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

Climatic changes resulting from mass extinctions at the K-T boundary (and other bio-events)

NASA Technical Reports Server (NTRS)

Rampino, Michael R.; Volk, Tyler

1988-01-01

The mass extinctions at the Cretaceous-Tertiary (K-T) boundary include about 90 percent of marine calcareous nannoplankton (coccoliths), and carbon-isotope data show that marine primary productivity was drastically reduced for about 500,000 years after the boundary event, the so-called Strangelove Ocean effect. One result of the elimination of most marine phytoplankton would have been a severe reduction in production of dimethyl sulfide (DMS), a biogenic gas that is believed to be the major precursor of cloud condensation nuclei (CCN) over the oceans. A drastic reduction in marine CCN should lead to a cloud canopy with significantly lower reflectivity, and hence cause a significant warming at the earth's surface. Calculations suggest that, all other things being held constant, a reduction in CCN of more than 80 percent (a reasonable value for the K-T extinctions) could have produced a rapid global warming of 6 C or more. Oxygen-isotope analyses of marine sediments, and other kinds of paleoclimatic data, have provided for a marked warming, and a general instability of climate coincident with the killoff of marine plankton at the K-T boundary. Similar reductions in phytoplankton abundance at other boundaries, as indicated by marked shifts in carbon-isotope curves, suggest that severe temperature changes may have accompanied other mass extinctions, and raises the intriguing possibility that the extinction events themselves could have contributed to the climatic instabilities at critical bio-events in the geologic record.

Identification of SLEEPLESS, a sleep-promoting factor.

PubMed

Koh, Kyunghee; Joiner, William J; Wu, Mark N; Yue, Zhifeng; Smith, Corinne J; Sehgal, Amita

2008-07-18

Sleep is an essential process conserved from flies to humans. The importance of sleep is underscored by its tight homeostatic control. Through a forward genetic screen, we identified a gene, sleepless, required for sleep in Drosophila. The sleepless gene encodes a brain-enriched, glycosylphosphatidylinositol-anchored protein. Loss of SLEEPLESS protein caused an extreme (>80%) reduction in sleep; a moderate reduction in SLEEPLESS had minimal effects on baseline sleep but markedly reduced the amount of recovery sleep after sleep deprivation. Genetic and molecular analyses revealed that quiver, a mutation that impairs Shaker-dependent potassium current, is an allele of sleepless. Consistent with this finding, Shaker protein levels were reduced in sleepless mutants. We propose that SLEEPLESS is a signaling molecule that connects sleep drive to lowered membrane excitability.

Adhesion of the clay minerals montmorillonite, kaolinite, and attapulgite reduces respiration of Histoplasma capsulatum.

PubMed Central

Lavie, S; Stotzky, G

1986-01-01

The respiration of three phenotypes of Histoplasma capsulatum, the causal agent of histoplasmosis in humans, was markedly reduced by low concentrations of montmorillonite but was reduced less by even higher concentrations of kaolinite or attapulgite (palygorskite). The reduction in respiration followed a pattern that suggested saturation-type kinetics: an initial sharp reduction that occurred with low concentrations of clay (0.01 to 0.5% [wt/vol]), followed by a more gradual reduction with higher concentrations (1 to 8%). Increases in viscosity (which could impair the movement of O2) caused by the clays were not responsible for the reduction in respiration, and the clays did not interfere with the availability of nutrients. Scanning electron microscopy after extensive washing showed that the clay particles were tightly bound to the hyphae, suggesting that the clays reduced the rate of respiration of H. capsulatum by adhering to the mycelial surface and, thereby, interfered with the movement of nutrients, metabolites, and gases across the mycelial wall. Images PMID:3954340

Adhesion of the clay minerals montmorillonite, kaolinite, and attapulgite reduces respiration of Histoplasma capsulatum.

PubMed

Lavie, S; Stotzky, G

1986-01-01

The respiration of three phenotypes of Histoplasma capsulatum, the causal agent of histoplasmosis in humans, was markedly reduced by low concentrations of montmorillonite but was reduced less by even higher concentrations of kaolinite or attapulgite (palygorskite). The reduction in respiration followed a pattern that suggested saturation-type kinetics: an initial sharp reduction that occurred with low concentrations of clay (0.01 to 0.5% [wt/vol]), followed by a more gradual reduction with higher concentrations (1 to 8%). Increases in viscosity (which could impair the movement of O2) caused by the clays were not responsible for the reduction in respiration, and the clays did not interfere with the availability of nutrients. Scanning electron microscopy after extensive washing showed that the clay particles were tightly bound to the hyphae, suggesting that the clays reduced the rate of respiration of H. capsulatum by adhering to the mycelial surface and, thereby, interfered with the movement of nutrients, metabolites, and gases across the mycelial wall.

Acetylcholine suppresses shoot formation and callusing in leaf explants of in vitro raised seedlings of tomato, Lycopersicon esculentum Miller var. Pusa Ruby.

PubMed

Bamel, Kiran; Gupta, Rajendra; Gupta, Shirish C

2016-06-02

We present experimental evidence to show that acetylcholine (ACh) causes decrease in shoot formation in leaf explants of tomato (Lycopersicon esculentum Miller var Pusa Ruby) when cultured on shoot regeneration medium. The optimum response was obtained at 10(-4) M ACh-enriched medium. ACh also causes decrease in percentage of cultures forming callus and reduces the callus mass. Inhibitors of enzymatic hydrolysis of ACh, neostigmine and physostigmine, also suppresses callogenesis and caulogenesis. On the other hand, the breakdown products of Ach, choline and acetate, do not alter the morphogenic response induced on the shoot regeneration medium. Neostigmine showed optimal reduction in shoot formation at 10(-5) M. The explants cultured on neostigmine augmented medium showed decline in the activity of ACh hydrolyzing enzyme acetylcholinesterase. ACh and neostigmine added together showed marked reduction in callus mass. These results strongly support the role of ACh as a natural regulator of morphogenesis in tomato plants.

Acetylcholine suppresses shoot formation and callusing in leaf explants of in vitro raised seedlings of tomato, Lycopersicon esculentum Miller var. Pusa Ruby

PubMed Central

Bamel, Kiran; Gupta, Rajendra; Gupta, Shirish C.

2016-01-01

ABSTRACT We present experimental evidence to show that acetylcholine (ACh) causes decrease in shoot formation in leaf explants of tomato (Lycopersicon esculentum Miller var Pusa Ruby) when cultured on shoot regeneration medium. The optimum response was obtained at 10−4 M ACh-enriched medium. ACh also causes decrease in percentage of cultures forming callus and reduces the callus mass. Inhibitors of enzymatic hydrolysis of ACh, neostigmine and physostigmine, also suppresses callogenesis and caulogenesis. On the other hand, the breakdown products of Ach, choline and acetate, do not alter the morphogenic response induced on the shoot regeneration medium. Neostigmine showed optimal reduction in shoot formation at 10−5 M. The explants cultured on neostigmine augmented medium showed decline in the activity of ACh hydrolyzing enzyme acetylcholinesterase. ACh and neostigmine added together showed marked reduction in callus mass. These results strongly support the role of ACh as a natural regulator of morphogenesis in tomato plants. PMID:27348536

Corneal limbal marking in the treatment of myopic astigmatism with the excimer laser.

PubMed

Bucher, Celine; Zuberbuhler, Bruno; Goggin, Michael; Esterman, Adrian; Schipper, Isaak

2010-07-01

To determine whether preoperative marking of the limbal cornea improves treatment of myopic astigmatism with the excimer laser. Retrospective study on 108 eyes with myopic astigmatism that underwent LASIK or laser epithelial keratomileusis (LASEK) with the Technolas 217 (Bausch & Lomb) excimer laser. Preoperative limbal marking was performed in 47 eyes (marked group). The 12-month results were used for refractive and visual analysis. The achieved cylinder reduction, spherical reduction, and refractive predictability were similar for the marked and unmarked groups in the overall study collective, in the LASIK and LASEK subgroup analysis, and in a higher astigmatism (> 1.25 diopters) subgroup analysis. Limbal marking showed no influence on the refractive results, and vector analysis showed no significant difference in angle of error among groups. Corneal limbal marking failed to improve the refractive outcome in LASIK and LASEK for myopic astigmatism.

Effects of parallelogram-shaped pavement markings on vehicle speed and safety of pedestrian crosswalks on urban roads in China.

PubMed

Guo, Yanyong; Liu, Pan; Liang, Qiyu; Wang, Wei

2016-10-01

The primary objective of this study was to evaluate the effects of parallelogram-shaped pavement markings on vehicle speed and crashes in the vicinity of urban pedestrian crosswalks. The research team measured speed data at twelve sites, and crash data at eleven sites. Observational cross-sectional studies were conducted to identify if the effects of parallelogram-shaped pavement markings on vehicle speeds and speed violations were statistically significant. The results showed that parallelogram-shaped pavement markings significantly reduced vehicle speeds and speed violations in the vicinity of pedestrian crosswalks. More specifically, the speed reduction effects varied from 1.89km/h to 4.41km/h with an average of 3.79km/h. The reduction in the 85th percentile speed varied from 0.81km/h to 5.34km/h with an average of 4.19km/h. Odds ratios (OR) showed that the parallelogram-shaped pavement markings had effects of a 7.1% reduction in the mean speed and a 6.9% reduction in the 85th percentile speed at the pedestrian crosswalks. The reduction of proportion of drivers exceeding the speed limit varied from 8.64% to 14.15% with an average of 11.03%. The results of the crash data analysis suggested that the use of parallelogram-shaped pavement markings reduced both the frequency and severity of crashes at pedestrian crosswalks. The parallelogram-shaped pavement markings had a significant effect on reducing the vehicle-pedestrian crashes. Two crash prediction models were developed for vehicle-pedestrian crashes and rear-end crashes. According to the crash models, the presence of parallelogram-shaped pavement markings reduced vehicle-pedestrian crashes at pedestrian crosswalks by 24.87% with a 95% confidence interval of [10.06-30.78%]. However, the model results also showed that the presence of parallelogram-shaped pavement markings increased rear-end crashes at pedestrian crosswalks by 5.4% with a 95% confidence interval of [0-11.2%]. Copyright © 2015 Elsevier Ltd. All rights reserved.

77 FR 14505 - Proposed Information Collection; Comment Request; Gear-Marking Requirement for Atlantic Large...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-12

... Collection; Comment Request; Gear-Marking Requirement for Atlantic Large Whale Take Reduction Plan AGENCY... of large whales, especially right whales, due to incidental entanglement in the United States (U.S... Large Whale Take Reduction Plan (ALWTRP), developed under the authority of the Marine Mammal Protection...

Intravenous Bevacizumab Causes Regression of Choroidal Neovascularization Secondary to Diseases Other Than Age-related Macular Degeneration

PubMed Central

NGUYEN, QUAN DONG; SHAH, SYED MAHMOOD; HAFIZ, GULNAR; DO, DIANA V.; HALLER, JULIA A.; PILI, ROBERTO; ZIMMER-GALLER, INGRID E.; JANJUA, KASHIF; SYMONS, R. C. ANDREW; CAMPOCHIARO, PETER A.

2016-01-01

PURPOSE To investigate the safety, tolerability, and bioactivity of intravenous infusions of bevacizumab in patients with choroidal neovascularization (CNV) attributable to causes other than age-related macular degeneration. DESIGN Nonrandomized clinical trial. METHODS Ten patients with CNV received infusions of 5 mg/kg of bevacizumab. The primary efficacy outcome measure was change in visual acuity (VA; Early Treatment Diabetic Retinopathy Study letters read at 4 meters) at 24 weeks and secondary measures were changes from baseline in excess foveal thickness (center subfield thickness), area of fluorescein leakage, and area of CNV. RESULTS Infusions were well tolerated and there were no ocular or systemic adverse events. At baseline, median VA was 25.5 letters read at 4 meters (20/80) and median foveal thickness was 346 μm. At the primary endpoint (24 weeks), median VA was 48.5 letters (20/32), representing four lines of improvement from baseline (P = .005), median foveal thickness was 248 μm representing a 72% reduction in excess foveal thickness (P = .007). Four of nine patients had complete elimination of fluorescein leakage, three had near complete elimination (reductions of 91%, 88%, and 87%), two had modest reductions, and one had no reduction. All patients except one showed a reduction in area of CNV with a median reduction of 43%. CONCLUSIONS Despite the small number of patients studied, the marked improvement in VA accompanied by prominent reductions in foveal thickness, fluorescein leakage, and area of CNV suggest a beneficial effect. It may be worthwhile to consider further evaluation of systemic bevacizumab in young patients with CNV. PMID:18054887

Compromised genomic integrity impedes muscle growth after Atrx inactivation

PubMed Central

Huh, Michael S.; Price O’Dea, Tina; Ouazia, Dahmane; McKay, Bruce C.; Parise, Gianni; Parks, Robin J.; Rudnicki, Michael A.; Picketts, David J.

2012-01-01

ATR-X syndrome is a severe intellectual disability disorder caused by mutations in the ATRX gene. Many ancillary clinical features are attributed to CNS deficiencies, yet most patients have muscle hypotonia, delayed ambulation, or kyphosis, pointing to an underlying skeletal muscle defect. Here, we identified a cell-intrinsic requirement for Atrx in postnatal muscle growth and regeneration in mice. Mice with skeletal muscle–specific Atrx conditional knockout (Atrx cKO mice) were viable, but by 3 weeks of age presented hallmarks of underdeveloped musculature, including kyphosis, 20% reduction in body mass, and 34% reduction in muscle fiber caliber. Atrx cKO mice also demonstrated a marked regeneration deficit that was not due to fewer resident satellite cells or their inability to terminally differentiate. However, activation of Atrx-null satellite cells from isolated muscle fibers resulted in a 9-fold reduction in myoblast expansion, caused by delayed progression through mid to late S phase. While in S phase, Atrx colocalized specifically to late-replicating chromatin, and its loss resulted in rampant signs of genomic instability. These observations support a model in which Atrx maintains chromatin integrity during the rapid developmental growth of a tissue. PMID:23114596

Lassa virus infection in experimentally infected marmosets: liver pathology and immunophenotypic alterations in target tissues.

PubMed

Carrion, Ricardo; Brasky, Kathleen; Mansfield, Keith; Johnson, Curtis; Gonzales, Monica; Ticer, Anysha; Lukashevich, Igor; Tardif, Suzette; Patterson, Jean

2007-06-01

Lassa virus causes thousands of deaths annually in western Africa and is considered a potential biological weapon. In an attempt to develop a small nonhuman primate model of Lassa fever, common marmosets were subcutaneously inoculated with Lassa virus strain Josiah. This inoculation resulted in a systemic disease with clinical and morphological features mirroring those in fatal human Lassa infection: fever, weight loss, high viremia and viral RNA load in tissues, elevated liver enzymes, and severe morbidity between days 15 and 20. The most prominent histopathology findings included multifocal hepatic necrosis with mild inflammation and hepatocyte proliferation, lymphoid depletion, and interstitial nephritis. Cellular aggregates in regions of hepatocellular necrosis were largely composed of HAM56-positive macrophages, devoid of CD3-positive and CD20-positive cells, and characterized by marked reductions in the intensity of HLA-DP, DQ, DR staining. A marked reduction in the major histocompatibility complex class II expression was also observed in the lymph nodes. Immunophenotypic alterations in spleen included reductions in overall numbers of CD20-positive and CD3-positive cells and the disruption of lymphoid follicular architecture. These findings identify the common marmoset as an appropriate model of human Lassa fever and present the first experimental evidence that replication of Lassa virus in tissues is associated with alterations that would be expected to impair adaptive immunity.

Omeprazole and dry mouth.

PubMed

Teare, J P; Spedding, C; Whitehead, M W; Greenfield, S M; Challacombe, S J; Thompson, R P

1995-03-01

Omeprazole causes irreversible inhibition of the hydrogen/potassium adenosine triphosphatase enzyme, leading to a marked reduction in both acid secretion and volume of gastric juice. Reported side-effects include nausea, vomiting, diarrhoea, constipation, and headache. We report the development of dry mouth during omeprazole therapy. We have identified six patients taking omeprazole for more than 6 weeks who complained of a dry mouth. Salivary production was measured as whole salivary flow produced over a 10-min period spat into a collecting vessel and as 5% citric acid-stimulated parotid salivary flow collected with a Lashley cup device placed over the parotid duct. Flow rates were evaluated both during and after cessation of treatment. Saliva produced was then cultured for microbes. Four of the six had subnormal parotid or whole salivary flow rates on treatment that recovered after stopping treatment. The increase after treatment was marked in four. Significant amounts of Candida albicans grew from the saliva of the three patients with the lowest salivary flows; one saliva also grew Staphylococcus aureus. Salivary flow is reduced in some patients treated with omeprazole, returning to normal after cessation of treatment. This reduction may predispose to opportunistic infection, particularly in the edentulous.

Dehydration reduces left ventricular filling at rest and during exercise independent of twist mechanics.

PubMed

Stöhr, Eric J; González-Alonso, José; Pearson, James; Low, David A; Ali, Leena; Barker, Horace; Shave, Rob

2011-09-01

The purpose of this study was to determine whether the reduction in stroke volume (SV), previously shown to occur with dehydration and increases in internal body temperatures during prolonged exercise, is caused by a reduction in left ventricular (LV) function, as indicated by LV volumes, strain, and twist ("LV mechanics"). Eight healthy men [age: 20 ± 2, maximal oxygen uptake (VO₂max): 58 ± 7 ml·kg⁻¹·min⁻¹] completed two, 1-h bouts of cycling in the heat (35°C, 50% peak power) without fluid replacement, resulting in 2% and 3.5% dehydration, respectively. Conventional and two-dimensional speckle-tracking echocardiography was used to determine LV volumes, strain, and twist at rest and during one-legged knee-extensor exercise at baseline, both levels of dehydration, and following rehydration. Progressive dehydration caused a significant reduction in end-diastolic volume (EDV) and SV at rest and during one-legged knee-extensor exercise (rest: Δ-33 ± 14 and Δ-21 ± 14 ml, respectively; exercise: Δ-30 ± 10 and Δ-22 ± 9 ml, respectively, during 3.5% dehydration). In contrast to the marked decline in EDV and SV, systolic and diastolic LV mechanics were either maintained or even enhanced with dehydration at rest and during knee-extensor exercise. We conclude that dehydration-induced reductions in SV at rest and during exercise are the result of reduced LV filling, as reflected by the decline in EDV. The concomitant maintenance of LV mechanics suggests that the decrease in LV filling, and consequently ejection, is likely caused by the reduction in blood volume and/or diminished filling time rather than impaired LV function.

3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of (/sup 3/H)paroxetine-labeled serotonin uptake sites

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

Battaglia, G.; Yeh, S.Y.; O'Hearn, E.

1987-09-01

This study examines the effects of repeated systemic administration (20 mg/kg s.c., twice daily for 4 days) of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) on levels of brain monoamines, their metabolites and on the density of monoamine uptake sites in various regions of rat brain. Marked reductions (30-60%) in the concentration of 5-hydroxyindoleacetic acid were observed in cerebral cortex, hippocampus, striatum, hypothalamus and midbrain at 2 weeks after a 4-day treatment regimen of MDMA or MDA; less consistent reductions in serotonin (5-HT) content were observed in these brain regions. In addition, both MDMA and MDA caused comparable and substantial reductions (50-75%)more » in the density of (/sup 3/H)paroxetine-labeled 5-HT uptake sites in all brain regions examined. In contrast, neither MDMA nor MDA caused any widespread or long-term changes in the content of the catecholaminergic markers (i.e., norepinephrine, dopamine, 3,4 dihydroxyphenylacetic acid and homovanillic acid) or in the number of (/sup 3/H)mazindol-labeled norepinephrine or dopamine uptake sites in the brain regions examined. These data demonstrate that MDMA and MDA cause long-lasting neurotoxic effects with respect to both the functional and structural integrity of serotonergic neurons in brain. Furthermore, our measurement of reductions in the density of 5-HT uptake sites provides a means for quantification of the neurodegenerative effects of MDMA and MDA on presynaptic 5-HT terminals.« less

Technique for systematic bone reduction for fixed implant-supported prosthesis in the edentulous maxilla.

PubMed

Bidra, Avinash S

2015-06-01

Bone reduction for maxillary fixed implant-supported prosthodontic treatment is often necessary to either gain prosthetic space or to conceal the prosthesis-tissue junction in patients with excessive gingival display (gummy smile). Inadequate bone reduction is often a cause of prosthetic failure due to material fractures, poor esthetics, or inability to perform oral hygiene procedures due to unfavorable ridge lap prosthetic contours. Various instruments and techniques are available for bone reduction. It would be helpful to have an accurate and efficient method for bone reduction at the time of surgery and subsequently create a smooth bony platform. This article presents a straightforward technique for systematic bone reduction by transferring the patient's maximum smile line, recorded clinically, to a clear radiographic smile guide for treatment planning using cone beam computed tomography (CBCT). The patient's smile line and the amount of required bone reduction are transferred clinically by marking bone with a sterile stationery graphite wood pencil at the time of surgery. This technique can help clinicians to accurately achieve the desired bone reduction during surgery, and provide confidence that the diagnostic and treatment planning goals have been achieved. Copyright © 2015 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Differential Regulation of Protein- and Polysaccharide-Specific Ig Isotype Production In Vivo in Response to Intact Streptococcus pneumoniae

DTIC Science & Technology

2006-01-01

IL-4-/- mice. A marked enhancement in the induction of pro-inflammatory cytokines was observed in the absence of IL- 10, relative to controls. IgG...that it was phenol-extractable. Immunization of wild-type mice with phenol-extracted PPS14 also resulted in a marked reduction in the IgG, although not...Thus, CBA/N (xid) mice [124], which have a loss-of-function point mutation in the Btk gene [125, 126] exhibit a marked reduction in peritoneal B-1a

Serious Non-AIDS Conditions in HIV: Benefit of Early ART.

PubMed

Lundgren, Jens D; Borges, Alvaro H; Neaton, James D

2018-04-01

Optimal control of HIV can be achieved by early diagnosis followed by the initiation of antiretroviral therapy (ART). Two large randomised trials (TEMPRANO and START) have recently been published documenting the clinical benefits to HIV-positive adults of early ART initiation. Main findings are reviewed with a focus on serious non-AIDS (SNA) conditions. Data from the two trials demonstrated that initiating ART early in the course of HIV infection resulted in marked reductions in the risk of opportunistic diseases and invasive bacterial infections. This indicates that HIV causes immune impairment in early infection that is remedied by controlling viral replication. Intriguingly, in START, a marked reduction in risk of cancers, both infection-related and unrelated types of cancers, was observed. Like the findings for opportunistic infections, this anti-cancer effect of early ART shows how the immune system influences important pro-oncogenic processes. In START, there was also some evidence suggesting that early ART initiation preserved kidney function, although the clinical consequence of this remains unclear. Conversely, while no adverse effects were evident, the trials did not demonstrate a clear effect on metabolic-related disease outcomes, pulmonary disease, or neurocognitive function. HIV causes immune impairment soon after acquisition of infection. ART reverses this harm at least partially. The biological nature of the immune impairment needs further elucidation, as well as mechanisms and clinical impact of innate immune activation. Based on the findings from TEMPRANO and START, and because ART lowers the risk of onward transmission, ART initiation should be offered to all persons following their diagnosis of HIV.

Metabolic effects of cortisol, ACTH, adrenalin and insulin in the marsupial sugar glider, Petaurus breviceps.

PubMed

Bradley, A J; Stoddart, D M

1990-11-01

The effects of cortisol, ACTH, adrenalin and insulin on indices of carbohydrate, fat and protein metabolism were investigated in the conscious marsupial sugar glider Petaurus breviceps. Short-term i.v. infusion of cortisol at dose rates of 0.02, 0.2 and 1.0 mg/kg per h caused the plasma glucose concentration to rise sharply from the normal range of 3.3-4.4 to 8.1-8.7 mmol/l at the end of the infusion period without significant alteration in plasma free fatty acid (FFA), amino acid or urea concentrations. Infusions of ACTH at dose rates of 0.02, 0.06 and 0.45 IU/kg per h caused a similar rise in plasma glucose concentration; however, this was now accompanied by an elevation in plasma FFA concentration, but again without significant changes in either plasma amino acid or urea concentrations. Infusion of adrenalin at 10 micrograms/kg per h caused an increase in the plasma concentrations of both glucose and FFA. Intravenous injections of 0.15 IU insulin/kg caused a rapid and marked decrease in the plasma glucose concentration within 30 min and an increase in the plasma free cortisol concentration. Associated with this change was a marked rise in the plasma concentration of both FFA and free cortisol. The rise in free cortisol was, however, significantly reduced by infusion of glucose. Pretreatment with five daily i.m. injections of 1 mg cortisol acetate/kg, which produced an increase in plasma free cortisol concentration to near the maximum of the physiological range, caused a marked reduction in insulin sensitivity. Cortisol pretreatment caused an increase in the plasma FFA and amino acid concentrations. Petaurus breviceps is highly sensitive to the metabolic effects of glucocorticoids and is similar in this respect to the brush-tailed possum Trichosurus vulpecula. The interactive effects between insulin and glucocorticoids on carbohydrate, fat and protein metabolism in Petaurus breviceps are similar to those shown by Trichosurus vulpecula and some eutherian mammals but contrast with the pattern described for two macropodid marsupials, the red kangaroo Macropus rufus and the quokka Setonix brachyurus.

Evaluation and differential diagnosis of marked, persistent eosinophilia

PubMed Central

Nutman, Thomas B.

2007-01-01

Synopsis: Hyperosinophilic syndromes (HES) are a group of heterogeneous disorders many of which remain ill-defined. By definition, the 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, the diagnostic approach must include non-infectious (non-parasitic) causes of marked eosinophilia as well. PMID:17868863

Tau hyperphosphorylation and P-CREB reduction are involved in acrylamide-induced spatial memory impairment: Suppression by curcumin.

PubMed

Yan, Dandan; Yao, Jianling; Liu, Ying; Zhang, Xing; Wang, Yiqi; Chen, Xiaoyi; Liu, Liegang; Shi, Nian; Yan, Hong

2018-04-26

Acrylamide (ACR) is an axonal toxicant that produces peripheral neuropathy in laboratory animals and humans. Epidemiological study found that diet ACR exposure was associated with a mild cognitive decline in men. However, limited information is available as regards its potential and underlying mechanism to cause memory alterations. Curcumin is a polyphenol with neuroprotective and cognitive-enhancing properties. In this study, we aimed to investigate the mechanism of ACR-induced spatial memory impairment and the beneficial effect of curcumin. ACR exposure at 10 mg/kg/d for 7 weeks caused slight gait abnormality and spatial memory deficits, which was associated with an activation of glial cells, a reduction of phosphorylated cAMP response elements binding protein (P-CREB) and an aggregation of hyperphosphorylated tau including p-tau (Ser 262 ), AT8 (p-tau Ser 202 /Thr 205 ) and PHF1 (p-tau Ser 396/404 ) in the hippocampus and cortex. ACR markedly regulate the expression of glycogen synthase kinase-3β (GSK-3β) and cyclin-dependent kinase-5 (cdk5) to accelerate tau hyperphosphorylation. ACR inhibited the protein phosphatase 2A (PP2A) and lysosomal protease cathepsin D to decrease the p-tau dephosphorylation and degradation. The P-CREB and brain derived neurotrophic factor (BDNF) were significantly decreased by ACR. The upstream signalings of P-CREB, extracellular signal-related kinase (ERK) and Akt were markedly inhibited. The protein kinase RNA-like endoplasmic reticulum kinase (PERK) -eukaryotic initiation factor-2α (eIF2α) - activating transcription factor 4 (ATF4) signaling which negatively regulate memory processes by suppressing CREB was activated by ACR. Curcumin alleviated ACR-induced spatial memory impairment through reversing tau abnormalities and P-CREB reduction in the hippocampus. These results offered deeper insight into the mechanisms of and presented a potential new treatment for ACR-induced neurotoxicity. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

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.

A Case of Treatment Refractory Hyperemesis Gravidarum in a Patient with Comorbid Anxiety, Treated Successfully with Adjunctive Gabapentin

PubMed Central

Webb, Kathryn

2012-01-01

Hyperemesis gravidarum occurs in 0.3 to 10 percent of pregnant women, with a 0.8 percent hospital admission rate. While older theories supported the psychosocial model as a cause for hyperemesis gravidarum, more recent studies have shown significant data to support a biological etiology. Hyperemesis gravidarum has serious complications including include increased risk for miscarriage, low birth weight infants, dehydration, Wernicke’s encephalopathy, secondary depression, and negative attitudes toward a consecutive pregnancy. Because of these life-threatening complications and complexity of the disease, it is important to treat both somatic and psychosocial causes of hyperemesis gravidarum to provide the best care for the patient. This paper presents a case of a woman with anxiety symptoms who was experiencing severe nausea and vomiting since Week 2 of pregnancy, with minimal reduction of these symptoms on standard medications utilized in hyperemesis gravidarum. The patient had marked reduction of nausea and vomiting with adjunctive gabapentin. After a brief review of relevant neurogastroenterology, we discuss a possible mechanism for the added gabapentin. PMID:23346516

Laminin α1 is essential for mouse cerebellar development

PubMed Central

Ichikawa-Tomikawa, Naoki; Ogawa, Junko; Douet, Vanessa; Xu, Zhuo; Kamikubo, Yuji; Sakurai, Takashi; Kohsaka, Shinichi; Chiba, Hideki; Hattori, Nobutaka; Yamada, Yoshihiko; Arikawa-Hirasawa, Eri

2011-01-01

Laminin α1 (Lama1), which is a subunit of laminin-1 (laminin-111), a heterotrimeric ECM protein, is essential for embryonic development and promotes neurite outgrowth in culture. Because the deletion of Lama1 causes lethality at early embryonic stages in mice, the in vivo role of Lama1 in neural development and functions has not yet been possible to determine. In this study, we generated conditional Lama1 knockout (Lama1CKO) mice in the epiblast lineage using Sox2-Cre mice. These Lama1CKO mice survived, but displayed behavioral disorders and impaired formation of the cerebellum. Deficiency of Lama1 in the pial basement membrane of the meninges resulted in defects in the conformation of the meninges. During cerebellar development, Lama1 deficiency also caused a decrease in the proliferation and migration of granule cell precursors, disorganization of Bergmann glial fibers and endfeet, and a transient reduction in the activity of Akt. A marked reduction in numbers of dendritic processes in Purkinje cells was observed in Lama1CKO mice. Together, these results indicate that Lama1 is required for cerebellar development and functions. PMID:21983115

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.

A Hypertension-Associated tRNAAla Mutation Alters tRNA Metabolism and Mitochondrial Function

PubMed Central

Jiang, Pingping; Wang, Meng; Xue, Ling; Xiao, Yun; Yu, Jialing; Wang, Hui; Yao, Juan; Liu, Hao; Peng, Yanyan; Liu, Hanqing; Li, Haiying; Chen, Ye

2016-01-01

In this report, we investigated the pathophysiology of a novel hypertension-associated mitochondrial tRNAAla 5655A → G (m.5655A → G) mutation. The destabilization of a highly conserved base pairing (A1-U72) at the aminoacyl acceptor stem by an m.5655A → G mutation altered the tRNAAla function. An in vitro processing analysis showed that the m.5655A → G mutation reduced the efficiency of tRNAAla precursor 5′ end cleavage catalyzed by RNase P. By using cybrids constructed by transferring mitochondria from lymphoblastoid cell lines derived from a Chinese family into mitochondrial DNA (mtDNA)-less (ρo) cells, we showed a 41% reduction in the steady-state level of tRNAAla in mutant cybrids. The mutation caused an improperly aminoacylated tRNAAla, as suggested by aberrantly aminoacylated tRNAAla and slower electrophoretic mobility of mutated tRNA. A failure in tRNAAla metabolism contributed to variable reductions in six mtDNA-encoded polypeptides in mutant cells, ranging from 21% to 37.5%, with an average of a 29.1% reduction, compared to levels of the controls. The impaired translation caused reduced activities of mitochondrial respiration chains. Furthermore, marked decreases in the levels of mitochondrial ATP and membrane potential were observed in mutant cells. These caused increases in the production of reactive oxygen species in the mutant cybrids. The data provide evidence for the association of the tRNAAla 5655A → G mutation with hypertension. PMID:27161322

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.

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.

Physiological Responses of Bryophytes Thuidium tamariscinum and Hylocomium splendens to Increased Nitrogen Deposition

PubMed Central

Koranda, M.; Kerschbaum, S.; Wanek, W.; Zechmeister, H.; Richter, A.

2007-01-01

Background and Aims Increased levels of nitrogen (N) deposition lead to enhanced N contents and reduced productivity of many bryophyte species. This study aimed at elucidating the mechanisms by which enhanced N uptake may cause growth reduction of bryophytes, focusing on the effects of N addition on carbon (C) metabolism of bryophytes. Methods Plantlets of Thuidium tamariscinum and Hylocomium splendens were fertilized with NH4NO3 (N load equalling 30 kg ha−1 year−1) for 80 d, including a pulse labelling experiment with 13CO2 to dissect the partitioning of carbon in response to N addition. Key Results Growth of T. tamariscinum was not affected by N addition, while H. splendens showed a trend towards growth reduction. Total N concentration was significantly increased by N addition in H. splendens, a significant increase in amino acid-N was found in T. tamariscinum only. In both bryophyte species, a reduction in concentration of lipids, the greatest C storage pool, as well as markedly enhanced turnover rates of C storage pools in fertilized plants were observed. Conclusions The results suggest that growth reduction of H. splendens under high levels of N deposition may be caused by enhanced synthesis of N-containing organic compounds, most probably of cell wall proteins. Disturbance of cellular C metabolism, as indicated by enhanced C pool turnover, may further contribute to the decline in productivity of H. splendens. PMID:17101638

Robotics in the rehabilitation treatment of patients with stroke.

PubMed

Volpe, Bruce T; Ferraro, Mark; Krebs, Hermano I; Hogan, Neville

2002-07-01

Stroke is the leading cause of permanent disability despite continued advances in prevention and novel interventional treatments. Post-stroke neuro-rehabilitation programs teach compensatory strategies that alter the degree of permanent disability. Robotic devices are new tools for therapists to deliver enhanced sensorimotor training and concentrate on impairment reduction. Results from several groups have registered success in reducing impairment and increasing motor power with task-specific exercise delivered by the robotic devices. Enhancing the rehabilitation experience with task-specific repetitive exercise marks a different approach to the patient with stroke. The clinical challenge will be to streamline, adapt, and expand the robot protocols to accommodate healthcare economies, to determine which patients sustain the greatest benefit, and to explore the relationship between impairment reduction and disability level. With these new tools, therapists will measure aspects of outcome objectively and contribute to the emerging scientific basis of neuro-rehabilitation.

Hormones and ethics: Understanding the biological basis of unethical conduct.

PubMed

Lee, Jooa Julia; Gino, Francesca; Jin, Ellie Shuo; Rice, Leslie K; Josephs, Robert A

2015-10-01

Globally, fraud has been rising sharply over the last decade, with current estimates placing financial losses at greater than $3.7 trillion annually. Unfortunately, fraud prevention has been stymied by lack of a clear and comprehensive understanding of its underlying causes and mechanisms. In this paper, we focus on an important but neglected topic--the biological antecedents and consequences of unethical conduct--using salivary collection of hormones (testosterone and cortisol). We hypothesized that preperformance cortisol levels would interact with preperformance levels of testosterone to regulate cheating behavior in 2 studies. Further, based on the previously untested cheating-as-stress-reduction hypothesis, we predicted a dose-response relationship between cheating and reductions in cortisol and negative affect. Taken together, this research marks the first foray into the possibility that endocrine-system activity plays an important role in the regulation of unethical behavior. (c) 2015 APA, all rights reserved).

Regional rat brain noradrenaline turnover in response to restraint stress.

PubMed

Glavin, G B; Tanaka, M; Tsuda, A; Kohno, Y; Hoaki, Y; Nagasaki, N

1983-08-01

Male Wistar rats were starved for 12 hr and then subjected to either 2 hr of wire mesh "envelope" restraint at room temperature; 2 hr of supine restraint in a specially constructed harness at room temperature or were not restrained. Eight brain regions were examined for NA level and the level of its major metabolite, MHPG-SO4. Plasma corticosterone and gastric ulcer incidence were also measured. All restrained rats displayed marked elevations in MHPG-SO4 levels in most brain regions. In addition, several brain regions in restrained animals showed a reduction in NA level. All restrained rats showed elevated plasma corticosterone levels and evidence of gastric lesions. In general, supine restraint produced greater alterations in regional brain NA turnover, greater evidence of ulcer disease, and higher plasma corticosterone levels than did wire mesh restraint. These data suggest that acute but intense stress in the form of restraint causes markedly altered brain NA activity--a possible neurochemical mechanism underlying the phenomenon of stress-induced disease.

A ketogenic diet supplemented with medium-chain triglycerides enhances the anti-tumor and anti-angiogenic efficacy of chemotherapy on neuroblastoma xenografts in a CD1-nu mouse model.

PubMed

Aminzadeh-Gohari, Sepideh; Feichtinger, René Günther; Vidali, Silvia; Locker, Felix; Rutherford, Tricia; O'Donnel, Maura; Stöger-Kleiber, Andrea; Mayr, Johannes Adalbert; Sperl, Wolfgang; Kofler, Barbara

2017-09-12

Neuroblastoma (NB) is a pediatric malignancy characterized by a marked reduction in aerobic energy metabolism. Recent preclinical data indicate that targeting this metabolic phenotype by a ketogenic diet (KD), especially in combination with calorie restriction, slows tumor growth and enhances metronomic cyclophosphamide (CP) therapy of NB xenografts. Because calorie restriction would be contraindicated in most cancer patients, the aim of the present study was to optimize the KD such that the tumors are sensitized to CP without the need of calorie restriction. In a NB xenograft model, metronomic CP was combined with KDs of different triglyceride compositions and fed to CD1-nu mice ad libitum . Metronomic CP in combination with a KD containing 8-carbon medium-chain triglycerides exerted a robust anti-tumor effect, suppressing growth and causing a significant reduction of tumor blood-vessel density and intratumoral hemorrhage, accompanied by activation of AMP-activated protein kinase in NB cells. Furthermore, the KDs caused a significant reduction in the serum levels of essential amino acids, but increased those of serine, glutamine and glycine. Our data suggest that targeting energy metabolism by a modified KD may be considered as part of a multimodal treatment regimen to improve the efficacy of classic anti-NB therapy.

Oxidative stress and hypertension: Possibility of hypertension therapy with antioxidants

PubMed Central

Baradaran, Azar; Nasri, Hamid; Rafieian-Kopaei, Mahmoud

2014-01-01

Hypertension is a major risk factor for myocardial infarction, heart failure, stroke, peripheral arterial disease, and aortic aneurysm, and is a cause of chronic kidney disease. Hypertension is often associated with metabolic abnormalities such as diabetes and dyslipidemia, and the rate of these diseases is increasing nowadays. Recently it has been hypothesized that oxidative stress is a key player in the pathogenesis of hypertension. A reduction in superoxide dismutase and glutathione peroxidase activity has been observed in newly diagnosed and untreated hypertensive subjects, which are inversely correlated with blood pressure. Hydrogen peroxide production is also higher in hypertensive subjects. Furthermore, hypertensive patients have higher lipid hydroperoxide production. Oxidative stress is also markedly increased in hypertensive patients with renovascular disease. If oxidative stress is indeed a cause of hypertension, then, antioxidants should have beneficial effects on hypertension control and reduction of oxidative damage should result in a reduction in blood pressure. Although dietary antioxidants may have beneficial effects on hypertension and cardiovascular risk factors, however, antioxidant supplementation has not been shown consistently to be effective and improvement is not usually seen in blood pressure after treatment with single or combination antioxidant therapy in subjects thought to be at high risk of cardiovascular disease. This matter is the main focus of this paper. A list of medicinal plants that have been reported to be effective in hypertension is also presented. PMID:25097610

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.

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.

50 CFR 229.32 - Atlantic large whale take reduction plan regulations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... marked with thin colored whipping line, thin colored plastic, or heat-shrink tubing, or other material... be dyed, painted, or marked with thin colored whipping line, thin colored plastic, or heat-shrink...

50 CFR 229.32 - Atlantic large whale take reduction plan regulations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... marked with thin colored whipping line, thin colored plastic, or heat-shrink tubing, or other material... be dyed, painted, or marked with thin colored whipping line, thin colored plastic, or heat-shrink...

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.

Cancer cachexia: mediators, signaling, and metabolic pathways.

PubMed

Fearon, Kenneth C H; Glass, David J; Guttridge, Denis C

2012-08-08

Cancer cachexia is characterized by a significant reduction in body weight resulting predominantly from loss of adipose tissue and skeletal muscle. Cachexia causes reduced cancer treatment tolerance and reduced quality and length of life, and remains an unmet medical need. Therapeutic progress has been impeded, in part, by the marked heterogeneity of mediators, signaling, and metabolic pathways both within and between model systems and the clinical syndrome. Recent progress in understanding conserved, molecular mechanisms of skeletal muscle atrophy/hypertrophy has provided a downstream platform for circumventing the variations and redundancy in upstream mediators and may ultimately translate into new targeted therapies. Copyright © 2012 Elsevier Inc. All rights reserved.

Presence and Possible Mode of Action of a Proteinaceous Gonadotropin-like Growth Regulating Factor in Plant Systems 1

PubMed Central

Leshem, Y.; Avtalion, R. R.; Schwarz, M.; Kahana, S.

1969-01-01

Antiserum to human chorionic gonadotropin (HCG) caused marked inhibition of adventitious rooting of Begonia semperflorens and Chrysanthemum morifolium stem cuttings. Immuno-absorption of crude protein extract from chrysanthemum foliage through a column of polymerized and unsolubilized HCG antibodies resulted in a significant reduction in adventitious root promoting activity of the extract. These results are discussed in the light of a hypothesis that an endogenous protein growth regulating substance which immunologically resembles HCG exists in plant systems. Further experimentation with HCG suggests that its mode of action is possibly via the regulation of peroxidase enzymatic control of auxin levels. PMID:5775851

Neoliberalism and Austerity in Spain, Portugal and South Africa: The Revolution of Older Persons.

PubMed

Ornellas, Abigail; Martínez-Román, María-Asunción; Tortosa-Martínez, Juan; Casanova, José Luís; das Dores Guerreiro, Maria; Engelbrecht, Lambert K

2017-01-01

In Portugal, Spain, and South Africa, there has been a noted anti-neoliberal resistance, marked by the significant participation of the older generation in protest movements. Changing demographics, the global financial crisis, unemployment, poverty, and the reliance of the family nucleus on the pensioner, coupled with neoliberal and austerity-based reductions to welfare programs, pensions, health, and social care, has caused the "silver revolution." As a population group that is often considered to be less politically active and robust members of society, such resistance is a noteworthy moment in society that needs to be considered and responded to.

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

PubMed Central

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

1974-01-01

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

Pharmacodynamically optimized erythropoietin treatment combined with phlebotomy reduction predicted to eliminate blood transfusions in selected preterm infants.

PubMed

Rosebraugh, Matthew R; Widness, John A; Nalbant, Demet; Cress, Gretchen; Veng-Pedersen, Peter

2014-02-01

Preterm very-low-birth-weight (VLBW) infants weighing <1.5 kg at birth develop anemia, often requiring multiple red blood cell transfusions (RBCTx). Because laboratory blood loss is a primary cause of anemia leading to RBCTx in VLBW infants, our purpose was to simulate the extent to which RBCTx can be reduced or eliminated by reducing laboratory blood loss in combination with pharmacodynamically optimized erythropoietin (Epo) treatment. Twenty-six VLBW ventilated infants receiving RBCTx were studied during the first month of life. RBCTx simulations were based on previously published RBCTx criteria and data-driven Epo pharmacodynamic optimization of literature-derived RBC life span and blood volume data corrected for phlebotomy loss. Simulated pharmacodynamic optimization of Epo administration and reduction in phlebotomy by ≥ 55% predicted a complete elimination of RBCTx in 1.0-1.5 kg infants. In infants <1.0 kg with 100% reduction in simulated phlebotomy and optimized Epo administration, a 45% reduction in RBCTx was predicted. The mean blood volume drawn from all infants was 63 ml/kg: 33% required for analysis and 67% discarded. When reduced laboratory blood loss and optimized Epo treatment are combined, marked reductions in RBCTx in ventilated VLBW infants were predicted, particularly among those with birth weights >1.0 kg.

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

Effect of peptide YY on gastric, pancreatic, and biliary function in humans.

PubMed

Adrian, T E; Savage, A P; Sagor, G R; Allen, J M; Bacarese-Hamilton, A J; Tatemoto, K; Polak, J M; Bloom, S R

1985-09-01

The effect of peptide YY (PYY) on gastric and pancreatico-biliary secretion was studied in humans. Peptide YY was infused into groups of 6 healthy volunteers at doses of 0.59, 0.20, and 0.064 pmol X kg-1 X min-1. The two higher doses caused a significant suppression of gastric acid and pepsin output during background stimulation with pentagastrin. The middle dose of PYY (0.20 pmol X kg-1 X min-1) that increased plasma PYY levels by 27 +/- 2 pM caused a 90% +/- 18% (mean +/- SEM; p less than 0.001) reduction in the incremental gastric volume response to pentagastrin. Similarly this dose of PYY caused a substantial inhibition of the acid (77% +/- 14%; p less than 0.005) and pepsin (96% +/- 22%; p less than 0.01) response to pentagastrin; in 2 subjects, pepsin output fell to below basal levels. In contrast, the highest dose of PYY (0.62 pmol X kg-1 X min-1) had no significant influence on duodenal juice volume, output of bicarbonate, trypsin, or bilirubin during low dose stimulation with secretin (0.25 pmol X kg-1 X min-1) and cholecystokinin-8 (0.15 pmol X kg-1 X min-1). Thus PYY concentrations in the circulation similar to those seen after the ingestion of food cause a marked reduction in gastric secretion. This peptide should therefore be considered as one of the possible candidates for the classical enterogastrone.

Reflex effects following selective stimulation of J receptors in the cat.

PubMed Central

Anand, A; Paintal, A S

1980-01-01

1. Experiments carried out on anaesthetized cats showed that increasing blood flow, through the lobes of a lung, by 133% (S.E. 33%) generated an average of 0.75 impulses/sec (S.E. 0.3) in ten almost silent J receptors. Equivalent activity was produced by injecting 12-18 micrograms phenyl diguanide/kg into the right atrium. Such activity caused marked reflex effects, i.e. apnoea, rapid shallow breathing and reduction in the knee jerk. 2. The reflex effects of J receptors were studied after blocking the activity from cardiac receptors by intrapericardial injections of xylocaine. This was necessary because left atrial injections of phenyl diguanide produced reflex respiratory effects and inhibition of the knee jerk. 3. Hypoxia, but not hypercapnia, attenuated the reflex effects of J receptors, apnoea being abolished if the Pa,O2 fell below 35 mmHg. This was a central effect as it occurred in spite of increased activity of J receptors following phenyl diguanide, and effects of hypoxia persisted after cutting both carotid nerves. 4. The only invariable reflex effect of J receptors was a reduction in the total number and the average frequency of phrenic impulses in each breath. The changes in inspiratory time (ti) and expiratory time (te) following apnoea were variable although most frequently both were reduced. In about half the observations the first effect before the apnoea was a reduction in ti, in the other half it was a reduction in te. It was concluded that an input from J receptors inhibits inspiratory and expiratory mechanisms directly. 5. In some cats apnoea and rapid shallow breathing produced by J receptors continued after interrupting their activity by vagotomy and this did not diminish the reduction in ti or te; in other cats it did. The reduction in te was at times quite independent of changes in ti, i.e. pulmonary stretch receptor activity. 6. It was concluded that J receptors must be stimulated during moderate exercise to levels that produce marked respiratory reflex effects and inhibition of muscles. PMID:6770080

Pure uptake blockers of dopamine can reduce prolactin secretion: studies with diclofensine

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

Di Renzo, G.; Amoroso, S.; Taglialatela, M.

1988-01-01

The effects of diclofensine, a pure dopamine (DA) uptake inhibitor on 1) /sup 3/H-DA uptake in rat arcuate-periventricular nucleus-median eminence synaptosomes, 2) basal and K+-evoked endogenous DA release from tuberoinfundibular dopaminergic (TIDA) neurons and 3) in vivo prolactin (PRL) secretion were studied. Diclofensine, in concentrations of 0.01, 0.1 and 1 ..mu..M caused a marked decrease of /sup 3/H-DA uptake. In addition, it was unable to stimulate basal endogenous DA release which, on the contrary, was elicited by d-amphetamine in the same concentration. On the other hand, diclofensine caused a 3 fold enhancement on K+-evoked DA release. Finally, the compound, whenmore » administered in vivo to male rats, significantly reduced basal serum PRL levels. The results of the present study seem to indicate that the pharmacological blockade of DA uptake in TIDA neurons is a condition sufficient to cause a reduction of PRL release.« less

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.

Acute allograft failure in thoracic organ transplantation.

PubMed

Jahania, M S; Mullett, T W; Sanchez, J A; Narayan, P; Lasley, R D; Mentzer, R M

2000-01-01

Thoracic organ transplantation is an effective form of treatment for end-stage heart and lung disease. Despite major advances in the field, transplant patients remain at risk for acute allograft dysfunction, a major cause of early and late mortality. The most common causes of allograft failure include primary graft failure secondary to inadequate heart and lung preservation during cold storage, cellular rejection, and various donor-recipient-related factors. During cold storage and early reperfusion, heart and lung allografts are vulnerable to intracellular calcium overload, acidosis, cell swelling, injury mediated by reactive oxygen species, and the inflammatory response. Brain death itself is associated with a reduction in myocardial contractility, and recipient-related factors such as preexisting pulmonary hypertension can lead to acute right heart failure and the pulmonary reimplantation response. The development of new methods to prevent or treat these various causes of acute graft failure could lead to a marked improvement in short- and long-term survival of patients undergoing thoracic organ transplantation.

Understanding the Influence of Parkinson Disease on Adolf Hitler's Decision-Making during World War II.

PubMed

Gupta, Raghav; Kim, Christopher; Agarwal, Nitin; Lieber, Bryan; Monaco, Edward A

2015-11-01

Parkinson disease (PD) is a common neurodegenerative disorder characterized by the presence of Lewy bodies and a reduction in the number of dopaminergic neurons in the substantia nigra of the basal ganglia. Common symptoms of PD include a reduction in control of voluntary movements, rigidity, and tremors. Such symptoms are marked by a severe deterioration in motor function. The causes of PD in many cases are unknown. PD has been found to be prominent in several notable people, including Adolf Hitler, the Chancellor of Germany and Führer of Nazi Germany during World War II. It is believed that Adolf Hitler suffered from idiopathic PD throughout his life. However, the effect of PD on Adolf Hitler's decision making during World War II is largely unknown. Here we examine the potential role of PD in shaping Hitler's personality and influencing his decision-making. We purport that Germany's defeat in World War II was influenced by Hitler's questionable and risky decision-making and his inhumane and callous personality, both of which were likely affected by his condition. Likewise his paranoid disorder marked by intense anti-Semitic beliefs influenced his treatment of Jews and other non-Germanic peoples. We also suggest that the condition played an important role in his eventual political decline. Copyright © 2015 Elsevier Inc. All rights reserved.

High-throughput microarray mapping of cell wall polymers in roots and tubers during the viscosity-reducing process.

PubMed

Huang, Yuhong; Willats, William G; Lange, Lene; Jin, Yanling; Fang, Yang; Salmeán, Armando A; Pedersen, Henriette L; Busk, Peter Kamp; Zhao, Hai

2016-01-01

Viscosity reduction has a great impact on the efficiency of ethanol production when using roots and tubers as feedstock. Plant cell wall-degrading enzymes have been successfully applied to overcome the challenges posed by high viscosity. However, the changes in cell wall polymers during the viscosity-reducing process are poorly characterized. Comprehensive microarray polymer profiling, which is a high-throughput microarray, was used for the first time to map changes in the cell wall polymers of sweet potato (Ipomoea batatas), cassava (Manihot esculenta), and Canna edulis Ker. over the entire viscosity-reducing process. The results indicated that the composition of cell wall polymers among these three roots and tubers was markedly different. The gel-like matrix and glycoprotein network in the C. edulis Ker. cell wall caused difficulty in viscosity reduction. The obvious viscosity reduction of the sweet potato and the cassava was attributed to the degradation of homogalacturonan and the released 1,4-β-d-galactan and 1,5-α-l-arabinan. © 2015 International Union of Biochemistry and Molecular Biology, Inc.

Disease and the extended phenotype: parasites control host performance and survival through induced changes in body plan.

PubMed

Goodman, Brett A; Johnson, Pieter T J

2011-01-01

By definition, parasites harm their hosts. However, some forms of parasite-induced alterations increase parasite transmission between hosts, such that manipulated hosts can be considered extensions of the parasite's phenotype. While well accepted in principle, surprisingly few studies have quantified how parasite manipulations alter host performance and survival under field and laboratory conditions. By interfering with limb development, the trematode Ribeiroia ondatrae causes particularly severe morphological alterations within amphibian hosts that provide an ideal system to evaluate parasite-induced changes in phenotype. Here, we coupled laboratory performance trials with a capture-mark-recapture study of 1388 Pacific chorus frogs (Pseudacris regilla) to quantify the effects of parasite-induced malformations on host locomotion, foraging, and survival. Malformations, which affected ∼ 50% of metamorphosing frogs in nature, caused dramatic reductions in all measures of organismal function. Malformed frogs exhibited significantly shorter jumping distances (41% reduction), slower swimming speeds (37% reduction), reduced endurance (66% reduction), and lower foraging success relative to infected hosts without malformations. Furthermore, while normal and malformed individuals had comparable survival within predator-free exclosures, deformed frogs in natural populations had 22% lower biweekly survival than normal frogs and rarely recruited to the adult population over a two-year period. Our results highlight the ability of parasites to deeply alter multiple dimensions of host phenotype with important consequences for performance and survival. These patterns were best explained by malformation status, rather than infection per se, helping to decouple the direct and indirect effects of parasitism on host fitness.

Disease and the Extended Phenotype: Parasites Control Host Performance and Survival through Induced Changes in Body Plan

PubMed Central

Goodman, Brett A.; Johnson, Pieter T. J.

