducing escapes requires the ability to trace individuals back to the point of escape, so that escape causes can be identified and technical standards improved. Here, we tested if stable isotope otolith fingerprint marks delivered during routine vaccination could be an accurate, feasible and cost effective marking method, suitable for industrial-scale application. We tested seven stable isotopes, 134Ba, 135Ba, 136Ba, 137Ba, 86Sr, 87Sr and 26Mg, on farmed Atlantic salmon reared in freshwater, in experimental conditions designed to reflect commercial practice. Marking was 100% successful with individual Ba isotopes at concentrations as low as 0.001 µg. g-1 fish and for Sr isotopes at 1 µg. g-1 fish. Our results suggest that 63 unique fingerprint marks can be made at low cost using Ba (0.0002 – 0.02 $US per mark) and Sr (0.46 – 0.82 $US per mark) isotopes. Stable isotope fingerprinting during vaccination is feasible for commercial application if applied at a company level within the world’s largest salmon producing nations. Introducing a mass marking scheme would enable tracing of escapees back to point of origin, which could drive greater compliance, better farm design and improved management practices to reduce escapes. PMID:25738955

Lung radiology and pulmonary function of children chronically exposed to air pollution.

PubMed

Calderón-Garcidueñas, Lilian; Mora-Tiscareño, Antonieta; Fordham, Lynn A; Chung, Charles J; Valencia-Salazar, Gildardo; Flores-Gómez, Silvia; Solt, Anna C; Gomez-del Campo, Alberto; Jardón-Torres, Ricardo; Henríquez-Roldán, Carlos; Hazucha, Milan J; Reed, William

2006-09-01

We analyzed the chest radiographs (CXRs) of 249 clinically healthy children, 230 from southwest Mexico City and 19 from Tlaxcala. In contrast to children from Tlaxcala, children from southwest Mexico City were chronically exposed to ozone levels exceeding the U.S. National Ambient Air Quality Standards for an average of 4.7 hr/day and to concentrations of particulate matter (PM) with aerodynamic diameters

Chronic active Epstein-Barr virus infection with marked pericardial effusion successfully treated with allogeneic peripheral blood stem cell transplantation.

PubMed

Matsui, Shinichiro; Takeda, Yusuke; Isshiki, Yusuke; Yamazaki, Atsuko; Nakao, Sanshiro; Takaishi, Koji; Nagao, Yuhei; Hasegawa, Nagisa; Togasaki, Emi; Shimizu, Ryoh; Kawajiri, Chika; Sakai, Shio; Mimura, Naoya; Takeuchi, Masahiro; Ohwada, Chikako; Sakaida, Emiko; Iseki, Tohru; Imadome, Ken-Ichi; Nakaseko, Chiaki

2016-05-01

A 23-year-old woman presented with a persistent fever and shortness of breath. Computed tomography showed marked pericardial effusion, hepatosplenomegaly, and cervical and mediastinal lymph node swelling. Epstein-Barr virus (EBV) antibody titers were abnormally elevated, and the copy number of EBV-DNA was increased in peripheral blood. Based on these observations, she was diagnosed with chronic active EBV infection (CAEBV). The EBV-infected cells in her peripheral blood were CD4(+)T lymphocytes. Fever and pericardial effusion improved following treatment with a combination of prednisolone, etoposide, and cyclosporine; however, peripheral blood EBV-DNA levels remained high. The patient underwent allogeneic peripheral blood stem cell transplantation from an EBV-seronegative, HLA-matched sibling donor, with fludarabine and melphalan conditioning. The post-transplantation course was uneventful, except for mild skin acute graft-versus-host disease (grade 2). EBV-DNA became undetectable in peripheral blood 98 days post transplantation. She has since been in good health without disease recurrence. CAEBV is a potentially fatal disease caused by persistent EBV infection of T lymphocytes or natural killer cells, thus requiring prompt treatment and allogeneic transplantation. Pericardial effusion is rarely observed in CAEBV and can impede its diagnosis. Therefore, we should be aware that patients may present with marked pericardial effusion as an initial manifestation of CAEBV.

Redistribution of pulmonary blood flow impacts thermodilution-based extravascular lung water measurements in a model of acute lung injury

PubMed Central

Easley, R. Blaine; Mulreany, Daniel G.; Lancaster, Christopher T.; Custer, Jason W.; Fernandez-Bustamante, Ana; Colantuoni, Elizabeth; Simon, Brett A.

2009-01-01

Background Studies using transthoracic thermodilution have demonstrated increased extravascular lung water (EVLW) measurements attributed to progression of edema and flooding during sepsis and acute lung injury. We hypothesize that redistribution of pulmonary blood flow can cause increased apparent EVLW secondary to increased perfusion of thermally silent tissue, not increased lung edema. Methods Anesthetized, mechanically ventilated canines were instrumented with PiCCO® (Pulsion Medical, Munich, Germany) catheters and underwent lung injury by repetitive saline lavage. Hemodynamic and respiratory physiologic data were recorded. After stabilized lung injury, endotoxin was administered to inactivate hypoxic pulmonary vasoconstriction. Computerized tomographic imaging was performed to quantify in vivo lung volume, total tissue (fluid) and air content, and regional distribution of blood flow. Results Lavage injury caused an increase in airway pressures and decreased arterial oxygen content with minimal hemodynamic effects. EVLW and shunt fraction increased after injury and then markedly following endotoxin administration. Computerized tomographic measurements quantified an endotoxin-induced increase in pulmonary blood flow to poorly aerated regions with no change in total lung tissue volume. Conclusions The abrupt increase in EVLW and shunt fraction after endotoxin administration is consistent with inactivation of hypoxic pulmonary vasoconstriction and increased perfusion to already flooded lung regions that were previously thermally silent. Computerized tomographic studies further demonstrate in vivo alterations in regional blood flow (but not lung water) and account for these alterations in shunt fraction and EVLW. PMID:19809280

Image-guided biopsy in the esophagus through comprehensive optical frequency domain imaging and laser marking: a study in living swine.

PubMed

Suter, Melissa J; Jillella, Priyanka A; Vakoc, Benjamin J; Halpern, Elkan F; Mino-Kenudson, Mari; Lauwers, Gregory Y; Bouma, Brett E; Nishioka, Norman S; Tearney, Guillermo J

2010-02-01

Random biopsy esophageal surveillance can be subject to sampling errors, resulting in diagnostic uncertainty. Optical frequency domain imaging (OFDI) is a high-speed, 3-dimensional endoscopic microscopy technique. When deployed through a balloon-centering catheter, OFDI can automatically image the entire distal esophagus (6.0 cm length) in approximately 2 minutes. To test a new platform for guided biopsy that allows the operator to select target regions of interest on an OFDI dataset, and then use a laser to mark the esophagus at corresponding locations. The specific goals include determining the optimal laser parameters, testing the accuracy of the laser marking process, evaluating the endoscopic visibility of the laser marks, and assessing the amount of mucosal damage produced by the laser. Experimental study conducted in 5 swine in vivo. Massachusetts General Hospital. Success rate, including endoscopic visibility of laser marks and accuracy of the laser marking process for selected target sites, and extent of the thermal damage caused by the laser marks. All of the laser-induced marks were visible by endoscopy. Target locations were correctly marked with a success rate of 97.07% (95% confidence interval, 89.8%-99.7%). Thermal damage was limited to the superficial layers of the mucosa and was observed to partially heal within 2 days. An animal study with artificially placed targets to simulate pathology. The study demonstrates that laser marking of esophageal sites identified in comprehensive OFDI datasets is feasible and can be performed with sufficient accuracy, precision, and visibility to guide biopsy in vivo.

Lethal graft-versus-host disease in congenital neutropenia caused by p14 deficiency after allogeneic bone marrow transplantation from an HLA-identical sibling.

PubMed

Bohn, Georg; Hardtke-Wolenski, Matthias; Zeidler, Cornelia; Maecker, Britta; Sauer, Martin; Sykora, Karl-Walter; Grigull, Lorenz; Welte, Karl; Klein, Christoph

2008-09-01

The molecular heterogeneity of severe congenital neutropenia (SCN) is increasingly recognized and may influence the risk-benefit assessment of therapeutic strategies. We report on a patient with p14 deficiency who succumbed to severe grade IV graft-versus-host disease (GvHD) after a human leukocyte antigen-identical bone marrow transplantion (BMT) from a sibling donor. Before BMT, in vitro generated p14-deficient dendritic cells showed a markedly elevated tumor necrosis factor (TNF-) alpha production upon toll-like receptor stimulation. We hypothesize that p14 deficiency predisposes to GvHD through increased TNF-alpha production. Adequate genetic testing is needed to prospectively assess potential risk factors for GvHD in defined SCN subgroups. (c) 2008 Wiley-Liss, Inc.

Diaphragm activity in obesity

PubMed Central

Lourenço, Ruy V.

1969-01-01

Diaphragm activity during carbon dioxide breathing and total chest compliance during diaphragm relaxation were measured in eight obese subjects: four with normal blood gases and four with hypercapnia and hypoxemia. Whereas there were no significant differences in the values of total chest compliance between the two groups, there were marked differences in diaphragm activity. The increase in integrated electrical activity in the diaphragm, per millimeter increment in carbon dioxide tension in the arterial blood, averaged 66 units (range: 48-90) in the obese-normal subjects and 17 units (range: 12-22) in the obese-hypoventilation subjects. These results suggest that an incapacity to increase the activity in the respiratory muscles, to levels necessary to overcome the load caused by obesity, plays a major role in the genesis of respiratory failure in obese subjects. PMID:5822573

[Peculiarities of the course of the repeated outhospital pneumonia by compulsory-duty servicemen].

PubMed

Lebedeva, M N; Grishchenko, A V

2009-07-01

The article presents data of peculiarities of the course of the repeated outhospital pneumonia of 68 compulsory-duty servicemen, which were ill for 2-5 times during the service time. In the given group was detected a high percent of ill persons with background pathology of upper and lower respiratory tracts (69%). In the group also were marked: clinical, laboratorial and instrument peculiarities of course of disease, increase of percent of patients with restrictive damages of respiratory function, increase of quantity of patients with complications and of term of hospital stay. Retrogression of vegetative securing of activity before discharge from the hospital after cases of secondary disease by pneumonia brings to light unpreparedness of patients even to minimal physical activity and causes to create individual rehabilitation programs on outhospital base.

Wildfires in Northern Siberian Larch Dominated Communities

NASA Technical Reports Server (NTRS)

Khaurk, Viacheslav I.; Ranson, Kenneth J.; Dvinskaya, Maria L.; Im, Sergey T.

2011-01-01

The fire history of the northern larch forests within the permafrost zone in a portion of northern Siberia (approx 66 deg N, 100 deg E) was studied. Since there is little to no human activities in this area fires within the study area were mostly caused by lightning. Fire return intervals (FRI) were estimated based on burn marks on tree stems and dates of tree natality. FRI values varied from 130 yr to 350 yr with 200 +/- 50 yr mean. In southerly larch dominated communities FRI was found to be shorter (77 +/- 20 yr at approx 61 deg. N, and 82 +/- 7 at 64 deg N), and longer at the northern boundary (approx 71 deg) of larch stands (320 +/- 50 yr). During the Little Ice Age period in the 16th to 18th centuries FRI was approximately twice as long as recorded in this study. Fire caused changes in the soil including increases in soil drainage and permafrost thawing depth and a radial growth increase of about 2 times (with more than 6 times observed). This effect may simulate the predicted warming impact on the larch growth in the permafrost zone.

The effect of oral mucositis on morbidity and mortality in bone marrow transplant.

PubMed

Gabriel, Don A; Shea, Thomas; Olajida, Oludamilola; Serody, Jonathan S; Comeau, Terrance

2003-12-01

Oral mucosal ulceration is a frequent complication in bone marrow transplantation, resulting from epithelial injury caused by cytotoxic chemotherapy and radiation conditioning, as well as from pre-existing infection. Oral mucositis causes pain, interferes with patient nutrition, and can lead to systemic infection and other complications that increase patient morbidity and mortality; this complication also markedly increases the expense of bone marrow transplantation. A variety of interventions have been assessed for preventing oral mucositis or reducing the severity of mucositis and its sequelae. These include meticulous pretransplantation and ongoing mouth care, calcium phosphate solution, near-infrared light and lower-energy laser treatment, interleukin-11, sucralfate, oral glutamine, granulocyte-macrophage colony-stimulating factor rinse, tretinoin, and keratinocyte growth factor; particularly promising results have been observed with use of the cytoprotectant/radioprotectant agent amifostine. Reduction in the severity and duration of oral mucositis and its sequelae in patients undergoing bone marrow transplantation can have a substantial impact on morbidity and mortality and cost of care. Further systematic evaluation of approaches to prevention and management of oral mucositis is necessary to define optimal strategies in the transplantation setting.

Exposure to 3-methyl-4-nitrophenol affects testicular morphology and induces spermatogenic cell apoptosis in immature male rats.

PubMed

Yue, Zhuo; She, Ruiping; Bao, Huihui; Li, Wengui; Wang, Decheng; Zhu, Jinfeng; Chang, Lingling; Yu, Pin

2011-10-01

The pollutant 3-methyl-4-nitrophenol (PNMC), a major component of diesel exhaust particles, can cause many adverse health problems. In the present study, we investigated the effects of PNMC on the testes of Sprague Dawley rats treated subcutaneously for 5 days with different doses of PNMC (1, 10 or 100mg/kg). Exposure to PNMC caused a significant decrease in the plasma testosterone levels and in the absolute and relative weights of the testes. Severe histological lesions were observed in the testes of PNMC-treated animals. The ratio of the epithelial height to the seminiferous tubule diameter increased markedly in the PNMC-treated rats compared with the corresponding controls. In addition, PNMC exposure significantly increased the number of apoptotic spermatogenic cells compared with the controls whereas a significant decrease in the ratios of Bcl-2/Bax was observed at the same doses. These results suggest that PNMC exerts its gonadotoxicity in the rat mainly via apoptosis. Crown Copyright © 2011. Published by Elsevier India Pvt Ltd. All rights reserved.

[The action of low-intensity extremely high-freguency electromagnetic radiation on growth parameters for bacteria Enterococcus hirae].

PubMed

Oganian, V; Sarkisian, A; Tadevosian, A; Torchunian, A

2008-01-01

It has been found that the exposure of Enterococcus hirae ATCC9790, grown under anaerobic conditions for 30 min or 1 h, to low-intensity (flux capacity 0.06 mW/sm2) coherent electromagnetic radiation (EMI) of extremely high-frequency 45 - 53 GHz), or millimeter waves causes a marked prolongation of the lag-growth phase and a decrease in their specific growth rate, the inhibitory effect increasing in the frequency range from 49 to 53 GHz. The effect enhanced as duration of expocure was encreased from 30 min to 1 h; however, further increase in exposure duration to 2 h did not cause an enhancement of the effect. It has been shown that the action of extremely high-frequency EMI on these bacteria does not depend on medium pH (pH 8.0 or pH 6.0). It is proposed that these bacteria have defensive or reparation mechanisms which compensate for the action of radiation; the occurrence of different mechanisms for pH regulation is not ruled out.

Alleviation of cadmium stress in Solanum lycopersicum L. by arbuscular mycorrhizal fungi via induction of acquired systemic tolerance

PubMed Central

Hashem, Abeer; Abd_Allah, E.F.; Alqarawi, A.A.; Al Huqail, Asma A.; Egamberdieva, D.; Wirth, S.

2015-01-01

Experiments were conducted to evaluate cadmium (Cd) stress-induced changes in growth, antioxidants and lipid composition of Solanum lycopersicum with and without arbuscular mycorrhizal fungi (AMF). Cadmium stress (50 μM) caused significant changes in the growth and physio-biochemical attributes studied. AMF mitigated the deleterious impact of Cd on the parameters studied. Cadmium stress increased malonaldehyde and hydrogen peroxide production but AMF reduced these parameters by mitigating oxidative stress. The activity of antioxidant enzymes enhanced under Cd treatment and AMF inoculation further enhanced their activity, thus strengthening the plant’s defense system. Proline and phenol content increased in Cd-treated as well as AMF-inoculated plants providing efficient protection against Cd stress. Cadmium treatment resulted in great alterations in the main lipid classes leading to a marked change in their composition. Cadmium stress caused a significant reduction in polyunsaturated fatty acids resulting in enhanced membrane leakage. The present study supports the use of AMF as a biological means to ameliorate Cd stress-induced changes in tomato. PMID:26981010

Effect of acetyl salicylic acid on increased production of thromboxane after aortic graft surgery.

PubMed

Lewin, J; Swedenborg, J; Egberg, N; Vesterqvist, O; Green, K

1989-06-01

Contact between blood and foreign surfaces, e.g. vascular grafts, causes activation and release of platelets. One consequence of platelet activation is production of thromboxane A2 (TxA2). The physiological effects of TxA2, i.e. platelet aggregation and vaso-constriction are counteracted by another prostanoid, prostacyclin (PGI2). Acetylsalicylic acid (ASA) causes a longlasting inhibition of platelet TxA2 production and a more shortlasting inhibition of PGI2 production. The present study examines TxA2 and PGI2 synthesis in patients receiving synthetic arterial grafts, some of which were treated with ASA. The prostanoid synthesis was evaluated by measurement of their main urinary metabolites with gas chromatography-mass spectrometry. Platelet release was evaluated by measurements of beta-thromboglobulin (beta-TG) and the plasma coagulation by measurements of fibrinopeptide A (FPA). These compounds were also measured in urine in order to avoid artifacts caused by activation of platelets and plasma coagulation during blood sampling. Following replacement of the abdominal aorta with a synthetic vascular graft there was a marked increase in the synthesis of TxA2 and PGI2. Increased levels of beta-TG and FPA were also demonstrated. Administration of ASA on the first and second postoperative days significantly reduced the synthesis of TxA2 but caused no significant effects on the other parameters measured. It is concluded that ASA may be beneficial in the postoperative period since it counteracts TxA2 with vasoconstricting and platelet aggregating properties but leaves PGI2 with vasodilating and antiaggregating properties relatively uneffected.

Too Little and Too Much: Hypoactivation and Disinhibition of Medial Prefrontal Cortex Cause Attentional Deficits

PubMed Central

McGarrity, Stephanie; Mason, Rob; Fone, Kevin C.

2014-01-01

Attentional deficits are core symptoms of schizophrenia, contributing strongly to disability. Prefrontal dysfunction has emerged as a candidate mechanism, with clinical evidence for prefrontal hypoactivation and disinhibition (reduced GABAergic inhibition), possibly reflecting different patient subpopulations. Here, we tested in rats whether imbalanced prefrontal neural activity impairs attention. To induce prefrontal hypoactivation or disinhibition, we microinfused the GABA-A receptor agonist muscimol (C4H6N2O2; 62.5, 125, 250 ng/side) or antagonist picrotoxin (C30H34O13; 75, 150, 300 ng/side), respectively, into the medial prefrontal cortex. Using the five-choice serial reaction time (5CSRT) test, we showed that both muscimol and picrotoxin impaired attention (reduced accuracy, increased omissions). Muscimol also impaired response control (increased premature responses). In addition, muscimol dose dependently reduced open-field locomotor activity, whereas 300 ng of picrotoxin caused locomotor hyperactivity; sensorimotor gating (startle prepulse inhibition) was unaffected. Therefore, infusion effects on the 5CSRT test can be dissociated from sensorimotor effects. Combining microinfusions with in vivo electrophysiology, we showed that muscimol inhibited prefrontal firing, whereas picrotoxin increased firing, mainly within bursts. Muscimol reduced and picrotoxin enhanced bursting and both drugs changed the temporal pattern of bursting. Picrotoxin also markedly enhanced prefrontal LFP power. Therefore, prefrontal hypoactivation and disinhibition both cause attentional deficits. Considering the electrophysiological findings, this suggests that attention requires appropriately tuned prefrontal activity. Apart from attentional deficits, prefrontal disinhibition caused additional neurobehavioral changes that may be relevant to schizophrenia pathophysiology, including enhanced prefrontal bursting and locomotor hyperactivity, which have been linked to psychosis-related dopamine hyperfunction. PMID:24899715

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.

Discoloration of titanium alloy in acidic saline solutions with peroxide.

PubMed

Takemoto, Shinji; Hattori, Masayuki; Yoshinari, Masao; Kawada, Eiji; Oda, Yutaka

2013-01-01

The objective of this study was to compare corrosion behavior in several titanium alloys with immersion in acidulated saline solutions containing hydrogen peroxide. Seven types of titanium alloy were immersed in saline solutions with varying levels of pH and hydrogen peroxide content, and resulting differences in color and release of metallic elements determined in each alloy. Some alloys were characterized using Auger electron spectroscopy. Ti-55Ni alloy showed a high level of dissolution and difference in color. With immersion in solution containing hydrogen peroxide at pH 4, the other alloys showed a marked difference in color but a low level of dissolution. The formation of a thick oxide film was observed in commercially pure titanium showing discoloration. The results suggest that discoloration in titanium alloys immersed in hydrogen peroxide-containing acidulated solutions is caused by an increase in the thickness of this oxide film, whereas discoloration of Ti-55Ni is caused by corrosion.

PLASMA AND RED CELL RADIOIRON FOLLOWING INTRAVENOUS INJECTION

PubMed Central

Yuile, C. L.; Bly, C. G.; Stewart, W. B.; Izzo, A. J.; Wells, J. C.; Whipple, G. H.

1949-01-01

Sterile inflammation induced by repeated subcutaneous injections of turpentine in non-anemic, non-iron—deficient dogs, leads to a fall in plasma iron concentration, the development of a moderate anemia, and a marked delay in the uptake by the red blood cells of intravenous radioiron. Similar periods of inflammation in anemic, iron-deficient dogs on a diet low in iron cause no increase in the degree of anemia and no inhibition of red blood cell uptake of intravenous radioiron. Radioiron appears only in traces in abscess exudates. Intravenous iron disappearance curves following a single injection are uninfluenced by sterile inflammation in either anemic or non-anemic dogs. The impairment of hemoglobin synthesis caused by inflammation is at most a relative matter, since the anemia that develops is seldom severe or progressive, and since the inhibition can be overcome if the marrow is sufficiently stimulated by the demands of a severe continuing anemia. PMID:18140660

Neonatal intensive care practices harmful to the developing brain.

PubMed

Chaudhari, Sudha

2011-06-01

There has been a marked increase in the survival of extremely low birth weight (ELBW) infants, but these babies have a long stay in the NICU. Strategies to decrease their neurodevelopmental impairment become very important. The maximum development of the brain occurs between 29-41 weeks. From the warm, dark, acquatic econiche, where the baby hears pleasant sounds like the mother's heart beat, the baby suddenly finds itself in the dry, cold, excessively bright, noisy, environment of the NICU. Noise, bright light, painful procedures, and ill-timed caregiving activities, adversely affect the infant's development. Excessive radiation from X-rays of babies on the ventilator and CT scans also affect the brain. Medications like steroids for chronic lung disease also cause damage to the brain. Aminoglycides and frusemide are known to cause hearing impairment. Hence a developmentally supportive, humanized care will go a long way in enhancing the developmental outcome of these babies.

Sulfuric acid induces airway hyperresponsiveness to substance P in the guinea pig.

PubMed

Stengel, P W; Bendele, A M; Cockerham, S L; Silbaugh, S A

1993-01-01

We investigated whether sulfuric acid inhalation would cause hyperresponsiveness to substance P. Guinea pigs became dyspneic during a 1 h sulfuric acid exposure, but recovered by 24 h when they were challenged with substance P or histamine aerosols. Eight minutes after the start of challenge, animals were killed and excised lung gas volumes measured. Sulfuric acid slightly increased histamine responsiveness compared to controls. However, sulfuric acid caused a much more pronounced leftward shift in the dose response to substance P. Coadministration of the neutral endopeptidase (NEP) inhibitor, thiorphan, did not reduce sulfuric acid-related hyperresponsiveness to substance P. By 72 h, sensitization to substance P was absent. Histological evaluation of sulfuric acid-treated lungs revealed mild alveolitis at 24 h, but not at 72 h. We conclude that sulfuric acid produces a marked sensitization to substance P. Inactivation of NEP does not appear to account for this effect.

Severe peripheral neuropathy and elevated plantar pressures causing foot ulceration in pituitary gigantism.

PubMed

Jennings, A M; Robinson, A; Kandler, R H; Betts, R P; Ryder, R E; Cullen, D R

1993-07-01

We report two patients with treated pituitary gigantism and peripheral neuropathy, one of whom has chronic foot ulceration. Detailed neurophysiological assessment was performed on both patients. The patient with foot ulceration had clinical and neurophysiological evidence of severe neuropathy, whereas the patient without ulceration had only neurophysiological abnormalities. The sweating response to acetylcholine was markedly impaired in the feet of both patients, suggesting pedal autonomic denervation. Neither patient had evidence of diabetes mellitus and detailed investigation failed to reveal an alternative cause of peripheral neuropathy. Optical pedobarography revealed abnormally high pressure (> 10 kg/cm2) under the metatarsal heads of both patients, one such area coinciding with the area of ulceration. Thus in pituitary gigantism elevated plantar pressures may contribute to the development of foot ulceration when severe peripheral neuropathy is present. Furthermore, as in diabetes mellitus, impaired sweating may also increase the risk of ulceration as the resultant dry skin may develop fissures.

Histological and histochemical studies on the female reproductive system of rose-ringed parakeet (Psittacula krameri) after testosterone propionate treatment.

PubMed

Sarker, A K; Seth, T N

1975-01-01

Intramuscular injections of testosterone propionate (Perandren, CIBA) at a dose level of 2.5 mg per day for 10 days into adult female parakeet caused an increment of differentiated follicles in the ovary. The histological study of the testosterone treated oviduct of the bird showed well developed villi with a significant number of tubular glands particularly in the middle and distal parts of the oviduct. The high level of alkaline phosphatase activity and ascorbic acid concentration in the distal part of the oviduct in treated birds probably increase the power of hatchable eggs which has a close relationship with the enzyme and vitamin C concentration in the uterus. The testosterone treatment causes a marked depletion of granulosal vitamins from ovary but augments the ascorbate mobilization in the thecal region to a very great extent probably due to more LH secretion from the pituitary.

Rotordynamic Characteristics of the HPOTP (High Pressure Oxygen Turbopump) of the SSME (Space Shuttle Main Engine)

NASA Technical Reports Server (NTRS)

Childs, D. W.

1984-01-01

Rotational stability of turbopump components in the space shuttle main engine was studied via analysis of component and structural dynamic models. Subsynchronous vibration caused unacceptable migration of the rotor/housing unit with unequal load sharing of the synchronous bearings that resulted in the failure of the High Pressure Oxygen Turbopump. Linear analysis shows that a shrouded inducer eliminates the second critical speed and the stability problem, a stiffened rotor improves the rotordynamic characteristics of the turbopump, and installing damper boost/impeller seals reduces bearing loads. Nonlinear analysis shows that by increasing the "dead band' clearances, a marked reduction in peak bearing loads occurs.

Depressed immune surveillance against cancer: role of deficient T cell: extracellular matrix interactions.

PubMed

Górski, A; Castronovo, V; Stepień-Sopniewska, B; Grieb, P; Ryba, M; Mrowiec, T; Korczak-Kowalska, G; Wierzbicki, P; Matysiak, W; Dybowska, B

1994-07-01

Although T cells infiltrate malignant tumors, the local immune response is usually inefficient and tumors escape destruction. While extracellular matrix proteins strongly costimulate T cell responses in normal individuals, our studies indicate that peripheral blood T cells from cancer patients and tumor infiltrating cells respond poorly or are resistant to stimulative signals mediated by collagen I and IV and fibronectin. Moreover, the adhesive properties of cancer T cells are markedly depressed. Those functional deficiencies are paralleled by variable deficits in integrin and non-integrin T cell receptors for extracellular matrix. Immunotherapy with BCG causes a dramatic but transient increase in T cell: ECM interactions.

[Activating effect of cyclophosphane at late stages of persistence of the tick-borne encephalitis virus].

PubMed

Frolova, T V; Pogodina, V V; Larina, G I; Frolova, M P; Karmysheva, V Ia

1982-01-01

Conditions of activation of persistent infection caused by subcutaneous inoculation of Syrian hamsters with the B-383 and Vasilchenko strains of tick-borne encephalitis virus (TBE) were studied. After 2 administrations of cyclophosphane (CP) on day 170 of infection clinically manifest disease developed in some animals with increasingly severe pathomorphological lesions in the CNS. Several variants of activated TBE virus were isolated from brains and spleens of CP-treated hamsters. The activation of persistent infection was observed in the presence of marked decreased of humoral immunity level, weight of the thymus, and values of spontaneous rosette-formation.

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.

The solar wind-magnetosphere-ionosphere system

PubMed

Lyon

2000-06-16

The solar wind, magnetosphere, and ionosphere form a single system driven by the transfer of energy and momentum from the solar wind to the magnetosphere and ionosphere. Variations in the solar wind can lead to disruptions of space- and ground-based systems caused by enhanced currents flowing into the ionosphere and increased radiation in the near-Earth environment. The coupling between the solar wind and the magnetosphere is mediated and controlled by the magnetic field in the solar wind through the process of magnetic reconnection. Understanding of the global behavior of this system has improved markedly in the recent past from coordinated observations with a constellation of satellite and ground instruments.

Whooping Cough: A Brief History to the 19th Century.

PubMed

Weston, Robert

2012-01-01

This paper examines the history of whooping cough (pertussis) from its first recorded mention in 1190 to the time when its microbial cause was identified. The historical records of the disease are complicated by the variation in the nomenclature employed and through using the same name for disorders with different symptoms. During the early-modern period it was considered to be a disease new to Europe-contagious, dangerous, and potentially epidemic. Believed to be confined to children, its significance was limited until the 18th century when its incidence increased markedly. This essay argues pertussis may have occurred in the late medieval period in individual, though not epidemical, cases.