2011-01-01

Background By definition, parasites harm their hosts. However, some forms of parasite-induced alterations increase parasite transmission between hosts, such that manipulated hosts can be considered extensions of the parasite's phenotype. While well accepted in principle, surprisingly few studies have quantified how parasite manipulations alter host performance and survival under field and laboratory conditions. Methodology/Principal Findings By interfering with limb development, the trematode Ribeiroia ondatrae causes particularly severe morphological alterations within amphibian hosts that provide an ideal system to evaluate parasite-induced changes in phenotype. Here, we coupled laboratory performance trials with a capture-mark-recapture study of 1388 Pacific chorus frogs (Pseudacris regilla) to quantify the effects of parasite-induced malformations on host locomotion, foraging, and survival. Malformations, which affected ∼50% of metamorphosing frogs in nature, caused dramatic reductions in all measures of organismal function. Malformed frogs exhibited significantly shorter jumping distances (41% reduction), slower swimming speeds (37% reduction), reduced endurance (66% reduction), and lower foraging success relative to infected hosts without malformations. Furthermore, while normal and malformed individuals had comparable survival within predator-free exclosures, deformed frogs in natural populations had 22% lower biweekly survival than normal frogs and rarely recruited to the adult population over a two-year period. Conclusions/Significance Our results highlight the ability of parasites to deeply alter multiple dimensions of host phenotype with important consequences for performance and survival. These patterns were best explained by malformation status, rather than infection per se, helping to decouple the direct and indirect effects of parasitism on host fitness. PMID:21633498

Cytotoxicity of Ultrasmall Gold Nanoparticles on Planktonic and Biofilm Encapsulated Gram-Positive Staphylococci.

PubMed

Boda, Sunil Kumar; Broda, Janine; Schiefer, Frank; Weber-Heynemann, Josefine; Hoss, Mareike; Simon, Ulrich; Basu, Bikramjit; Jahnen-Dechent, Willi

2015-07-01

The emergence of multidrug resistant bacteria, especially biofilm-associated Staphylococci, urgently requires novel antimicrobial agents. The antibacterial activity of ultrasmall gold nanoparticles (AuNPs) is tested against two gram positive: S. aureus and S. epidermidis and two gram negative: Escherichia coli and Pseudomonas aeruginosa strains. Ultrasmall AuNPs with core diameters of 0.8 and 1.4 nm and a triphenylphosphine-monosulfonate shell (Au0.8MS and Au1.4MS) both have minimum inhibitory concentration (MIC) and minimum bactericidal concentration of 25 × 10(-6) m [Au]. Disc agar diffusion test demonstrates greater bactericidal activity of the Au0.8MS nanoparticles over Au1.4MS. In contrast, thiol-stabilized AuNPs with a diameter of 1.9 nm (AuroVist) cause no significant toxicity in any of the bacterial strains. Ultrasmall AuNPs cause a near 5 log bacterial growth reduction in the first 5 h of exposure, and incomplete recovery after 21 h. Bacteria show marked membrane blebbing and lysis in biofilm-associated bacteria treated with ultrasmall AuNP. Importantly, a twofold MIC dosage of Au0.8MS and Au1.4MS each cause around 80%-90% reduction in the viability of Staphylococci enveloped in biofilms. Altogether, this study demonstrates potential therapeutic activity of ultrasmall AuNPs as an effective treatment option against staphylococcal infections. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Exogenous NO administration and alpha-adrenergic vasoconstriction in human limbs.

PubMed

Rosenmeier, Jaya B; Fritzlar, Sandy J; Dinenno, Frank A; Joyner, Michael J

2003-12-01

Nitric oxide (NO) is capable of blunting alpha-adrenergic vasoconstriction in contracting skeletal muscles of experimental animals (functional sympatholysis). We therefore tested the hypothesis that exogenous NO administration can blunt alpha-adrenergic vasoconstriction in resting human limbs by measuring forearm blood flow (FBF; Doppler ultrasound) and blood pressure in eight healthy males during brachial artery infusions of three alpha-adrenergic constrictors (tyramine, which evokes endogenous norepinephrine release; phenylephrine, an alpha1-agonist; and clonidine, an alpha2-agonist). To simulate exercise hyperemia, the vasoconstriction caused by the alpha-agonists was compared during adenosine-mediated (>50% NO independent) and sodium nitroprusside-mediated (SNP; NO donor) vasodilation of the forearm. Both adenosine and SNP increased FBF from approximately 35-40 to approximately 200-250 ml/min. All three alpha-adrenergic constrictor drugs caused marked reductions in FBF and calculated forearm vascular conductance (P < 0.05). The relative reductions in forearm vascular conductance caused by the alpha-adrenergic constrictors during SNP infusion were similar (tyramine, -74 +/- 3 vs. -65 +/- 2%; clonidine, -44 +/- 6 vs. -44 +/- 6%; P > 0.05) or slightly greater (phenylephrine, -47 +/- 6 vs. -33 +/- 6%; P < 0.05) compared with the responses during adenosine. In conclusion, these results indicate that exogenous NO sufficient to raise blood flow to levels simulating those seen during exercise does not blunt alpha-adrenergic vasoconstriction in the resting human forearm.

Zn2+ reduction induces neuronal death with changes in voltage-gated potassium and sodium channel currents.

PubMed

Tian, Kun; He, Cong-Cong; Xu, Hui-Nan; Wang, Yu-Xiang; Wang, Hong-Gang; An, Di; Heng, Bin; Pang, Wei; Jiang, Yu-Gang; Liu, Yan-Qiang

2017-05-01

In the present study, cultured rat primary neurons were exposed to a medium containing N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), a specific cell membrane-permeant Zn 2+ chelator, to establish a model of free Zn 2+ deficiency in neurons. The effects of TPEN-mediated free Zn 2+ ion reduction on neuronal viability and on the performance of voltage-gated sodium channels (VGSCs) and potassium channels (Kvs) were assessed. Free Zn 2+ deficiency 1) markedly reduced the neuronal survival rate, 2) reduced the peak amplitude of I Na , 3) shifted the I Na activation curve towards depolarization, 4) modulated the sensitivity of sodium channel voltage-dependent inactivation to a depolarization voltage, and 5) increased the time course of recovery from sodium channel inactivation. In addition, free Zn 2+ deficiency by TPEN notably enhanced the peak amplitude of transient outward K + currents (I A ) and delayed rectifier K + currents (I K ), as well as caused hyperpolarization and depolarization directional shifts in their steady-state activation curves, respectively. Zn 2+ supplementation reversed the effects induced by TPEN. Our results indicate that free Zn 2+ deficiency causes neuronal damage and alters the dynamic characteristics of VGSC and Kv currents. Thus, neuronal injury caused by free Zn 2+ deficiency may correlate with its modulation of the electrophysiological properties of VGSCs and Kvs. Copyright © 2017 Elsevier GmbH. All rights reserved.

[Listeria monocytogenes outbreaks: a review of the routes that favor bacterial presence].

PubMed

Rossi, M Laura; Paiva, Analía; Tornese, Mariela; Chianelli, Sabrina; Troncoso, Alcides

2008-10-01

Listeria monocytogenes is a foodborne pathogen that causes serious invasive illness, mainly in certain well-defined high-risk groups, including immunocompromised patients, pregnant women and neonates. L. monocytogenes primarily causes abortion, septicaemia or infections of the central nervous systems. Listeriosis outbreaks have mostly been linked to consumption of raw milk or cheese made of unpasteurized milk. Previous outbreaks of listeriosis have been linked to a variety of foods especially processed meats (such as hot dogs, deli meats, and páté). The public health importance of listeriosis is not always recognized, particularly since listeriosis is a relatively rare disease compared with other common foodborne illnesses such as salmonellosis or botulism. However, because of its high case fatality rate, listeriosis ranks among the most frequent causes of death due to foodborne illness: second after salmonellosis. Changes in the manner food is produced, distributed and stored have created the potential for widespread outbreaks involving many countries. The pasteurization of raw milk, which destroys L. monocytogenes, does not eliminate later risk of L. monocytogenes contamination in dairy products. Extensive work has been ongoing in many countries during the last decade to prevent outbreaks and decrease the incidence of listeriosis. A marked reduction has occurred in its incidence in some of these countries during the 1990s, suggesting a relationship between preventive measures and reduction on human cases listeriosis.

Sudden generalized lung atelectasis during thoracotomy following thoracic lavage in 3 dogs.

PubMed

Drynan, Eleanor; Musk, Gabrielle; Raisis, Anthea

2012-08-01

To describe sudden onset of generalized pulmonary atelectasis following thoracic lavage in 3 dogs. Thoracic lavage was performed following ligation of a patent ductus arteriosus in case 1, prior to closure of a large traumatic full thickness wound in the chest wall in case 2, and during investigation of an idiopathic spontaneous pneumothorax in case 3. In each case anesthesia and surgery were uneventful until thoracic lavage was performed, after which sudden generalized pulmonary atelectasis was observed. The atelectasis was visualized and was associated with oxyhemoglobin desaturation, decreased end-tidal carbon dioxide partial pressure (ETCO(2)), and a marked increase in the peak inspiratory pressure (PIP) required to achieve visible lung inflation. Occlusion of the endotracheal tube and cervical trachea was directly eliminated as the cause of atelectasis in cases 1 and 2, and indirectly eliminated in case 3. Improvement in pulmonary function occurred in all cases in response to increased PIP ± positive end expiratory pressure (PEEP). Generalized atelectasis should be considered a possible complication of thoracic lavage performed during thoracotomy. In the cases presented here, it is suspected that pre-existing reduction in lung volume (due to inadequate ventilation, surgical compression, absorption atelectasis) was exacerbated by the addition of the lavage fluid to the thoracic cavity. This pre-existing lung collapse is believed to have resulted in reduction of lung volume and that further reduction below the critical closing volume occurred following instillation of saline into the thorax resulting in the subsequent development of generalized atelectasis. The performance of regular arterial blood gas analyses and different ventilation protocols may have prevented the marked atelectasis that was observed in these cases. © Veterinary Emergency and Critical Care Society 2012.

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 ...

CT perfusion for determination of pharmacologically mediated blood flow changes in an animal tumor model.

PubMed

Hakimé, Antoine; Peddi, Himaja; Hines-Peralta, Andrew U; Wilcox, Carol J; Kruskal, Jonathan; Lin, Shezhang; de Baere, Thierry; Raptopoulos, Vassilios D; Goldberg, S Nahum

2007-06-01

To prospectively compare single- and multisection computed tomographic (CT) perfusion for tumor blood flow determination in an animal model. All animal protocols and experiments were approved by the institutional animal care and use committee before the study was initiated. R3230 mammary adenocarcinoma was implanted in 11 rats. Tumors (18-20 mm) were scanned with dynamic 16-section CT at baseline and after administration of arsenic trioxide, which is known to cause acute reduction in blood flow. The concentration of arsenic was titrated (0-6 mg of arsenic per kilogram of body weight) to achieve a defined blood flow reduction (0%-75%) from baseline levels at 60 minutes, as determined with correlative laser Doppler flowmetry. The mean blood flow was calculated for each of four 5-mm sections that covered the entire tumor, as well as for the entire tumor after multiple sections were processed. Measurements obtained with both methods were correlated with laser Doppler flowmetry measurements. Interobserver agreement was determined for two blinded radiologists, who calculated the percentage of blood flow reduction for the "most representative" single sections at baseline and after arsenic administration. These results were compared with the interobserver variability of the same radiologists obtained by summing blood flow changes for the entire tumor volume. Overall correlations for acute blood flow reduction were demonstrated between laser Doppler flowmetry and the two CT perfusion approaches (single-section CT, r=0.85 and r(2)=0.73; multisection CT, r=0.93 and r(2)=0.87; pooled data, P=.01). CT perfusion disclosed marked heterogeneity of blood flow, with variations of 36% +/- 13 between adjacent 5-mm sections. Given these marked differences, interobserver agreement was much lower for single-section CT (standard deviation, 0.22) than for multisection CT (standard deviation, 0.10; P=.01). Multisection CT perfusion techniques may provide an accurate and more reproducible method of tumor perfusion surveillance than comparison of single representative tumor sections. (c) RSNA, 2007.

How does multilevel upper airway surgery influence the lives of dogs with severe brachycephaly? Results of a structured pre- and postoperative owner questionnaire.

PubMed

Pohl, Sabine; Roedler, Frauke S; Oechtering, Gerhard U

2016-04-01

Brachycephalic airway syndrome in dogs is typified by a variety of anatomical abnormalities causing a diverse spectrum of clinical signs of varying intensity. This variability makes the assessment of the surgical outcome after upper airway surgery difficult. Using a structured questionnaire, the present study investigated the dog owner-perceived severity and frequency of a broad spectrum of welfare-relevant impairments 2 weeks before and 6 months after brachycephalic dogs underwent a recently developed multi-level upper airway surgery. All dogs underwent surgical treatment of stenotic nares (ala-vestibuloplasty), the nasal cavity (laser-assisted turbinectomy, LATE), the pharynx (palatoplasty and tonsillotomy), and if indicated, laryngeal surgery (laser-assisted ablation of everted ventricles and partial cuneiformectomy). Owners of brachycephalic dogs (n = 102) referred for upper airway surgery were eligible to participate. Questionnaire data from owners of 37 Pugs and 25 French bulldogs were evaluated. In all dogs, the clinical signs associated with brachycephaly improved markedly after surgery. Most encouraging was the striking reduction in life-threatening events by 90% (choking fits decreased from 60% to 5% and collapse from 27% to 3%). The incidence of sleeping problems decreased from 55% to 3%, and the occurrence of breathing sounds declined by approximately 50%. There was a marked improvement in exercise tolerance and a modest improvement in heat tolerance. Dogs with severe brachycephaly benefitted substantially from multi-level surgery, and there were particular improvements in the incidences of severe impairment and life-threatening events. However, despite the marked improvement perceived by dog owners, these dogs remained clinically affected and continued to show welfare-relevant impairments caused by these hereditary disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

Deficient GABAergic gliotransmission may cause broader sensory tuning in schizophrenia.

PubMed

Hoshino, Osamu

2013-12-01

We examined how the depression of intracortical inhibition due to a reduction in ambient GABA concentration impairs perceptual information processing in schizophrenia. A neural network model with a gliotransmission-mediated ambient GABA regulatory mechanism was simulated. In the network, interneuron-to-glial-cell and principal-cell-to-glial-cell synaptic contacts were made. The former hyperpolarized glial cells and let their transporters import (remove) GABA from the extracellular space, thereby lowering ambient GABA concentration, reducing extrasynaptic GABAa receptor-mediated tonic inhibitory current, and thus exciting principal cells. In contrast, the latter depolarized the glial cells and let the transporters export GABA into the extracellular space, thereby elevating the ambient GABA concentration and thus inhibiting the principal cells. A reduction in ambient GABA concentration was assumed for a schizophrenia network. Multiple dynamic cell assemblies were organized as sensory feature columns. Each cell assembly responded to one specific feature stimulus. The tuning performance of the network to an applied feature stimulus was evaluated in relation to the level of ambient GABA. Transporter-deficient glial cells caused a deficit in GABAergic gliotransmission and reduced ambient GABA concentration, which markedly deteriorated the tuning performance of the network, broadening the sensory tuning. Interestingly, the GABAergic gliotransmission mechanism could regulate local ambient GABA levels: it augmented ambient GABA around stimulus-irrelevant principal cells, while reducing ambient GABA around stimulus-relevant principal cells, thereby ensuring their selective responsiveness to the applied stimulus. We suggest that a deficit in GABAergic gliotransmission may cause a reduction in ambient GABA concentration, leading to a broadening of sensory tuning in schizophrenia. The GABAergic gliotransmission mechanism proposed here may have an important role in the regulation of local ambient GABA levels, thereby improving the sensory tuning performance of the cortex.

Does IQ explain socio-economic differentials in total and cardiovascular disease mortality? Comparison with the explanatory power of traditional cardiovascular disease risk factors in the Vietnam Experience Study.

PubMed

Batty, G David; Shipley, Martin J; Dundas, Ruth; Macintyre, Sally; Der, Geoff; Mortensen, Laust H; Deary, Ian J

2009-08-01

The aim of this study was to examine the explanatory power of intelligence (IQ) compared with traditional cardiovascular disease (CVD) risk factors in the relationship of socio-economic disadvantage with total and CVD mortality, that is the extent to which IQ may account for the variance in this well-documented association. Cohort study of 4289 US male former military personnel with data on four widely used markers of socio-economic position (early adulthood and current income, occupational prestige, and education), IQ test scores (early adulthood and middle-age), a range of nine established CVD risk factors (systolic and diastolic blood pressure, total blood cholesterol, HDL cholesterol, body mass index, smoking, blood glucose, resting heart rate, and forced expiratory volume in 1 s), and later mortality. We used the relative index of inequality (RII) to quantify the relation between each index of socio-economic position and mortality. Fifteen years of mortality surveillance gave rise to 237 deaths (62 from CVD and 175 from 'other' causes). In age-adjusted analyses, as expected, each of the four indices of socio-economic position was inversely associated with total, CVD, and 'other' causes of mortality, such that elevated rates were evident in the most socio-economically disadvantaged men. When IQ in middle-age was introduced to the age-adjusted model, there was marked attenuation in the RII across the socio-economic predictors for total mortality (average 50% attenuation in RII), CVD (55%), and 'other' causes of death (49%). When the nine traditional risk factors were added to the age-adjusted model, the comparable reduction in RII was less marked than that seen after IQ adjustment: all-causes (40%), CVD (40%), and 'other' mortality (43%). Adding IQ to the latter model resulted in marked, additional explanatory power for all outcomes in comparison to the age-adjusted analyses: all-causes (63%), CVD (63%), and 'other' mortality (65%). When we utilized IQ in early adulthood rather than middle-age as an explanatory variable, the attenuating effect on the socio-economic gradient was less pronounced although the same pattern was still present. In the present analyses of socio-economic gradients in total and CVD mortality, IQ appeared to offer greater explanatory power than that apparent for traditional CVD risk factors.

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

Waste-minimization opportunity assessment: Naval Undersea Warfare Engineering Station, Keyport, Washington. Final report

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

Not Available

The report describes the application of EPA's waste minimization assessment procedures to a torpedo maintenance facility at the Naval Undersea Warfare Engineering Station, Keyport, WA. The assessment focused on the Mark 48 shop and the Mark 46 shop. These shops service the Mark 48 torpedo and the Mark 46 torpedo respectively. The five waste minimization options presented are volume reduction of contaminated clothing, automated cleaning of parts, automated fuel tank draining, modification of the deep sink draining schedule and recycling of mineral spirits.

Premature Brain Aging in Baboons Resulting from Moderate Fetal Undernutrition.

PubMed

Franke, Katja; Clarke, Geoffrey D; Dahnke, Robert; Gaser, Christian; Kuo, Anderson H; Li, Cun; Schwab, Matthias; Nathanielsz, Peter W

2017-01-01

Contrary to the known benefits from a moderate dietary reduction during adulthood on life span and health, maternal nutrient reduction during pregnancy is supposed to affect the developing brain, probably resulting in impaired brain structure and function throughout life. Decreased fetal nutrition delivery is widespread in both developing and developed countries, caused by poverty and natural disasters, but also due to maternal dieting, teenage pregnancy, pregnancy in women over 35 years of age, placental insufficiency, or multiples. Compromised development of fetal cerebral structures was already shown in our baboon model of moderate maternal nutrient reduction. The present study was designed to follow-up and evaluate the effects of moderate maternal nutrient reduction on individual brain aging in the baboon during young adulthood (4-7 years; human equivalent 14-24 years), applying a novel, non-invasive neuroimaging aging biomarker. The study reveals premature brain aging of +2.7 years ( p < 0.01) in the female baboon exposed to fetal undernutrition. The effects of moderate maternal nutrient reduction on individual brain aging occurred in the absence of fetal growth restriction or marked maternal weight reduction at birth, which stresses the significance of early nutritional conditions in life-long developmental programming. This non-invasive MRI biomarker allows further longitudinal in vivo tracking of individual brain aging trajectories to assess the life-long effects of developmental and environmental influences in programming paradigms, aiding preventive and curative treatments on cerebral atrophy in experimental animal models and humans.

Premature Brain Aging in Baboons Resulting from Moderate Fetal Undernutrition

PubMed Central

Franke, Katja; Clarke, Geoffrey D.; Dahnke, Robert; Gaser, Christian; Kuo, Anderson H.; Li, Cun; Schwab, Matthias; Nathanielsz, Peter W.

2017-01-01

Contrary to the known benefits from a moderate dietary reduction during adulthood on life span and health, maternal nutrient reduction during pregnancy is supposed to affect the developing brain, probably resulting in impaired brain structure and function throughout life. Decreased fetal nutrition delivery is widespread in both developing and developed countries, caused by poverty and natural disasters, but also due to maternal dieting, teenage pregnancy, pregnancy in women over 35 years of age, placental insufficiency, or multiples. Compromised development of fetal cerebral structures was already shown in our baboon model of moderate maternal nutrient reduction. The present study was designed to follow-up and evaluate the effects of moderate maternal nutrient reduction on individual brain aging in the baboon during young adulthood (4–7 years; human equivalent 14–24 years), applying a novel, non-invasive neuroimaging aging biomarker. The study reveals premature brain aging of +2.7 years (p < 0.01) in the female baboon exposed to fetal undernutrition. The effects of moderate maternal nutrient reduction on individual brain aging occurred in the absence of fetal growth restriction or marked maternal weight reduction at birth, which stresses the significance of early nutritional conditions in life-long developmental programming. This non-invasive MRI biomarker allows further longitudinal in vivo tracking of individual brain aging trajectories to assess the life-long effects of developmental and environmental influences in programming paradigms, aiding preventive and curative treatments on cerebral atrophy in experimental animal models and humans. PMID:28443017

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

Vinpocetine ameliorates acute hepatic damage caused by administration of carbon tetrachloride in rats.

PubMed

Abdel Salam, O M E; Oraby, Fatma Hassan; Hassan, Nabila S

2007-12-01

Vinpocetine is a widely used drug for the treatment of cerebrovascular and memory disorders. This study aimed to investigate the effect of vinpocetine on the acute hepatic injury caused in the rat by the administration of CCl4 in vivo. Vinpocetine (2.1, 4.2, 8.4 mg/kg) or silymarin (30 mg/kg) was given once daily orally simultaneously with CCl4 and for 15 days thereafter. Liver damage was assessed by determining serum enzyme activities and hepatic histopathology. Stained sections were subjected to morphometric evaluation using computerized image analyzer. The results showed that vinpocetine administered to CCl4-treated rats decreased the elevated alanine aminotransferase (ALT) by 49.3, 58.1 and 63.6%, aspartate aminotransferase (AST) by 10.5, 22.6 and 27.2% and alkaline phosphatase (ALP) by 52.5, 59.6 and 64.9%, respectively, and in a dose-dependent manner. Meanwhile, silymarin reduced elevated ALT, AST and ALP levels by 53.1, 26.9 and 66%, respectively. Histological examination of liver specimens revealed a marked reduction in liver cell necrosis in vinpocetine and silymarin-treated rats compared with vehicle-treated CCl4-treated rats. Quantitative analysis of the area of damage showed 85.3% reduction in the area of damage after silymarin and 72.2, 78.9 and 82.6% reduction after vinpocetine treatment at 2.1, 4.2, 8.4 mg/kg, respectively. It is concluded that administration of vinpocetine in a model of CCl4-induced liver injury in rats reduced liver damage. The reduction obtained by 4.2 mg/kg of vinpocetine was similar to that obtained by 30 mg/kg silymarin. Therefore, it is suggested that vinpocetine might be a good pharmacological agent in the treatment of liver disease besides its neuroprotective effects.

Stillbirth rates among Indigenous and non-Indigenous women in Queensland, Australia: is the gap closing?

PubMed

Ibiebele, I; Coory, M; Boyle, F M; Humphrey, M; Vlack, S; Flenady, V

2015-10-01

To determine whether the disparity gap is closing between stillbirth rates for Indigenous and non-Indigenous women and to identify focal areas for future prevention efforts according to gestational age and geographic location. Population-based retrospective cohort study. Queensland, Australia. All singleton births of at least 20 weeks of gestation or at least 400 g birthweight. Routinely collected data on births were obtained for the period 1995 to 2011. Indigenous and non-Indigenous stillbirth rates and percent reduction in the gap were compared over time and by geographic location and gestational age. All-cause and cause-specific stillbirth rates (per 1000 ongoing pregnancies). Over the study period there was a 57.3% reduction in the disparity gap. Although marked reductions in the gap were shown for women in regional (57.0%) and remote (56.1%) locations, these women remained at increased risk compared with those in urban regions. There was no reduction for term stillbirths. Major conditions contributing to the disparity were maternal conditions (diabetes) (relative risk [RR] 3.78, 95% confidence intervals [95% CI] 2.59-5.51), perinatal infection (RR 3.70, 95% CI 2.54-5.39), spontaneous preterm birth (RR 3.08, 95% CI 2.51-3.77), hypertension (RR 2.22, 95% CI 1.45-3.39), fetal growth restriction (RR 1.78, 95% CI 1.17-2.71) and antepartum haemorrhage (RR 1.58, 95% CI 1.13-2.22). The gap in stillbirth rates between Indigenous and non-Indigenous women is closing, but Indigenous women continue to be at increased risk due to a number of potentially preventable conditions. There is little change in the gap at term gestational ages. © 2014 Royal College of Obstetricians and Gynaecologists.

A comparison of long-chain triglycerides and medium-chain triglycerides on weight loss and tumour size in a cachexia model.

PubMed Central

Tisdale, M. J.; Brennan, R. A.

1988-01-01

A comparison has been made between the ability of long-chain triglycerides (LCT) and medium-chain triglycerides (MCT) to prevent weight loss induced by the cachexia-inducing colon adenocarcinoma (MAC16) and to reduce tumour size. There was no difference in calorie consumption or nitrogen intake between the various groups. When compared with a normal control high carbohydrate, low fat diet, animals fed MCT showed a reduced weight loss and a marked reduction in tumour size. In contrast neither weight loss nor tumour size differed significantly from the controls in animals fed the LCT diet. An elevated plasma level of 3-hydroxybuturate was found only in the animals fed the MCT diets. Administration of LCT caused an increase in the plasma level of FFA, which was not observed in the MCT group. These results suggest that diets containing MCT would provide the best ketogenic regime to reverse the weight loss in cancer cachexia with a concomitant reduction in tumour size. PMID:3219268

Hypoglycemia associated with fluoxetine treatment in a patient with type 1 diabetes

PubMed Central

Biagetti, Betina; Corcoy, Rosa

2013-01-01

We report on a patient with type 1 diabetes mellitus who presented with recurrent episodes of hypoglycemia and a marked reduction in her daily insulin requirements after introduction of fluoxetine. This 25-year-old Caucasian woman had been followed up at the outpatient clinic for type 1 diabetes mellitus and pre-pregnancy care. She used a continuous subcutaneous insulin infusion with lispro and her daily insulin dose was 0.5 IU/kg per day. She had no chronic diabetic complications or hypoglycemia unawareness. Fluoxetine at a daily dose of 20 mg had been started because of depressive symptoms and within one week, she presented recurrent hypoglycemic episodes that prompted a progressive reduction in the insulin dose down to 0.3 IU/kg per day. The reduced insulin requirements continued during the period of fluoxetine treatment while glycated hemoglobin remained stable. She had no concurrent additional cause to explain the reduced insulin requirements. After fluoxetine was stopped, insulin requirements progressively increased and returned to the patient´s usual dose. PMID:24303494

Biphasic kill curve of isoniazid reveals the presence of drug-tolerant, not drug-resistant, Mycobacterium tuberculosis in the guinea pig.

PubMed

Ahmad, Zahoor; Klinkenberg, Lee G; Pinn, Michael L; Fraig, Mostafa M; Peloquin, Charles A; Bishai, William R; Nuermberger, Eric L; Grosset, Jacques H; Karakousis, Petros C

2009-10-01

The marked reduction in the potent early bactericidal activity of isoniazid during the initial phase of antituberculosis (anti-TB) therapy has been attributed not only to the depletion of logarithmically growing bacilli but also to the emergence of isoniazid resistance. We studied the anti-TB activity of isoniazid and its ability to select for drug-resistant mutant strains in guinea pigs, in which the histopathology of TB closely resembles that of human TB. Prior mouse passage did not appear to enhance the virulence of Mycobacterium tuberculosis in guinea pigs. The human-equivalent dose of isoniazid was determined to be 60 mg/kg. Although isoniazid therapy caused rapid killing of bacilli in guinea pig lungs during the first 14 days of administration and rescued guinea pigs from acute death, its activity was dramatically reduced thereafter. This reduction in activity was not associated with the emergence of isoniazid-resistant mutant strains but, rather, with the selection of phenotypically tolerant "persisters."

Best practice in the use of natalizumab in multiple sclerosis.

PubMed

Fernández, Oscar

2013-03-01

Natalizumab is approved for the treatment of patients with relapsing-remitting multiple sclerosis who have failed first-line treatment with traditional disease-modifying therapies or who have highly active disease. The drug has proved highly effective, both in a clinical trial setting and in clinical practice, with marked reductions in the rate of clinical relapses and slowed disease progression. These clinical outcomes are mirrored by a marked reduction in disease activity as evidenced by magnetic resonance imaging of the brain. However, natalizumab treatment has been associated with a risk of progressive multifocal leukoencephalopathy (PML), a potentially fatal condition caused by JC virus (JCV) activation. When this condition was detected in a clinical trial shortly after approval, the drug was immediately and voluntarily withdrawn from the market. As a condition of its reinstatement, stringent pharmacovigilance measures and a risk management plan were enforced. The recent availability of a two-step enzyme-linked immunosorbent assay (ELISA) test for the presence of anti-JCV antibodies (free testing is available in a central laboratory for registered centers), along with an ever-improving understanding of other risk factors such as prior immunosuppressant use and duration of treatment, allow an increasingly refined stratification of the risk of PML. This improved stratification of risk can help guide decisions about treatment. This review will also deal with other topics of relevance to clinical practice such as the development of antinatalizumab antibodies and their negative implications in terms of hypersensitivity reactions and loss of efficacy, withdrawal of treatment, and compassionate pediatric use.

Pulmonary and central nervous system pathology in fatal cases of hand foot and mouth disease caused by enterovirus A71 infection.

PubMed

Wang, Zijun; Nicholls, John M; Liu, Fengfeng; Wang, Joshua; Feng, Zijian; Liu, Dongge; Sun, Yanni; Zhou, Cheng; Li, Yunqian; Li, Hai; Qi, Shunxiang; Huang, Xueyong; Sui, Jilin; Liao, Qiaohong; Peiris, Malik; Yu, Hongjie; Wang, Yu

2016-04-01

In the past 17 years, neurological disease associated with enterovirus A71 (EV-A71) has increased dramatically in the Asia-Pacific region with a high fatality rate in young infants, often due to pulmonary oedema, however the mechanism of this oedema remains obscure. We analysed the brainstem, heart and lungs of 15 fatal cases of confirmed EV-A71 infection in order to understand the pathophysiological mechanism of death and pulmonary oedema. In keeping with other case studies, the main cause of death was neurogenic pulmonary oedema. In the brainstem, 11 cases showed inflammation and all cases showed parenchymal inflammation with seven cases showing moderate or severe clasmatodendrosis. No viral antigen was detected in sections of the brainstem in any of the cases. All fatal cases showed evidence of pulmonary oedema; however, there was absence of direct pulmonary viral damage or myocarditis-induced damage and EV-A71 viral antigen staining was negative. Though there was no increase in staining for Na/K-ATPase, 11 of the 15 cases showed a marked reduction in aquaporin-4 staining in the lung, and this reduction may contribute to the development of fatal pulmonary oedema. Copyright © 2016. Published by Elsevier B.V.

Strangelove ocean at era boundaries, terrestrial or extraterrestrial cause

NASA Astrophysics Data System (ADS)

Hsue, Kenneth J.

Negative perturbations in carbon-isotope value of calcite in pelagic sediments were found at times of biotic crisis, marking horizons which are, or were proposed as era boundaries: Cretaceous/Tertiary (K/T), Permian/Triassic (P/T), and Precambrian/Cambrian (PreC/C). The anomaly was also found at several other mass-extinction horizons, such as terminal Ordovician, Frasnian-Famenian, etc. Studies of K/T boundary indicate that only the planktic fraction of the sediments has the negative isotope anomaly, whereas the benthic fraction has the same value across the boundary. This geochemical signal is thus considered a record of strangelove ocean, or an ocean where isotope fractionation of dissolved carbonate ions in surface waters (by biotic function of planktic organisms) has been significantly reduced because of the drastic reduction of the biomass in the oceans. The reduction of marine biomass at each of the era boundaries was related to chemical pollution of the oceans as a consequence of a catastrophic event; a pH decrease of 0.5 could inhibit the fertility of planktons. Studies of earthquakes, volcanic eruptions, and meteorite-impact occurrences have indicated a linearly inverse log/log relationship between the magnitude and frequency of events. The frequency of era boundaries in geologic history supports the postulate that the rare events causing those biotic crises were large bolide-impacts.

Strangelove ocean at era boundaries, terrestrial or extraterrestrial cause

NASA Technical Reports Server (NTRS)

Hsue, Kenneth J.

1988-01-01

Negative perturbations in carbon-isotope value of calcite in pelagic sediments were found at times of biotic crisis, marking horizons which are, or were proposed as era boundaries: Cretaceous/Tertiary (K/T), Permian/Triassic (P/T), and Precambrian/Cambrian (PreC/C). The anomaly was also found at several other mass-extinction horizons, such as terminal Ordovician, Frasnian-Famenian, etc. Studies of K/T boundary indicate that only the planktic fraction of the sediments has the negative isotope anomaly, whereas the benthic fraction has the same value across the boundary. This geochemical signal is thus considered a record of strangelove ocean, or an ocean where isotope fractionation of dissolved carbonate ions in surface waters (by biotic function of planktic organisms) has been significantly reduced because of the drastic reduction of the biomass in the oceans. The reduction of marine biomass at each of the era boundaries was related to chemical pollution of the oceans as a consequence of a catastrophic event; a pH decrease of 0.5 could inhibit the fertility of planktons. Studies of earthquakes, volcanic eruptions, and meteorite-impact occurrences have indicated a linearly inverse log/log relationship between the magnitude and frequency of events. The frequency of era boundaries in geologic history supports the postulate that the rare events causing those biotic crises were large bolide-impacts.

Extreme longevity in freshwater mussels revisited: sources of bias in age estimates derived from mark-recapture experiments

Treesearch

Wendell R. Haag

2009-01-01

There may be bias associated with mark–recapture experiments used to estimate age and growth of freshwater mussels. Using subsets of a mark–recapture dataset for Quadrula pustulosa, I examined how age and growth parameter estimates are affected by (i) the range and skew of the data and (ii) growth reduction due to handling. I compared predictions...

The effect of pavement markings on driving behaviour in curves: a simulator study.

PubMed

Ariën, Caroline; Brijs, Kris; Vanroelen, Giovanni; Ceulemans, Wesley; Jongen, Ellen M M; Daniels, Stijn; Brijs, Tom; Wets, Geert

2017-05-01

This study investigates the effect of two pavement markings (transverse rumble strips (TRS) and a backward pointing herringbone pattern (HP)) on speed and lateral control in and nearby curves. Two real-world curves with strong indications of a safety problem were replicated as realistic as possible in the simulator. Results show that both speed and lateral control differ between the curves. These behavioural differences are probably due to curve-related dissimilarities with respect to geometric alignment, cross-sectional design and speed limit. TRS and HP both influenced mean speed and mean acceleration/deceleration but not lateral control. TRS generated an earlier and more stable speed reduction than HP which induced significant speed reductions along the curve. The TRS gives drivers more time to generate the right expectations about the upcoming curve. When accidents occur primarily near the curve entry, TRS is recommended. The HP has the potential to reduce accidents at the curve end. Practitioner Summary: Two pavement markings (transversal rumble strips and HP) nearby dangerous curves were investigated in the driving simulator. TRS generated an earlier and more stable speed reduction than HP which induced speed reductions along the curve. The TRS gives drivers more time to generate right expectations about the upcoming curve.

Defeaturing CAD models using a geometry-based size field and facet-based reduction operators.

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

Quadros, William Roshan; Owen, Steven James

2010-04-01

We propose a method to automatically defeature a CAD model by detecting irrelevant features using a geometry-based size field and a method to remove the irrelevant features via facet-based operations on a discrete representation. A discrete B-Rep model is first created by obtaining a faceted representation of the CAD entities. The candidate facet entities are then marked for reduction by using a geometry-based size field. This is accomplished by estimating local mesh sizes based on geometric criteria. If the field value at a facet entity goes below a user specified threshold value then it is identified as an irrelevant featuremore » and is marked for reduction. The reduction of marked facet entities is primarily performed using an edge collapse operator. Care is taken to retain a valid geometry and topology of the discrete model throughout the procedure. The original model is not altered as the defeaturing is performed on a separate discrete model. Associativity between the entities of the discrete model and that of original CAD model is maintained in order to decode the attributes and boundary conditions applied on the original CAD entities onto the mesh via the entities of the discrete model. Example models are presented to illustrate the effectiveness of the proposed approach.« less

Modelling Variable Fire Severity in Boreal Forests: Effects of Fire Intensity and Stand Structure

PubMed Central

Miquelajauregui, Yosune; Cumming, Steven G.; Gauthier, Sylvie

2016-01-01

It is becoming clear that fires in boreal forests are not uniformly stand-replacing. On the contrary, marked variation in fire severity, measured as tree mortality, has been found both within and among individual fires. It is important to understand the conditions under which this variation can arise. We integrated forest sample plot data, tree allometries and historical forest fire records within a diameter class-structured model of 1.0 ha patches of mono-specific black spruce and jack pine stands in northern Québec, Canada. The model accounts for crown fire initiation and vertical spread into the canopy. It uses empirical relations between fire intensity, scorch height, the percent of crown scorched and tree mortality to simulate fire severity, specifically the percent reduction in patch basal area due to fire-caused mortality. A random forest and a regression tree analysis of a large random sample of simulated fires were used to test for an effect of fireline intensity, stand structure, species composition and pyrogeographic regions on resultant severity. Severity increased with intensity and was lower for jack pine stands. The proportion of simulated fires that burned at high severity (e.g. >75% reduction in patch basal area) was 0.80 for black spruce and 0.11 for jack pine. We identified thresholds in intensity below which there was a marked sensitivity of simulated fire severity to stand structure, and to interactions between intensity and structure. We found no evidence for a residual effect of pyrogeographic region on simulated severity, after the effects of stand structure and species composition were accounted for. The model presented here was able to produce variation in fire severity under a range of fire intensity conditions. This suggests that variation in stand structure is one of the factors causing the observed variation in boreal fire severity. PMID:26919456

Modelling Variable Fire Severity in Boreal Forests: Effects of Fire Intensity and Stand Structure.

PubMed

Miquelajauregui, Yosune; Cumming, Steven G; Gauthier, Sylvie

2016-01-01

It is becoming clear that fires in boreal forests are not uniformly stand-replacing. On the contrary, marked variation in fire severity, measured as tree mortality, has been found both within and among individual fires. It is important to understand the conditions under which this variation can arise. We integrated forest sample plot data, tree allometries and historical forest fire records within a diameter class-structured model of 1.0 ha patches of mono-specific black spruce and jack pine stands in northern Québec, Canada. The model accounts for crown fire initiation and vertical spread into the canopy. It uses empirical relations between fire intensity, scorch height, the percent of crown scorched and tree mortality to simulate fire severity, specifically the percent reduction in patch basal area due to fire-caused mortality. A random forest and a regression tree analysis of a large random sample of simulated fires were used to test for an effect of fireline intensity, stand structure, species composition and pyrogeographic regions on resultant severity. Severity increased with intensity and was lower for jack pine stands. The proportion of simulated fires that burned at high severity (e.g. >75% reduction in patch basal area) was 0.80 for black spruce and 0.11 for jack pine. We identified thresholds in intensity below which there was a marked sensitivity of simulated fire severity to stand structure, and to interactions between intensity and structure. We found no evidence for a residual effect of pyrogeographic region on simulated severity, after the effects of stand structure and species composition were accounted for. The model presented here was able to produce variation in fire severity under a range of fire intensity conditions. This suggests that variation in stand structure is one of the factors causing the observed variation in boreal fire severity.

A marked decrease in bispectral index with elevation of suppression ratio by cervical haematoma reducing cerebral perfusion pressure.

PubMed

Umegaki, N; Hirota, K; Kitayama, M; Yatsu, Y; Ishihara, H; Mtasuki, A

2003-11-01

A 77-year-old man with a ruptured abdominal aortic aneurysm undergoing aneurysmectomy were anaesthetised with ketamine under bispectral index (BIS) monitoring, which is a clinical EEG monitor for measurement of depth of anaesthesia/sedation. First marked BIS reduction with elevation of suppression ratio (SR) was observed following severe hypotension by deflation of the aortic occlusion balloon. The re-inflation and rapid blood transfusion improved haemodyanamics and BIS and SR. At second marked BIS reduction with SR elevation, a heavy cervical swelling due to a massive subcutaneous haematoma around the previously mis-punctured right carotid artery extending throughout the whole neck was observed without hypotension. Cervical relief incision improved the BIS and SR. The present case suggests that BIS monitor may be a simple and convenient monitor for cerebral ischaemia detection.

Epidemiology of invasive fungal infections in patients with acquired immunodeficiency syndrome at a reference hospital for infectious diseases in Brazil.

PubMed

de Oliveira, Renata Buccheri; Atobe, Jane Harumi; Souza, Simone Aparecida; de Castro Lima Santos, Daniel Wagner

2014-08-01

Invasive fungal infections (IFIs) represent one of the main causes of morbimortality in immunocompromised patients. Pneumocystosis, cryptococcosis and histoplasmosis are the most frequently occurring IFIs in patients with acquired immunodeficiency syndrome (AIDS). Fungi, such as Candida spp. and Aspergillus spp., may cause severe diseases during the course of an HIV infection. Following the introduction of highly active anti-retroviral therapy, there has been a marked reduction of opportunistic fungal infections, which today is 20-25 % of the number of infections observed in the mid-1990s. This study is an observational and retrospective study aimed at the characterising IFI incidence and describing the epidemiology, clinical diagnostic and therapeutic features and denouement in HIV/AIDS patients. In HIV/AIDS patients, the IFI incidence is 54.3/1,000 hospitalisation/year, with a lethality of 37.7 %. Cryptococcosis represents the main opportunistic IFI in the population, followed by histoplasmosis. Nosocomial pathogenic yeast infections are caused principally by Candida spp., with a higher candidemia incidence at our institution compared to other Brazilian centres.

Subacute peripheral and optic neuropathy syndrome with no evidence of a toxic or nutritional cause.

PubMed

Allen, D; Riordan-Eva, P; Paterson, R W; Hadden, R D M

2013-08-01

The syndrome of subacute simultaneous peripheral neuropathy and bilateral optic neuropathy is known to occur in tropical countries, probably due to malnutrition or toxicity, but not often seen in developed countries. We report seven patients in London who were not malnourished or alcoholic, and in whom no clear cause was found. We retrospectively reviewed the case notes and arranged some further investigations. All patients developed peripheral and bilateral optic neuropathy within 6 months. Patients were aged 30-52, and all of Jamaican birth and race but lived in the UK. Most had subacute, painful ataxic sensory axonal neuropathy or neuronopathy, some with myelopathy. Nerve conduction studies revealed minor demyelinating features in two cases. The optic neuropathy was symmetrical, subacute and monophasic, usually with marked reduction in visual acuity. CSF protein concentration was usually elevated but other laboratory investigations were normal. Patients showed only modest improvement at follow-up. These patients share a common clinical and electrophysiological phenotype, age, ethnicity and elevated CSF protein, but otherwise normal laboratory investigations. The syndrome is a cause of significant morbidity in young people. The cause remains uncertain despite thorough investigation. Copyright © 2013 Elsevier B.V. All rights reserved.

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.

Kinesin Mutations Cause Motor Neuron Disease Phenotypes by Disrupting Fast Axonal Transport in Drosophila

PubMed Central

Hurd, D. D.; Saxton, W. M.

1996-01-01

Previous work has shown that mutation of the gene that encodes the microtubule motor subunit kinesin heavy chain (Khc) in Drosophila inhibits neuronal sodium channel activity, action potentials and neurotransmitter secretion. These physiological defects cause progressive distal paralysis in larvae. To identify the cellular defects that cause these phenotypes, larval nerves were studied by light and electron microscopy. The axons of Khc mutants develop dramatic focal swellings along their lengths. The swellings are packed with fast axonal transport cargoes including vesicles, synaptic membrane proteins, mitochondria and prelysosomal organelles, but not with slow axonal transport cargoes such as cytoskeletal elements. Khc mutations also impair the development of larval motor axon terminals, causing dystrophic morphology and marked reductions in synaptic bouton numbers. These observations suggest that as the concentration of maternally provided wild-type KHC decreases, axonal organelles transported by kinesin periodically stall. This causes organelle jams that disrupt retrograde as well as anterograde fast axonal transport, leading to defective action potentials, dystrophic terminals, reduced transmitter secretion and progressive distal paralysis. These phenotypes parallel the pathologies of some vertebrate motor neuron diseases, including some forms of amyotrophic lateral sclerosis (ALS), and suggest that impaired fast axonal transport is a key element in those diseases. PMID:8913751

Experimental research on the effectiveness and adaptability of speed reduction markings in downhill sections on urban roads: a driving simulation study.

PubMed

Ding, Han; Zhao, Xiaohua; Rong, Jian; Ma, Jianming

2015-02-01

The objective of this paper is to test the effectiveness and adaptability of speed reduction markings (SRMs) in downhill sections on urban roads with distinct roadway grades. Empirical data including vehicle speed and acceleration were collected in a driving simulator. Subjective questionnaires were conducted, and two indexes - the relative speed difference and standard deviation of acceleration - were developed to evaluate the effectiveness and adaptability of SRMs. Meanwhile, the effectiveness of driving simulator related to different road alignments and types of SRMs has been validated through a field test. Results of subjective questionnaires showed that the majority of subjects had no feelings of nervousness, but they were affected by SRMs while driving through downhill sections in all four scenarios (i.e., downhill sections with vertical grades of 3, 2, 1.5 and 1%). In terms of vehicle speed and acceleration, the results of the analysis of variance (ANOVA) and the contrast analysis (S-N-K method) indicated that SRMs were significantly effective when roadway grades of downgrade sections were 1.5, 2 and 3%, while transverse speed reduction markings (TSRMs) had significantly worse adaptability (P<0.05). Therefore, this research recommends that TSRMs could be placed in downhill sections with roadway grades of 1.5 or 2%; longitudinal speed reduction markings (LSRMs) could be placed in downhill sections with a roadway grade of 3%. Whether SRMs are placed in downhill sections with a roadway grade of 1% would depend on other factors such as financial issues and crash records, which are not considered in this paper. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

Design of a 3-dimensional visual illusion speed reduction marking scheme.

PubMed

Liang, Guohua; Qian, Guomin; Wang, Ye; Yi, Zige; Ru, Xiaolei; Ye, Wei

2017-03-01

To determine which graphic and color combination for a 3-dimensional visual illusion speed reduction marking scheme presents the best visual stimulus, five parameters were designed. According to the Balanced Incomplete Blocks-Law of Comparative Judgment, three schemes, which produce strong stereoscopic impressions, were screened from the 25 initial design schemes of different combinations of graphics and colors. Three-dimensional experimental simulation scenes of the three screened schemes were created to evaluate four different effects according to a semantic analysis. The following conclusions were drawn: schemes with a red color are more effective than those without; the combination of red, yellow and blue produces the best visual stimulus; a larger area from the top surface and the front surface should be colored red; and a triangular prism should be painted as the graphic of the marking according to the stereoscopic impression and the coordination of graphics with the road.

Reducing risks from hazardous glacier lakes in the Cordillera Blanca (Peru): Six decades of experience and perspectives for the future

NASA Astrophysics Data System (ADS)

Portocarrero, Cesar; Cochachin, Alejo; Frey, Holger; González, Cesar; Haeberli, Wilfried; Huggel, Christian

2016-04-01

Outbursts from glacier lakes at various spatial and temporal scales have had marked geomorphological effects in many mountain ranges. In many glacierized Andean mountain regions substrates of human settlements made out of flood and debris-flow deposits are testimonies of such events. Examples in the Cordillera Blanca, Peru, are the towns of Caraz, Carhuaz or parts of Huaraz. Continued glacier shrinking since the end of the Little Ice Age caused the formation or enlargement of numerous lakes. The outburst of Laguna Palcacocha, destroying the centre of Huaraz and causing more than 1800 losses of life in December 1941, marked the beginning of systematic risk reduction work in Peru. Corresponding efforts included glacier and lake inventories, hazard assessments, definition of high-risk situations, and completion of engineering work for lake-level lowering in more than 30 cases. The latter comprises outlet reinforcements on morainic dams as well as artificial tunnels in bedrock thresholds. This work has been remarkably efficient as documented in the latest case of the Laguna Huallcacocha (Carhuaz-Ancash), where the earlier made installations withstood the erosive power of an impact wave from an ice avalanche in 2015. In the case of the Laguna 513, the impact wave and far-reaching flood caused by a rock/ice avalanche from Nevado Hualcán in April 2010 showed that the risk had been essentially reduced by the preventive lake-level lowering in the early 1990s but not to zero. Risk assessments, planning, construction and non-structural risk reduction efforts continue. Work is in progress to increase the safety of Laguna Palcacocha where extensive assessments and model calculations had been carried out. Risks related to rock/ice avalanches into lakes from steep icy slopes and related to de-buttressing processes as well as long-term permafrost degradation increases. Based on morphological indications and numerical modelling (GlabTop) an inventory of possible future lakes likely to form with continued atmospheric warming and glacier retreat has been compiled. The possibility of monitoring the stability of slopes around lakes using satellite-based radar interferometry techniques has been tested in the case of Laguna Parón and a number of other lakes. Hence risk reduction measures applied to critical glacier lakes is based on rigorous science and research progress. For the future it is essential to integrate risk reduction with water resource management because shrinking glaciers reduce water availability during the dry season when various economic sectors depend on melt water. First experiences with development of multi-purpose projects combining risk and water resource management have shown the associated scientific, technical, social and legal challenges. A multi-disciplinary process involving multiple institutions and actors is necessary to secure sustainable development in the Andes of Peru, and related experiences are valuable for other high-mountain regions as well.

Use of the short-term inflammatory response in the mouse peritoneal cavity to assess the biological activity of leached vitreous fibers.

PubMed Central

Donaldson, K; Addison, J; Miller, B G; Cullen, R T; Davis, J M

1994-01-01

We used a special-purpose glass microfiber sample, Johns-Manville Code 100/475, to study the effects of various acid and alkali treatments on biological activity as assessed by inflammation in the mouse peritoneal cavity, the leaching of Si, and the phase contrast optical microscopy (PCOM) fiber number. We used mild and medium treatments with oxalic acid and Tris buffer and harsh treatment with concentrated HCl and NaOH. Mild oxalic acid and Tris treatment for 2 weeks had no effect on any of the end-points, but prolonging the mild oxalic acid treatment time to 2 months reduced the biological activity and the fiber number. Medium oxalic acid treatment reduced the biological activity and the fiber number and caused a loss of Si. Medium Tris alkali treatment reduced the PCOM-countable fibers and the biological activity but did not cause a substantial loss of Si. Harsh treatment with strong HCl did not affect the fiber number or cause leaching but the biological activity was reduced; strong NaOH reduced the fiber number and biological activity, and caused marked leaching of Si. The medium oxalic acid conditions (pH 1.4) were more acid than those found in lung cells but produced the same effects (reduction in fiber number and biological activity) as the more physiological mild treatment (pH 4.0), when prolonged. This study suggests that medium oxalic acid treatment can be used as a short-term assay to compare loss of Si, reduction in fiber number, and change in biological activity of vitreous fibers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7882922

Comparison of the effects of intraocular irrigating solutions on the corneal endothelium in intraocular lens implantation.

PubMed Central

Matsuda, M; Kinoshita, S; Ohashi, Y; Shimomura, Y; Ohguro, N; Okamoto, H; Omoto, T; Hosotani, H; Yoshida, H

1991-01-01

We conducted a randomised prospective controlled study to determine the effects of a glucose glutathione bicarbonate solution (BSS Plus) and a citrate acetate bicarbonate solution (S-MA2) on the corneal endothelium in patients undergoing extracapsular cataract extraction with posterior chamber lens implantation. One eye of each patient was randomly assigned to receive BSS Plus, and the other eye to receive S-MA2. BSS Plus caused significantly less corneal swelling on the first postoperative day than did S-MA2. There was no difference between the two solutions in their effect on corneal thickness one week and one month postoperatively. Computer assisted morphometric analysis of wide-field specular microscopic photographs demonstrated minimal changes in endothelial morphological characteristics in the eyes irrigated with BSS Plus. By comparison S-MA2, caused a significant loss of endothelial cells and a marked reduction in the figure coefficient. These results indicated that BSS Plus has a clinical advantage over S-MA2 with respect to the corneal endothelium. PMID:1873266

Biphasic non-adrenergic, non-cholinergic relaxations of the mouse anococcygeus muscle.

PubMed Central

Gibson, A.; Yu, O.

1983-01-01

Trains of field stimulation of 60 s duration caused a biphasic relaxation of carbachol (50 microM)-induced tone in the mouse anococcygeus. The optimal pulse frequency and width were 10 Hz and 1 ms respectively. Tetrodotoxin (31, 124, and 310 nM) caused a dose-dependent reduction in the magnitude of both phases. Neither phase was affected by (+/-)-propranolol (1 microM), neostigmine (1 microM), (+)-tubocurarine (100 microM), or apamin (500 nM). Biphasic relaxations were observed in muscles from 6-hydroxydopamine pretreated mice. Haemolysed blood (10, 40, and 100 microliter/ml) reduced the magnitude of the first phase of nerve-induced relaxation to a greater extent than the second. This effect was reversible. Following a prolonged train of inhibitory nerve stimulation (10 Hz; 10 min) the magnitude of the first phase was reduced only slightly, but the second markedly. The possible relationships between the biphasic relaxation to field stimulation and putative non-adrenergic, non-cholinergic transmitters in the mouse anococcygeus are discussed. PMID:6652345

Effect of verapamil on nitric oxide synthase in a portal vein-ligated rat model: Role of prostaglandin

PubMed Central

Lay, Chii-Shyan; May, CMY; Lee, Fa-Yauh; Tsai, Yang-Te; Lee, Shou-Dong; Chien, Shu; Sinchon, Shlomoh

2006-01-01

AIM: To investigate the effects of verapamil on nitric oxide (NO) synthesis in a portal vein-ligated rat model. METHODS: Systemic and splanchnic hemodynamics were measured by radiolabeled microspheres in portal hypertensive rats after acute administration of verapamil (2 mg/kg) on chronic treatment with Nw–nitro-L-arginine (NNA)(80 mg/kg) and/or indomethacin (2 mg/kg) . RESULTS: Verapamil (2 mg/kg) caused a marked fall in both arterial pressure and cardiac output accompanied by an insignificant change in the portal pressure and no change in portal venous inflow. This result suggested that verapamil did not cause a reduction in portal vascular resistance of portal hypertensive rats, which was similar between Nw- nitro–L-arginine-treated and indomethacin-treated groups. CONCLUSION: In portal hypertensive rats pretreated with NNA and/or indomethacin, acute verapamil administration can not reduce the portal pressure, suggesting that NO and prostaglandin play an important role in the pathogenesis of splanchnic arterial vasodilation in portal hypertension. PMID:16688824

Understanding and preventing contrast-induced acute kidney injury.

PubMed

Fähling, Michael; Seeliger, Erdmann; Patzak, Andreas; Persson, Pontus B

2017-03-01

Contrast-induced acute kidney injury (CIAKI) occurs in up to 30% of patients who receive iodinated contrast media and is generally considered to be the third most common cause of hospital-acquired AKI. Accurate assessment of the incidence of CIAKI is obscured, however, by the use of various definitions for diagnosis, the different populations studied and the prophylactic measures put in place. A deeper understanding of the mechanisms that underlie CIAKI is required to enable reliable risk assessment for individual patients, as their medical histories will determine the specific pathways by which contrast media administration might lead to kidney damage. Here, we highlight common triggers that prompt the development of CIAKI and the subsequent mechanisms that ultimately cause kidney damage. We also discuss effective protective measures, such as rapidly acting oral hydration schemes and loop diuretics, in the context of CIAKI pathophysiology. Understanding of how CIAKI arises in different patient groups could enable a marked reduction in incidence and improved outcomes. The ultimate goal is to shape CIAKI prevention strategies for individual patients.

Multi-targeted inhibition of tumor growth and lung metastasis by redox-sensitive shell crosslinked micelles loading disulfiram

NASA Astrophysics Data System (ADS)

Duan, Xiaopin; Xiao, Jisheng; Yin, Qi; Zhang, Zhiwen; Yu, Haijun; Mao, Shirui; Li, Yaping

2014-03-01

Metastasis, the main cause of cancer related deaths, remains the greatest challenge in cancer treatment. Disulfiram (DSF), which has multi-targeted anti-tumor activity, was encapsulated into redox-sensitive shell crosslinked micelles to achieve intracellular targeted delivery and finally inhibit tumor growth and metastasis. The crosslinked micelles demonstrated good stability in circulation and specifically released DSF under a reductive environment that mimicked the intracellular conditions of tumor cells. As a result, the DSF-loaded redox-sensitive shell crosslinked micelles (DCMs) dramatically inhibited cell proliferation, induced cell apoptosis and suppressed cell invasion, as well as impairing tube formation of HMEC-1 cells. In addition, the DCMs could accumulate in tumor tissue and stay there for a long time, thereby causing significant inhibition of 4T1 tumor growth and marked prevention in lung metastasis of 4T1 tumors. These results suggested that DCMs could be a promising delivery system in inhibiting the growth and metastasis of breast cancer.

CT Dose Optimization in Pediatric Radiology: A Multiyear Effort to Preserve the Benefits of Imaging While Reducing the Risks.

PubMed

Greenwood, Taylor J; Lopez-Costa, Rodrigo I; Rhoades, Patrick D; Ramírez-Giraldo, Juan C; Starr, Matthew; Street, Mandie; Duncan, James; McKinstry, Robert C

2015-01-01

The marked increase in radiation exposure from medical imaging, especially in children, has caused considerable alarm and spurred efforts to preserve the benefits but reduce the risks of imaging. Applying the principles of the Image Gently campaign, data-driven process and quality improvement techniques such as process mapping and flowcharting, cause-and-effect diagrams, Pareto analysis, statistical process control (control charts), failure mode and effects analysis, "lean" or Six Sigma methodology, and closed feedback loops led to a multiyear program that has reduced overall computed tomographic (CT) examination volume by more than fourfold and concurrently decreased radiation exposure per CT study without compromising diagnostic utility. This systematic approach involving education, streamlining access to magnetic resonance imaging and ultrasonography, auditing with comparison with benchmarks, applying modern CT technology, and revising CT protocols has led to a more than twofold reduction in CT radiation exposure between 2005 and 2012 for patients at the authors' institution while maintaining diagnostic utility. (©)RSNA, 2015.

Primary CNS lymphoma as a cause of Korsakoff syndrome.

PubMed

Toth, Cory; Voll, Chris; Macaulay, Robert

2002-01-01

Korsakoff syndrome presents with memory dysfunction with retrograde amnesia, anterograde amnesia, limited insight into dysfunction, and confabulation. The most common etiology of Korsakoff syndrome is thiamine deficiency secondary to alcoholism. There are limited case reports of structural lesions causing Korsakoff syndrome. A 46-year-old male with a long history of alcoholism presented with a history of confusion, amnesia, and confabulation with no localizing features on neurological examination. The patient showed no clinical change with intravenous thiamine. Computed tomography of the brain revealed a heterogenous, enhancing mass lesion centered within the third ventricle, with other lesions found throughout cortical and subcortical regions. The patient was given dexamethasone i.v. without noticeable clinical improvement but with marked radiological improvement with mass reduction. Stereotactic biopsy revealed a diagnosis of primary central nervous system (CNS) lymphoma. Most patients presenting with Korsakoff syndrome have thiamine deficiency; however, mass lesions can produce an identical clinical picture. This is the first case report of a patient with primary CNS lymphoma presenting as Korsakoff syndrome.

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

Acarbose is an effective adjunct to dietary therapy in the treatment of hypertriglyceridaemias

PubMed Central

Malaguarnera, M; Giugno, I; Ruello, P; Rizzo, M; Motta, M; Mazzoleni, G

1999-01-01

Aims In diabetics, acarbose causes a reduction of blood glucose and triglyceride levels. The aim of this study was to assess the effect of this drug in non diabetic subjects with hypertriglyceridaemia. Methods Thirty non diabetic patients with hypertriglyceridaemia type IIb or IV (24 males, six females; mean age 51.1 ±10.2 years) were studied. They were stratified into two groups depending on their basal triglyceride concentration (group A: triglyceride values ≤4.5 mmol l−1; group B triglyceride values > 4.5 mmol l− 1). Treatment consisted of 4 week courses of diet plus acarbose (50 mg twice daily) alternating with 4 weeks of diet alone for a total period of 16 weeks. Results Mean triglyceride values decreased significantly during the first and third cycles of therapy, i.e. diet plus acarbose treatment cycles in both patient groups. Group A also had significant reductions in total cholesterol and HDL cholesterol concentrations after completion of the acarbose treatment. Reduction of triglyceride levels was observed after both acarbose courses in patients affected by hypertriglyceridaemia type IIb. A marked reduction of triglyceride concentrations was achieved by patients affected by hypertriglyceridaemia type IV after the second acarbose course only. Conclusions Diet alone did not reduce triglyceride concentrations to normal values in our patients. The data suggest that acarbose is a useful adjunct to dietary control in non-diabetic patients affected by severe hypertriglyceridaemia. PMID:10583032

Hexavalent Molybdenum Reduction to Mo-Blue by a Sodium-Dodecyl-Sulfate-Degrading Klebsiella oxytoca Strain DRY14

PubMed Central

Halmi, M. I. E.; Zuhainis, S. W.; Yusof, M. T.; Shaharuddin, N. A.; Helmi, W.; Shukor, Y.; Syed, M. A.; Ahmad, S. A.

2013-01-01

Bacteria with the ability to tolerate, remove, and/or degrade several xenobiotics simultaneously are urgently needed for remediation of polluted sites. A previously isolated bacterium with sodium dodecyl sulfate- (SDS-) degrading capacity was found to be able to reduce molybdenum to the nontoxic molybdenum blue. The optimal pH, carbon source, molybdate concentration, and temperature supporting molybdate reduction were pH 7.0, glucose at 1.5% (w/v), between 25 and 30 mM, and 25°C, respectively. The optimum phosphate concentration for molybdate reduction was 5 mM. The Mo-blue produced exhibits an absorption spectrum with a maximum peak at 865 nm and a shoulder at 700 nm. None of the respiratory inhibitors tested showed any inhibition to the molybdenum-reducing activity suggesting that the electron transport system of this bacterium is not the site of molybdenum reduction. Chromium, cadmium, silver, copper, mercury, and lead caused approximately 77, 65, 77, 89, 80, and 80% inhibition of the molybdenum-reducing activity, respectively. Ferrous and stannous ions markedly increased the activity of molybdenum-reducing activity in this bacterium. The maximum tolerable concentration of SDS as a cocontaminant was 3 g/L. The characteristics of this bacterium make it a suitable candidate for molybdenum bioremediation of sites cocontaminated with detergent pollutant. PMID:24383052

Effects of chlorhexidine on a tongue-flora microcosm and VSC production using an in vitro biofilm perfusion model.

PubMed

Greenman, J; McKenzie, C; Saad, S; Wiegand, B; Zguris, J C

2008-12-01

An in vitro perfusion biofilm model, derived from tongue-scrape microflora removed from one individual, was employed to study sulfide biogenesis and the effects of repeated exposure to chlorhexidine (CHX). Volatile sulfur compounds (VSC) were measured using a carbon veil electrode within the biofilm and a halimeter for liquid and gas phase levels, respectively. The microflora of the perfusate and the biofilm were assessed by microbiological techniques and polymerase chain reaction (PCR) to estimate diversity. Biofilms treated with a 1 mL pulse of 0.1% CHX twice a day for three days showed (1) a large reduction in viable count (>90% kill), (2) a (slow) reduction in the VSC production rate, consistent with the reduction in microbes rather than direct inhibitory effects on the biotransformation steps, and (3) a preferential reduction of strict anaerobes. Treated biofilms allowed to recover over 3-5 days showed a nominal amount of regrowth in some experiments, although population numbers were still well below those found in untreated controls. The microbiological composition of biofilms treated but allowed to recover was markedly different from the controls, with proportionally fewer strict anaerobes. Thus, CHX treatment caused detectable ecological shifts with consequent long-term effects on the response of the biofilm in terms of VSC generation, consistent with clinical observations. The model appears highly suited for testing the efficacy of putative anti-malodour or antimicrobial agents.

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

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.

Does phosphate enhance the natural attenuation of crude oil in groundwater under defined redox conditions?

PubMed

Ponsin, Violaine; Mouloubou, Olsen Raïnness; Prudent, Pascale; Höhener, Patrick

2014-11-15

After a crude oil spill caused by a broken pipeline in 2009 to a gravel aquifer in southern France, degradation processes under various redox conditions progressively established, but at rates that predict a long life-time of the source under natural attenuation after partial source removal. In this study, we aimed at identifying the rate-limiting factors for each redox condition, with special emphasis on phosphate as limiting nutrient. The study was conducted in laboratory microcosms assembled with material collected on site: sediments, water from monitoring wells, oil and microbial sludge. Redox conditions were promoted by adding electron acceptors (either oxygen, nitrate, limonite (FeO(OH)), cryptomelane (K(Mn(4+),Mn(2+))8O16), or sulfate). For each condition, the role of phosphate was studied by repeated additions for up to 290days. The results showed a very strong stimulation of aerobic and denitrifying rates of oil degradation by phosphate, provided that oxygen and nitrate were repeatedly supplied. Phosphate caused also a marked stimulation of methanogenic degradation, and a relatively small stimulation of metal reduction. These anaerobic processes started only after marked lag phases, and phosphate shortened the lag phase for methanogenic degradation. Degradation of aromatic and aliphatic hydrocarbons with less than 8 carbons, including benzene, was confirmed even under unstimulated conditions. It is concluded that degradation rates at the site are limited by both, availability of electron acceptors and availability of phosphate needed for promoting microbial growth. Copyright © 2014 Elsevier B.V. All rights reserved.

[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.

Best practice in the use of natalizumab in multiple sclerosis

PubMed Central

2013-01-01

Natalizumab is approved for the treatment of patients with relapsing–remitting multiple sclerosis who have failed first-line treatment with traditional disease-modifying therapies or who have highly active disease. The drug has proved highly effective, both in a clinical trial setting and in clinical practice, with marked reductions in the rate of clinical relapses and slowed disease progression. These clinical outcomes are mirrored by a marked reduction in disease activity as evidenced by magnetic resonance imaging of the brain. However, natalizumab treatment has been associated with a risk of progressive multifocal leukoencephalopathy (PML), a potentially fatal condition caused by JC virus (JCV) activation. When this condition was detected in a clinical trial shortly after approval, the drug was immediately and voluntarily withdrawn from the market. As a condition of its reinstatement, stringent pharmacovigilance measures and a risk management plan were enforced. The recent availability of a two-step enzyme-linked immunosorbent assay (ELISA) test for the presence of anti-JCV antibodies (free testing is available in a central laboratory for registered centers), along with an ever-improving understanding of other risk factors such as prior immunosuppressant use and duration of treatment, allow an increasingly refined stratification of the risk of PML. This improved stratification of risk can help guide decisions about treatment. This review will also deal with other topics of relevance to clinical practice such as the development of antinatalizumab antibodies and their negative implications in terms of hypersensitivity reactions and loss of efficacy, withdrawal of treatment, and compassionate pediatric use. PMID:23483450

Pathogenesis of mitral valve disease in mucopolysaccharidosis VII dogs.

PubMed

Bigg, Paul W; Baldo, Guilherme; Sleeper, Meg M; O'Donnell, Patricia A; Bai, Hanqing; Rokkam, Venkata R P; Liu, Yuli; Wu, Susan; Giugliani, Roberto; Casal, Margret L; Haskins, Mark E; Ponder, Katherine P

2013-11-01

Mucopolysaccharidosis VII (MPS VII) is due to the deficient activity of β-glucuronidase (GUSB) and results in the accumulation of glycosaminoglycans (GAGs) in lysosomes and multisystemic disease with cardiovascular manifestations. The goal here was to determine the pathogenesis of mitral valve (MV) disease in MPS VII dogs. Untreated MPS VII dogs had a marked reduction in the histochemical signal for structurally-intact collagen in the MV at 6 months of age, when mitral regurgitation had developed. Electron microscopy demonstrated that collagen fibrils were of normal diameter, but failed to align into large parallel arrays. mRNA analysis demonstrated a modest reduction in the expression of genes that encode collagen or collagen-associated proteins such as the proteoglycan decorin which helps collagen fibrils assemble, and a marked increase for genes that encode proteases such as cathepsins. Indeed, enzyme activity for cathepsin B (CtsB) was 19-fold normal. MPS VII dogs that received neonatal intravenous injection of a gamma retroviral vector had an improved signal for structurally-intact collagen, and reduced CtsB activity relative to that seen in untreated MPS VII dogs. We conclude that MR in untreated MPS VII dogs was likely due to abnormalities in MV collagen structure. This could be due to upregulation of enzymes that degrade collagen or collagen-associated proteins, to the accumulation of GAGs that compete with proteoglycans such as decorin for binding to collagen, or to other causes. Further delineation of the etiology of abnormal collagen structure may lead to treatments that improve biomechanical properties of the MV and other tissues. © 2013.

Pathogenesis of Mitral Valve Disease in Mucopolysaccharidosis VII Dogs

PubMed Central

Bigg, Paul W.; Baldo, Guilherme; Sleeper, Meg M.; O'Donnell, Patricia A.; Bai, Hanqing; Rokkam, Venkata R.P.; Liu, Yuli; Wu, Susan; Giugliani, Roberto; Casal, Margret L.; Haskins, Mark E.; Ponder, Katherine P.

2013-01-01

Mucopolysaccharidosis VII (MPS VII) is due to deficient activity of β-glucuronidase (GUSB) and results in the accumulation of glycosaminoglycans (GAGs) in lysosomes and multisystemic disease with cardiavascular manifestations. The goal here was to determine the pathogenesis of mitral valve (MV) disease in MPS VII dogs. Untreated MPS VII dogs had a marked reduction in the histochemical signal for structurally-intact collagen in the MV at 6 months of age, when mitral regurgitation had developed. Electron microscopy demonstrated that collagen fibrils were of normal diameter, but failed to align into large parallel arrays. mRNA analysis demonstrated a modest reduction in the expression of genes that encode collagen or collagen-associated proteins such as the proteoglycan decorin which helps collagen fibrils assemble, and a marked increase for genes that encode proteases such as cathepsins. Indeed, enzyme activity for cathepsin B (CtsB) was 19-fold normal. MPS VII dogs that received neonatal intravenous injection of a gamma retroviral vector had an improved signal for structurally-intact collagen, and reduced CtsB activity relative to that seen in untreated MPS VII dogs. We conclude that MR in untreated MPS VII dogs was likely due to abnormalities in MV collagen structure. This could be due to upregulation of enzymes that degrade collagen or collagen-associated proteins, to the accumulation of GAGs that compete with proteoglycans such as decorin for binding to collagen, or to other causes. Further delineation of the etiology of abnormal collagen structure may lead to treatments that improve biomechanical properties of the MV and other tissues. PMID:23856419

Statin-induced myotoxicity is exacerbated by aging: A biophysical and molecular biology study in rats treated with atorvastatin

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

Camerino, Giulia Maria; De Bellis, Michela; Conte,

Statin-induced skeletal muscle damage in rats is associated to the reduction of the resting sarcolemmal chloride conductance (gCl) and ClC-1 chloride channel expression. These drugs also affect the ClC-1 regulation by increasing protein kinase C (PKC) activity, which phosphorylate and close the channel. Also the intracellular resting calcium (restCa) level is increased. Similar alterations are observed in skeletal muscles of aged rats, suggesting a higher risk of statin myotoxicity. To verify this hypothesis, we performed a 4–5-weeks atorvastatin treatment of 24-months-old rats to evaluate the ClC-1 channel function by the two-intracellular microelectrodes technique as well as transcript and protein expressionmore » of different genes sensitive to statins by quantitative real-time-PCR and western blot analysis. The restCa was measured using FURA-2 imaging, and histological analysis of muscle sections was performed. The results show a marked reduction of resting gCl, in agreement with the reduced ClC-1 mRNA and protein expression in atorvastatin-treated aged rats, with respect to treated adult animals. The observed changes in myocyte-enhancer factor-2 (MEF2) expression may be involved in ClC-1 expression changes. The activity of PKC was also increased and further modulate the gCl in treated aged rats. In parallel, a marked reduction of the expression of glycolytic and mitochondrial enzymes demonstrates an impairment of muscle metabolism. No worsening of restCa or histological features was found in statin-treated aged animals. These findings suggest that a strong reduction of gCl and alteration of muscle metabolism coupled to muscle atrophy may contribute to the increased risk of statin-induced myopathy in the elderly. - Highlights: • This work characterizes the causes of atorvastatin related myotoxicity in aged rats. • Skeletal muscle chloride channel ClC-1 is a target of statin-induced side effects. • ClC-1 dysfunction is worsened by aging process. • Age-related changes of energy production contribute to statin-induced myotoxicity. • These findings suggest caution with statin therapy during aging.« less

Relative costs of transporting low-level waste according to four postulated regional-management cases

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

Wilmot, E.L.; Shirley, C.G.

1982-01-01

Results presented in this paper show that almost any compact binding states into cooperating regions for disposal of LLW will reduce nationwide transportation costs markedly. As a corollary, the reduction of costs may reflect a two- to four-fold reduction of transportation distances with consequent reduction of risk to the public since risk generally decreases directly as transport distances decrease.

Flaxseed oil as a neuroprotective agent on lead acetate-induced monoamineric alterations and neurotoxicity in rats.

PubMed

Abdel Moneim, Ahmed E

2012-09-01

Lead remains a considerable occupational and public health problem, which is known to cause a number of adverse effects in both man and animals. Here, the neuroprotective effect of flaxseed oil (1,000 mg/kg) on lead acetate (20 mg/kg) induced alternation in monoamines and brain oxidative stress was examined in rats. The levels of lead, dopamine (DA), norepinephrine (NE), serotonin (5-HT), lipid peroxidation, nitrite/nitrate (NO), and glutathione (GSH) were determined; also, the activity of acetylcholinesterase (AChE) and Na(+)-K(+)-ATPase were estimated on different brain regions of adult male albino rats. The level of lead was markedly elevated in different brain regions of rats. This leads to enhancement of lipid peroxidation and NO production in brain with concomitant reduction in AChE activity and GSH level. In addition, the levels of DA, NE, and 5-HT were decreased in the brain. These findings were associated with BAX over expression. Treatment of rats with flaxseed oil induced a marked improvement in most of the studied parameters as well as the immunohistochemistry features. These data indicated that dietary flaxseed oil provide protection against lead-induced oxidative stress and neurotoxic effects.

Hereditary and acquired abnormalities in erythrocyte phosphofructokinase activity: the close association with altered 2,3-diphosphoglycerate levels.

PubMed

Tarui, S; Kono, N; Kuwajima, M; Kitani, T

1980-01-01

Specific deficiency of erythrocyte phosphofructokinase (PFK) activity in Type VII glycogenosis presents a good model for the analysis of the relationship between 2,3 diphosphoglycerate (2,3 DPG) level and glycolysis in erythrocytes since glycolytic flow is partially blocked at the regulatory step. Enzymatic analyses of glycolytic intermediates of erythrocytes from a patient with Type VII glycogenosis demonstrated that 2,3 DPG is markedly decreased in parallel with fructose-1,6-phosphate (FDP). In acidosis including diabetic ketoacidosis and uremic acidosis a fall in 2,3 DPG is also associated with a marked reduction in FDP. On the other hand, in respiratory alkalosis glycolytic intermediates shift to the opposite direction and forward crossover at PFK step appears, being associated with an elevation of 2,3 DPG. These data indicate a close relationship between 2,3 DPG level and PFK activity in erythrocytes. At least in acidosis and alkalosis the alteration in 2,3 DPG level may well be explained by changes in PFK activity caused mainly through allosteric mechanism. In addition, twelve cases with hereditary PFK deficiency in muscle and erythrocytes reported in the world are reviewed and discussed briefly.

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.

Evidence of acrylamide induced oxidative stress and neurotoxicity in Drosophila melanogaster - its amelioration with spice active enrichment: relevance to neuropathy.

PubMed

Prasad, Sathya N; Muralidhara

2012-10-01

Acrylamide (ACR) intoxication in its monomeric form leads to neuronal damage in both experimental animals and humans. Oxidative stress is one of the principle mechanisms related to the neurotoxicity of ACR exposure. Hence, the present study aimed to recapitulate the potential of ACR to cause oxidative stress and neurotoxic effects in Drosophila melanogaster. Exposure of adult male flies (Oregon K strain) to ACR (1-10 mM, 7 d) in the diet resulted in a concentration and time dependent mortality, while the survivors exhibited significant locomotor deficits. Further, ACR exposure (1-5 mM, 3 d) caused robust oxidative stress as evidenced by markedly elevated levels of reactive oxygen species and hypdroperoxides in head/body regions. Enhanced lipid peroxidation, perturbations in the activities of antioxidant enzymes accompanied with depletion of reduced glutathione levels in head region at high concentrations suggested induction of oxidative stress. Further, marked diminution in the activities of complexes I-III, Succinic dehydrogenase, with concomitant reduction in MTT suggested the propensity of ACR to impair mitochondrial function. Furthermore, ACR-induced neurotoxic effects were discernible in terms of diminished ATPase activity, enhanced activity of acetylcholinesterase and dopamine depletion. In a satellite study, employing a co-exposure paradigm, we tested the propensity of spice actives namely eugenol (EU) and isoeugenol (IE) to ameliorate ACR-induced neurotoxicity. EU/IE enriched diet offered marked protection against ACR-induced mortality, locomotor dysfunctions and oxidative stress. Furthermore, the spice actives prevented the depletion of reduced GSH levels, maintained the activity of AChE enzyme and dopamine levels in head region. Collectively, these findings clearly demonstrate that ACR induced neurotoxicity in Drosophila may be mediated through oxidative stress mechanisms and the potential of spice actives to abrogate the condition. These data suggest that Drosophila may serve as a suitable model to understand the possible mechanism/s associated with ACR associated neuropathy. Copyright © 2012 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.

Prevention of abnormal pulmonary mechanics in the postmortem guinea pig lung.

PubMed

Reynolds, A M; McEvoy, R D

1988-04-01

Severe postmortem bronchoconstriction has been shown previously in guinea pig lungs and linked to pulmonary blood loss during exsanguination (Lai et al., J. Appl. Physiol. 56: 308-314, 1984). To reexamine this phenomenon we measured postmortem airway function in anesthetized open-chest guinea pigs after sudden circulatory arrest. Animals were divided into 4 groups of 10 and ventilated for 15 min postmortem with different gases: 1) room air, 2) conditioned air, 3) dry 5% CO2-21% O2-74% N2, and 4) conditioned 5% CO2-21% O2-74% N2. In room air-ventilated lungs there was a 50% decrease in dynamic compliance (Cdyn) by 15 min and marked gas trapping compared with control lungs. Conditioning the room air did not attenuate these changes, but when 5% CO2 was added to the conditioned postmortem inspirate, gas trapping was eliminated and the fall in Cdyn was almost abolished. Ventilation with a dry 5% CO2 gas mixture at room temperature resulted in a 31% fall in Cdyn at 15 min but no gas trapping. We conclude that marked abnormalities of airway function occur postmortem in room air-ventilated guinea pig lungs in the absence of pulmonary blood loss. The changes are mainly due to airway hypocarbia, a known cause of bronchoconstriction, but a reduction in Cdyn can also occur if there is marked airway cooling and drying. Acute postmortem airway dysfunction can be prevented in the guinea pig by maintaining normal airway gas composition.

The Effect of Mass Distribution on the Lateral Stability and Control Characteristics of an Airplane as Determined by Tests of a Model in the Free-Flight Tunnel

NASA Technical Reports Server (NTRS)

Seacord, Charles L; Campbell, John P.

1943-01-01

The effects of mass distribution on lateral stability and control characteristics of an airplane have been determined by flight tests of a model in the NACA free-flight tunnel. In the investigation, the rolling and yawing movements of inertia were increased from normal values to values up to five times normal. For each moment-of-inertia condition, combinations of dihedral and vertical-tail area representing a variety of airplane configurations were tested. The results of the flight tests of the model were correlated with calculated stability and control characteristics and, in general, good agreement was obtained. The tests showed the following effects of increased rolling and yawing moments of inertia: no appreciable change in spiral stability; reductions in oscillatory stability that were serious at high values of dihedral; a reduction in the sensitivity of the model to gust disturbances; and a reduction in rolling acceleration provided by the ailerons, which caused a marked increase in time to reach a given angle of bank. The general flight behavior of the model became worse with increasing moments of inertia but, with combinations of small effective dihedral and large vertical-tail area, satisfactory flight characteristics were obtained at all moment-of-inertia conditions.

Cell oxidation-reduction imbalance after modulated radiofrequency radiation.

PubMed

Marjanovic, Ana Marija; Pavicic, Ivan; Trosic, Ivancica

2015-01-01

Aim of this study was to evaluate an influence of modulated radiofrequency field (RF) of 1800 MHz, strength of 30 V/m on oxidation-reduction processes within the cell. The assigned RF field was generated within Gigahertz Transversal Electromagnetic Mode cell equipped by signal generator, modulator, and amplifier. Cell line V79, was irradiated for 10, 30, and 60 min, specific absorption rate was calculated to be 1.6 W/kg. Cell metabolic activity and viability was determined by MTT assay. In order to define total protein content, colorimetric method was used. Concentration of oxidised proteins was evaluated by enzyme-linked immunosorbent assay. Reactive oxygen species (ROS) marked with fluorescent probe 2',7'-dichlorofluorescin diacetate were measured by means of plate reader device. In comparison with control cell samples, metabolic activity and total protein content in exposed cells did not differ significantly. Concentrations of carbonyl derivates, a product of protein oxidation, insignificantly but continuously increase with duration of exposure. In exposed samples, ROS level significantly (p < 0.05) increased after 10 min of exposure. Decrease in ROS level was observed after 30-min treatment indicating antioxidant defence mechanism activation. In conclusion, under the given laboratory conditions, modulated RF radiation might cause impairment in cell oxidation-reduction equilibrium within the growing cells.

Gastric acid reduction leads to an alteration in lower intestinal microflora

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

Kanno, Takayuki; Matsuki, Takahiro; Oka, Masashi

2009-04-17

To clarify the alterations in lower intestinal microflora induced by gastric acid reduction, the dynamics of 12 major genera or groups of bacteria comprising the microflora in feces and colonic contents were examined by quantitative real-time PCR in proton pump inhibitor-treated rats and in asymptomatic human subjects with hypochlorhydria. In both rat and human experiments, most genera or groups of intestinal microflora (facultative and obligate anaerobes) proliferated by gastric acid reduction, and marked and significant increases in the Lactobacilli group and Veillonella, oropharyngeal bacteria, were observed. In rats, potent gastric acid inhibition led to a marked and significant increase ofmore » intestinal bacteria, including the Bacteroidesfragilis group, while Bifidobacterium, a beneficial bacterial species, remained at a constant level. These results strongly indicate that the gastric acid barrier not only controls the colonization and growth of oropharyngeal bacteria, but also regulates the population and composition of lower intestinal microflora.« less

Estrogen-associated severe hypertriglyceridemia with pancreatitis.

PubMed

Aljenedil, Sumayah; Hegele, Robert A; Genest, Jacques; Awan, Zuhier

Estrogen, whether therapeutic or physiologic, can cause hypertriglyceridemia. Hypertriglyceridemia-induced pancreatitis is a rare complication. We report 2 women who developed estrogen-associated severe hypertriglyceridemia with pancreatitis. The first patient developed pancreatitis secondary to hypertriglyceridemia associated with in vitro fertilization cycles. Marked reduction in her triglyceride was achieved with dietary restrictions and fibrate. The second patient developed pancreatitis secondary to hypertriglyceridemia during her pregnancies. She was noncompliant with the treatment; therefore, her triglyceride remained high after delivery. In both patients, no hypertriglyceridemia-associated genes mutations were identified, although the second patient had strong polygenic susceptibility to hypertriglyceridemia. Estrogen-induced severe hypertriglyceridemia with pancreatitis can be a life-threatening condition. Screening in high-risk patients is crucial to prevent subsequent complications. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

EFFECT OF TETRACYCLINES ON THE INTRACELLULAR AMINO ACIDS OF MOLDS

PubMed Central

Freeman, Bob A.; Circo, Richard

1963-01-01

Freeman, Bob A. (University of Chicago, Chicago, Ill.) and Richard Circo. Effect of tetracyclines on the intracellular amino acids of molds. J. Bacteriol. 86:38–44. 1963.—The tetracycline antibiotics were shown to alter the amino acid metabolism of molds whose growth is not markedly affected. Eight molds were grown in the presence of these antiobiotics; four exhibited a general reduction in the concentration of the intracellular amino acids, except for glutamic acid and alanine. In most of these four cultures, the tetracyclines also caused the complete disappearance of arginine, lysine, proline, phenylalanine, and tyrosine from the intracellular amino acid pool. The significance of these observations and the usefulness of the method in the study of the mechanisms of antibiotic action are discussed. PMID:14051820

Mass killings and detection of impacts

NASA Technical Reports Server (NTRS)

Mclaren, Digby J.

1988-01-01

Highly energetic bolide impacts occur and their flux is known. For larger bodies the energy release is greater than for any other short-term global phenomenon. Such impacts produce or release a large variety of shock induced changes including major atmospheric, sedimentologic, seismic and volcanic events. These events must necessarily leave a variety of records in the stratigraphic column, including mass killings resulting in major changes in population density and reduction or extinction of many taxonomic groups, followed by characteristic patterns of faunal and flora replacement. Of these effects, mass killings, marked by large-scale loss of biomass, are the most easily detected evidence in the field but must be manifest on a near-global scale. Such mass killings that appear to be approximately synchronous and involve disappearance of biomass at a bedding plane in many sedimentologically independent sections globally suggest a common cause and probable synchroneity. Mass killings identify an horizon which may be examined for evidence of cause. Geochemical markers may be ephemeral and absence may not be significant. There appears to be no reason why ongoing phenomena such as climate and sea-level changes are primary causes of anomolous episodic events.

Mass killings and detection of impacts

NASA Astrophysics Data System (ADS)

McLaren, Digby J.

Highly energetic bolide impacts occur and their flux is known. For larger bodies the energy release is greater than for any other short-term global phenomenon. Such impacts produce or release a large variety of shock induced changes including major atmospheric, sedimentologic, seismic and volcanic events. These events must necessarily leave a variety of records in the stratigraphic column, including mass killings resulting in major changes in population density and reduction or extinction of many taxonomic groups, followed by characteristic patterns of faunal and flora replacement. Of these effects, mass killings, marked by large-scale loss of biomass, are the most easily detected evidence in the field but must be manifest on a near-global scale. Such mass killings that appear to be approximately synchronous and involve disappearance of biomass at a bedding plane in many sedimentologically independent sections globally suggest a common cause and probable synchroneity. Mass killings identify an horizon which may be examined for evidence of cause. Geochemical markers may be ephemeral and absence may not be significant. There appears to be no reason why ongoing phenomena such as climate and sea-level changes are primary causes of anomolous episodic events.

Sildenafil protects against bile duct ligation induced hepatic fibrosis in rats: Potential role for silent information regulator 1 (SIRT1).

PubMed

Abd El Motteleb, Dalia M; Ibrahim, Islam A A E-H; Elshazly, Shimaa M

2017-11-15

Hepatic fibrosis is a potential health problem that may end with life-threatening cirrhosis and primary liver cancer. Recent studies point out to the protective effects of silent information regulator1 (SIRT1), against different models of organs fibrosis. This work aimed to investigate the possible protective effect of sildenafil (SIRT1 activator) against hepatic fibrosis induced by bile duct ligation (BDL). Firstly, three different doses of sildenafil (5, 10, 20mg/kg/day) were investigated; to detect the most protective one against BDL induced liver dysfunction and hepatic fibrosis. The most protective dose is then used; to study its effect on BDL induced SIRT1 downregulation, imbalance of oxidant/antioxidant status, increased inflammatory cytokines and fibrosis. Sildenafil (20mg/kg/day) was the most protective one, it caused upregulation of SIRT1, reduction of hepatic malondialdehyde (MDA) content, increase in expression of nuclear factor erythroid 2-related factor 2 (Nrf2), hemeoxygenease (HO)-1, reduced glutathione (GSH) content and superoxide dismutase (SOD) activity. Hepatic content of tumor necrosis factor-α (TNF-α) and nuclear factor κB (NFκB) expression & content displayed significant reductions with sildenafil treatment, Furthermore, sildenafil caused marked reductions of transforming growth factor (TGF)-β content, expression of plasminogen activator inhibitor-1 (PAI-1), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), α-smooth muscle actin (α-SMA), fibronectin, collagen I (α1) and hydroxyproline content. However, sildenafil protective effects were significantly reduced by co-administration of EX527 (SIRT1 inhibitor). Our work showed, for the first time that, sildenafil has promising protective effects against BDL induced liver dysfunction and hepatic fibrosis. These effects may be, in part, mediated by up regulation of SIRT1. Copyright © 2017. Published by Elsevier Inc.

[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.

Outbreak of diffuse lamellar keratitis caused by marking-pen toxicity.

PubMed

Hadden, Osmond Bruce; McGhee, Charles N J; Morris, Antony Trevor; Gray, Trevor Buchanan; Ring, Charles Peter; Watson, Adam Stewart John

2008-07-01

To examine the evidence that a series of cases of diffuse lamellar keratitis (DLK) after laser in situ keratomileusis (LASIK) was caused by a type of marker pen. Eye Institute, Auckland, New Zealand. During a 10-week period, 522 consecutive LASIK procedures were performed using a 60 Hz IntraLase femtosecond laser (IntraLase Corp.) to create the LASIK flap and a 217Z 100 Hz excimer laser (Bausch & Lomb) to perform the refractive ablation. As standard practice, a marking pen was used to enable accurate flap realignment. Three weeks after a sudden increase in the incidence of DLK was identified, one of the 5 surgeons performed 5 consecutive bilateral cases using the marking pen in the right eyes but not in the left eyes. Of the 522 LASIK cases (119 without marking pen, 403 with marking pen), DLK developed in 49 (9.4%). No eye treated without the marking pen developed DLK; of those in which the marking pen was used, 49 (12.2%) developed DLK (P<0.0001, Fischer exact test; odds ratio, 27). In the 5 consecutive bilateral cases in which the marking pen was used in the right eye but not the left eye, 4 right eyes and no left eye developed DLK (P=0.03). Forty-five of the 49 eyes with DLK quickly recovered. The other 4 developed central toxic keratopathy. There is strong statistical evidence that the marking pen was a factor in the occurrence of DLK.

High-bandwidth generation of duobinary and alternate-mark-inversion modulation formats using SOA-based signal processing.

PubMed

Dailey, James M; Power, Mark J; Webb, Roderick P; Manning, Robert J

2011-12-19

We report on the novel all-optical generation of duobinary (DB) and alternate-mark-inversion (AMI) modulation formats at 42.6 Gb/s from an input on-off keyed signal. The modulation converter consists of two semiconductor optical amplifier (SOA)-based Mach-Zehnder interferometer gates. A detailed SOA model numerically confirms the operational principles and experimental data shows successful AMI and DB conversion at 42.6 Gb/s. We also predict that the operational bandwidth can be extended beyond 40 Gb/s by utilizing a new pattern-effect suppression scheme, and demonstrate dramatic reductions in patterning up to 160 Gb/s. We show an increasing trade-off between pattern-effect reduction and mean output power with increasing bitrate.

Protective effect of tangeritin in transgenic Drosophila model of Parkinson's disease.

PubMed

Fatima, Ambreen; Khanam, Saba; Rahul, Rahul; Jyoti, Smita; Naz, Falaq; Ali, Fahad; Siddique, Yasir Hasan

2017-01-01

Parkinson's disease (PD) is a neurodegenerative disorder caused due to the loss of dopaminergic neurons in substantia nigra region of midbrain. The disease is characterized by the accumulation of alpha-synuclein into depositions known as lewy bodies. Till date there is no cure for PD but the limited number of medications may provide temporary relief from the PD symptoms. Flavonoids are a group of polyphenols found in plants. The health benefits of flavonoids have been universally accepted. Tangeritin is a pentamethoxy flavone found in the peels of Mandarin oranges ( Citrus reticulata ). The present study was conducted to study the effect of tangeritin on the symptoms of PD exhibited by the PD model transgenic flies ( Drosophila melanogaster) . Tangeritin at a final concentration of 5, 10 and 20 microM was added to the diet and the flies were allowed to feed on it for 24 days. At the same time other set of PD flies were allowed to feed on a diet having 10-3 M of L-Dopa. The effect of tangeritin was studied on the activity pattern, climbing ability, dopamine content, oxidative stress markers (lipid peroxidation, reduced glutathione, glutathione-S-transferase, protein carbonyl content and monoamine oxidase activity) and on the histopathology of the brain of PD model flies. The study showed that the exposure of PD flies to different doses of tangeritin showed a marked delay in the loss of climbing ability and increase in the dopamine content. Tangeritin also showed a reduction in various oxidative stress markers. Hence it is concluded that tangeritin showed a marked reduction in the PD symptoms and thus could be of great importance for further research in treating PD.

Macrophage Liver Kinase B1 Inhibits Foam Cell Formation and Atherosclerosis.

PubMed

Liu, Zhaoyu; Zhu, Huaiping; Dai, Xiaoyan; Wang, Cheng; Ding, Ye; Song, Ping; Zou, Ming-Hui

2017-10-13

LKB1 (liver kinase B1) is a serine/threonine kinase and tumor suppressor, which regulates the homeostasis of hematopoietic cells and immune responses. Macrophages transform into foam cells upon taking-in lipids. No role for LKB1 in foam cell formation has previously been reported. We sought to establish the role of LKB1 in atherosclerotic foam cell formation. LKB1 expression was examined in human carotid atherosclerotic plaques and in western diet-fed atherosclerosis-prone Ldlr -/- and ApoE -/- mice. LKB1 expression was markedly reduced in human plaques when compared with nonatherosclerotic vessels. Consistently, time-dependent reduction of LKB1 levels occurred in atherosclerotic lesions in western diet-fed Ldlr -/- and ApoE -/- mice. Exposure of macrophages to oxidized low-density lipoprotein downregulated LKB1 in vitro. Furthermore, LKB1 deficiency in macrophages significantly increased the expression of SRA (scavenger receptor A), modified low-density lipoprotein uptake and foam cell formation, all of which were abolished by blocking SRA. Further, we found LKB1 phosphorylates SRA resulting in its lysosome degradation. To further investigate the role of macrophage LKB1 in vivo, ApoE -/- LKB1 fl/fl LysM cre and ApoE -/- LKB1 fl/fl mice were fed with western diet for 16 weeks. Compared with ApoE -/- LKB1 fl/fl wild-type control, ApoE -/- LKB1 fl/fl LysM cre mice developed more atherosclerotic lesions in whole aorta and aortic root area, with markedly increased SRA expression in aortic root lesions. We conclude that macrophage LKB1 reduction caused by oxidized low-density lipoprotein promotes foam cell formation and the progression of atherosclerosis. © 2017 American Heart Association, Inc.

"Summer Shift": A Potential Effect of Sunshine on the Time Onset of ST-Elevation Acute Myocardial Infarction.

PubMed

Cannistraci, Carlo Vittorio; Nieminen, Tuomo; Nishi, Masahiro; Khachigian, Levon M; Viikilä, Juho; Laine, Mika; Cianflone, Domenico; Maseri, Attilio; Yeo, Khung Keong; Bhindi, Ravinay; Ammirati, Enrico

2018-04-06

ST-elevation acute myocardial infarction (STEMI) represents one of the leading causes of death. The time of STEMI onset has a circadian rhythm with a peak during diurnal hours, and the occurrence of STEMI follows a seasonal pattern with a salient peak of cases in the winter months and a marked reduction of cases in the summer months. Scholars investigated the reason behind the winter peak, suggesting that environmental and climatic factors concur in STEMI pathogenesis, but no studies have investigated whether the circadian rhythm is modified with the seasonal pattern, in particular during the summer reduction in STEMI occurrence. Here, we provide a multiethnic and multination epidemiological study (from both hemispheres at different latitudes, n=2270 cases) that investigates whether the circadian variation of STEMI onset is altered in the summer season. The main finding is that the difference between numbers of diurnal (6:00 to 18:00) and nocturnal (18:00 to 6:00) STEMI is markedly decreased in the summer season, and this is a prodrome of a complex mechanism according to which the circadian rhythm of STEMI time onset seems season dependent. The "summer shift" of STEMI to the nocturnal interval is consistent across different populations, and the sunshine duration (a measure related to cloudiness and solar irradiance) underpins this season-dependent circadian perturbation. Vitamin D, which in our results seems correlated with this summer shift, is also primarily regulated by the sunshine duration, and future studies should investigate their joint role in the mechanisms of STEMI etiogenesis. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

MHC-mismatched mixed chimerism augments thymic regulatory T-cell production and prevents relapse of EAE in mice

PubMed Central

Wu, Limin; Li, Nainong; Zhang, Mingfeng; Xue, Sheng-Li; Cassady, Kaniel; Lin, Qing; Riggs, Arthur D.; Zeng, Defu

2015-01-01

Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system with demyelination, axon damage, and paralysis. Induction of mixed chimerism with allogeneic donors has been shown to not cause graft-versus-host disease (GVHD) in animal models and humans. We have reported that induction of MHC-mismatched mixed chimerism can cure autoimmunity in autoimmune NOD mice, but this approach has not yet been tested in animal models of MS, such as experimental autoimmune encephalomyelitis (EAE). Here, we report that MHC-mismatched mixed chimerism with C57BL/6 (H-2b) donor in SJL/J (H-2s) EAE recipients eliminates clinical symptoms and prevents relapse. This cure is demonstrated by not only disappearance of clinical signs but also reversal of autoimmunity; elimination of infiltrating T, B, and macrophage cells in the spinal cord; and regeneration of myelin sheath. The reversal of autoimmunity is associated with a marked reduction of autoreactivity of CD4+ T cells and significant increase in the percentage of Foxp3+ Treg among host-type CD4+ T cells in the spleen and lymph nodes. The latter is associated with a marked reduction of the percentage of host-type CD4+CD8+ thymocytes and an increase of Treg percentage among the CD4+CD8+ and CD4+CD8− thymocytes. Thymectomy leads to loss of prevention of EAE relapse by induction of mixed chimerism, although there is a dramatic expansion of host-type Treg cells in the lymph nodes. These results indicate that induction of MHC-mismatched mixed chimerism can restore thymic negative selection of autoreactive CD4+ T cells, augment production of Foxp3+ Treg, and cure EAE. PMID:26647186

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

Marine Food Protection in Testicular Damages Caused by Diabetes Mellitus.

PubMed

Caiaffo, Vitor; Ribeiro de Oliveira, Belisa Duarte; de Sa, Fabricio Bezerra; Neto, Joaqvim Evencio; da Silva Junior, Voldemiro Amaro

2017-01-01

Diabetes Mellitus (DM) is a chronic hyperglycemic condition with major health concern on a global scale. DM is a heterogeneous metabolic disorder stemming from defective insulin secretion and/or resistance to action of insulin. Diabetes is recognized cause of male sexual dysfunction and affects reproductive function in humans and animal models, including the endocrine control of spermatogenesis, erectile dysfunction and ejaculation disorder. Testicular disorder is characteristically marked by reductions of testicle weight, sperm count and motility, as well as changes in the morphology of the seminiferous epithelium. Altered testosterone level is another characteristic of diabetic animals. Studies have demonstrated that DM increases apoptosis in germ cells and lead to the interruption of spermatogenesis, mainly by exerting an influence on Bcl-2 protein and cysteinedependent aspartate-directed proteases. DM also increases oxidative stress in testicular cells and excessive production of radical oxygen species has been demonstrated. Several strategies can be used as means of prevention and/or treatment for diverse types of damage to testicles by DM such as regular physical exercise, stress reduction and food intake of substances with antioxidant potential. A hypoglycemic and antioxidant potential diet, in particular, the seafood, can be a valuable instrument of guard against damage caused by DM, both the systemic level as testicular level. The objective of this review is to summarize evidences that study the antioxidant, anti-inflammatory and anti-apoptosis role of seafood in testicles morphology damages induced by diabetes mellitus. The seafood plays an antioxidant, anti-inflammatory and anti-apoptosis role in testicles morphology damages induced by diabetes mellitus. This relation seems to be associated with Omega-3 and carotenoids (astaxanthin) levels. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Downregulation of Aquaporins (AQP1 and AQP5) and Na,K-ATPase in Porcine Reproductive and Respiratory Syndrome Virus-Infected Pig Lungs.

PubMed

Zhang, Jianping; Yan, Meiping; Gu, Wei; Chen, Ao; Liu, Jie; Li, Lexing; Zhang, Songlin; Liu, Guoquan

2018-06-01

Aquaporins (AQPs) and Na,K-ATPase control water transport across the air space-capillary barrier in the distal lung and play an important role in the formation and resolution of lung edema. Porcine reproductive and respiratory syndrome virus (PRRSV) infection usually causes pulmonary inflammation and edema in the infected pig lungs. To investigate the possibility that PRRSV infection may cause altered expression of AQPs and Na,K-ATPase messenger RNA (mRNA) levels and protein expression of AQP1, AQP5, and Na,K-ATPase in the PRRSV-infected pig lungs were detected. Quantitative real-time PCR (qRT-PCR) analysis showed markedly decreased mRNA levels of AQP1 and AQP5 and Na,K-ATPase in the PRRSV-infected pig lungs compared to those of uninfected pig lungs. Western blot studies also revealed significantly reduced levels of AQP1, AQP5, and Na,K-ATPase proteins in the PRRSV-infected pig lungs. In addition, immunohistochemical (IHC) analysis showed decreased protein expression of AQP1 and AQP5 in the endothelial cells of the capillaries and venules and secretory cells of terminal bronchiole and the alveolar type I cells, respectively. The expression of Na,K-ATPase in the basolateral membrane of alveolar type II cells presented great reduction in the PRRSV-infected pig lungs. To further understand the reduction of these proteins, the ubiquitination of AQP1 and Na,K-ATPase was examined in uninfected and PRRSV-infected pig lungs. The results showed that there is no difference of ubiquitination for these proteins. Thus, our results suggest that PRRSV infection may induce downregulation of these proteins and cause impairment of edema resolution by failed water clearance in the infected pig lungs.

Evaporative loss from soil, native vegetation, and snow as affected by hexadecanol

Treesearch

Henry W. Anderson; Allan J. West; Robert R. Ziemer; Franklin R. Adams

1963-01-01

Abstract - Only in a bulldozed brush field and with heavy applications of hexadecanol under snow did significant reductions in evapotranspiration occur with application of hexadecanol to natural stands. Marked reductions in evaporation from snow occurred when hexadecanol emulsion was applied to the snow surface. More than two-thirds of the precipitation in the United...

CytoSorb, a novel therapeutic approach for patients with septic shock: a case report.

PubMed

Hinz, Burkhard; Jauch, Oliver; Noky, Toralf; Friesecke, Sigrun; Abel, Peter; Kaiser, Rolf

2015-08-01

Hemoadsorption using CytoSorb has gained attention as a potential immunotherapy to control systemic inflammation and sepsis. We report on a patient with septic shock, successfully treated with CytoSorb therapy. A 72-year-old male with periodically recurring infectious episodes was admitted with the suspicion of urosepsis. In the following hours his hemodynamic situation deteriorated markedly, exhibiting respiratory-metabolic acidosis, elevated inflammatory marker plasma levels, a severely disturbed coagulation, increased retention parameters, liver dysfunction, and confirmation of bacteria and leucocytes in urine. After admission to the ICU in a state of septic shock the patient received renal support with additional hemoadsorption using CytoSorb. Three CytoSorb sessions were run during the following days. The first and consecutive second session resulted in a reduction of procalcitonin, C-reactive protein and bilirubin and a markedly reduced need for vasopressors while hemodynamics improved significantly (i.e., cardiac index, extravascular lung water). Due to a recurring inflammatory "second hit" episode, another session with CytoSorb was run, resulting in a marked decrease in leukocytosis and liver (dys)function parameters. The rapid hemodynamic stabilization with reduction of vasopressor needs within hours and reduction of the capillary leakage as well as a quick reduction in infection markers were the main conclusions drawn from the use of CytoSorb in this patient. Additionally, treatment appeared to be safe and was well tolerated. Despite the promising results of CytoSorb application in this patient, further studies are necessary to elucidate to what extent these favorable consequences are attributable to the adsorber itself.

Effect of a pore-forming protein derived from Flammulina velutipes on the Caco-2 intestinal epithelial cell monolayer.

PubMed

Narai, Asako; Watanabe, Hirohito; Iwanaga, Toshihiko; Tomita, Toshio; Shimizu, Makoto

2004-11-01

We have previously found a transepithelial electrical resistance (TEER)-decreasing protein derived from Flammulina velutipes, which was revealed to be identical to flammutoxin (FTX) that is known as a hemolytic pore-forming protein. This protein induced a rapid decrease in TEER and parallel increase in paracellular permeability in the intestinal epithelial Caco-2 cell monolayer without any cytotoxicity. An immunoblotting analysis revealed that the FTX-induced decrease in TEER was accompanied by the formation of a high-molecular-weight complex on the surface of Caco-2 cells. Intracellular Ca(2+) imaging showed that exposure to FTX caused a rapid Ca(2+) influx. It was observed by electron microscopy that FTX induced swelling of microvilli and expansion of the cellular surface. Staining with fluorescent phalloidin showed a marked change to filamentous actin in the FTX-treated cells. These results suggest that TEER reduction could sensitively detect small membrane pore formation by FTX in the intestinal epithelium which causes a morphological alteration and disruption of the paracellular barrier function.

[Changes in fish communities of coral reefs at Sabana-Camagüey Archipelago, Cuba].

PubMed

Claro, Rodolfo; Cantelar, Karel; Amargós, Fabián Pina; García-Arteaga, Juan P

2007-06-01

A comparison of fish community structure in the Sabana-Camagüey Archipelago (1988-1989 and 2000) using visual census surveys (eight belt transects 2x50 m in each site) suggests a notable decrease on species richness, and a two thirds reduction in fish density and biomass on coral reefs. This decrease in fish populations may be related to the alarming decrease of scleractinian coral cover, and an enormous proliferation of algae, which currently covers 70-80% of the hard substrate, impeding the recovery of corals and other benthic organisms. High coral mortalities occurred between the study periods, which correlate with the high temperatures caused by the ENSO events of 1995, 1997 and 1998. These events caused massive bleaching of corals and subsequent algae overgrowth. Evidence of nutrient enrichment from the inner lagoons and overfishing are also present. Collectively, these effects have provoked a marked degradation of reef habitats. These changes appear to have affected the availability of refuges and food for fishes, and may be constraining individual growth potential and population size.

The contribution of mitochondrial thymidylate synthesis in preventing the nuclear genome stress.

PubMed

Lee, Ming-Hsiang; Wang, Liya; Chang, Zee-Fen

2014-04-01

In quiescent fibroblasts, the expression levels of cytosolic enzymes for thymidine triphosphate (dTTP) synthesis are down-regulated, causing a marked reduction in the dTTP pool. In this study, we provide evidence that mitochondrial thymidylate synthesis via thymidine kinase 2 (TK2) is a limiting factor for the repair of ultraviolet (UV) damage in the nuclear compartment in quiescent fibroblasts. We found that TK2 deficiency causes secondary DNA double-strand breaks formation in the nuclear genome of quiescent cells at the late stage of recovery from UV damage. Despite slower repair of quiescent fibroblast deficient in TK2, DNA damage signals eventually disappeared, and these cells were capable of re-entering the S phase after serum stimulation. However, these cells displayed severe genome stress as revealed by the dramatic increase in 53BP1 nuclear body in the G1 phase of the successive cell cycle. Here, we conclude that mitochondrial thymidylate synthesis via TK2 plays a role in facilitating the quality repair of UV damage for the maintenance of genome integrity in the cells that are temporarily arrested in the quiescent state.

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.

A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys.

PubMed

Barnhart, Kirstin F; Christianson, Dawn R; Hanley, Patrick W; Driessen, Wouter H P; Bernacky, Bruce J; Baze, Wallace B; Wen, Sijin; Tian, Mei; Ma, Jingfei; Kolonin, Mikhail G; Saha, Pradip K; Do, Kim-Anh; Hulvat, James F; Gelovani, Juri G; Chan, Lawrence; Arap, Wadih; Pasqualini, Renata

2011-11-09

Obesity, defined as body mass index greater than 30, is a leading cause of morbidity and mortality and a financial burden worldwide. Despite significant efforts in the past decade, very few drugs have been successfully developed for the treatment of obese patients. Biological differences between rodents and primates are a major hurdle for translation of anti-obesity strategies either discovered or developed in rodents into effective human therapeutics. Here, we evaluate the ligand-directed peptidomimetic CKGGRAKDC-GG-(D)(KLAKLAK)(2) (henceforth termed adipotide) in obese Old World monkeys. Treatment with adipotide induced targeted apoptosis within blood vessels of white adipose tissue and resulted in rapid weight loss and improved insulin resistance in obese monkeys. Magnetic resonance imaging and dual-energy x-ray absorptiometry confirmed a marked reduction in white adipose tissue. At experimentally determined optimal doses, monkeys from three different species displayed predictable and reversible changes in renal proximal tubule function. Together, these data in primates establish adipotide as a prototype in a new class of candidate drugs that may be useful for treating obesity in humans.