Inflammation-induced lymphangiogenesis and lymphatic dysfunction

PubMed Central

Liao, Shan; von der Weid, Pierre-Yves

2014-01-01

The lymphatic system is intimately linked to tissue fluid homeostasis and immune cell trafficking. These functions are paramount in the establishment and development of an inflammatory response. In the past decade, an increasing number of reports has revealed that marked changes, such as lymphangiogenesis and lymphatic contractile dysfunction occur in both vascular and nodal parts of the lymphatic system during inflammation, as well as other disease processes. This review provides a critical update on the role of the lymphatic system in disease process such as chronic inflammation and cancer and examines the changes in lymphatic functions the diseases cause and the influence these changes have on the progression of the diseases. PMID:24449090

Severe congenital neutropenia resulting from G6PC3 deficiency with increased neutrophil CXCR4 expression and myelokathexis.

PubMed

McDermott, David H; De Ravin, Suk See; Jun, Hyun Sik; Liu, Qian; Priel, Debra A Long; Noel, Pierre; Takemoto, Clifford M; Ojode, Teresa; Paul, Scott M; Dunsmore, Kimberly P; Hilligoss, Dianne; Marquesen, Martha; Ulrick, Jean; Kuhns, Douglas B; Chou, Janice Y; Malech, Harry L; Murphy, Philip M

2010-10-14

Mutations in more than 15 genes are now known to cause severe congenital neutropenia (SCN); however, the pathologic mechanisms of most genetic defects are not fully defined. Deficiency of G6PC3, a glucose-6-phosphatase, causes a rare multisystem syndrome with SCN first described in 2009. We identified a family with 2 children with homozygous G6PC3 G260R mutations, a loss of enzymatic function, and typical syndrome features with the exception that their bone marrow biopsy pathology revealed abundant neutrophils consistent with myelokathexis. This pathologic finding is a hallmark of another type of SCN, WHIM syndrome, which is caused by gain-of-function mutations in CXCR4, a chemokine receptor and known neutrophil bone marrow retention factor. We found markedly increased CXCR4 expression on neutrophils from both our G6PC3-deficient patients and G6pc3(-/-) mice. In both patients, granulocyte colony-stimulating factor treatment normalized CXCR4 expression and neutrophil counts. In G6pc3(-/-) mice, the specific CXCR4 antagonist AMD3100 rapidly reversed neutropenia. Thus, myelokathexis associated with abnormally high neutrophil CXCR4 expression may contribute to neutropenia in G6PC3 deficiency and responds well to granulocyte colony-stimulating factor.

Prenatal cadmium exposure alters postnatal immune cell development and function

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

Hanson, Miranda L.; Holásková, Ida; Elliott, Meenal

2012-06-01

Cadmium (Cd) is generally found in low concentrations in the environment due to its widespread and continual use, however, its concentration in some foods and cigarette smoke is high. Although evidence demonstrates that adult exposure to Cd causes changes in the immune system, there are limited reports of immunomodulatory effects of prenatal exposure to Cd. This study was designed to investigate the effects of prenatal exposure to Cd on the immune system of the offspring. Pregnant C57Bl/6 mice were exposed to an environmentally relevant dose of CdCl{sub 2} (10 ppm) and the effects on the immune system of the offspringmore » were assessed at two time points following birth (2 and 7 weeks of age). Thymocyte and splenocyte phenotypes were analyzed by flow cytometry. Prenatal Cd exposure did not affect thymocyte populations at 2 and 7 weeks of age. In the spleen, the only significant effect on phenotype was a decrease in the number of macrophages in male offspring at both time points. Analysis of cytokine production by stimulated splenocytes demonstrated that prenatal Cd exposure decreased IL-2 and IL-4 production by cells from female offspring at 2 weeks of age. At 7 weeks of age, splenocyte IL-2 production was decreased in Cd-exposed males while IFN-γ production was decreased from both male and female Cd-exposed offspring. The ability of the Cd-exposed offspring to respond to immunization with a S. pneumoniae vaccine expressing T-dependent and T-independent streptococcal antigens showed marked increases in the levels of both T-dependent and T-independent serum antibody levels compared to control animals. CD4{sup +}FoxP3{sup +}CD25{sup +} (nTreg) cell percentages were increased in the spleen and thymus in all Cd-exposed offspring except in the female spleen where a decrease was seen. CD8{sup +}CD223{sup +} T cells were markedly decreased in the spleens in all offspring at 7 weeks of age. These findings suggest that even very low levels of Cd exposure during gestation can result in long term detrimental effects on the immune system of the offspring and these effects are to some extent sex-specific. -- Highlights: ► Prenatal exposure to Cd causes no thymocyte phenotype changes in the offspring ► Analysis of the splenocyte phenotype demonstrates a macrophage-specific effect only in male offspring ► The cytokine profiles suggest an effect on peripheral Th1 cells in female and to a lesser degree in male offspring ► There was a marked increase in serum anti-streptococcal antibody levels after immunization in both sexes ► There was a marked decrease in the numbers of splenic CD8{sup +}CD223{sup +} cells in both sexes.« less

Evaluation of retroreflective markings to increase rail car conspicuity

DOT National Transportation Integrated Search

1998-10-01

The purpose of this study was to develop guidelines and recommendations for the design of retroreflective marking systems to enhance the conspicuity of rail cars at night. Three methods were used to generate and evaluate the marking systems for a sta...

A case of severe anorexia, excessive weight loss and high peptide YY levels after sleeve gastrectomy.

PubMed

Pucci, Andrea; Cheung, Wui Hang; Jones, Jenny; Manning, Sean; Kingett, Helen; Adamo, Marco; Elkalaawy, Mohamed; Jenkinson, Andrew; Finer, Nicholas; Doyle, Jacqueline; Hashemi, Majid; Batterham, Rachel L

2015-01-01

Sleeve gastrectomy (SG) is the second most commonly performed bariatric procedure worldwide. Altered circulating gut hormones have been suggested to contribute post-operatively to appetite suppression, decreased caloric intake and weight reduction. In the present study, we report a 22-year-old woman who underwent laparoscopic SG for obesity (BMI 46 kg/m(2)). Post-operatively, she reported marked appetite reduction, which resulted in excessive weight loss (1-year post-SG: BMI 22 kg/m(2), weight loss 52%, >99th centile of 1-year percentage of weight loss from 453 SG patients). Gastrointestinal (GI) imaging, GI physiology/motility studies and endoscopy revealed no anatomical cause for her symptoms, and psychological assessments excluded an eating disorder. Despite nutritional supplements and anti-emetics, her weight loss continued (BMI 19 kg/m(2)), and she required nasogastric feeding. A random gut hormone assessment revealed high plasma peptide YY (PYY) levels. She underwent a 3 h meal study following an overnight fast to assess her subjective appetite and circulating gut hormone levels. Her fasted nausea scores were high, with low hunger, and these worsened with nutrient ingestion. Compared to ten other post-SG female patients, her fasted circulating PYY and nutrient-stimulated PYY and active glucagon-like peptide 1 (GLP1) levels were markedly elevated. Octreotide treatment was associated with suppressed circulating PYY and GLP1 levels, increased appetite, increased caloric intake and weight gain (BMI 22 kg/m(2) after 6 months). The present case highlights the value of measuring gut hormones in patients following bariatric surgery who present with anorexia and excessive weight loss and suggests that octreotide treatment can produce symptomatic relief and weight regain in this setting. Roux-en-Y gastric bypass and SG produce marked sustained weight reduction. However, there is a marked individual variability in this reduction, and post-operative weight loss follows a normal distribution with extremes of 'good' and 'poor' response.Profound anorexia and excessive weight loss post-SG may be associated with markedly elevated circulating fasted PYY and post-meal PYY and GLP1 levels.Octreotide treatment can produce symptomatic relief and weight regain for post-SG patients that have an extreme anorectic and weight loss response.The present case highlights the value of measuring circulating gut hormone levels in patients with post-operative anorexia and extreme weight loss.

Performance comparison for Barnes model 12-1000, Exotech model 100, and Ideas Inc. Biometer Mark 2

NASA Technical Reports Server (NTRS)

Robinson, B. (Principal Investigator)

1981-01-01

Results of tests show that all channels of all instruments, except channel 3 of the Biometer Mark 2, were stable in response to input signals were linear, and were adequately stable in response to temperature changes. The Biometer Mark 2 is labelled with an inappropriate description of the units measured and the dynamic range is a inappropriate for field measurements causing unnecessarily high fractional errors. This instrument is, therefore, quantization limited. The dynamic range and noise performance of the Model 12-1000 are appropriate for remote sensing field research. The field of view and performance of the Model 100A and the Model 12-1000 are satisfactory. The Biometer Mark 2 has not, as yet, been satisfactorily equipped with an acceptable field of view determining device. Neither the widely used aperture plate nor the 24 deg cone are acceptable.

Lethal mechanisms in gastric volvulus.

PubMed

Omond, Kimberley J; Byard, Roger W

2017-01-01

A 55-year-old wheelchair-bound woman with severe cerebral palsy was found at autopsy to have marked distention of the stomach due to a volvulus. The stomach was viable, and filled with air and fluid and had pushed the left dome of the diaphragm upwards causing marked compression of the left lung with a mediastinal shift to the right (including the heart). There was no evidence of gastric perforation, ischaemic necrosis or peritonitis. Removal of the organ block revealed marked kyphoscoliosis. Histology confirmed the viability of the stomach and biochemistry showed no dehydration. Death in cases of acute gastric volvulus usually occurs because of compromise of the gastric blood supply resulting in ischaemic necrosis with distention from swallowed air and fluid resulting in perforation with lethal peritonitis. Hypovolaemic shock may also occur. However, the current case demonstrates an alternative lethal mechanism, that of respiratory compromise due to marked thoracic organ compression.

Decoupled direct tracking control system based on use of a virtual track for multilayer disk with a separate guide layer

NASA Astrophysics Data System (ADS)

Tanaka, Yukinobu; Ogata, Takeshi; Imagawa, Seiji

2015-09-01

We developed a decoupled direct tracking control system for multilayer optical disk that uses a separate guide layer. Data marks are recorded on a recording layer immediately above the guide layer by using two spatially separated spots with different wavelengths. Accurate data mark recording requires that the relative positions of the corresponding spots on the recording layer and guide layer are maintained. However, a disk tilt can shift their relative positions and cause previously recorded data marks to be overwritten. Additionally, a two-input/two-output control system is susceptible to mutual interference phenomenon between the two outputs, which can destabilize tracking control. A tracking control system based on use of data marks previously recorded as a virtual track has been developed that prevents spot shifting and mutual interference even if the disk tilt reaches 0.7°, thereby preventing overwriting.

Renin stimulation by passive tilting: the influence of an anti-gravity suit on postural changes in plasma renin activity, plasma noradrenaline concentration and kidney function in normal man.

PubMed

Hesse, B; Ring-Larsen, H; Nielsen, I; Christensen, N J

1978-04-01

Plasma renin activity (PRA), plasma noradrenaline concentration, heart rate, blood pressure, and clearances of para-aminohippurate and inulin were measured in twelve normal subjects (clearances in only three subjects) before and after 40 min of 60 degrees upright tilting. The tilting experiments were repeated after inflation of an anti-gravity suit to 60 mmHg on the lower extremities. Inflation of the anti-gravity suit caused an abolition of the postural PRA increase, a marked reduction of the postural increases in plasma noradrenaline and heart rate, and elimination of the decreases in pulse pressure, inulin and para-aminohippurate clearances and sodium excretion. The results suggest a decisive role of the sympathetic nervous system for postural renin increase, probably mainly activated by stretch receptors in the low-pressure cardiopulmoanry area.

Modification of Lightweight Aggregates' Microstructure by Used Motor Oil Addition.

PubMed

Franus, Małgorzata; Jozefaciuk, Grzegorz; Bandura, Lidia; Lamorski, Krzysztof; Hajnos, Mieczysław; Franus, Wojciech

2016-10-18

An admixture of lightweight aggregate substrates (beidellitic clay containing 10 wt % of natural clinoptilolite or Na-P1 zeolite) with used motor oil (1 wt %-8 wt %) caused marked changes in the aggregates' microstructure, measured by a combination of mercury porosimetry (MIP), microtomography (MT), and scanning electron microscopy. Maximum porosity was produced at low (1%-2%) oil concentrations and it dropped at higher concentrations, opposite to the aggregates' bulk density. Average pore radii, measured by MIP, decreased with an increasing oil concentration, whereas larger (MT) pore sizes tended to increase. Fractal dimension, derived from MIP data, changed similarly to the MIP pore radius, while that derived from MT remained unaltered. Solid phase density, measured by helium pycnometry, initially dropped slightly and then increased with the amount of oil added, which was most probably connected to changes in the formation of extremely small closed pores that were not available for He atoms.

Modification of Lightweight Aggregates’ Microstructure by Used Motor Oil Addition

PubMed Central

Franus, Małgorzata; Jozefaciuk, Grzegorz; Bandura, Lidia; Lamorski, Krzysztof; Hajnos, Mieczysław; Franus, Wojciech

2016-01-01

An admixture of lightweight aggregate substrates (beidellitic clay containing 10 wt % of natural clinoptilolite or Na-P1 zeolite) with used motor oil (1 wt %–8 wt %) caused marked changes in the aggregates’ microstructure, measured by a combination of mercury porosimetry (MIP), microtomography (MT), and scanning electron microscopy. Maximum porosity was produced at low (1%–2%) oil concentrations and it dropped at higher concentrations, opposite to the aggregates’ bulk density. Average pore radii, measured by MIP, decreased with an increasing oil concentration, whereas larger (MT) pore sizes tended to increase. Fractal dimension, derived from MIP data, changed similarly to the MIP pore radius, while that derived from MT remained unaltered. Solid phase density, measured by helium pycnometry, initially dropped slightly and then increased with the amount of oil added, which was most probably connected to changes in the formation of extremely small closed pores that were not available for He atoms. PMID:28773964

Juvenile Paget’s Disease In An Iranian Kindred With Vitamin D Deficiency And Novel Homozygous TNFRSF11B Mutation

PubMed Central

Saki, Forough; Karamizadeh, Zohreh; Nasirabadi, Shiva; Mumm, Steven; McAlister, William H.; Whyte, Michael P.

2013-01-01

Juvenile Paget’s disease (JPD) is a rare heritable osteopathy characterized biochemically by markedly increased serum alkaline phosphatase (ALP) activity emanating from generalized acceleration of skeletal turnover. Affected infants and children typically suffer bone pain and fractures and deformities, become deaf, and have macrocranium. Some who survive to young adult life develop blindness from retinopathy engendered by vascular microcalcification. Most cases of JPD are caused by osteoprotegerin (OPG) deficiency due to homozygous loss-of-function mutations within the TNFRSF11B gene that encodes OPG. We report a 3-year-old Iranian girl with JPD and craniosynostosis who had vitamin D deficiency in infancy. She presented with fractures during the first year-of-life followed by bone deformities, delayed development, failure-to-thrive, and pneumonias. At 1 year-of-age, biochemical studies of serum revealed marked hyperphosphatasemia together with low-normal calcium and low inorganic phosphate and 25-hydroxyvitamin D levels. Several family members in previous generations of this consanguineous kindred may also have had JPD and vitamin D deficiency. Mutation analysis showed homozygosity for a unique missense change (c.130T>C, p.Cys44Arg) in TNFRSF11B that would compromise the cysteine-rich domain of OPG that binds receptor activator of NF-κB ligand (RANKL). Both parents were heterozygous for this mutation. The patient’s serum OPG level was extremely low and RANKL level markedly elevated. She responded well to rapid oral vitamin D repletion followed by pamidronate treatment given intravenously. Our patient is the first Iranian reported with JPD. Her novel mutation in TNFRSF11B plus vitamin D deficiency in infancy was associated with severe JPD uniquely complicated by craniosynostosis. Pamidronate treatment with vitamin D sufficiency can be effective treatment for the skeletal disease caused by the OPG deficiency form of JPD. PMID:23322328

Surfactant properties of human meibomian lipids.

PubMed

Mudgil, Poonam; Millar, Thomas J

2011-03-25

Human meibomian lipids are the major part of the lipid layer of the tear film. Their surfactant properties enable their spread across the aqueous layer and help maintain a stable tear film. The purpose of this study was to investigate surfactant properties of human meibomian lipids in vitro and to determine effects of different physical conditions such as temperature and increased osmolarity, such as occur in dry eye, on these properties. Human meibomian lipids were spread on an artificial tear solution in a Langmuir trough. The lipid films were compressed and expanded to record the surface pressure-area (Π-A) isocycles. The isocycles were recorded under different physical conditions such as high pressure, increasing concentration and size of divalent cations, increasing osmolarity, and varying temperature. Π-A isocycles of meibomian lipids showed that they form liquid films that are compressible and multilayered. The isocycles were unaffected by increasing concentration or size of divalent cations and increasing osmolarity in the subphase. Temperature had a marked effect on the lipids. Increase in temperature caused lipid films to become fluid, an expected feature, but decrease in temperature unexpectedly caused expansion of lipids and an increase in pressure suggesting enhanced surfactant properties. Human meibomian lipids form highly compressible, non-collapsible, multilayered liquid films. These lipids have surfactants that allow them to spread across an aqueous subphase. Their surfactant properties are unaffected by increasing divalent cations or hyperosmolarity but are sensitive to temperature. Cooling of meibomian lipids enhances their surfactant properties.

Acanthosis nigricans

MedlinePlus

... cause any symptoms other than skin changes. Eventually, dark, velvety skin with very visible markings and creases ... your provider if you develop areas of thick, dark, velvety skin. Alternative Names AN; Skin pigment disorder - ...

Biochemical and Ultrastructural Changes in Sida cordifolia L. and Catharanthus roseus L. to Auto Pollution.

PubMed

Verma, Vijeta; Chandra, Neelam

2014-01-01

Auto pollution is the by-product of our mechanized mobility, which adversely affects both plant and human life. However, plants growing in the urban locations provide a great respite to us from the brunt of auto pollution by absorbing the pollutants at their foliar surface. Foliar surface configuration and biochemical changes in plant species, namely, Sida cordifolia L. and Catharanthus roseus L. grown at roadside (polluted site 1, Talkatora; polluted site 2, Charbagh) in Lucknow city and in the garden of the university campus, which has been taken as reference site, were investigated. It was observed that air pollution caused by auto exhaust showed marked alterations in photosynthetic pigments (chlorophyll, carotenoid, and phaeophytin), and relative water content was reduced while antioxidative enzymes like catalase and peroxidase were found to be enhanced. The changes in the foliar configuration reveal marked alteration in epidermal traits, with decreased number of stomata, stomatal indices, and epidermal cells per unit area, while length and breadth of stomata and epidermal cells were found to be increased in leaves samples wich can be used as biomarkers of auto pollution.

Biochemical and Ultrastructural Changes in Sida cordifolia L. and Catharanthus roseus L. to Auto Pollution

PubMed Central

Verma, Vijeta; Chandra, Neelam

2014-01-01

Auto pollution is the by-product of our mechanized mobility, which adversely affects both plant and human life. However, plants growing in the urban locations provide a great respite to us from the brunt of auto pollution by absorbing the pollutants at their foliar surface. Foliar surface configuration and biochemical changes in plant species, namely, Sida cordifolia L. and Catharanthus roseus L. grown at roadside (polluted site 1, Talkatora; polluted site 2, Charbagh) in Lucknow city and in the garden of the university campus, which has been taken as reference site, were investigated. It was observed that air pollution caused by auto exhaust showed marked alterations in photosynthetic pigments (chlorophyll, carotenoid, and phaeophytin), and relative water content was reduced while antioxidative enzymes like catalase and peroxidase were found to be enhanced. The changes in the foliar configuration reveal marked alteration in epidermal traits, with decreased number of stomata, stomatal indices, and epidermal cells per unit area, while length and breadth of stomata and epidermal cells were found to be increased in leaves samples wich can be used as biomarkers of auto pollution. PMID:27355010

[Respiratory infections caused by metapneumovirus in elderly patients].

PubMed

Fica C, Alberto; Hernández C, Loreto; Porte T, Lorena; Castro S, Marcelo; Weitzel, Thomas

2011-04-01

Human metapneumovirus infections are increasingly recognized among adult patients and the aim of this report is to present a series of 4 cases admitted during the winter of 2010. All were detected by direct fluorescence anti-bodies assay of respiratory samples and all were female patients with an age range of 79 to 95 years, including two bedridden cases, one with dementia and three with chronic obstructive pulmonary disease. One patient presented with parainfluenza 3 virus coinfection. Patients presented with pneumonía in 3 cases (interstitial pattern in 2 and lobar consolidation in the other) or acute exacerbation of chronic bronchitis in the remaining case. Symptoms were present for 3 to 7 days before admission and 3 have wheezing. All had hypoxemic or global respiratory failure and lymphopenia (< 1.000/mm³). Hospitalization lasted for 5 to 20 days, marked in the 3 cases that survived by prolonged bronchial obstructive manifestations. Two cases required non invasive mechanical ventilation. Human metapneumovirus infections can decompensate elderly patients with chronic respiratory diseases generating hospital admission and a prolonged morbidity marked by obstructive manifestations and sometimes can become into death.

Hepatic lipidosis and other test findings in two captive adult porcupines (Erethizon dorsatum) dying from a "sudden death syndrome".

PubMed

Barigye, Robert; Schamber, Ev; Newell, Teresa K; Dyer, Neil W

2007-11-01

Routine postmortem examination and histologic evaluation of tissue sections demonstrated hepatic lipidosis (HL) in 2 adult captive porcupines with a history of sudden death. The male porcupine had a markedly enlarged pale liver that microscopically showed large unilocular vacuoles within hepatocellular cytoplasm. The periparturient female had similar but less marked hepatic lesions and an incidental pulmonary mycosis. These findings suggest HL as an important differential of spontaneous death in captive porcupines. It is hypothesized that in addition to the widely documented causes, HL in captive porcupines may be specifically associated with nutritional imbalances caused by the feeding of unsuitable commercial diets. The possible association of the condition with dietary and other factors in captive porcupines needs to be thoroughly investigated.

Mechanisms of Developmental Regression in Autism and the Broader Phenotype: A Neural Network Modeling Approach

ERIC Educational Resources Information Center

Thomas, Michael S. C.; Knowland, Victoria C. P.; Karmiloff-Smith, Annette

2011-01-01

Loss of previously established behaviors in early childhood constitutes a markedly atypical developmental trajectory. It is found almost uniquely in autism and its cause is currently unknown (Baird et al., 2008). We present an artificial neural network model of developmental regression, exploring the hypothesis that regression is caused by…

1-Nitropyrene (1-NP) induces apoptosis and apparently a non-apoptotic programmed cell death (paraptosis) in Hepa1c1c7 cells

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

Asare, Nana; Landvik, Nina E.; Lagadic-Gossmann, Dominique

2008-07-15

Mechanistic studies of nitro-PAHs (polycyclic aromatic hydrocarbons) of interest might help elucidate which chemical characteristics are most important in eliciting toxic effects. 1-Nitropyrene (1-NP) is the predominant nitrated PAH emitted in diesel exhaust. 1-NP-exposed Hepa1c1c7 cells exhibited marked changes in cellular morphology, decreased proliferation and different forms of cell death. A dramatic increase in cytoplasmic vacuolization was observed already after 6 h of exposure and the cells started to round up at 12 h. The rate of cell proliferation was markedly reduced at 24 h and apoptotic as well as propidium iodide (PI)-positive cells appeared. Electron microscopic examination revealed thatmore » the vacuolization was partly due to mitochondria swelling. The caspase inhibitor Z-VAD-FMK inhibited only the apoptotic cell death and Nec-1 (an inhibitor of necroptosis) exhibited no inhibitory effects on either cell death or vacuolization. In contrast, cycloheximide markedly reduced both the number of apoptotic and PI-positive cells as well as the cytoplasmic vacuolization, suggesting that 1-NP induced paraptotic cell death. All the MAPKs; ERK1/2, p38 and JNK, appear to be involved in the death process since marked activation was observed upon 1-NP exposure, and their inhibitors partly reduced the induced cell death. The ERK1/2 inhibitor PD 98057 completely blocked the induced vacuolization, whereas the other MAPKs inhibitors only had minor effects on this process. These findings suggest that 1-NP may cause apoptosis and paraptosis. In contrast, the corresponding amine (1-aminopyrene) elicited only minor apoptotic and necrotic cell death, and cells with characteristics typical of paraptosis were absent.« less

The mitochondrial transporter ABC-me (ABCB10), a downstream target of GATA-1, is essential for erythropoiesis in vivo

PubMed Central

Hyde, B B; Liesa, M; Elorza, A A; Qiu, W; Haigh, S E; Richey, L; Mikkola, H K; Schlaeger, T M; Shirihai, O S

2012-01-01

The mitochondrial transporter ATP binding cassette mitochondrial erythroid (ABC-me/ABCB10) is highly induced during erythroid differentiation by GATA-1 and its overexpression increases hemoglobin production rates in vitro. However, the role of ABC-me in erythropoiesis in vivo is unknown. Here we report for the first time that erythrocyte development in mice requires ABC-me. ABC-me−/− mice die at day 12.5 of gestation, showing nearly complete eradication of primitive erythropoiesis and lack of hemoglobinized cells at day 10.5. ABC-me−/− erythroid cells fail to differentiate because they exhibit a marked increase in apoptosis, both in vivo and ex vivo. Erythroid precursors are particularly sensitive to oxidative stress and ABC-me in the heart and its yeast ortholog multidrug resistance-like 1 have been shown to protect against oxidative stress. Thus, we hypothesized that increased apoptosis in ABC-me−/− erythroid precursors was caused by oxidative stress. Within this context, ABC-me deletion causes an increase in mitochondrial superoxide production and protein carbonylation in erythroid precursors. Furthermore, treatment of ABC-me−/− erythroid progenitors with the mitochondrial antioxidant MnTBAP (superoxide dismutase 2 mimetic) supports survival, ex vivo differentiation and increased hemoglobin production. Altogether, our findings demonstrate that ABC-me is essential for erythropoiesis in vivo. PMID:22240895

Cytochrome P450 1B1 contributes to angiotensin II-induced hypertension and associated pathophysiology.

PubMed

Jennings, Brett L; Sahan-Firat, Seyhan; Estes, Anne M; Das, Kanak; Farjana, Nasreen; Fang, Xiao R; Gonzalez, Frank J; Malik, Kafait U

2010-10-01

Hypertension is the leading cause of cardiovascular diseases, and angiotensin II is one of the major components of the mechanisms that contribute to the development of hypertension. However, the precise mechanisms for the development of hypertension are unknown. Our recent study showing that angiotensin II-induced vascular smooth muscle cell growth depends on cytochrome P450 1B1 led us to investigate its contribution to hypertension caused by this peptide. Angiotensin II was infused via miniosmotic pump into rats (150 ng/kg per minute) or mice (1000 μg/kg per day) for 13 days resulting in increased blood pressure, increased cardiac and vascular hypertrophy, increased vascular reactivity to vasoconstrictor agents, increased vascular reactive oxygen species production, and endothelial dysfunction in both species. The increase in blood pressure and associated pathophysiological changes were minimized by the cytochrome P450 1B1 inhibitor 2,3',4,5'-tetramethoxystilbene in both species and was markedly reduced in Cyp1b1(-/-) mice. These data suggest that cytochrome P450 1B1 contributes to angiotensin II-induced hypertension and associated pathophysiological changes. Moreover, 2,3',4,5'-tetramethoxystilbene, which prevents both cytochrome P450 1B1-dependent and -independent components of angiotensin II-induced hypertension and inhibits associated pathophysiological changes could be clinically useful in the treatment of hypertension and associated cardiovascular and inflammatory diseases.

CYTOCHROME P450 1B1 CONTRIBUTES TO ANGIOTENSIN II-INDUCED HYPERTENSION AND ASSOCIATED PATHOPHYSIOLOGY

PubMed Central

Jennings, Brett L.; Sahan-Firat, Seyhan; Estes, Anne M.; Das, Kanak; Farjana, Nasreen; Fang, Xiao R.; Gonzalez, Frank J.; Malik, Kafait U.

2010-01-01

Hypertension is the leading cause of cardiovascular diseases, and angiotensin II is one of the major components of the mechanisms that contribute to the development of hypertension. However, the precise mechanisms for the development of hypertension are unknown. Our recent study that angiotensin II-induced vascular smooth muscle cell growth is dependent on cytochrome P450 1B1 led us to investigate its contribution to hypertension caused by this peptide. Angiotensin II was infused via miniosmotic pump into rats (150 ng/kg/min) or mice (1000 μg/kg/day) for 13 days resulting in increased blood pressure, increased cardiac and vascular hypertrophy, increased vascular reactivity to vasoconstrictor agents, increased reactive oxygen species production, and endothelial dysfunction in both species. The increase in blood pressure and associated pathophysiological changes were minimized by the cytochrome P450 1B1 inhibitor, 2,3′,4,5′-tetramethoxystilbene in both species and was markedly reduced in Cyp1b1-/- mice. These data suggest that cytochrome P450 1B1 contributes to angiotensin II-induced hypertension and associated pathophysiological changes. Moreover, 2,3′,4,5′-tetramethoxystilbene which prevents both cytochrome P450 1B1-dependent and independent components of angiotensin II-induced hypertension and inhibits associated pathophysiological changes could be clinically useful in the treatment of hypertension and associated cardiovascular and inflammatory diseases. PMID:20805442

Need For Long-Term Care in Children is Increasingly Caused by Disorders of Psychological Development. Changes in the Care Causing Diagnoses According to German Social Code (SGB XI) Between 2009-2014.