RNCR3 knockdown inhibits diabetes mellitus-induced retinal reactive gliosis

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

Liu, Chang; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai; The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing

Retinal reactive gliosis is an important pathological feature of diabetic retinopathy. Identifying the underlying mechanisms causing reactive gliosis will be important for developing new therapeutic strategies for treating diabetic retinopathy. Herein, we show that long noncoding RNA-RNCR3 knockdown significantly inhibits retinal reactive gliosis. RNCR3 knockdown leads to a marked reduction in the release of several cytokines. RNCR3 knockdown alleviates diabetes mellitus-induced retinal neurodegeneration, as shown by less apoptotic retinal cells and ameliorative visual function. RNCR3 knockdown could also decrease Müller glial cell viability and proliferation, and reduce the expression of glial reactivity-related genes including GFAP and vimentin in vitro. Collectively, thismore » study shows that RNCR3 knockdown may be a promising strategy for the prevention of diabetes mellitus-induced retinal neurodegeneration. - Highlights: • RNCR3 knockdown inhibits retinal reactive gliosis. • RNCR3 knockdown causes a significant change in cytokine profile. • RNCR3 knockdown alleviates diabetes mellitus-induced retinal neurodegeneration. • RNCR3 knockdown affects Müller glial cell function in vitro.« less

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

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

Boustany, R.M.; Qian, W.H.; Suzuki, K.

The authors describe four new mutations in the [beta]-galactosidase gene. These are the first mutations causing infantile and juvenile GM[sub 1]-gangliosidosis to be described in American patients. Cell lines from two patients with juvenile and from six patients with infantile GM[sub 1]-gangliosidosis were analyzed. Northern blot analysis showed the acid [beta]-galactosidase message to be of normal size and quantity in two juvenile and four infantile cases and of normal size but reduced quantity in two infantile cases. The mutations are distinct from the Japanese mutations. All are point mutations leading to amino acid substitutions: Lys[sup 577] [yields] Arg, Arg[sup 590]more » [yields] His, and Glu[sup 632] [yields] Gly. The fourth mutation, Arg[sup 208] [yields] Cys, accounts for 10 of 16 possible alleles. Two infantile cases from Puerto Rico of Spanish ancestry are homozygous for this mutation, suggesting that this allele may have come to South America and North America via Puerto Rico. That these mutations cause clinical disease was confirmed by marked reduction in catalytic activity of the mutant proteins in the Cos-1 cell expression system. 12 refs., 5 figs., 2 tabs.« less

Improving awareness of mercury pollution in small-scale gold mining communities: challenges and ways forward in rural Ghana.

PubMed

Hilson, Gavin; Hilson, Christopher J; Pardie, Sandra

2007-02-01

This paper critiques the approach taken by the Ghanaian Government to address mercury pollution in the artisanal and small-scale gold mining sector. Unmonitored releases of mercury-used in the gold-amalgamation process-have caused numerous environmental complications throughout rural Ghana. Certain policy, technological and educational initiatives taken to address the mounting problem, however, have proved marginally effective at best, having been designed and implemented without careful analysis of mine community dynamics, the organization of activities, operators' needs and local geological conditions. Marked improvements can only be achieved in this area through increased government-initiated dialogue with the now-ostracized illegal galamsey mining community; introducing simple, cost-effective techniques for the reduction of mercury emissions; and effecting government-sponsored participatory training exercises as mediums for communicating information about appropriate technologies and the environment.

The Pathophysiology of Malabsorption

PubMed Central

Keller, Jutta; Layer, Peter

2014-01-01

Summary Physiological digestion and absorption of nutrients within the gastrointestinal tract requires a complex interaction between motor, secretory, digestive, and absorptive functions that is vulnerable to a multitude of potential disturbances which may lead to global or specific malabsorption syndromes. Potential pathomechanisms that are illustrated in this article include insufficient mechanical breakdown of harder food components due to chewing problems and/or decreased antral contractility, critical reduction of time for absorption in patients with markedly enhanced upper gastrointestinal transit (e.g. dumping syndrome), impaired digestion and absorption of nutrient components caused by reduced gastric acid secretion, pancreatic exocrine insufficiency or reduced biliary secretion, defects of the enteral mucosa with enzyme deficiencies (e.g. disaccharidases) or lack of specific carrier mechanisms (e.g. hexose or aminoacid transporters), and critical quantitative loss of intestinal mucosa in patients with short bowel syndrome. PMID:26288588

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.

Proliferative enteritis in leopard geckos (Eublepharis macularius) associated with Cryptosporidium sp. infection.

PubMed

Terrell, Scott P; Uhl, Elizabeth W; Funk, Richard S

2003-03-01

Twenty-three leopard geckos (Eublepharis macularius) with various clinical histories of weight loss, anorexia, lethargy, and diarrhea were submitted either intact or as biopsy specimens to the University of Florida Anatomic Pathology Service. Gross necropsy findings in the intact geckos included marked reduction of subcutaneous adipose tissue stores at the tail base and mild thickening and reddening of the small intestine. Histologic examination revealed Cryptosporidium sp. infection associated with hyperplasia and mononuclear inflammation of the small intestine in all geckos. Parasites and lesions were only rarely observed in the stomach and large intestine of geckos. The histologic and ultrastructural lesions in the small intestine of leopard geckos infected with Cryptosporidium sp. have not been well characterized previously. This report implicates Cryptosporidium sp. as the cause of disease in the geckos and describes the range of histologic lesions observed.

Molecular and clinical characterization of the myopathic form of mitochondrial DNA depletion syndrome caused by mutations in the thymidine kinase (TK2) gene.

PubMed

Chanprasert, Sirisak; Wang, Jing; Weng, Shao-Wen; Enns, Gregory M; Boué, Daniel R; Wong, Brenda L; Mendell, Jerry R; Perry, Deborah A; Sahenk, Zarife; Craigen, William J; Alcala, Francisco J Climent; Pascual, Juan M; Melancon, Serge; Zhang, Victor Wei; Scaglia, Fernando; Wong, Lee-Jun C

2013-01-01

Mitochondrial DNA (mtDNA) depletion syndromes (MDSs) are a clinically and molecularly heterogeneous group of mitochondrial cytopathies characterized by severe mtDNA copy number reduction in affected tissues. Clinically, MDSs are mainly categorized as myopathic, encephalomyopathic, hepatocerebral, or multi-systemic forms. To date, the myopathic form of MDS is mainly caused by mutations in the TK2 gene, which encodes thymidine kinase 2, the first and rate limiting step enzyme in the phosphorylation of pyrimidine nucleosides. We analyzed 9 unrelated families with 11 affected subjects exhibiting the myopathic form of MDS, by sequencing the TK2 gene. Twelve mutations including 4 novel mutations were detected in 9 families. Skeletal muscle specimens were available from 7 out of 11 subjects. Respiratory chain enzymatic activities in skeletal muscle were measured in 6 subjects, and enzymatic activities were reduced in 3 subjects. Quantitative analysis of mtDNA content in skeletal muscle was performed in 5 subjects, and marked mtDNA content reduction was observed in each. In addition, we outline the molecular and clinical characteristics of this syndrome in a total of 52 patients including those previously reported, and a total of 36 TK2 mutations are summarized. Clinically, hypotonia and proximal muscle weakness are the major phenotypes present in all subjects. In summary, our study expands the molecular and clinical spectrum associated with TK2 deficiency. © 2013.

Immobilized tannase treatment alters polyphenolic composition in teas and their potential anti-obesity and hypoglycemic activities in vitro.

PubMed

Roberto, Bruna Sampaio; Macedo, Gabriela Alves; Macedo, Juliana Alves; Martins, Isabela Mateus; Nakajima, Vânia Mayumi; Allwood, J William; Stewart, Derek; McDougall, Gordon J

2016-09-14

The aim of this work was to assess the effect of immobilized-tannase treatment on black, green, white and mate tea components and on their bioactivities relevant to obesity. Tannase treatment caused predictable changes in polyphenol composition with substantial reduction in galloylated catechins in green, white and black tea. Mate tea, which is rich in chlorogenic acids, was much less affected by tannase treatment although some degradation of caffeoyl quinic acid derivatives was noted. The original tea samples were effective in inhibiting digestive enzymes in vitro. They inhibited amylase activity, some with IC50 values ∼70 μg mL(-1), but were much less effective against α-glucosidase. They also inhibited lipase activity in vitro and caused dose-dependent reductions in lipid accumulation in cultured adipocytes. The bio-transformed tea samples generally matched the effectiveness of the original samples but in some cases they were markedly improved. In particular, tannase treatment reduced the IC50 value for amylase inhibition for green tea and white tea by 15- and 6-fold respectively. In addition, the bio-transformed samples were more effective than the original samples in preventing lipid accumulation in adipocytes. These in vitro studies indicate that bio-transformed tea polyphenols could assist in the management of obesity through improvement in energy uptake and lipid metabolism and also indicate that biotechnological modification of natural food molecules can improve the benefits of a common beverage such as tea.

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.

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.

Risk factors for progressive axonal degeneration of the retinal nerve fibre layer in multiple sclerosis patients.

PubMed

Garcia-Martin, Elena; Pueyo, Victoria; Almarcegui, Carmen; Martin, Jesus; Ara, Jose R; Sancho, Eva; Pablo, Luis E; Dolz, Isabel; Fernandez, Javier

2011-11-01

To quantify structural and functional degeneration in the retinal nerve fibre layer (RNFL) of patients with multiple sclerosis (MS) over a 2-year time period, and to analyse the effect of prior optic neuritis (ON) as well as the duration and incidence of MS relapses. 166 MS patients and 120 healthy controls underwent assessment of visual acuity and colour vision, visual field examination, optical coherence tomography, scanning laser polarimetry and visual evoked potentials (VEPs). All subjects were re-evaluated after a period of 12 and 24 months. Changes in the optic nerve were detected by structural measurements but not by functional assessments. Changes registered in MS patients were greater than changes in healthy controls (p<0.05). Eyes with previous ON showed a greater reduction of parameters in the baseline evaluation, but RNFL atrophy was not significantly greater in the longitudinal study. Patients with MS relapses showed a greater reduction of RNFL thickness and VEP amplitude compared with non-relapsing cases. Patients with and without treatment showed similar measurement reduction, but the non-treated group had a significantly higher increase in Expanded Disability Status Scale (p=0.029). MS causes progressive axonal loss in the optic nerve, regardless of a history of ON. This ganglion cell atrophy occurs in all eyes but is more marked in MS eyes than in healthy eyes.

Inhibition of Fusarium Growth and Mycotoxin Production in Culture Medium and in Maize Kernels by Natural Phenolic Acids.

PubMed

Ferruz, Elena; Loran, Susana; Herrera, Marta; Gimenez, Isabel; Bervis, Noemi; Barcena, Carmen; Carramiñana, Juan Jose; Juan, Teresa; Herrera, Antonio; Ariño, Agustin

2016-10-01

The possible role of natural phenolic compounds in inhibiting fungal growth and toxin production has been of recent interest as an alternative strategy to the use of chemical fungicides for the maintenance of food safety. Fusarium is a worldwide fungal genus mainly associated with cereal crops. The most important Fusarium mycotoxins are trichothecenes, zearalenone, and fumonisins. This study was conducted to evaluate the potential of four natural phenolic acids (caffeic, ferulic, p-coumaric, and chlorogenic) for the control of mycelial growth and mycotoxin production by six toxigenic species of Fusarium . The addition of phenolic acids to corn meal agar had a marked inhibitory effect on the radial growth of all Fusarium species at levels of 2.5 to 10 mM in a dose-response pattern, causing total inhibition (100%) in all species except F. sporotrichioides and F. langsethiae . However, the effects of phenolic acids on mycotoxin production in maize kernels were less evident than the effects on growth. The fungal species differed in their responses to the phenolic acid treatments, and significant reductions in toxin concentrations were observed only for T-2 and HT-2 (90% reduction) and zearalenone (48 to 77% reduction). These results provide data that could be used for developing pre- and postharvest strategies for controlling Fusarium infection and subsequent toxin production in cereal grains.

Plasma cholesterol homeostasis, HDL remodeling and function during the acute phase reaction.

PubMed

Zimetti, Francesca; De Vuono, Stefano; Gomaraschi, Monica; Adorni, Maria Pia; Favari, Elda; Ronda, Nicoletta; Ricci, Maria Anastasia; Veglia, Fabrizio; Calabresi, Laura; Lupattelli, Graziana

2017-10-01

Acute phase reaction (APR) is a systemic inflammation triggered by several conditions associated with lipid profile alterations. We evaluated whether APR also associates with changes in cholesterol synthesis and absorption, HDL structure, composition, and cholesterol efflux capacity (CEC). We analyzed 59 subjects with APR related to infections, oncologic causes, or autoimmune diseases and 39 controls. We detected no difference in markers of cholesterol synthesis and absorption. Conversely, a significant reduction of LpA-I- and LpAI:AII-containing HDL (-28% and -44.8%, respectively) and of medium-sized HDL (-10.5%) occurred in APR. Total HDL CEC was impaired in APR subjects (-18%). Evaluating specific CEC pathways, we found significant reductions in CEC by aqueous diffusion and by the transporters scavenger receptor B-I and ABCG1 (-25.5, -41.1 and -30.4%, respectively). ABCA1-mediated CEC was not affected. Analyses adjusted for age and gender provided similar results. In addition, correcting for HDL-cholesterol (HDL-C) levels, the differences in aqueous diffusion total and ABCG1-CEC remained significant. APR subjects displayed higher levels of HDL serum amyloid A (+20-folds; P = 0.003). In conclusion, APR does not associate with cholesterol synthesis and absorption changes but with alterations of HDL composition and a marked impairment of HDL CEC, partly independent of HDL-C serum level reduction. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Suckling induced insulin-like growth factor-1 (IGF-1) release in mother rats.

PubMed

Lékó, András H; Cservenák, Melinda; Dobolyi, Árpád

2017-12-01

Lactation involves significant neuroendocrine changes. The elevated prolactin (PRL) release from the pituitary, induced markedly by suckling, is the most relevant example. Suckling also causes a significant and rapid elevation in growth hormone (GH) levels. GH is necessary for milk synthesis as milk yield is stopped completely in the absence of PRL and GH, while the absence of PRL alone causes only a 50% reduction. Insulin-like growth factor-1 (IGF-1) plays an important role in the GH axis. GH exerts its effects through IGF-1 in the periphery, for example in the mammary gland. In addition, IGF-1 is responsible for the long-loop feedback control of GH secretion. IGF-1 secretion has not been established yet in mothers. Therefore, in the present study, we investigated the effect of suckling on serum IGF-1 level in rat mothers and correlated it with serum PRL levels. We examined a potential mechanism of the regulation of IGF-1 level during suckling by administering IGF-1 into the lateral ventricle of rat mothers continuously for 12days, or acutely, right before the start of suckling. We described that suckling affected IGF-1 release based on one-way repeated measures ANOVA (F=10.8 and p<0.001) and caused a marked increase of IGF-1 level 30min after the start of suckling (p<0.001). We demonstrated a significant (p<0.05; the correlation coefficient was 0.29) correlation to PRL level during suckling which supports that PRL could induce IGF-1 release. The prolonged central IGF-1 administration diminished the suckling-induced IGF-1 surge (F=9.19 and p<0.001) while the acute treatment did not have any effect compared to artificial cerebrospinal fluid injection, analysed with two-way repeated measures ANOVA. In conclusion, suckling induces IGF-1 release either by elevating PRL or GH. Long-loop feedback via IGF-1 in the GH axis can diminish this action. Copyright © 2017 Elsevier Ltd. All rights reserved.

Uganda: The Challenge of Growth and Poverty Reduction. A World Bank Country Study.

ERIC Educational Resources Information Center

World Bank, Washington, DC.

This report examines the outcomes of economic reform in Uganda and defines issues that Uganda must address in medium- and long-term strategies for poverty reduction. With a per capita income of approximately $220, Uganda is one of the poorest countries in the world. Its economy and social indicators bear the marks of nearly 15 years of political…

Ultrafast lasers for precise and corrosion free marking on chirurgical steels

NASA Astrophysics Data System (ADS)

Neugebauer, Christoph; Aalderink, Dennis; Maurer, Erich; Faisst, Birgit; Budnicki, Aleksander

2017-02-01

The unique properties of ultrashort laser pulses and the decrease of invest pave the way to numerous novel applications. Even in the very price sensitive field of laser marking, ultrashort laser can compete due to a new cost structure and remarkable properties of the marking results. In this study we concentrated on industrial marking of medical equipment by using IR ultrashort lasers and compared the results with common marking laser systems. We demonstrate the benefits of ultrashort lasers marking on chirurgical devices, observing the influence of pulse energy, pulse duration, scanning velocity in respect to the visibility, corrosion resistance and long term durability under clinical conditions. Nowadays many parts and products are marked for the purpose of identification and traceability. One kind of laser marking is the well known annealing of stainless steel by nanosecond marking lasers. When annealing occurs a colored oxide layer grows due to the local heating of the material surface. Compared to the raw material, the annealed marking shows increased corrosion sensitivity. Regarding the traceability, the poor durability of the ns marking resulting in contrast reduction and the corrosion susceptibility are a huge problem. Therefore three different laser sources with ns-psfs pulse duration were observed. The focus rests on the realization of parameter studies (various lasers) and their effect on the corrosion and passivation behavior. Furthermore analysis of the oxide layers by use of EDX and XRD were performed to obtain further information on the composition and structure of the markings.

[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.

Reduction in dynamin-2 is implicated in ischaemic cardiac arrhythmias

PubMed Central

Shi, Dan; Xie, Duanyang; Zhang, Hong; Zhao, Hong; Huang, Jian; Li, Changming; Liu, Yi; Lv, Fei; The, Erlinda; Liu, Yuan; Yuan, Tianyou; Wang, Shiyi; Chen, Jinjin; Pan, Lei; Yu, Zuoren; Liang, Dandan; Zhu, Weidong; Zhang, Yuzhen; Li, Li; Peng, Luying; Li, Jun; Chen, Yi-Han

2014-01-01

Ischaemic cardiac arrhythmias cause a large proportion of sudden cardiac deaths worldwide. The ischaemic arrhythmogenesis is primarily because of the dysfunction and adverse remodelling of sarcolemma ion channels. However, the potential regulators of sarcolemma ion channel turnover and function in ischaemic cardiac arrhythmias remains unknown. Our previous studies indicate that dynamin-2 (DNM2), a cardiac membrane-remodelling GTPase, modulates ion channels membrane trafficking in the cardiomyocytes. Here, we have found that DNM2 plays an important role in acute ischaemic arrhythmias. In rat ventricular tissues and primary cardiomyocytes subjected to acute ischaemic stress, the DNM2 protein and transcription levels were markedly down-regulated. This DNM2 reduction was coupled with severe ventricular arrhythmias. Moreover, we identified that the down-regulation of DNM2 within cardiomyocytes increases the action potential amplitude and prolongs the re-polarization duration by depressing the retrograde trafficking of Nav1.5 and Kir2.1 channels. These effects are likely to account for the DNM2 defect-induced arrhythmogenic potentials. These results suggest that DNM2, with its multi-ion channel targeting properties, could be a promising target for novel antiarrhythmic therapies. PMID:25092467

Creation of a genetic calcium channel blocker by targeted gem gene transfer in the heart.

PubMed

Murata, Mitsushige; Cingolani, Eugenio; McDonald, Amy D; Donahue, J Kevin; Marbán, Eduardo

2004-08-20

Calcium channel blockers are among the most commonly used therapeutic drugs. Nevertheless, the utility of calcium channel blockers for heart disease is limited because of the potent vasodilatory effect that causes hypotension, and other side effects attributable to blockade of noncardiac channels. Therefore, focal calcium channel blockade by gene transfer is highly desirable. With a view to creating a focally applicable genetic calcium channel blocker, we overexpressed the ras-related small G-protein Gem in the heart by somatic gene transfer. Adenovirus-mediated delivery of Gem markedly decreased L-type calcium current density in ventricular myocytes, resulting in the abbreviation of action potential duration. Furthermore, transduction of Gem resulted in a significant shortening of the electrocardiographic QTc interval and reduction of left ventricular systolic function. Focal delivery of Gem to the atrioventricular (AV) node significantly slowed AV nodal conduction (prolongation of PR and AH intervals), which was effective in the reduction of heart rate during atrial fibrillation. Thus, these results indicate that gene transfer of Gem functions as a genetic calcium channel blocker, the local application of which can effectively modulate cardiac electrical and contractile function.

Effects of basic calponin on the flexural mechanics and stability of F-actin.

PubMed

Jensen, Mikkel Herholdt; Watt, James; Hodgkinson, Julie L; Gallant, Cynthia; Appel, Sarah; El-Mezgueldi, Mohammed; Angelini, Thomas E; Morgan, Kathleen G; Lehman, William; Moore, Jeffrey R

2012-01-01

The cellular actin cytoskeleton plays a central role in the ability of cells to properly sense, propagate, and respond to external stresses and other mechanical stimuli. Calponin, an actin-binding protein found both in muscle and non-muscle cells, has been implicated in actin cytoskeletal organization and regulation. In this work, we studied the mechanical and structural interaction of actin with basic calponin, a differentiation marker in smooth muscle cells, on a single filament level. We imaged fluorescently labeled thermally fluctuating actin filaments and found that at moderate calponin binding densities, actin filaments were more flexible, evident as a reduction in persistence length from 8.0 to 5.8 μm. When calponin-decorated actin filaments were subjected to shear, we observed a marked reduction of filament lengths after decoration with calponin, which we argue was due to shear-induced filament rupture rather than depolymerization. This increased shear susceptibility was exacerbated with calponin concentration. Cryo-electron microscopy results confirmed previously published negative stain electron microscopy results and suggested alterations in actin involving actin subdomain 2. A weakening of F-actin intermolecular association is discussed as the underlying cause of the observed mechanical perturbations. Copyright © 2011 Wiley Periodicals, Inc.

Impact of acid mine drainage on haematological, histopathological and genotoxic effects in golden mahaseer, Tor putitora.

PubMed

Shahi, Neetu; Sarma, Debaji; Pandey, Jyoti; Das, Partha; Sarma, Dandadhar; Mallik, Sumanta Kumar

2016-07-01

The present study was carried out to evaluate sub-lethal mechanism of acid mine drainage toxicity in fingerlings (9.5 ± 2.4 cm) of golden mahseer, Tor putitora. Exposed fingerlings showed significant reduction (P < 0.01) in blood erythrocytes, neutrophils, thrombocytes, lymphocytes and leukocytes in contrast to increase in number of immature circulating cells. Hyperplasia, degeneration of glomeruli, presence of inflammatory cells and increased number of melanomacrophage aggregates, vacuolization of cell cytoplasm, hepatocyte swelling were marked in kidney and liver of fish. Ladder in, an increment of 180-200 bp of hepatic and kidney DNA, by electrophoresis were consistent with DNA damage. 10 day exposure to acid mine drainage resulted in reduction of double stranded DNA to 46.0 and 48.0 in hepatocytes and kidney cells respectively. Significant increase (P < 0.01) in tail length and percent tail DNA was evident by comet assay. The results suggest that exposure to acid mine drainage might cause irreversible damage to immune cells, tissue and DNA of fish, and this model of DNA damage may contribute in identifying novel molecular mechanism of interest for bioremediation application.

Pathobiology and management of hypergastrinemia and the Zollinger-Ellison syndrome.

PubMed

Hirschowitz, B I

1992-01-01

Gastrin is both stimulatory and trophic to the cells of the gastric fundus--parietal and peptic cells, and enterochromaffin-like (ECL) cells which are major intermediaries of the gastrin effect. Gastrin (from the antrum) and acid (from the fundus) represent the interactive positive and negative limbs of a feedback loop. The nature and extent of sub-loops, perhaps involving the vagus, acetylcholine, histamine, and other peptides and cell products are at present unclear or unknown. Loss of either gastrin or acid has predictable consequences. Absent acid, as in pernicious anemia or as a result of omeprazole, leads to hypergastrinemia. In rats, such hypergastrinemia (gastrin > 1,000 pg/ml) causes fundic ECL hyperplasia and, eventually, carcinoids; in humans with pernicious anemia, hypergastrinemia causes ECL-cell hyperplasia, which may progress to carcinoids that are reversible upon withdrawal of gastrin, illustrated by three cases described here. Loss of gastrin by antrectomy for duodenal ulcer leads to fundic involution and marked reduction in basal acid output, maximal acid output, and fundic histamine. An uncontrolled excess of gastrin, as from a gastrinoma outside the negative feedback loop, causes acid and pepsin hypersecretion with upper GI mucosal damage, the Zollinger-Ellison syndrome. This paper summarizes the abnormal regulation of gastrin and the biology, natural history, diagnosis, and management of ZE syndrome by medical and surgical means.

Mucopolysaccharidosis VI in cats - clarification regarding genetic testing.

PubMed

Lyons, Leslie A; Grahn, Robert A; Genova, Francesca; Beccaglia, Michela; Hopwood, John J; Longeri, Maria

2016-07-02

The release of new DNA-based diagnostic tools has increased tremendously in companion animals. Over 70 different DNA variants are now known for the cat, including DNA variants in disease-associated genes and genes causing aesthetically interesting traits. The impact genetic tests have on animal breeding and health management is significant because of the ability to control the breeding of domestic cats, especially breed cats. If used properly, genetic testing can prevent the production of diseased animals, causing the reduction of the frequency of the causal variant in the population, and, potentially, the eventual eradication of the disease. However, testing of some identified DNA variants may be unwarranted and cause undo strife within the cat breeding community and unnecessary reduction of gene pools and availability of breeding animals. Testing for mucopolysaccharidosis Type VI (MPS VI) in cats, specifically the genetic testing of the L476P (c.1427T>C) and the D520N (c.1558G>A) variants in arylsulfatase B (ARSB), has come under scrutiny. No health problems are associated with the D520N (c.1558G>A) variant, however, breeders that obtain positive results for this variant are speculating as to possible correlation with health concerns. Birman cats already have a markedly reduced gene pool and have a high frequency of the MPS VI D520N variant. Further reduction of the gene pool by eliminating cats that are heterozygous or homozygous for only the MPS VI D520N variant could lead to more inbreeding depression effects on the breed population. Herein is debated the genetic testing of the MPS VI D520N variant in cats. Surveys from different laboratories suggest the L476P (c.1427T>C) disease-associated variant should be monitored in the cat breed populations, particularly breeds with Siamese derivations and outcrosses. However, the D520N has no evidence of association with disease in cats and testing is not recommended in the absence of L476P genotyping. Selection against the D520N is not warranted in cat populations. More rigorous guidelines may be required to support the genetic testing of DNA variants in all animal species.

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

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.

IL-17A promotes protective IgA responses and expression of other potential effectors against the lumen-dwelling enteric parasite Giardia.

PubMed

Dann, Sara M; Manthey, Carolin F; Le, Christine; Miyamoto, Yukiko; Gima, Lauren; Abrahim, Andrew; Cao, Anthony T; Hanson, Elaine M; Kolls, Jay K; Raz, Eyal; Cong, Yingzi; Eckmann, Lars

2015-09-01

Giardia lamblia is a leading protozoan cause of diarrheal disease worldwide. It colonizes the lumen and epithelial surface of the small intestine, but does not invade the mucosa. Acute infection causes only minimal mucosal inflammation. Effective immune defenses exist, yet their identity and mechanisms remain incompletely understood. Interleukin (IL)-17A has emerged as an important cytokine involved in inflammation and antimicrobial defense against bacterial pathogens at mucosal surfaces. In this study, we demonstrate that IL-17A has a crucial function in host defense against Giardia infection. Using murine infection models with G. muris and G. lamblia, we observed marked and selective induction of intestinal IL-17A with peak expression after 2 weeks. Th17 cells in the lamina propria and innate immune cells in the epithelial compartment of the small intestine were responsible for the IL-17A response. Experiments in gene-targeted mice revealed that the cytokine, and its cognate receptor IL-17RA, were required for eradication of the parasite. The actions of the cytokine were mediated by hematopoietic cells, and were required for the transport of IgA into the intestinal lumen, since IL-17A deficiency led to marked reduction of fecal IgA levels, as well as for increased intestinal expression of several other potential effectors, including β-defensin 1 and resistin-like molecule β. In contrast, intestinal hypermotility, another major antigiardial defense mechanism, was not impacted by IL-17A loss. Taken together, these findings demonstrate that IL-17A and IL-17 receptor signaling are essential for intestinal defense against the important lumen-dwelling intestinal parasite Giardia. Copyright © 2015 Elsevier Inc. All rights reserved.

Elucidating the impact of the pneumococcal conjugate vaccine programme on pneumonia, sepsis and otitis media hospital admissions in England using a composite control.

PubMed

Thorrington, Dominic; Andrews, Nick; Stowe, Julia; Miller, Elizabeth; van Hoek, Albert Jan

2018-02-08

The seven-valent pneumococcal conjugate vaccine (PCV) was introduced in England in September 2006, changing to the 13-valent vaccine in April 2010. PCV impact on invasive pneumococcal disease (IPD) has been extensively reported, but less described is its impact on the burden of pneumonia, sepsis and otitis media in the hospital. Using details on all admissions to hospitals in England, we compared the incidence of pneumococcal-specific and syndromic disease endpoints in a 24-month pre-PCV period beginning April 2004 to the 24-month period ending March 2015 to derive incidence rate ratios (IRRs). To adjust for possible secular trends in admission practice, IRRs were compared to the IRRs for five control conditions over the same period and the relative change assessed using the geometric mean of the five control IRRs as a composite, and individually for each control condition to give the min-max range. Relative changes were also compared with IRRs for IPD from the national laboratory database. The effect of stratifying cases into those with and without clinical risk factors for pneumococcal infection was explored. Relative reductions in pneumococcal pneumonia were seen in all age groups and in those with and without risk factors; in children under 15 years old reductions were similar in magnitude to reductions in IPD. For pneumonia of unspecified cause, relative reductions were seen in those under 15 years old (maximum reduction in children under 2 years of 34%, min-max: 11-49%) with a relative increase in 65+ year olds most marked in those with underlying risk conditions (41%, min-max: 0-82%). Reductions in pneumococcal sepsis were seen in all age groups, with the largest reduction in children younger than 2 years (67%, min-max 56-75%). Reductions in empyema and lung abscess were also seen in under 15 year olds. Results for other disease endpoints were varied. For disease endpoints showing an increase in raw IRR, the increase was generally reduced when expressed as a relative change. Use of a composite control and stratification by risk group status can help elucidate the impact of PCV on non-IPD disease endpoints and in vulnerable population groups. We estimate a substantial reduction in the hospitalised burden of pneumococcal pneumonia in all age groups and pneumonia of unspecified cause, empyema and lung abscess in children under 15 years of age since PCV introduction. The increase in unspecified pneumonia in high-risk 65+ year olds may in part reflect their greater susceptibility to develop pneumonia from less pathogenic serotypes that are replacing vaccine types in the nasopharynx.

Differential Isotopic Fractionation during Cr(VI) Reduction by an Aquifer-Derived Bacterium under Aerobic versus Denitrifying Conditions

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

Han, R.; Qin, L.; Brown, S. T.

2012-01-27

We studied Cr isotopic fractionation during Cr(VI) reduction by Pseudomonas stutzeri strain RCH2. Finally, despite the fact that strain RCH2 reduces Cr(VI) cometabolically under both aerobic and denitrifying conditions and at similar specific rates, fractionation was markedly different under these two conditions (ε was ~2‰ aerobically and ~0.4‰ under denitrifying conditions).

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...

Histone 3 lysine 9 acetylation is a biomarker of the effects of culture on zygotes

PubMed Central

Rollo, C; Li, Y; Jin, X L

2017-01-01

Acetylation of histone proteins is a major determinant of chromatin structure and function. Fertilisation triggers a round of chromatin remodelling that prepares the genome for the first round of transcription from the new embryonic genome. In this study we confirm that fertilisation leads to a marked progressive increase in the level of histone 3 lysine 9 acetylation in both the paternally and maternally derived genomes. The culture of zygotes in simple defined media caused a marked increase in the global level of acetylation and this affected the male pronucleus more than the female. The culture created a marked asymmetry in staining between the two pronuclei that was not readily detected in zygotes collected directly from the reproductive tract and was ameliorated to some extent by optimized culture media. The increased acetylation caused by culture resulted in increased transcription of Hspa1b, a marker of embryonic genome activation. Pharmacological analyses showed the hyperacetylation of H3K9 and the increased expression of Hspa1b caused by culture were due to the altered net activity of a range of histone acetylases and deacetylases. The marked hyperacetylation of histone 3 lysine 9 caused by culture of zygotes may serve as an early biomarker for the effects of culture on the normal function of the embryo. The results also provide further evidence for an effect of the stresses associated with assisted reproductive technologies on the normal patterns of epigenetic reprogramming in the early embryo. PMID:28878090

Effects of Induction-System Icing on Aircraft-Engine Operating Characteristics

NASA Technical Reports Server (NTRS)

Stevens, Howard C., Jr.

1947-01-01

An investigation was conducted on a multicylinder aircraft engine on a dynamometer stand to determine the effect of induction-system icing on engine operating characteristics and to compare the results with those of a previous laboratory investigation in which only the carburetor and the engine-stage supercharger assembly from the engine were used. The experiments were conducted at simulated glide power, low cruise power, and normal rated power through a range of humidity ratios and air temperatures at approximately sea-level pressure. Induction-system icing was found to occur within approximately the same limits as those established by the previous laboratory investigation after making suitable allowances for the difference in fuel volatility and throttle angles. Rough operation of the engine was experienced when ice caused a marked reduction in the air flow. Photographs of typical ice formations from this investigation indicate close similarity to icing previously observed in the laboratory.

Acute Myocardial Infarction in Women: A Scientific Statement From the American Heart Association.

PubMed

Mehta, Laxmi S; Beckie, Theresa M; DeVon, Holli A; Grines, Cindy L; Krumholz, Harlan M; Johnson, Michelle N; Lindley, Kathryn J; Vaccarino, Viola; Wang, Tracy Y; Watson, Karol E; Wenger, Nanette K

2016-03-01

Cardiovascular disease is the leading cause of mortality in American women. Since 1984, the annual cardiovascular disease mortality rate has remained greater for women than men; however, over the last decade, there have been marked reductions in cardiovascular disease mortality in women. The dramatic decline in mortality rates for women is attributed partly to an increase in awareness, a greater focus on women and cardiovascular disease risk, and the increased application of evidence-based treatments for established coronary heart disease. This is the first scientific statement from the American Heart Association on acute myocardial infarction in women. Sex-specific differences exist in the presentation, pathophysiological mechanisms, and outcomes in patients with acute myocardial infarction. This statement provides a comprehensive review of the current evidence of the clinical presentation, pathophysiology, treatment, and outcomes of women with acute myocardial infarction. © 2016 American Heart Association, Inc.

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.

Humans have already increased the risk of major disruptions to Pacific rainfall

NASA Astrophysics Data System (ADS)

Power, Scott B.; Delage, François P. D.; Chung, Christine T. Y.; Ye, Hua; Murphy, Bradley F.

2017-02-01

Intermittent disruptions to rainfall patterns and intensity over the Pacific Ocean lasting up to ~ 1 year have major impacts on severe weather, agricultural production, ecosystems, and disease within 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 humans may have contributed to the major disruption that occurred in the real world during the late 20th century. We demonstrate 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.

Humans have already increased the risk of major disruptions to Pacific rainfall

PubMed Central

Power, Scott B.; Delage, François P. D.; Chung, Christine T. Y.; Ye, Hua; Murphy, Bradley F.

2017-01-01

Intermittent disruptions to rainfall patterns and intensity over the Pacific Ocean lasting up to ∼ 1 year have major impacts on severe weather, agricultural production, ecosystems, and disease within 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 humans may have contributed to the major disruption that occurred in the real world during the late 20th century. We demonstrate 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. PMID:28176783

Rifaximin, gut microbes and mucosal inflammation: unraveling a complex relationship.

PubMed

Gao, Jun; Gillilland, Merritt G; Owyang, Chung

2014-07-01

Rifaximin is a non-systemic, broad-spectrum antibiotic that acts against gram-positive, gram-negative, and anaerobic bacteria. Clinical studies indicate that rifaximin is beneficial in treating irritable bowel syndrome (IBS). The mechanism responsible for the beneficial effects of rifaximin is not clear. In a recent study, we reported that rifaximin alters the bacterial population in the ileum of rats, leading to a relative abundance of Lactobacillus species. These changes prevent gut inflammation and visceral hyperalgesia caused by chronic stress. To more closely mirror human clinical studies in which rifaximin is used to treat IBS symptoms, we performed additional studies and showed that rifaximin reversed mucosal inflammation and barrier dysfunction evoked by chronic stress. These beneficial effects were accompanied by a striking increase in the abundance of Lactobacillaceae and a marked reduction in the number of segmented filamentous bacteria after rifaximin treatment. These microbial changes may contribute to the antiinflammatory effects of rifaximin on the intestinal mucosa.

Apoptosis of rat renal cells by organophosphate pesticide, quinalphos: Ultrastructural study.

PubMed

Eid, Refaat A

2017-01-01

Quinalphos or Ekalux, an organophosphate pesticide, is used in controlling the pests of a variety of crops. Quinalphos was studied on male Sprague-Dawley albino rats. The acute po LD50 of technical Ekalux was 19.95 mg/kg in males. Ekalux, produced several pathological changes in the kidney. A glomerulus demonstrated capillary lumina occluded by degenerated cellular debris. Basement membrane showed irregular wrinkling and branching. The proximal tubular cells showed damage such as dilation of endoplasmic reticulum, accumulation of glycogen granules, and pyknotic nucleus. The changes also included swelling of the mitochondria and reduction of the cristae up to total destruction. The distal tubular changes included electron lucency and vacuolation of cytoplasm. The distal convoluted tubule wall showed edematous epithelial cells, formation of blebs, and microvilli loss. These results suggest that subchronic exposure of rats to Ekalux causes ultrastructural changes in renal corpuscle and marked ultrastructural changes in proximal and distal tubules.

Chemical Burns of the Eye: The Role of Retinal Injury and New Therapeutic Possibilities.

PubMed

Dohlman, Claes H; Cade, Fabiano; Regatieri, Caio V; Zhou, Chengxin; Lei, Fengyang; Crnej, Alja; Harissi-Dagher, Mona; Robert, Marie-Claude; Papaliodis, George N; Chen, Dongfeng; Aquavella, James V; Akpek, Esen K; Aldave, Anthony J; Sippel, Kimberly C; DʼAmico, Donald J; Dohlman, Jan G; Fagerholm, Per; Wang, Liqiang; Shen, Lucy Q; González-Andrades, Miguel; Chodosh, James; Kenyon, Kenneth R; Foster, C Stephen; Pineda, Roberto; Melki, Samir; Colby, Kathryn A; Ciolino, Joseph B; Vavvas, Demetrios G; Kinoshita, Shigeru; Dana, Reza; Paschalis, Eleftherios I

2018-02-01

To propose a new treatment paradigm for chemical burns to the eye - in the acute and chronic phases. Recent laboratory and clinical data on the biology and treatment of chemical burns are analyzed. Corneal blindness from chemical burns can now be successfully treated with a keratoprosthesis, on immediate and intermediate bases. Long term outcomes, however, are hampered by early retinal damage causing glaucoma. New data suggest that rapid diffusion of inflammatory cytokines posteriorly (TNF-α, etc) can severely damage the ganglion cells. Prompt anti-TNF-α treatment is markedly neuroprotective. Long term profound reduction of the intraocular pressure is also vital. A new regimen, in addition to standard treatment, for severe chemical burns is proposed. This involves tumor necrosis factor alpha (TNF-α) inhibition promptly after the accident (primarily for retinal neuroprotection), prophylactic maximal lowering of the intraocular pressure (starting immediately), and keratoprosthesis implantation in a later quiet state.

Sequential biodegradation of TNT, RDX and HMX in a mixture.

PubMed

Sagi-Ben Moshe, S; Ronen, Z; Dahan, O; Weisbrod, N; Groisman, L; Adar, E; Nativ, R

2009-01-01

We describe TNT's inhibition of RDX and HMX anaerobic degradation in contaminated soil containing indigenous microbial populations. Biodegradation of RDX or HMX alone was markedly faster than their degradation in a mixture with TNT, implying biodegradation inhibition by the latter. The delay caused by the presence of TNT continued even after its disappearance and was linked to the presence of its intermediate, tetranitroazoxytoluene. PCR-DGGE analysis of cultures derived from the soil indicated a clear reduction in microbial biomass and diversity with increasing TNT concentration. At high-TNT concentrations (30 and 90 mg/L), only a single band, related to Clostridium nitrophenolicum, was observed after 3 days of incubation. We propose that the mechanism of TNT inhibition involves a cytotoxic effect on the RDX- and HMX-degrading microbial population. TNT inhibition in the top active soil can therefore initiate rapid transport of RDX and HMX to the less active subsurface and groundwater.

Modulation by acetylcholine of the electrically-evoked release of [3H]-acetylcholine from the ileum of the guinea-pig.

PubMed Central

Fosbraey, P.; Johnson, E. S.

1980-01-01

1 Acetylcholine (ACh) stores within neurones of the myenteric plexus of the guinea-pig were labelled with [3H]-choline and the influence of unlabelled ACh, atropine, or atropine and unlabelled ACh on the electrically-evoked output of [3H]-ACh was evaluated. 2 Electrical transmural stimulation (5 Hz) of the ileum led to an increase in the output of [3H]-ACh over that released spontaneously. Superfusion with unlabelled ACh (6.8 microM) caused a marked reduction in the release of [3H]-ACh which was reversed by atropine (3.5 microM). Atropine itself had no effect on the electrically-evoked [3H]-ACh. 3 These experiments provide further evidence for the existence in the guinea-pig ileum of neuronal muscarinic receptors for ACh subserving an inhibitory role on transmitter release. PMID:7378653

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

The effects of endothelin-1 on the cardiorespiratory physiology of the freshwater trout (Oncorhynchus mykiss) and the marine dogfish (Squalus acanthias).

PubMed

Perry, S F; Montpetit, C J; McKendry, J; Desforges, P R; Gilmour, K M; Wood, C M; Olson, K R

2001-11-01

The aim of the present study was to evaluate the effects of endothelin-l-elicited cardiovascular events on respiratory gas transfer in the freshwater rainbow trout (Oncorhynchus mykiss) and the marine dogfish (Squalus acanthias). In both species, endothelin-1 (666 pmol kg(-1)) caused a rapid (within 4 min) reduction (ca. 30-50 mmHg) in arterial blood partial pressure of O2. The effects of endothelin-1 on arterial blood partial pressure of CO2 were not synchronised with the changes in O2 partial pressure and the responses were markedly different in trout and dogfish. In trout, arterial CO2 partial pressure was increased transiently by approximately 1.0 mmHg but the onset of the response was delayed and occurred 12 min after endothelin-1 injection. In contrast, CO2 partial pressure remained more-or-less constant in dogfish after injection of endothelin-1 and was increased only slightly (approximately 0.1 mmHg) after 60 min. Pre-treatment of trout with bovine carbonic anhydrase (5 mg ml(-1)) eliminated the increase in CO2 partial pressure that was normally observed after endothelin-1 injection. In both species, endothelin-1 injection caused a decrease in arterial blood pH that mirrored the changes in CO2 partial pressure. Endothelin-1 injection was associated with transient (trout) or persistent (dogfish) hyperventilation as indicated by pronounced increases in breathing frequency and amplitude. In trout, arterial blood pressure remained constant or was decreased slightly and was accompanied by a transient increase in systemic resistance, and a temporary reduction in cardiac output. The decrease in cardiac output was caused solely by a reduction in cardiac frequency; cardiac stroke volume was unaffected. In dogfish, arterial blood pressure was lowered by approximately 10 mmHg at 6-10 min after endothelin-1 injection but then was rapidly restored to pre-injection levels. The decrease in arterial blood pressure reflected an increase in branchial vascular resistance (as determined using in situ perfused gill preparations) that was accompanied by simultaneous decreases in systemic resistance and cardiac output. Cardiac frequency and stroke volume were reduced by endothelin-1 injection and thus both variables contributed to the changes in cardiac output. We conclude that the net consequences of endothelin-1 on arterial blood gases result from the opposing effects of reduced gill functional surface area (caused by vasoconstriction) and an increase in blood residence time within the gill (caused by decreased cardiac output.

PAPAIN-INDUCED CHANGES IN RABBIT CARTILAGE

PubMed Central

Tsaltas, Theodore T.

1958-01-01

Some biochemical aspects of the collapse of the rabbit ears produced by the intravenous injection of papain have been studied. A marked depletion of chondromucoprotein (M.C.S.) and a reduction of the S35 content of cartilage matrix were found to coincide with the gross and histologic changes in the cartilage. At the same time there was a marked increase in the amount of S35 in the serum and an increase of S35 and glucuronic acid excreted in the urine. Alteration in the composition of the M.C.S. remaining in the cartilage of the papain-injected animals was detected. The findings indicate that the collapse of the rabbit ears is due to loss of chondromucoprotein from cartilage and reduction of chondroitin sulfate in the chondromucoprotein that remains. All these changes were reversed in recovery. PMID:13575681

Multi-organ sarcoidosis treatment with fumaric acid esters: a case report and review of the literature.

PubMed

Zouboulis, Christos C; Lippert, Undine; Karagiannidis, Ioannis

2014-01-01

Sarcoidosis is a rare, systemic disease that is characterized by the formation of granulomas in various organs, including the skin. As the etiology remains unknown, the treatment of sarcoidosis is challenging. We present a 47-year-old female patient with progressive, multi-organ sarcoidosis who had a complete clinical improvement of the skin lesions, a moderate reduction in pulmonary opacities on chest X-ray, a marked subjective improvement in general status and pulmonary efficiency and a marked reduction in serum angiotensin-converting enzyme and soluble interleukin-2 receptor after 6 months of therapy with fumaric acid esters. The present case and similar reports in the literature highlight the probable efficacy of fumaric acid esters in the treatment of sarcoidosis and other non-infectious, granulomatous diseases. © 2014 S. Karger AG, Basel.

[Polyethylene abrasion: cause or consequence of an endoprosthesis loosening? Investigations of firm and loosened hip implants].

PubMed

Busse, B; Niecke, M; Püschel, K; Delling, G; Katzer, A; Hahn, M

2007-01-01

Periprosthetic tissue was analysed by the combination of different investigation techniques without destruction. The localisation and geometry of polyethylene abrasion particles were determined quantitatively to differentiate between abrasion due to function and abrasion due to implant loosening. Non-polyethylene particles from implant components which contaminate the tissue were micro-analytically measured. The results will help us to understand loosening mechanisms and thus lead to implant optimisations. A non-destructive particle analysis using highly sensitive proton-induced X-ray emission (PIXE) was developed to achieve a better histological allocation. Five autopsy cases with firmly fitting hip endoprosthesis (2 x Endo-Modell Mark III, 1 x St. Georg Mark II, LINK, Germany; 2 x Spongiosa Metal II, ESKA, Germany) were prepared as ground tissue specimens. Wear investigations were accomplished with a combined application of different microscopic techniques and microanalysis. The abrasion due to implant loosening was histologically evaluated on 293 loosened cup implants (St. Georg Mark II, LINK, Germany). Wear particles are heterogeneously distributed in the soft tissue. In cases of cemented prostheses, cement particles are dominating whereas metal particles could rarely be detected. The concentration of the alloy constituent cobalt (Co) is increased in the mineralised bone tissue. The measured co-depositions depend on the localisation and/or lifetime of an implant. Functional polyethylene (PE) abrasion needs to be differentiated from PE abrasion of another genesis (loosening, impingement) morphologically and by different tissue reactions. In the past a reduction of abrasion was targeted primarily by the optimisation of the bearing surfaces and tribology. The interpretation of our findings indicates that different mechanisms of origin in terms of tissue contamination with wear debris and the alloy should be included in the improvement of implants or implantation techniques.

Improvement in racial disparities in years of life lost in the USA since 1990.

PubMed

Buchanich, Jeanine M; Doerfler, Shannon M; Lann, Michael F; Marsh, Gary M; Burke, Donald S

2018-01-01

To examine changes in cause-specific Years of Life Lost (YLL) by age, race, and sex group in the USA from 1990 to 2014. 60 million death reports from the National Center for Health Statistics (NCHS) were categorized by age group, sex, race, and cause of death. YLL were calculated using age-specific life expectancies. Age groups were: infants <1, children 1-19, adults 20-64, and older adults 65+. Blacks have historically experienced more years of life lost than whites or other racial groups in the USA. In the year 1990 the YLL per 100,000 population was 21,103 for blacks, 14,160 for whites, and 7,417 for others. Between 1990 and 2014 overall YLL in the USA improved by 10%, but with marked variations in the rate of change across age, race, and sex groups. Blacks (all ages, both sexes) showed substantial improvement with a 28% reduction in YLL, compared to whites (all ages, both sexes) who showed a 4% reduction. Among blacks, improvements were seen in all age groups: reductions of 43%, 48%, 28%, and 25% among infants, children, adults, and older adults, respectively. Among whites, reductions of 33%, 44%, and 18% were seen in infants, children, and older adults, but there was a 6% increase in YLL among white adults. YLL increased by 18% in white adult females and declined 1% in white adult males. American Indian/Alaska Native women also had worsening in YLL, with an 8% increase. Asian Pacific Islanders consistently had the lowest YLL across all ages. Whites had a higher proportion of YLL due to overdose; blacks had a higher proportion due to homicide at younger ages and to heart disease at older ages. Race-based disparities in YLL in the USA since 1990 have narrowed considerably, largely as a result of improvements among blacks compared to whites. Adult white and American Indian / Alaskan Native females have experienced worsening YLL, while white males have experienced essentially no change. If recent trajectories continue, adult black/white disparities in YLL will continue to narrow.

Assessment of sulforaphane-induced protective mechanisms against cadmium toxicity in human mesenchymal stem cells.

PubMed

Alkharashi, Nouf Abdulkareem Omer; Periasamy, Vaiyapuri Subbarayan; Athinarayanan, Jegan; Alshatwi, Ali A

2018-04-01

Cd is a hazardous substance and carcinogen that is present in the environment; it is known to cause toxic effects in living organisms. Sulforaphane is a naturally available phytochemical with antioxidant, anti-inflammatory, and anticarcinogenic properties. However, the effects of sulforaphane on Cd toxicity in human mesenchymal stem cells (hMSCs) are unknown. In the present study, we investigated the molecular mechanisms of the effects of sulforaphane on Cd toxicity in hMSCs by using MTT assays, acridine orange/ethidium bromide staining, Hoechst staining, LysoRed staining, assessment of mitochondrial membrane potential, and gene expression analysis. Cd decreased hMSC viability in a dose-dependent manner with an IC 50 value of 56.5 μM. However, sulforaphane did not induce any significant reduction in cell viability. Nuclear morphological analysis revealed that Cd induced necrotic cell death. Additionally, Cd caused mitochondrial membrane potential loss in hMSCs. The treatment of Cd-exposed cells with sulforaphane (Cd-sulforaphane co-treatment) resulted in a significant recovery of the cell viability and nuclear morphological changes compared with that of cells treated with Cd only. The gene expression pattern of cells co-treated with Cd-sulforaphane was markedly different from that of Cd-treated cells, owing to the reduction in Cd toxicity. Our results clearly indicated that sulforaphane reduced Cd-induced toxic effects in hMSCs. Overall, the results of our study suggested that sulforaphane-rich vegetables and fruits can help to improve human health through amelioration of the molecular effects of Cd poisoning.

Naringenin regulates production of matrix metalloproteinases in the knee-joint and primary cultured articular chondrocytes and alleviates pain in rat osteoarthritis model.

PubMed

Wang, C C; Guo, L; Tian, F D; An, N; Luo, L; Hao, R H; Wang, B; Zhou, Z H

2017-03-23

Inflammation of cartilage is a primary symptom for knee-joint osteoarthritis. Matrix metalloproteinases (MMPs) are known to play an important role in the articular cartilage destruction related to osteoarthritis. Naringenin is a plant-derived flavonoid known for its anti-inflammatory properties. We studied the effect of naringenin on the transcriptional expression, secretion and enzymatic activity of MMP-3 in vivo in the murine monosodium iodoacetate (MIA) osteoarthritis model. The assessment of pain behavior was also performed in the MIA rats. The destruction of knee-joint tissues was analyzed microscopically. Moreover, the effect of naringenin was also studied in vitro in IL-1β activated articular chondrocytes. The transcriptional expression of MMP-3, MMP-1, MMP-13, thrombospondin motifs (ADAMTS-4) and ADAMTS-5 was also studied in primary cultured chondrocytes of rats. Naringenin caused significant reduction in pain behavior and showed marked improvement in the tissue morphology of MIA rats. Moreover, a significant inhibition of MMP-3 expression in MIA rats was observed upon treatment with naringenin. In the in vitro tests, naringenin caused a significant reduction in the transcriptional expression, secretion and enzymatic activity of the studied degradative enzymes. The NF-κB pathway was also found to be inhibited upon treatment with naringenin in vitro. Overall, the study suggests that naringenin alleviated pain and regulated the production of matrix-metalloproteinases via regulation of NF-κB pathway. Thus, naringenin could be a potent therapeutic option for the treatment of osteoarthritis.

Transporter Protein-Coupled DPCPX Nanoconjugates Induce Diaphragmatic Recovery after SCI by Blocking Adenosine A1 Receptors.

PubMed

Minic, Zeljka; Zhang, Yanhua; Mao, Guangzhao; Goshgarian, Harry G

2016-03-23

Respiratory complications in patients with spinal cord injury (SCI) are common and have a negative impact on the quality of patients' lives. Systemic administration of drugs that improve respiratory function often cause deleterious side effects. The present study examines the applicability of a novel nanotechnology-based drug delivery system, which induces recovery of diaphragm function after SCI in the adult rat model. We developed a protein-coupled nanoconjugate to selectively deliver by transsynaptic transport small therapeutic amounts of an A1 adenosine receptor antagonist to the respiratory centers. A single administration of the nanoconjugate restored 75% of the respiratory drive at 0.1% of the systemic therapeutic drug dose. The reduction of the systemic dose may obviate the side effects. The recovery lasted for 4 weeks (the longest period studied). These findings have translational implications for patients with respiratory dysfunction after SCI. The leading causes of death in humans following SCI are respiratory complications secondary to paralysis of respiratory muscles. Systemic administration of methylxantines improves respiratory function but also leads to the development of deleterious side effects due to actions of the drug on nonrespiratory sites. The importance of the present study lies in the novel drug delivery approach that uses nanotechnology to selectively deliver recovery-inducing drugs to the respiratory centers exclusively. This strategy allows for a reduction in the therapeutic drug dose, which may reduce harmful side effects and markedly improve the quality of life for SCI patients. Copyright © 2016 the authors 0270-6474/16/363441-12$15.00/0.

Efficacy of laminar air flow room with or without clean nursing for preventing infection in patients with acute leukemia.

PubMed

Ueda, T; Shibata, H; Nakamura, H; Takubo, T; Kubota, Y; Oguma, S; Tani, Y; Masaoka, T; Nagao, T; Takeo, H; Hasegawa, H; Moriyama, Y

1983-01-01

The clinical effectiveness of bioclean rooms was studied in relation to prevention of infection during treatment for induction of remission of acute leukemia. According to the steps in clean patient care, patients were divided into three groups, Group A consisting of 106 patients who were accommodated in laminar air flow (LAF) rooms under strictly clean nursing, Group B consisting of 99 patients who were treated in disinfected rooms with LAF without any clean nursing techniques and Group C consisting of 188 patients who stayed in conventional wards. Since all patients were treated with antileukemic drugs and preventive administration of antimicrobial drugs under the same regimen, any difference between groups should be attributable to LAF or LAF and clean nursing. A marked and stepwise reduction in the incidence of infection between Groups A, B and C was observed. A statistically significant reduction in pneumonia, upper respiratory tract infection, periproctitis and skin abscesses was also observed in Groups A and B. As to the causative organisms, a relative increase in incidence of infections caused by Pseudomonas aeruginosa and Escherichia coli and a decrease in those caused by Proteus and fungi were observed in Groups A and B, as compared with Group C. These data suggest that pneumonia etc. may be exogenous infections and that Proteus and fungi are exogenous organisms, while Pseudomonas aeruginosa and Escherichia coli are endogenous bacteria. These data seem very helpful for setting up several steps in bioclean rooms for effective and economic patient care.

Effects of cefonicid and other cephalosporin antibiotics on male sexual development in rats.

PubMed Central

Manson, J M; Zolna, L E; Kang, Y J; Johnson, C M

1987-01-01

The purpose of this study was to determine whether cefonicid, a cephalosporin antibiotic with a modified N-methylthiotetrazole (MTT) side chain, caused testicular toxicity when subcutaneously administered to Sprague-Dawley male rats from days 6 to 36 postpartum at doses of 50 to 1,000 mg/kg per day. Moxalactam (a cephamycin antibiotic which will be referred to as a cephalosporin for convenience throughout), which contains the MTT side chain, was used as a positive control and was administered at 100 to 1,000 mg/kg per day, and cephalothin, which lacks an MTT side chain, was used as the negative control at 1,000 mg/kg per day. Moxalactam caused a significant reduction in testicular and seminal vesicle weights in 37-day-old animals, and histological examination revealed bilateral multifocal atrophy of the seminiferous tubules at all dose levels. Animals reared to reproductive maturity had significant deficits in fertility, and histological examination revealed multifocal or diffuse atrophy of the seminiferous tubules at all doses with a severity greater than that observed in the 37-day-old animals. The histological findings were confirmed by marked reductions in testicular sperm production rates and cauda epididymal sperm numbers. Cephalothin and cefonicid had no treatment-related adverse effects on the sexual maturation of prepubertal, juvenile, or adult males. The absence (in cephalothin) or modification (in cefonicid) of the MTT side chain was not associated with adverse reproductive effects. The relevance of these findings to humans in prenatal and prepubertal stages of life cannot be determined at this time. Images PMID:3662478

Hyperuricemia induces endothelial dysfunction via mitochondrial Na+/Ca2+ exchanger-mediated mitochondrial calcium overload.

PubMed

Hong, Quan; Qi, Ka; Feng, Zhe; Huang, Zhiyong; Cui, Shaoyuan; Wang, Liyuan; Fu, Bo; Ding, Rui; Yang, Jurong; Chen, Xiangmei; Wu, Di

2012-05-01

Uric acid (UA) has proven to be a causal agent in endothelial dysfunction in which ROS production plays an important role. Calcium overload in mitochondria can promote the mitochondrial production of ROS. We hypothesize that calcium transduction in mitochondria contributes to UA-induced endothelial dysfunction. We first demonstrated that high concentrations of UA cause endothelial dysfunction, marked by a reduction in eNOS protein expression and NO release in vitro. We further found that a high concentration of UA increased levels of [Ca2+]mito, total intracellular ROS, H2O2, and mitochondrial O2·-, and Δψmito but not the [Ca2+]cyt level. When the mitochondrial calcium channels NCXmito and MCU were blocked by CGP-37157 and Ru360, respectively, the UA-induced increases in the levels of [Ca2+]mito and total intracellular ROS were significantly reduced. Mitochondrial levels of O2·- and Δψmito were reduced by inhibition of NCXmito but not of MCU. Moreover, inhibition of NCXmito, but not of MCU, blocked the UA-induced reductions in eNOS protein expression and NO release. The increased generation of mitochondrial O2·- induced by a high concentration of UA is triggered by mitochondrial calcium overload and ultimately leads to endothelial dysfunction. In this process, the activation of NCXmito is the major cause of the influx of calcium into mitochondria. Our results provide a new pathophysiological mechanism for UA-induced endothelial dysfunction and may offer a new therapeutic target for clinicians. Copyright © 2012 Elsevier Ltd. All rights reserved.

Strategies for effective roundabout approach speed reduction : final report.

DOT National Transportation Integrated Search

2017-05-01

Appropriate deceleration on approaches to roundabouts is primarily accomplished through the use of applicable geometric design principles; however, traffic control devices (specifically signing and markings on the approach) also serve a vital role in...

Treatment of erythemato-telangiectatic rosacea with brimonidine alone or combined with vascular laser based on preliminary instrumental evaluation of the vascular component.

PubMed

Micali, Giuseppe; Dall'Oglio, Federica; Verzì, Anna Elisa; Luppino, Ivano; Bhatt, Karishma; Lacarrubba, Francesco

2017-09-09

The purpose of this study is to evaluate the outcome of a series of patients with erythematotelangiectatic rosacea (ETR) affected by persistent erythema and varying degree of telangiectasias being treated with brimonidine alone or combined with a vascular laser based on the type of vascular components preliminarily evaluated by clinical and instrumental observation. Ten patients affected by ETR were enrolled in a pilot, open study. Instrumental evaluation included erythema-directed digital photography by VISIA-CR™ system and X10 dermoscopy. Those patients showing marked background erythema and minimal telangiectasias (group A) were treated with a single application of brimonidine 0.33% gel, while patients showing both marked background erythema and marked telangiectasias (group B) were treated with a session of Nd:YAG laser and reevaluated 1 month later after a single application of brimonidine. An Investigator Global Assessment (IGA) of treatment outcome was performed at the end of treatment in both groups. In group A, 6 h after brimonidine application, a marked reduction of the background erythema was observed in all patients, and IGA was rated as excellent. In group B, 6 h following the application of brimonidine, a marked reduction of the background erythema was observed in all cases, while telangiectasias remained unchanged. A further treatment with brimonidine 1 month after the Nd:YAG laser session determined complete clearing of facial erythema, and IGA was rated as excellent. In conclusion, a preliminary evaluation of the vascular component by erythema-directed digital photography and dermoscopy in ETR may be helpful to select the most appropriate therapeutic strategy.

Cadmium modulates adipocyte functions in metallothionein-null mice

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

Kawakami, Takashige; Nishiyama, Kaori; Kadota, Yoshito

2013-11-01

Our previous study has demonstrated that exposure to cadmium (Cd), a toxic heavy metal, causes a reduction of adipocyte size and the modulation of adipokine expression. To further investigate the significance of the Cd action, we studied the effect of Cd on the white adipose tissue (WAT) of metallothionein null (MT{sup −/−}) mice, which cannot form atoxic Cd–MT complexes and are used for evaluating Cd as free ions, and wild type (MT{sup +/+}) mice. Cd administration more significantly reduced the adipocyte size of MT{sup −/−} mice than that of MT{sup +/+} mice. Cd exposure also induced macrophage recruitment to WATmore » with an increase in the expression level of Ccl2 (MCP-1) in the MT{sup −/−} mice. The in vitro exposure of Cd to adipocytes induce triglyceride release into culture medium, decrease in the expression levels of genes involved in fatty acid synthesis and lipid hydrolysis at 24 h, and at 48 h increase in phosphorylation of the lipid-droplet-associated protein perilipin, which facilitates the degradation of stored lipids in adipocytes. Therefore, the reduction in adipocyte size by Cd may arise from an imbalance between lipid synthesis and lipolysis. In addition, the expression levels of leptin, adiponectin and resistin decreased in adipocytes. Taken together, exposure to Cd may induce unusually small adipocytes and modulate the expression of adipokines differently from the case of physiologically small adipocytes, and may accelerate the risk of developing insulin resistance and type 2 diabetes. - Highlights: • Cd causes a marked reduction in adipocyte size in MT-null mice. • Cd enhances macrophage migration into adipose tissue and disrupt adipokine secretion. • MT gene alleviates Cd-induced adipocyte dysfunctions. • Cd enhances the degradation of stored lipids in adipocytes, mediated by perilipin. • Cd induces unusually small adipocytes and the abnormal expression of adipokines.« less

Altered surfactant homeostasis and recurrent respiratory failure secondary to TTF-1 nuclear targeting defect.

PubMed

Peca, Donatella; Petrini, Stefania; Tzialla, Chryssoula; Boldrini, Renata; Morini, Francesco; Stronati, Mauro; Carnielli, Virgilio P; Cogo, Paola E; Danhaive, Olivier

2011-08-25

Mutations of genes affecting surfactant homeostasis, such as SFTPB, SFTPC and ABCA3, lead to diffuse lung disease in neonates and children. Haploinsufficiency of NKX2.1, the gene encoding the thyroid transcription factor-1 (TTF-1)--critical for lung, thyroid and central nervous system morphogenesis and function--causes a rare form of progressive respiratory failure designated brain-lung-thyroid syndrome. Molecular mechanisms involved in this syndrome are heterogeneous and poorly explored. We report a novel TTF-1 molecular defect causing recurrent respiratory failure episodes in an infant. The subject was an infant with severe neonatal respiratory distress syndrome followed by recurrent respiratory failure episodes, hypopituitarism and neurological abnormalities. Lung histology and ultrastructure were assessed by surgical biopsy. Surfactant-related genes were studied by direct genomic DNA sequencing and array chromatine genomic hybridization (aCGH). Surfactant protein expression in lung tissue was analyzed by confocal immunofluorescence microscopy. For kinetics studies, surfactant protein B and disaturated phosphatidylcholine (DSPC) were isolated from serial tracheal aspirates after intravenous administration of stable isotope-labeled (2)H(2)O and (13)C-leucine; fractional synthetic rate was derived from gas chromatography/mass spectrometry (2)H and (13)C enrichment curves. Six intubated infants with no primary lung disease were used as controls. Lung biopsy showed desquamative interstitial pneumonitis and lamellar body abnormalities suggestive of genetic surfactant deficiency. Genetic studies identified a heterozygous ABCA3 mutation, L941P, previously unreported. No SFTPB, SFTPC or NKX2.1 mutations or deletions were found. However, immunofluorescence studies showed TTF-1 prevalently expressed in type II cell cytoplasm instead of nucleus, indicating defective nuclear targeting. This pattern has not been reported in human and was not found in two healthy controls and in five ABCA3 mutation carriers. Kinetic studies demonstrated a marked reduction of SP-B synthesis (43.2 vs. 76.5 ± 24.8%/day); conversely, DSPC synthesis was higher (12.4 vs. 6.3 ± 0.5%/day) compared to controls, although there was a marked reduction of DSPC content in tracheal aspirates (29.8 vs. 56.1 ± 12.4% of total phospholipid content). Defective TTF-1 signaling may result in profound surfactant homeostasis disruption and neonatal/pediatric diffuse lung disease. Heterozygous ABCA3 missense mutations may act as disease modifiers in other genetic surfactant defects.

Altered surfactant homeostasis and recurrent respiratory failure secondary to TTF-1 nuclear targeting defect

PubMed Central

2011-01-01

Background Mutations of genes affecting surfactant homeostasis, such as SFTPB, SFTPC and ABCA3, lead to diffuse lung disease in neonates and children. Haploinsufficiency of NKX2.1, the gene encoding the thyroid transcription factor-1 (TTF-1) - critical for lung, thyroid and central nervous system morphogenesis and function - causes a rare form of progressive respiratory failure designated brain-lung-thyroid syndrome. Molecular mechanisms involved in this syndrome are heterogeneous and poorly explored. We report a novel TTF-1 molecular defect causing recurrent respiratory failure episodes in an infant. Methods The subject was an infant with severe neonatal respiratory distress syndrome followed by recurrent respiratory failure episodes, hypopituitarism and neurological abnormalities. Lung histology and ultrastructure were assessed by surgical biopsy. Surfactant-related genes were studied by direct genomic DNA sequencing and array chromatine genomic hybridization (aCGH). Surfactant protein expression in lung tissue was analyzed by confocal immunofluorescence microscopy. For kinetics studies, surfactant protein B and disaturated phosphatidylcholine (DSPC) were isolated from serial tracheal aspirates after intravenous administration of stable isotope-labeled 2H2O and 13C-leucine; fractional synthetic rate was derived from gas chromatography/mass spectrometry 2H and 13C enrichment curves. Six intubated infants with no primary lung disease were used as controls. Results Lung biopsy showed desquamative interstitial pneumonitis and lamellar body abnormalities suggestive of genetic surfactant deficiency. Genetic studies identified a heterozygous ABCA3 mutation, L941P, previously unreported. No SFTPB, SFTPC or NKX2.1 mutations or deletions were found. However, immunofluorescence studies showed TTF-1 prevalently expressed in type II cell cytoplasm instead of nucleus, indicating defective nuclear targeting. This pattern has not been reported in human and was not found in two healthy controls and in five ABCA3 mutation carriers. Kinetic studies demonstrated a marked reduction of SP-B synthesis (43.2 vs. 76.5 ± 24.8%/day); conversely, DSPC synthesis was higher (12.4 vs. 6.3 ± 0.5%/day) compared to controls, although there was a marked reduction of DSPC content in tracheal aspirates (29.8 vs. 56.1 ± 12.4% of total phospholipid content). Conclusion Defective TTF-1 signaling may result in profound surfactant homeostasis disruption and neonatal/pediatric diffuse lung disease. Heterozygous ABCA3 missense mutations may act as disease modifiers in other genetic surfactant defects. PMID:21867529

A mouse model for creatine transporter deficiency reveals early onset cognitive impairment and neuropathology associated with brain aging.

PubMed

Baroncelli, Laura; Molinaro, Angelo; Cacciante, Francesco; Alessandrì, Maria Grazia; Napoli, Debora; Putignano, Elena; Tola, Jonida; Leuzzi, Vincenzo; Cioni, Giovanni; Pizzorusso, Tommaso

2016-10-01

Mutations in the creatine (Cr) transporter (CrT) gene lead to cerebral creatine deficiency syndrome-1 (CCDS1), an X-linked metabolic disorder characterized by cerebral Cr deficiency causing intellectual disability, seizures, movement and autistic-like behavioural disturbances, language and speech impairment. Since no data are available about the neural and molecular underpinnings of this disease, we performed a longitudinal analysis of behavioural and pathological alterations associated with CrT deficiency in a CCDS1 mouse model. We found precocious cognitive and autistic-like defects, mimicking the early key features of human CCDS1. Moreover, mutant mice displayed a progressive impairment of short and long-term declarative memory denoting an early brain aging. Pathological examination showed a prominent loss of GABAergic synapses, marked activation of microglia, reduction of hippocampal neurogenesis and the accumulation of autofluorescent lipofuscin. Our data suggest that brain Cr depletion causes both early intellectual disability and late progressive cognitive decline, and identify novel targets to design intervention strategies aimed at overcoming brain CCDS1 alterations. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Mutation in WDR4 impairs tRNA m(7)G46 methylation and causes a distinct form of microcephalic primordial dwarfism.

PubMed

Shaheen, Ranad; Abdel-Salam, Ghada M H; Guy, Michael P; Alomar, Rana; Abdel-Hamid, Mohamed S; Afifi, Hanan H; Ismail, Samira I; Emam, Bayoumi A; Phizicky, Eric M; Alkuraya, Fowzan S

2015-09-28

Primordial dwarfism is a state of extreme prenatal and postnatal growth deficiency, and is characterized by marked clinical and genetic heterogeneity. Two presumably unrelated consanguineous families presented with an apparently novel form of primordial dwarfism in which severe growth deficiency is accompanied by distinct facial dysmorphism, brain malformation (microcephaly, agenesis of corpus callosum, and simplified gyration), and severe encephalopathy with seizures. Combined autozygome/exome analysis revealed a novel missense mutation in WDR4 as the likely causal variant. WDR4 is the human ortholog of the yeast Trm82, an essential component of the Trm8/Trm82 holoenzyme that effects a highly conserved and specific (m(7)G46) methylation of tRNA. The human mutation and the corresponding yeast mutation result in a significant reduction of m(7)G46 methylation of specific tRNA species, which provides a potential mechanism for primordial dwarfism associated with this lesion, since reduced m(7)G46 modification causes a growth deficiency phenotype in yeast. Our study expands the number of biological pathways underlying primordial dwarfism and adds to a growing list of human diseases linked to abnormal tRNA modification.

The contribution of mitochondrial thymidylate synthesis in preventing the nuclear genome stress

PubMed Central

Lee, Ming-Hsiang; Wang, Liya; Chang, Zee-Fen

2014-01-01

In quiescent fibroblasts, the expression levels of cytosolic enzymes for thymidine triphosphate (dTTP) synthesis are down-regulated, causing a marked reduction in the dTTP pool. In this study, we provide evidence that mitochondrial thymidylate synthesis via thymidine kinase 2 (TK2) is a limiting factor for the repair of ultraviolet (UV) damage in the nuclear compartment in quiescent fibroblasts. We found that TK2 deficiency causes secondary DNA double-strand breaks formation in the nuclear genome of quiescent cells at the late stage of recovery from UV damage. Despite slower repair of quiescent fibroblast deficient in TK2, DNA damage signals eventually disappeared, and these cells were capable of re-entering the S phase after serum stimulation. However, these cells displayed severe genome stress as revealed by the dramatic increase in 53BP1 nuclear body in the G1 phase of the successive cell cycle. Here, we conclude that mitochondrial thymidylate synthesis via TK2 plays a role in facilitating the quality repair of UV damage for the maintenance of genome integrity in the cells that are temporarily arrested in the quiescent state. PMID:24561807

Tricho-odonto-onycho-dermal dysplasia and WNT10A mutations.

PubMed

Kantaputra, P; Kaewgahya, M; Jotikasthira, D; Kantaputra, W

2014-04-01

We report on three novel (IVS2+1G>A splice site, c.1066G>T, and c.1039G>T, and one previously reported (c.637G>A) WNT10A mutations in three patients affected with odonto-onycho-dermal dysplasia (OODD; OMIM 275980). OODD is a rare form of autosomal recessive ectodermal dysplasia involving hair, teeth, nails, and skin, characterized by hypodontia (tooth agenesis), smooth tongue with marked reduction of filiform and fungiform papillae, nail dysplasia, dry skin, palmoplantar keratoderma, and hyperhidrosis of palms and soles. The novel IVS+1G>A splice site mutation is predicted to cause significant protein alteration. The other novel mutations we found including c.1066G>T and c.1039G>T are predicted to cause p.Gly356Cys and p.Glu347X, respectively. Barrel-shaped mandibular incisors and severe hypodontia appear to be associated with homozygous or compound heterozygous mutations of WNT10A. The name "tricho-odonto-onycho-dermal dysplasia" is suggested to replace "odonto-onycho-dermal dysplasia" because hair anomalies including hypotrichosis and slow-growing hair have been reported in numerous reported patients with this syndrome. © 2014 Wiley Periodicals, Inc.

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

Age-Related Sleep Disruption and Reduction in the Circadian Rhythm of Urine Output: Contribution to Nocturia?

PubMed Central

Duffy, Jeanne F.; Scheuermaier, Karine; Loughlin, Kevin R.

2015-01-01

Aging is associated with a marked increase in sleep complaints, and one factor causing sleep disruption is waking to void (nocturia). Urological surveys have found that few young adults report nocturia symptoms, but about half of those in their 60’s and nearly 80% of older age groups are affected. Sleep surveys have found nocturia is a major cause of sleep disruption, with a majority of older adults with sleep disruption citing the need to void as the cause of their awakening. While much of the urological literature implies that nocturia causes sleep disruption, age-related changes in sleep depth and continuity may make it more likely that an older adult will wake in response to a filling bladder, or that an older adult will wake for another reason and then decide to void. There is also evidence that age-related changes in the amplitude of circadian rhythms contribute to nocturia. There is a well-described circadian rhythm in urine output, and evidence of circadian rhythmicity in some diuretic and anti-diuretic hormones. In this article we describe how age-related changes in sleep depth and continuity and age-related changes in circadian rhythm amplitude may contribute to nocturia, and how nocturia in turn leads to sleep disruption. Better understanding of how changes in sleep and circadian rhythmicity impact nocturia may lead to improved treatments and better quality of life for older adults. PMID:26632430

The MANDELA study: A multicenter, randomized, open-label, parallel group trial to refine the use of everolimus after heart transplantation.

PubMed

Deuse, Tobias; Bara, Christoph; Barten, Markus J; Hirt, Stephan W; Doesch, Andreas O; Knosalla, Christoph; Grinninger, Carola; Stypmann, Jörg; Garbade, Jens; Wimmer, Peter; May, Christoph; Porstner, Martina; Schulz, Uwe

2015-11-01

In recent years a series of trials has sought to define the optimal protocol for everolimus-based immunosuppression in heart transplantation, with the goal of minimizing exposure to calcineurin inhibitors (CNIs) and harnessing the non-immunosuppressive benefits of everolimus. Randomized studies have demonstrated that immunosuppressive potency can be maintained in heart transplant patients receiving everolimus despite marked CNI reduction, although very early CNI withdrawal may be inadvisable. A potential renal advantage has been shown for everolimus, but the optimal time for conversion and the adequate reduction in CNI exposure remain to be defined. Other reasons for use of everolimus include a substantial reduction in the risk of cytomegalovirus infection, and evidence for inhibition of cardiac allograft vasculopathy, a major cause of graft loss. The ongoing MANDELA study is a 12-month multicenter, randomized, open-label, parallel-group study in which efficacy, renal function and safety are compared in approximately 200 heart transplant patients. Patients receive CNI therapy, steroids and everolimus or mycophenolic acid during months 3 to 6 post-transplant, and are then randomized at month 6 post-transplant (i) to convert to CNI-free immunosuppression with everolimus and mycophenolic acid or (ii) to continue reduced-exposure CNI, with concomitant everolimus. Patients are then followed to month 18 post-transplant The rationale and expectations for the trial and its methodology are described herein. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of high-pressure homogenization on droplet size distribution and rheological properties of ice cream mixes.

PubMed

Innocente, N; Biasutti, M; Venir, E; Spaziani, M; Marchesini, G

2009-05-01

The effect of different homogenization pressures (15/3 MPa and 97/3 MPa) on fat globule size and distribution as well as on structure-property relationships of ice cream mixes was investigated. Dynamic light scattering, steady shear, and dynamic rheological analyses were performed on mixes with different fat contents (5 and 8%) and different aging times (4 and 20 h). The homogenization of ice cream mixes determined a change from bimodal to monomodal particle size distributions and a reduction in the mean particle diameter. Mean fat globule diameters were reduced at higher pressure, but the homogenization effect on size reduction was less marked with the highest fat content. The rheological behavior of mixes was influenced by both the dispersed and the continuous phases. Higher fat contents caused greater viscosity and dynamic moduli. The lower homogenization pressure (15/3 MPa) mainly affected the dispersed phase and resulted in a more pronounced viscosity reduction in the higher fat content mixes. High-pressure homogenization (97/3 MPa) greatly enhanced the viscoelastic properties and the apparent viscosity. Rheological results indicated that unhomogenized and 15/3 MPa homogenized mixes behaved as weak gels. The 97/3 MPa treatment led to stronger gels, perhaps as the overall result of a network rearrangement or interpenetrating network formation, and the fat globules were found to behave as interactive fillers. High-pressure homogenization determined the apparent viscosity of 5% fat to be comparable to that of 8% fat unhomogenized mix.

Effects of intraocular injection of a low concentration of zinc on the rat retina.

PubMed

Nakamichi, N; Chidlow, G; Osborne, N N

2003-10-01

The main aim of this study was to investigate whether intraocular injection of low concentrations of zinc (no greater than 10 microM) aid the survival of ganglion cells in the rat retina after excitotoxic (NMDA) and ischemia/reperfusion injuries. We also determined whether low amounts of zinc cause any detectable retinal toxicity. Intraocular injection of NMDA caused substantial reductions in the mRNA levels of the ganglion cell-specific markers Thy-1 and neurofilament light (NF-L). Co-injection of 0.1 or 1 nmol zinc neither diminished nor exacerbated the effect of NMDA on the levels of these mRNAs. Likewise, ischemia/reperfusion caused significant decreases in the levels of Thy-1 and NF-L mRNAs and in the b-wave amplitude of the electroretinogram. These effects were not counteracted by injection of zinc. Intraocular injection of NMDA caused marked toxicological effects in retinal glial cells, including upregulations of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), glial fibrial acidic protein (GFAP), basic fibroblast growth factor (FGF-2) and ciliary neurotrophic factor (CNTF). Interestingly, injection of 1 nmol zinc caused no changes in the levels of COX-2 and iNOS, yet produced similar, although quantitatively less pronounced, changes in FGF-2, GFAP and CNTF. The upregulations of FGF-2 and CNTF suggest that increasing zinc intake may benefit injured retinal neurons. However, this was not found to be the case in the present studies, perhaps due to the acute nature of the injury paradigms utilised.

Correlates of individual differences in compensatory nicotine self-administration in rats following a decrease in nicotine unit dose

PubMed Central

Harris, Andrew C.; Pentel, Paul R.; LeSage, Mark G.

2013-01-01

Rationale The ability of tobacco harm reduction strategies to produce significant reductions in toxin exposure is limited by compensatory increases in smoking behavior. Characterizing factors contributing to the marked individual variability in compensation may be useful for understanding this phenomenon and assessing the feasibility of harm reduction interventions. Objective To use an animal model of human compensatory smoking that involves a decrease in unit dose supporting nicotine self-administration (NSA) to examine potential contributors to individual differences in compensation. Methods Rats were trained for NSA during daily 23 hr sessions at a unit dose of 0.06 mg/kg/inf until responding was stable. The unit dose was then reduced to 0.03 mg/kg/inf for at least 10 sessions. Following reacquisition of NSA at the training dose and extinction, single-dose nicotine pharmacokinetic parameters were determined. Results Decreases in nicotine intake following dose reduction were proportionally less than the decrease in unit dose, indicating partial compensation. Compensatory increases in infusion rates were observed across the course of the 23 hr sessions. The magnitude of compensation differed considerably between rats. Rats exhibiting the highest baseline infusion rates exhibited the lowest levels of compensation. Nicotine pharmacokinetic parameters were not significantly correlated with compensation. Infusion rates immediately returned to pre-reduction levels when baseline conditions were restored. Conclusions These findings provide initial insights into correlates of individual differences in compensation following a reduction in nicotine unit dose. The present assay may be useful for characterizing mechanisms and potential consequences of the marked individual differences in compensatory smoking observed in humans. PMID:19475400

In vivo human cardiac shortening and lengthening velocity is region dependent and not coupled with heart rate: 'longitudinal' strain rate markedly underestimates apical contribution.

PubMed

Stöhr, Eric J; Stembridge, Mike; Esformes, Joseph I

2015-04-20

What is the central question of this study? Regulation of cardiac function is typically achieved by changes in heart rate (HR) and cardiac shortening velocity (strain rate; SR), but their interdependence in vivo remains poorly understood. What is the main finding and its importance? Using resistance exercise to increase heart rate and arterial resistance physiologically in humans and measuring regional cardiac SR (at the base and apex), we found that HR and SR were not strictly coupled because SR at the base and apex responded differently, despite the same HR. Importantly, our data show that the region-averaged 'longitudinal' SR, which is currently popular in the clinical setting, markedly underestimates the contribution of the apex. The fundamental importance of cardiac shortening and lengthening velocity (i.e. strain rate; SR) has been demonstrated in vitro. Currently, the interdependence between in vivo SR and HR is poorly understood because studies have typically assessed region-averaged 'longitudinal' strain rate, which is likely to underestimate the apical contribution, and have used non-physiological interventions that may also have been influenced by multicollinearity caused by concomitant reductions in arterial resistance. Resistance exercise acutely raises HR, blood pressure and arterial resistance and transiently disassociates these cardiovascular factors following exercise. Therefore, we measured SR, HR, blood pressure and arterial resistance in nine healthy men (aged 20 ± 1 years) immediately before, during and after double-leg-press exercise at 30 and 60% of maximal strength. Resistance exercise caused a disproportionate SR response at the left ventricular base and apex (interaction effect, P < 0.05). Consequently, associations between HR and regional peak SR were inconsistent and mostly very weak (r(2)  = 0.0004-0.24). Likewise, the areas under the curve for systolic and diastolic SR and their relationship with systolic and diastolic duration were variable and weak. Importantly, region-averaged 'longitudinal' SR was identical to basal SR, thus, markedly underestimating the apical contribution. In conclusion, in vivo HR and SR are not strictly coupled in healthy humans, which is explained by the region-specific responses of SR that are not captured by 'longitudinal SR'. This novel observation emphasizes the independent role of in vivo SR in overall cardiac function during stress and may cause a 'revival' of SR as a marker of regional left ventricular (dys)function. © 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.

Acute phase response in lactating dairy cows during hyperinsulinemic hypoglycaemic and hyperinsulinemic euglycaemic clamps and after intramammary LPS challenge.

PubMed

De Matteis, L; Bertoni, G; Lombardelli, R; Wellnitz, O; Van Dorland, H A; Vernay, M C M B; Bruckmaier, R M; Trevisi, E

2017-06-01

The link between energy availability, turnover of energy substrates and the onset of inflammation in dairy cows is complex and poorly investigated. To clarify this, plasma inflammatory variables were measured in mid-lactating dairy cows allocated to three groups: hyperinsulinemic hypoglycaemic clamp, induced by insulin infusion (HypoG, n = 5); hyperinsulinemic euglycaemic clamp, induced by insulin and glucose infusion (EuG; n = 6); control, receiving a saline solution infusion (NaCl; n = 6). At 48 h after the start of i.v. infusions, two udder quarters per cow were challenged with 200 μg of E. coli lipopolysaccharide (LPS). Individual blood samples were taken before clamps, before LPS challenge (i.e. 48 h after clamps) and 6.5 h after. At 48 h, positive acute phase proteins (posAPP) did not differ among groups, whereas albumin and cholesterol (index of lipoproteins), negative APP (negAPP), were lower (p < 0.05) in EuG compared to NaCl and HypoG. The concentration of IL-6 was greater in EuG (p < 0.05) but only vs. HypoG. At 6.5 h following LPS challenge, IL-6 increased in the NaCl and EuG clamps (p < 0.05), while TNF-α increased (p < 0.05) in the EuG only. Among the posAPP, haptoglobin markedly increased in EuG (p < 0.05), but not in NaCl (p = 0.76) and in HypoG; ceruloplasmin tended to decline during LPS challenge, the reduction was significant when all animals were considered (p < 0.05). Conversely, all the negAPP showed a marked reduction 6.5 h after LPS challenge in the three groups. In conclusion, EuG caused an inflammatory status after 48-h infusion (i.e. decrease of negAPP) and induced a quicker acute phase response (e.g. marked rise of TNF-α, IL-6) after the intramammary LPS challenge. These data suggest that the simultaneous high availability of glucose and insulin at the tissue-level makes dairy cows more susceptible to inflammatory events. In contrast, HypoG seems to attenuate the inflammatory response. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

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.

Over-expression of mammalian sialidase NEU3 reduces Newcastle disease virus entry and propagation in COS7 cells.

PubMed

Anastasia, Luigi; Holguera, Javier; Bianchi, Anna; D'Avila, Francesca; Papini, Nadia; Tringali, Cristina; Monti, Eugenio; Villar, Enrique; Venerando, Bruno; Muñoz-Barroso, Isabel; Tettamanti, Guido

2008-03-01

The paramyxovirus Newcastle Disease Virus (NDV) binds to sialic acid-containing glycoconjugates, sialoglycoproteins and sialoglycolipids (gangliosides) of host cell plasma membrane through its hemagglutinin-neuraminidase (sialidase) HN glycoprotein. We hypothesized that the modifications of the cell surface ganglioside pattern determined by over-expression of the mammalian plasma-membrane associated, ganglioside specific, sialidase NEU3 would affect the virus-host cell interactions. Using COS7 cells as a model system, we observed that over-expression of the murine MmNEU3 did not affect NDV binding but caused a marked reduction in NDV infection and virus propagation through cell-cell fusion. Moreover, since GD1a was greatly reduced in COS7 cells following NEU3-over-expression, we added [(3)H]-labelled GD1a to COS7 cells under conditions that block intralysosomal metabolic processing, and we observed a marked increase of GD1a cleavage to GM1 during NDV infection, indicating a direct involvement of the virus sialidase and host cell GD1a in NDV infectivity. Therefore, the decrease of GD1a in COS7 cell membrane upon MmNEU3 over-expression is likely to be instrumental to NDV reduced infection. Evidence was also provided for the preferential association of NDV-HN at 4 degrees C to detergent resistant microdomains (DRMs) of COS7 cells plasma membranes.

Triamcinolone hexacetonide protects against fibrillation and osteophyte formation following chemically induced articular cartilage damage.

PubMed

Williams, J M; Brandt, K D

1985-11-01

Although corticosteroids have been shown to cause articular cartilage degeneration, recent studies of experimentally induced osteoarthritis indicate that under certain conditions they may protect against cartilage damage and osteophyte formation. The present study examines the in vivo effect of triamcinolone hexacetonide on the degeneration of articular cartilage which occurs following intraarticular injection of sodium iodoacetate. Three weeks after a single injection of iodoacetate into the knees of guinea pigs, ipsilateral femoral condylar cartilage exhibited fibrillation, loss of staining with Safranin O, depletion of chondrocytes, and prominent osteophytes. In striking contrast, when triamcinolone hexacetonide was injected into the ipsilateral knee 24 hours after the intraarticular injection of iodoacetate, fibrillation was noted in only 1 of 6 samples, osteophytes were much less prominent, pericellular staining with Safranin O persisted, and cell loss was less extensive. Knees of animals which received only one-tenth as much intraarticular triamcinolone hexacetonide after the iodoacetate injection also exhibited marked reduction in size and extent of osteophytes. However, the degree of fibrillation, loss of Safranin O staining, and chondrocyte depletion was similar to that observed in animals injected with iodoacetate but not treated with intraarticular steroid. No apparent morphologic or histochemical changes were observed after intraarticular injection of the steroid preparation alone. Thus, triamcinolone hexacetonide produced a marked, dose-dependent protective effect in this model of chemically induced articular cartilage damage.

Effect of Hydroxyurea on Staphylococcus epidermidis and Micrococcus lysodeikticus: Thickening of the Cell Wall

PubMed Central

Feiner, Rose R.; Coward, Joe E.; Rosenkranz, Herbert S.

1973-01-01

Hydroxyurea-sensitive strains of Staphylococcus epidermidis and Micrococcus lysodeikticus showed marked thickening of cell walls and reduction in deoxyribonucleic acid synthesis when grown in the presence of hydroxyurea. Images PMID:4790602

Piper betle leaf extract affects the quorum sensing and hence virulence of Pseudomonas aeruginosa PAO1.

PubMed

Datta, Siraj; Jana, Debanjan; Maity, Tilak Raj; Samanta, Aveek; Banerjee, Rajarshi

2016-06-01

Quorum sensing (QS) plays an important role in virulence of Pseudomonas aeruginosa, blocking of QS ability are viewed as viable antimicrobial chemotherapy and which may prove to be a safe anti-virulent drug. Bioactive components from Piper betle have been reported to possess antimicrobial ability. This study envisages on the anti-QS properties of ethanolic extract of P. betle leaf (PbLE) using P. aeruginosa PAO1 as a model organism. A marked reduction in swarming, swimming, and twitching ability of the bacteria is demonstrated in presence of PbLE. The biofilm and pyocyanin production also shows a marked reduction in presence of PbLE, though it does not affect the bacterial growth. Thus, the studies hint on the possible effect of the bioactive components of PbLE on reducing the virulent ability of the bacteria; identification of bioactive compounds should be investigated further.

Effect of aromatherapy massage on elderly patients under long-term hospitalization in Japan.

PubMed

Satou, Tadaaki; Chikama, Mizuki; Chikama, Yoshiko; Hachigo, Masato; Urayama, Haruna; Murakami, Shio; Hayashi, Shinichiro; Koikem, Kazuo

2013-03-01

To verify the effectiveness of aromatherapy massage on elderly patients under long-term hospitalization. Aromatherapy massage was performed twice a week for a total of eight times. Nursing home. Elderly women under long-term hospitalization. Questionnaire and measurement of stress marker levels (salivary amylase activity) before and after the first, fifth, and eighth aromatherapy massages. Questionnaire (Face scale, General Health Questionnaire-12 [GHQ-12]), measurement of salivary amylase activity. A decrease in stress after aromatherapy massage compared to before each massage was confirmed at all measurement times and with the stress marker. No marked reduction was observed in Face scale or saliva amylase activity as a whole over the long term, although decreasing tendencies were seen. Marked reductions in GHQ-12 were observed over the long term. Aroma massage appears likely to prove effective in reducing psychological stress among elderly patients under long-term hospitalization.

Papain-induced changes in rabbit cartilage; alterations in the chemical structure of the cartilage matrix.

PubMed

TSALTAS, T T

1958-10-01

Some biochemical aspects of the collapse of the rabbit ears produced by the intravenous injection of papain have been studied. A marked depletion of chondromucoprotein (M.C.S.) and a reduction of the S(35) content of cartilage matrix were found to coincide with the gross and histologic changes in the cartilage. At the same time there was a marked increase in the amount of S(35) in the serum and an increase of S(35) and glucuronic acid excreted in the urine. Alteration in the composition of the M.C.S. remaining in the cartilage of the papain-injected animals was detected. The findings indicate that the collapse of the rabbit ears is due to loss of chondromucoprotein from cartilage and reduction of chondroitin sulfate in the chondromucoprotein that remains. All these changes were reversed in recovery.

Decommissioning of the TRIGA mark II and III and radioactive waste management

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

Doo Seong Hwang; Yoon Ji Lee; Gyeong Hwan Chung

2013-07-01

KAERI has carried out decommissioning projects for two research reactors (KRR-1 and 2). The decommissioning project of KRR-1 (TRIGA Mark II) and 2 (TRIGA Mark III) was launched in 1997 with a total budget of 23.25 million US dollars. KRR-2 and all auxiliary facilities were already decommissioned, and KRR-1 is being decommissioned now. Much more dismantled waste is generated than in any other operations of nuclear facilities. Thus, the waste needs to be reduced and stabilized through decontamination or treatment before disposal. This paper introduces the current status of the decommissioning projects and describes the volume reduction and conditioning ofmore » decommissioning waste for final disposal. (authors)« less

Potential Gains in Life Expectancy from Reductions in Leading Causes of Death, Los Angeles County: a Quantitative Approach to Identify Candidate Diseases for Prevention and Burden Disparities Elimination.

PubMed

Ho, Alex; Hameed, Heena; Lee, Alice W; Shih, Margaret

2016-09-01

Despite overall gains in life expectancy at birth among Los Angeles County residents, significant disparities persist across population subgroups. The purpose of this study was to quantify the potential sex- and race/ethnicity-specific gains in life expectancy had we been able to fully or partially eliminate the leading causes of death in Los Angeles County. Complete annual life tables for local residents were generated by applying the same method used for the National Center of Health Statistics US life tables published in 1999. Based on 2010 Los Angeles County mortality records, sex- and race/ethnicity-specific potential gains in life expectancy were calculated using scenarios of 10, 20, 50, and 100 % elimination of 12 major causes of death. Coronary heart disease, the leading cause of death, was found to be most impactful on life expectancy. Its hypothetical full elimination would result in life expectancy gains ranging from 2.2 years among white females to 3.7 years among black males. Gains from complete elimination of lung cancer and stroke ranked second, with almost an additional year of life for each gender. However, marked disparities across racial/ethnic groups were noted from the elimination of several other causes of death, such as homicide, from which the gain among black males exceeded 13 times more than their white counterparts. By differentially targeting specific causes of death in disease prevention, not only can findings of this study aid in efficiently narrowing racial/ethnic disparities, they can also provide a quantitative means to identify and rank priorities in local health policymaking.

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.

Near-Roadway Pollution and Childhood Asthma: Implications for Developing “Win–Win” Compact Urban Development and Clean Vehicle Strategies

PubMed Central

Perez, Laura; Lurmann, Fred; Wilson, John; Pastor, Manuel; Brandt, Sylvia J.; Künzli, Nino

2012-01-01

Background: The emerging consensus that exposure to near-roadway traffic-related pollution causes asthma has implications for compact urban development policies designed to reduce driving and greenhouse gases. Objectives: We estimated the current burden of childhood asthma-related disease attributable to near-roadway and regional air pollution in Los Angeles County (LAC) and the potential health impact of regional pollution reduction associated with changes in population along major traffic corridors. Methods: The burden of asthma attributable to the dual effects of near-roadway and regional air pollution was estimated, using nitrogen dioxide and ozone as markers of urban combustion-related and secondary oxidant pollution, respectively. We also estimated the impact of alternative scenarios that assumed a 20% reduction in regional pollution in combination with a 3.6% reduction or 3.6% increase in the proportion of the total population living near major roads, a proxy for near-roadway exposure. Results: We estimated that 27,100 cases of childhood asthma (8% of total) in LAC were at least partly attributable to pollution associated with residential location within 75 m of a major road. As a result, a substantial proportion of asthma-related morbidity is a consequence of near-roadway pollution, even if symptoms are triggered by other factors. Benefits resulting from a 20% regional pollution reduction varied markedly depending on the associated change in near-roadway proximity. Conclusions: Our findings suggest that there are large and previously unappreciated public health consequences of air pollution in LAC and probably in other metropolitan areas with dense traffic corridors. To maximize health benefits, compact urban development strategies should be coupled with policies to reduce near-roadway pollution exposure. PMID:23008270

Near-roadway pollution and childhood asthma: implications for developing "win-win" compact urban development and clean vehicle strategies.

PubMed

Perez, Laura; Lurmann, Fred; Wilson, John; Pastor, Manuel; Brandt, Sylvia J; Künzli, Nino; McConnell, Rob

2012-11-01

The emerging consensus that exposure to near-roadway traffic-related pollution causes asthma has implications for compact urban development policies designed to reduce driving and greenhouse gases. We estimated the current burden of childhood asthma-related disease attributable to near-roadway and regional air pollution in Los Angeles County (LAC) and the potential health impact of regional pollution reduction associated with changes in population along major traffic corridors. The burden of asthma attributable to the dual effects of near-roadway and regional air pollution was estimated, using nitrogen dioxide and ozone as markers of urban combustion-related and secondary oxidant pollution, respectively. We also estimated the impact of alternative scenarios that assumed a 20% reduction in regional pollution in combination with a 3.6% reduction or 3.6% increase in the proportion of the total population living near major roads, a proxy for near-roadway exposure. We estimated that 27,100 cases of childhood asthma (8% of total) in LAC were at least partly attributable to pollution associated with residential location within 75 m of a major road. As a result, a substantial proportion of asthma-related morbidity is a consequence of near-roadway pollution, even if symptoms are triggered by other factors. Benefits resulting from a 20% regional pollution reduction varied markedly depending on the associated change in near-roadway proximity. Our findings suggest that there are large and previously unappreciated public health consequences of air pollution in LAC and probably in other metropolitan areas with dense traffic corridors. To maximize health benefits, compact urban development strategies should be coupled with policies to reduce near-roadway pollution exposure.

Reduction in voltage-gated K+ channel activity in primary sensory neurons in painful diabetic neuropathy: role of brain-derived neurotrophic factor.

PubMed

Cao, Xue-Hong; Byun, Hee-Sun; Chen, Shao-Rui; Cai, You-Qing; Pan, Hui-Lin

2010-09-01

Abnormal hyperexcitability of primary sensory neurons plays an important role in neuropathic pain. Voltage-gated potassium (Kv) channels regulate neuronal excitability by affecting the resting membrane potential and influencing the repolarization and frequency of the action potential. In this study, we determined changes in Kv channels in dorsal root ganglion (DRG) neurons in a rat model of diabetic neuropathic pain. The densities of total Kv, A-type (IA) and sustained delayed (IK) currents were markedly reduced in medium- and large-, but not in small-, diameter DRG neurons in diabetic rats. Quantitative RT-PCR analysis revealed that the mRNA levels of IA subunits, including Kv1.4, Kv3.4, Kv4.2, and Kv4.3, in the DRG were reduced approximately 50% in diabetic rats compared with those in control rats. However, there were no significant differences in the mRNA levels of IK subunits (Kv1.1, Kv1.2, Kv2.1, and Kv2.2) in the DRG between the two groups. Incubation with brain-derived neurotrophic factor (BDNF) caused a large reduction in Kv currents, especially IA currents, in medium and large DRG neurons from control rats. Furthermore, the reductions in Kv currents and mRNA levels of IA subunits in diabetic rats were normalized by pre-treatment with anti-BDNF antibody or K252a, a TrkB tyrosine kinase inhibitor. In addition, the number of medium and large DRG neurons with BDNF immunoreactivity was greater in diabetic than control rats. Collectively, our findings suggest that diabetes primarily reduces Kv channel activity in medium and large DRG neurons. Increased BDNF activity in these neurons likely contributes to the reduction in Kv channel function through TrkB receptor stimulation in painful diabetic neuropathy.

Gene therapy ameliorates cardiovascular disease in dogs with mucopolysaccharidosis VII.

PubMed

Sleeper, M M; Fornasari, B; Ellinwood, N M; Weil, M A; Melniczek, J; O'Malley, T M; Sammarco, C D; Xu, L; Ponder, K P; Haskins, M E

2004-08-17

Mucopolysaccharidosis VII (MPS VII) is a lysosomal storage disease caused by deficient beta-glucuronidase (GUSB) activity resulting in defective catabolism of glycosaminoglycans (GAGs). Cardiac disease is a major cause of death in MPS VII because of accumulation of GAGs in cardiovascular cells. Manifestations include cardiomyopathy, mitral and aortic valve thickening, and aortic root dilation and may cause death in the early months of life or may be compatible with a fairly normal lifespan. We previously reported that neonatal administration of a retroviral vector (RV) resulted in transduction of hepatocytes, which secreted GUSB into the blood and could be taken up by cells throughout the body. The goal of this study was to evaluate the effect on cardiac disease. Six MPS VII dogs were treated intravenously with an RV-expressing canine GUSB. Echocardiographic parameters, cardiovascular lesions, and biochemical parameters of these dogs were compared with those of normal and untreated MPS VII dogs. RV-treated dogs were markedly improved compared with untreated MPS VII dogs. Most RV-treated MPS VII dogs had mild or moderate mitral regurgitation at 4 to 5 months after birth, which improved or disappeared when evaluated at 9 to 11 and at 24 months. Similarly, mitral valve thickening present early in some animals disappeared over time, whereas aortic dilation and aortic valve thickening were absent at all times. Both myocardium and aorta had significant levels of GUSB and reduction in GAGs.

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.

[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.

The global role of natural disaster fatalities in decision-making: statistics, trends and analysis from 116 years of disaster data compared to fatality rates from other causes

NASA Astrophysics Data System (ADS)

Daniell, James; Wenzel, Friedemann; McLennan, Amy; Daniell, Katherine; Kunz-Plapp, Tina; Khazai, Bijan; Schaefer, Andreas; Kunz, Michael; Girard, Trevor

2016-04-01

In this study, analysis is undertaken showing disaster fatalities trends from around the world using the CATDAT Natural Disaster and Socioeconomic Indicator databases from 1900-2015. Earthquakes have caused over 2.3 million fatalities since 1900; however absolute numbers of deaths caused by them have remained rather constant over time. However, floods have caused somewhere between 1.7 and 5.4 million fatalities, mostly in the earlier half of the 20th century (depending on the 1931 China floods). Storm and storm surges (ca. 1.3 million fatalities), on the other hand, have shown an opposite trend with increasing fatalities over the century (or a lack of records in the early 1900s). Earthquakes due to their sporadic nature, do not inspire investment pre-disaster. When looking at the investment in flood control vs. earthquakes, there is a marked difference in the total investment, which has resulted in a much larger reduction in fatalities. However, a key consideration for decision-makers in different countries around the world when choosing to implement disaster sensitive design is the risk of a natural disaster death, compared to other types of deaths in their country. The creation of empirical annualised ratios of earthquake, flood and storm fatalities from the year 1900 onwards vs. other methods of fatalities (cancer, diseases, accidents etc.) for each country using the CATDAT damaging natural disasters database is undertaken. On an annualised level, very few countries show earthquakes and other disaster types to be one of the highest probability methods for death. However, in particular years with large events, annual rates can easily exceed the total death count for a particular country. An example of this is Haiti, with the equivalent earthquake death rate in 2010 exceeding the total all-cause death rate in the country. Globally, fatality rates due to disasters are generally at least 1 order of magnitude lower than other causes such as heart disease. However, in some locations in countries such as Armenia, Turkmenistan, Peru and Guatemala, the annual probability of being killed in an earthquake is as high as that of being killed due to heart disease. In this study, around 50 countries have been shown to have at least one single event year for earthquake exceeding that of all traffic fatalities, and 15 countries higher than the equivalent total death rate of the country. China has shown very high death rates due to flood, however, with from 1900-2015, this rate has reduced significantly. Floods are generally an order of magnitude less than traffic accidents measured in micromorts likely due to improved flood risk reduction. However, recent events in Philippines and Myanmar show mortality reduction due to storm surge and cyclones still require much effort. The role of life safety is increasing with risk-based disaster resistant codes becoming more commonplace globally. An examination of government funding around the world shows the correlation between retrofitting investment and disaster fatality reduction. New methods of presenting disaster statistics for political use have been used to present the information upon which such decisions are made.

Reduction in the write error rate of voltage-induced dynamic magnetization switching using the reverse bias method

NASA Astrophysics Data System (ADS)

Ikeura, Takuro; Nozaki, Takayuki; Shiota, Yoichi; Yamamoto, Tatsuya; Imamura, Hiroshi; Kubota, Hitoshi; Fukushima, Akio; Suzuki, Yoshishige; Yuasa, Shinji

2018-04-01

Using macro-spin modeling, we studied the reduction in the write error rate (WER) of voltage-induced dynamic magnetization switching by enhancing the effective thermal stability of the free layer using a voltage-controlled magnetic anisotropy change. Marked reductions in WER can be achieved by introducing reverse bias voltage pulses both before and after the write pulse. This procedure suppresses the thermal fluctuations of magnetization in the initial and final states. The proposed reverse bias method can offer a new way of improving the writing stability of voltage-driven spintronic devices.

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

Steep declines in atmospheric base cations in regions of Europe and North America

NASA Astrophysics Data System (ADS)

Hedin, Lars O.; Granat, Lennart; Likens, Gene E.; Adri Buishand, T.; Galloway, James N.; Butler, Thomas J.; Rodhe, Henning

1994-01-01

HUMAN activities have caused marked changes in atmospheric chemistry over large regions of Europe and North America. Although considerable attention has been paid to the effects of changes in the deposition of acid anions (such as sulphate and nitrate) on terrestrial and aquatic ecosystems1-7, little is known about whether the concentrations of basic components of the atmosphere have changed over time8,9 and what the biogeochemical consequences of such potential changes might be. In particular, there has been some controversy8-12 as to whether declines in base-cation deposition have countered effects of recent reductions in SO2emission. Here we report evidence for steep declines in the atmospheric concentrations of base cations (sum of non-sea-salt Ca2+, Mg2+, K+ and Na+) over the past 10 to 26 years from high-quality precipitation chemistry records in Europe and North America. To varying but generally significant degrees, these base-cation trends have offset recent reductions in sulphate deposition in the regions examined. The observed trends seem to be ecologically important on decadal timescales, and support earlier contentions8-10 that declines in the deposition of base cations may have contributed to increased sensitivity of poorly buffered ecosystems.

The hyperoxic switch: assessing respiratory water loss rates in tracheate arthropods with continuous gas exchange.

PubMed

Lighton, John R B; Schilman, Pablo E; Holway, David A

2004-12-01

Partitioning the relative contributions of cuticular and respiratory water loss in a tracheate arthropod is relatively easy if it undergoes discontinuous gas exchange cycles or DGCs, leaving its rate of cuticular water loss in primary evidence while its spiracles are closed. Many arthropods are not so obliging and emit CO(2) continuously, making cuticular and respiratory water losses difficult or impossible to partition. We report here that by switching ambient air from 21 to 100% O(2), marked spiracular constriction takes place, causing a transient but substantial - up to 90% - reduction in CO(2) output. A reduction in water loss rate occurs at the same time. Using this approach, we investigated respiratory water loss in Drosophila melanogaster and in two ant species, Forelius mccooki and Pogonomyrmex californicus. Our results - respiratory water loss estimates of 23%, 7.6% and 5.6% of total water loss rates, respectively - are reasonable in light of literature estimates, and suggest that the 'hyperoxic switch' may allow straightforward estimation of respiratory water loss rates in arthropods lacking discontinuous gas exchange. In P. californicus, which we were able to measure with and without a DGC, presence or absence of a DGC did not affect respiratory vs total water loss rates.

Antispermatogenic, antiandrogenic activities of Albizia lebbeck (L.) Benth bark extract in male albino rats.