PubMed

Beck-Ripp, Julia Christiane; Dressel, Holger

2018-05-22

There is an ongoing discussion on the increasing number of children with mental and developmental disorders, with some even needing long-term care according to the German Social Code XI. This study was performed to identify the main diagnoses justifying such care in children and to analyse their prevalence over time. The diagnoses justifying long-term care were evaluated using care assessments of Bavarian children and adolescents between 2009 to 2014 by the medical service of statutory health insurance. Over the years investigated, the percentage of assessments due to a mental and behavioural disorder rose significantly from 36.2 to 42.2%. Since 2012, the most common diagnose changed from Down's syndrome to pervasive developmental disorders with marked increase of also mixed specific developmental disorders. In new applications for nursing insurance services the proportion of pervasive developmental disorders rose gradually from 151 in 2010 to 254 in 2014. During the whole period of time, the overall care dependency in children seemed to be stable. These observations might rather be influenced by altered awareness of health and illness, increasing readiness to seek help with psychological or developmental impairments as well as changed diagnostic criteria than by a steady increase in affected individuals. © Georg Thieme Verlag KG Stuttgart · New York.

Telephone-Directory Program

NASA Technical Reports Server (NTRS)

Vlahos, William

2005-01-01

eDirectory is a computer program that makes it possible to view entries in the Jet Propulsion Laboratory (JPL) telephone directory by use of PalmPilot(TradeMark) (or equivalent) personal digital assistants. When one uses eDirectory, a single click causes the downloading of a current copy of the directory (which is updated nightly) from a server. The downloaded directory data can be sorted and searched. The program can append a "JPL" category and save directory information in a file that can be imported into the Palm Desktop(TradeMark) software.

Late Holocene vegetation and fire dynamics from a savanna-forest ecotone in Roraima state, northern Brazilian Amazon

NASA Astrophysics Data System (ADS)

da Silva Meneses, Maria Ecilene Nunes; da Costa, Marcondes Lima; Behling, Hermann

2013-03-01

Two sediment cores from Mauritia flexuosa palm swamps have been studied by pollen and charcoal analysis. The cores Fazenda Cigana (FC) and Terra Indígena Aningal (TIA) were taken from a savanna-forest ecotone area in the Roraima State, northern Brazilian Amazon. Based on 5 radiocarbon dates, these records allow the reconstruction of the vegetation fire and climate dynamics during the past 1550 years. At the FC site was recorded a higher proportion of forest cover, suggesting local wetter climatic conditions favorable for forest expansion, especially by gallery forests, between 1550 and 1400 cal yr BP. Stands of M. flexuosa started to establish on the site indicating sufficient soil moisture. From 1400 to 1050 cal yr BP, forest cover retreated while savanna, and the Mauritia palm swamp expanded considerably. The FC site was marked by savanna and Mauritia cover with a slight increase of forest between ca. 1050 and 900 cal yr BP. From 900 to 300 cal yr BP the savanna and palm swamp taxa became dominant and the forest area decreased. At the TIA site the savanna cover was dominant between 1200 and 1000 cal yr BP. From 1000 to 700 forest expanded while savanna and Mauritia palm swamp reduced. Between 700 and 300 cal yr BP savanna and Mauritia palm swamp increased and forest area decreased. The high amount of charred particles found in the sediments, indicate fires with a marked increase between 1400 to 1000 cal yr BP (FC site) and 700 to 300 cal yr BP (TIA site), and probably caused the retreat of forest cover during these two time intervals. The relatively lower fire activity after 300 cal yr BP until present-day favored the increase of forested area at both TIA and FC sites. The arrival of the European settler and the subsequent introduction of cattle, is suggested as the main reason for the decrease of fire in the study region. The results point the fire caused by indigenous people as the principal controlling factor for forest and savanna dynamics during the past 1550 years.

Contribution of mast cells to the oedema induced by Bothrops moojeni snake venom and a pharmacological assessment of the inflammatory mediators involved.

PubMed

Galvão Nascimento, Neide; Sampaio, Marlos Cortez; Amaral Olivo, Renata; Teixeira, Catarina

2010-01-01

The ability of Bothrops moojeni venom (BmV) to induce oedema in mice, the involvement of principal inflammatory mediators and mast cells (MCs) were investigated. The intraplantar injection of BmV (0.3-6 microg/paw) caused a dose- and time-dependent oedema with a peak between 30 and 60 min after venom injection (0.3-1 microg/paw), disappearing within 24h. Either MCs granule inhibition or depletion by cromoglycate or C48/80, respectively, markedly reduced BmV-induced oedema. MCs depletion by imatinib also reduced oedema. Intraperitoneal BmV injection (2.5-10 microg/site) induced MCs degranulation and release of PGD(2). Treatment with promethazine, cimetidine or thioperamide, histamine H1, H2 and H3/H4 receptor antagonists, respectively, markedly reduced the initial phase of oedema. Combined treatment with these antagonists further reduced, but not abrogated oedema. Indomethacin or eterocoxib (cyclooxygenase inhibitors) reduced oedema until 180 min, whereas zileuton (lipoxygenase inhibitor) affected this event until 60 min. Dexamethazone caused a long lasting reduction of oedema. However, L-NAME and aminoguanidine (NO synthase inhibitors) significantly increased BmV-induced oedema. In conclusion, BmV induces oedema, mediated by MCs degranulation, histamine by H1, H2, H3/H4 receptors, prostaglandins and leukotrienes, and down-regulated by NO. Partial neutralization of oedema was observed even when polyspecific bothropic antivenom was injected immediately after venom. Copyright 2009 Elsevier Ltd. All rights reserved.

Inhibition of sickle red cell adhesion and vasoocclusion in the microcirculation by antioxidants.

PubMed

Kaul, Dhananjay K; Liu, Xiao-du; Zhang, Xiaoqin; Ma, Li; Hsia, Carleton J C; Nagel, Ronald L

2006-07-01

In sickle cell anemia (SCA), inflammatory (i.e., intravascular sickling and transient vasoocclusive) events result in chronic endothelial activation. In addition to sickling behavior, sickle (SS) red blood cells exhibit abnormal interaction with the vascular endothelium, which is considered to have an important role in initiation of vasoocclusion. Upregulation of endothelial adhesion molecules caused by oxidants (and cytokines) may lead to increased SS red cell adhesion. We hypothesize that endothelial activation is indispensable in SS red cell adhesion to the endothelium and that antioxidants will have an inhibitory effect on this interaction. We examined the effect of selected antioxidants in ex vivo mesocecum vasculature, a well-established model that allows measurement of hemodynamic parameters and, by intravital microscopy, can allow quantification of adhesion. We tested antioxidant enzymes (SOD and catalase) and an intravascular SOD mimetic, polynitroxyl albumin (PNA), in the presence of platelet-activating factor (PAF); the latter causes endothelial oxidant generation and endothelial activation, which characterize SCA. In ex vivo preparations, PAF not only induced marked endothelial oxidant generation, it also enhanced SS red cell adhesion, resulting in frequent blockage of small-diameter venules. The adhesion, inversely related to venular diameter, and vasoocclusion were markedly inhibited by antioxidants, resulting in improved hemodynamics. PNA, the most effective antioxidant, also abolished SS red cell adhesion in non-PAF-activated preparations. Thus SS red cell adhesion and related vasoocclusion may be ameliorated by antioxidant therapy with a stable and long-acting molecule (e.g., PNA).

Pancreatic abscess caused by Corynebacterium coyleae mimicking malignant neoplasm.

PubMed

Taguchi, Masashi; Nishikawa, Shoichiro; Matsuoka, Hidehiko; Narita, Ryoichi; Abe, Shintaro; Fukuda, Kazumasa; Miyamoto, Hiroshi; Taniguchi, Hatsumi; Otsuki, Makoto

2006-11-01

A 50-year-old female was referred to our hospital because of postprandial epigastric pain and pancreatic head mass. On admission, an elastic hard mass with tenderness was palpable in the epigastric region. Laboratory findings showed no abnormalities, except for a slightly elevated C-reactive protein value and iron deficiency anemia. Serum levels of pancreatic enzymes and tumor markers were also within the reference range. Computed tomography (CT) demonstrated a 5-cm heterogenous mass at the head of the pancreas. Angiography showed that gastroduodenal artery was transformed and narrowed by the mass. Smooth stenosis of portal vein was also observed. Fusion CT-positron emission tomography with 2-deoxy-2-[F]fluoro-D-glucose demonstrated a focus of increased uptake in the pancreatic head mass. We suspected the mass of malignancy but, surprisingly, tumor size was gradually decreased without any therapies. Biopsy specimens from the mass of the pancreas showed marked inflammatory cell infiltration and marked interstitial fibrosis without malignant cells. Thereafter, we could isolate Corynebacterium coyleae from the biopsy specimen. We diagnosed the mass as a pancreatic abscess caused by C. coyleae and started with the intravenous antibiotics therapy. Subsequent follow-up CT and ultrasonography showed dramatic improvement in pancreatic mass. We present here a case of pancreatic abscess which was difficult to differentiate from malignant lesion by various imaging studies. Moreover, we could culture and identify C. coyleae which had never been reported to be the source of pancreatic abscess.

Effect of pregnancy on periodontal and dental health.

PubMed

Laine, Merja Anneli

2002-10-01

Clinical studies have shown that oral tissues can be affected by pregnancy. Pregnancy-related changes are most frequent and most marked in gingival tissue. Pregnancy does not cause gingivitis, but may aggravate pre-existing disease. The most marked changes are seen in gingival vasculature. Characteristic of pregnancy gingivitis is that the gingiva is dark red, swollen, smooth and bleeds easily. Women with pregnancy gingivitis may sometimes develop localized gingival enlargements. The gingival changes usually resolve within a few months of delivery if local irritants are eliminated. The inflammatory changes are usually restricted to the gingiva and probably do not cause permanent changes in periodontal tissues more often than those in the non-pregnant state. Although it is widely believed that pregnancy is harmful to the teeth, the effect of pregnancy on the initiation or progression of caries is not clear. Previous studies, however, indicate that the teeth do not soften, i.e. no significant withdrawal of calcium or other minerals occurs in the teeth. It is mainly the environment of the tooth that is affected. The number of certain salivary cariogenic microorganisms may increase in pregnancy, concurrently with a decrease in salivary pH and buffer effect. Changes in salivary composition in late pregnancy and during lactation may temporarily predispose to dental caries and erosion. Although their underlying mechanisms of action are not fully understood, pregnancy-related changes in the oral environment may have some untoward temporary or permanent effects on oral health. Most of these effects could be avoided by practising good oral hygiene.

Contribution of methylglyoxal to delayed healing of bone injury in diabetes.

PubMed

Aikawa, Takao; Matsubara, Hidenori; Ugaji, Shuhei; Shirakawa, Junichi; Nagai, Ryoji; Munesue, Seiichi; Harashima, Ai; Yamamoto, Yasuhiko; Tsuchiya, Hiroyuki

2017-07-01

Patients with diabetes are vulnerable to delayed bone fracture healing or pseudoarthrosis. Chronic sustained hyperglycemia, reactive intermediate derivatives of glucose metabolism, such as methylglyoxal (MGO), and advanced glycation end‑products (AGEs) are implicated in diabetic complications. In the present study, it was examined whether MGO is able to cause disturbed bone healing in diabetes. Diabetes was induced in male mice by injection of streptozotocin (50 mg/kg) for 5 days. A bone defect (1.0‑mm diameter) was created in the left distal femur, and bone repair was assessed from an examination of computed tomography scans. ST2 cells were exposed to MGO (0‑400 µM) to investigate osteoblastic differentiation, cell viability, and damage. Consequently, blood glucose and hemoglobin A1c levels in diabetic mice were determined to be 493±14.1 mg/dl and 8.0±0.05%, respectively. Compared with non‑diabetic control mice, diabetic mice exhibited markedly delayed bone healing, with increased levels of the MGO‑derived AGEs, Nε‑(carboxymethyl)‑lysine and Nδ‑(5‑hydro‑5‑methyl‑4‑imidazolone‑2‑yl)‑ornithine, in the sera and femurs. MGO inhibited the osteoblastic differentiation of ST2 cells in a dose‑dependent manner, and markedly decreased cell proliferation through cytotoxicity. In conclusion, MGO has been demonstrated to cause impaired osteoblastic differentiation and delayed bone repair in diabetes. Therefore, detoxification of MGO may be a potentially useful strategy against bone problems in patients with diabetes.

Protein kinase cα regulates the expression of complement receptor Ig in human monocyte-derived macrophages.

PubMed

Ma, Yuefang; Usuwanthim, Kanchana; Munawara, Usma; Quach, Alex; Gorgani, Nick N; Abbott, Catherine A; Hii, Charles S; Ferrante, Antonio

2015-03-15

The complement receptor Ig (CRIg) is selectively expressed by macrophages. This receptor not only promotes the rapid phagocytosis of bacteria by macrophages but also has anti-inflammatory and immunosuppressive functions. Previous findings have suggested that protein kinase C (PKC) may be involved in the regulation of CRIg expression in human macrophages. We have now examined the role of PKCα in CRIg expression in human monocyte-derived macrophages (MDM). Macrophages nucleofected with plasmid containing short hairpin RNA against PKCα showed markedly reduced expression of PKCα, but normal PKCζ expression, by Western blotting analysis, and vice versa. PKCα-deficient MDM showed increased expression of CRIg mRNA and protein (both the long and short form), an increase in phagocytosis of complement-opsonized Candida albicans, and decreased production of TNF-α and IL-6. TNF-α caused a marked decrease in CRIg expression, and addition of anti-TNF mAb to the TNF-α-producing MDMs increased CRIg expression. PKCα-deficient macrophages also showed significantly less bacterial LPS-induced downregulation of CRIg. In contrast, cells deficient in PKCα showed decreased expression of CR type 3 (CR3) and decreased production of TNF-α and IL-6 in response to LPS. MDM developed under conditions that increased expression of CRIg over CR3 showed significantly reduced production of TNF-α in response to opsonized C. albicans. The findings indicate that PKCα promotes the downregulation of CRIg and upregulation of CR3 expression and TNF-α and IL-6 production, a mechanism that may promote inflammation. Copyright © 2015 by The American Association of Immunologists, Inc.

Chemoprevention studies of the flavonoids quercetin and rutin in normal and azoxymethane-treated mouse colon.

PubMed

Yang, K; Lamprecht, S A; Liu, Y; Shinozaki, H; Fan, K; Leung, D; Newmark, H; Steele, V E; Kelloff, G J; Lipkin, M

2000-09-01

In this study we investigated the chemopreventive effects of quercetin and rutin when added to standard AIN-76A diet and fed to normal and azoxymethane (AOM)-treated mice. Early changes in colonic mucosa were analyzed, including colonic cell proliferation, apoptotic cell death, cyclin D(1) expression and focal areas of dysplasia (FAD). The findings show that the number of colonic epithelial cells per crypt column increased (P: < 0.01) in each normal mouse group fed the flavonoids; AOM administration increased colonic crypt cell proliferation and resulted in a marked rise of bromodeoxyuridine-labeled cells in the lower proliferative zone of the crypt. Both supplementary dietary quercetin and rutin increased the apoptotic index and caused a redistribution of apoptotic cells along the crypt axis in normal mice fed a standard AIN-76A diet. The number of apoptotic cells/column and apoptotic indices markedly increased (P: < 0.01) in the AOM-treated group compared with untreated animals; apoptotic cells expanded throughout the colonic crypts after flavonoid supplementation and AOM administration. Positive cyclin D(1) expression was detected in mice on diets supplemented either with quercetin (P: < 0.01) or rutin (P: < 0.05). AOM administration resulted in the formation of FAD. Both the number of mice exhibiting FAD and the total numer of FAD observed were significantly reduced (P: < 0.01) in AOM-treated animals fed flavonoids compared with mice maintained on the standard AIN-76A diet. Surprisingly, however, quercetin alone was able to induce FAD in 22% of normal mice fed the standard AIN-76A diet.

Ecological intensification of cereal production systems: yield potential, soil quality, and precision agriculture.

PubMed

Cassman, K G

1999-05-25

Wheat (Triticum aestivum L.), rice (Oryza sativa L.), and maize (Zea mays L.) provide about two-thirds of all energy in human diets, and four major cropping systems in which these cereals are grown represent the foundation of human food supply. Yield per unit time and land has increased markedly during the past 30 years in these systems, a result of intensified crop management involving improved germplasm, greater inputs of fertilizer, production of two or more crops per year on the same piece of land, and irrigation. Meeting future food demand while minimizing expansion of cultivated area primarily will depend on continued intensification of these same four systems. The manner in which further intensification is achieved, however, will differ markedly from the past because the exploitable gap between average farm yields and genetic yield potential is closing. At present, the rate of increase in yield potential is much less than the expected increase in demand. Hence, average farm yields must reach 70-80% of the yield potential ceiling within 30 years in each of these major cereal systems. Achieving consistent production at these high levels without causing environmental damage requires improvements in soil quality and precise management of all production factors in time and space. The scope of the scientific challenge related to these objectives is discussed. It is concluded that major scientific breakthroughs must occur in basic plant physiology, ecophysiology, agroecology, and soil science to achieve the ecological intensification that is needed to meet the expected increase in food demand.

Distension of the uterus induces HspB1 expression in rat uterine smooth muscle.

PubMed

White, B G; MacPhee, D J

2011-11-01

The uterine musculature, or myometrium, demonstrates tremendous plasticity during pregnancy under the influences of the endocrine environment and mechanical stresses. Expression of the small stress protein heat shock protein B1 (HspB1) has been reported to increase dramatically during late pregnancy, a period marked by myometrial hypertrophy caused by fetal growth-induced uterine distension. Thus, using unilaterally pregnant rat models and ovariectomized nonpregnant rats with uteri containing laminaria tents to induce uterine distension, we examined the effect of uterine distension on myometrial HspB1 expression. In unilaterally pregnant rats, HspB1 mRNA and Ser(15)-phosphorylated HspB1 (pSer(15) HspB1) protein expression were significantly elevated in distended gravid uterine horns at days 19 and 23 (labor) of gestation compared with nongravid horns. Similarly, pSer(15) HspB1 protein in situ was only readily detectable in the distended horns compared with the nongravid horns at days 19 and 23; however, pSer(15) HspB1 was primarily detectable in situ at day 19 in membrane-associated regions, while it had primarily a cytoplasmic localization in myometrial cells at day 23. HspB1 mRNA and pSer(15) HspB1 protein expression were also markedly increased in ovariectomized nonpregnant rat myometrium distended for 24 h with laminaria tents compared with empty horns. Therefore, uterine distension plays a major role in the stimulation of myometrial HspB1 expression, and increased expression of this small stress protein could be a mechanoadaptive response to the increasing uterine distension that occurs during pregnancy.

11β-Hydoxylase Inhibitors Protect Against Seizures in Mice by Increasing Endogenous Neurosteroid Synthesis

PubMed Central

Kaminski, Rafal M.; Rogawski, Michael A.

2011-01-01

Steroid 11β-hydroxylase (CYP11B1; EC 1.14.15.4) is a mitochondrial enzyme located in the zona fasciculata of the adrenal cortex and also in the brain that mediates the conversion of 11-deoxycortisol to cortisol and 11-deoxycorticosterone (DOC) to corticosterone. Inhibitors of CYP11B1, such as metyrapone and etomidate, reduce glucocorticoid synthesis and raise levels of DOC providing greater availability for metabolic conversion to the GABAA receptor modulating neurosteroid allotetrahydrodeoxycorticosterone (THDOC). Because THDOC is a potent anticonvulsant, it is plausible that CYP11B1 inhibitors could protect against seizures. Here we demonstrate that metyrapone affords dose-dependent protection against 6-Hz seizures 30 min after injection (ED50, 191 mg/kg), but is markedly more potent at 6 h (ED50, 30 mg/kg). Similarly, etomidate is also protective at 30 min and 6 h (ED50 values, 4.5 and 1.7 mg/kg). Finasteride, an inhibitor of neurosteroid synthesis, attenuated the anticonvulsant effects of both CYP11B1 inhibitors at 6 h, but not 30 min following their injection. Plasma THDOC levels measured by liquid chromatography-mass spectrometry were markedly increased 6 h after injection of both CYP11B1 inhibitors and this increase was attenuated by finasteride pretreatment. We conclude that inhibition of CYP11B1 causes delayed seizure protection due to slow build-up of neurosteroids. Early seizure protection is independent of neurosteroids. PMID:21458468

Dynamics of L-Carnitine in Plasma and Urine in Patients Undergoing Cisplatin Chemotherapy.

PubMed

Gomi, Daisuke; Tanaka, Aika; Fukushima, Toshirou; Kobayashi, Takashi; Matsushita, Hirohide; Sekiguchi, Nodoka; Sakamoto, Akiyuki; Sasaki, Shigeru; Mamiya, Keiko; Koizumi, Tomonobu

2017-01-01

Several studies have indicated that cisplatin (cis-diamminedichloroplatinum II; CDDP) causes urinary excretion of L-carnitine (LC). However, the underlying cofactors affecting the increased urinary excretion remain unclear. The present study was performed to evaluate the dynamics of LC in plasma and urine after CDDP chemotherapy and to examine the relations with clinical parameters, such as gender, body mass index (BMI), and renal function. Twenty-two patients treated with CDDP therapy were selected. Blood and urine samples were taken from patients before starting CDDP treatment (day 0), on the next day (day 1), and on the seventh day (day 7). We measured plasma and urine concentrations of total, free, and acyl-LC, and examined the relationships with gender, age, treatment cycle, skeletal muscle mass, BMI, glomerular filtration rate, and change in creatinine concentration after CDDP administration. Both urinary and plasma concentrations of 3 types of LC increased markedly on day 1 and subsequently reverted to the pre-CDDP level on day 7. There was a positive correlation between the % changes in plasma and urine LC (correlation coefficient 0.59, p = 0.003) on day 1, but no significant relations were seen in other clinical parameters. CDDP transiently increased plasma LC levels. The mechanism seemed to involve recruitment for marked urinary loss of LC. However, these changes in plasma and urinary LC levels were not related to clinical factors, suggesting that the dynamics of LC were independent of preexisting physical parameters. © 2017 S. Karger AG, Basel.

Two routes to expertise in mental rotation.

PubMed

Provost, Alexander; Johnson, Blake; Karayanidis, Frini; Brown, Scott D; Heathcote, Andrew

2013-01-01

The ability to imagine objects undergoing rotation (mental rotation) improves markedly with practice, but an explanation of this plasticity remains controversial. Some researchers propose that practice speeds up the rate of a general-purpose rotation algorithm. Others maintain that performance improvements arise through the adoption of a new cognitive strategy-repeated exposure leads to rapid retrieval from memory of the required response to familiar mental rotation stimuli. In two experiments we provide support for an integrated explanation of practice effects in mental rotation by combining behavioral and EEG measures in a way that provides more rigorous inference than is available from either measure alone. Before practice, participants displayed two well-established signatures of mental rotation: Both response time and EEG negativity increased linearly with rotation angle. After extensive practice with a small set of stimuli, both signatures of mental rotation had all but disappeared. In contrast, after the same amount of practice with a much larger set both signatures remained, even though performance improved markedly. Taken together, these results constitute a reversed association, which cannot arise from variation in a single cause, and so they provide compelling evidence for the existence of two routes to expertise in mental rotation. We also found novel evidence that practice with the large but not the small stimulus set increased the magnitude of an early visual evoked potential, suggesting increased rotation speed is enabled by improved efficiency in extracting three-dimensional information from two-dimensional stimuli. © 2013 Cognitive Science Society, Inc.

Onion and garlic extracts as potential antidotes for cadmium-induced biochemical alterations in prostate glands of rats.

PubMed

Ola-Mudathir, F K; Suru, S M

2015-11-01

Cadmium (Cd) has been implicated in increased prostate gland malignancy risk in both wildlife and humans. This study examines the chemoprotective roles of onion and garlic extracts on Cd-induced biochemical alterations in the prostate glands of rats. Adult male Wistar rats were randomly divided into nine groups: control group received double distilled water; Cd group received Cd alone (1.5 mg/100 g bwt per day); extract-treated groups were pre-treated with varied doses of onion and/or garlic extract (0.5 ml and 1.0 ml/100 g bwt per day) for 1 week and then co-treated with Cd (1.5 mg/100 g bwt per day) for additional 3 weeks. Oxidant/antioxidant status and acid phosphatase (ACPtotal and ACPprostatic ) activity were examined in prostate glands. Cd intoxication caused a marked (P < 0.001) increase in lipid peroxidation (LPO) and glutathione S-transferase (GST) levels, whereas glutathione (GSH), superoxide dismutase and catalase levels were markedly (P < 0.001) decreased. We also observed significant (P < 0.001) decrease in ACPtotal and ACPprostatic activities in prostate glands and a concomitant significant (P < 0.001) increase in the plasma. However, treatment of Cd-intoxicated rats with onion and/or garlic extract significantly minimised these alterations. The onion extract offered a dose-dependent protection. Our findings suggest a chemoprotective capability for onion and garlic extracts against Cd-induced biochemical alteration in the prostate glands. © 2014 Blackwell Verlag GmbH.

Pseudohypoparathyroidism: defective excretion of 3′,5′-AMP in response to parathyroid hormone

PubMed Central

Chase, Lewis R.; Melson, G. Leland; Aurbach, G. D.

1969-01-01

Urinary excretion of cyclic adenosine 3′,5′-monophosphate (3′,5′-AMP) was tested in normal subjects and patients with pseudohypoparathyroidism, idiopathic hypoparathyroidism, surgical hypoparathyroidism, and pseudopseudohypoparathyroidism under basal conditions and after a 15 min infusion of purified parathyroid hormone. Basal excretion of the nucleotide was less than normal in the patients with hypocalcemic disorders and greater than normal in pseudopseudohypoparathyroidism. Parathyroid hormone caused a marked increase in excretion of 3′,5′-AMP in all subjects except those with pseudohypoparathyroidism; nine patients with this disorder did not respond to the hormone and four showed a markedly deficient response. Radioimmunoassay showed that parathyroid hormone circulated in increased amounts in plasma from patients with pseudohypoparathyroidism and became undetectable when serum calcium was increased above 12 mg/100 ml. Suppression of parathyroid hormone secretion by induction of hypercalcemia did not alter the deficient response to exogenous hormone. The results indicate that: (a) parathyroid hormone circulates in abnormally high concentrations in pseudohypoparathyroidism and secretion of the hormone responds normally to physiological control by calcium; (b) testing urinary excretion of 3′,5′-AMP in response to infusion of purified parathyroid hormone appears to be an accurate and sensitive index for establishing the diagnosis of pseudohypoparathyroidism; and (c) the metabolic defect of the disorder can be accounted for by a lack of or defective form of parathyroid hormone-sensitive adenyl cyclase in bone and kidney. PMID:4309802

Congenital gigantism due to growth hormone-releasing hormone excess and pituitary hyperplasia with adenomatous transformation.

PubMed

Zimmerman, D; Young, W F; Ebersold, M J; Scheithauer, B W; Kovacs, K; Horvath, E; Whitaker, M D; Eberhardt, N L; Downs, T R; Frohman, L A

1993-01-01

The cause of gigantism in most patients is a GH-secreting pituitary tumor. In this report, a case of congenital gigantism due to probable central hypersection of GH-releasing hormone (GHRH) is described. Normal at birth (4.4 kg; 53 cm), our 7-yr-old male patient grew progressively thereafter to attain a height of 182 cm and a weight of 99.4 kg at the time of our evaluation. The markedly increased baseline plasma levels of GH (730 micrograms/L) did not suppress during a standard 3-h oral glucose tolerance test, but did increase 54% after iv infusion of GHRH. Baseline plasma levels of insulin-like growth factor-I, PRL, and immunoreactive GHRH were also markedly increased. Computed imaging of the head showed a large, partially cystic sellar and suprasellar mass. Extensive imaging studies did not localize a potential source of GHRH. Preoperative treatment with octreotide and bromocriptine for 4 months resulted in a 25% reduction of suprasellar tissue mass. The pituitary tissue removed at transsphenoidal and transfrontal operations showed massive somatotroph, lactotroph, and mammosomatotroph hyperplasia. Areas of GH- and PRL-secreting cell adenomatous transformation were also evident. No histological or immunohistochemical evidence of a pituitary source of GHRH was found. The peripheral plasma immunoreactive GHRH concentration remained unaffected by pharmacological and surgical interventions. We suspect that a congenital hypothalamic regulatory defect may be responsible for the GHRH excess in this case.

Implications of chronic wasting disease, cougar predation, and reduced recruitment for elk management

USGS Publications Warehouse

Sargeant, G.A.; Weber, D.C.; Roddy, D.E.

2011-01-01

Emerging diseases and expanding carnivore populations may have profound implications for ungulate harvest management and population regulation. To better understand effects of chronic wasting disease (CWD) and cougar (Puma concolor) predation, we studied mortality and recruitment of elk (Cervus elaphus) at Wind Cave National Park (WICA) during 2005-2009. We marked 202 elk (83 subadult M and 119 subadult and ad F) with Global Positioning System (GPS) collars, observed 28 deaths during 74,220 days of monitoring, and investigated 42 additional deaths of unmarked elk found dead. Survival rates were similar for males and females and averaged 0.863 (SE = 0.025) annually. Leading causes of mortality included hunting (0.065, SE = 0.019), CWD (0.034, SE = 0.012), and cougar predation (0.029, SE = 0.012). Marked elk killed by hunters and cougars typically were in good physical condition and not infected with CWD. Effects of mortality on population growth were exacerbated by low rates of pregnancy (subadults = 9.5%, SE = 6.6%; ad = 76.9%, SE = 4.2%) and perinatal survival (0.49, SE = 0.085 from 1 Feb to 1 Sep). Chronic wasting disease, increased predation, and reduced recruitment reduced the rate of increase for elk at WICA to approximately ?? = 1.00 (SE = 0.027) during the past decade. Lower rates of increase are mitigating effects of elk on park vegetation, other wildlife, and neighboring lands and will facilitate population control, but may reduce opportunities for elk hunting outside the park. ?? 2011 The Wildlife Society.