PubMed

Gupta, R S; Kachhawa, J B S; Chaudhary, R

2006-03-01

Methanolic extract of Albizia lebbeck bark when administered orally at the dose level of 100 mg/rat/day to male rats of proven fertility for 60 days did not cause any significant loss in their body weights but the weights of reproductive organs, i.e. testis, epididymides, seminal vesicle and ventral prostate were decreased in a significant manner when compared to controls. Sperm motility as well as sperm density were reduced significantly which resulted in reduction of male fertility by 100%. Marked decline in the germ cell population was noticed. Population of preleptotene, pachytene, secondary spermatocytes and step-19 spermatid were declined by 60.86%, 65.81%, 71.56% and 66.55%, respectively. Cross-sectional surface area of sertoli cells as well as the cells counts were found to be depleted significantly. Leydig cells nuclear area and number of mature Leydig cells were decreased by 60.03% and 51.56%, respectively. Serum testosterone levels showed significant reduction after A. lebbeck extract feeding. Oral administration of the extract did not affect red blood cell (RBC) and white blood cell (WBC) count, haemoglobin, haematocrit and glucose in the blood and cholesterol, protein, triglyceride and phospholipid in the serum. In conclusion, A. lebbeck bark extract administration arrests spermatogenesis in male rats without noticeable side effects.

mTORC1 Plays an Important Role in Skeletal Development by Controlling Preosteoblast Differentiation

PubMed Central

Matthews, Mary P.; Martin, Sally K.; Xie, Jianling; Ooi, Soo Siang; Walkley, Carl R.; Codrington, John D.; Ruegg, Markus A.; Hall, Michael N.; Proud, Christopher G.; Gronthos, Stan; Zannettino, Andrew C. W.

2017-01-01

ABSTRACT The mammalian target of rapamycin complex 1 (mTORC1) is activated by extracellular factors that control bone accrual. However, the direct role of this complex in osteoblast biology remains to be determined. To investigate this question, we disrupted mTORC1 function in preosteoblasts by targeted deletion of Raptor (Rptor) in Osterix-expressing cells. Deletion of Rptor resulted in reduced limb length that was associated with smaller epiphyseal growth plates in the postnatal skeleton. Rptor deletion caused a marked reduction in pre- and postnatal bone accrual, which was evident in skeletal elements derived from both intramembranous and endochondrial ossification. The decrease in bone accrual, as well as the associated increase in skeletal fragility, was due to a reduction in osteoblast function. In vitro, osteoblasts derived from knockout mice display a reduced osteogenic potential, and an assessment of bone-developmental markers in Rptor knockout osteoblasts revealed a transcriptional profile consistent with an immature osteoblast phenotype suggesting that osteoblast differentiation was stalled early in osteogenesis. Metabolic labeling and an assessment of cell size of Rptor knockout osteoblasts revealed a significant decrease in protein synthesis, a major driver of cell growth. These findings demonstrate that mTORC1 plays an important role in skeletal development by regulating mRNA translation during preosteoblast differentiation. PMID:28069737

Effects of technological processes on enniatin levels in pasta.

PubMed

Serrano, Ana B; Font, Guillermina; Mañes, Jordi; Ferrer, Emilia

2016-03-30

Potential human health risks posed by enniatins (ENs) require their control primarily from cereal products, creating a demand for harvesting, food processing and storage techniques capable to prevent, reduce and/or eliminate the contamination. In this study, different methodologies to pasta processing simulating traditional and industrial processes were developed in order to know the fate of the mycotoxin ENs. The levels of ENs were studied at different steps of pasta processing. The effect of the temperature during processing was evaluated in two types of pasta (white and whole-grain pasta). Mycotoxin analysis was performed by LC-MS/MS. High reductions (up to 50% and 80%) were achieved during drying pasta at 45-55°C and 70-90°C, respectively. The treatments at low temperature (25°C) did not change EN levels. The effect of pasta composition did not cause a significant effect on the stability of ENs. The effect of the temperature allowed a marked mycotoxin reduction during pasta processing. Generally, ENA1 and ENB showed higher thermal stability than did ENA and ENB1 . The findings from the present study suggested that pasta processing at medium-high temperatures is a potential tool to remove an important fraction of ENs from the initial durum wheat semolina. © 2015 Society of Chemical Industry.

Acute and chronic hypoglycemic effect of Ibervillea sonorae root extracts-II.

PubMed

Alarcon-Aguilar, F J; Calzada-Bermejo, F; Hernandez-Galicia, E; Ruiz-Angeles, C; Roman-Ramos, R

2005-03-21

Ibervillea sonorae's root, or "wareque" (Cucurbitaceae), is widely used in Mexican traditional medicine for the control of diabetes mellitus. In the present study, the hypoglycemic effects produced by the acute and chronic administration of various extracts of Ibervillea sonorae were investigated. Both the traditional preparation (aqueous decoction) and the raw extract (juice) from the root resulted in significant reductions of glycemia in healthy mice after intraperitoneal administration at a dose of 600 mg/kg. Additionally, ground dried root was used to obtain a dichloromethane (DCM) extract and a methanol (MeOH) extract. The DCM extract induced a clear reduction of glycemia in healthy (P < 0.05) and in alloxan-diabetic mice. The intraperitoneally administered DCM extract caused a severe hypoglycemia that produced lethality in all the treated animals when doses of 300 and 600 mg/kg body weight were used. Since the DCM extract showed a marked hypoglycemic activity, it was administered daily per os to alloxan diabetic rats, employing corn oil and tolbutamide as controls. After 41 days of DCM extract administration at a dose of 300 mg/kg/day, diabetic rats showed improvement in glycemia, body weight, triglycerides, and GPT in comparison with the diabetic control group. Total cholesterol, GOT, and uric acid blood levels were not affected.

Effect of industrial processing on the IgE reactivity of three commonly consumed Mo-roccan fish species in Fez region.

PubMed

Mejrhit, N; Azdad, O; Aarab, L

2018-03-02

Objectives. The aim of this work was to study the effect of industrial processing on the allergenicity of three commonly consumed Moroccan fish species in Fez region (sardine, common pandora, and shrimp). Methods. This work was conducted by a sera-bank obtained from 1248 patients recruited from Fez Hospitals. Their sera were analyzed for specific IgE binding to raw fish extracts. Among them, 60 patients with higher specific IgE levels were selected, and used to estimate the binding variation of IgE to these products under several processing (frying, cooking, canning, marinade, and fermentation) using ELISA analysis. Results. ELISA results demonstrated that all the studied processing cause a reduction in the immunoreactivity of human IgE to fish products, with a high action with marinade and fermentation compared to other processing. This alteration was also observed with rabbit IgG in all processed products, showing that the maximum reduction was marked in fermented sardine with 64.5%, in cooked common pandora with 58%, and in fermented shrimp with 69.2%. Conclusion. In conclusion, our study has shown that the allergenicity of the three studied fish could be reduced by different industrial processes with different degrees.

Mechanisms of decreased left ventricular preload during continuous positive pressure ventilation in ARDS

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

Dhainaut, J.F.; Devaux, J.Y.; Monsallier, J.F.

1986-07-01

Continuous positive pressure ventilation is associated with a reduction in left ventricular preload and cardiac output, but the mechanisms responsible are controversial. The decrease in left ventricular preload may result exclusively from a decreased systemic venous return due to increased pleural pressure, or from an additional effect such as decreased left ventricular compliance. To determine the mechanisms responsible, we studied the changes in cardiac output induced by continuous positive pressure ventilation in eight patients with the adult respiratory distress syndrome. We measured cardiac output by thermodilution, and biventricular ejection fraction by equilibrium gated blood pool scintigraphy. Biventricular end-diastolic volumes weremore » then calculated by dividing stroke volume by ejection fraction. As positive end-expiratory pressure increased from 0 to 20 cm H/sub 2/O, stroke volume and biventricular end-diastolic volumes fell about 25 percent, and biventricular ejection fraction remained unchanged. At 20 cm H/sub 2/O positive end-expiratory pressure, volume expansion for normalizing cardiac output restored biventricular end-diastolic volumes without markedly changing biventricular end-diastolic transmural pressures. The primary cause of the reduction in left ventricular preload with continuous positive pressure ventilation appears to be a fall in venous return and hence in right ventricular stroke volume, without evidence of change in left ventricular diastolic compliance.« less

[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.

Pigment Epithelium Derived Factor Peptide Protects Murine Hepatocytes from Carbon Tetrachloride-Induced Injury

PubMed Central

Shih, Shou-Chuan; Ho, Tsung-Chuan; Chen, Show-Li; Tsao, Yeou-Ping

2016-01-01

Fibrogenesis is induced by repeated injury to the liver and reactive regeneration and leads eventually to liver cirrhosis. Pigment epithelium derived factor (PEDF) has been shown to prevent liver fibrosis induced by carbon tetrachloride (CCl4). A 44 amino acid domain of PEDF (44-mer) was found to have a protective effect against various insults to several cell types. In this study, we investigated the capability of synthetic 44-mer to protect against liver injury in mice and in primary cultured hepatocytes. Acute liver injury, induced by CCl4, was evident from histological changes, such as cell necrosis, inflammation and apoptosis, and a concomitant reduction of glutathione (GSH) and GSH redox enzyme activities in the liver. Intraperitoneal injection of the 44-mer into CCl4-treated mice abolished the induction of AST and ALT and markedly reduced histological signs of liver injury. The 44-mer treatment can reduce hepatic oxidative stress as evident from lower levels of lipid hydroperoxide, and higher levels of GSH. CCl4 caused a reduction of Bcl-xL, PEDF and PPARγ, which was markedly restored by the 44-mer treatment. Consequently, the 44-mer suppressed liver fibrosis induced by repeated CCl4 injury. Furthermore, our observations in primary culture of rat hepatocytes showed that PEDF and the 44-mer protected primary rat hepatocytes against apoptosis induced by serum deprivation and TGF-β1. PEDF/44-mer induced cell protective STAT3 phosphorylation. Pharmacological STAT3 inhibition prevented the antiapoptotic action of PEDF/44-mer. Among several PEDF receptor candidates that may be responsible for hepatocyte protection, we demonstrated that PNPLA2 was essential for PEDF/44-mer-mediated STAT3 phosphorylation and antiapoptotic activity by using siRNA to selectively knockdown PNPLA2. In conclusion, the PEDF 44-mer protects hepatocytes from single and repeated CCl4 injury. This protective effect may stem from strengthening the counter oxidative stress capacity and induction of hepatoprotective factors. PMID:27384427

Colon luminal content and epithelial cell morphology are markedly modified in rats fed with a high-protein diet.

PubMed

Andriamihaja, Mireille; Davila, Anne-Marie; Eklou-Lawson, Mamy; Petit, Nathalie; Delpal, Serge; Allek, Fadhila; Blais, Anne; Delteil, Corine; Tomé, Daniel; Blachier, François

2010-11-01

Hyperproteic diets are used in human nutrition to obtain body weight reduction. Although increased protein ingestion results in an increased transfer of proteins from the small to the large intestine, there is little information on the consequences of the use of such diets on the composition of large intestine content and on epithelial cell morphology and metabolism. Rats were fed for 15 days with either a normoproteic (NP, 14% protein) or a hyperproteic isocaloric diet (HP, 53% protein), and absorptive colonocytes were observed by electron microscopy or isolated for enzyme activity studies. The colonic luminal content was recovered for biochemical analysis. Absorbing colonocytes were characterized by a 1.7-fold reduction in the height of the brush-border membranes (P = 0.0001) after HP diet consumption when compared with NP. This coincided in the whole colon content of HP animals with a 1.8-fold higher mass content (P = 0.0020), a 2.2-fold higher water content (P = 0.0240), a 5.2-fold higher protease activity (P = 0.0104), a 5.5-fold higher ammonia content (P = 0.0008), and a more than twofold higher propionate, valerate, isobutyrate, and isovalerate content (P < 0.05). The basal oxygen consumption of colonocytes was similar in the NP and HP groups, but ammonia was found to provoke a dose-dependent decrease of oxygen consumption in the isolated absorbing colonocytes. The activity of glutamine synthetase (which condenses ammonia and glutamate) was found to be much higher in colonocytes than in small intestine enterocytes and was 1.6-fold higher (P = 0.0304) in colonocytes isolated from HP animals than NP. Glutaminase activity remained unchanged. Thus hyperproteic diet ingestion causes marked changes both in the luminal environment of colonocytes and in the characteristics of these cells, demonstrating that hyperproteic diet interferes with colonocyte metabolism and morphology. Possible causal relationships between energy metabolism, reduced height of colonocyte brush-border membranes, and reduced water absorption are discussed.

Sometimes doing the right thing sucks: frame combinations and multi-fetal pregnancy reduction decision difficulty.

PubMed

Britt, David W; Evans, Mark I

2007-12-01

Data are analyzed for 54 women who made an appointment with a North American Center specializing in multifetal pregnancy reduction (MFPR) to be counseled and possibly have a reduction. The impact on decision difficulty of combinations of three frames through which patients may understand and consider their options and use to justify their decisions are examined: a conceptional frame marked by a belief that life begins at conception; a medical frame marked by a belief in the statistics regarding risk and risk prevention through selective reduction; and a lifestyle frame marked by a belief that a balance of children and career has normative value. All data were gathered through semi-structured interviews and observation during the visit to the center over an average 2.5h period. Decision difficulty was indicated by self-assessed decision difficulty and by residual emotional turmoil surrounding the decision. Qualitative comparative analysis was used to analyze the impact of combinations of frames on decision difficulty. Separate analyses were conducted for those reducing only to three fetuses (or deciding not to reduce) and women who chose to reduce below three fetuses. Results indicated that for those with a non-intense conceptional frame, the decision was comparatively easy no matter whether the patients had high or low values of medical and lifestyle frames. For those with an intense conceptional frame, the decision was almost uniformly difficult, with the exception of those who chose to reduce only to three fetuses. Simplifying the results to their most parsimonious scenarios oversimplifies the results and precludes an understanding of how women can feel pulled in different directions by the dictates of the frames they hold. Variations in the characterization of intense medical frames, for example, can both pull toward reduction to two fetuses and neutralize shame and guilt by seeming to remove personal responsibility for the decision. We conclude that the examination of frame combinations is an important tool for understanding the way women carrying multiple fetuses negotiate their way through multi-fetal pregnancies, and that it may have more general relevance for understanding pregnancy decisions in context.

Causes and Effects of Changes in Xylem Functionality in Apple Fruit

PubMed Central

DRAŽETA, LAZAR; LANG, ALEXANDER; HALL, ALISTAIR J.; VOLZ, RICHARD K.; JAMESON, PAULA E.

2004-01-01

• Background and Aims The xylem in fruit of a number of species becomes dysfunctional as the fruit develops, resulting in a reduction of xylem inflow to the fruit. Such a reduction may have consequential effects on the mineral balance of the fruit. The aim of this study was to elucidate the dynamics and nature of xylem failure in developing apples (Malus domestica) showing differing susceptibilities to bitter pit, a calcium‐related disorder. • Methods Developmental changes in xylem functionality of the fruit were investigated in ‘Braeburn’ and ‘Granny Smith’ apples by using a dye infusion technique, to stain the vasculature along the path of dye movement. The vascular bundles were clearly visible in transverse section when fruit were sectioned equatorially. The intensity of staining of the vascular bundles in the fruit was recorded at regular intervals throughout the season. Tissue containing dysfunctional bundles was fixed and embedded in wax for subsequent sectioning and examination. • Key Results As the season progressed, an increasing proportion of vascular bundles failed to show any staining, with the most marked change occurring in the primary bundles, and in nearly all bundles with increasing distance from the stalk end of the fruit. Decreased conductance in the primary bundles of ‘Braeburn’ occurred earlier than in ‘Granny Smith’. Microscopy revealed that the xylem in vascular bundles of the fruit suffered substantial damage, indicating that the mode of dysfunction was via the physical disruption of the xylem caused by expansion of the flesh. • Conclusions Results support the view that the relative calcium deficiency of apple fruit is due to a progressive breakdown of xylem conductance caused by growth‐induced damage to the xylem strand in the bundle. The earlier onset of xylem dysfunction in the cultivar more susceptible to bitter pit suggests that the relative growth dynamics of the fruit may control the occurrence of calcium‐related disorders. PMID:14988096

Role of the cyclooxygenase 2-thromboxane pathway in 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced decrease in mesencephalic vein blood flow in the zebrafish embryo

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

Teraoka, Hiroki; Kubota, Akira; Dong, Wu

2009-01-01

Previously, we reported that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) evoked developmental toxicity required activation of aryl hydrocarbon receptor type 2 (AHR2), using zebrafish embryos. However, the downstream molecular targets of AHR2 activation are largely unknown and are the focus of the present investigation. TCDD induces cyclooxygenase 2 (COX2), a rate-limiting enzyme for prostaglandin synthesis in certain cells. In the present study, we investigated the role of the COX2-thromboxane pathway in causing a specific endpoint of TCDD developmental toxicity in the zebrafish embryo, namely, a decrease in regional blood flow in the dorsal midbrain. It was found that the TCDD-induced reduction in mesencephalic veinmore » blood flow was markedly inhibited by selective COX2 inhibitors, NS-398 and SC-236, and by a general COX inhibitor, indomethacin, but not by a selective COX1 inhibitor, SC-560. Gene knock-down of COX2 by two different types of morpholino antisense oligonucleotides, but not by their negative homologs, also protected the zebrafish embryos from mesencephalic vein circulation failure caused by TCDD. This inhibitory effect of TCDD on regional blood flow in the dorsal midbrain was also blocked by selective antagonists of the thromboxane receptor (TP). Treatment of control zebrafish embryos with a TP agonist also caused a reduction in mesencephalic vein blood flow and it too was blocked by a TP antagonist, without any effect on trunk circulation. Finally, gene knock-down of thromboxane A synthase 1 (TBXS) with morpholinos but not by the morpholinos' negative homologs provided significant protection against TCDD-induced mesencephalic circulation failure. Taken together, these results point to a role of the prostanoid synthesis pathway via COX2-TBXS-TP in the local circulation failure induced by TCDD in the dorsal midbrain of the zebrafish embryo.« less

Using road markings as a continuous cue for speed choice.

PubMed

Charlton, Samuel G; Starkey, Nicola J; Malhotra, Neha

2018-08-01

The potential for using road markings to indicate speed limits was investigated in a driving simulator over the course of two sessions. Two types of experimental road markings, an "Attentional" set designed to provide visually distinct cues to indicate speed limits of 60, 80 and 100 km/h, and a "Perceptual" set designed to also affect drivers' perception of speed, were compared to a standard undifferentiated set of markings. Participants (n = 20 per group) were assigned to one of four experimental groups (Attentional-Explicit, Attentional-Implicit, Perceptual-Explicit, Perceptual-Implicit) or a Control group (n = 22; standard road markings). The Explicit groups were instructed about the meaning of the road markings while those in the Implicit and Control groups did not receive any explanation. Participants drove five 10 km simulated roads containing three speed zones (60, 80 and 100 km/h) during the first session. The participants returned to the laboratory approximately 3 days later to drive five more trials including roads they had not seen before, a trial that included a secondary task, and a trial where speed signs were removed and only markings were present. The findings indicated that both types of road markings improved drivers' compliance with speed limits compared to the control group, but that explicit instruction as to the meaning of the markings was needed to realise their full benefit. Although previous research has indicated the benefit of road markings used as warnings to indicate speed reductions in advance of horizontal or vertical curves, the findings of the present experiment also suggest that systematically associating road markings with specific speed limits may be a useful way to improve speed limit compliance and increase speed homogeneity. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Widespread Dependence of Backup NHEJ on Growth State: Ramifications for the Use of DNA-PK Inhibitors

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

Singh, Satyendra K.; Wu Wenqi; Zhang Lihua

2011-02-01

Purpose: The backup pathway of nonhomologous end joining (B-NHEJ) enables cells to process DNA double-strand breaks (DSBs) when the DNA-PK-dependent pathway of NHEJ (D-NHEJ) is compromised. Our previous results show marked reduction in the activity of B-NHEJ when LIG4{sup -/-} mouse embryo fibroblasts (MEFs) cease to grow and enter a plateau phase. The dependence of B-NHEJ on growth state is substantially stronger than that of D-NHEJ and points to regulatory mechanisms or processing determinants that require elucidation. Because the different D-NHEJ mutants show phenotypes distinct in their details, it is necessary to characterize the dependence of their DSB repair capacitymore » on growth state and to explore species-specific responses. Methods and Materials: DSB repair was measured in cells of different genetic background from various species using pulsed-field gel electrophoresis, or the formation of {gamma}-H2AX foci, at different stages of growth. Results: Using pulsed-field gel electrophoresis, we report a marked reduction of B-NHEJ during the plateau phase of growth in KU and XRCC4, mouse or Chinese hamster, mutants. Notably, this reduction is only marginal in DNA-PKcs-deficient cells. However, reduced B-NHEJ is also observed in repair proficient, plateau-phase cells after treatment with DNA-PK inhibitors. The reduction of B-NHEJ activity in the plateau phase of growth does not derive from the reduced expression of participating proteins, is detectable by {gamma}-H2AX foci analysis, and leads to enhanced cell killing. Conclusions: These results further document the marked dependence on growth state of an essential DSB repair pathway and show the general nature of the effect. Molecular characterization of the mechanism underlying this response will help to optimize the administration of DNA repair inhibitors as adjuvants in radiation therapy.« less

Coastal eutrophication thresholds: a matter of sediment microbial processes.

PubMed

Lehtoranta, Jouni; Ekholm, Petri; Pitkänen, Heikki

2009-09-01

In marine sediments, the major anaerobic mineralization processes are Fe(III) oxide reduction and sulfate reduction. In this article, we propose that the two alternative microbial mineralization pathways in sediments exert decisively different impacts on aquatic ecosystems. In systems where iron reduction dominates in the recently deposited sediment layers, the fraction of Fe(III) oxides that is dissolved to Fe(II) upon reduction will ultimately be transported to the oxic layer, where it will be reoxidized. Phosphorus, which is released from Fe(III) oxides and decomposing organic matter from the sediment, will be largely trapped by this newly formed Fe(III) oxide layer. Consequently, there are low concentrations of phosphorus in near-bottom and productive water layers and primary production tends to be limited by phosphorus (State 1). By contrast, in systems where sulfate reduction dominates, Fe(III) oxides are reduced by sulfides. This chemical reduction leads to the formation and permanent burial of iron as solid iron sulfides that are unable to capture phosphorus. In addition, the cycling of iron is blocked, and phosphorus is released to overlying water. Owing to the enrichment of phosphorus in water, the nitrogen : phosphorus ratio is lowered and nitrogen tends to limit algal growth, giving an advantage to nitrogen-fixing blue-green algae (State 2). A major factor causing a shift from State 1 to State 2 is an increase in the flux of labile organic carbon to the bottom sediments; upon accelerating eutrophication a critical point will be reached when the availability of Fe(III) oxides in sediments will be exhausted and sulfate reduction will become dominant. Because the reserves of Fe(III) oxides are replenished only slowly, reversal to State 1 may markedly exceed the time needed to reduce the flux of organic carbon to the sediment. A key factor affecting the sensitivity of a coastal system to such a regime shift is formed by the hydrodynamic alterations that decrease the transport of O2 to the near-bottom water, e.g., due to variations in salinity and temperature stratification.

Response of brown treesnakes to reduction of their rodent prey

USGS Publications Warehouse

Gragg, J.E.; Rodda, G.H.; Savidge, J.A.; White, Gary C.; Dean-Bradley, K.; Ellingson, A.R.

2007-01-01

Trapping brown treesnakes (Boiga irregularis; BTS) with live-mouse (Mus domesticus) lures is the principal control technique for this invasive species on Guam. Lure-based trapping is also used on other islands as a precaution against undetected arrivals and in response to verified BTS sightings. However, the effectiveness of lure-based trapping on other islands is questionable, as it has yielded no BTS despite other evidence of their presence. Some evidence suggests that high rodent numbers may interfere with BTS control. To test the relationship between rodent abundance and snake trappability, we conducted a controlled, replicated field experiment incorporating a rodenticide treatment during a BTS mark-recapture study. Using open population modeling in Program MARK, we estimated BTS apparent survival and recapture probabilities. Rodent reduction increased BTS recapture probabilities by 52-65% in 2002 and 22-36% in 2003, and it decreased apparent survival by <1% both years. This appears to be the first published instance of manipulating wild prey to influence snake behavior. Rodent reduction may enhance detection and control of BTS with traps on Guam and other islands. It may also amplify the effectiveness of oral toxicants against BTS.

[Pharmacological study of nicergoline. (III). Effects on cerebral and peripheral circulation in animals].

PubMed

Shintomi, K; Ogawa, Y; Yoshimoto, K; Narita, H

1986-05-01

Effects of nicergoline on the cerebral and peripheral circulation were compared with those of dihydroergotoxine (DHE) and papaverine (PAP) in anesthetized and/or immobilized cats. The i.a. injection of nicergoline (0.032 approximately 32 micrograms/kg), similarly to PAP, caused dose-dependent increases in intramaxillary artery (as the human intracarotid artery) blood flow (IMBF) and femoral artery blood flow, but the injection of DHE had no effect on these blood flows. The i.v. injection of nicergoline (32 approximately 128 micrograms/kg) caused a dose-dependent fall in blood pressure (BP) and a transient slight decrease in cerebral vascular resistance, but did not affect IMBF, regional cerebral blood flow (r-CBF), intracranial pressure (ICP) and heart rate (HR). The i.v. injection of DHE produced a slight fall in BP and a marked long-lasting decrease in HR, without affecting other parameters. The i.v. injection of PAP (4 mg/kg) induced marked increases in IMBF, r-CBF, ICP and HR and caused a transient fall followed by a marked elevation in BP. The p.o. administration of nicergoline (0.06 approximately 4 mg/kg) caused a dose-dependent fall in BP and selective inhibition of pressure response to adrenaline (ID50: 0.25 mg/kg). The administration of DHE produced marked inhibition of pressure responses to both adrenaline and noradrenaline, accompanied with a slight fall in BP. Furthermore, the administration of nicergoline (3 approximately 100 mg/kg) induced a dose-dependent fall in BP in SHR. These results suggest that the cerebral and peripheral circulatory effects of nicergoline may be due to direct vasodilating action and alpha-blocking action in the animals.

Adenosine A3 receptors regulate heart rate, motor activity and body temperature

PubMed Central

Yang, Jiangning; Wang, Yingqing; Garcia-Roves, Pablo; Björnholm, Marie; Fredholm, Bertil B.

2010-01-01

Aim We wanted to examine the phenotype of mice that lack the adenosine A3 receptor (A3R). Methods We examined the heart rate, body temperature and locomotion continuously by telemetry over several days. In addition the effect of the adenosine analogue R - N6- phenylisopropyl-adenosine (R-PIA) was examined. In addition, we examined heat production and food intake. Results We found that the marked diurnal variation in activity, heart rate and body temperature, with markedly higher values at night than during day time, was reduced in the A3R knockout mice. Surprisingly, the reduction in heart rate, activity and body temperature seen after injection of R-PIA in wild type mice was virtually eliminated in the A3R knock-out mice. The marked reduction in activity was associated with a decreased heat production, as expected. However, the A3R knock-out mice, surprisingly, had a higher food intake but no difference in body weight compared to wild type mice. Conclusions The mice lacking adenosine A3 receptors exhibit a surprisingly clear phenotype with changes in e.g. diurnal rhythm and temperature regulation. Whether these effects are due to a physiological role of A3 receptors in these processes or if they represent a role in development remains to be elucidated. PMID:20121716

SIRT2 Inhibition Confers Neuroprotection by Downregulation of FOXO3a and MAPK Signaling Pathways in Ischemic Stroke.

PubMed

She, David T; Wong, Lap Jack; Baik, Sang-Ha; Arumugam, Thiruma V

2018-04-14

Sirtuin 2 (SIRT2) is a family member of nicotinamide adenine dinucleotide (NAD + )-dependent deacetylases which appears to have detrimental roles in an array of neurological disorders such as Parkinson's disease (PD) and Huntington's disease (HD). In light of the recently emerging roles of sirtuins in normal physiology and pathological conditions such as ischemic stroke, we investigated the role of SIRT2 in ischemic stroke-induced neuronal cell death. Primary cortical neurons were subjected to oxygen-glucose deprivation (OGD) under in vitro ischemic conditions, and subsequently tested for the efficacy of SIRT2 inhibitors AK1 and AGK2 in attenuating apoptotic cell death caused by OGD. We have also evaluated the effect of SIRT2 inhibition in C57BL/6 mice subjected to 1 h middle cerebral artery occlusion (MCAO) followed by 24 h reperfusion, which is a model for ischemic reperfusion injury in vivo. Significant reductions in apoptotic cell death were noted in neurons treated with AK1 or AGK2, as evidenced by reduced cleaved caspase-3 and other apoptotic markers such as Bim and Bad. In addition, downregulation of phosphorylated-AKT and FOXO3a proteins of the AKT/FOXO3a pathway, as well as a marked reduction of JNK activity and its downstream target c-Jun, were also observed. When tested in animals subjected to MCAO, the neuroprotective effects of AGK2 in vivo were evidenced by a substantial reduction in ipsilateral infarct area and a significant improvement in neurological outcomes. A similar reduction in the levels of pro-apoptotic proteins in the infarct tissue, as well as downregulation of AKT/FOXO3a and JNK pathway, were also noted. In summary, the current study demonstrated the neuroprotective effects of SIRT2 inhibition in ischemic stroke, and identified the downregulation of AKT/FOXO3a and MAPK pathways as intermediary mechanisms which may contribute to the reduction in apoptotic cell death by SIRT2 inhibition.

Estimating parasitic sea lamprey abundance in Lake Huron from heterogenous data sources

USGS Publications Warehouse

Young, Robert J.; Jones, Michael L.; Bence, James R.; McDonald, Rodney B.; Mullett, Katherine M.; Bergstedt, Roger A.

2003-01-01

The Great Lakes Fishery Commission uses time series of transformer, parasitic, and spawning population estimates to evaluate the effectiveness of its sea lamprey (Petromyzon marinus) control program. This study used an inverse variance weighting method to integrate Lake Huron sea lamprey population estimates derived from two estimation procedures: 1) prediction of the lake-wide spawning population from a regression model based on stream size and, 2) whole-lake mark and recapture estimates. In addition, we used a re-sampling procedure to evaluate the effect of trading off sampling effort between the regression and mark-recapture models. Population estimates derived from the regression model ranged from 132,000 to 377,000 while mark-recapture estimates of marked recently metamorphosed juveniles and parasitic sea lampreys ranged from 536,000 to 634,000 and 484,000 to 1,608,000, respectively. The precision of the estimates varied greatly among estimation procedures and years. The integrated estimate of the mark-recapture and spawner regression procedures ranged from 252,000 to 702,000 transformers. The re-sampling procedure indicated that the regression model is more sensitive to reduction in sampling effort than the mark-recapture model. Reliance on either the regression or mark-recapture model alone could produce misleading estimates of abundance of sea lampreys and the effect of the control program on sea lamprey abundance. These analyses indicate that the precision of the lakewide population estimate can be maximized by re-allocating sampling effort from marking sea lampreys to trapping additional streams.

Molecular mechanisms of phoxim-induced silk gland damage and TiO2 nanoparticle-attenuated damage in Bombyx mori.

PubMed

Li, Bing; Yu, Xiaohong; Gui, Suxin; Xie, Yi; Zhao, Xiaoyang; Hong, Jie; Sun, Qingqing; Sang, Xuezi; Sheng, Lei; Cheng, Zhe; Cheng, Jie; Hu, Rengping; Wang, Ling; Shen, Weide; Hong, Fashui

2014-06-01

Phoxim is a useful organophosphate (OP) pesticide used in agriculture in China, however, exposure to this pesticide can result in a significant reduction in cocooning in Bombyx mori (B. mori). Titanium dioxide nanoparticles (TiO2 NPs) have been shown to decrease phoxim-induced toxicity in B. mori; however, very little is known about the molecular mechanisms of silk gland damage due to OP exposure and repair of gland damage by TiO2 NP pretreatment. In the present study, exposure to phoxim resulted in a significant reduction in cocooning rate in addition to silk gland damage, whereas TiO2 NP attenuated phoxim-induced gland damage, increased the antioxidant capacity of the gland, and increased cocooning rate in B. mori. Furthermore, digital gene expression data suggested that phoxim exposure led to significant alterations in the expression of 833 genes. In particular, phoxim exposure caused significant down-regulation of Fib-L, Ser2, Ser3, and P25 genes involved in silk protein synthesis, and up-regulation of SFGH, UCH3, and Salhh genes involved in silk protein hydrolysis. A combination of both phoxim and TiO2 NP treatment resulted in marked changes in the expression of 754 genes, while treatment with TiO2 NPs led to significant alterations in the expression of 308 genes. Importantly, pretreatment with TiO2 NPs increased Fib-L, Ser2, Ser3, and P25 expression, and decreased SFGH, UCH3, and Salhh expression in silk protein in the silk gland under phoxim stress. Therefore, Fib-L, Ser2, Ser3, P25, SFGH, UCH3, and Salhh may be potential biomarkers of silk gland toxicity in B. mori caused by phoxim exposure. Copyright © 2013 Elsevier Ltd. All rights reserved.

Integrated arc suppression unit for defect reduction in PVD applications

NASA Astrophysics Data System (ADS)

Li, Jason; Narasimhan, Murali K.; Pavate, Vikram; Loo, David; Rosenblum, Steve; Trubell, Larry; Scholl, Richard; Seamons, Scott; Hagerty, Chris; Ramaswami, Sesh

1997-09-01

Arcing between the target and plasma during PVD deposition causes substantial damage to the target and splats and other contamination on the deposited films. Arc-related damages and defects are frequently encountered in microelectronics manufacturing and contributes largely to reduced wafer yields. Arcing is caused largely by the charge buildup at the contaminated sites on the target surface that contains either nonconducting inclusions or nodules. Arc suppression is a key issue for defect reduction, yield improvement and for reliable high quality metallization. An Integrated Arc Suppression Unit (IASU) has been designed for Endura HP PVDTM sputtering sources. The integrated design reduces cable length from unit to source and reduces electrical energy stored in the cable. Active arc handling mode, proactive arc prevention mode, and passive by-pass arc counting mode are incorporated into the same unit. The active mode is designed to quickly respond to chamber conditions, like a large chamber voltage drop, that signals a arc. The self run mode is designed to proactively prevent arc formation by pulsing and reversing target voltage at 50 kHz. The design of the IASU, also called mini small package arc repression circuit--low energy unit (mini Sparc-le), has been optimized for various DC magnetron sources, plasma stability, chamber impedance, power matching, CE MARK test, and power dissipation. Process characterization with Ti, TiN and Al sputtering indicates that the unit has little adverse impact on film properties. Mini Sparc-le unit has been shown here to significantly reduce splats occurrence in Al sputtering. Marathon test of the unit with Ti/TiN test demonstrated the unit's reliability and its ability to reduce sensitivity of defects to target characteristics.

Involvement of CAT in the detoxification of HT-induced ROS burst in rice anther and its relation to pollen fertility.

PubMed

Zhao, Qian; Zhou, Lujian; Liu, Jianchao; Cao, Zhenzhen; Du, Xiaoxia; Huang, Fudeng; Pan, Gang; Cheng, Fangmin

2018-05-01

HT-induced ROS burst in developing anther is closely related to the lowered CAT activity as the result of the markedly suppressed OsCATB transcript, thereby causing severe fertility injury for rice plants exposed to HT at meiosis stage. The reproductive stage of rice plants is highly sensitive to heat stress. In this paper, different rice cultivars were used to investigate the relationship of HT-induced floret sterility with reactive oxygen species (ROS) detoxification in rice anthers under well-controlled climatic conditions. Results showed that high temperature (HT) exposure significantly enhanced the ROS level and malondialdehyde (MDA) content in developing anther, and the increase in ROS amount in rice anther under HT exposure was closely associated with HT-induced decline in the activities of several antioxidant enzymes. For various antioxidant enzymes, SOD and CAT were more susceptible to the ROS burst in rice anther induced by HT exposure than APX and POD, in which SOD and CAT activity in developing anther decreased significantly by HT exposure, whereas APX activity was relatively stable among different temperature regimes. HT-induced decrease in CAT activity was attributable to the suppressed transcript of OsCATB. This occurrence was strongly responsible for HT-induced increase in ROS level and oxidative-damage in rice anther, thereby it finally caused significant reduction in pollen viability and floret fertility for the rice plants exposed to HT during meiosis. Exogenous application of 1000 µM salicylic acid (SA) may alleviate HT-induced reduction in pollen viability and floret fertility, concomitantly with the increased CAT activity and reduced ROS level in rice anther.

Deoxynucleoside stress exacerbates the phenotype of a mouse model of mitochondrial neurogastrointestinal encephalopathy

PubMed Central

Garcia-Diaz, Beatriz; Garone, Caterina; Barca, Emanuele; Mojahed, Hamed; Gutierrez, Purification; Pizzorno, Giuseppe; Tanji, Kurenai; Arias-Mendoza, Fernando; Quinzii, Caterina M.

2014-01-01

Balanced pools of deoxyribonucleoside triphosphate precursors are required for DNA replication, and alterations of this balance are relevant to human mitochondrial diseases including mitochondrial neurogastrointestinal encephalopathy. In this disease, autosomal recessive TYMP mutations cause severe reductions of thymidine phosphorylase activity; marked elevations of the pyrimidine nucleosides thymidine and deoxyuridine in plasma and tissues, and somatic multiple deletions, depletion and site-specific point mutations of mitochondrial DNA. Thymidine phosphorylase and uridine phosphorylase double knockout mice recapitulated several features of these patients including thymidine phosphorylase activity deficiency, elevated thymidine and deoxyuridine in tissues, mitochondrial DNA depletion, respiratory chain defects and white matter changes. However, in contrast to patients with this disease, mutant mice showed mitochondrial alterations only in the brain. To test the hypothesis that elevated levels of nucleotides cause unbalanced deoxyribonucleoside triphosphate pools and, in turn, pathogenic mitochondrial DNA instability, we have stressed double knockout mice with exogenous thymidine and deoxyuridine, and assessed clinical, neuroradiological, histological, molecular, and biochemical consequences. Mutant mice treated with exogenous thymidine and deoxyuridine showed reduced survival, body weight, and muscle strength, relative to untreated animals. Moreover, in treated mutants, leukoencephalopathy, a hallmark of the disease, was enhanced and the small intestine showed a reduction of smooth muscle cells and increased fibrosis. Levels of mitochondrial DNA were depleted not only in the brain but also in the small intestine, and deoxyribonucleoside triphosphate imbalance was observed in the brain. The relative proportion, rather than the absolute amount of deoxyribonucleoside triphosphate, was critical for mitochondrial DNA maintenance. Thus, our results demonstrate that stress of exogenous pyrimidine nucleosides enhances the mitochondrial phenotype of our knockout mice. Our mouse studies provide insights into the pathogenic role of thymidine and deoxyuridine imbalance in mitochondrial neurogastrointestinal encephalopathy and an excellent model to study new therapeutic approaches. PMID:24727567

Structural and Mechanical Repair of Diffuse Damage in Cortical Bone in vivo

PubMed Central

Seref-Ferlengez, Zeynep; Basta-Pljakic, Jelena; Kennedy, Oran D.; Philemon, Claudy J.; Schaffler, Mitchell B.

2014-01-01

Physiological wear and tear causes bone microdamage at several hierarchical levels, and these have different biological consequences. Bone remodeling is widely held to be the mechanism by which bone microdamage is repaired. However, recent studies showed that unlike typical linear microcracks, small crack damage, the clusters of submicron-sized matrix cracks also known as diffuse damage (Dif.Dx), does not activate remodeling. Thus, the fate of diffuse damage in vivo is not known. To examine this, we induced selectively Dif.Dx in rat ulnae in vivo by using end-load ulnar bending creep model. Changes in damage content were assessed by histomorphometry and mechanical testing immediately after loading (i.e., acute loaded) or at 14 days after damage induction (i.e., survival ulnae). Dif.Dx area was markedly reduced over the 14-day survival period after loading (p<0.02). We did not observe any intracortical resorption and there was no increase in cortical bone area in survival ulnae. The reduction in whole bone stiffness in acute loaded ulnae was restored to baseline levels in survival ulnae (p>0.6). Microindentation studies showed that Dif.Dx caused a highly localized reduction in elastic modulus in diffuse damage regions of the ulnar cortex. Moduli in these previously damaged bone areas were restored to control values by 14 days after loading. Our current findings indicate that small crack damage in bone can be repaired without bone remodeling, and suggest that alternative repair mechanisms exist in bone to deal with submicron-sized matrix cracks. Those mechanisms are currently unknown and further investigations are needed to elucidate the mechanisms by which this direct repair occurs. PMID:25042459

Suppression of Rapidly Progressive Mouse Glomerulonephritis with the Non-Steroidal Mineralocorticoid Receptor Antagonist BR-4628.

PubMed

Ma, Frank Y; Han, Yingjie; Nikolic-Paterson, David J; Kolkhof, Peter; Tesch, Greg H

2015-01-01

Steroidal mineralocorticoid receptor antagonists (MRAs) are effective in the treatment of kidney disease; however, the side effect of hyperkalaemia, particularly in the context of renal impairment, is a major limitation to their clinical use. Recently developed non-steroidal MRAs have distinct characteristics suggesting that they may be superior to steroidal MRAs. Therefore, we explored the benefits of a non-steroidal MRA in a model of rapidly progressive glomerulonephritis. Accelerated anti-glomerular basement membrane (GBM) glomerulonephritis was induced in groups of C57BL/6J mice which received no treatment, vehicle or a non-steroidal MRA (BR-4628, 5mg/kg/bid) from day 0 until being killed on day 15 of disease. Mice were examined for renal injury. Mice with anti-GBM glomerulonephritis which received no treatment or vehicle developed similar disease with severe albuminuria, impaired renal function, glomerular tuft damage and crescents in 40% of glomeruli. In comparison, mice which received BR-4628 displayed similar albuminuria, but had improved renal function, reduced severity of glomerular tuft lesions and a 50% reduction in crescents. The protection seen in BR-4628 treated mice was associated with a marked reduction in glomerular macrophages and T-cells and reduced kidney gene expression of proinflammatory (CCL2, TNF-α, IFN-γ) and profibrotic molecules (collagen I, fibronectin). In addition, treatment with BR-4626 did not cause hyperkalaemia or increase urine Na+/K+ excretion (a marker of tubular dysfunction). The non-steroidal MRA (BR-4628) provided substantial suppression of mouse crescentic glomerulonephritis without causing tubular dysfunction. This finding warrants further investigation of non-steroidal MRAs as a therapy for inflammatory kidney diseases.

Effects of salicylic acid on thermotolerance and cardenolide accumulation under high temperature stress in Digitalis trojana Ivanina.

PubMed

Cingoz, Gunce Sahin; Gurel, Ekrem

2016-08-01

Long periods of high temperature or transitory increased temperature, a widespread agricultural problem, may lead to a drastic reduction in economic yield, affecting plant growth and development in many areas of the world. Heat stress causes many anatomical and physiological changes in plants. Its unfavorable effects can be alleviated by thermotolerance induced by exogenous application of plant growth regulators and osmoprotectants or by gradual application of temperature stress. Digitalis trojana Ivanina is an important medicinal plant species well known mainly for its cardenolides. The production of cardenolides via traditional agriculture is commercially inadequate. In this study, elicitation strategies were employed for improving crop thermotolerance and accumulation of cardenolides. For these purposes, the effects of salicylic acid (SA) and/or high temperature treatments in inducing cardenolide accumulation and thermotolerance were tested in callus cultures of D. trojana. Considerable increases in the production of cardenolides (up to 472.28 μg.g(-1) dry weight, dw) and induction of thermotolerance capacity were observed when callus cultures were exposed to high temperature for 2 h after pretreating with SA. High temperature treatments (2 h and 4 h) caused a marked reduction in superoxide dismutase (SOD; EC 1.15.1.1) and catalase (CAT; EC 1.11.1.6) activities, while SA pretreatment increased their activities. High temperature and/or SA appeared to increase the levels of proline, total phenolic, and flavonoid content. Elevated phenolic accumulation could be associated with increased stress protection. These results indicated that SA treatments induced synthesis of antioxidants and cardenolides, which may play a significant role in resistance to high temperature stress. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Survival of Mice with Gastrointestinal Acute Radiation Syndrome through Control of Bacterial Translocation.

PubMed

Suzuki, Fujio; Loucas, Bradford D; Ito, Ichiaki; Asai, Akira; Suzuki, Sumihiro; Kobayashi, Makiko

2018-07-01

Macrophages (Mϕ) with the M2b phenotype (Pheno2b-Mϕ) in bacterial translocation sites have been described as cells responsible for the increased susceptibility of mice with gastrointestinal acute radiation syndrome to sepsis caused by gut bacteria. In this study, we tried to reduce the mortality of mice exposed to 7-10 Gy of gamma rays by controlling Pheno2b-Mϕ polarization in bacterial translocation sites. MicroRNA-222 was induced in association with gamma irradiation. Pheno2b-Mϕ polarization was promoted and maintained in gamma-irradiated mice through the reduction of a long noncoding RNA growth arrest-specific transcript 5 (a CCL1 gene silencer) influenced by this microRNA. Therefore, the host resistance of 7-9-Gy gamma-irradiated mice to sepsis caused by bacterial translocation was improved after treatment with CCL1 antisense oligodeoxynucleotide. However, the mortality of 10-Gy gamma-irradiated mice was not alleviated by this treatment. The crypts and villi in the ileum of 10-Gy gamma-irradiated mice were severely damaged, but these were markedly improved after transplantation of intestinal lineage cells differentiated from murine embryonic stem cells. All 10-Gy gamma-irradiated mice given both of the oligodeoxynucleotide and intestinal lineage cells survived, whereas all of the same mice given either of them died. These results indicate that high mortality rates of mice irradiated with 7-10 Gy of gamma rays are reducible by depleting CCL1 in combination with the intestinal lineage cell transplantation. These findings support the novel therapeutic possibility of victims who have gastrointestinal acute radiation syndrome for the reduction of their high mortality rates. Copyright © 2018 by The American Association of Immunologists, Inc.

Sea level during the Phanerozoic - what causes the fluctuations

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

Harrison, C.G.A.

1985-01-01

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

Pharmacodynamic and pharmacokinetic effects of TPA023, a GABA(A) alpha(2,3) subtype-selective agonist, compared to lorazepam and placebo in healthy volunteers.

PubMed

de Haas, S L; de Visser, S J; van der Post, J P; de Smet, M; Schoemaker, R C; Rijnbeek, B; Cohen, A F; Vega, J M; Agrawal, N G B; Goel, T V; Simpson, R C; Pearson, L K; Li, S; Hesney, M; Murphy, M G; van Gerven, J M A

2007-06-01

TPA023, a GABA(A) alpha2,3 alphasubtype-selective partial agonist, is expected to have comparable anxiolytic efficacy as benzodiazepines with reduced sedating effects. The compound lacks efficacy at the alpha1 subtype, which is believed to mediate these effects. This study investigated the effects of 0.5 and 1.5 mg TPA023 and compared them with placebo and lorazepam 2 mg (therapeutic anxiolytic dose). Twelve healthy male volunteers participated in this placebo-controlled, double-blind, double-dummy, four-way, cross-over study. Saccadic eye movements and visual analogue scales (VAS) were used to assess the sedative properties of TPA023. The effects on posturaL stability and cognition were assessed using body sway and a standardized battery of neurophysiological memory tests. Lorazepam caused a significant reduction in saccadic peak velocity, the VAS alertness score and impairment of memory and body sway. TPA023 had significant dose dependent effects on saccadic peak velocity (85 deg/sec maximum reduction at the higher dose) that approximated the effects of lorazepam. In contrast to lorazepam, TPA023 had no detectabLe effects on saccadic latency or inaccuracy. Also unlike lorazepam, TPA023 did not affect VAS alertness, memory or body sway. These results show that the effect profile of TPA023 differs markedly from that of lorazepam, at doses that were equipotent with regard to effects on saccadic peak veLocity. Contrary to lorazepam, TPA023 caused no detectable memory impairment or postural imbalance. These differences reflect the selectivity of TPA023 for different GABA(A) receptor subtypes.

2,3,4,7,8-Pentachlorodibenzofuran is far less potent than 2,3,7,8-tetrachlorodibenzo-p-dioxin in disrupting the pituitary–gonad axis of the rat fetus

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

Taura, Junki; Takeda, Tomoki; Fujii, Misaki

The effect of 2,3,4,7,8-pentachlorodibenzofuran (PnCDF) on the fetal pituitary–gonad axis was compared with that produced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in Wistar rats. Maternal treatment at gestational day (GD) 15 with PnCDF and TCDD reduced the fetal expression at GD20 of pituitary luteinizing hormone (LH) and the testicular proteins necessary for steroidogenesis. The relative potencies of PnCDF ranged from 1/42nd to 1/63rd of the TCDD effect. While PnCDF, at a dose sufficient to cause a reduction in fetal LH, provoked defects in sexual behavior at adulthood, a dose less than the ED{sub 50} failed to produce any abnormality. There was a lossmore » of fetal body weight following in utero exposure to PnCDF, and the effect of PnCDF was also much less than that of TCDD. The disturbance in fetal growth was suggested to be due to a reduction in the level of fetal growth hormone (GH) by dioxins. The disorder caused by PnCDF/TCDD in the fetal pituitary–gonad axis occurred at doses less than those needed to cause wasting syndrome in pubertal rats. The harmful effect of PnCDF relative to TCDD was more pronounced in fetal rats than in pubertal rats. These lines of evidence suggest that: 1) PnCDF as well as TCDD imprints defects in sexual behavior by disrupting the fetal pituitary–gonad axis; 2) these dioxins hinder fetal growth by reducing the expression of fetal GH; and 3) the fetal effects of PnCDF/TCDD are more sensitive than sub-acute toxicity during puberty, and the relative effect of PnCDF varies markedly depending on the indices used. - Highlights: • 2,3,4,7,8-Pentachlorodibenzofuran (PnCDF) lowers gonadal steroidogenesis in fetuses. • PnCDF exerts the above effect through an initial attenuation in gonadotropin level. • PnCDF imprints sexual immaturity by transiently disrupting the pituitary–gonad axis. • PnCDF also disturbs pup growth probably due to a reduction in growth hormone level. • The above effects are far lesser in PnCDF than 2,3,7,8-tetrachlorodibenzo-p-dioxin.« less

Foraging behavior of Anastrepha Ludens, A. obliqua, and A. serpentina in response to feces extracts containing host marking pheromone.

PubMed

Aluja, Martin; Díaz-Fleischer, Francisco

2006-02-01

Following oviposition, females of many Tephritid flies deposit host marking pheromones (HMPs) to indicate that the host fruit has been occupied. We describe the foraging behavior of these three economically important species (Anastrepha ludens and A. obliqua from the fraterculus species group and A. serpentina from the serpentina species group) when they encounter an artificial fruit (green agar spheres wrapped in Parafilm) marked with intra- and interspecific feces extracts that contain, among other substances, host marking pheromone. When flies encountered fruit treated with either 1 or 100 mg/ml feces extract, there were drastic and statistically significant reductions in tree residence time, mean time spent on fruit, and in the number of oviposition attempts or actual ovipositions when compared to the control treatment (clean fruit). These responses were almost identical irrespective of extract origin (i.e., fly species), indicating complete interspecific HMP cross-recognition by all three Anastrepha species tested. We discuss the ecological and practical implications of our findings.

Specimen Orientation by Marking the Peripheral End: (Potential) Clinical Advantages in Prostate Biopsy

PubMed Central

Galosi, Andrea Benedetto; Muzzonigro, Giovanni; Lacetera, Vito; Mazzucchelli, Roberta

2011-01-01

The aim of this paper is to identify advantages that could be obtained by orientation of the biopsy specimen using the marking technique. We reviewed our experience (4,500 cases) and the published literature. The peripheral (proximal) end of the fresh specimen is marked with ink soon after needle delivering in a few minutes. It is performed easily in association with pre-embedding method. Five potential clinical advantages were identified: (1) tumor localization, (2) atypical lesions localization and planning rebiopsy strategy, (3) planning surgical strategy, (4) selection criteria for focal therapy and active surveillance, and (5) cost reduction. Peripheral end marking is low cost, easy and reproducible. It drives several potential advantages in cancer diagnosis or isolated atypical lesions, in particular, spatial localization within the biopsy (transition versus peripheral zone, anterior versus posterior, subcapsular versus intraparenchima, and extraprostatic extension) should be easy and reliable. We can add a new pathological parameter: pathological orientation or biopsy polarity. PMID:22096654

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.

The cytoskeletal inhibitors latrunculin A and blebbistatin exert antitumorigenic properties in human hepatocellular carcinoma cells by interfering with intracellular HuR trafficking

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

Doller, Anke; Badawi, Amel; Schmid, Tobias

The impact of the RNA-binding protein HuR for the post-transcriptional deregulation of tumor-relevant genes is well established. Despite of elevations in HuR expression levels, an increase in cytoplasmic HuR abundance in many cases correlates with a high grade of malignancy. Here, we demonstrated that administration of the actin-depolymerizing macrolide latrunculin A, or blebbistatin, an inhibitor of myosin II ATPase activity, caused a dose- and time-dependent reduction in the high cytoplasmic HuR content of HepG2 and Huh7 hepatocellular carcinoma (HCC) cells. Subcellular fractionation revealed that in addition, both inhibitors strongly attenuated cytoskeletal and membrane-bound HuR abundance and conversely increased the HuRmore » amount in nuclear cell fractions. Concomitant with changes in intracellular HuR localization, both cytoskeletal inhibitors markedly decreased the half-lives of cyclooxygenase-2 (COX-2), cyclin A and cyclin D{sub 1} encoding mRNAs resulting in a significant reduction in their expression levels in HepG2 cells. Importantly, a similar reduction in the expression of these HuR targets was achieved by a RNA interference (RNAi)-mediated knockdown of either HuR or nonmuscle myoin IIA. Using polysomal fractionation, we further demonstrate that the decrease in cytoplasmic HuR by latrunculin A or blebbistatin is accompanied by a marked change in the allocation of HuR and its mRNA cargo from polysomes to ribonucleoprotein (RNP) particles. Functionally, the basal migration and prostaglandin E{sub 2} synthesis are similarly impaired in inhibitor-treated and stable HuR-knockdown HepG2 cells. Our data demonstrate that interfering with the actomyosin-dependent HuR trafficking may comprise a valid therapeutic option for antagonizing pathologic posttranscriptional gene expression by HuR and furthermore emphasize the potential benefit of HuR inhibitory strategies for treatment of HCC. - Highlights: • We tested the effects of latrunculin A and blebbistatin on different HuR activities. • Both cytoskeletal inhibitors disturbed the RNP-polysome HuR allocation in HepG2 cells. • Accordingly, both inhibitors reduced the stability and levels of HuR controlled mRNAs. • Functionally, important HuR-triggered cell functions were impaired by both compounds. • Targeting of HuR trafficking implies a useful approach for novel antitumor therapy.« less

The effect of infection order of porcine circovirus type 2 and porcine reproductive and respiratory syndrome virus on dually infected swine alveolar macrophages

PubMed Central

2012-01-01

Background Concurrent infection with porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) is known as one of the major causes for porcine respiratory disease complex (PRDC). Dual infection with PCV2 and PRRSV is consistently to have more severe clinical presentations and pulmonary lesions than infection with PCV2 alone or PRRSV alone. However, it is not known if dual infections with PCV2 and PRRSV in different infection order may lead to different clinical symptoms in the host. To mimic the possible field conditions, swine alveolar macrophages (AMs) were inoculated with PCV2 and PRRSV in vitro simultaneously or with one virus 18 h earlier than the other. The cell viability, cytopathic effects, antigen-containing rates, phagocytotic and microbial killing capabilities, cytokine profiles (IL-8, TNF-α, and IFN-α) and FasL transcripts were determined, analyzed, and compared to prove the hypothesis. Results A marked reduction in PRRSV antigen-containing rate, cytopathic effect, and TNF-α expression level was revealed in AMs inoculated with PCV2 and PRRSV simultaneously and in AMs inoculated with PCV2 first then PRRSV 18 h later, but not in AMs inoculated with PRRSV first then PCV2 18 h later. Transient decrease in phagocytosis but constant reduction in microbicidal capability in AMs in the group inoculated with PCV2 alone and constant decrease in phagocytosis and microbicidal capability in AMs in all PRRSV-inoculated groups were noted. The levels of IL-8, TNF-α, IFN-α, and FasL transcripts in AMs in all groups with dual inoculation of PCV2 and PRRSV were significantly increased regardless of the infection orders as compared with infection by PCV2 alone or PRRSV alone. Conclusions Swine AMs infected with PCV2 first then PRRSV later or infected with PCV2 and PRRSV simultaneously displayed marked reduction in PRRSV antigen-containing rate, cytopathic effect, and TNF-α expression level. The different inoculation orders of PCV2 and PRRSV in AMs leading to different results in viral antigen positivity, cytopathology, and cytokine profile may explain, at least partially, the underlying mechanism of the enhanced pulmonary lesions in PRDC exerted by dual infection with PCV2 and PRRSV and the variable clinical manifestations of PRDC-affected pigs in the field. PMID:23009687

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.

Cause-specific mortality in professional flight crew and air traffic control officers: findings from two UK population-based cohorts of over 20,000 subjects.

PubMed

De Stavola, Bianca L; Pizzi, Costanza; Clemens, Felicity; Evans, Sally Ann; Evans, Anthony D; dos Santos Silva, Isabel

2012-04-01

Flight crew are exposed to several potential occupational hazards. This study compares mortality rates in UK flight crew to those in air traffic control officers (ATCOs) and the general population. A total of 19,489 flight crew and ATCOs were identified from the UK Civil Aviation Authority medical records and followed to the end of 2006. Consented access to medical records and questionnaire data provided information on demographic, behavioral, clinical, and occupational variables. Standardized mortality ratios (SMR) were estimated for these two occupational groups using the UK general population. Adjusted mortality hazard ratios (HR) for flight crew versus ATCOs were estimated via Cox regression models. A total of 577 deaths occurred during follow-up. Relative to the general population, both flight crew (SMR 0.32; 95% CI 0.30, 0.35) and ATCOs (0.39; 0.32, 0.47) had lower all-cause mortality, mainly due to marked reductions in mortality from neoplasms and cardiovascular diseases, although flight crew had higher mortality from aircraft accidents (SMR 42.8; 27.9, 65.6). There were no differences in all-cause mortality (HR 0.99; 95% CI 0.79, 1.25), or in mortality from any major cause, between the two occupational groups after adjustment for health-related variables, again except for those from aircraft accidents. The latter ratios, however, declined with increasing number of hours. The low all-cause mortality observed in both occupational groups relative to the general population is consistent with a strong "healthy worker effect" and their low prevalence of smoking and other risk factors. Mortality among flight crew did not appear to be influenced by occupational exposures, except for a rise in mortality from aircraft accidents.

Banking crises and mortality during the Great Depression: evidence from US urban populations, 1929-1937.

PubMed

Stuckler, David; Meissner, Christopher; Fishback, Price; Basu, Sanjay; McKee, Martin

2012-05-01

Previous research suggests that the Great Depression led to improvements in public health. However, these studies rely on highly aggregated national data (using fewer than 25 data points) and potentially biased measures of the Great Depression. The authors assess the effects of the Great Depression using city-level estimates of US mortality and an underlying measure of economic crisis, bank suspensions, at the state level. Cause-specific mortalities covering 114 US cities in 36 states between 1929 and 1937 were regressed against bank suspensions and income data from the Federal Deposit Insurance Corporation Database, using dynamic fixed-effects models and adjustments for potential confounding variables. Reductions in all-cause mortalities were mainly attributable to declines in death rates owing to pneumonia (26.4% of total), flu (13.1% of total) and respiratory tuberculosis (11.2% of total), while death rates increased from heart disease (19.4% of total), cancer (8.1% of total) and diabetes (2.9%). Only heart disease can plausibly relate to the contemporaneous economic shocks. The authors found that a higher rate of bank suspensions was significantly associated with higher suicide rates (β=0.32, 95% CI 0.24 to 0.41) but lower death rates from motor-vehicle accidents (β=-0.18, 95% CI -0.29 to -0.07); no significant effects were observed for 30 other causes of death or with a time lag. In contrast with existing research, the authors find that many of the changes in deaths from different causes during the Great Depression were unrelated to economic shocks. Further research is needed to understand the causes of the marked variations in mortality change across cities and states, including the effects of the New Deal and Prohibition.

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...

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.

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.

Effects of Laparoscopic Sleeve Gastrectomy on Central Obesity and Metabolic Syndrome in Indian Adults- A Prospective Study

PubMed Central

Thillai, Manoj; Nain, Prabhdeep Singh; Ahuja, Ashish; Vayoth, Sudheer Othiyil; Khurana, Preetika

2017-01-01

Introduction Increasing incidence of obesity in Indian population has led to an exponential rise in the number of bariatric operations performed annually. Laparoscopic Sleeve Gastrectomy (LSG) has been proposed to cause rapid remission of Type 2 Diabetes Melitus (T2DM) and metabolic syndrome in a weight loss independent manner. Aim To evaluate the effects of LSG on metabolic syndrome and central obesity in morbidly and severely obese Indian adults. Material and Methods: Study was conducted on 91 morbidly obese [Body Mass Index (BMI)>40 kg/m2] and severely obese (BMI>35 kg/m2) individuals who were suffering from diabetes, hypertension or dyslipidemia. The patients were followed up for six months and the trends of glycaemic control, mean blood pressure, lipid profile, weight loss parameters and changes in parameters of central obesity were studied. Results Weight loss was significant at three months postsurgery and was sustained through six months. There was significant improvement in glycaemic control leading to reduction in need for oral hypoglycaemic agents or insulin in majority of them and even discontinuation of these medications in few patients. Hypertension and dyslipidemia also showed an improving trend through six months postsurgery. There was a significant impact on reduction of central obesity in these patients as marked by significant reduction in waist to hip ratio. Conclusion LSG produces sustainable weight loss with significant improvement in glycaemic status and control of metabolic syndrome in severe to morbidly obese patients. LSG is also efficacious in reducing central obesity in Indian population which is a major depressive ailment amongst obese individuals. PMID:28273998

Effects of Laparoscopic Sleeve Gastrectomy on Central Obesity and Metabolic Syndrome in Indian Adults- A Prospective Study.

PubMed

Sethi, Pulkit; Thillai, Manoj; Nain, Prabhdeep Singh; Ahuja, Ashish; Vayoth, Sudheer Othiyil; Khurana, Preetika

2017-01-01

Increasing incidence of obesity in Indian population has led to an exponential rise in the number of bariatric operations performed annually. Laparoscopic Sleeve Gastrectomy (LSG) has been proposed to cause rapid remission of Type 2 Diabetes Melitus (T2DM) and metabolic syndrome in a weight loss independent manner. To evaluate the effects of LSG on metabolic syndrome and central obesity in morbidly and severely obese Indian adults. Material and Methods: Study was conducted on 91 morbidly obese [Body Mass Index (BMI)>40 kg/m 2 ] and severely obese (BMI>35 kg/m 2 ) individuals who were suffering from diabetes, hypertension or dyslipidemia. The patients were followed up for six months and the trends of glycaemic control, mean blood pressure, lipid profile, weight loss parameters and changes in parameters of central obesity were studied. Weight loss was significant at three months postsurgery and was sustained through six months. There was significant improvement in glycaemic control leading to reduction in need for oral hypoglycaemic agents or insulin in majority of them and even discontinuation of these medications in few patients. Hypertension and dyslipidemia also showed an improving trend through six months postsurgery. There was a significant impact on reduction of central obesity in these patients as marked by significant reduction in waist to hip ratio. LSG produces sustainable weight loss with significant improvement in glycaemic status and control of metabolic syndrome in severe to morbidly obese patients. LSG is also efficacious in reducing central obesity in Indian population which is a major depressive ailment amongst obese individuals.

Responses of female rock lizards to multiple scent marks of males: effects of male age, male density and scent over-marking.

PubMed

Martín, José; López, Pilar

2013-03-01

Scent-marked substrates may inform conspecifics on the characteristics of territorial males. Scent-marks of male Carpetan rock lizards (Iberolacerta cyreni) affect space use of females, which by selecting an area may increase the probability of mating with the male that has scent-marked that area. However, males do not hold exclusive territories, and scent-marks of different individual males are often together. This may provide complex information from multiple sources on the social structure. Here, we examined female preference in response to scent marks of various males and combinations in a laboratory experiment. Females preferred areas scent-marked by territorial old males against those scent-marked by young satellite-sneaker males. This reflected the known preference of females for mating with old males. In a second experiment, females preferred areas scent-marked by two males to areas of similar size marked by a single male. This may increase the probability of obtaining multiple copulations with different males, which may favour sperm competition and cryptic female choice, or may be a way to avoid infertile males. Finally, when we experimentally over-marked the scent-marks of an old male with scent-marks of a young male, females did not avoid, nor prefer, the over-marked area, suggesting that the quality of the old male may override the presence of a satellite male. We suggest that, irrespective of the causes underlying why a female selects a scent-marked area, this strategy may affect her reproductive success, which may have the same evolutionary consequences that "direct" mate choice decisions of other animals. Copyright © 2013 Elsevier B.V. All rights reserved.

Lights and siren: a review of emergency vehicle warning systems.

PubMed

De Lorenzo, R A; Eilers, M A

1991-12-01

Emergency medical services providers routinely respond to emergencies using lights and siren. This practice is not without risk of collision. Audible and visual warning devices and vehicle markings are integral to efficient negotiation of traffic and reduction of collision risk. An understanding of warning system characteristics is necessary to implement appropriate guidelines for prehospital transportation systems. The pertinent literature on emergency vehicle warning systems is reviewed, with emphasis on potential health hazards associated with these techniques. Important findings inferred from the literature are 1) red flashing lights alone may not be as effective as other color combinations, 2) there are no data to support a seizure risk with strobe lights, 3) lime-yellow is probably superior to traditional emergency vehicle colors, 4) the siren is an extremely limited warning device, and 5) exposure to siren noise can cause hearing loss. Emergency physicians must ensure that emergency medical services transportation systems consider the pertinent literature on emergency vehicle warning systems.

Likelihood testing of seismicity-based rate forecasts of induced earthquakes in Oklahoma and Kansas

USGS Publications Warehouse

Moschetti, Morgan P.; Hoover, Susan M.; Mueller, Charles

2016-01-01

Likelihood testing of induced earthquakes in Oklahoma and Kansas has identified the parameters that optimize the forecasting ability of smoothed seismicity models and quantified the recent temporal stability of the spatial seismicity patterns. Use of the most recent 1-year period of earthquake data and use of 10–20-km smoothing distances produced the greatest likelihood. The likelihood that the locations of January–June 2015 earthquakes were consistent with optimized forecasts decayed with increasing elapsed time between the catalogs used for model development and testing. Likelihood tests with two additional sets of earthquakes from 2014 exhibit a strong sensitivity of the rate of decay to the smoothing distance. Marked reductions in likelihood are caused by the nonstationarity of the induced earthquake locations. Our results indicate a multiple-fold benefit from smoothed seismicity models in developing short-term earthquake rate forecasts for induced earthquakes in Oklahoma and Kansas, relative to the use of seismic source zones.

Effect of a pre-treatment of milk with high pressure homogenization on yield as well as on microbiological, lipolytic and proteolytic patterns of "Pecorino" cheese.

PubMed

Vannini, Lucia; Patrignani, Francesca; Iucci, Luciana; Ndagijimana, Maurice; Vallicelli, Melania; Lanciotti, Rosalba; Guerzoni, Maria Elisabetta

2008-12-10

The principal aim of this work was to compare Pecorino cheeses obtained from ewes' milk previously subjected to high pressure homogenization (HPH) at 100 MPa with those produced from raw and heat treated ewes' milk. The HPH milk treatment induced a significant increase of the cheese yield and caused a reduction of enterococci, lactococci and yeasts in the curds. Enterococci cell loads remained at lower levels in cheeses obtained from HPH milk over the ripening period. Analyses of free fatty acids, Sodium Dodecil Sulphate (SDS)-PAGE profiles, Gas Chromatography-Mass Spectrometry-Solid Phase Microextraction (GC-MS-SPME) measurements of volatile compounds and sensory traits evidenced that the pressure treatment can be regarded also as a useful tool to differentiate products obtained from the same raw material. In fact such a milk treatment induced a marked lipolysis, an early proteolysis, a relevant modification of the volatile molecule profiles and sensory properties of Pecorino cheese.

Discovery of a novel glucose metabolism in cancer: The role of endoplasmic reticulum beyond glycolysis and pentose phosphate shunt

PubMed Central

Marini, Cecilia; Ravera, Silvia; Buschiazzo, Ambra; Bianchi, Giovanna; Orengo, Anna Maria; Bruno, Silvia; Bottoni, Gianluca; Emionite, Laura; Pastorino, Fabio; Monteverde, Elena; Garaboldi, Lucia; Martella, Roberto; Salani, Barbara; Maggi, Davide; Ponzoni, Mirco; Fais, Franco; Raffaghello, Lizzia; Sambuceti, Gianmario

2016-01-01

Cancer metabolism is characterized by an accelerated glycolytic rate facing reduced activity of oxidative phosphorylation. This “Warburg effect” represents a standard to diagnose and monitor tumor aggressiveness with 18F-fluorodeoxyglucose whose uptake is currently regarded as an accurate index of total glucose consumption. Studying cancer metabolic response to respiratory chain inhibition by metformin, we repeatedly observed a reduction of tracer uptake facing a marked increase in glucose consumption. This puzzling discordance brought us to discover that 18F-fluorodeoxyglucose preferentially accumulates within endoplasmic reticulum by exploiting the catalytic function of hexose-6-phosphate-dehydrogenase. Silencing enzyme expression and activity decreased both tracer uptake and glucose consumption, caused severe energy depletion and decreased NADPH content without altering mitochondrial function. These data document the existence of an unknown glucose metabolism triggered by hexose-6-phosphate-dehydrogenase within endoplasmic reticulum of cancer cells. Besides its basic relevance, this finding can improve clinical cancer diagnosis and might represent potential target for therapy. PMID:27121192

Adverse effects of the anabolic steroid, boldenone undecylenate, on reproductive functions of male rabbits

PubMed Central

Oda, Samah S; El-Ashmawy, Ibrahim M

2012-01-01

Summary This study was conducted to evaluate the adverse effects of the anabolic steroid, boldenone undecylenate (BOL) on reproductive functions of male rabbits. Thirty white New Zealand mature male rabbits were divided into three groups (10 rabbits each). Group A rabbits served as a control group. Group B rabbits received 4.4 mg/kg body weight (bwt) BOL 5% oily solution. Group C rabbits received 8.8 mg/kg bwt BOL. Rabbits were injected intramuscularly twice weekly for two months. BOL had no significant effect on the bwt and bwt gain. Testes and epididymis weights were decreased significantly in the BOL-treated groups. BOL caused significant reduction in serum testosterone level, seminal volume, sperm motility, and sperm count. No abnormalities were detected in the sperm morphology of the BOL-treated groups. Histopathological alterations in the testes and epididymis were marked in the group C rabbits. These results indicate that administration of BOL exerts a significant harmful effect on the reproductive functions of male rabbits. PMID:22583130

Hydroxyl-HIF2-alpha is potential therapeutic target for renal cell carcinomas

PubMed Central

Isono, Takahiro; Chano, Tokuhiro; Yoshida, Tetsuya; Kageyama, Susumu; Kawauchi, Akihiro; Suzaki, Masafumi; Yuasa, Takeshi

2016-01-01

Dormant cancer cells are deprivation-resistant, and cause a number of problems for therapeutic approaches for cancers. Renal cell carcinomas (RCCs) include deprivation-resistant cells that are resistant to various treatments. In this study, the specific characteristics of deprivation-resistant cells were transcriptionally identified by next generation sequencing. The hypoxia-inducible factors (HIF) transcription factor network was significantly enhanced in deprivation-resistant RCCs compared to the sensitive RCCs. Deprivation-resistant RCCs, that had lost Von Hippel-Lindau tumor suppressor expression, expressed hydroxyl-HIF2-alpha in the nucleus, but not sensitive-RCCs. Hydroxyl-HIF-alpha was also expressed in nuclei of RCC tissue samples. Knockdown for HIF2-alpha, but not HIF1-alpha, induced cell death related to a reduction in HIF-related gene expression in deprivation-resistant RCC cells. Chetomin, a nuclear HIF-inhibitor, induced marked level of cytotoxicity in deprivation-resistant cells, similar to the knockdown of HIF2-alpha. Therefore, hydroxyl-HIF2-alpha might be a potential therapeutic target for RCCs. PMID:27822416

Influence of processing on the allergenic properties of pistachio nut assessed in vitro.

PubMed

Noorbakhsh, Reihaneh; Mortazavi, Seyed Ali; Sankian, Mojtaba; Shahidi, Fakhri; Maleki, Soheila J; Nasiraii, Leila Roozbeh; Falak, Reza; Sima, Hamid Reza; Varasteh, AbdolReza

2010-09-22

Pistachio (Pistacia vera) is a tree nut that has been reported to cause IgE-mediated allergic reactions. This study was undertaken to investigate the distinctions between different cultivars of pistachio nut and the influence of different processing on the IgE-binding capacity of whole pistachio protein extracts. The influence of different processes on allergenicity was investigated using competitive inhibition ELISA and Western blotting assays. The Western blotting results of extracts from pistachio cultivars showed no marked difference among them. The IgE-binding capacity was significantly lower for the protein extract prepared from steam-roasted than from raw and dry-roasted pistachio nuts. The results of sensory evaluation analysis and hedonic rating proved no significant differences in color, taste, flavor, and overall quality of raw, roasted, and steam-roasted pistachio nut treatments. The most significant finding of the present study was the successful reduction of IgE-binding by pistachio extracts using steam-roast processing without any significant changes in sensory quality of product.

Rifaximin, gut microbes and mucosal inflammation: unraveling a complex relationship

PubMed Central

Gao, Jun; Gillilland, Merritt G; Owyang, Chung

2018-01-01

Rifaximin is a non-systemic, broad-spectrum antibiotic that acts against gram-positive, gram-negative, and anaerobic bacteria. Clinical studies indicate that rifaximin is beneficial in treating irritable bowel syndrome (IBS). The mechanism responsible for the beneficial effects of rifaximin is not clear. In a recent study, we reported that rifaximin alters the bacterial population in the ileum of rats, leading to a relative abundance of Lactobacillus species. These changes prevent gut inflammation and visceral hyperalgesia caused by chronic stress. To more closely mirror human clinical studies in which rifaximin is used to treat IBS symptoms, we performed additional studies and showed that rifaximin reversed mucosal inflammation and barrier dysfunction evoked by chronic stress. These beneficial effects were accompanied by a striking increase in the abundance of Lactobacillaceae and a marked reduction in the number of segmented filamentous bacteria after rifaximin treatment. These microbial changes may contribute to the antiinflammatory effects of rifaximin on the intestinal mucosa. PMID:25244596

Ring current impoundment of the Io plasma torus

NASA Technical Reports Server (NTRS)

Siscoe, G. L.; Thorne, R. M.; Richardson, J. D.; Bagenal, F.; Sullivan, J. D.; Eviatar, A.

1981-01-01

A newly discovered feature in the Io plasma formation that may be described as a ramp separating a high-density plasma ledge on its Jupiterward side from the lower-density radially distended Io plasma disc on its anti-Jupiterward side is observed to coincide with a marked inward decrease in the ring current population. The spatial congruency of the counter-directed maximal gradients in both plasma bodies reveals a profound coupling between them. The existence of the ramp requires a local order-of-magnitude reduction in the diffusion coefficient that governs radial mass transport. It is demonstrated that the diminished diffusive efficiency there is caused by strong pressure gradient inhibition of the interchange instability that underlies mass transport. The Io plasma torus, which is defined as the region of strong ultraviolet emissions, is identified as the plasma ledge. The plasma density in the ledge is high and, incidentally therefore, able to emit strongly because it is impounded against rapid, centrifugal expulsion by the inwardly directed pressure of the ring current at its inner edge.

Repetition priming influences distinct brain systems: evidence from task-evoked data and resting-state correlations.

PubMed

Wig, Gagan S; Buckner, Randy L; Schacter, Daniel L

2009-05-01

Behavioral dissociations suggest that a single experience can separately influence multiple processing components. Here we used a repetition priming functional magnetic resonance imaging paradigm that directly contrasted the effects of stimulus and decision changes to identify the underlying brain systems. Direct repetition of stimulus features caused marked reductions in posterior regions of the inferior temporal lobe that were insensitive to whether the decision was held constant or changed between study and test. By contrast, prefrontal cortex showed repetition effects that were sensitive to the exact stimulus-to-decision mapping. Analysis of resting-state functional connectivity revealed that the dissociated repetition effects are embedded within distinct brain systems. Regions that were sensitive to changes in the stimulus correlated with perceptual cortices, whereas the decision changes attenuated activity in regions correlated with middle-temporal regions and a frontoparietal control system. These results thus explain the long-known dissociation between perceptual and conceptual components of priming by revealing how a single experience can separately influence distinct, concurrently active brain systems.

Protective effects of platinum nanoparticles against UV-light-induced epidermal inflammation.

PubMed

Yoshihisa, Yoko; Honda, Ayumi; Zhao, Qing-Li; Makino, Teruhiko; Abe, Riichiro; Matsui, Kotaro; Shimizu, Hiroshi; Miyamoto, Yusei; Kondo, Takashi; Shimizu, Tadamichi

2010-11-01

Intracellular reactive oxygen species (ROS) and apoptosis play important roles in the ultraviolet (UV)-induced inflammatory responses in the skin. Metal nanoparticles have been developed to increase the catalytic activity of metals, which is because of the large surface area of smaller particles. Platinum nanoparticles (nano-Pt) protected by poly acrylic acid were manufactured by reduction with ethanol. A marked increase in ROS production was observed in UV-treated HaCaT keratinocytes cell lines, while a decrease in ROS production was observed in nano-Pt-treated cells. Pretreatment of the cells with nano-Pt also caused a significant inhibition of UVB- and UVC-induced apoptosis. Furthermore, we found that mice treated with nano-Pt gel prior to UV irradiation showed significant inhibition of UVB-induced inflammation and UVA-induced photoallergy compared to UV-irradiated control mice. These results suggest that nano-Pt effectively protects against UV-induced inflammation by decreasing ROS production and inhibiting apoptosis in keratinocytes. © 2010 John Wiley & Sons A/S.

Lycium chinense leaves extract ameliorates diabetic nephropathy by suppressing hyperglycemia mediated renal oxidative stress and inflammation.

PubMed

Olatunji, Opeyemi Joshua; Chen, Hongxia; Zhou, Yifeng

2018-06-01

Diabetic nephropathy is one of the most serious and most frequently encountered diabetic complication, accounting for the highest cause of end-stage renal disease. This present study was aimed at exploring the protective/attenuative effect of Lycium chinense leaf extract (MELC) on streptozotocin induced diabetic nephropathy in experimental Sprague Dawley rats. The oral administration of diabetic rats with MELC markedly ameliorated renal dysfunction as observed in the significant reduction in the serum levels of creatinine, blood urea nitrogen (BUN), albumin and TGF-β1 as compared to the untreated diabetic control rats. In addition, the elevated levels of renal oxidative stress markers and pro-inflammatory parameters (GSH, SOD, CAT, MDA, TNF-α, IL-6 and IL-1β) were significantly reduced in MELC treated diabetic rats. The results obtained in this study suggests that L. chinense leaf might have the potential as possible pharmacological agent against diabetic nephropathy by suppressing renal oxidative stress and inflammation. Copyright © 2018. Published by Elsevier Masson SAS.

TALEN-based generation of a cynomolgus monkey disease model for human microcephaly

PubMed Central

Ke, Qiong; Li, Weiqiang; Lai, Xingqiang; Chen, Hong; Huang, Lihua; Kang, Zhuang; Li, Kai; Ren, Jie; Lin, Xiaofeng; Zheng, Haiqing; Huang, Weijun; Ma, Yunhan; Xu, Dongdong; Chen, Zheng; Song, Xinming; Lin, Xinyi; Zhuang, Min; Wang, Tao; Zhuang, Fengfeng; Xi, Jianzhong; Mao, Frank Fuxiang; Xia, Huimin; Lahn, Bruce T; Zhou, Qi; Yang, Shihua; Xiang, Andy Peng

2016-01-01

Gene editing in non-human primates may lead to valuable models for exploring the etiologies and therapeutic strategies of genetically based neurological disorders in humans. However, a monkey model of neurological disorders that closely mimics pathological and behavioral deficits in humans has not yet been successfully generated. Microcephalin 1 (MCPH1) is implicated in the evolution of the human brain, and MCPH1 mutation causes microcephaly accompanied by mental retardation. Here we generated a cynomolgus monkey (Macaca fascicularis) carrying biallelic MCPH1 mutations using transcription activator-like effector nucleases. The monkey recapitulated most of the important clinical features observed in patients, including marked reductions in head circumference, premature chromosome condensation (PCC), hypoplasia of the corpus callosum and upper limb spasticity. Moreover, overexpression of MCPH1 in mutated dermal fibroblasts rescued the PCC syndrome. This monkey model may help us elucidate the role of MCPH1 in the pathogenesis of human microcephaly and better understand the function of this protein in the evolution of primate brain size. PMID:27502025

Vaccination: a novel strategy for inhibiting the renin-angiotensin-aldosterone system.

PubMed

Gradman, Alan H; Pinto, Rehka

2008-12-01

Immunologic approaches to renin-angiotensin-aldosterone system (RAAS) inhibition have been studied for more than 50 years. In animal models, vaccination against renin was effective but resulted in fatal autoimmune renal disease; vaccines directed at small peptides including angiotensin I and II and a segment of the AT(1) receptor reduced blood pressure (BP) without causing autoimmune disease. In humans, angiotensin I vaccination did not reduce BP. More promising is the AngQb vaccine, which uses an immunization technology involving conjugation of angiotensin II to virus-like particles. In a phase 2 trial, hypertensive patients vaccinated with 300 microg showed a difference of 9.0/4.0 mm Hg from baseline in mean daytime ambulatory BP after 14 weeks (P = 0.015 for systolic BP, P = 0.064 for diastolic BP), and a marked reduction in early morning BP. No serious adverse events were attributed to vaccine administration. Although questions remain regarding efficacy and safety, RAAS immunization represents an innovative and promising approach to hypertension treatment.

Echinococcus granulosus infection in Spain.

PubMed

Carmena, D; Sánchez-Serrano, L P; Barbero-Martínez, I

2008-04-01

Cystic echinococcosis (CE) caused by the cestode Echinococcus granulosus is an endemic disease in Spain. Although specific control programmes initiated in the 1980s have led to marked reductions in CE infection rates in Spain, the disease still remains an important human and animal health problem in many regions of the country. Human incidence and livestock (including sheep, cattle, pigs and horses) prevalence data were gathered from national epidemiological surveillance information systems and regional institutions for the period 2000-2005. Additionally, data on the prevalence of E. granulosus infection in dogs were obtained from published literature. The most affected regions were those of the North Eastern, Central and Western parts of the country, (Autonomous Regions of Aragon, Castile-La Mancha, Castile-Leon, Extremadura, Navarre and La Rioja), where human CE incidence rates in the range of 1.1-3.4 cases per 10(5) inhabitants coexist with ovine/bovine CE prevalence rates up to 23%. Control programmes of hydatidosis/echinococcosis should be reinforced in these regions to reduce the prevalence of the disease.

A single mutation that causes phosphatidylglycerol deficiency impairs synthesis of photosystem II cores in Chlamydomonas reinhardtii.

PubMed

Pineau, Bernard; Girard-Bascou, Jacqueline; Eberhard, Stephan; Choquet, Yves; Trémolières, Antoine; Gérard-Hirne, Catherine; Bennardo-Connan, Annick; Decottignies, Paulette; Gillet, Sylvie; Wollman, Francis-André

2004-01-01

Two mutants of Chlamydomonas reinhardtii, mf1 and mf2, characterized by a marked reduction in their phosphatidylglycerol content together with a complete loss in its Delta3-trans hexadecenoic acid-containing form, also lost photosystem II (PSII) activity. Genetic analysis of crosses between mf2 and wild-type strains shows a strict cosegregation of the PSII and lipid deficiencies, while phenotypic analysis of phototrophic revertant strains suggests that one single nuclear mutation is responsible for the pleiotropic phenotype of the mutants. The nearly complete absence of PSII core is due to a severely decreased synthesis of two subunits, D1 and apoCP47, which is not due to a decrease in translation initiation. Trace amounts of PSII cores that were detected in the mutants did not associate with the light-harvesting chlorophyll a/b-binding protein antenna (LHCII). We discuss the possible role of phosphatidylglycerol in the coupled process of cotranslational insertion and assembly of PSII core subunits.

Trend of bacterial meningitis in Bahrain from 1990 to 2013 and effect of introduction of new vaccines.

PubMed

Saeed, N; AlAnsari, H; AlKhawaja, S; Jawad, J S; Nasser, K; AlYousef, E

2016-06-15

Meningitis is among the 10 commonest infectious causes of death worldwide. This retrospective analysis of reported cases of meningitis in Bahrain aimed to assess the trend in the incidence of bacterial meningitis from 1990 to 2013, before and after the introduction of new vaccines. Of 1455 reported cases of meningitis during the study period 73.1% were viral and 26.9% were bacterial etiology (tuberculous meningitis 8.3%; Streptococcus pneumoniae 4.9%, Haemophilus influenzae 3.6% and Neisseria meningitidis 1.7%). There was a peak of meningitis cases in 1995-1996. The incidence of meningitis due to H. influenzae and N. meningitidis showed a marked reduction after the introduction of the corresponding vaccines in 1998 and 2001 respectively, and S. pneumoniae became the predominant organism after Mycobacterium tuberculosis. The changing trend in the etiology of bacterial meningitis points to the need to study vaccination programme modifications, such as pneumococcal vaccine for the adult population, especially high-risk groups.

Antimutagenic and antirecombinagenic activities of noni fruit juice in somatic cells of Drosophila melanogaster.

PubMed

Franchi, Leonardo P; Guimarães, Nilza N; De Andrade, Laise R; De Andrade, Heloísa H R; Lehmann, Maurício; Dihl, Rafael R; Cunha, Kênya S

2013-01-01

Noni, a Hawaiian name for the fruit of Morinda citrifolia L., is a traditional medicinal plant from Polynesia widely used for the treatment of many diseases including arthritis, diabetes, asthma, hypertension and cancer. Here, a commercial noni juice (TNJ) was evaluated for its protective activities against the lesions induced by mitomycin C (MMC) and doxorrubicin (DXR) using the Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster. Three-day-old larvae, trans-heterozygous for two genetic markers (mwh and flr3 ), were co-treated with TNJ plus MMC or DXR. We have observed a reduction in genotoxic effects of MMC and DXR caused by the juice. TNJ provoked a marked decrease in all kinds of MMC- and DXR-induced mutant spots, mainly due to its antirecombinagenic activity. The TNJ protective effects were concentration-dependent, indicating a dose-response correlation, that can be attributed to a powerful antioxidant and/or free radical scavenger ability of TNJ.

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...

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.

Computer-aided mass detection in mammography: False positive reduction via gray-scale invariant ranklet texture features

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

Masotti, Matteo; Lanconelli, Nico; Campanini, Renato

In this work, gray-scale invariant ranklet texture features are proposed for false positive reduction (FPR) in computer-aided detection (CAD) of breast masses. Two main considerations are at the basis of this proposal. First, false positive (FP) marks surviving our previous CAD system seem to be characterized by specific texture properties that can be used to discriminate them from masses. Second, our previous CAD system achieves invariance to linear/nonlinear monotonic gray-scale transformations by encoding regions of interest into ranklet images through the ranklet transform, an image transformation similar to the wavelet transform, yet dealing with pixels' ranks rather than with theirmore » gray-scale values. Therefore, the new FPR approach proposed herein defines a set of texture features which are calculated directly from the ranklet images corresponding to the regions of interest surviving our previous CAD system, hence, ranklet texture features; then, a support vector machine (SVM) classifier is used for discrimination. As a result of this approach, texture-based information is used to discriminate FP marks surviving our previous CAD system; at the same time, invariance to linear/nonlinear monotonic gray-scale transformations of the new CAD system is guaranteed, as ranklet texture features are calculated from ranklet images that have this property themselves by construction. To emphasize the gray-scale invariance of both the previous and new CAD systems, training and testing are carried out without any in-between parameters' adjustment on mammograms having different gray-scale dynamics; in particular, training is carried out on analog digitized mammograms taken from a publicly available digital database, whereas testing is performed on full-field digital mammograms taken from an in-house database. Free-response receiver operating characteristic (FROC) curve analysis of the two CAD systems demonstrates that the new approach achieves a higher reduction of FP marks when compared to the previous one. Specifically, at 60%, 65%, and 70% per-mammogram sensitivity, the new CAD system achieves 0.50, 0.68, and 0.92 FP marks per mammogram, whereas at 70%, 75%, and 80% per-case sensitivity it achieves 0.37, 0.48, and 0.71 FP marks per mammogram, respectively. Conversely, at the same sensitivities, the previous CAD system reached 0.71, 0.87, and 1.15 FP marks per mammogram, and 0.57, 0.73, and 0.92 FPs per mammogram. Also, statistical significance of the difference between the two per-mammogram and per-case FROC curves is demonstrated by the p-value<0.001 returned by jackknife FROC analysis performed on the two CAD systems.« less

Leading causes of child mortality in Brazil, in 1990 and 2015: estimates from the Global Burden of Disease study.

PubMed

França, Elisabeth Barboza; Lansky, Sônia; Rego, Maria Albertina Santiago; Malta, Deborah Carvalho; França, Julia Santiago; Teixeira, Renato; Porto, Denise; Almeida, Marcia Furquim de; Souza, Maria de Fatima Marinho de; Szwarcwald, Célia Landman; Mooney, Meghan; Naghavi, Mohsen; Vasconcelos, Ana Maria Nogales

2017-05-01

To analyze under-5 mortality rates and leading causes in Brazil and states in 1990 and 2015, using the Global Burden of Disease Study (GBD) 2015 estimates. The main sources of data for all-causes under-5 mortality and live births estimates were the mortality information system, surveys, and censuses. Proportions and rates per 1,000 live births (LB) were calculated for total deaths and leading causes. Estimates of under-5 deaths in Brazil were 191,505 in 1990, and 51,226 in 2015, 90% of which were infant deaths. The rates per 1,000 LB showed a reduction of 67.6% from 1990 to 2015, achieving the proposed target established by the Millennium Development Goals (MDGs). The reduction generally was more than 60% in states, with a faster reduction in the poorest Northeast region. The ratio of the highest and lowest rates in the states decreased from 4.9 in 1990 to 2.3 in 2015, indicating a reduction in socioeconomic regional disparities. Although prematurity showed a 72% reduction, it still remains as the leading cause of death (COD), followed by diarrheal diseases in 1990, and congenital anomalies, birth asphyxia and septicemia neonatal in 2015. Under-5 mortality has decreased over the past 25 years, with reduction of regional disparities. However, pregnancy and childbirth-related causes remain as major causes of death, together with congenital anomalies. Intersectoral and specific public health policies must be continued to improve living conditions and health care in order to achieve further reduction of under-5 mortality rates in Brazil.

Development of a CAD Model Simplification Framework for Finite Element Analysis

DTIC Science & Technology

2012-01-01

A. Senthil Kumar , and KH Lee. Automatic solid decomposition and reduction for non-manifold geometric model generation. Computer-Aided Design, 36(13...CAD/CAM: concepts, techniques, and applications. Wiley-interscience, 1995. [38] Avneesh Sud, Mark Foskey, and Dinesh Manocha. Homotopy-preserving

The reduction of retinal autofluorescence caused by light exposure.

PubMed

Morgan, Jessica I W; Hunter, Jennifer J; Merigan, William H; Williams, David R

2009-12-01

A prior study showed that long exposure to 568-nm light at levels below the maximum permissible exposure safety limit produces retinal damage preceded by a transient reduction in the autofluorescence of retinal pigment epithelial (RPE) cells in vivo. The present study shows how the effects of exposure power and duration combine to produce this autofluorescence reduction and find the minimum exposure causing a detectable autofluorescence reduction. Macaque retinas were imaged using a fluorescence adaptive optics scanning laser ophthalmoscope to resolve individual RPE cells in vivo. The retina was exposed to 568-nm light over a square subtending 0.5 degrees with energies ranging from 1 to 788 J/cm(2), where power and duration were independently varied. In vivo exposures of 5 J/cm(2) and higher caused an immediate decrease in autofluorescence followed by either full autofluorescence recovery (exposures or= 247 J/cm(2)). No significant autofluorescence reduction was observed for exposures of 2 J/cm(2) and lower. Reciprocity of exposure power and duration held for the exposures tested, implying that the total energy delivered to the retina, rather than its distribution in time, determines the amount of autofluorescence reduction. That reciprocity held is consistent with a photochemical origin, which may or may not cause retinal degeneration. The implementation of safe methods for delivering light to the retina requires a better understanding of the mechanism causing autofluorescence reduction. Finally, RPE imaging was demonstrated using light levels that do not cause a detectable reduction in autofluorescence.

The Reduction of Retinal Autofluorescence Caused by Light Exposure

PubMed Central

Morgan, Jessica I. W.; Hunter, Jennifer J.; Merigan, William H.; Williams, David R.

2009-01-01

Purpose We have previously shown that long exposure to 568 nm light at levels below the maximum permissible exposure safety limit produces retinal damage preceded by a transient reduction in the autofluorescence of retinal pigment epithelial (RPE) cells in vivo. Here, we determine how the effects of exposure power and duration combine to produce this autofluorescence reduction and find the minimum exposure causing a detectable autofluorescence reduction. Methods Macaque retinas were imaged using a fluorescence adaptive optics scanning laser ophthalmoscope to resolve individual RPE cells in vivo. The retina was exposed to 568 nm light over a square subtending 0.5° with energies ranging from 1 J/cm2 to 788 J/cm2, where power and duration were independently varied. Results In vivo exposures of 5 J/cm2 and higher caused an immediate decrease in autofluorescence followed by either full autofluorescence recovery (exposures ≤ 210 J/cm2) or permanent RPE cell damage (exposures ≥ 247 J/cm2). No significant autofluorescence reduction was observed for exposures of 2 J/cm2 and lower. Reciprocity of exposure power and duration held for the exposures tested, implying that the total energy delivered to the retina, rather than its distribution in time, determines the amount of autofluorescence reduction. Conclusions That reciprocity holds is consistent with a photochemical origin, which may or may not cause retinal degeneration. The implementation of safe methods for delivering light to the retina requires a better understanding of the mechanism causing autofluorescence reduction. Finally, RPE imaging was demonstrated using light levels that do not cause a detectable reduction in autofluorescence. PMID:19628734

Sphingolipids as New Biomarkers for Assessment of Delayed-Type Hypersensitivity and Response to Triptolide

PubMed Central

Qu, Feng; Wu, Cai-Sheng; Hou, Jin-Feng; Jin, Ying; Zhang, Jin-Lan

2012-01-01

Background Hypersensitivity diseases are associated with many severe human illnesses, including leprosy and tuberculosis. Emerging evidence suggests that the pathogenesis and pathological mechanisms of treating these diseases may be attributable to sphingolipid metabolism. Methods High performance liquid chromatography-tandem mass spectrometry was employed to target and measure 43 core sphingolipids in the plasma, kidneys, livers and spleens of BALB/c mice from four experimental groups: control, delayed-type hypersensitivity (DTH) model, DTH+triptolide, and control+triptolide. Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to identify potential biomarkers associated with variance between groups. Relationships between the identified biomarkers and disease markers were evaluated by Spearman correlation. Results As a treatment to hypersensitivity disease, triptolide significantly inhibit the ear swelling and recover the reduction of splenic index caused by DTH. The sphingolipidomic result revealed marked alterations in sphingolipid levels between groups that were associated with the effects of the disease and triptolide treatment. Based on this data, 23 potential biomarkers were identified by OPLS-DA, and seven of these biomarkers correlated markedly with the disease markers (p<0.05) by Spearman correlation. Conclusions These data indicate that differences in sphingolipid levels in plasma and tissues are related to DTH and treatment with triptolide. Restoration of proper sphingolipid levels may attribute to the therapeutic effect of triptolide treatment. Furthermore, these findings demonstrate that targeted sphingolipidomic analysis followed by multivariate analysis presents a novel strategy for the identification of biomarkers in biological samples. PMID:23300675

Resurgence of Mumps in Korea

PubMed Central

2015-01-01

Routine vaccination against mumps has markedly reduced its incidence. However, the incidence of mumps continuously has increased since 2007. In 2013, a large mumps epidemic occurred in Korea, and this epidemic is still an ongoing problem. This epidemic occurred primarily in school settings and affected vaccinated adolescents, predominantly male students. The recent resurgence of mumps is caused by multiple factors: suboptimal effectiveness of the current mumps vaccines, use of the Rubini strain vaccine, waning immunity in the absence of natural boosting due to the marked reduction in the mumps incidence, genotype mismatch between the vaccine and circulating mumps virus strains, and environmental conditions that foster intense exposures. Containment of mumps outbreaks is challenging because the sensitivity of diagnostic tests is low among vaccinees and control measures are less efficient because of the inherent nature of the mumps virus. Despite the suboptimal vaccine effectiveness in outbreak settings, maintaining the high vaccine coverage is an important strategy to prevent mumps outbreaks, given that the routine use of mumps vaccines has substantially reduced the incidence of mumps and its complications as compared with that in the pre-vaccine era. In order to control the current mumps epidemic and prevent further outbreaks, we need to better understand the dynamics of mumps among vaccinated populations and the changing epidemiology in Korea. Concerted efforts should be made to systematically monitor the immunization status of the Korean population and to improve diagnosis efficiency. Furthermore, more effective mumps vaccines need to be developed in the future. PMID:25844258

Conditional immortalization of human thyroid epithelial cells: a tool for analysis of oncogene action.

PubMed Central

Wynford-Thomas, D; Bond, J A; Wyllie, F S; Burns, J S; Williams, E D; Jones, T; Sheer, D; Lemoine, N R

1990-01-01

To overcome the difficulty of assessing oncogene action in human epithelial cell types, such as thyroid, which have limited proliferative potential in culture, we have explored the use of temperature-sensitive (ts) mutants of simian virus 40 (SV40) early region to create conditionally immortalized epithelial cell lines. Normal primary cultures of human thyroid follicular cells were transfected with a plasmid containing the SV40 early region from mutant tsA58. Expanding epithelial colonies were observed after 2 to 3 months, all of which grew to greater than 200 population doublings without crisis. All showed tight temperature dependence for growth. After switch-up to the restrictive temperature (40.5 degrees C), no further increase in cell number was seen after 1 to 2 days. However, DNA synthesis declined much more slowly; the dissociation from cell division led to marked polyploidy. Viability was maintained for up to 2 weeks. Introduction of an inducible mutant ras gene into ts thyroid cells led, as expected, to morphological transformation at the permissive temperature when ras was induced. Interestingly, this was associated with a marked reduction in net growth rate. At the restrictive temperature, induction of mutant ras caused rapid cell death. These results demonstrate the utility of a ts SV40 mutant to permit the study of oncogene action in an otherwise nonproliferative target cell and reveal important differences in the interaction between ras and SV40 T in these epithelial cells compared with previously studied cell types. Images PMID:1697930

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.

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

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.

Generation and characterization of function-blocking anti-ectodysplasin A (EDA) monoclonal antibodies that induce ectodermal dysplasia.

PubMed

Kowalczyk-Quintas, Christine; Willen, Laure; Dang, Anh Thu; Sarrasin, Heidi; Tardivel, Aubry; Hermes, Katharina; Schneider, Holm; Gaide, Olivier; Donzé, Olivier; Kirby, Neil; Headon, Denis J; Schneider, Pascal

2014-02-14

Development of ectodermal appendages, such as hair, teeth, sweat glands, sebaceous glands, and mammary glands, requires the action of the TNF family ligand ectodysplasin A (EDA). Mutations of the X-linked EDA gene cause reduction or absence of many ectodermal appendages and have been identified as a cause of ectodermal dysplasia in humans, mice, dogs, and cattle. We have generated blocking antibodies, raised in Eda-deficient mice, against the conserved, receptor-binding domain of EDA. These antibodies recognize epitopes overlapping the receptor-binding site and prevent EDA from binding and activating EDAR at close to stoichiometric ratios in in vitro binding and activity assays. The antibodies block EDA1 and EDA2 of both mammalian and avian origin and, in vivo, suppress the ability of recombinant Fc-EDA1 to rescue ectodermal dysplasia in Eda-deficient Tabby mice. Moreover, administration of EDA blocking antibodies to pregnant wild type mice induced in developing wild type fetuses a marked and permanent ectodermal dysplasia. These function-blocking anti-EDA antibodies with wide cross-species reactivity will enable study of the developmental and postdevelopmental roles of EDA in a variety of organisms and open the route to therapeutic intervention in conditions in which EDA may be implicated.

Generation and Characterization of Function-blocking Anti-ectodysplasin A (EDA) Monoclonal Antibodies That Induce Ectodermal Dysplasia*

PubMed Central

Kowalczyk-Quintas, Christine; Willen, Laure; Dang, Anh Thu; Sarrasin, Heidi; Tardivel, Aubry; Hermes, Katharina; Schneider, Holm; Gaide, Olivier; Donzé, Olivier; Kirby, Neil; Headon, Denis J.; Schneider, Pascal

2014-01-01

Development of ectodermal appendages, such as hair, teeth, sweat glands, sebaceous glands, and mammary glands, requires the action of the TNF family ligand ectodysplasin A (EDA). Mutations of the X-linked EDA gene cause reduction or absence of many ectodermal appendages and have been identified as a cause of ectodermal dysplasia in humans, mice, dogs, and cattle. We have generated blocking antibodies, raised in Eda-deficient mice, against the conserved, receptor-binding domain of EDA. These antibodies recognize epitopes overlapping the receptor-binding site and prevent EDA from binding and activating EDAR at close to stoichiometric ratios in in vitro binding and activity assays. The antibodies block EDA1 and EDA2 of both mammalian and avian origin and, in vivo, suppress the ability of recombinant Fc-EDA1 to rescue ectodermal dysplasia in Eda-deficient Tabby mice. Moreover, administration of EDA blocking antibodies to pregnant wild type mice induced in developing wild type fetuses a marked and permanent ectodermal dysplasia. These function-blocking anti-EDA antibodies with wide cross-species reactivity will enable study of the developmental and postdevelopmental roles of EDA in a variety of organisms and open the route to therapeutic intervention in conditions in which EDA may be implicated. PMID:24391090

Mutations in FOXC2 in humans (lymphoedema distichiasis syndrome) cause lymphatic dysfunction on dependency.

PubMed

Mellor, Russell H; Tate, Naomi; Stanton, Anthony W B; Hubert, Charlotte; Mäkinen, Taija; Smith, Alberto; Burnand, Kevin G; Jeffery, Steve; Levick, J Rodney; Mortimer, Peter S

2011-01-01

Human lymphoedema distichiasis syndrome (LDS) results from germline mutations in transcription factor FOXC2. In a mouse model, lack of lymphatic and venous valves is observed plus abnormal smooth muscle cell recruitment to initial lymphatics. We investigated the mechanism of lymphoedema in humans with FOXC2 mutations, specifically the effect of gravitational forces on dermal lymphatic function. We performed (1) quantitative fluorescence microlymphangiography (FML) on the skin of the forearm (non-swollen region) at heart level, and the foot (swollen region) below heart level (dependent) and then at heart level, and (2) immunohistochemical staining of microlymphatics in forearm and foot skin biopsies, using antibodies to podoplanin, LYVE-1 and smooth muscle actin. FML revealed a marked reduction in fluid uptake by initial lymphatics in the LDS foot during dependency, yet normal uptake (similar to controls) in the same foot at heart level and in LDS forearms. In control subjects, dependency did not impair initial lymphatic filling. Immunohistochemical microlymphatic density in forearm and foot did not differ between LDS and controls. FOXC2 mutations cause a functional failure of dermal initial lymphatics during gravitational stress (dependency), but not hypoplasia. The results reveal a pathophysiological mechanism contributing to swelling in LDS. Copyright © 2011 S. Karger AG, Basel.

Salicylic Acid and Ethylene Pathways Are Differentially Activated in Melon Cotyledons by Active or Heat-Denatured Cellulase from Trichoderma longibrachiatum

PubMed Central

Martinez, Christelle; Blanc, Frédéric; Le Claire, Emilie; Besnard, Olivier; Nicole, Michel; Baccou, Jean-Claude

2001-01-01

Infiltration of cellulase (EC 3.2.1.4) from Trichoderma longibrachiatum into melon (Cucumis melo) cotyledons induced several key defense mechanisms and hypersensitive reaction-like symptoms. An oxidative burst was observed 3 hours after treatment and was followed by activation of ethylene and salicylic acid (SA) signaling pathways leading to marked induction of peroxidase and chitinase activities. The treatment of cotyledons by heat-denatured cellulase also led to some induction of peroxidase and chitinase activities, but the oxidative burst and SA production were not observed. Co-infiltration of aminoethoxyvinil-glycine (an ethylene inhibitor) with the active cellulase did not affect the high increase of peroxidase and chitinase activities. In contrast, co-infiltration of aminoethoxyvinil-glycine with the denatured enzyme blocked peroxidase and chitinase activities. Our data suggest that the SA pathway (induced by the cellulase activity) and ethylene pathway (induced by heat-denatured and active protein) together coordinate the activation of defense mechanisms. We found a partial interaction between both signaling pathways since SA caused an inhibition of the ethylene production and a decrease in peroxidase activity when co-infiltrated with denatured cellulase. Treatments with active or denatured cellulase caused a reduction in powdery mildew (Sphaerotheca fuliginea) disease. PMID:11553761

Correcting spacecraft jitter in HiRISE images

USGS Publications Warehouse

Sutton, S. S.; Boyd, A.K.; Kirk, Randolph L.; Cook, Debbie; Backer, Jean; Fennema, A.; Heyd, R.; McEwen, A.S.; Mirchandani, S.D.; Wu, B.; Di, K.; Oberst, J.; Karachevtseva, I.

2017-01-01

Mechanical oscillations or vibrations on spacecraft, also called pointing jitter, cause geometric distortions and/or smear in high resolution digital images acquired from orbit. Geometric distortion is especially a problem with pushbroom type sensors, such as the High Resolution Imaging Science Experiment (HiRISE) instrument on board the Mars Reconnaissance Orbiter (MRO). Geometric distortions occur at a range of frequencies that may not be obvious in the image products, but can cause problems with stereo image correlation in the production of digital elevation models, and in measuring surface changes over time in orthorectified images. The HiRISE focal plane comprises a staggered array of fourteen charge-coupled devices (CCDs) with pixel IFOV of 1 microradian. The high spatial resolution of HiRISE makes it both sensitive to, and an excellent recorder of jitter. We present an algorithm using Fourier analysis to resolve the jitter function for a HiRISE image that is then used to update instrument pointing information to remove geometric distortions from the image. Implementation of the jitter analysis and image correction is performed on selected HiRISE images. Resulting corrected images and updated pointing information are made available to the public. Results show marked reduction of geometric distortions. This work has applications to similar cameras operating now, and to the design of future instruments (such as the Europa Imaging System).

Effects of nitrogen nutrients on the volatile organic compound emissions from Microcystis aeruginosa.

PubMed

Zuo, Zhaojiang; Yang, Lin; Chen, Silan; Ye, Chaolin; Han, Yujie; Wang, Sutong; Ma, Yuandan

2018-06-06

Cyanobacteria release abundant volatile organic compounds (VOCs), which can poison other algae and cause water odor. To uncover the effects of nitrogen (N) nutrients on the formation of cyanobacteria VOCs, the cell growth, VOC emission and the expression of genes involving in VOC formation in Microcystis aeruginosa were investigated under different N conditions. With the supplement of NaNO 3 , NaNO 2 , NH 4 Cl, urea, Serine (Ser) and Arginine (Arg) as the sole N source, NaNO 3 , urea and Arg showed the best effects on M. aeruginosa cell growth, and limited N supply inhibited the cell growth. M. aeruginosa released 26, 25, 23, 27, 23 and 25 compounds, respectively, in response to different N forms, including furans, sulfocompounds, terpenoids, benzenes, hydrocarbons, aldehydes, and esters. Low-N especially Non-N condition markedly promoted the VOC emission. Under Non-N condition, four up-regulated genes involving in VOC precursor formation were identified, including the genes of pyruvate kinase, malic enzyme and phosphotransacetylase for terpenoids, the gene of aspartate aminotransferase for benzenes and sulfocompounds. In eutrophic water, cyanobacteria release different VOC blends using various N forms, and the reduction of N amount caused by cyanobacteria massive growth can promote algal VOC emission by up-regulating the gene expression. Copyright © 2018 Elsevier Inc. All rights reserved.

Common cold decreases lung function in infants with recurrent wheezing.

PubMed

Mallol, J; Aguirre, V; Wandalsen, G

2010-01-01

Common acute viral respiratory infections (colds) are the most frequent cause of exacerbations in infants with recurrent wheezing (RW). However, there is no quantitative information about the effect of colds on the lung function of infants with RW. This study was undertaken to determine the effect of common cold on forced expiratory parameters measured from raised lung volume in infants with RW. Spirometric lung function (expiratory flows from raised lung volume) was randomly assessed in 28 infants with RW while they had a common cold and when asymptomatic. It was found that during colds there was a significant decrease in all forced expiratory parameters and this was much more evident for flows (FEF(50%), FEF(75%) and FEF(25-75%)) which were definitively abnormal (less than -1.65 z-score) in the majority of infants. There was not association between family asthma, tobacco exposure, and other factors, with the extent of lung function decrease during colds. Tobacco during pregnancy but not a history of family asthma was significantly associated to lower expiratory flows; however, the association was significant only when infants were asymptomatic. This study shows that common colds cause a marked reduction of lung function in infants with RW. 2009 SEICAP. Published by Elsevier Espana. All rights reserved.