Release of Rhizobium spp. from Tropical Soils and Recovery for Immunofluorescence Enumeration

PubMed Central

Kingsley, Mark T.; Bohlool, B. Ben

1981-01-01

Limitations associated with immunofluorescence enumeration of bacteria in soil derive largely from the efficiency with which cells can be separated from soil particles and collected on membrane filters for staining. Many tropical soils fix added bacteria tightly, resulting in low recoveries. Eight soils, representative of three of the major soil orders found in the tropics (oxisols, vertisols, and inceptisols), were tested for recovery of added Rhizobium strains. All except one Hawaiian andept (Typic Eutrandept) yielded recoveries ranging from <1 to 13%. Recovery from the andept was 100%. In soil-sand mixtures, addition of only a small amount of soil caused a dramatic decrease in recovery of added rhizobia. Increasing the soil content of the mixture from 0% (10 g of sand) to 50% (5 g of soil-5 g of sand) reduced recoveries from >90 to <1%. Varying the ionic strength and pH of the extracting solution did not cause marked increases in recovery. Protein solutions, ethylenediaminetetraacetate, and NaHCO3, on the other hand, improved release of bacteria. We report a modification to the usual membrane filter immunofluorescence procedure which yielded consistently high and reproducible recovery (coefficient of variation, 30%) of rhizobia from several tropical soils. In the modified procedure, partially hydrolyzed gelatin, diluted in ammonium phosphate, was used to suspend the soil. This caused dispersion of the soil and release of the bacteria from soil flocs. The efficiency of recovery of Rhizobium spp. from several tropical and two temperate soils remained high as the content of these soils in soil-sand mixtures was increased from 0 to 100%. The modified membrane filter immunofluorescence procedure was used to follow the growth of a strain of chickpea (Cicer arietinum) Rhizobium in a sterilized oxisol. The results showed a close agreement with viable counts at different stages during the growth cycle. Diluent for the hydrolyzed gelatin also had a marked effect on recovery. The efficiency of release of Rhizobium spp. from an oxisol was in the following order for the diluents used: 0.1 M (NH4)2HPO4 > 0.1 M Na2HPO4 = 0.1 M sodium-phosphate-buffered saline (pH 7.2) > 0.2 M NH4Cl > 0.2 KCl > NaCl = LiCl > water. Images PMID:16345824

Release of Rhizobium spp. from Tropical Soils and Recovery for Immunofluorescence Enumeration.

PubMed

Kingsley, M T; Bohlool, B B

1981-08-01

Limitations associated with immunofluorescence enumeration of bacteria in soil derive largely from the efficiency with which cells can be separated from soil particles and collected on membrane filters for staining. Many tropical soils fix added bacteria tightly, resulting in low recoveries. Eight soils, representative of three of the major soil orders found in the tropics (oxisols, vertisols, and inceptisols), were tested for recovery of added Rhizobium strains. All except one Hawaiian andept (Typic Eutrandept) yielded recoveries ranging from <1 to 13%. Recovery from the andept was 100%. In soil-sand mixtures, addition of only a small amount of soil caused a dramatic decrease in recovery of added rhizobia. Increasing the soil content of the mixture from 0% (10 g of sand) to 50% (5 g of soil-5 g of sand) reduced recoveries from >90 to <1%. Varying the ionic strength and pH of the extracting solution did not cause marked increases in recovery. Protein solutions, ethylenediaminetetraacetate, and NaHCO(3), on the other hand, improved release of bacteria. We report a modification to the usual membrane filter immunofluorescence procedure which yielded consistently high and reproducible recovery (coefficient of variation, 30%) of rhizobia from several tropical soils. In the modified procedure, partially hydrolyzed gelatin, diluted in ammonium phosphate, was used to suspend the soil. This caused dispersion of the soil and release of the bacteria from soil flocs. The efficiency of recovery of Rhizobium spp. from several tropical and two temperate soils remained high as the content of these soils in soil-sand mixtures was increased from 0 to 100%. The modified membrane filter immunofluorescence procedure was used to follow the growth of a strain of chickpea (Cicer arietinum) Rhizobium in a sterilized oxisol. The results showed a close agreement with viable counts at different stages during the growth cycle. Diluent for the hydrolyzed gelatin also had a marked effect on recovery. The efficiency of release of Rhizobium spp. from an oxisol was in the following order for the diluents used: 0.1 M (NH(4))(2)HPO(4) > 0.1 M Na(2)HPO(4) = 0.1 M sodium-phosphate-buffered saline (pH 7.2) > 0.2 M NH(4)Cl > 0.2 KCl > NaCl = LiCl > water.

Identification of Skin Electrical Injury Using Infrared Imaging: A Possible Complementary Tool for Histological Examination

PubMed Central

Lin, Hancheng; Wang, Zhenyuan; Dong, Hongmei

2017-01-01

In forensic practice, determination of electrocution as a cause of death usually depends on the conventional histological examination of electrical mark in the body skin, but the limitation of this method includes subjective bias by different forensic pathologists, especially for identifying suspicious electrical mark. The aim of our work is to introduce Fourier transform infrared (FTIR) spectroscopy in combination with chemometrics as a complementary tool for providing an relatively objective diagnosis. The results of principle component analysis (PCA) showed that there were significant differences of protein structural profile between electrical mark and normal skin in terms of α-helix, antiparallel β-sheet and β-sheet content. Then a partial least square (PLS) model was established based on this spectral dataset and used to discriminate electrical mark from normal skin areas in independent tissue sections as revealed by color-coded digital maps, making the visualization of electrical injury more intuitively. Our pilot study demonstrates the potential of FTIR spectroscopy as a complementary tool for diagnosis of electrical mark. PMID:28118398

Image-Guided Biopsy in the Esophagus through Comprehensive Optical Frequency Domain Imaging and Laser Marking: A Study in Living Swine

PubMed Central

Suter, Melissa J.; Jillella, Priyanka A.; Vakoc, Benjamin J.; Halpern, Elkan F.; Mino-Kenudson, Mari; Lauwers, Gregory Y.; Bouma, Brett E.; Nishioka, Norman S.; Tearney, Guillermo J.

2010-01-01

Background Random biopsy esophageal surveillance can be subject to sampling errors, resulting in diagnostic uncertainty. Optical frequency domain imaging (OFDI) is a high-speed, three-dimensional endoscopic microscopy technique. When deployed through a balloon-centering catheter, OFDI can automatically image the entire distal esophagus (6.0 cm length) in approximately 2 minutes. Objective To test a new platform for guided biopsy that allows the operator to select target regions of interest on an OFDI dataset, and then use a laser to mark the esophagus at corresponding locations. The specific goals include determining the optimal laser parameters, testing the accuracy of the laser marking process, evaluating the endoscopic visibility of the laser marks, and assessing the amount of mucosal damage produced by the laser. Design Experimental study conducted in five swine in vivo. Setting Massachusetts General Hospital. Main Outcome Measurements Success rate, including endoscopic visibility of laser marks and accuracy of the laser marking process for selected target sites, and extent of the thermal damage caused by the laser marks. Results All of the laser-induced marks were visible by endoscopy. Target locations were correctly marked with a success rate of 97.07% (95% CI, 89.8%-99.7%). Thermal damage was limited to the superficial layers of the mucosa and was observed to partially heal within 2 days. Limitations An animal study with artificially placed targets to simulate pathology. Conclusions The study demonstrates that laser marking of esophageal sites identified in comprehensive OFDI datasets is feasible and can be performed with sufficient accuracy, precision, and visibility to guide biopsy in vivo. PMID:19879573

Causes of Death Data in the Global Burden of Disease Estimates for Ischemic and Hemorrhagic Stroke.

PubMed

Truelsen, Thomas; Krarup, Lars-Henrik; Iversen, Helle K; Mensah, George A; Feigin, Valery L; Sposato, Luciano A; Naghavi, Mohsen

2015-01-01

Stroke mortality estimates in the Global Burden of Disease (GBD) study are based on routine mortality statistics and redistribution of ill-defined codes that cannot be a cause of death, the so-called 'garbage codes' (GCs). This study describes the contribution of these codes to stroke mortality estimates. All available mortality data were compiled and non-specific cause codes were redistributed based on literature review and statistical methods. Ill-defined codes were redistributed to their specific cause of disease by age, sex, country and year. The reassignment was done based on the International Classification of Diseases and the pathology behind each code by checking multiple causes of death and literature review. Unspecified stroke and primary and secondary hypertension are leading contributing 'GCs' to stroke mortality estimates for hemorrhagic stroke (HS) and ischemic stroke (IS). There were marked differences in the fraction of death assigned to IS and HS for unspecified stroke and hypertension between GBD regions and between age groups. A large proportion of stroke fatalities are derived from the redistribution of 'unspecified stroke' and 'hypertension' with marked regional differences. Future advancements in stroke certification, data collections and statistical analyses may improve the estimation of the global stroke burden. © 2015 S. Karger AG, Basel.

Causes of Death Data in the Global Burden of Disease Estimates for Ischemic and Hemorrhagic Stroke

PubMed Central

Truelsen, Thomas; Krarup, Lars-Henrik; Iversen, Helle; Mensah, George A.; Feigin, Valery; Sposato, Luciano; Naghavi, Mohsen

2015-01-01

Background Stroke mortality estimates in the Global Burden of Disease (GBD) study are based on routine mortality statistics and redistribution of ill-defined codes that cannot be a cause of death, the so-called “garbage codes”. This study describes the contribution of these codes to stroke mortality estimates. Methods All available mortality data were compiled and non-specific cause codes were redistributed based on literature review and statistical methods. Ill-defined codes were redistributed to their specific cause of disease by age, sex, country, and year. The reassignment was done based on the international classification of diseases and the pathology behind each code by checking multiple causes of death and literature review. Results Unspecified stroke, and primary and secondary hypertension are leading contributing “garbage codes” to stroke mortality estimates for intracranial hemorrhagic stroke and ischemic stroke. There were marked differences in the fraction of death assigned to ischemic stroke and hemorrhagic stroke for unspecified stroke and hypertension between GBD regions and between age groups. Conclusions A large proportion of stroke fatalities is derived from the redistribution of “unspecified stroke” and “hypertension” with marked regional differences. Future advancements in stroke certification, data collections, and statistical analyses may improve the estimation of the global stroke burden. PMID:26505189

Parkinson-causing α-synuclein missense mutations shift native tetramers to monomers as a mechanism for disease initiation

PubMed Central

Dettmer, Ulf; Newman, Andrew J.; Soldner, Frank; Luth, Eric S.; Kim, Nora C.; von Saucken, Victoria E.; Sanderson, John B.; Jaenisch, Rudolf; Bartels, Tim; Selkoe, Dennis

2015-01-01

β-Sheet-rich α-synuclein (αS) aggregates characterize Parkinson's disease (PD). αS was long believed to be a natively unfolded monomer, but recent work suggests it also occurs in α-helix-rich tetramers. Crosslinking traps principally tetrameric αS in intact normal neurons, but not after cell lysis, suggesting a dynamic equilibrium. Here we show that freshly biopsied normal human brain contains abundant αS tetramers. The PD-causing mutation A53T decreases tetramers in mouse brain. Neurons derived from an A53T patient have decreased tetramers. Neurons expressing E46K do also, and adding 1-2 E46K-like mutations into the canonical αS repeat motifs (KTKEGV) further reduces tetramers, decreases αS solubility and induces neurotoxicity and round inclusions. The other three fPD missense mutations likewise decrease tetramer:monomer ratios. The destabilization of physiological tetramers by PD-causing missense mutations and the neurotoxicity and inclusions induced by markedly decreasing tetramers suggest that decreased α-helical tetramers and increased unfolded monomers initiate pathogenesis. Tetramer-stabilizing compounds should prevent this. PMID:26076669

Vitamin D and the risk of dementia and Alzheimer disease.

PubMed

Littlejohns, Thomas J; Henley, William E; Lang, Iain A; Annweiler, Cedric; Beauchet, Olivier; Chaves, Paulo H M; Fried, Linda; Kestenbaum, Bryan R; Kuller, Lewis H; Langa, Kenneth M; Lopez, Oscar L; Kos, Katarina; Soni, Maya; Llewellyn, David J

2014-09-02

To determine whether low vitamin D concentrations are associated with an increased risk of incident all-cause dementia and Alzheimer disease. One thousand six hundred fifty-eight elderly ambulatory adults free from dementia, cardiovascular disease, and stroke who participated in the US population-based Cardiovascular Health Study between 1992-1993 and 1999 were included. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected in 1992-1993. Incident all-cause dementia and Alzheimer disease status were assessed during follow-up using National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria. During a mean follow-up of 5.6 years, 171 participants developed all-cause dementia, including 102 cases of Alzheimer disease. Using Cox proportional hazards models, the multivariate adjusted hazard ratios (95% confidence interval [CI]) for incident all-cause dementia in participants who were severely 25(OH)D deficient (<25 nmol/L) and deficient (≥25 to <50 nmol/L) were 2.25 (95% CI: 1.23-4.13) and 1.53 (95% CI: 1.06-2.21) compared to participants with sufficient concentrations (≥50 nmol/L). The multivariate adjusted hazard ratios for incident Alzheimer disease in participants who were severely 25(OH)D deficient and deficient compared to participants with sufficient concentrations were 2.22 (95% CI: 1.02-4.83) and 1.69 (95% CI: 1.06-2.69). In multivariate adjusted penalized smoothing spline plots, the risk of all-cause dementia and Alzheimer disease markedly increased below a threshold of 50 nmol/L. Our results confirm that vitamin D deficiency is associated with a substantially increased risk of all-cause dementia and Alzheimer disease. This adds to the ongoing debate about the role of vitamin D in nonskeletal conditions. © 2014 American Academy of Neurology.

Trends in licit and illicit drug-related deaths in Florida from 2001 to 2012.

PubMed

Lee, Dayong; Delcher, Chris; Maldonado-Molina, Mildred M; Bazydlo, Lindsay A L; Thogmartin, Jon R; Goldberger, Bruce A

2014-12-01

Florida, the epicenter of the recent prescription drug epidemic in the United States, maintains a statewide drug mortality surveillance system. We evaluated yearly profiles, demographic characteristics, and correlation between drug trends to understand the factors influencing drug-induced mortality. All drug-related deaths reported to the Florida Medical Examiners Commission during 2001-2012 were included (n=92,596). A death was considered "drug-related" if at least one drug was identified in the decedent. Depending on its contribution to death, a drug could be listed as a causative agent or merely present, but not both. Rate of drug-caused deaths was 8.0 per 100,000 population in 2001, increasing to 17.0 in 2010 and then decreasing to 13.9 in 2012. Benzodiazepines had the highest mortality rate in 2010, although <10% were solely due these drugs. Opioid-caused mortality rate also peaked in 2010 and started to decline (-28%) in 2010-2012. The heroin-caused mortality rates were negatively correlated with opioids and benzodiazepines (ρ's ≥ -0.670; P≤0.034). Ethanol- and cocaine-mortality rates stabilized to 3.0-3.1 and 2.8-3.0 per 100,000 over 2009-2012, respectively. Amphetamines, zolpidem, and inhalants-caused deaths were on the rise with rates of ≤0.6 per 100,000. Overall declines in benzodiazepine- and opioid-caused deaths in 2011-2012 may have been related to Florida's attempts to regulate prescription drug abuse. This period, however, was also marked by a rise in heroin-caused mortality, which may reflect growing use of heroin as an alternative. Increases in amphetamines, zolpidem, and inhalants-induced mortality are an additional public health concern. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Pyloric motor response to central and peripheral nitric oxide in the ferret.

PubMed

Lingenfelser, T; Blackshaw, L A; Sun, W M; Dent, J

1997-09-01

This study has investigated the relative importance of central nervous and peripheral nitroxidergic mechanisms in the control of pyloric motility. In 10 urethane-anaesthetized ferrets, drugs were administered directly to the CNS via a 0.5-mm-diameter cannula inserted into the 4th ventricle, approximately at the obex. Drugs were also given directly to the upper GI tract by close intra-arterial (i.a.) injection at the coeliac axis. Antropyloroduodenal pressures were recorded with a five-channel sleeve/sidehole micromanometric assembly (1.35 x 1.75 mm o.d.), which was introduced via the duodenum. Pyloric motility was stimulated throughout the main part of each study with a continuous i.v. infusion of CCK-8 (30 pmol min-1). This infusion produced an immediate and sustained increase in tonic and phasic pyloric activity, and sustained abolition of antral pressure waves. CCK-8 also induced a duodenal motor response, but this was short-lived (11.4 +/- 7.9 min). Coeliac axis injection of the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) decreased phasic pyloric activity (from 330 +/- 35 to 148 +/- 21 mmHg min-1 after SNAP 5 micrograms, P < 0.01). By comparison central SNAP administration over the same dose range had no effect on CCK-stimulated pyloric motlity. Inhibition of endogenous NO synthase with L-Nitro Arginine Methyl Ester (L-NAME, 100 mg kg-1 close i.a.) caused a marked increase of phase pyloric motor activity from 349 +/- 59 to 1044 +/- 140 mmHg min-1 (P < 0.01). In addition, SNAP caused marked stimulation of pyloric tone from 2.6 +/- 0.5 to 13.1 +/- 2.8 mmHg (P < 0.01). Central nervous administration of L-NAME caused modest enhancement of phasic pyloric activity (248 +/- 31 to 283 +/- 32 mmHg min-1 P < 0.05) and pyloric tone (2.6 +/- 0.5 to 3.7 +/- 0.7 mmHg, P < 0.05). Our data indicate that motor activity of the ferret pylorus is potently modulated by NO released within the upper gut. Additionally, there is potential for modulation of pyloric motility by central nervous system production of NO.

Connective tissue growth factor stimulates the proliferation, migration and differentiation of lung fibroblasts during paraquat-induced pulmonary fibrosis.

PubMed

Yang, Zhizhou; Sun, Zhaorui; Liu, Hongmei; Ren, Yi; Shao, Danbing; Zhang, Wei; Lin, Jinfeng; Wolfram, Joy; Wang, Feng; Nie, Shinan

2015-07-01

It is well established that paraquat (PQ) poisoning can cause severe lung injury during the early stages of exposure, finally leading to irreversible pulmonary fibrosis. Connective tissue growth factor (CTGF) is an essential growth factor that is involved in tissue repair and pulmonary fibrogenesis. In the present study, the role of CTGF was examined in a rat model of pulmonary fibrosis induced by PQ poisoning. Histological examination revealed interstitial edema and extensive cellular thickening of interalveolar septa at the early stages of poisoning. At 2 weeks after PQ administration, lung tissue sections exhibited a marked thickening of the alveolar walls with an accumulation of interstitial cells with a fibroblastic appearance. Masson's trichrome staining revealed a patchy distribution of collagen deposition, indicating pulmonary fibrogenesis. Western blot analysis and immunohistochemical staining of tissue samples demonstrated that CTGF expression was significantly upregulated in the PQ-treated group. Similarly, PQ treatment of MRC-5 human lung fibroblast cells caused an increase in CTGF in a dose-dependent manner. Furthermore, the addition of CTGF to MRC-5 cells triggered cellular proliferation and migration. In addition, CTGF induced the differentiation of fibroblasts to myofibroblasts, as was evident from increased expression of α-smooth muscle actin (α-SMA) and collagen. These findings demonstrate that PQ causes increased CTGF expression, which triggers proliferation, migration and differentiation of lung fibroblasts. Therefore, CTGF may be important in PQ-induced pulmonary fibrogenesis, rendering this growth factor a potential pharmacological target for reducing lung injury.

On denture marking.

PubMed

Borrman, H I; DiZinno, J A; Wasén, J; René, N

1999-06-01

During the last decades in Sweden dentures have been permanently marked with a stainless steel metal band incorporated into the acrylic and containing the patient's birth date, a special number, and "S" for Sweden. The last recommendation issued by the National Board of Health and Welfare states that "the patients shall always be offered denture marking and be informed about the benefit thereof. Denture marking is not permitted if the patient refuses it". Requirements for denture markers have been that they should be biologically inert (when incorporated into the denture), not be expensive, be easy to inscribe, be possible to retrieve after an accident, and survive elevated temperatures for a reasonable time under normal circumstances. Although the frequency of edentulousness has decreased in recent years due to the improvement in oral health there remains a need to address the issue of marking of complete dentures, because there is a large variation in the oral status of populations in different countries. Given that only one marked denture can reveal the identity of a deceased person when all other methods fail to do so, makes it worthwhile. Furthermore, denture marking is important in long-term care facilities. We have investigated the issue of denture marking in Europe and in the United States. The results from the European survey show that denture marking is, to our knowledge regulated by law only in Sweden and Iceland. In the US denture marking is so far mandatory in 21 states while New York State requires dentures to be marked if the patient requests it and several other states impose the obligation to mark dentures on long-term care facilities. Since there is no international consensus regarding the issue of denture marking it is important to address it. A survey from the Nordic countries has shown that if denture marking was in general use, the contribution to the establishment of identity by forensic odontology in cases of fire would increase by about 10%. This means that about 25 more individuals could have been identified if their dentures were marked. Increased international collaboration is needed to solve the issue of denture marking for clinical and forensic purposes.

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.

Spine problems in young athletes.

PubMed

Sucato, Daniel J; Micheli, Lyle J; Estes, A Reed; Tolo, Vernon T

2012-01-01

As the number of young people involved in sports activities increases, acute and chronic back pain has become more common. With a careful medical history and physical examination, along with the judicious use of imaging modalities, the causes of back pain can be correctly diagnosed and treated so that young athletes can quickly return to sports participation. Although most back pain in these young patients is muscular in origin, findings that should trigger increased concern include night pain, marked hamstring tightness, pain with lumbar spine hyperextension, or any neurologic finding. When recently developed vague back pain is present, a delay in radiographic imaging is warranted. With new back pain after trauma, AP and lateral radiographs of the symptomatic spinal area are indicated. CT, bone scans, and MRI should be reserved for special circumstances. Spondylolysis is the most common bony cause of back pain in young athletes. Spondylolysis can be treated with activity limitation, a specific exercise program, a thoracolumbar orthosis, and/or surgery. Treatment should be based on the amount of pain as well as the desire of the young athlete to continue in the sports activity that caused the pain. Other significant causes of back pain that require more extensive treatment in these young athletes include spondylolisthesis, lumbar disk disorders, and sacral stress fractures. It is anticipated that nearly all young athletes can return to sports activity after successful treatment. Even if surgical treatment is needed, return to all sports is expected, with the occasional exception of collision sports.

Upregulation of NAD(P)H:Quinone Oxidoreductase By Radiation Potentiates the Effect of Bioreductive β-Lapachone on Cancer Cells1

PubMed Central

Choi, Eun K; Terai, Kaoru; Ji, In-Mi; Kook, Yeon H; Park, Kyung H; Oh, Eun T; Griffin, Robert J; Lim, Byung U; Kim, Jin-Seok; Lee, Doo S; Boothman, David A; Loren, Melissa; Song, Chang W; Park, Heon Joo

2007-01-01

We found that β-lapachone (β-lap), a novel bioreductive drug, caused rapid apoptosis and clonogenic cell death in A549 human lung epithelial cancer cells in vitro in a dose-dependent manner. The clonogenic cell death caused by β-lap could be significantly inhibited by dicoumarol, an inhibitor of NAD(P)H:quinone oxido-reductase (NQO1), and also by siRNA for NQO1, demonstrating that NQO1-induced bioreduction of β-lap is an essential step in β-lap-induced cell death. Irradiation of A549 cells with 4 Gy caused a long-lasting upregulation of NQO1, thereby increasing NQO1-mediated β-lap-induced cell deaths. Although the direct cause of β-lap-induced apoptosis is not yet clear, β-lap treatment reduced the expression of p53 and NF-κB, whereas it increased cytochrome C release, caspase-3 activity, and γH2AX foci formation. Importantly, β-lap treatment immediately after irradiation enhanced radiation-induced cell death, indicating that β-lap sensitizes cancer cells to radiation, in addition to directly killing some of the cells. The growth of A549 tumors induced in immunocompromised mice could be markedly suppressed by local radiation therapy when followed by β-lap treatment. This is the first study to demonstrate that combined radiotherapy and β-lap treatment can have a significant effect on human tumor xenografts. PMID:17786182

Acute Ozone-Induced Pulmonary and Systemic Metabolic Effects Are Diminished in Adrenalectomized Rats

PubMed Central

Miller, Desinia B.; Snow, Samantha J.; Schladweiler, Mette C.; Richards, Judy E.; Ghio, Andrew J.; Ledbetter, Allen D.; Kodavanti, Urmila P.

2016-01-01

Acute ozone exposure increases circulating stress hormones and induces metabolic alterations in animals. We hypothesized that the increase of adrenal-derived stress hormones is necessary for both ozone-induced metabolic effects and lung injury. Male Wistar-Kyoto rats underwent bilateral adrenal demedullation (DEMED), total bilateral adrenalectomy (ADREX), or sham surgery (SHAM). After a 4 day recovery, rats were exposed to air or ozone (1 ppm), 4 h/day for 1 or 2 days and responses assessed immediately postexposure. Circulating adrenaline levels dropped to nearly zero in DEMED and ADREX rats relative to SHAM. Corticosterone tended to be low in DEMED rats and dropped to nearly zero in ADREX rats. Adrenalectomy in air-exposed rats caused modest changes in metabolites and lung toxicity parameters. Ozone-induced hyperglycemia and glucose intolerance were markedly attenuated in DEMED rats with nearly complete reversal in ADREX rats. Ozone increased circulating epinephrine and corticosterone in SHAM but not in DEMED or ADREX rats. Free fatty acids (P = .15) and branched-chain amino acids increased after ozone exposure in SHAM but not in DEMED or ADREX rats. Lung minute volume was not affected by surgery or ozone but ozone-induced labored breathing was less pronounced in ADREX rats. Ozone-induced increases in lung protein leakage and neutrophilic inflammation were markedly reduced in DEMED and ADREX rats (ADREX > DEMED). Ozone-mediated decreases in circulating white blood cells in SHAM were not observed in DEMED and ADREX rats. We demonstrate that ozone-induced peripheral metabolic effects and lung injury/inflammation are mediated through adrenal-derived stress hormones likely via the activation of stress response pathway. PMID:26732886

Epidermal growth factor receptor plays a role in the regulation of liver and plasma lipid levels in adult male mice.

PubMed

Scheving, Lawrence A; Zhang, Xiuqi; Garcia, Oscar A; Wang, Rebecca F; Stevenson, Mary C; Threadgill, David W; Russell, William E

2014-03-01

Dsk5 mice have a gain of function in the epidermal growth factor receptor (EGFR), caused by a point mutation in the kinase domain. We analyzed the effect of this mutation on liver size, histology, and composition. We found that the livers of 12-wk-old male Dsk5 heterozygotes (+/Dsk5) were 62% heavier compared with those of wild-type controls (+/+). The livers of the +/Dsk5 mice compared with +/+ mice had larger hepatocytes with prominent, polyploid nuclei and showed modestly increased cell proliferation indices in both hepatocytes and nonparenchymal cells. An analysis of total protein, DNA, and RNA (expressed relative to liver weight) revealed no differences between the mutant and wild-type mice. However, the livers of the +/Dsk5 mice had more cholesterol but less phospholipid and fatty acid. Circulating cholesterol levels were twice as high in adult male +/Dsk5 mice but not in postweaned young male or female mice. The elevated total plasma cholesterol resulted mainly from an increase in low-density lipoprotein (LDL). The +/Dsk5 adult mouse liver expressed markedly reduced protein levels of LDL receptor, no change in proprotein convertase subtilisin/kexin type 9, and a markedly increased fatty acid synthase and 3-hydroxy-3-methyl-glutaryl-CoA reductase. Increased expression of transcription factors associated with enhanced cholesterol synthesis was also observed. Together, these findings suggest that the EGFR may play a regulatory role in hepatocyte proliferation and lipid metabolism in adult male mice, explaining why elevated levels of EGF or EGF-like peptides have been positively correlated to increased cholesterol levels in human studies.

Bone anabolic effects of S-40503, a novel nonsteroidal selective androgen receptor modulator (SARM), in rat models of osteoporosis.

PubMed

Hanada, Keigo; Furuya, Kazuyuki; Yamamoto, Noriko; Nejishima, Hiroaki; Ichikawa, Kiyonoshin; Nakamura, Tsutomu; Miyakawa, Motonori; Amano, Seiji; Sumita, Yuji; Oguro, Nao

2003-11-01

A novel nonsteroidal androgen receptor (AR) binder, S-40503, was successfully generated in order to develop selective androgen receptor modulators (SARMs). We evaluated the binding specificity for nuclear receptors (NRs) and osteoanabolic activities of S-40503 in comparison with a natural nonaromatizable steroid, 5alpha-dihydrotestosterone (DHT). The compound preferentially bound to AR with nanomolar affinity among NRs. When S-40503 was administrated into orchiectomized (ORX) rats for 4 weeks, bone mineral density (BMD) of femur and muscle weight of levator ani were increased as markedly as DHT, but prostate weight was not elevated over the normal at any doses tested. In contrast, DHT administration caused about 1.5-fold increase in prostate weight. The reduced virilizing activity was clearly evident from the result that 4-week treatment of normal rats with S-40503 showed no enlargement of prostate. To confirm the bone anabolic effect, S-40503 was given to ovariectomized (OVX) rats for 2 months. The compound significantly increased the BMD and biomechanical strength of femoral cortical bone, whereas estrogen, anti-bone resorptive hormone, did not. The increase in periosteal mineral apposition rate (MAR) of the femur revealed direct bone formation activity of S-40503. It was unlikely that the osteoanabolic effect of the compound was attribute to the enhancement of muscle mass, because immobilized ORX rats treated with S-40503 showed a marked increase in BMD of tibial cortical bone without any actions on the surrounding muscle tissue. Collectively, our novel compound served as a prototype for SARMs, which had unique tissue selectivity with high potency for bone formation and lower impact upon sex accessory tissues.

75 FR 4485 - Airworthiness Directives; Fokker Services B.V. Model F.28 Mark 0070 and 0100 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-28

... have been reported where a passenger door actuator detached from the passenger door. This caused the... result in injury to persons on the ground and damage to the aircraft. * * * * * We are issuing this AD to... where a passenger door actuator detached from the passenger door. This caused the passenger door to drop...

A Primer on Vibrational Ball Bearing Feature Generation for Prognostics and Diagnostics Algorithms

DTIC Science & Technology

2015-03-01

Atlas -Marks (Cone-Shaped Kernel) ........................................................36 8.7.7 Hilbert-Huang Transform...bearing surface and eventually progress to the surface where the material will separate. Also known as pitting, spalling, or flaking. • Wear ...normal degradation caused by dirt and foreign particles causing abrasion of the contact surfaces over time resulting in alterations in the raceway and

Loss of anion transport without increased sodium absorption characterizes newborn porcine cystic fibrosis airway epithelia

PubMed Central

Chen, Jeng-Haur; Stoltz, David A.; Karp, Philip H.; Ernst, Sarah E.; Pezzulo, Alejandro A.; Moninger, Thomas O.; Rector, Michael V.; Reznikov, Leah R.; Launspach, Janice L.; Chaloner, Kathryn; Zabner, Joseph; Welsh, Michael J.

2011-01-01

SUMMARY Defective transepithelial electrolyte transport is thought to initiate cystic fibrosis (CF) lung disease. Yet, how loss of CFTR affects electrolyte transport remains uncertain. CFTR−/− pigs spontaneously develop lung disease resembling human CF. At birth, their airways exhibit a bacterial host defense defect, but are not inflamed. Therefore, we studied ion transport in newborn nasal and tracheal/bronchial epithelia in tissue, cultures, and in vivo. CFTR−/− epithelia showed markedly reduced Cl− and HCO3− transport. However, in contrast to a widely held view, lack of CFTR did not increase transepithelial Na+ or liquid absorption or reduce periciliary liquid depth. Like human CF, CFTR−/− pigs showed increased amiloride-sensitive voltage and current, but lack of apical Cl− conductance caused the change, not increased Na+ transport. These results indicate that CFTR provides the predominant transcellular pathway for Cl− and HCO3− in porcine airway epithelia, and reduced anion permeability may initiate CF airway disease. PMID:21145458

The effect of extracorporeal albumin dialysis on plasma phospholipid fatty acids in patients with end-stage liver disease.

PubMed

Zeh, Nina; Rossi, Steven S; Hofmann, Alan F; Steinbach, Joseph H; Hagey, Lee R; Oliver, Deanna; Stange, Jan; Hassanein, Tarek

2003-01-01

The effect of extracorporeal albumin dialysis (ECAD) using the MARS device on plasma phospholipid fatty acids (PLFA) in patients with end-stage liver disease (ESLD) was examined. Phospholipids were isolated from plasma and the fatty acid (FA) composition of non-sphingomyelin PL determined using capillary gas chromatography (GC). Plasma samples were also obtained from six patients with ESLD undergoing ECAD and from five patients with similar ESLD who were not treated, as well as from non-fasting healthy subjects. PLFA were much lower [506 +/- 62 microg/mL (M +/- SD)] in patients with ESLD than in healthy subjects (2709 +/- 688 microg/mL). In addition, the proportion of n3 and n6 polyunsaturated FA was much lower in patients with ESLD (n3, 1.7 +/- 0.1%, n6, 19.6 +/- 1.4%) than in healthy controls (n3, 4.1 +/- 2.4%, n6, 31.9 +/- 6.2%) ECAD caused an immediate increase in PLFA, averaging 56% in all patients, but PLFA levels decreased some hours later after treatment. ECAD also caused a small increase in the proportion of n3 and n6 of PLFA. During the 5 days of the study, PLFA rose in both ECAD-treated and untreated patients, but the increase was significantly greater in ECAD treated patient. It is concluded that patients with ESLD have markedly decreased PLFA; these PLFA have a lower proportion of the polyunsaturated n3 and n6 FA with the result that the plasma level of these essential polyunsaturated PLFA is extremely low compared to that of healthy subjects. ECAD causes a transient increase in PLFA toward normal levels and also increases the proportion of n3 and n6 FA.

Traumatic brain injury causes long-term behavioral changes related to region-specific increases of cerebral blood flow.

PubMed

Pöttker, Bruno; Stöber, Franziska; Hummel, Regina; Angenstein, Frank; Radyushkin, Konstantin; Goldschmidt, Jürgen; Schäfer, Michael K E

2017-12-01

Traumatic brain injury (TBI) is a leading cause of disability and death and survivors often suffer from long-lasting motor impairment, cognitive deficits, anxiety disorders and epilepsy. Few experimental studies have investigated long-term sequelae after TBI and relations between behavioral changes and neural activity patterns remain elusive. We examined these issues in a murine model of TBI combining histology, behavioral analyses and single-photon emission computed tomography (SPECT) imaging of regional cerebral blood flow (CBF) as a proxy for neural activity. Adult C57Bl/6N mice were subjected to unilateral cortical impact injury and investigated at early (15-57 days after lesion, dal) and late (184-225 dal) post-traumatic time points. TBI caused pronounced tissue loss of the parietal cortex and subcortical structures and enduring neurological deficits. Marked perilesional astro- and microgliosis was found at 57 dal and declined at 225 dal. Motor and gait pattern deficits occurred at early time points after TBI and improved over the time. In contrast, impaired performance in the Morris water maze test and decreased anxiety-like behavior persisted together with an increased susceptibility to pentylenetetrazole-induced seizures suggesting alterations in neural activity patterns. Accordingly, SPECT imaging of CBF indicated asymmetric hemispheric baseline neural activity patterns. In the ipsilateral hemisphere, increased baseline neural activity was found in the amygdala. In the contralateral hemisphere, homotopic to the structural brain damage, the hippocampus and distinct cortex regions displayed increased baseline neural activity. Thus, regionally elevated CBF along with behavioral alterations indicate that increased neural activity is critically involved in the long-lasting consequences of TBI.

Effects of phencyclidine (PCP) and MK 801 on the EEGq in the prefrontal cortex of conscious rats; antagonism by clozapine, and antagonists of AMPA-, alpha(1)- and 5-HT(2A)-receptors.

PubMed

Sebban, Claude; Tesolin-Decros, Brigitte; Ciprian-Ollivier, Jorge; Perret, Laurent; Spedding, Michael

2002-01-01

1. The electroencephalographic (EEG) effects of the propsychotic agent phencyclidine (PCP), were studied in conscious rats using power spectra (0 - 30 Hz), from the prefrontal cortex or sensorimotor cortex. PCP (0.1 - 3 mg kg(-1) s.c.) caused a marked dose-dependent increase in EEG power in the frontal cortex at 1 - 3 Hz with decreases in power at higher frequencies (9 - 30 Hz). At high doses (3 mg kg(-1) s.c.) the entire spectrum shifted to more positive values, indicating an increase in cortical synchronization. MK 801 (0.05 - 0.1 mg kg(-1) i.p.) caused similar effects but with lesser changes in power. 2. In contrast, the non-competitive AMPA antagonists GYKI 52466 and GYKI 53655 increased EEG power over the whole power spectrum (1 - 10 mg kg(-1) i.p.). The atypical antipsychotic clozapine (0.2 mg kg(-1) s.c.) synchronized the EEG (peak 8 Hz). The 5-HT(2A)-antagonist, M100907, specifically increased EEG power at 2 - 3 Hz at low doses (10 and 50 microg kg(-1) s.c.), whereas at higher doses (0.1 mg kg(-1) s.c.) the profile resembled that of clozapine. 3. Clozapine (0.2 mg kg(-1) s.c. ), GYKI 53655 (5 mg kg(-1) i.p.), prazosin (0.05 and 0.1 mg kg(-1) i.p.), and M100907 (0.01 and 0.05 mg kg(-1) s.c.) antagonized the decrease in power between 5 and 30 Hz caused by PCP (1 mg kg(-1) s.c.), but not the increase in power at 1 - 3 Hz in prefrontal cortex.

Identification of danger signals in nevirapine-induced skin rash.

PubMed

Zhang, Xiaochu; Sharma, Amy M; Uetrecht, Jack

2013-09-16

Nevirapine (NVP) can cause serious skin rashes and hepatotoxicity. It also causes an immune-mediated skin rash in rats but not hepatotoxicity. This rash is caused by a metabolite of NVP; specifically, NVP is oxidized in the liver to a benzylic alcohol (12-OH-NVP), which travels to the skin where it forms a reactive benzylic sulfate. This could both act as a hapten and induce a danger signal. In contrast, most of the covalent binding in the liver involves oxidation of the methyl group leading to a reactive quinone methide. In this study, we examined the effects of NVP and 12-OH-NVP on gene expression in the liver and skin. Both NVP and 12-OH-NVP induced changes in the liver, but the list of genes was different, presumably reflecting different bioactivation pathways. In contrast, many more genes were up-regulated in the skin by 12-OH-NVP than by NVP, which is consistent with the fact that 12-OH-NVP is an obligate intermediate in the formation of the reactive sulfate in the skin. Genes up-regulated by 12-OH-NVP in the skin included TRIM63 (18-fold increase), S100a7a (7-fold increase), IL22-RA2 (4-fold increase), and DAPK1 (3-fold increase). TRIM63 acts as a ubiquitin ligase, which is consistent with protein damage leading to an increase in protein turnover. In addition, TRIM proteins are involved in inflammasome activation, and it appears that inflammasome activation is an essential step in the induction of NVP-induced skin rash. S100A7 is considered a danger signal, and its upregulation supports the danger hypothesis. Upregulation of the IL-22 RA2 gene marks an immune response. DAPK1 is involved with inflammasome assembly through binding directly to NLRP3, a NOD-like receptor expressed in keratinocytes. These results provide important clues to how NVP causes the induction of an immune response, in this case leading to skin rash.

Effect of radon on the immune system: alterations in the cellularity and functions of T cells in lymphoid organs of mouse.

PubMed

Nagarkatti, M; Nagarkatti, P S; Brooks, A

1996-04-19

Exposure to radon and its progeny induces significant damage to the cells of the respiratory tract and causes lung cancer. Whether a similar exposure to radon would alter the functions of the immune system has not been previously investigated. In the current study, we investigated the effect of exposure of C57BL/6 mice to 1000 or 2500 working-level months (WLM) of radon and its progeny by inhalation, on the number and function of T lymphocytes in lymphoid organs. The control mice received uranium ore dust carrier aerosol by inhalation. Exposure to radon induced marked decrease in the total cellularity of most lymphoid organs such as thymus, peripheral lymph nodes (PLN), and lung-associated lymph nodes (LALN), when compared to the controls. The percentage of T cells increased, while that of non-T cells decreased, in all peripheral lymphoid organs at both the doses of radon. In the thymus, particularly at 2500 WLM of radon exposure, there was a marked decrease in CD4+CD8+ T cells and an increase in the immature CD4-CD8- T cells. Such alterations in both the numbers and percentages of lymphocytes and macrophages in radon-exposed mice may have resulted from the cell killing by the alpha particles as the immune cells were migrating through the lungs, or it may have been caused by altered migration of cells, inasmuch as expression of CD44, a molecule involved in migration and homing of immune cells, was significantly altered on cells found in different lymphoid organs. In the LALN, where one would predict the largest number of damaged cells to be present, there was a significant decrease in the T-cell responsiveness to mitogens while the B-cell response was not affected. Such alterations may have resulted from the direct effect of alpha-particle exposure on the migrating lymphocytes, altered percentage of lymphocytes as seen in secondary lymphoid organs, or altered expression of adhesion molecules involved in cell activation such as CD44 and CD3. Interestingly, radon exposure caused and increase in the T- and B-cell responsiveness to mitogens in the spleen and PLN. Since there is little evidence of direct radiation dose from radon in lymphoid organs, our studies demonstrating immunological alterations suggest an indirect effect of radon exposure that may have significant repercussions on the development of hypersensitivity and increased susceptibility to infections and cancer in the lung.

The Biomechanical Properties of Pedicle Screw Fixation Combined With Trajectory Bone Cement Augmentation in Osteoporotic Vertebrae.

PubMed

Fan, Haitao T; Zhang, Renjie J; Shen, Cailiang L; Dong, Fulong L; Li, Yong; Song, Peiwen W; Gong, Chen; Wang, Yijin J

2016-03-01

The biomechanics of pedicle screw fixation combined with trajectory cement augmentation with various filling volumes were measured by pull-out, periodic antibending, and compression fatigue tests. To investigate the biomechanical properties of the pedicle screw fixation combined with trajectory bone cement (polymethylmethacrylate) augmentation in osteoporotic vertebrae and to explore the optimum filling volume of the bone cement. Pedicle screw fixation is considered to be the most effective posterior fixation method. The decrease of the bone mineral density apparently increases the fixation failure risk caused by screw loosening and displacement. Trajectory bone cement augmentation has been confirmed to be an effective method to increase the bone intensity and could markedly increase the stability of the fixation interface. Sixteen elderly cadaveric 1-5 lumbar vertebral specimens were diagnosed with osteoporosis. The left and right vertebral pedicles were alternatively randomized for treatment in all groups, with the contralateral pedicles as control. The study groups included: group A (pedicle screw fixation with full trajectory bone cement augmentation), group B (75% filling), group C (50% filling), and group D (25% filling). Finally, the bone cement leakage and dispersion were assessed and the mechanical testing was conducted. The bone cement was well dispersed around the pedicle screw. The augmented bone intensity, pull-out strength, periodic loading times, and compression fatigue performance were markedly higher than those of the control groups. With the increase in trajectory bone cement, the leakage was also increased (P<0.05). The pull-out strength of the pedicle screw was increased with an increase in bone mineral density and trajectory bone cement. It peaked at 75% filling, with the largest power consumption. The optimal filling volume of the bone cement was 75% of the trajectory volume (about 1.03 mL). The use of excessive bone cement did not increase the fixation intensity but increased the risk of leakage.

Angiotensin II Infusion Induces Marked Diaphragmatic Skeletal Muscle Atrophy

PubMed Central

Rezk, Bashir M.; Yoshida, Tadashi; Semprun-Prieto, Laura; Higashi, Yusuke; Sukhanov, Sergiy; Delafontaine, Patrice

2012-01-01

Advanced congestive heart failure (CHF) and chronic kidney disease (CKD) are characterized by increased angiotensin II (Ang II) levels and are often accompanied by significant skeletal muscle wasting that negatively impacts mortality and morbidity. Both CHF and CKD patients have respiratory muscle dysfunction, however the potential effects of Ang II on respiratory muscles are unknown. We investigated the effects of Ang II on diaphragm muscle in FVB mice. Ang II induced significant diaphragm muscle wasting (18.7±1.6% decrease in weight at one week) and reduction in fiber cross-sectional area. Expression of the E3 ubiquitin ligases atrogin-1 and muscle ring finger-1 (MuRF-1) and of the pro-apoptotic factor BAX was increased after 24 h of Ang II infusion (4.4±0.3 fold, 3.1±0.5 fold and 1.6±0.2 fold, respectively, compared to sham infused control) suggesting increased muscle protein degradation and apoptosis. In Ang II infused animals, there was significant regeneration of injured diaphragm muscles at 7 days as indicated by an increase in the number of myofibers with centralized nuclei and high expression of embryonic myosin heavy chain (E-MyHC, 11.2±3.3 fold increase) and of the satellite cell marker M-cadherin (59.2±22.2% increase). Furthermore, there was an increase in expression of insulin-like growth factor-1 (IGF-1, 1.8±0.3 fold increase) in Ang II infused diaphragm, suggesting the involvement of IGF-1 in diaphragm muscle regeneration. Bone-marrow transplantation experiments indicated that although there was recruitment of bone-marrow derived cells to the injured diaphragm in Ang II infused mice (267.0±74.6% increase), those cells did not express markers of muscle stem cells or regenerating myofibers. In conclusion, Ang II causes marked diaphragm muscle wasting, which may be important for the pathophysiology of respiratory muscle dysfunction and cachexia in conditions such as CHF and CKD. PMID:22276172

Multiple Sclerosis: Can It Cause Seizures?

MedlinePlus

... Is there any connection between multiple sclerosis and epilepsy? Answers from B Mark Keegan, M.D. Epileptic ... E, et al. The prevalence and characteristics of epilepsy in patients with multiple sclerosis in Nordland County, ...

7 CFR 51.1015 - Serious damage.

Code of Federal Regulations, 2013 CFR

2013-01-01

... diameter; (c) Exanthema (ammoniation) which occurs as small spots over more than 25 percent of the fruit... circle one-half inch in diameter; (g) Sunburn which causes decided flattening of the fruit, marked drying...

7 CFR 51.1015 - Serious damage.

Code of Federal Regulations, 2014 CFR

2014-01-01

... diameter; (c) Exanthema (ammoniation) which occurs as small spots over more than 25 percent of the fruit... circle one-half inch in diameter; (g) Sunburn which causes decided flattening of the fruit, marked drying...

7 CFR 51.1521 - U.S. No. 1.

Code of Federal Regulations, 2010 CFR

2010-01-01

...; which are free from decay and sunscald, and free from damage caused by broken skins, heat injury, growth cracks, sunburn, split pits, hail marks, drought spots, gum spots, russeting, scars, other disease...

Pluronic Microemulsions as Nanoreservoirs for Extraction of Bupivacaine from Normal Saline

PubMed Central

Varshney, Manoj; Morey, Timothy E.; Shah, Dinesh O.; Flint, Jason A.; Moudgil, Brij M.; Seubert, Christoph N.

2013-01-01

We hypothesized that custom-designed microemulsions would effectively scavenge compounds from bulk media. Pluronic-based oil-in-water microemulsions were synthesized that efficiently reduced the free concentration of the local anesthetic bupivacaine in 0.9% NaCl. Both the molecular nature and concentration of the constituents in the microemulsions significantly affected extraction efficiencies. Pluronic F127-based microemulsions extracted bupivacaine more efficiently than microemulsions synthesized using other Pluronic surfactants (L44, L62, L64, F77, F87, F88, P104). Extraction was markedly increased by addition of fatty acid sodium salts due to greater oil/water interface area, increased columbic interaction between bupivacaine and fatty acids sodium salt, and greater surface activity. These data suggest that oil-in-water microemulsions may be an effective agent to treat cardiotoxicity caused by bupivacaine or other lipophilic drugs. PMID:15099093

Review of oil and gas exploitation impacts on grizzly bears

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

Schallenberger, A.

It is concluded that available information indicates that impacts of oil and gas exploitation should be considered primarily detrimental for grizzly bears in northwestern Montana. Research has shown that grizzlies tend to react strongly to aircraft, especially helicopters. Marked animals previously captured by aircraft show the greatest reaction. Helicopter disturbance may cause den abandonment. Biologists suggest that road development has contributed to a decline in numbers of bears by accelerating habitat loss and increasing hunting and poaching pressure. Use of river valleys for transportation corridors, campsites, and other activities magnifies the effect of human presence by concentrating it in somemore » of the most vulnerable and essential grizzly habitat. Bear-human conflicts may increase as a result of secondary development such as recreation, logging, livestock grazing, and construction of subdivisions.« less

Towards a Structural View of Drug Binding to hERG K+ Channels.

PubMed

Vandenberg, Jamie I; Perozo, Eduardo; Allen, Toby W

2017-10-01

The human ether-a-go-go-related gene (hERG) K + channel is of great medical and pharmaceutical relevance. Inherited mutations in hERG result in congenital long-QT syndrome which is associated with a markedly increased risk of cardiac arrhythmia and sudden death. hERG K + channels are also remarkably susceptible to block by a wide range of drugs, which in turn can cause drug-induced long-QT syndrome and an increased risk of sudden death. The recent determination of the near-atomic resolution structure of the hERG K + channel, using single-particle cryo-electron microscopy (cryo-EM), provides tremendous insights into how these channels work. It also suggests a way forward in our quest to understand why these channels are so promiscuous with respect to drug binding. Copyright © 2017 Elsevier Ltd. All rights reserved.

Central diabetes insipidus following cardiopulmonary arrest in a dog.

PubMed

Bellis, Tara; Daly, Meredith; Davidson, Benjamin

2015-01-01

To describe a clinical case of transient central diabetes insipidus (CDI) occurring post cardiopulmonary arrest (CPA) in a dog. An 8-week-old dog presented for intensive care after successful resuscitation following CPA. The patient exhibited neurologic deficits at initial presentation and over the following days developed marked polyuria, isosthenuria, and low urine osmolality. Treatment with synthetic vasopressin resulted in a reduction in urine output, increase in urine specific gravity (>50%), and increase in urine osmolality, suggesting a diagnosis of partial CDI. Clinical signs resolved over the following weeks and treatment was discontinued. CPA has been described as a cause of ischemic injury to the pituitary gland resulting in CDI in people. To the authors' knowledge, this is the first report of a dog developing transient partial CDI following CPA and successful resuscitation. © Veterinary Emergency and Critical Care Society 2015.

Interplay Between Cytosolic Free Zn2+ and Mitochondrion Morphological Changes in Rat Ventricular Cardiomyocytes.

PubMed

Billur, Deniz; Tuncay, Erkan; Okatan, Esma Nur; Olgar, Yusuf; Durak, Aysegul Toy; Degirmenci, Sinan; Can, Belgin; Turan, Belma

2016-11-01

The Zn 2+ in cardiomyocytes is buffered by structures near T-tubulus and/or sarcoplasmic/endoplasmic reticulum (S(E)R) while playing roles as either an antioxidant or a toxic agent, depending on the concentration. Therefore, we aimed first to examine a direct effect of ZnPO 4 (extracellular exposure) or Zn 2+ pyrithione (ZnPT) (intracellular exposure) application on the structure of the mitochondrion in ventricular cardiomyocytes by using histological investigations. The light microscopy data demonstrated that Zn 2+ exposure induced marked increases on cellular surface area, an indication of hypertrophy, in a concentration-dependent manner. Furthermore, a whole-cell patch-clamp measurement of cell capacitance also supported the hypertrophy in the cells. We observed marked increases in mitochondrial matrix/cristae area and matrix volume together with increased lysosome numbers in ZnPO 4 - or ZnPT-incubated cells by using transmission electron microscopy, again in a concentration-dependent manner. Furthermore, we observed notable clustering and vacuolated mitochondrion, markedly disrupted and damaged myofibrils, and electron-dense small granules in Zn 2+ -exposed cells together with some implications of fission-fusion defects in the mitochondria. Moreover, we observed marked depolarization in mitochondrial membrane potential during 1-μM ZnPT minute applications by using confocal microscopy. We also showed that 1-μM ZnPT incubation induced significant increases in the phosphorylation levels of GSK3β (Ser21 and Ser9), Akt (Ser473), and NFκB (Ser276 and Thr254) together with increased expression levels in ER stress proteins such as GRP78 and calregulin. Furthermore, a new key player at ER-mitochondria sites, promyelocytic leukemia protein (PML) level, was markedly increased in ZnPT-incubated cells. As a summary, our present data suggest that increased cytosolic free Zn 2+ can induce marked alterations in mitochondrion morphology as well as depolarization in mitochondrion membrane potential and changes in some cytosolic signaling proteins as well as a defect in ER-mitochondria cross talk.

Aid to planning the marketing of mining area boundaries

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

Giles, R.H. Jr.

Reducing trespass, legal costs, and timber and wildlife poaching and increasing control, safety, and security are key reasons why mine land boundaries need to be marked. Accidents may be reduced, especially when associated with blast area boundaries, and in some cases increased income may be gained from hunting and recreational fees on well-marked areas. A BASIC computer program for an IBM-PC has been developed that requires minimum inputs to estimate boundary marking costs. This paper describes the rationale for the program and shows representative outputs. 3 references, 3 tables.

Valproic acid triggers increased mitochondrial biogenesis in POLG-deficient fibroblasts

PubMed Central

Sitarz, Kamil S.; Elliott, Hannah R.; Karaman, Betül S.; Relton, Caroline; Chinnery, Patrick F.; Horvath, Rita

2014-01-01

Valproic acid (VPA) is a widely used antiepileptic drug and also prescribed to treat migraine, chronic headache and bipolar disorder. Although it is usually well tolerated, a severe hepatotoxic reaction has been repeatedly reported after VPA administration. A profound toxic reaction on administration of VPA has been observed in several patients carrying POLG mutations, and heterozygous genetic variation in POLG has been strongly associated with VPA-induced liver toxicity. Here we studied the effect of VPA in fibroblasts of five patients carrying pathogenic mutations in the POLG gene. VPA administration caused a significant increase in the expression of POLG and several regulators of mitochondrial biogenesis. It was further supported by elevated mtDNA copy numbers. The effect of VPA on mitochondrial biogenesis was observed in both control and patient cell lines, but the capacity of mutant POLG to increase the expression of mitochondrial genes and to increase mtDNA copy numbers was less effective. No evidence of substantive differences in DNA methylation across the genome was observed between POLG mutated patients and controls. Given the marked perturbation of gene expression observed in the cell lines studied, we conclude that altered DNA methylation is unlikely to make a major contribution to POLG-mediated VPA toxicity. Our data provide experimental evidence that VPA triggers increased mitochondrial biogenesis by altering the expression of several mitochondrial genes; however, the capacity of POLG-deficient liver cells to address the increased metabolic rate caused by VPA administration is significantly impaired. PMID:24725338

Increased Glyburide Clearance in the Pregnant Mouse Model

PubMed Central

Zhou, Lin; Zhang, Yi; Hebert, Mary F.; Unadkat, Jashvant D.

2010-01-01

Glyburide (GLB) is an oral sulfonylurea, commonly used for the treatment of gestational diabetes mellitus. It has been reported that the clearance of GLB in pregnant women is significantly higher than that in nonpregnant women. The molecular mechanism by which pregnancy increases the clearance of GLB is not known, but it may be caused by increased CYP3A activity. Because liver tissue from pregnant women is not readily available, in the present study, we investigated the mechanism of such pregnancy-related changes in GLB disposition in a mouse model. We demonstrated that the systemic clearance of GLB in pregnant mice was increased approximately 2-fold (p < 0.01) compared with nonpregnant mice, a magnitude of change similar to that observed in the clinical study. Plasma protein binding of GLB in mice was not altered by pregnancy. The half-life of GLB depletion in hepatic S-9 fractions of pregnant mice was significantly shorter than that of nonpregnant mice. Moreover, GLB depletion was markedly inhibited by ketoconazole, a potent inhibitor of mouse Cyp3a, suggesting that GLB metabolism in mice is primarily mediated by hepatic Cyp3a. These data suggest that the increased systemic clearance of GLB in pregnant mice is likely caused by an increase in hepatic Cyp3a activity during pregnancy, and they provide a basis for further mechanistic understanding and analysis of pregnancy-induced alterations in the disposition of GLB and drugs that are predominantly and extensively metabolized by CYP3A/Cyp3a. PMID:20558597

High-water marks from flooding in Lake Champlain from April through June 2011 and Tropical Storm Irene in August 2011 in Vermont

USGS Publications Warehouse

Medalie, Laura; Olson, S.A.

2013-01-01

The U.S. Geological Survey, in cooperation with the Federal Emergency Management Agency, identified high-water marks after two floods in Vermont during 2011. Following a snowy winter, new monthly precipitation records were set in Burlington, Vermont, in April and May 2011, causing extensive flooding from April through June. The spring 2011 flooding resulted in a new record for stage (103.27 feet, referenced to the National Geodetic Vertical Datum of 1929) at the Lake Champlain at Burlington, Vt., gaging station (04294500). During August 28 and 29, 2011, tropical storm Irene delivered rainfall totals of 3 to more than 7 inches throughout Vermont, which resulted in extensive flooding and new streamflow records at nine streamgaging stations. Four presidential declarations of disaster were made following the 2011 flood events in Vermont. Thirty-nine high-water marks were identified and flagged to mark the highest levels of Lake Champlain from the May 2011 flooding, and 1,138 high-water marks were identified and flagged along Vermont rivers after flooding from tropical storm Irene in August 2011. Seventy-four percent of the high-water marks that were flagged were later found and surveyed to the North American Vertical Datum of 1988.

Mortality of those who attended drug services in Scotland 1996-2006: record-linkage study.

PubMed

Merrall, Elizabeth L C; Bird, Sheila M; Hutchinson, Sharon J

2012-01-01

We examine major causes of death amongst persons in contact with drug-treatment services across Scotland during April 1996-March 2006, hereafter Scottish Drug Misuse Database (SDMD) cohort. Drug-treatment records were linked to national registers of deaths and hepatitis C virus (HCV) diagnoses. For eras 1996/97-2000/01 and 2001/02-2005/06, we calculated cause-specific death-rates and standardised mortality ratios (SMRs) using age-, sex- and calendar-rates of the general Scottish population. Major causes of death were identified by high SMRs (>5 across eras) or rates (>50 per 100,000 person-years in either era), and their time-specific influences characterised by proportional hazards analyses. The SDMD cohort comprised 69,456 individuals, 350,315 person-years and 2590 deaths. The overall SMR reduced from 6.4 (95% CI: 6.0-6.9) to 4.8 (95% CI: 4.6-5.0) between eras. We identified five major causes of death: drug-related (1383 deaths), homicide (118) and infectious diseases (90) with high SMRs; suicide (269) and digestive system disease (168) with high rates. HCV diagnosis marked individuals with at least double the risk of cause-specific mortality, including adjusted hazard ratio (HR) for no HCV diagnosis of 0.46 (95% CI: 0.41-0.53) for drug-related deaths (DRDs) and 0.15 (95% CI: 0.10-0.22) for death from digestive system disease. Increased DRD risk at older age (>34 years) appeared specific to HCV-diagnosed individuals (interaction: χ₁²=7.7, p=0.01). Alcohol misuse increased HRs: for DRD (1.76, 95% CI: 1.50-2.06), suicide (1.88, 95% CI: 1.35-2.60), deaths from digestive system disease (3.19, 95% CI: 2.21-4.60) and non-major causes (1.87, 95% CI: 1.49-2.35). Stimulant misuse increased suicide risk: adjusted HR 1.91 (95% CI: 1.43-2.54). Drug-users in Scotland are exposed to variously increased mortality risks. HCV-diagnosed individuals are particularly vulnerable, and may need additional support. Copyright © 2011 Elsevier B.V. All rights reserved.

Influence of the ionophore A23187 on the plastic behavior of normal erythrocytes.

PubMed

Kuettner, J F; Dreher, K L; Rao, G H; Eaton, J W; Blackshear, P L; White, J G

1977-07-01

Previous studies have demonstrated that A23187, an ionophore which selectively transports divalent cations across cell membranes, has profound effects on human erythrocytes: it causes red cells to take up calcium; lose potassium, water, and ATP; convert from biconcave discs to echinocytes and spheroechinocytes; and become more rigid. The present study has explored the influence of calcium uptake induced by the ionophore on the behavior of individual erythrocyte membranes by the micropipette aspiration technique. Exposure of erythrocytes to calcium and A23187 for intervals of up to 30 minutes resulted in marked changes in membrane viscoelastic properties, including the development of increased resistance to aspiration. The most striking manifestation of altered membrane mechanics was apparent after 10 minutes on incubation. Cells pulled into the pipette for a few seconds and the extruded back into the medium retained the deformity imposed by the pipette for several seconds to a few minutes before regaining the form they manifested prior to initial aspiration. The calcium-induced changes in erythrocyte behavior observed in this study strongly support the concept that extrinsic proteins located inside the membrane provide mechanical support to the cell wall, and that increased levels of calcium cause precipitation or cross-linking of the proteins responsible for the increased resistence to deformation and recoil observed after aspiration into micropipettes.

Physiological Notch Signaling Maintains Bone Homeostasis via RBPjk and Hey Upstream of NFATc1

PubMed Central

Tu, Xiaolin; Chen, Jianquan; Lim, Joohyun; Karner, Courtney M.; Lee, Seung-Yon; Heisig, Julia; Wiese, Cornelia; Surendran, Kameswaran; Kopan, Raphael; Gessler, Manfred; Long, Fanxin

2012-01-01

Notch signaling between neighboring cells controls many cell fate decisions in metazoans both during embryogenesis and in postnatal life. Previously, we uncovered a critical role for physiological Notch signaling in suppressing osteoblast differentiation in vivo. However, the contribution of individual Notch receptors and the downstream signaling mechanism have not been elucidated. Here we report that removal of Notch2, but not Notch1, from the embryonic limb mesenchyme markedly increased trabecular bone mass in adolescent mice. Deletion of the transcription factor RBPjk, a mediator of all canonical Notch signaling, in the mesenchymal progenitors but not the more mature osteoblast-lineage cells, caused a dramatic high-bone-mass phenotype characterized by increased osteoblast numbers, diminished bone marrow mesenchymal progenitor pool, and rapid age-dependent bone loss. Moreover, mice deficient in Hey1 and HeyL, two target genes of Notch-RBPjk signaling, exhibited high bone mass. Interestingly, Hey1 bound to and suppressed the NFATc1 promoter, and RBPjk deletion increased NFATc1 expression in bone. Finally, pharmacological inhibition of NFAT alleviated the high-bone-mass phenotype caused by RBPjk deletion. Thus, Notch-RBPjk signaling functions in part through Hey1-mediated inhibition of NFATc1 to suppress osteoblastogenesis, contributing to bone homeostasis in vivo. PMID:22457635

Rising Mediterranean Sea Surface Temperatures Amplify Extreme Summer Precipitation in Central Europe

NASA Astrophysics Data System (ADS)

Volosciuk, Claudia; Maraun, Douglas; Semenov, Vladimir A.; Tilinina, Natalia; Gulev, Sergey K.; Latif, Mojib

2016-08-01

The beginning of the 21st century was marked by a number of severe summer floods in Central Europe associated with extreme precipitation (e.g., Elbe 2002, Oder 2010 and Danube 2013). Extratropical storms, known as Vb-cyclones, cause summer extreme precipitation events over Central Europe and can thus lead to such floodings. Vb-cyclones develop over the Mediterranean Sea, which itself strongly warmed during recent decades. Here we investigate the influence of increased Mediterranean Sea surface temperature (SST) on extreme precipitation events in Central Europe. To this end, we carry out atmosphere model simulations forced by average Mediterranean SSTs during 1970-1999 and 2000-2012. Extreme precipitation events occurring on average every 20 summers in the warmer-SST-simulation (2000-2012) amplify along the Vb-cyclone track compared to those in the colder-SST-simulation (1970-1999), on average by 17% in Central Europe. The largest increase is located southeast of maximum precipitation for both simulated heavy events and historical Vb-events. The responsible physical mechanism is increased evaporation from and enhanced atmospheric moisture content over the Mediterranean Sea. The excess in precipitable water is transported from the Mediterranean Sea to Central Europe causing stronger precipitation extremes over that region. Our findings suggest that Mediterranean Sea surface warming amplifies Central European precipitation extremes.

Succinylcholine-induced hyperkalemia in the rat following radiation injury to muscle

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

Cairoli, V.J.; Ivankovich, A.D.; Vucicevic, D.

1982-02-01

During anesthetic preparation of a patient who had received routine radiation therapy for sarcoma of the leg, cardiac collapse occurred following succinylcholine (SCh) administration. Experiments were designed to test the hypothesis that radiation injury to muscle might cause increased sensitivity to SCh similar to that reported in patients with muscle trauma, severe burns, and lesions causing muscle denervation. Venous plasma potassium levels and arterial blood gas tensions were measured in rats after they were given SCh (3 mg/kg) at various times following /sup 60/Co irradiation of the hind legs. Nonirradiated rats responded to SCh with a slight but statistically significantmore » increase in plasma K+. Rats subjected to high levels of radiation (10,000 to 20,000 R) and given SCh 4 to 7 days later responded in the same way as the control rats. Plasma K+ levels in rats exposed to a fractionated irradiated dosage (2500 R given twice with a 1-week interval) followed by SCh 1 week later were similar to those in the control group, but when SCh was given 2 weeks later (3 weeks after initial irradiation) there was a marked elevation of plasma K+, from 3.6 to 7.7 meq/L, a statistically significant increase.« less

Sodium Lauryl Sulfate Increases the Efficacy of a Topical Formulation of Foscarnet against Herpes Simplex Virus Type 1 Cutaneous Lesions in Mice

PubMed Central

Piret, Jocelyne; Désormeaux, André; Cormier, Hélène; Lamontagne, Julie; Gourde, Pierrette; Juhász, Julianna; Bergeron, Michel G.

2000-01-01

The influence of sodium lauryl sulfate (SLS) on the efficacies of topical gel formulations of foscarnet against herpes simplex virus type 1 (HSV-1) cutaneous infection has been evaluated in mice. A single application of the gel formulation containing 3% foscarnet given 24 h postinfection exerted only a modest effect on the development of herpetic skin lesions. Of prime interest, the addition of 5% SLS to this gel formulation markedly reduced the mean lesion score. The improved efficacy of the foscarnet formulation containing SLS could be attributed to an increased penetration of the antiviral agent into the epidermis. In vitro, SLS decreased in a concentration-dependent manner the infectivities of herpesviruses for Vero cells. SLS also inhibited the HSV-1 strain F-induced cytopathic effect. Combinations of foscarnet and SLS resulted in subsynergistic to subantagonistic effects, depending on the concentration used. Foscarnet in phosphate-buffered saline decreased in a dose-dependent manner the viability of cultured human skin fibroblasts. This toxic effect was markedly decreased when foscarnet was incorporated into the polymer matrix. The presence of SLS in the gel formulations did not alter the viabilities of these cells. The use of gel formulations containing foscarnet and SLS could represent an attractive approach to the treatment of herpetic mucocutaneous lesions, especially those caused by acyclovir-resistant strains. PMID:10952566

MicroRNA-486–dependent modulation of DOCK3/PTEN/AKT signaling pathways improves muscular dystrophy–associated symptoms

PubMed Central

Alexander, Matthew S.; Casar, Juan Carlos; Motohashi, Norio; Vieira, Natássia M.; Eisenberg, Iris; Marshall, Jamie L.; Gasperini, Molly J.; Lek, Angela; Myers, Jennifer A.; Estrella, Elicia A.; Kang, Peter B.; Shapiro, Frederic; Rahimov, Fedik; Kawahara, Genri; Widrick, Jeffrey J.; Kunkel, Louis M.

2014-01-01

Duchenne muscular dystrophy (DMD) is caused by mutations in the gene encoding dystrophin, which results in dysfunctional signaling pathways within muscle. Previously, we identified microRNA-486 (miR-486) as a muscle-enriched microRNA that is markedly reduced in the muscles of dystrophin-deficient mice (Dmdmdx-5Cv mice) and in DMD patient muscles. Here, we determined that muscle-specific transgenic overexpression of miR-486 in muscle of Dmdmdx-5Cv mice results in reduced serum creatine kinase levels, improved sarcolemmal integrity, fewer centralized myonuclei, increased myofiber size, and improved muscle physiology and performance. Additionally, we identified dedicator of cytokinesis 3 (DOCK3) as a miR-486 target in skeletal muscle and determined that DOCK3 expression is induced in dystrophic muscles. DOCK3 overexpression in human myotubes modulated PTEN/AKT signaling, which regulates muscle hypertrophy and growth, and induced apoptosis. Furthermore, several components of the PTEN/AKT pathway were markedly modulated by miR-486 in dystrophin-deficient muscle. Skeletal muscle–specific miR-486 overexpression in Dmdmdx-5Cv animals decreased levels of DOCK3, reduced PTEN expression, and subsequently increased levels of phosphorylated AKT, which resulted in an overall beneficial effect. Together, these studies demonstrate that stable overexpression of miR-486 ameliorates the disease progression of dystrophin-deficient skeletal muscle. PMID:24789910

Interstitial lung disease in an adult with Fanconi anemia: Clues to the pathogenesis

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

Rubinstein, W.S.; Wenger, S.L.; Hoffman, R.M.

1997-03-31

We have studied a 38-year-old man with a prior diagnosis of Holt-Oram syndrome, who presented with diabetes mellitus. He had recently taken prednisone for idiopathic interstitial lung disease and trimethoprim-sulfamethoxazole for sinusitis. Thrombocytopenia progressed to pancytopenia. The patient had skeletal, cardiac, renal, cutaneous, endocrine, hepatic, neurologic, and hematologic manifestations of Fanconi anemia (FA). Chest radiographs showed increased interstitial markings at age 25, dyspnea began in his late 20s, and he stopped smoking at age 32. At age 38, computerized tomography showed bilateral upper lobe fibrosis, lower lobe honeycombing, and bronchiectasis. Pulmonary function tests, compromised at age 29, showed a moderatelymore » severe obstructive and restrictive pattern by age 38. Serum alpha-1 antitrypsin level was 224 (normal 85-213) mg/dL and PI phenotype was M1. Karyotype was 46,X-Y with a marked increase in chromosome aberrations induced in vitro by diepoxybutane. The early onset and degree of pulmonary disease in this patient cannot be fully explained by environmental or known genetic causes. The International Fanconi Anemia Registry (IFAR) contains no example of a similar pulmonary presentation. Gene-environment (ecogenetic) interactions in FA seem evident in the final phenotype. The pathogenic mechanism of lung involvement in FA may relate to oxidative injury and cytokine anomalies. 49 refs., 2 figs., 1 tab.« less

The Characterization of AT1 Expression in the Dorsal Root Ganglia After Chronic Constriction Injury.

PubMed

Oroszova, Zuzana; Hricova, Ludmila; Stropkovska, Andrea; Lukacova, Nadezda; Pavel, Jaroslav

2017-04-01

To clarify the role of Angiotensin II in the regulation of sensory signaling, we characterized the AT 1 expression in neuronal subpopulation of lower lumbar dorsal root ganglia under normal conditions and its alteration in neuropathic pain model. The characterization of AT 1 expression was done under control and after the chronic constriction injury induced by four loose ligatures of the sciatic nerve representing the model of posttraumatic painful peripheral neuropathy. Major Angiotensin II receptor type was expressed in approximately 43 % of small-sized and 62 % of large-sized neurons in control. The AT 1 overexpression after sciatic nerve ligation lasting 7 days was detected predominantly in small-sized AT 1 immunoreactive neurons (about 38 % increase). Chronic constriction injury caused a statistically marked increase in number of the small-sized peptidergic (CGRP immunoreactive) neuronal subpopulation expressing AT 1 (about 64 %). The subpopulations of AT 1 -immunoreactive and nonpeptide-containing primary sensory neurons revealed by IB4 binding, tyrosine hydroxylase- and parvalbumin-immunoreactive neurons were not markedly changed. Our results indicate that: (1) the AT 1 overexpression after the chronic constriction injury is an important factor in Angiotensin II-potentiated pain perception; (2) Angiotensin II is involved in pathological mechanisms of neuropathic pain and this effect can be mediated perhaps in combination with other neuropeptides synthesized in the primary sensory neurons.

Expression of mutant Sftpcin murine alveolar epithelia drives spontaneous lung fibrosis.

PubMed

Nureki, Shin-Ichi; Tomer, Yaniv; Venosa, Alessandro; Katzen, Jeremy; Russo, Scott J; Jamil, Sarita; Barrett, Matthew; Nguyen, Vivian; Kopp, Meghan; Mulugeta, Surafel; Beers, Michael F

2018-06-19

Epithelial cell dysfunction is postulated as an important component in the pathogenesis of Idiopathic Pulmonary Fibrosis (IPF). Mutations in the Surfactant Protein C [SP-C] gene [SFTPC], an alveolar type 2 (AT2) cell restricted protein, have been found in sporadic and familial IPF. To causally link these events, we developed a knock-in mouse model capable of regulated expression of an IPF-associated Isoleucine to Threonine substitution at codon 73 [I73T] in Sftpc (SP-CI73T). Tamoxifen treated SP-CI73T cohorts developed rapid increases in SftpcI73T mRNA and misprocessed proSP-CI73T protein accompanied by increased early mortality (days 7-14). This acute phase was marked by diffuse parenchymal lung injury, tissue infiltration by monocytes, polycellular alveolitis, and elevations in bronchoalveolar lavage and AT2 mRNA contents of select inflammatory cytokines. Resolution of alveolitis (2-4 weeks), commensurate with a rise in TGFB1, was followed by aberrant remodeling marked by collagen deposition, AT2 cell hyperplasia, a-SMA positive cells, and restrictive lung physiology. The translational relevance of the model was supported by detection of multiple IPF biomarkers previously reported in human cohorts. These data provide proof of principle that mutant SP-C expression in vivo causes spontaneous lung fibrosis strengthening the role of AT2 dysfunction as a key upstream driver of IPF pathogenesis.

Effect of dietary zinc on morphological characteristics and apoptosis related gene expression in the small intestine of Bama miniature pigs.

PubMed

Zhou, Xin; Li, Yansen; Li, Zhaojian; Cao, Yun; Wang, Fei; Li, ChunMei

2017-04-01

To investigate the effects of dietary zinc (Zn) on small intestinal mucosal epithelium, 6-month-old male Bama miniature pigs were randomly allocated into three groups and treated with three levels of Zn (Control, T1, and T2 diet supplemented with 0, 50, and 1500mg/kg Zn, respectively, as zinc sulfate) for 38days. The samples of small intestine tissues, serum, and feces were collected. The results showed that Zn concentrations of small intestine in the T2 group were higher than those in the control and T1 groups (p<0.05). In the T2 group, the pharmacological dose of dietary Zn treatment caused marked damage to the small intestinal epithelium. The expression of Bax, cleaved caspase-3, and caspase-8 were increased in the duodenum and the jejunum of the T2 group (p<0.05). The mRNA transcript levels of BAX, CYCS and CASP3 genes were upregulated in the duodenum and the jejunum of the T2 group. We concluded that a diet with a pharmacological dose of Zn increased the accumulation of Zn and the expression of Bax, cleaved caspase-3, and caspase-8, which might activate the apoptosis and lead to the marked injury of porcine small intestinal epithelium. Copyright © 2017 Elsevier GmbH. All rights reserved.

The Ionic Permeability Changes during Acetylcholine-Induced Responses of Aplysia Ganglion Cells

PubMed Central

Sato, Makoto; Austin, George; Yai, Hideko; Maruhashi, Juro

1968-01-01

ACh-induced depolarization (D response) in D cells markedly decreases as the external Na+ is reduced. However, when Na+ is completely replaced with Mg++, the D response remains unchanged. When Na+ is replaced with Tris(hydroxymethyl)aminomethane, the D response completely disappears, except for a slight decrease in membrane resistance. ACh-induced hyperpolarization (H response) in H cells is markedly depressed as the external Cl- is reduced. Frequently, the reversal of the H response; i.e., depolarization, is observed during perfusion with Cl--free media. In cells which show both D and H responses superimposed, it was possible to separate these responses from each other by perfusing the cells with either Na+-free or Cl--free Ringer's solution. High [K+]0 often caused a marked hyperpolarization in either D or H cells. This is due to the primary effect of high [K+]0 on the presynaptic inhibitory fibers. The removal of this inhibitory afferent interference by applying Nembutal readily disclosed the predicted K+ depolarization. In perfusates containing normal [Na+]0, the effects of Ca++ and Mg++ on the activities of postsynaptic membrane were minimal, supporting the current theory that the effects of these ions on the synaptic transmission are mainly presynaptic. The possible mechanism of the hyperpolarization produced by simultaneous perfusion with both high [K+]0 and ACh in certain H cells is explained quantitatively under the assumption that ACh induces exclusively an increase in Cl- permeability of the H membrane. PMID:5648831

Pediatric lead poisoning from folk prescription for treating epilepsy.

PubMed

Ying, Xiao-Lan; Xu, Jian; Markowitz, Morri; Yan, Chong-Huai

2016-10-01

A case of lead poisoning resulting from the ingestion of a folk remedy for treating epilepsy is reported. The initial blood lead concentration of this 6-y-old boy was 63.6μg/dl upon admission. He presented with abdominal pain, constipation, and irritability. The patient's liver function tests were significantly increased. Through chelation therapy, the blood lead concentration dropped markedly and clinical symptoms greatly improved. His blood and urine samples were collected for the kinetic analysis of lead elimination. Folk prescriptions for epilepsy should be considered as potential sources of lead intoxication. Lead poisoning should be taken into consideration for unknown causes of abdominal pain. Copyright © 2016. Published by Elsevier B.V.

Sudden unexpected death under acute influence of cannabis.

PubMed

Hartung, Benno; Kauferstein, Silke; Ritz-Timme, Stefanie; Daldrup, Thomas

2014-04-01

The acute toxicity of cannabinoids is said to be low and there is little public awareness of the potentially hazardous cardiovascular effects of cannabis, e.g. marked increase in heart rate or supine blood pressure. We describe the cases of two young, putative healthy men who died unexpectedly under the acute influence of cannabinoids. To our knowledge, these are the first cases of suspected fatal cannabis intoxications where full postmortem investigations, including autopsy, toxicological, histological, immunohistochemical and genetical examinations, were carried out. The results of these examinations are presented. After exclusion of other causes of death we assume that the young men experienced fatal cardiovascular complications evoked by smoking cannabis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Psychological Factors and Cardiac Risk And Impact of Exercise Training Programs—A Review of Ochsner Studies

PubMed Central

Lavie, Carl J.; Milani, Richard V.; Artham, Surya M.; Gilliland, Yvonne

2007-01-01

Although under-emphasized, substantial evidence indicates that psychological distress, especially depression, hostility, and anxiety, are risk factors for coronary heart disease (CHD) and affect recovery following major coronary heart disease events. We review several major studies from Ochsner Medical Center demonstrating the high prevalence of psychological distress in CHD patients and the marked benefits that occur following formal cardiac rehabilitation and exercise training programs. These benefits include reductions in psychological stress, improvements in CHD risk factors that accompany high stress, and reduced all-cause mortality. These data support the benefits of exercise training and increased levels of fitness to improve psychological stress and subsequent prognosis. PMID:21603539

Rectal perforation by compressed air

PubMed Central

2017-01-01

As the use of compressed air in industrial work has increased, so has the risk of associated pneumatic injury from its improper use. However, damage of large intestine caused by compressed air is uncommon. Herein a case of pneumatic rupture of the rectum is described. The patient was admitted to the Emergency Room complaining of abdominal pain and distension. His colleague triggered a compressed air nozzle over his buttock. On arrival, vital signs were stable but physical examination revealed peritoneal irritation and marked distension of the abdomen. Computed tomography showed a large volume of air in the peritoneal cavity and subcutaneous emphysema at the perineum. A rectal perforation was found at laparotomy and the Hartmann procedure was performed. PMID:28706893

Rectal perforation by compressed air.

PubMed

Park, Young Jin

2017-07-01

As the use of compressed air in industrial work has increased, so has the risk of associated pneumatic injury from its improper use. However, damage of large intestine caused by compressed air is uncommon. Herein a case of pneumatic rupture of the rectum is described. The patient was admitted to the Emergency Room complaining of abdominal pain and distension. His colleague triggered a compressed air nozzle over his buttock. On arrival, vital signs were stable but physical examination revealed peritoneal irritation and marked distension of the abdomen. Computed tomography showed a large volume of air in the peritoneal cavity and subcutaneous emphysema at the perineum. A rectal perforation was found at laparotomy and the Hartmann procedure was performed.

Postmenopausal Osteoporosis: The Role of Immune System Cells

PubMed Central

Faienza, Maria Felicia; Ventura, Annamaria; Marzano, Flaviana; Cavallo, Luciano

2013-01-01

In the last years, new evidences of the relationship between immune system and bone have been accumulated both in animal models and in humans affected by bone disease, such as rheumatoid arthritis, bone metastasis, periodontitis, and osteoporosis. Osteoporosis is characterized by low bone mass and microarchitectural deterioration of bone tissue with a subsequent increase in bone fragility and susceptibility to fractures. The combined effects of estrogen deprivation and raising of FSH production occurring in menopause cause a marked stimulation of bone resorption and a rapid bone loss which is central for the onset of postmenopausal osteoporosis. This review focuses on the role of immune system in postmenopausal osteoporosis and on therapeutic strategies targeting osteoimmunology pathways. PMID:23762093

False positive indium-111 white blood cell scan in a closed clavicle fracture

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

Friedman, R.J.; Gordon, L.

1988-01-01

Aggressive treatment of the multiply injured patient often requires early fixation of many fractures, some of which may be open. Often, patients develop postoperative fevers requiring a thorough workup to rule out infection. Recently, indium-111 white blood cell (WBC) imaging has become a valuable adjunct in the diagnosis of acute infection. The patient described had a simple, closed clavicle fracture with markedly increased activity on an indium-111 WBC scan obtained for fever workup. This subsequently proved to be a normal, healing, noninfected fracture by other diagnostic techniques. Noninfected, simple closed fractures should be added to the list of causes formore » a false-positive indium-111 WBC scan.« less

[The accumulation of lipid peroxidation products in the eye structures of mice under whole-body x-ray irradiation].

PubMed

Sakina, N L; Dontsov, A E; Afanas'ev, G G; Ostrovski, M A; Pelevina, I I

1990-01-01

In studying the effect of whole-body X-irradiation on the accumulation of lipid peroxidation products (conjugated dienes, TBA-active products, and Schiff bases) in retina and retinal pigmented epithelium of pigmented and nonpigmented mice it was shown that irradiation of dark-pigmented mice does not cause even a slight accumulation of lipid peroxidation products as compared to that in the controls. Albino mice exhibited a marked increase in the level of lipid peroxidation products which was manifested soon after irradiation and persisted for at least 3 months after irradiation. Melanine is suggested to participate in protecting eye structures against pro-oxidizing action of ionizing radiation.

A different kind of hedgehog pathway: tinea manus due to Trichophyton erinacei transmitted by an African pygmy hedgehog (Atelerix albiventris).

PubMed

Weishaupt, Julia; Kolb-Mäurer, Annette; Lempert, Sigrid; Nenoff, Pietro; Uhrlaß, Silke; Hamm, Henning; Goebeler, Matthias

2014-02-01

The unusual case of a 29-year-old woman with tinea manus caused by infection due to Trichophyton erinacei is described. The patient presented with marked erosive inflammation of the entire fifth finger of her right hand. Mycological and genomic diagnostics resulted in identification of T. erinacei as the responsible pathogen, which had been transmitted by a domestic African pygmy hedgehog, Atelerix albiventris. Upon prolonged treatment with topical and systemic antifungal agents skin lesions slowly resolved. This case illustrates that the increasingly popular keeping of extraordinary pets such as hedgehogs may bear the risk of infections with uncommon dermatophytes. © 2013 Blackwell Verlag GmbH.

The global increase in dental caries. A pending public health crisis.

PubMed

Bagramian, Robert A; Garcia-Godoy, Franklin; Volpe, Anthony R

2009-02-01

A current review of the available epidemiological data from many countries clearly indicates that there is a marked increase in the prevalence of dental caries. This global increase in dental caries prevalence affects children as well as adults, primary as well as permanent teeth, and coronal as well as root surfaces. This increase in dental caries signals a pending public health crisis. Although there are differences of opinion regarding the cause of this global dental caries increase, the remedy is well known: a return to the public health strategies that were so successful in the past, a renewed campaign for water fluoridation, topical fluoride application, the use of fluoride rinses, a return to school oral health educational programs, an emphasis on proper tooth brushing with a fluoride dentifrice, as well as flossing, a proper diet and regular dental office visits. If these remedies are not initiated, there could be a serious negative impact upon the future oral health (and systemic health) of the global community, as well as a strain on the dental profession along with a major increase in the cost of dental services.

GCF Mark IV development

NASA Technical Reports Server (NTRS)

Mortensen, L. O.

1982-01-01

The Mark IV ground communication facility (GCF) as it is implemented to support the network consolidation program is reviewed. Changes in the GCF are made in the area of increased capacity. Common carrier circuits are the medium for data transfer. The message multiplexing in the Mark IV era differs from the Mark III era, in that all multiplexing is done in a GCF computer under GCF software control, which is similar to the multiplexing currently done in the high speed data subsystem.

Dietary calcein marking of brook trout, Atlantic salmon, yellow perch, and coho salmon scales

USGS Publications Warehouse

Honeyfield, D.C.; Ostrowski, C.S.; Fletcher, J.W.; Mohler, J.W.

2006-01-01

Brook trout Salvelinus fontinalis, Atlantic salmon Salmo salar, coho salmon Oncorhynchus kisutch, and yellow perch Perca flavescens fed calcein for 5 d showed characteristic calcein scale marks 7-10 d postmarking. In fish fed 0.75 or 1.25 g of calcein per kilogram of feed, the percentage of fish that exhibited a calcein mark was 100% in brook trout, 93-98% in Atlantic salmon, 60% in yellow perch, and 0% in coho salmon. However, when coho salmon were fed 5.25 g calcein/kg feed, 100% marking was observed 7-10 d postmarking. Brook trout were successfully marked twice with distinct bands when fed calcein 5 months apart. Brook trout scale pixel luminosity increased as dietary calcein increased in experiment 2. For the second calcein mark, scale pixel luminosity from brook trout fed 1.25 g calcein/kg feed was numerically higher (P < 0.08) than scales from fish fed 0.75 g calcein/kg feed. Mean pixel luminosity of calcein-marked Atlantic salmon scales was 57.7 for fish fed 0.75 g calcein/kg feed and 55.2 for fish fed 1.25 g calcein/kg feed. Although feed acceptance presented a problem in yellow perch, these experiments provide evidence that dietary calcein is a viable tool for marking fish for stock identification. ?? Copyright by the American Fisheries Society 2006.

Mortality due to poisoning in a developing agricultural country: trends over 20 years.

PubMed

Senanayake, N; Peiris, H

1995-10-01

The cause of death as recorded in 37,125 death certificates (DCs) issued in the Kandy District over 20 years at 5-year intervals beginning in 1967 were analysed to determine the trends in mortality caused by poisoning in the community. Poisoning accounted for 718 (19.3 per 1000) deaths, the highest number being in the third decade of life (41.9%). Male:female ratio was 3:1. The agent responsible for 77% of the deaths was pesticides. Acids and chemicals accounted for 6.9% of the deaths. Other poisons each contributing to less than 1% of the deaths were: plant poisons, food items, drugs, kerosine oil and alcohol. Nearly half the deaths had occurred outside the town area, at home or in small hospitals in the periphery. Mortality due to poisoning showed an increasing trend during the 20 years, from 11.8 to 43/1000 deaths, and this increase was most marked in the periphery, from 8/1000 to 70/1000. This increase paralleled the increase in suicide figures in the country. Our findings call for a shift in emphasis in public education towards first-aid management of intoxication. Health services of developing countries should provide appropriate resuscitative equipment, and ensure a regular supply of antidotes and other medication to all rural hospitals. Management of pesticide poisoning should be emphasised in the curricula for medical graduates, nurses, and paramedics.

THE RECENT REJUVENATION OF THE SUN’S LARGE-SCALE MAGNETIC FIELD: A CLUE FOR UNDERSTANDING PAST AND FUTURE SUNSPOT CYCLES

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

Sheeley, N. R. Jr.; Wang, Y.-M.

The quiet nature of sunspot cycle 24 was disrupted during the second half of 2014 when the Sun’s large-scale field underwent a sudden rejuvenation: the solar mean field reached its highest value since 1991, the interplanetary field strength doubled, and galactic cosmic rays showed their strongest 27-day modulation since neutron-monitor observations began in 1957; in the outer corona, the large increase of field strength was reflected by unprecedentedly large numbers of coronal loops collapsing inward along the heliospheric current sheet. Here, we show that this rejuvenation was not caused by a significant increase in the level of solar activity asmore » measured by the smoothed sunspot number and CME rate, but instead was caused by the systematic emergence of flux in active regions whose longitudinal distribution greatly increased the Sun’s dipole moment. A similar post-maximum increase in the dipole moment occurred during each of the previous three sunspot cycles, and marked the start of the declining phase of each cycle. We note that the north–south component of this peak dipole moment provides an early indicator of the amplitude of the next cycle, and conclude that the amplitude of cycle 25 may be comparable to that of cycle 24, and well above the amplitudes obtained during the Maunder Minimum.« less

The research of laser marking control technology

NASA Astrophysics Data System (ADS)

Zhang, Qiue; Zhang, Rong

2009-08-01

In the area of Laser marking, the general control method is insert control card to computer's mother board, it can not support hot swap, it is difficult to assemble or it. Moreover, the one marking system must to equip one computer. In the system marking, the computer can not to do the other things except to transmit marking digital information. Otherwise it can affect marking precision. Based on traditional control methods existed some problems, introduced marking graphic editing and digital processing by the computer finish, high-speed digital signal processor (DSP) control marking the whole process. The laser marking controller is mainly contain DSP2812, digital memorizer, DAC (digital analog converting) transform unit circuit, USB interface control circuit, man-machine interface circuit, and other logic control circuit. Download the marking information which is processed by computer to U disk, DSP read the information by USB interface on time, then processing it, adopt the DSP inter timer control the marking time sequence, output the scanner control signal by D/A parts. Apply the technology can realize marking offline, thereby reduce the product cost, increase the product efficiency. The system have good effect in actual unit markings, the marking speed is more quickly than PCI control card to 20 percent. It has application value in practicality.

49 CFR 173.311 - Metal hydride storage systems.

Code of Federal Regulations, 2012 CFR

2012-10-01

... that a steel UN pressure receptacle bearing an “H” mark must be used for hydrogen bearing gases or other gases that may cause hydrogen embrittlement. Requalification intervals must be no more than every...

Stationary states in quantum walk search

NASA Astrophysics Data System (ADS)

PrÅ«sis, Krišjānis; Vihrovs, Jevgěnijs; Wong, Thomas G.

2016-09-01

When classically searching a database, having additional correct answers makes the search easier. For a discrete-time quantum walk searching a graph for a marked vertex, however, additional marked vertices can make the search harder by causing the system to approximately begin in a stationary state, so the system fails to evolve. In this paper, we completely characterize the stationary states, or 1-eigenvectors, of the quantum walk search operator for general graphs and configurations of marked vertices by decomposing their amplitudes into uniform and flip states. This infinitely expands the number of known stationary states and gives an optimization procedure to find the stationary state closest to the initial uniform state of the walk. We further prove theorems on the existence of stationary states, with them conditionally existing if the marked vertices form a bipartite connected component and always existing if nonbipartite. These results utilize the standard oracle in Grover's algorithm, but we show that a different type of oracle prevents stationary states from interfering with the search algorithm.

Diffraction-based overlay measurement on dedicated mark using rigorous modeling method

NASA Astrophysics Data System (ADS)

Lu, Hailiang; Wang, Fan; Zhang, Qingyun; Chen, Yonghui; Zhou, Chang

2012-03-01

Diffraction Based Overlay (DBO) is widely evaluated by numerous authors, results show DBO can provide better performance than Imaging Based Overlay (IBO). However, DBO has its own problems. As well known, Modeling based DBO (mDBO) faces challenges of low measurement sensitivity and crosstalk between various structure parameters, which may result in poor accuracy and precision. Meanwhile, main obstacle encountered by empirical DBO (eDBO) is that a few pads must be employed to gain sufficient information on overlay-induced diffraction signature variations, which consumes more wafer space and costs more measuring time. Also, eDBO may suffer from mark profile asymmetry caused by processes. In this paper, we propose an alternative DBO technology that employs a dedicated overlay mark and takes a rigorous modeling approach. This technology needs only two or three pads for each direction, which is economic and time saving. While overlay measurement error induced by mark profile asymmetry being reduced, this technology is expected to be as accurate and precise as scatterometry technologies.

Ongoing Impact of HIV Infection on Mortality among Persons who Inject Drugs Despite Free Antiretroviral Therapy

PubMed Central

Lappalainen, Leslie; Hayashi, Kanna; Dong, Huiru; Milloy, M-J; Kerr, Thomas; Wood, Evan

2014-01-01

Aims To determine the impact of HIV infection on mortality over time among persons who inject drugs (PWID) in settings with free HIV/AIDS care. Design and Setting Prospective cohort study of PWID in Vancouver, Canada, recruited between May 1996 and December 2011. We ascertained morality rates and causes of death through a confidential linkage with the provincial vital statistics registry. Participants 2283 individuals were followed for a median of 60.9 months (Interquartile range: 34.4 – 113.1) among whom 622 (27.2%) individuals were HIV-positive at baseline, and 179 (7.8%) seroconverted during follow-up. Measurements The primary and secondary outcomes of interests were all-cause mortality and cause of death, respectively. The main independent variable of interest was HIV serostatus (positive vs. negative). We used Cox proportional hazards regression to determine factors associated with mortality, including socio-demographic variables, drug use behaviors and other risk behaviors. Findings Over the study period, 491 (21.5%) individuals died. In multivariate analyses, HIV infection remained independently associated with all-cause mortality (adjusted hazard ratio = 3.15; 95% CI: 2.59 – 3.82). While all-cause mortality rates declined markedly during the study period (p < 0.001, the independent effect of HIV infection on mortality remained unchanged over time (p = 0.640). Among HIV-positive individuals, significant changes in causes of death from infectious and AIDS-related causes to non-AIDS-related etiologies were observed. Conclusions HIV infection continues to have a persistent impact on mortality rates among persons who inject drugs in settings with free HIV/AIDS care, though causes of death have shifted markedly from infectious and AIDS-related causes to non-AIDS-related etiologies. PMID:25203392

Oestrogen upregulates the expression levels and functional activities of duodenal mucosal CFTR and SLC26A6.

PubMed

Jin, Hai; Wen, Guorong; Deng, Shili; Wan, Shuo; Xu, Jingyu; Liu, Xuemei; Xie, Rui; Dong, Hui; Tuo, Biguang

2016-11-01

What is the central question of this study? Duodenal ulcer is a common disease. A sex-based difference in the incidence of duodenal ulcer has long been observed clinically, but the cause is unclear. What is the main finding and its importance? Duodenal mucosal bicarbonate secretion is the most important protective factor in duodenal mucosa against acid-induced damage. The cystic fibrosis transmembrane conductance regulator (CFTR) and the solute-linked carrier 26 gene family A6 (SLC26A6) are two key bicarbonate transport proteins that mediate duodenal mucosal bicarbonate secretion. We demonstrate that endogenous oestrogen upregulates the expression levels and functional activities of duodenal mucosal CFTR and SLC26A6, which contributes to the sex difference in the prevalence of duodenal ulcer. The incidence of duodenal ulcer is markedly lower in women than men, but the cause of the sex difference is not clear. The cystic fibrosis transmembrane conductance regulator (CFTR) and the solute-linked carrier 26 gene family A6 (SLC26A6) are two key bicarbonate transport proteins that mediate duodenal mucosal bicarbonate secretion, which is an important protective factor against acid-induced duodenal injury. The aim of this study was to investigate the effect of oestrogen on the expressions and functional activities of CFTR and SLC26A6 in duodenal mucosa. We found that the expression levels of duodenal CFTR and SLC26A6 were markedly higher in young (20- to 30-year-old) women than in young men and old (60- to 70-year-old) women and men. The expression levels of CFTR and SLC26A6 in young women were markedly higher in preovulatory phases than in premenstrual phases, which was consistent with the changes of serum estradiol concentrations. Further results showed that duodenal CFTR and SLC26A6 expression levels in female mice were markedly decreased after ovariectomy, and supplementation with estradiol reversed the changes in CFTR and SLC26A6. 17β-Estradiol increased CFTR and SLC26A6 expression levels of human duodenocytes in experiments in vitro. Functional experiments showed that basal and forskolin- and prostaglandin E 2 -stimulated duodenal bicarbonate secretion in ovariectomized mice was markedly decreased and, likewise, supplementation with 17β-estradiol reversed the changes. In conclusion, endogenous oestrogen upregulates the expressions and functional activities of CFTR and SLC26A6 in duodenal mucosa, which could contribute to protection of the duodenum and explain the sex difference in the prevalence of duodenal ulcer. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

The effect of hyperkalaemia on cardiac rhythm devices.

PubMed

Barold, S Serge; Herweg, Bengt

2014-04-01

In patients with pacemakers, hyperkalaemia causes three important abnormalities that usually become manifest when the K level exceeds 7 mEq/L: (i) widening of the paced QRS complex from delayed intraventricular conduction velocity, (ii) Increased atrial and ventricular pacing thresholds that may cause failure to capture. In this respect, the atria are more susceptible to loss of capture than the ventricles, and (iii) Increased latency (usually with ventricular pacing) manifested by a greater delay of the interval from the pacemaker stimulus to the onset of depolarization. First-degree ventricular pacemaker exit block may progress to second-degree Wenckebach (type I) exit block characterized by gradual prolongation of the interval from the pacemaker stimulus to the onset of the paced QRS complex ultimately resulting in an ineffectual stimulus. The disturbance may then progress to 2 : 1, 3 : 1 pacemaker exit block, etc., and eventually to complete exit block with total lack of capture. Ventricular undersensing is uncommonly observed because of frequent antibradycardia pacing. During managed ventricular pacing, hyperkalaemia-induced marked first-degree atrioventricular block may induce a pacemaker syndrome. With implantable cardioverter-defibrillators (ICDs) oversensing of the paced or spontaneous T-wave may occur. The latter may cause inappropriate shocks. A raised impedance from the right ventricular coil to the superior vena cava coil may become an important sign of hyperkalaemia in the asymptomatic or the minimally symptomatic ICD patient.

Severe chronic hepatitis secondary to prolonged use of ecstasy and cocaine.

PubMed

Payancé, Audrey; Scotto, Béatrice; Perarnau, Jean-Marc; de Muret, Anne; Bacq, Yannick

2013-11-01

Severe acute hepatotoxicity is a well known complication following the ingestion of ecstasy (3,4-methylenedioxymethamphetamine [MDMA] ecstasy). Hepatic dysfunction has also been reported after acute cocaine intoxication. However, chronic hepatitis after prolonged use of ecstasy and/or cocaine has rarely been reported. We report the case of a 27-year-old woman hospitalized with edema, ascites and severe liver failure (prothrombin rate 33%), following the use of ecstasy and cocaine over the previous 9 months. Clinical, biological, radiological and pathology findings were recorded at admission and over 8 years' follow-up. Liver biopsy showed architectural distortion caused by bridging fibrosis, proliferation of cholangioles, and lesions of active interface hepatitis. Other causes of acute and chronic liver disease were excluded. Magnetic resonance imaging showed marked liver fibrosis. After withdrawal of both substances clinical examination and liver function tests progressively normalized. Long-term monitoring with magnetic resonance imaging showed progressive regression of fibrosis. Use of ecstasy and cocaine may cause chronic hepatitis leading to marked liver fibrosis, which may regress after withdrawal of both substances. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Coma measurement by use of an alternating phase-shifting mask mark with a specific phase width

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

Qiu Zicheng; Wang Xiangzhao; Yuan Qiongyan

2009-01-10

The correlation between the coma sensitivity of the alternating phase-shifting mask (Alt-PSM) mark and the mark's structure is studied based on the Hopkins theory of partially coherent imaging and positive resist optical lithography (PROLITH) simulation. It is found that an optimized Alt-PSM mark with its phase width being two-thirds its pitch has a higher sensitivity to coma than Alt-PSM marks with the same pitch and the different phase widths. The pitch of the Alt-PSM mark is also optimized by PROLITH simulation, and the structure of p=1.92{lambda}/NA and pw=2p/3 proves to be with the highest sensitivity. The optimized Alt-PSM mark ismore » used as a measurement mark to retrieve coma aberration from the projection optics in lithographic tools. In comparison with an ordinary Alt-PSM mark with its phase width being a half its pitch, the measurement accuracies of Z7 and Z14 apparently increase.« less

Advances in process overlay on 300-mm wafers

NASA Astrophysics Data System (ADS)

Staecker, Jens; Arendt, Stefanie; Schumacher, Karl; Mos, Evert C.; van Haren, Richard J. F.; van der Schaar, Maurits; Edart, Remi; Demmerle, Wolfgang; Tolsma, Hoite

2002-07-01

Overlay budgets are getting tighter within 300 mm volume production and as a consequence the process effects on alignment and off-line metrology becomes more important. In a short loop experiment, with cleared reference marks in each image field, the isolated effect of processing was measured with a sub-nanometer accuracy. The examined processes are Shallow Trench Isolation (STI), Tungsten-Chemical Mechanical Processing (W-CMP) and resist spinning. The alignment measurements were done on an ASML TWINSCANT scanner and the off-line metrology measurements on a KLA Tencor. Mark type and mark position dependency of the process effects are analyzed. The mean plus 3 (sigma) of the maximum overlay after correcting batch average wafer parameters is used as an overlay performance indicator (OPI). 3 (sigma) residuals to the wafer-model are used as an indicator of the noise that is added by the process. The results are in agreement with existing knowledge of process effects on 200 mm wafers. The W-CMP process introduces an additional wafer rotation and scaling that is similar for alignment marks and metrology targets. The effects depend on the mark type; in general they get less severe for higher spatial frequencies. For a 7th order alignment mark, the OPI measured about 12 nm and the added noise about 12 nm. For the examined metrology targets the OPI is about 20 nm with an added noise of about 90 nm. Two different types of alignment marks were tested in the STI process, i.e., zero layer marks and marks that were exposed together with the STI product. The overlay contribution due to processing on both types of alignment marks is very low (smaller than 5 nm OPI) and independent on mark type. Some flyers are observed fot the zero layer marks. The flyers can be explained by the residues of oxide and nitride that is left behind in the spaces of the alignment marks. Resist spinning is examined on single layer resist and resist with an organic Bottom Anti-Reflective Coating (BARC) underneath. Single layer resist showed scaling on unsegmented marks that disappears using higher diffraction orders and/or mark segmentation. Resist with a planarizing BARC caused additional effects on the wafer edge for measurements with the red laser signal. The effects disappear using the green laser of ATHENAT.

Estimating sample size for landscape-scale mark-recapture studies of North American migratory tree bats

USGS Publications Warehouse

Ellison, Laura E.; Lukacs, Paul M.

2014-01-01

Concern for migratory tree-roosting bats in North America has grown because of possible population declines from wind energy development. This concern has driven interest in estimating population-level changes. Mark-recapture methodology is one possible analytical framework for assessing bat population changes, but sample size requirements to produce reliable estimates have not been estimated. To illustrate the sample sizes necessary for a mark-recapture-based monitoring program we conducted power analyses using a statistical model that allows reencounters of live and dead marked individuals. We ran 1,000 simulations for each of five broad sample size categories in a Burnham joint model, and then compared the proportion of simulations in which 95% confidence intervals overlapped between and among years for a 4-year study. Additionally, we conducted sensitivity analyses of sample size to various capture probabilities and recovery probabilities. More than 50,000 individuals per year would need to be captured and released to accurately determine 10% and 15% declines in annual survival. To detect more dramatic declines of 33% or 50% survival over four years, then sample sizes of 25,000 or 10,000 per year, respectively, would be sufficient. Sensitivity analyses reveal that increasing recovery of dead marked individuals may be more valuable than increasing capture probability of marked individuals. Because of the extraordinary effort that would be required, we advise caution should such a mark-recapture effort be initiated because of the difficulty in attaining reliable estimates. We make recommendations for what techniques show the most promise for mark-recapture studies of bats because some techniques violate the assumptions of mark-recapture methodology when used to mark bats.

Maternal bradycardia occurring prior to onset of HELLP syndrome in a woman with pre-eclampsia.

PubMed

Hosokawa, Ami; Umazume, Takeshi; Yamada, Takahiro; Minakami, Hisanori

2017-05-13

A 36-year-old nulliparous woman developed pre-eclampsia at gestational week (GW) 28 -6/7 Cardiac status was checked regularly. Heart rate of 93 beats per minute (bpm) with left atrial diameter (LAD) of 35 mm, left ventricular hypertrophy and inferior vena cava diameter (IVCD) of 8 mm at GW 32 -0/7 decreased to 48 bpm with an expanded IVCD to 25 mm, dilated left atrium (LAD to 39 mm), increased pulmonary arterial pressure, increased systemic vascular resistance (approximate 3000  dyn s/cm 5 ) and biphasic intrarenal venous flow pattern 3.5 hours prior to childbirth at GW 32 -3/7 Epigastralgia, tachycardia (160 bpm) and marked hypertension (201/111 mm Hg) occurring 2 hours after echocardiography necessitated caesarean section, with subsequent development of HELLP syndrome. Acute fluid shift from the splanchnic vasculature to central vasculature may have occurred causing HELLP syndrome as a result from vasospasm associated with sympathetic hyperactivity. The cause of bradycardia prior to tachycardia remains unclear. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Care of the infant of the diabetic mother.

PubMed

Hay, William W

2012-02-01

Gestational diabetes mellitus (GDM) from all causes of diabetes is the most common medical complication of pregnancy and is increasing in incidence, particularly as type 2 diabetes continues to increase worldwide. Despite advances in perinatal care, infants of diabetic mothers (IDMs) remain at risk for a multitude of physiologic, metabolic, and congenital complications such as preterm birth, macrosomia, asphyxia, respiratory distress, hypoglycemia, hypocalcemia, hyperbilirubinemia, polycythemia and hyperviscosity, hypertrophic cardiomyopathy, and congenital anomalies, particularly of the central nervous system. Overt type 1 diabetes around conception produces marked risk of embryopathy (neural tube defects, cardiac defects, caudal regression syndrome), whereas later in gestation, severe and unstable type 1 maternal diabetes carries a higher risk of intrauterine growth restriction, asphyxia, and fetal death. IDMs born to mothers with type 2 diabetes are more commonly obese (macrosomic) with milder conditions of the common problems found in IDMs. IDMs from all causes of GDM also are predisposed to later-life risk of obesity, diabetes, and cardiovascular disease. Care of the IDM neonate needs to focus on ensuring adequate cardiorespiratory adaptation at birth, possible birth injuries, maintenance of normal glucose metabolism, and close observation for polycythemia, hyperbilirubinemia, and feeding intolerance.

Role of central and peripheral opiate receptors in the effects of fentanyl on analgesia, ventilation and arterial blood-gas chemistry in conscious rats

PubMed Central

Henderson, Fraser; May, Walter J.; Gruber, Ryan B.; Discala, Joseph F.; Puscovic, Veljko; Young, Alex P.; Baby, Santhosh M.; Lewis, Stephen J.

2015-01-01

This study determined the effects of the peripherally restricted µ-opiate receptor (µ-OR) antagonist, naloxone methiodide (NLXmi) on fentanyl (25 µg/kg, i.v.)-induced changes in (1) analgesia, (2) arterial blood gas chemistry (ABG) and alveolar-arterial gradient (A-a gradient), and (3) ventilatory parameters, in conscious rats. The fentanyl-induced increase in analgesia was minimally affected by a 1.5 mg/kg of NLXmi but was attenuated by a 5.0 mg/kg dose. Fentanyl decreased arterial blood pH, pO2 and sO2 and increased pCO2 and A-a gradient. These responses were markedly diminished in NLXmi (1.5 mg/kg)-pretreated rats. Fentanyl caused ventilatory depression (e.g., decreases in tidal volume and peak inspiratory flow). Pretreatment with NLXmi (1.5 mg/kg, i.v.) antagonized the fentanyl decrease in tidal volume but minimally affected the other responses. These findings suggest that (1) the analgesia and ventilatory depression caused by fentanyl involve peripheral µ-ORs and (2) NLXmi prevents the fentanyl effects on ABG by blocking the negative actions of the opioid on tidal volume and A-a gradient. PMID:24284037

Effects of Zinc Gluconate and 2 Other Divalent Cationic Compounds on Olfactory Function in Mice

PubMed Central

Duncan-Lewis, Christopher A; Lukman, Roy L; Banks, Robert K

2011-01-01

Intranasal application of zinc gluconate has commonly been used to treat the common cold. The safety of this treatment, however, has come into question recently. In addition to a United States recall of a homeopathic product that contains zinc gluconate, abundant literature reports cytotoxic effects of zinc on the olfactory epithelium. Additional research suggests that divalent cations (such as zinc) can block ion channels that facilitate the transduction of odors into electrical signals on the olfactory epithelium. The purpose of the current study was 2-fold: to confirm whether zinc gluconate causes anosmia and to reveal whether any other divalent cationic compounds produce a similar effect. Groups of mice underwent a buried food-pellet test to gauge olfactory function and then were nasally irrigated with 1 of 3 divalent cationic compounds. When tested after treatment, mice irrigated with zinc gluconate and copper gluconate experienced a marked increase in food-finding time, indicating that they had lost their ability to smell a hidden food source. Control mice irrigated with saline had a significantly lower increase in times. These results confirm that zinc gluconate can cause anosmia and reveal that multiple divalent cations can negatively affect olfaction. PMID:22330252

Effects of radio transmitters on migrating wood thrushes

USGS Publications Warehouse

Powell, L.A.; Krementz, D.G.; Lang, J.D.; Conroy, M.J.

1998-01-01

We quantified the effects of radio transmitters on Wood Thrushes (Hylocichla mustelina) using 4 yr of banding and telemetry data from Piedmont National Wildlife Refuge, Georgia. Flight performance models suggest that the 1.6-g transmitter shortens the migratory range of Wood Thrushes by only 60 km, and the estimated migratory range is adequate to accomplish migration even with limited fat stores. We used two strengths of line, 5- and 9-kg test-strength braided Dacron, to attach the transmitters using the thigh-harness method. We recaptured 13 returning radio-marked Wood Thrushes, seven of which were still marked. Six of the seven birds marked with the 5-kg test harnesses lost their transmitters within 1 yr while all six of the 9-kg test harnesses were still attached up to 21 mo later. Radio-marking did not reduce the return rates of adults and immatures, and the transmitters did not cause radio-marked birds to lose more mass than banded-only birds. Wood Thrushes can successfully carry a transmitter during migration with no detectable negative effects. We recommend continued use of the thigh-harness method, but we encourage the use of 5-kg cotton line.

An overview of regular dialysis treatment in Japan (as of 31 December 2012).

PubMed

Nakai, Shigeru; Hanafusa, Norio; Masakane, Ikuto; Taniguchi, Masatomo; Hamano, Takayuki; Shoji, Tetsuo; Hasegawa, Takeshi; Itami, Noritomo; Yamagata, Kunihiro; Shinoda, Toshio; Kazama, Junichiro James; Watanabe, Yuzo; Shigematsu, Takashi; Marubayashi, Seiji; Morita, Osamu; Wada, Atsushi; Hashimoto, Seiji; Suzuki, Kazuyuki; Nakamoto, Hidetomo; Kimata, Naoki; Wakai, Kenji; Fujii, Naohiko; Ogata, Satoshi; Tsuchida, Kenji; Nishi, Hiroshi; Iseki, Kunitoshi; Tsubakihara, Yoshiharu

2014-12-01

A nationwide statistical survey of 4279 dialysis facilities was conducted at the end of 2012, among which 4238 responded (99.0%). The number of new dialysis patients was 38055 in 2012. Since 2008, the number of new dialysis patients has remained almost the same without any marked increase or decrease. The number of dialysis patients who died in 2012 was 30710; a slight decrease from 2011 (30743). The dialysis patient population has been growing every year in Japan; it was 310007 at the end of 2012, which exceeded 310000 for the first time. The number of dialysis patients per million at the end of 2012 was 2431.2. The crude death rate of dialysis patients in 2012 was 10.0%, a slight decrease from that in 2011 (10.2%). The mean age of new dialysis patients was 68.5 years and the mean age of the entire dialysis patient population was 66.9 years. The most common primary cause of renal failure among new dialysis patients was diabetic nephropathy (44.2%). The actual number of new dialysis patients with diabetic nephropathy has been approximately 16000 for the last few years. Diabetic nephropathy was also the most common primary disease among the entire dialysis patient population (37.1%), followed by chronic glomerulonephritis (33.6%). The percentage of dialysis patients with diabetic nephropathy has been continuously increasing, whereas not only the percentage but also the actual number of dialysis patients with chronic glomerulonephritis has decreased. The number of patients who underwent hemodiafiltration (HDF) at the end of 2012 was 21725, a marked increase from that in 2011 (14115). In particular, the number of patients who underwent on-line HDF increased threefold from 4890 in 2011 to 14069 in 2012. From the results of the facility survey, the number of patients who underwent peritoneal dialysis (PD) was 9514 and that of patients who did not undergo PD despite having a PD catheter in the abdominal cavity was 347. From the results of the patient survey, among the PD patients, 1932 also underwent another dialysis method using extracorporeal circulation, such as hemodialysis (HD) and HDF. The number of patients who underwent HD at home in 2012 was 393, a marked increase from that in 2011 (327). © 2014 Japanese Society for Dialysis Therapy. Reproduced with permission.

Color Changes Mark Polymer Reactions.

ERIC Educational Resources Information Center

Krieger, James H.

1980-01-01

Describes how polydiacetylenes can be used as educational aids. These polymers have conjugated backbones, which cause changes in color when the polydiacetylenes undergo various chemical and physical processes. Diagrams summarize all chemical reactions and their associated color changes. (CS)

Initial observations using a novel "cine" magnetic resonance imaging technique to detect changes in abdominal motion caused by encapsulating peritoneal sclerosis.

PubMed

Wright, Benjamin; Summers, Angela; Fenner, John; Gillott, Richard; Hutchinson, Charles E; Spencer, Paul A; Wilkie, Martin; Hurst, Helen; Herrick, Sarah; Brenchley, Paul; Augustine, Titus; Bardhan, Karna D

2011-01-01

Encapsulating peritoneal sclerosis (EPS) is an uncommon complication of peritoneal dialysis (PD), with high mortality and morbidity. The peritoneum thickens, dysfunctions, and forms a cocoon that progressively "strangulates" the small intestine, causing malnutrition, ischemia, and infarction. There is as yet no reliable noninvasive means of diagnosis, but recent developments in image analysis of cine magnetic resonance imaging for the recognition of adhesions offers a way forward. We used this protocol before surgery in 3 patients with suspected EPS. Image analysis revealed patterns of abdominal movement that were markedly different from the patterns in healthy volunteers. The volunteers showed marked movement throughout the abdomen; in contrast, movement in EPS patients was restricted to just below the diaphragm. This clear difference provides early "proof of principle" of the approach that we have developed.

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

Survival of female mallards along the Vermont–Quebec border region

USGS Publications Warehouse

Longcore, Jerry R.; McAuley, Daniel G.; Heisey, Dennis M.; Bunck, Christine M.; Clugston, David A.

2016-01-01

Understanding effects of location and timing of harvest seasons on mortality of ducks and geese from hunting is important in forming regulations that sustain viable waterfowl populations throughout their range. During 1990 and 1991 we alternately marked 80 hatching year (HY), female mallards along the Vermont–Quebec border; half with radio-transmitters and bands and half with only aluminum leg bands. We monitored radio-marked ducks daily and recorded survival status weekly for 15 weeks from August until December each year. Mallard mortalities began 25 September when the hunting season opened in the Province of Quebec, Canada. Overall survival of mallards at week 10 did not differ between years (0.51 in 1990 vs. 0.43 in 1991) or differ from that of HY American black ducks (0.44 females, 0.42 males) based on proportional hazard analysis in a Bayesian framework. The mortality rates for mallards from hunting (0.47) and causes unrelated to hunting (0.06) were similar between years and to those rates for HY black ducks at that same site. Hunter harvest accounted for most of the mortality recorded during this study and illegal feeding (i.e., baiting) at sites just before and during the hunting season was observed. Females with lower body condition index had greater mortality rates; a 1-standard-deviation increase in condition index would reduce mortality hazard by about 29%. Management options that may increase mallard survival in the area include lowering daily bag limit in Quebec and suspending split hunting seasons in Vermont that increase harvest, delaying opening date of hunting in Quebec to allow for increased body condition before hunting season opens, and improving enforcement of baiting restrictions.

Up-regulation of hepatic Acyl CoA: Diacylglycerol acyltransferase-1 (DGAT-1) expression in nephrotic syndrome.

PubMed

Vaziri, Nosratola D; Kim, Choong H; Phan, Dennis; Kim, Sara; Liang, Kaihui

2004-07-01

Nephrotic syndrome is associated with hypercholesterolemia, hypertriglyceridemia, and marked elevations of plasma low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL). Hypertriglyceridemia in nephrotic syndrome is accompanied by increased hepatic fatty acid synthesis, elevated triglyceride secretion, as well as lipoprotein lipase, VLDL-receptor, and hepatic triglyceride lipase deficiencies, which lead to impaired clearance of triglyceride-rich lipoproteins. Acyl CoA: diacylglycerol acyltransferase (DGAT) is a microsomal enzyme that joins acyl CoA to 1, 2-diacylglycerol to form triglyceride. Two distinct DGATs (DGAT-1 and DGAT2) have recently been identified in the liver and other tissues. The present study tested the hypothesis that the reported increase in hepatic triglyceride secretion in nephrotic syndrome may be caused by up-regulation of DGAT. Male Sprague-Dawley rats were rendered nephrotic by two sequential injections of puromycin aminonucleoside (130 mg/kg on day 1 and 60 mg/kg on day 14) and studied on day 30. Placebo-treated rats served as controls. Hepatic DGAT-1 and DGAT-2 mRNA abundance and enzymatic activity were measured. The nephrotic group exhibited heavy proteinuria, hypoalbuminemia, hypercholesterolemia, hypertriglyceridemia, and marked elevation of VLDL concentration. Hepatic DGAT-1 mRNA, DGAT-1, and total DGAT activity were significantly increased, whereas DGAT-2 mRNA abundance and activity were unchanged in the nephrotic rats compared to the control animals. The functional significance of elevation of DGAT activity was illustrated by the reduction in microsomal free fatty acid concentration in the liver of nephrotic animals. Nephrotic syndrome results in up-regulation of hepatic DGAT-1 expression and activity, which can potentially contribute to the associated hypertriglyceridemia by enhancing triglyceride synthesis. Thus, it appears that both depressed catabolism and increased synthetic capacity contribute to hypertriglyceridemia of nephrotic syndrome.

Effects of phosphoramidon on endothelin-1 and big endothelin-1 production in human aortic endothelial cells.

PubMed

Matsumura, Y; Tsukahara, Y; Kojima, T; Murata, S; Murakami, A; Takada, K; Takaoka, M; Morimoto, S

1995-03-01

Using cultured human aortic endothelial cells, we examined the effects of phosphoramidon, an endothelin converting enzyme (ECE) inhibitor, on the release of endogenous endothelin-1 (ET-1) and big endothelin-1 (big ET-1), and on the generation of ET-1 from exogenously applied big ET-1. Phosphoramidon, at concentrations of 10(-6) to 2 x 10(-4) M, caused a biphasic alteration of the ET-1 release, i.e., at lower concentrations of the drug, there were slight but unexpected increases of the release, whereas higher concentrations led to a decrease which is due to the drug-induced inhibition of ECE. The former effect appears to be based on the inhibition of ET-1 degradation by neutral endopeptidase 24.11 (NEP), since kelatorphan, a specific NEP inhibitor, produced a similar increasing effect on ET-1 release. Phosphoramidon enhanced the big ET-1 release from the cells in a concentration-dependent manner. When high concentrations of phosphoramidon were added, there was a dramatic increase in the release of big ET-1, which cannot be explained only by the drug-induced inhibition of ECE. This increase in big ET-1 release appeared to be partly due to a transient stimulation of the expression of prepro ET-1 mRNA. The amount of ET-1 generated from exogenously applied big ET-1 was markedly decreased by phosphoramidon in a concentration-dependent manner. In a similar fashion, phosphoramidon markedly inhibited ECE activity of the membrane fraction of cultured cells. Thus, ET-1 generation from exogenously applied big ET-1 reflects the functional phosphoramidon-sensitive ECE activities in human aortic endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

A Phex Mutation in a Murine Model of X-linked Hypophosphatemia Alters Phosphate Responsiveness of Bone Cells

PubMed Central

Ichikawa, Shoji; Austin, Anthony M.; Gray, Amie K.; Econs, Michael J.

2011-01-01

Mutations in the PHEX gene cause X-linked hypophosphatemia (XLH). Hypophosphatemia in XLH results from increased circulating levels of a phosphaturic hormone, fibroblast growth factor 23 (FGF23), which inhibits renal phosphate reabsorption and 1,25-dihydroxyvitamin D (calcitriol) synthesis. The current standard therapy for XLH – high dose phosphate and calcitriol – further increases FGF23 concentrations, suggesting that patients with XLH may have an altered response to extracellular phosphate. To test for the presence of abnormal phosphate responsiveness, we compared serum biochemistries and femoral Fgf23 mRNA expression between wild-type mice, murine models of XLH (PhexK496X) and hyperphosphatemic tumoral calcinosis (Galnt3 -/-), and Galnt3/Phex double mutant mice. Phex mutant mice had not only increased Fgf23 expression, but also reduced proteolytic cleavage of intact Fgf23 protein, resulting in markedly elevated intact Fgf23 levels and consequent hypophosphatemia. In contrast, despite markedly increased Fgf23 expression, Galnt3 knockout mice had significantly high proteolytic cleavage of Fgf23 protein, leading to low intact Fgf23 concentrations and hyperphosphatemia. Galnt3/Phex double mutant mice had an intermediate biochemical phenotype between wild-type and Phex mutant mice, including slightly elevated intact Fgf23 concentrations with milder hypophosphatemia. Despite the hypophosphatemia, double mutant mice attempted to reduce serum phosphate back to the level of Phex mutant mice by up-regulating Fgf23 expression as much as 24 fold higher than Phex mutant mice. These data suggest that Phex mutations alter the responsiveness of bone cells to extracellular phosphate concentrations and may create a lower set point for “normal” phosphate levels. PMID:22006791

A Phex mutation in a murine model of X-linked hypophosphatemia alters phosphate responsiveness of bone cells.

PubMed

Ichikawa, Shoji; Austin, Anthony M; Gray, Amie K; Econs, Michael J

2012-02-01

Mutations in the PHEX gene cause X-linked hypophosphatemia (XLH). Hypophosphatemia in XLH results from increased circulating levels of a phosphaturic hormone, fibroblast growth factor 23 (FGF23), which inhibits renal phosphate reabsorption and 1,25-dihydroxyvitamin D (calcitriol) synthesis. The current standard therapy for XLH--high-dose phosphate and calcitriol--further increases FGF23 concentrations, suggesting that patients with XLH may have an altered response to extracellular phosphate. To test for the presence of abnormal phosphate responsiveness, we compared serum biochemistries and femoral Fgf23 mRNA expression between wild-type mice, murine models of XLH (Phex(K496X)) and hyperphosphatemic tumoral calcinosis (Galnt3(-/-)), and Galnt3/Phex double-mutant mice. Phex mutant mice had not only increased Fgf23 expression but also reduced proteolytic cleavage of intact Fgf23 protein, resulting in markedly elevated intact Fgf23 levels and consequent hypophosphatemia. In contrast, despite markedly increased Fgf23 expression, Galnt3 knockout mice had significantly high proteolytic cleavage of Fgf23 protein, leading to low intact Fgf23 concentrations and hyperphosphatemia. Galnt3/Phex double-mutant mice had an intermediate biochemical phenotype between wild-type and Phex mutant mice, including slightly elevated intact Fgf23 concentrations with milder hypophosphatemia. Despite the hypophosphatemia, double-mutant mice attempted to reduce serum phosphate back to the level of Phex mutant mice by upregulating Fgf23 expression as much as 24-fold higher than Phex mutant mice. These data suggest that Phex mutations alter the responsiveness of bone cells to extracellular phosphate concentrations and may create a lower set point for "normal" phosphate levels.

Leukotriene B4 receptor type 2 protects against pneumolysin-dependent acute lung injury.

PubMed

Shigematsu, Misako; Koga, Tomoaki; Ishimori, Ayako; Saeki, Kazuko; Ishii, Yumiko; Taketomi, Yoshitaka; Ohba, Mai; Jo-Watanabe, Airi; Okuno, Toshiaki; Harada, Norihiro; Harayama, Takeshi; Shindou, Hideo; Li, Jian-Dong; Murakami, Makoto; Hoka, Sumio; Yokomizo, Takehiko

2016-10-05

Although pneumococcal infection is a serious problem worldwide and has a high mortality rate, the molecular mechanisms underlying the lethality caused by pneumococcus remain elusive. Here, we show that BLT2, a G protein-coupled receptor for leukotriene B 4 and 12(S)-hydroxyheptadecatrienoic acid (12-HHT), protects mice from lung injury caused by a pneumococcal toxin, pneumolysin (PLY). Intratracheal injection of PLY caused lethal acute lung injury (ALI) in BLT2-deficient mice, with evident vascular leakage and bronchoconstriction. Large amounts of cysteinyl leukotrienes (cysLTs), classically known as a slow reactive substance of anaphylaxis, were detected in PLY-treated lungs. PLY-dependent vascular leakage, bronchoconstriction, and death were markedly ameliorated by treatment with a CysLT1 receptor antagonist. Upon stimulation by PLY, mast cells produced cysLTs that activated CysLT1 expressed in vascular endothelial cells and bronchial smooth muscle cells, leading to lethal vascular leakage and bronchoconstriction. Treatment of mice with aspirin or loxoprofen inhibited the production of 12-HHT and increased the sensitivity toward PLY, which was also ameliorated by the CysLT1 antagonist. Thus, the present study identifies the molecular mechanism underlying PLY-dependent ALI and suggests the possible use of CysLT1 antagonists as a therapeutic tool to protect against ALI caused by pneumococcal infection.

Leukotriene B4 receptor type 2 protects against pneumolysin-dependent acute lung injury

PubMed Central

Shigematsu, Misako; Koga, Tomoaki; Ishimori, Ayako; Saeki, Kazuko; Ishii, Yumiko; Taketomi, Yoshitaka; Ohba, Mai; Jo-Watanabe, Airi; Okuno, Toshiaki; Harada, Norihiro; Harayama, Takeshi; Shindou, Hideo; Li, Jian-Dong; Murakami, Makoto; Hoka, Sumio; Yokomizo, Takehiko

2016-01-01

Although pneumococcal infection is a serious problem worldwide and has a high mortality rate, the molecular mechanisms underlying the lethality caused by pneumococcus remain elusive. Here, we show that BLT2, a G protein-coupled receptor for leukotriene B4 and 12(S)-hydroxyheptadecatrienoic acid (12-HHT), protects mice from lung injury caused by a pneumococcal toxin, pneumolysin (PLY). Intratracheal injection of PLY caused lethal acute lung injury (ALI) in BLT2-deficient mice, with evident vascular leakage and bronchoconstriction. Large amounts of cysteinyl leukotrienes (cysLTs), classically known as a slow reactive substance of anaphylaxis, were detected in PLY-treated lungs. PLY-dependent vascular leakage, bronchoconstriction, and death were markedly ameliorated by treatment with a CysLT1 receptor antagonist. Upon stimulation by PLY, mast cells produced cysLTs that activated CysLT1 expressed in vascular endothelial cells and bronchial smooth muscle cells, leading to lethal vascular leakage and bronchoconstriction. Treatment of mice with aspirin or loxoprofen inhibited the production of 12-HHT and increased the sensitivity toward PLY, which was also ameliorated by the CysLT1 antagonist. Thus, the present study identifies the molecular mechanism underlying PLY-dependent ALI and suggests the possible use of CysLT1 antagonists as a therapeutic tool to protect against ALI caused by pneumococcal infection. PMID:27703200

Snake fungal disease: an emerging threat to wild snakes.

PubMed

Lorch, Jeffrey M; Knowles, Susan; Lankton, Julia S; Michell, Kathy; Edwards, Jaime L; Kapfer, Joshua M; Staffen, Richard A; Wild, Erik R; Schmidt, Katie Z; Ballmann, Anne E; Blodgett, Doug; Farrell, Terence M; Glorioso, Brad M; Last, Lisa A; Price, Steven J; Schuler, Krysten L; Smith, Christopher E; Wellehan, James F X; Blehert, David S

2016-12-05

Since 2006, there has been a marked increase in the number of reports of severe and often fatal fungal skin infections in wild snakes in the eastern USA. The emerging condition, referred to as snake fungal disease (SFD), was initially documented in rattlesnakes, where the infections were believed to pose a risk to the viability of affected populations. The disease is caused by Ophidiomyces ophiodiicola, a fungus recently split from a complex of fungi long referred to as the Chrysosporium anamorph of Nannizziopsis vriesii (CANV). Here we review the current state of knowledge about O. ophiodiicola and SFD. In addition, we provide original findings which demonstrate that O. ophiodiicola is widely distributed in eastern North America, has a broad host range, is the predominant cause of fungal skin infections in wild snakes and often causes mild infections in snakes emerging from hibernation. This new information, together with what is already available in the scientific literature, advances our knowledge of the cause, pathogenesis and ecology of SFD. However, additional research is necessary to elucidate the factors driving the emergence of this disease and develop strategies to mitigate its impacts.This article is part of the themed issue 'Tackling emerging fungal threats to animal health, food security and ecosystem resilience'. © 2016 The Author(s).

Snake fungal disease: an emerging threat to wild snakes

PubMed Central

Lorch, Jeffrey M.; Knowles, Susan; Lankton, Julia S.; Michell, Kathy; Edwards, Jaime L.; Kapfer, Joshua M.; Staffen, Richard A.; Wild, Erik R.; Schmidt, Katie Z.; Ballmann, Anne E.; Blodgett, Doug; Farrell, Terence M.; Glorioso, Brad M.; Last, Lisa A.; Price, Steven J.; Schuler, Krysten L.; Smith, Christopher E.; Wellehan, James F. X.; Blehert, David S.

2016-01-01

Since 2006, there has been a marked increase in the number of reports of severe and often fatal fungal skin infections in wild snakes in the eastern USA. The emerging condition, referred to as snake fungal disease (SFD), was initially documented in rattlesnakes, where the infections were believed to pose a risk to the viability of affected populations. The disease is caused by Ophidiomyces ophiodiicola, a fungus recently split from a complex of fungi long referred to as the Chrysosporium anamorph of Nannizziopsis vriesii (CANV). Here we review the current state of knowledge about O. ophiodiicola and SFD. In addition, we provide original findings which demonstrate that O. ophiodiicola is widely distributed in eastern North America, has a broad host range, is the predominant cause of fungal skin infections in wild snakes and often causes mild infections in snakes emerging from hibernation. This new information, together with what is already available in the scientific literature, advances our knowledge of the cause, pathogenesis and ecology of SFD. However, additional research is necessary to elucidate the factors driving the emergence of this disease and develop strategies to mitigate its impacts. This article is part of the themed issue ‘Tackling emerging fungal threats to animal health, food security and ecosystem resilience’. PMID:28080983

[Increasing cost of insulin therapy in Belgium. From a critical analysis of the situation to a search for practical solutions].

PubMed

Scheen, A J

2006-09-01

Cost related to insulin therapy is markedly increasing in Belgium, as in other Eucopean countries. In the present paper, we will briefly analyze the main reasons for such aa increase, integrate such observation withIn the global context of diabetes management and suggest some solutions to provide best care to insulin-treated diabetic patients at a reasonable cost. The rise of the cost of insulin therapy has a multifactorial origin. It mainly results from an increase in the number of diabetic patients, a more intensive management, In both type 1 and type 2 diabetes, and a greater use of more expansive insulin analogues. It is important to analyze the increase of the cost of insulin therapy within the global burden of diabetes melitus. Only a better responsibility of all health care partners, patients, physicians, pharmaceutical companies, public health authorities, could provide solutions allowing diabetic people to profit from best treatments they should receive in order to prevent diabetic complications, by far the main cause of expenses.

Development of acute pancreatitis caused by sodium valproate in a patient with bipolar disorder on hemodialysis for chronic renal failure: a case report.

PubMed

Okayasu, Hiroaki; Shinozaki, Takahiro; Osone, Akira; Ozeki, Yuji; Shimoda, Kazutaka

2014-03-29

Cases of acute pancreatitis caused by sodium valproate (VPA) have been reported by many authors thus far. However, most of these were cases with epilepsy. Chronic renal failure is also regarded as a risk factor for acute pancreatitis. Here, we report a case of acute pancreatitis development due to VPA in a patient with bipolar disorder on hemodialysis for chronic renal failure. The patient was a 52-year-old Japanese male who was diagnosed as bipolar disorder on hemodialysis for renal failure. He was treated with VPA and manic symptoms gradually stabilized. However, the patient complained of severe abdominal pain. Blood amylase was found to be markedly high, and computed tomography revealed pancreatomegaly and an increased amount of peripancreatic fat. Hence, we diagnosed the case as acute pancreatitis caused by VPA. We discontinued oral medication, and he was started on a pancreatic enzyme inhibitor, antibiotics, and transfusion, and he showed improvement. It has been reported that acute pancreatitis induced by VPA is caused by intermediate metabolites of VPA. We consider that patients with renal failure are prone to pancreatitis caused by VPA because of the accumulation of these intermediate metabolites. We need close monitoring for serious adverse effects such as pancreatitis when we prescribe VPA to patients with bipolar disorder on hemodialysis for chronic renal failure, although VPA is safer than other mood stabilizers.

Comparison of Anorectic and Emetic Potencies of Deoxynivalenol (Vomitoxin) to the Plant Metabolite Deoxynivalenol-3-Glucoside and Synthetic Deoxynivalenol Derivatives EN139528 and EN139544

PubMed Central

Wu, Wenda; Zhou, Hui-Ren; Bursian, Steven J.; Pan, Xiao; Link, Jane E.; Berthiller, Franz; Adam, Gerhard; Krantis, Anthony; Durst, Tony; Pestka, James J.

2014-01-01

The mycotoxin deoxynivalenol (DON) elicits robust anorectic and emetic effects in several animal species. However, less is known about the potential for naturally occurring and synthetic congeners of this trichothecene to cause analogous responses. Here we tested the hypothesis that alterations in DON structure found in the plant metabolite deoxynivalenol-3-glucoside (D3G) and two pharmacologically active synthetic DON derivatives, EN139528 and EN139544, differentially impact their potential to evoke food refusal and emesis. In a nocturnal mouse food consumption model, oral administration with DON, D3G, EN139528, or EN139544 at doses from 2.5 to 10 mg/kg BW induced anorectic responses that lasted up to 16, 6, 6, and 3 h, respectively. Anorectic potency rank orders were EN139544>DON>EN139528>D3G from 0 to 0.5 h but DON>D3G>EN139528>EN139544 from 0 to 3 h. Oral exposure to each of the four compounds at a common dose (2.5 mg/kg BW) stimulated plasma elevations of the gut satiety peptides cholecystokinin and to a lesser extent, peptide YY3–36 that corresponded to reduced food consumption. In a mink emesis model, oral administration of increasing doses of the congeners differentially induced emesis, causing marked decreases in latency to emesis with corresponding increases in both the duration and number of emetic events. The minimum emetic doses for DON, EN139528, D3G, and EN139544 were 0.05, 0.5, 2, and 5 mg/kg BW, respectively. Taken together, the results suggest that although all three DON congeners elicited anorectic responses that mimicked DON over a narrow dose range, they were markedly less potent than the parent mycotoxin at inducing emesis. PMID:25173790

2001-2012 trends on air quality in Spain.

PubMed

Querol, X; Alastuey, A; Pandolfi, M; Reche, C; Pérez, N; Minguillón, M C; Moreno, T; Viana, M; Escudero, M; Orio, A; Pallarés, M; Reina, F

2014-08-15

This study aims at interpreting the 2001-2012 trends of major air pollutants in Spain, with a major focus on evaluating their relationship with those of the national emission inventories (NEI) and policy actions. Marked downward concentration trends were evidenced for PM10, PM2.5 and CO. Concentrations of NO2 and NOx also declined but in a lesser proportion at rural and traffic sites. At rural sites O3 has been kept constant, whereas it clearly increased at urban and industrial sites. Comparison of the air quality trends and major inflection points with those from NEIs, the National Energy Consumption and the calendar of the implementation of major policy actions allowed us to clearly identify major benefits of European directives on power generation and industrial sources (such as the Large Combustion Plants and the Integrated Pollution Prevention and Control Directives). This, together with a sharp 2007-2008 decrease of coal consumption has probably caused the marked parallel decline of SO2, NOx and for PM2.5 concentrations. Also the effect of the EURO 4 and 5 vehicle emission standards on decreasing emissions of PM and CO from vehicles is noticeable. The smooth decline in NO2-NOx levels is mostly attributed to the low efficiency of EURO 4 and 5 standards in reducing real life urban driving NO2 emissions. The low NOx decrease together with the complexity of the reactions of O3 formation is responsible for the constant O3 concentrations, or even the urban increase. The financial crisis has also contributed to the decrease of the ambient concentration of pollutants; however this caused a major reduction of the primary energy consumption from 2008 to 2009, and not from 2007 to 2008 when ambient air PM and SO2 sharply decreased. The meteorological influence was characterized by a 2008-2012 period favorable to the dispersion of pollutants when compared to the 2001-2007. Copyright © 2014. Published by Elsevier B.V.

Effect of detomidine on visceral and somatic nociception and duodenal motility in conscious adult horses.

PubMed

Elfenbein, Johanna R; Sanchez, L Chris; Robertson, Sheilah A; Cole, Cynthia A; Sams, Richard

2009-03-01

To evaluate the effects of detomidine on visceral and somatic nociception, heart and respiratory rates, sedation, and duodenal motility and to correlate these effects with serum detomidine concentrations. Nonrandomized, experimental trial. Five adult horses, each with a permanent gastric cannula weighing 534 +/- 46 kg. Visceral nociception was evaluated by colorectal (CRD) and duodenal distension (DD). The duodenal balloon was used to assess motility. Somatic nociception was assessed via thermal threshold (TT). Nose-to-ground (NTG) height was used as a measure of sedation. Serum was collected for pharmacokinetic analysis. Detomidine (10 or 20 microg kg(-1)) was administered intravenously. Data were analyzed by means of a three-factor anova with fixed factors of treatment and time and random factor of horse. When a significant time x treatment interaction was detected, differences were compared with a simple t-test or Bonferroni t-test. Significance was set at p < 0.05. Detomidine produced a significant, dose-dependent decrease in NTG height, heart rate, and skin temperature and a significant, nondose-dependent decrease in respiratory rate. Colorectal distension threshold was significantly increased with 10 microg kg(-1) for 15 minutes and for at least 165 minutes with 20 microg kg(-1). Duodenal distension threshold was significantly increased at 15 minutes for the 20 microg kg(-1) dose. A significant change in TT was not observed at either dose. A marked, immediate decrease in amplitude of duodenal contractions followed detomidine administration at both doses for 50 minutes. Detomidine caused a longer period of visceral anti-nociception as determined by CRD but a shorter period of anti-nociception as determined by DD than has been previously reported. The lack of somatic anti-nociception as determined by TT testing may be related to the marked decrease in skin temperature, likely caused by peripheral vasoconstriction and the low temperature cut-off of the testing device.

Anticipating implementation of colorectal cancer screening in The Netherlands: a nation wide survey on endoscopic supply and demand

PubMed Central

2012-01-01

Background Colorectal cancer (CRC) screening requires sufficient endoscopic resources. The present study aims to determine the Dutch endoscopic production and manpower for 2009, evaluate trends since 2004, determine additional workload which would be caused by implementation of a CRC screening program, and inventory colonoscopy rates performed in other European countries. Methods All Dutch endoscopy units (N = 101) were surveyed for manpower and the numbers of endoscopy procedures performed in 2009. Based on calculations in the report issued by the Dutch Health Council, future additional workload caused by faecal immunochemical test (FIT) screening was estimated. The number of colonoscopies performed in Europe was evaluated by a literature search and an email-inquiry. Results Compared to 2004, there was a 24% increase in total endoscopies (N = 505,226 in 2009), and a 64% increase in colonoscopies (N = 191,339 in 2009) in The Netherlands. The number of endoscopists had increased by 4.6% (N = 583 in 2009). Five years after stepwise implementation of FIT-based CRC screening, endoscopic capacity needs to be increased an additional 15%. A lack of published data on the number of endoscopies performed in Europe was found. Based on our email-inquiry, the number of colonoscopies per 100,000 inhabitants ranged from 126 to 3,031 in 15 European countries. Conclusions Over the last years, endoscopic procedures increased markedly in The Netherlands without a corresponding increase in manpower. A FIT-based CRC screening program requires an estimated additional 15% increase in endoscopic procedures. It is very likely that current colonoscopy density varies widely across European countries. PMID:22280408

Phospholipases A2 isolated from Micrurus lemniscatus coral snake venom: behavioral, electroencephalographic, and neuropathological aspects.

PubMed

Oliveira, D A; Harasawa, C; Seibert, C S; Casais e Silva, L L; Pimenta, D C; Lebrun, I; Sandoval, M R L

2008-03-28

The present study evaluated four phospholipase A2 (PLA2) (Mlx-8, Mlx-9, Mlx-11 and Mlx-12) isolated from Micrurus lemniscatus snake venom (Elapidae). The effects of intrahippocampal administration of these toxins have been determined on behavior, electroencephalography, and neuronal degeneration in rats. These four PLA2 toxins induced motor and EEG alterations in a dose-dependent manner. Behavioral convulsions were characterized by clonic movements and were often accompanied by EEG alterations. Mlx toxins were convulsive but weakly epileptogenic, since low rates of seizure discharges were observed in EEG records. Neuronal injury seemed to depend on the dose of the toxin used. The highest doses of toxins caused severe intoxication and death of some animals. The injury of hippocampal cells was characterized by massive neuronal loss and hippocampal gliosis. A high occurrence of compulsive scratching was observed. Moreover, the onset of seizures induced by Mlx toxins was markedly delayed. The similarities between the effects of Mlx PLA2s and those isolated from other Elapidae snakes venoms suggest that their toxicity are probably due to their specific binding to neuronal membranes and to the catalysis of phospholipid hydrolysis, producing lysophospholipids and fatty acids. These compounds likely disturb the membrane conformation, causing a marked increase in the release of neurotransmitters and concurrent inhibition of vesicle fission and recycling. These toxins can be a useful tool to investigate properties of endogenous secretory PLA2s and therefore may be important both to study mechanisms involved in neurotransmitter release at nerve terminals and to explain the convulsive properties of PLA2s toxins.

Effects of Fiber Type and Size on the Heterogeneity of Oxygen Distribution in Exercising Skeletal Muscle

PubMed Central

Liu, Gang; Mac Gabhann, Feilim; Popel, Aleksander S.

2012-01-01

The process of oxygen delivery from capillary to muscle fiber is essential for a tissue with variable oxygen demand, such as skeletal muscle. Oxygen distribution in exercising skeletal muscle is regulated by convective oxygen transport in the blood vessels, oxygen diffusion and consumption in the tissue. Spatial heterogeneities in oxygen supply, such as microvascular architecture and hemodynamic variables, had been observed experimentally and their marked effects on oxygen exchange had been confirmed using mathematical models. In this study, we investigate the effects of heterogeneities in oxygen demand on tissue oxygenation distribution using a multiscale oxygen transport model. Muscles are composed of different ratios of the various fiber types. Each fiber type has characteristic values of several parameters, including fiber size, oxygen consumption, myoglobin concentration, and oxygen diffusivity. Using experimentally measured parameters for different fiber types and applying them to the rat extensor digitorum longus muscle, we evaluated the effects of heterogeneous fiber size and fiber type properties on the oxygen distribution profile. Our simulation results suggest a marked increase in spatial heterogeneity of oxygen due to fiber size distribution in a mixed muscle. Our simulations also suggest that the combined effects of fiber type properties, except size, do not contribute significantly to the tissue oxygen spatial heterogeneity. However, the incorporation of the difference in oxygen consumption rates of different fiber types alone causes higher oxygen heterogeneity compared to control cases with uniform fiber properties. In contrast, incorporating variation in other fiber type-specific properties, such as myoglobin concentration, causes little change in spatial tissue oxygenation profiles. PMID:23028531

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.

Wave intensity analysis and its application to the coronary circulation

PubMed Central

Davies, JE; Escaned, JE; Hughes, A; Parker, K

Wave intensity analysis (WIA) is a technique developed from the field of gas dynamics that is now being applied to assess cardiovascular physiology. It allows quantification of the forces acting to alter flow and pressure within a fluid system, and as such it is highly insightful in ascribing cause to dynamic blood pressure or velocity changes. When co-incident waves arrive at the same spatial location they exert either counteracting or summative effects on flow and pressure. WIA however allows waves of different origins to be measured uninfluenced by other simultaneously arriving waves. It therefore has found particular applicability within the coronary circulation where both proximal (aortic) and distal (myocardial) ends of the coronary artery can markedly influence blood flow. Using these concepts, a repeating pattern of 6 waves has been consistently identified within the coronary arteries, 3 originating proximally and 3 distally. Each has been associated with a particular part of the cardiac cycle. The most clinically relevant wave to date is the backward decompression wave, which causes the marked increase in coronary flow velocity observed at the start of the diastole. It has been proposed that this wave is generated by the elastic re-expansion of the intra-myocardial blood vessels that are compressed during systolic contraction. Particularly by quantifying this wave, WIA has been used to provide mechanistic and prognostic insight into a number of conditions including aortic stenosis, left ventricular hypertrophy, coronary artery disease and heart failure. It has proven itself to be highly sensitive and as such a number of novel research directions are encouraged where further insights would be beneficial. PMID:28971104

Synergism between thrombin and adrenaline (epinephrine) in human platelets. Marked potentiation of inositol phospholipid metabolism.

PubMed Central

Steen, V M; Tysnes, O B; Holmsen, H

1988-01-01

We have studied synergism between adrenaline (epinephrine) and low concentrations of thrombin in gel-filtered human platelets prelabelled with [32P]Pi. Suspensions of platelets, which did not contain added fibrinogen, were incubated at 37 degrees C to measure changes in the levels of 32P-labelled phosphatidylinositol 4,5-bisphosphate (PIP2), phosphatidylinositol 4-phosphate (PIP) and phosphatidate (PA), aggregation and dense-granule secretion after stimulation. Adrenaline alone (3.5-4.0 microM) did not cause a change in any parameter (phosphoinositide metabolism, aggregation and dense-granule secretion), but markedly enhanced the thrombin-induced responses over a narrow range of thrombin concentrations (0.03-0.08 units/ml). The thrombin-induced hydrolysis of inositol phospholipids by phospholipase C, which was measured as the formation of [32P]PA, was potentiated by adrenaline, as was the increase in the levels of [32P]PIP2 and [32P]PIP. The presence of adrenaline caused a shift to the left for the thrombin-induced changes in the phosphoinositide metabolism, without affecting the maximal levels of 32P-labelled compounds obtained. A similar shift by adrenaline in the dose-response relationship was previously demonstrated for thrombin-induced aggregation and dense-granule secretion. Also, the narrow range of concentrations of thrombin over which adrenaline potentiates thrombin-induced platelet responses is the same for changes in phosphoinositide metabolism and physiological responses (aggregation and dense-granule secretion). Our observations clearly indicate that adrenaline directly or indirectly influences thrombin-induced changes in phosphoinositide metabolism. PMID:2845924