Apoptosis and dysfunction of blood dendritic cells in patients with falciparum and vivax malaria

PubMed Central

Woodberry, Tonia; Kienzle, Vivian; McPhun, Virginia; Minigo, Gabriela; Lampah, Daniel A.; Kenangalem, Enny; Engwerda, Christian; López, J. Alejandro; Anstey, Nicholas M.

2013-01-01

Malaria causes significant morbidity worldwide and a vaccine is urgently required. Plasmodium infection causes considerable immune dysregulation, and elicitation of vaccine immunity remains challenging. Given the central role of dendritic cells (DCs) in initiating immunity, understanding their biology during malaria will improve vaccination outcomes. Circulating DCs are particularly important, as they shape immune responses in vivo and reflect the functional status of other subpopulations. We performed cross-sectional and longitudinal assessments of the frequency, phenotype, and function of circulating DC in 67 Papuan adults during acute uncomplicated P. falciparum, P. vivax, and convalescent P. falciparum infections. We demonstrate that malaria patients display a significant reduction in circulating DC numbers and the concurrent accumulation of immature cells. Such alteration is associated with marked levels of spontaneous apoptosis and impairment in the ability of DC to mature, capture, and present antigens to T cells. Interestingly, sustained levels of plasma IL-10 were observed in patients with acute infection and were implicated in the induction of DC apoptosis. DC apoptosis was reversed upon IL-10 blockade, and DC function recovered when IL-10 levels returned to baseline by convalescence. Our data provide key information on the mechanisms behind DC suppression during malaria and will assist in developing strategies to better harness DC’s immunotherapeutic potential. PMID:23835848

Transition metal dissolution, ion migration, electrocatalytic reduction and capacity loss in Lithium-ion full cells

DOE PAGES

Gilbert, James A.; Shkrob, Ilya A.; Abraham, Daniel P.

2017-01-05

Continuous operation of full cells with layered transition metal (TM) oxide positive electrodes (NCM523) leads to dissolution of TM ions and their migration and incorporation into the solid electrolyte interphase (SEI) of the graphite-based negative electrode. These processes correlate with cell capacity fade and accelerate markedly as the upper cutoff voltage (UCV) exceeds 4.30 V. At voltages ≥ 4.4 V there is enhanced fracture of the oxide during cycling that creates new surfaces and causes increased solvent oxidation and TM dissolution. Despite this deterioration, cell capacity fade still mainly results from lithium loss in the negative electrode SEI. Among TMs,more » Mn content in the SEI shows a better correlation with cell capacity loss than Co and Ni contents. As Mn ions become incorporated into the SEI, the kinetics of lithium trapping change from power to linear at the higher UCVs, indicating a large effect of these ions on SEI growth and implicating (electro)catalytic reactions. Lastly, we estimate that each Mn II ion deposited in the SEI causes trapping of ~10 2 additional Li + ions thereby hastening the depletion of cyclable lithium ions. Using these results, we sketch a mechanism for cell capacity fade, emphasizing the conceptual picture over the chemical detail.« less

Effects of a Meal on the Hemorheologic Responses to Exercise in Young Males

PubMed Central

Bilski, Jan; Teległów, Aneta; Pokorski, Janusz; Nitecki, Jacek; Pokorska, Joanna; Nitecka, Ewa; Marchewka, Anna; Dąbrowski, Zbigniew; Marchewka, Jakub

2014-01-01

Aim. This study investigates the changes in hemorheologic parameters resulting from exercise followed by a standard meal. Methods. In twelve moderately active men a period of exercise on a bicycle ergometer for 30 min at 60% VO2max was followed by a test meal or by 30 min rest. Venous blood was sampled for further analysis at baseline, after exercise, and after the meal/rest period. Results. The elongation index (EI) was reduced and a marked rise in plasma viscosity was observed after exercise. A significant decrease in half time of total aggregation (T 1/2) and a rise in aggregation index (AI) after exercise were observed; however, after the postexercise period these changes were reversed. Conclusion. The present study demonstrates that physical exercise causes several changes in blood rheology parameters, such as an increase of blood viscosity, a decrease in EI and an increase in AI, and a fall in the T 1/2 values. The meal eaten in the postexercise period caused a further reduction in EI values indicating higher red cell rigidity, but not in plasma viscosity or aggregations indices. Such alterations in hemorheologic parameters should not impair the function of the cardiovascular system in fit and healthy people but it could constitute a serious risk under various pathophysiological conditions. PMID:25089277

Effects of a meal on the hemorheologic responses to exercise in young males.

PubMed

Bilski, Jan; Teległów, Aneta; Pokorski, Janusz; Nitecki, Jacek; Pokorska, Joanna; Nitecka, Ewa; Marchewka, Anna; Dąbrowski, Zbigniew; Marchewka, Jakub

2014-01-01

This study investigates the changes in hemorheologic parameters resulting from exercise followed by a standard meal. In twelve moderately active men a period of exercise on a bicycle ergometer for 30 min at 60% VO2max was followed by a test meal or by 30 min rest. Venous blood was sampled for further analysis at baseline, after exercise, and after the meal/rest period. The elongation index (EI) was reduced and a marked rise in plasma viscosity was observed after exercise. A significant decrease in half time of total aggregation (T 1/2) and a rise in aggregation index (AI) after exercise were observed; however, after the postexercise period these changes were reversed. The present study demonstrates that physical exercise causes several changes in blood rheology parameters, such as an increase of blood viscosity, a decrease in EI and an increase in AI, and a fall in the T 1/2 values. The meal eaten in the postexercise period caused a further reduction in EI values indicating higher red cell rigidity, but not in plasma viscosity or aggregations indices. Such alterations in hemorheologic parameters should not impair the function of the cardiovascular system in fit and healthy people but it could constitute a serious risk under various pathophysiological conditions.

Pleiotropic role of the Sco1/SenC family copper chaperone in the physiology of Streptomyces

PubMed Central

Fujimoto, Masahiro; Yamada, Akio; Kurosawa, Junpei; Kawata, Akihiro; Beppu, Teruhiko; Takano, Hideaki; Ueda, Kenji

2012-01-01

Summary Antibiotic production and cell differentiation in Streptomyces is stimulated by micromolar levels of Cu2+. Here, we knocked out the Sco1/SenC family copper chaperone (ScoC) encoded in the conserved gene cluster ‘sco’ (the S treptomycescopper utilization) in Streptomyces coelicolor A3(2) and S. griseus. It is known that the Sco1/SenC family incorporates Cu2+ into the active centre of cytochrome oxidase (cox). The knockout caused a marked delay in antibiotic production and aerial mycelium formation on solid medium, temporal pH decline in glucose‐containing liquid medium, and significant reduction of cox activity in S. coelicolor. The scoC mutant produced two‐ to threefold higher cellular mass of the wild type exhibiting a marked cox activity in liquid medium supplied with 10 µM CuSO4, suggesting that ScoC is involved in not only the construction but also the deactivation of cox. The scoC mutant was defective in the monoamine oxidase activity responsible for cell aggregation and sedimentation. These features were similarly observed with regard to the scoC mutant of S. griseus. The scoC mutant of S. griseus was also defective in the extracellular activity oxidizing N,N′‐dimethyl‐p‐phenylenediamine sulfate. Addition of 10 µM CuSO4 repressed the activity of the conserved promoter preceding scoA and caused phenylalanine auxotrophy in some Streptomyces spp. probably because of the repression of pheA; pheA encodes prephenate dehydratase, which is located at the 3′ terminus of the putative operon structure. Overall, the evidence indicates that Sco is crucial for the utilization of copper under a low‐copper condition and for the activation of the multiple Cu2+‐containing oxidases that play divergent roles in the complex physiology of Streptomyces. PMID:22117562

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.

21 CFR 558.665 - Zilpaterol.

Code of Federal Regulations, 2010 CFR

2010-04-01

.... zuernii; and for reduction of incidence of liver abscesses caused by Fusobacterium necrophorum and.... zuernii; for reduction of incidence of liver abscesses caused by Fusobacterium necrophorum and...

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.

Inactivation of lipoprotein lipase occurs on the surface of THP-1 macrophages where oligomers of angiopoietin-like protein 4 are formed.

PubMed

Makoveichuk, Elena; Sukonina, Valentina; Kroupa, Olessia; Thulin, Petra; Ehrenborg, Ewa; Olivecrona, Thomas; Olivecrona, Gunilla

2012-08-24

Lipoprotein lipase (LPL) hydrolyzes triglycerides in plasma lipoproteins causing release of fatty acids for metabolic purposes in muscles and adipose tissue. LPL in macrophages in the artery wall may, however, promote foam cell formation and atherosclerosis. Angiopoietin-like protein (ANGPTL) 4 inactivates LPL and ANGPTL4 expression is controlled by peroxisome proliferator-activated receptors (PPAR). The mechanisms for inactivation of LPL by ANGPTL4 was studied in THP-1 macrophages where active LPL is associated with cell surfaces in a heparin-releasable form, while LPL in the culture medium is mostly inactive. The PPARδ agonist GW501516 had no effect on LPL mRNA, but increased ANGPTL4 mRNA and caused a marked reduction of the heparin-releasable LPL activity concomitantly with accumulation of inactive, monomeric LPL in the medium. Intracellular ANGPTL4 was monomeric, while dimers and tetramers of ANGPTL4 were present in the heparin-releasable fraction and medium. GW501516 caused an increase in the amount of ANGPTL4 oligomers on the cell surface that paralleled the decrease in LPL activity. Actinomycin D blocked the effects of GW501516 on ANGPTL4 oligomer formation and prevented the inactivation of LPL. Antibodies against ANGPTL4 interfered with the inactivation of LPL. We conclude that inactivation of LPL in THP-1 macrophages primarily occurs on the cell surface where oligomers of ANGPTL4 are formed. Copyright © 2012 Elsevier Inc. All rights reserved.

Dandelion-enriched diet of mothers alleviates lead-induced damages in liver of newborn rats.

PubMed

Gargouri, M; Magné, C; Ben Amara, I; Ben Saad, H; El Feki, A

2017-02-28

Lead (Pb) is a highly toxic metal present in the environment. It causes disturbances of several functions, including hematologic, renal, reproductive and nervous ones. Preventive or curative use of medicinal plants against these disorders may be a promising and safe therapeutic strategy. This study evaluated the hepatic toxic effects of prenatal exposure to lead in rats and the possible protective effect of dandelion (Taraxacum officinale) added to the diet. Female rats were given a normal diet (control) or a diet enriched with dandelion (treated). In addition, lead acetate was administered to half of the rats through drinking water from the 5th day of gestation until the 14th day postpartum. Lead toxicity was evaluated in their offspring by measuring body and liver weights, plasma biochemical parameters, liver damage, as well as protein content and activities of antioxidant enzymes in the liver tissues. Lead poisoning of mothers caused lead deposition in blood and stomach of their pups as well as hepatic tissue damages. Moreover, significant decreases in liver weight and protein content were found. Lead treatment caused oxidative stress and marked changes in the activity of antioxidant enzymes. However, no damages or biochemical changes were observed in puppies from the rats co-treated with lead and dandelion. These results indicate that supplementation of pregnant and lactating rats with dandelion protects their offspring against lead poisoning, likely through reduction of oxidative stress and liver damages.

Disturbed subsurface microbial communities follow equivalent trajectories despite different structural starting points

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

Handley, Kim M.; Wrighton, Kelly C.; Miller, Christopher S.

2015-03-01

We explored the impact of the starting community composition and structure on ecosystem response to perturbations using organic carbon amendment experiments. Subsurface sediment was partitioned into flow-through columns, and the microbial communities were initially stimulated in situ by addition of acetate as a carbon and electron donor source. This drove community richness and evenness down, and pushed the system into a new biogeochemical state characterized by iron reduction. Reconstructed near-full-length 16S rRNA gene sequence analysis indicated a concomitant enrichment of Desulfuromonadales, Comamonadaceae and Bacteroidetes lineages. After 10 to 12 days, acetate was exchange for lactate in a subset of columns.more » Following the clear onset of sulfate reduction (35 days after acetate-amendment), acetate was substituted for lactate in additional columns. Acetatestimulated communities differed markedly during each biogeochemical regime and at each lactate-switch. Regardless, however, of when communities were switched to lactate, they followed comparable trajectories with respect to composition and structure, with convergence evident one week after each switch, and marked after one month of lactate amendment. During sulfate reduction all treatments were enriched in Firmicutes and a number of species likely involved in sulfate reduction (notably Desulfobulbus, Desulfosporosinus, Desulfitobacterium and Desulfotomaculum). Lactate treatments were distinguished by substantially lower relative abundances of Desulfotomaculum and Bacteroidetes, and enrichments of Psychrosinus and Clostridiales species. Results imply that the structure of the starting community was not significant in controlling organism selection in community succession.« less

Postsynaptic degeneration as revealed by PSD-95 reduction occurs after advanced Aβ and tau pathology in transgenic mouse models of Alzheimer's disease.

PubMed

Shao, Charles Y; Mirra, Suzanne S; Sait, Hameetha B R; Sacktor, Todd C; Sigurdsson, Einar M

2011-09-01

Impairment of synaptic plasticity underlies memory dysfunction in Alzheimer's disease (AD). Molecules involved in this plasticity such as PSD-95, a major postsynaptic scaffold protein at excitatory synapses, may play an important role in AD pathogenesis. We examined the distribution of PSD-95 in transgenic mice of amyloidopathy (5XFAD) and tauopathy (JNPL3) as well as in AD brains using double-labeling immunofluorescence and confocal microscopy. In wild type control mice, PSD-95 primarily labeled neuropil with distinct distribution in hippocampal apical dendrites. In 3-month-old 5XFAD mice, PSD-95 distribution was similar to that of wild type mice despite significant Aβ deposition. However, in 6-month-old 5XFAD mice, PSD-95 immunoreactivity in apical dendrites markedly decreased and prominent immunoreactivity was noted in neuronal soma in CA1 neurons. Similarly, PSD-95 immunoreactivity disappeared from apical dendrites and accumulated in neuronal soma in 14-month-old, but not in 3-month-old, JNPL3 mice. In AD brains, PSD-95 accumulated in Hirano bodies in hippocampal neurons. Our findings support the notion that either Aβ or tau can induce reduction of PSD-95 in excitatory synapses in hippocampus. Furthermore, this PSD-95 reduction is not an early event but occurs as the pathologies advance. Thus, the time-dependent PSD-95 reduction from synapses and accumulation in neuronal soma in transgenic mice and Hirano bodies in AD may mark postsynaptic degeneration that underlies long-term functional deficits.

78 FR 59340 - Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-26

...; Comment Request AGENCY: Defense Logistics Agency, DoD. ACTION: Notice. SUMMARY: In compliance with Section 3506(c)(2)(A) of the Paperwork Reduction Act of 1995, the Defense Logistics Agency announces a proposed... instructions for submitting comments. Mail: Federal Docket Management System Office, 4800 Mark Center Drive...

77 FR 8820 - Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-15

...; Comment Request AGENCY: Defense Logistics Agency, DoD. ACTION: Notice. SUMMARY: In compliance with Section 3506(c)(2)(A) of the Paperwork Reduction Act of 1995, the Defense Logistics Agency announces a proposed... instructions for submitting comments. Mail: Federal Docket Management System Office, 4800 Mark Center Drive...

A possible trade-off between clean air and clean water

USDA-ARS?s Scientific Manuscript database

Harmful algal blooms in Lake Erie have increased since 2002, coincidentally during this same period soluble reactive phosphorus loads have increased from rivers that flow into the lake. Also during this time, reductions in atmospheric sulfur emissions have resulted in marked increases in rainfall p...

New Light on Autism and Other Puzzling Disorders of Childhood. Science Reports.

ERIC Educational Resources Information Center

Yahraes, Herbert

The pamphlet discusses several puzzling disorders of childhood, including autism, atypical personality development (childhood psychosis), psychosocial dwarfism, and Tourette's syndrome. Psychosocial dwarfism is said to be characterized by a marked reduction in physical development and by immaturity in behavior, while Tourette's syndrome involves…

Immunity-dependent reduction of segmented filamentous bacteria in mice infected with the helminthic parasite Nippostrongylus brasiliensis

USDA-ARS?s Scientific Manuscript database

Immune modulation by helminth (worm) parasites could protect the host against autoimmune diseases. We report that the parasitic nematode Nippostrongylus brasiliensis induces changes in the expression of antimicrobial peptides that are associated with marked microbial composition shifts, including re...

[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.

PPARγ activation attenuates opioid consumption and modulates mesolimbic dopamine transmission.

PubMed

de Guglielmo, Giordano; Melis, Miriam; De Luca, Maria Antonietta; Kallupi, Marsida; Li, Hong Wu; Niswender, Kevin; Giordano, Antonio; Senzacqua, Martina; Somaini, Lorenzo; Cippitelli, Andrea; Gaitanaris, George; Demopulos, Gregory; Damadzic, Ruslan; Tapocik, Jenica; Heilig, Markus; Ciccocioppo, Roberto

2015-03-01

PPARγ is one of the three isoforms identified for the peroxisome proliferator-activated receptors (PPARs) and is the receptor for the thiazolidinedione class of anti-diabetic medications including pioglitazone. PPARγ has been long studied for its role in adipogenesis and glucose metabolism, but the discovery of the localization in ventral tegmental area (VTA) neurons opens new vistas for a potential role in the regulation of reward processing and motivated behavior in drug addiction. Here, we demonstrate that activation of PPARγ by pioglitazone reduces the motivation for heroin and attenuates its rewarding properties. These effects are associated with a marked reduction of heroin-induced increase in phosphorylation of DARPP-32 protein in the nucleus accumbens (NAc) and with a marked and selective reduction of acute heroin-induced elevation of extracellular dopamine (DA) levels in the NAc shell, as measured by in vivo microdialysis. Through ex vivo electrophysiology in acute midbrain slices, we also show that stimulation of PPARγ attenuates opioid-induced excitation of VTA DA neurons via reduction of presynaptic GABA release from the rostromedial tegmental nucleus (RMTg). Consistent with this finding, site-specific microinjection of pioglitazone into the RMTg but not into the VTA reduced heroin taking. Our data illustrate that activation of PPARγ may represent a new pharmacotherapeutic option for the treatment of opioid addiction.

Dissociation between the effects of P1, P4-diadenosine tetraphosphate (Ap4A) on renal haemodynamics and tubular function in anaesthetized rats.

PubMed

Jankowski, M; Angielski, S; Szczepańska-Konkel, M

2008-03-01

Previous studies from our laboratory have reported a marked reduction in glomerular filtration rate (GFR) and sodium reabsorption in renal proximal tubule during intravenous infusion of P(1),P(4)-diadenosine tetraphosphate (Ap(4)A) at dose of 1.0 micromol/kg + 10 nmol/kg/min (i.v., injection followed by infusion) in anaesthetized Wistar rats. In the present study, the changes of GFR and urine sodium excretion were investigated in response to systemic infusion of Ap(4)A at different doses. Ap(4)A at dose of 0.1 micromol/kg + 1.0 nmol/kg/min did not change GFR and sodium urinary excretion whereas 2-fold higher dose produced significant (3.4-fold) increase in sodium excretion without changes in GFR. Significant but transient reduction in GFR by approximately 21% was observed during infusion of Ap(4)A at dose of 0.5 micromol/kg + 5.0 nmol/kg/min. Higher doses of Ap(4)A (1.0 micromol/kg + 10 nmol/kg/min and 2.0 micromol/kg + 20 nmol/kg/min) reduction in GFR and marked natriuresis. Our results suggest that tubular sodium transport systems are more sensitive to Ap(4)A than systems involved in GFR regulation.

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.

Further weight reduction of applications in long glass reinforced polymers

NASA Astrophysics Data System (ADS)

Yanev, A.; Schijve, W.; Martin, C.; Brands, D.

2014-05-01

Long glass reinforced materials are broadly used in the automotive industry due to their good mechanical performance, competitive price and options for functional integration in order to reduce weight. With rapidly changing environmental requirements, a demand for further weight reduction is growing constantly. Designs in LGF-PP can bring light weight solutions in combination with system cost improvement. There are quite some possibilities for applying weight reduction technologies nowadays. These technologies have to be evaluated based on weight reduction potential, but also on mechanical performance of the end application, where the latter is often the key to success. Different weight reduction technologies are applied to SABIC®STAMAX{trade mark, serif} material, a long glass fiber reinforced polypropylene (LGF-PP), in order to investigate and define best application performance. These techniques include: chemical foaming, physical foaming and thin wall applications. Results from this research will be presented, giving a guideline for your development.

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...

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

PubMed

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

2011-01-30

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

Angiogenin: a novel inhibitor of neutrophil lactoferrin release during extracorporeal circulation.

PubMed

Schmaldienst, Sabine; Oberpichler, André; Tschesche, Harald; Hörl, Walter H

2003-01-01

Degranulation of polymorphonuclear leukocytes (PMNL) occurs during extracorporeal circulation. A degranulation-inhibiting protein identical to angiogenin was recently isolated from high-flux dialyzer ultrafiltrate. This protein inhibits the release of lactoferrin and metalloproteinases from PMNL in vitro. In the present study, we investigated end-stage renal disease patients undergoing regular hemodialysis treatment with either high-flux dialyzers (n = 51) or low-flux dialyzers (n = 44), and chronically uremic patients undergoing hemodiafiltration (n = 30). Hemodialysis therapy with low-flux polysulfone or cellulose triacetate membranes caused no or only minimal reduction (

Identification and validation of a gene causing cross-resistance between insecticide classes in Anopheles gambiae from Ghana.

PubMed

Mitchell, Sara N; Stevenson, Bradley J; Müller, Pie; Wilding, Craig S; Egyir-Yawson, Alexander; Field, Stuart G; Hemingway, Janet; Paine, Mark J I; Ranson, Hilary; Donnelly, Martin James

2012-04-17

In the last decade there have been marked reductions in malaria incidence in sub-Saharan Africa. Sustaining these reductions will rely upon insecticides to control the mosquito malaria vectors. We report that in the primary African malaria vector, Anopheles gambiae sensu stricto, a single enzyme, CYP6M2, confers resistance to two classes of insecticide. This is unique evidence in a disease vector of cross-resistance associated with a single metabolic gene that simultaneously reduces the efficacy of two of the four classes of insecticide routinely used for malaria control. The gene-expression profile of a highly DDT-resistant population of A. gambiae s.s. from Ghana was characterized using a unique whole-genome microarray. A number of genes were significantly overexpressed compared with two susceptible West African colonies, including genes from metabolic families previously linked to insecticide resistance. One of the most significantly overexpressed probe groups (false-discovery rate-adjusted P < 0.0001) belonged to the cytochrome P450 gene CYP6M2. This gene is associated with pyrethroid resistance in wild A. gambiae s.s. populations) and can metabolize both type I and type II pyrethroids in recombinant protein assays. Using in vitro assays we show that recombinant CYP6M2 is also capable of metabolizing the organochlorine insecticide DDT in the presence of solubilizing factor sodium cholate.

Premature chain termination is a unifying mechanism for COL1A1 null alleles in osteogenesis imperfecta type I cell strains

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

Willing, M.C.; Deschenes, S.P.; Roberts, E.J.

Nonsense and frameshift mutations, which predict premature termination of translation, often cause a dramatic reduction in the amount of transcript from the mutant allele (nonsense-mediated mRNA decay). In some genes, these mutations also influence RNA splicing and induce skipping of the exon that contains the nonsense codon. To begin to dissect how premature termination alters the metabolism of RNA from the COL1A1 gene, we studied nonsense and frameshift mutations distributed over exons 11-49 of the gene. These mutations were originally identified in 10 unrelated families with osteogenesis imperfecta (OI) type I. We observed marked reduction in steady-state amounts of mRNAmore » from the mutant allele in both total cellular and nuclear RNA extracts of cells from affected individuals, suggesting that nonsense-mediated decay of COL1A1 RNA is a nuclear phenomenon. Position of the mutation within the gene did not influence this observation. None of the mutations induced skipping of either the exon containing the mutation or, for the frameshifts, the downstream exons with the new termination sites. Our data suggest that nonsense and frameshift mutations throughout most of the COL1A1 gene result in a null allele, which is associated with the predictable mild clinical phenotype, OI type I. 42 refs., 6 figs., 1 tab.« less

Effect of antioxidant-enriched diets on glutathione redox status in tissue homogenates and mitochondria of the senescence-accelerated mouse

PubMed Central

Rebrin, Igor; Zicker, Steven; Wedekind, Karen J.; Paetau-Robinson, Inke; Packer, Lester; Sohal, Rajindar S.

2010-01-01

The main purpose of this study was to investigate whether consumption of diets enriched in antioxidants attenuates the level of oxidative stress in the senescence-accelerated mouse (SAM). In separate and independent studies, two different dietary mixtures, one enriched with vitamin E, vitamin C, L-carnitine, and lipoic acid (Diet I) and another diet including vitamins E and C and 13 additional ingredients containing micronutrients with bioflavonoids, polyphenols, and carotenoids (Diet II), were fed for 8 and 10 months, respectively. The amounts of glutathione (GSH) and glutathione disulfides (GSSG) and GSH:GSSG ratios were determined in plasma, tissue homogenates, and mitochondria isolated from five different tissues of SAM (P8) mice. Both diets had a reductive effect in plasma; however Diet I had relatively little effect on the glutathione redox status in tissue homogenates or mitochondria. Remarkably, Diet II caused a large increase in the amount of glutathione and a marked reductive shift in glutathione redox state in mitochondria. Overall, the effects of Diet II were tissue and gender specific. Results indicated that the glutathione redox state in mitochondria and tissues can be altered by supplemental intake of a relatively complex mixture of dietary antioxidants that contains substances known to induce phase 2 enzymes, glutathione, and antioxidant defenses. Whether corresponding attenuations occur in age-associated deleterious changes in physiological functions or life span remains unknown. PMID:16043026

Effect of antioxidant-enriched diets on glutathione redox status in tissue homogenates and mitochondria of the senescence-accelerated mouse.

PubMed

Rebrin, Igor; Zicker, Steven; Wedekind, Karen J; Paetau-Robinson, Inke; Packer, Lester; Sohal, Rajindar S

2005-08-15

The main purpose of this study was to investigate whether consumption of diets enriched in antioxidants attenuates the level of oxidative stress in the senescence-accelerated mouse (SAM). In separate and independent studies, two different dietary mixtures, one enriched with vitamin E, vitamin C, L-carnitine, and lipoic acid (Diet I) and another diet including vitamins E and C and 13 additional ingredients containing micronutrients with bioflavonoids, polyphenols, and carotenoids (Diet II), were fed for 8 and 10 months, respectively. The amounts of glutathione (GSH) and glutathione disulfides (GSSG) and GSH:GSSG ratios were determined in plasma, tissue homogenates, and mitochondria isolated from five different tissues of SAM (P8) mice. Both diets had a reductive effect in plasma; however Diet I had relatively little effect on the glutathione redox status in tissue homogenates or mitochondria. Remarkably, Diet II caused a large increase in the amount of glutathione and a marked reductive shift in glutathione redox state in mitochondria. Overall, the effects of Diet II were tissue and gender specific. Results indicated that the glutathione redox state in mitochondria and tissues can be altered by supplemental intake of a relatively complex mixture of dietary antioxidants that contains substances known to induce phase 2 enzymes, glutathione, and antioxidant defenses. Whether corresponding attenuations occur in age-associated deleterious changes in physiological functions or life span remains unknown.

Experimental defaunation of terrestrial mammalian herbivores alters tropical rainforest understorey diversity.

PubMed

Camargo-Sanabria, Angela A; Mendoza, Eduardo; Guevara, Roger; Martínez-Ramos, Miguel; Dirzo, Rodolfo

2015-02-07

It has been suggested that tropical defaunation may unleash community-wide cascading effects, leading to reductions in plant diversity. However, experimental evidence establishing cause-effect relationships thereof is poor. Through a 5 year exclosure experiment, we tested the hypothesis that mammalian defaunation affects tree seedling/sapling community dynamics leading to reductions in understorey plant diversity. We established plot triplets (n = 25) representing three defaunation contexts: terrestrial-mammal exclosure (TE), medium/large mammal exclosure (PE) and open access controls (C). Seedlings/saplings 30-100 cm tall were marked and identified within each of these plots and re-censused three times to record survival and recruitment. In the periods 2010-2011 and 2011-2013, survival was greater in PE than in C plots and recruitment was higher in TE plots than in C plots. Overall, seedling density increased by 61% in TE plots and 23% in PE plots, whereas it decreased by 5% in C plots. Common species highly consumed by mammals (e.g. Brosimum alicastrum and Ampelocera hottlei) increased in their abundance in TE plots. Rarefaction curves showed that species diversity decreased in TE plots from 2008 to 2013, whereas it remained similar for C plots. Given the prevalence of tropical defaunation, we posit this is an anthropogenic effect threatening the maintenance of tropical forest diversity. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Identification and validation of a gene causing cross-resistance between insecticide classes in Anopheles gambiae from Ghana

PubMed Central

Mitchell, Sara N.; Stevenson, Bradley J.; Müller, Pie; Wilding, Craig S.; Egyir-Yawson, Alexander; Field, Stuart G.; Hemingway, Janet; Paine, Mark J. I.; Ranson, Hilary; Donnelly, Martin James

2012-01-01

In the last decade there have been marked reductions in malaria incidence in sub-Saharan Africa. Sustaining these reductions will rely upon insecticides to control the mosquito malaria vectors. We report that in the primary African malaria vector, Anopheles gambiae sensu stricto, a single enzyme, CYP6M2, confers resistance to two classes of insecticide. This is unique evidence in a disease vector of cross-resistance associated with a single metabolic gene that simultaneously reduces the efficacy of two of the four classes of insecticide routinely used for malaria control. The gene-expression profile of a highly DDT-resistant population of A. gambiae s.s. from Ghana was characterized using a unique whole-genome microarray. A number of genes were significantly overexpressed compared with two susceptible West African colonies, including genes from metabolic families previously linked to insecticide resistance. One of the most significantly overexpressed probe groups (false-discovery rate-adjusted P < 0.0001) belonged to the cytochrome P450 gene CYP6M2. This gene is associated with pyrethroid resistance in wild A. gambiae s.s. populations) and can metabolize both type I and type II pyrethroids in recombinant protein assays. Using in vitro assays we show that recombinant CYP6M2 is also capable of metabolizing the organochlorine insecticide DDT in the presence of solubilizing factor sodium cholate. PMID:22460795

Pten Knockdown in vivo Increases Excitatory Drive onto Dentate Granule Cells

PubMed Central

Luikart, Bryan W.; Schnell, Eric; Washburn, Eric K.; Bensen, AeSoon L.; Tovar, Kenneth R.; Westbrook, Gary L.

2011-01-01

Some cases of autism spectrum disorder (ASD) have mutations in the lipid phosphatase, Pten (phosphatase and tensin homolog on chromosome 10). Tissue specific deletion of Pten in the hippocampus and cortex of mice causes anatomical and behavioral abnormalities similar to human autism. However, the impact of reductions in Pten on synaptic and circuit function remains unexplored. We used in vivo stereotaxic injections of lentivirus expressing an shRNA to knockdown Pten in mouse neonatal and young adult dentate granule cells. We then assessed the morphology and synaptic physiology between two weeks and four months later. Confocal imaging of the hippocampus revealed a marked increase in granule cell size and an increase in dendritic spine density. The onset of morphological changes occurred earlier in neonatal mice than in young adults. We used whole-cell recordings from granule cells in acute slices to assess synaptic function following Pten knockdown. Consistent with the increase in dendritic spines, the frequency of excitatory miniature and spontaneous postsynaptic currents increased. However, there was little or no effect on inhibitory postsynaptic currents. Thus Pten knockdown results in an imbalance between excitatory and inhibitory synaptic activity. Because reductions in Pten affected mature granule cells as well as developing granule cells, we suggest that the disruption of circuit function by Pten hypofunction may be ongoing well beyond early development. PMID:21411674

Baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF).

PubMed

McMurray, John J V; Anand, Inder S; Diaz, Rafael; Maggioni, Aldo P; O'Connor, Christopher; Pfeffer, Marc A; Solomon, Scott D; Tendera, Michal; van Veldhuisen, Dirk J; Albizem, Moetaz; Cheng, Sunfa; Scarlata, Debra; Swedberg, Karl; Young, James B

2013-03-01

This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes. Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate < 60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106-117) g/L. The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.

Prior exposure to repeated immobilization or chronic unpredictable stress protects from some negative sequels of an acute immobilization.

PubMed

Pastor-Ciurana, Jordi; Rabasa, Cristina; Ortega-Sánchez, Juan A; Sanchís-Ollè, Maria; Gabriel-Salazar, Marina; Ginesta, Marta; Belda, Xavier; Daviu, Núria; Nadal, Roser; Armario, Antonio

2014-05-15

Exposure to chronic unpredictable stress (CUS) is gaining acceptance as a putative animal model of depression. However, there is evidence that chronic exposure to stress can offer non-specific stress protection from some effects of acute superimposed stressors. We then compared in adult male rats the protection afforded by prior exposure to CUS with the one offered by repeated immobilization on boards (IMO) regarding some of the negative consequences of an acute exposure to IMO. Repeated exposure to IMO protected from the negative consequences of an acute IMO on activity in an open-field, saccharin intake and body weight gain. Active coping during IMO (struggling) was markedly reduced by repeated exposure to the same stressor, but it was not affected by a prior history of CUS, suggesting that our CUS protocol does not appear to impair active coping responses. CUS exposure itself caused a strong reduction of activity in the open-field but appeared to protect from the hypo-activity induced by acute IMO. Moreover, prior CUS offered partial protection from acute IMO-induced reduction of saccharin intake and body weight gain. It can be concluded that a prior history of CUS protects from some of the negative consequences of exposure to a novel severe stressor, suggesting the development of partial cross-adaptation whose precise mechanisms remain to be studied. Copyright © 2014 Elsevier B.V. All rights reserved.

A novel design for maskless direct laser writing nanolithography: Combination of diffractive optical element and nonlinear absorption inorganic resists

NASA Astrophysics Data System (ADS)

Zha, Yikun; Wei, Jingsong; Gan, Fuxi

2013-09-01

Maskless laser direct writing lithography has been applied in the fabrication of optical elements and electric-optical devices. With the development of technology, the feature size of the elements and devices is required to reduce down to nanoscale. Increasing the numerical aperture of converging lens and shortening the laser wavelength are good methods to obtain the small spot and reduce the feature size to nanoscale, while this will cause the reduction of the depth of focus. The reduction of depth of focus will lead to some difficulties in the focusing and tracking servo controlling during the high speed laser direct writing lithography. In this work, the combination of the diffractive optical elements and the nonlinear absorption inorganic resist thin films cannot only extend the depth of focus, but also reduce the feature size of the lithographic marks down to nanoscale. By using the five-zone annular phase-only binary pupil filter as the diffractive optical elements and AgInSbTe as the nonlinear absorption inorganic resist thin film, the depth of focus cannot only extend to 7.39 times that of the focused spot, but also reduce the lithographic feature size down to 54.6 nm. The ill-effect of sidelobe on the lithography is also eliminated by the nonlinear reverse saturable absorption and the phase change threshold lithographic characteristics.

The p53 inhibitor, pifithrin-{alpha}, suppresses self-renewal of embryonic stem cells

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

Abdelalim, Essam Mohamed, E-mail: essam_abdelalim@yahoo.com; Department of Cytology and Histology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522; Tooyama, Ikuo

2012-04-13

Highlights: Black-Right-Pointing-Pointer We determine the role of p53 in ES cells under unstressful conditions. Black-Right-Pointing-Pointer PFT-{alpha} suppresses ES cell proliferation. Black-Right-Pointing-Pointer PFT-{alpha} induces ES cell cycle arrest. Black-Right-Pointing-Pointer PFT-{alpha} downregulates Nanog and cyclin D1. -- Abstract: Recent studies have reported the role of p53 in suppressing the pluripotency of embryonic stem (ES) cells after DNA damage and blocking the reprogramming of somatic cells into induced pluripotent stem (iPS) cells. However, to date no evidence has been presented to support the function of p53 in unstressed ES cells. In this study, we investigated the effect of pifithrin (PFT)-{alpha}, an inhibitor ofmore » p53-dependent transcriptional activation, on self-renewal of ES cells. Our results revealed that treatment of ES cells with PFT-{alpha} resulted in the inhibition of ES cell propagation in a dose-dependent manner, as indicated by a marked reduction in the cell number and colony size. Also, PFT-{alpha} caused a cell cycle arrest and significant reduction in DNA synthesis. In addition, inhibition of p53 activity reduced the expression levels of cyclin D1 and Nanog. These findings indicate that p53 pathway in ES cells rather than acting as an inactive gene, is required for ES cell proliferation and self-renewal under unstressful conditions.« less

Persistently Altered Epigenetic Marks in the Mouse Uterus After Neonatal Estrogen Exposure

PubMed Central

Jefferson, Wendy N.; Chevalier, Dominique M.; Phelps, Jazma Y.; Cantor, Amy M.; Padilla-Banks, Elizabeth; Newbold, Retha R.; Archer, Trevor K.; Kinyamu, H. Karimi

2013-01-01

Neonatal exposure to diethylstilbestrol (DES) causes permanent alterations in female reproductive tract gene expression, infertility, and uterine cancer in mice. To determine whether epigenetic mechanisms could explain these phenotypes, we first tested whether DES altered uterine expression of chromatin-modifying proteins. DES treatment significantly reduced expression of methylcytosine dioxygenase TET oncogene family, member 1 (TET1) on postnatal day 5; this decrease was correlated with a subtle decrease in DNA 5-hydroxymethylcytosine in adults. There were also significant reductions in histone methyltransferase enhancer of zeste homolog 2 (EZH2), histone lysine acetyltransferase 2A (KAT2A), and histone deacetylases HDAC1, HDAC2, and HDAC3. Uterine chromatin immunoprecipitation was used to analyze the locus-specific association of modified histones with 2 genes, lactoferrin (Ltf) and sine oculis homeobox 1 (Six1), which are permanently upregulated in adults after neonatal DES treatment. Three histone modifications associated with active transcription, histone H3 lysine 9 acetylation (H3K9ac), H3 lysine 4 trimethylation (H3K4me3), and H4 lysine 5 acetylation (H4K5ac) were enriched at specific Ltf promoter regions after DES treatment, but this enrichment was not maintained in adults. H3K9ac, H4K5ac, and H3K4me3 were enriched at Six1 exon 1 immediately after neonatal DES treatment. As adults, DES-treated mice had greater differences in H4K5ac and H3K4me3 occupancy at Six1 exon 1 and new differences in these histone marks at an upstream region. These findings indicate that neonatal DES exposure temporarily alters expression of multiple chromatin-modifying proteins and persistently alters epigenetic marks in the adult uterus at the Six1 locus, suggesting a mechanism for developmental exposures leading to altered reproductive function and increased cancer risk. PMID:24002655

Impact of bariatric surgery on apolipoprotein C-III levels and lipoprotein distribution in obese human subjects.

PubMed

Maraninchi, Marie; Padilla, Nadège; Béliard, Sophie; Berthet, Bruno; Nogueira, Juan-Patricio; Dupont-Roussel, Jeanine; Mancini, Julien; Bégu-Le Corroller, Audrey; Dubois, Noémie; Grangeot, Rachel; Mattei, Catherine; Monclar, Marion; Calabrese, Anastasia; Guérin, Carole; Desmarchelier, Charles; Nicolay, Alain; Xiao, Changting; Borel, Patrick; Lewis, Gary F; Valéro, René

Elevated apolipoprotein C-III (apoC-III) has been postulated to contribute to the atherogenic dyslipidemia seen in obesity and insulin-resistant states, mainly by impairing plasma triglyceride-rich lipoprotein (TRL) metabolism. Bariatric surgery is associated with improvements of several obesity-associated metabolic abnormalities, including a reduction in plasma triglycerides (TGs) and an increase in plasma high-density lipoprotein cholesterol (HDL-C). We investigated the specific effect of bariatric surgery on apoC-III concentrations in plasma, non-HDL, and HDL fractions in relation to lipid profile parameters evolution. A total of 132 obese subjects undergoing bariatric surgery, gastric bypass (n = 61) or sleeve gastrectomy (n = 71), were studied 1 month before surgery and 6 and 12 months after surgery. Plasma apoC-III, non-HDL-apoC-III, and HDL-apoC-III concentrations were markedly reduced after surgery and strongly associated with reduction in plasma TG. This decrease was accompanied by a redistribution of apoC-III from TRL to HDL fractions. In multivariate analysis, plasma apoC-III was the strongest predictor of TG reduction after surgery, and the increase of HDL-C was positively associated with plasma adiponectin and negatively with body mass index. Marked reduction of apoC-III and changes in its distribution between TRL and HDL consistent with a better lipid profile are achieved in obese patients after bariatric surgery. These apoC-III beneficial modifications may have implications in dyslipidemia improvement and contribute to cardiovascular risk reduction after surgery. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Marked surface inversions and wind shear: A safety risk for departing aircraft

NASA Technical Reports Server (NTRS)

Korhonen, O.

1983-01-01

Marked surface inversions occur most frequently in dry continental climates, where low atmospheric humidity allows heat transfer by long wave thermal radiation. In the northern latitudes, surface inversions reach their maximum intensity during the winter, when the incoming Sun's radiation is negligible and radiative cooling is dominant during the long nights. During winter, air mass boundaries are sharp, which causes formation of marked surface inversions. The existence of these inversions and sharp boundaries increase the risk of wind shear. The information should refer to marked inversions exceeding a temperature difference of 10 deg C up to 1000 feet. The need to determine the temperature range over which he information is operationally needed and the magnitude of the inversion required before a notification to pilots prior to departure is warranted are outlined.

Bombesin, somatostatin, and related peptides: actions on thermoregulation

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

Brown, M.R.

1981-11-01

Bombesin acts within the anterior hypothalamic preoptic area to interfere with thermoregulation in the rat. The body temperature (T/sub b/) of animals receiving bombesin varies in parallel with ambient temperature (T/sub a/). Bombesin-induced reduction of T/sub b/ in animals at low T/sub a/ is associated with a marked reduction of oxygen consumption (Vo/sub 2/). Some somatostatin-related peptides, e.g., desAA/sup 1,2,4,5,12,13/ (D-Trp/sup 8/)-somatostatin (ODT8-SS), act within the brain to prevent bombesin-induced reduction of Vo/sub 2/ and T/sub b/. ODT8-SS also produces hyperthermia not associated with an increase in Vo/sub 2/.

Laser-Marking Mechanism of Thermoplastic Polyurethane/Bi2O3 Composites.

PubMed

Zhong, Wei; Cao, Zheng; Qiu, Pengfei; Wu, Dun; Liu, Chunlin; Li, Huili; Zhu, He

2015-11-04

Using bismuth oxide (Bi2O3) as a laser-marking additive and thermoplastic polyurethane (TPU) as the matrix, TPU/Bi2O3 composite materials were prepared by melt blending in a torque rheometer. The sheet samples prepared from the TPU/Bi2O3 composites were treated in air by scanning with a neodymium-doped yttrium aluminum garnet (Nd: YAG) pulsed laser beam at a wavelength of 1064 nm. Compared with the pure TPU sample, the laser-marked composite samples exhibited differences in marking contrast as the Bi2O3 content increased from 0.1% to 1.0% based on stereomicroscope analysis. Scanning electron microscopy, X-ray photoelectron spectroscopy, Raman spectroscopy, thermogravimetry analysis, and X-ray diffraction were used to characterize the laser-marked surface material of the composite samples. Furthermore, a mechanism for the laser-effected darkening of the TPU/Bi2O3 composites was proposed. The results herein indicated that the addition of the Bi2O3 laser-sensitive additive to TPU resulted in laser darkening of the TPU/Bi2O3 composites. The marking contrast and visual appearance of the surface of the TPU/Bi2O3 composites after laser irradiation was due to a synergistic effect consisting of carbonization via TPU pyrolysis and reduction of Bi2O3 to black bismuth metal.

Forensic surface metrology: tool mark evidence.

PubMed

Gambino, Carol; McLaughlin, Patrick; Kuo, Loretta; Kammerman, Frani; Shenkin, Peter; Diaczuk, Peter; Petraco, Nicholas; Hamby, James; Petraco, Nicholas D K

2011-01-01

Over the last several decades, forensic examiners of impression evidence have come under scrutiny in the courtroom due to analysis methods that rely heavily on subjective morphological comparisons. Currently, there is no universally accepted system that generates numerical data to independently corroborate visual comparisons. Our research attempts to develop such a system for tool mark evidence, proposing a methodology that objectively evaluates the association of striated tool marks with the tools that generated them. In our study, 58 primer shear marks on 9 mm cartridge cases, fired from four Glock model 19 pistols, were collected using high-resolution white light confocal microscopy. The resulting three-dimensional surface topographies were filtered to extract all "waviness surfaces"-the essential "line" information that firearm and tool mark examiners view under a microscope. Extracted waviness profiles were processed with principal component analysis (PCA) for dimension reduction. Support vector machines (SVM) were used to make the profile-gun associations, and conformal prediction theory (CPT) for establishing confidence levels. At the 95% confidence level, CPT coupled with PCA-SVM yielded an empirical error rate of 3.5%. Complementary, bootstrap-based computations for estimated error rates were 0%, indicating that the error rate for the algorithmic procedure is likely to remain low on larger data sets. Finally, suggestions are made for practical courtroom application of CPT for assigning levels of confidence to SVM identifications of tool marks recorded with confocal microscopy. Copyright © 2011 Wiley Periodicals, Inc.

Advances in radiation mutagenesis through studies on Drosophila

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

Muller, H. J.

The approximately linear relation between radiation dose and induced lethals, known for Drosophila spermatozoa, is now extended to spermatids. Data are included regarding oogonia. The linearity principle has been confirmed for minute structural changes in spermatozoa. The dependence of gross structural changes, as multi-hit events, on about the 1.5 power of the dose, long known for spermatozoa, is now extended to spermatids and late oocytes, for relatively short exposures. However, these stages unlike spermatozoa are found to allow union of broken chromosomes. Therefore, the frequencies are lower for more dispersed exposures of these stages, and the precise dose relation variesmore » with the timing. Part of the dominant and even recessive lethals induced in late oocytes follow the same frequency pattern and therefore are multi-hit events. Yet there is a much lower chance after oocytic than spermatozoan irradiation that two broken ends derived from different hits will unite, hence most such unions are nonreciprocal. The following is the order of decreasing radiation mutability of different stages found by ourselves and others: spermatids, spermatozoa in females, spermatozoa 0 to 1 day before ejaculation, earlier spermatozoa, late oocytes, gonia of either sex. Lethal frequencies for these stages range over approximately an order of magnitude, gross structural changes far more widely. Of potential usefulness is our extension of the principle of marked reduction of radiation mutagenesis by anoxia, known for spermatozoa in adult males, to those in pupal males and in females to spermatids and to oocytes. In spermatids this reduction is especially marked but the increase caused by substituting oxygen for air is less marked, perhaps because of enzymatic differences. In contrast, the induction of gross structural changes in oocytes, but not in spermatids, is markedly reduced by oxygen post-treatment; it is increased by dehydration. The efficacy of induction of structural changes by treatment of spermatozoa, whether with radiation or chemical mutagens, is correlated with the conditions of sperm utilization and egg production. Improving our perspective on radiation effects, some 800,000 offspring have been scored for spontaneous visible mutations of 13 specific loci. The average point-mutation rate was 0.5 to 1.0 per locus among 10/sup 5/ germ cells. Most mutations occurred in peri-fertilization stages. All loci studied mutated from one to nine times. Loci mutating oftener spontaneously also gave more radiation mutation, in other studies. Spectra of individual loci prove similar for spontaneous and induced mutation. Studies on back-mutations also showed similarity of spontaneous and radiation mutations. The doubling dose for back-mutations of forked induced in spermatozoa was several hundred roentgens, similar to that for direct point-mutations induced in gonia at diverse loci. Recent analyses of human mutational load lead to mutation-rate estimates like those earlier based on extrapolations from Drosophila, thus supporting the significance for man of the present studies. (auth)« less

Accomplishments in Photovoltaic Manufacturing R&D | Photovoltaic Research |

Science.gov Websites

made that significantly reduced the cost of solar modules while increasing their reliability and -area efficiency. Manufacturing Processes Half the cost of producing a solar module is incurred in wafer project partners marked significant progress in module cost reduction. A few notable examples follow

Alterations in gut microflora populations and brush border functionality following intra-amniotic daidzein administration

USDA-ARS?s Scientific Manuscript database

Daidzein is an isoflavone found primarily in soybean and various soy-based products such as tofu. In the intestines, daidzein is reductively transformed to its constituent metabolites equol and O-desmethylangolensin. Although the ingestion of daidzein has been associated with marked physiological im...

Three-dimensional interconnected network of graphene-wrapped porous silicon spheres: in situ magnesiothermic-reduction synthesis and enhanced lithium-storage capabilities.

PubMed

Wu, Ping; Wang, Hui; Tang, Yawen; Zhou, Yiming; Lu, Tianhong

2014-03-12

A novel type of 3D porous Si-G micro/nanostructure (i.e., 3D interconnected network of graphene-wrapped porous silicon spheres, Si@G network) was constructed through layer-by-layer assembly and subsequent in situ magnesiothermic-reduction methodology. Compared with bare Si spheres, the as-synthesized Si@G network exhibits markedly enhanced anodic performance in terms of specific capacity, cycling stability, and rate capability, making it an ideal anode candidate for high-energy, long-life, and high-power lithium-ion batteries.

New Structural Patterns in Moribund Grammar: Case Marking in Heritage German

PubMed Central

Yager, Lisa; Hellmold, Nora; Joo, Hyoun-A; Putnam, Michael T.; Rossi, Eleonora; Stafford, Catherine; Salmons, Joseph

2015-01-01

Research treats divergences between monolingual and heritage grammars in terms of performance—‘L1 attrition,’ e.g., lexical retrieval—or competence—‘incomplete acquisition’, e.g., lack of overt tense markers (e.g., Polinsky, 1995; Sorace, 2004; Montrul, 2008; Schmid, 2010). One classic difference between monolingual and Heritage German is reduction in morphological case in the latter, especially loss of dative marking. Our evidence from several Heritage German varieties suggests that speakers have not merely lost case, but rather developed innovative structures to mark it. More specifically, Heritage German speakers produce dative forms in line with established patterns of Differential Object Marking (Bossong, 1985, 1991; Aissen, 2003), suggesting a reallocated mapping of case. We take this as evidence for innovative reanalysis in heritage grammars (Putnam and Sánchez, 2013). Following Kamp and Reyle (1993) and Wechsler (2011, 2014), the dative adopts a more indexical discourse function, forging a tighter connection between morphosyntax and semantic properties. Moribund grammars deploy linguistic resources in novel ways, a finding which can help move us beyond simple narratives of ‘attrition’ and ‘incomplete acquisition.’ PMID:26635649

Cellular content and biosynthesis of polyamines during rooster spermatogenesis.

PubMed Central

Oliva, R; Vidal, S; Mezquita, C

1982-01-01

The natural polyamines spermine and spermidine, and the diamine putrescine, were extracted from rooster testis cells separated by sedimentation at unit gravity, and from vas-deferens spermatozoa. The ratios spermine/DNA and spermidine/DNA were kept relatively constant throughout spermatogenesis, whereas the ratio putrescine/DNA rose in elongated spermatids. The cellular content of spermine, spermidine and putrescine decreased markedly in mature spermatozoa. Two rate-limiting enzymes in the biosynthetic pathway of polyamines, ornithine decarboxylase and S-adenosyl-L-methionine decarboxylase, showed their highest activities at the end of spermiogenesis and were not detectable in vas-deferens spermatozoa. A marked reduction in cell volume during spermiogenesis without a parallel decrease in the cellular content of polyamines suggests the possibility that the marked changes in chromatin composition and structure occurring in rooster late spermatids could take place in an ambience of high polyamine concentration. Images PLATE 1 PMID:7159401

Comparison of Lives Saved Tool model child mortality estimates against measured data from vector control studies in sub-Saharan Africa

PubMed Central

2011-01-01

Background Insecticide-treated mosquito nets (ITNs) and indoor-residual spraying have been scaled-up across sub-Saharan Africa as part of international efforts to control malaria. These interventions have the potential to significantly impact child survival. The Lives Saved Tool (LiST) was developed to provide national and regional estimates of cause-specific mortality based on the extent of intervention coverage scale-up. We compared the percent reduction in all-cause child mortality estimated by LiST against measured reductions in all-cause child mortality from studies assessing the impact of vector control interventions in Africa. Methods We performed a literature search for appropriate studies and compared reductions in all-cause child mortality estimated by LiST to 4 studies that estimated changes in all-cause child mortality following the scale-up of vector control interventions. The following key parameters measured by each study were applied to available country projections: baseline all-cause child mortality rate, proportion of mortality due to malaria, and population coverage of vector control interventions at baseline and follow-up years. Results The percent reduction in all-cause child mortality estimated by the LiST model fell within the confidence intervals around the measured mortality reductions for all 4 studies. Two of the LiST estimates overestimated the mortality reductions by 6.1 and 4.2 percentage points (33% and 35% relative to the measured estimates), while two underestimated the mortality reductions by 4.7 and 6.2 percentage points (22% and 25% relative to the measured estimates). Conclusions The LiST model did not systematically under- or overestimate the impact of ITNs on all-cause child mortality. These results show the LiST model to perform reasonably well at estimating the effect of vector control scale-up on child mortality when compared against measured data from studies across a range of malaria transmission settings. The LiST model appears to be a useful tool in estimating the potential mortality reduction achieved from scaling-up malaria control interventions. PMID:21501453

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

INVESTIGATION OF REDUCTION OF ABSORPTION OF RADIOACTIVE MATERIAL BY MEANS OF ASTRINGENTS (in German)

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

Lehrnbecher, W.

1963-02-01

An attempt was made to use the astringent properties of two substances, adrenalin and tannin, for reducing skin absorption of radioactive substances on female Wistar rats. The effect of 1/2% adrenalin emulsion and of a 2% tannin solution on the absorption of a BETA -emitting substance (Sr/sup 89/Cl/sub 2/ solution) was observed over three periods of 30, 60, and 90 min. A reduction of absorption was found after using adrenalin and tanning. The effect of adrenalin was small, particularly over prolonged periods of observation, and there was a marked reduction of absorption resulting from the use of tannin during allmore » periods of observation-. A method is described that permits an estimate of the reduction in skin absorption of BETA rays. (P.C.H.)« less

Chlorophyll Synthase under Epigenetic Surveillance Is Critical for Vitamin E Synthesis, and Altered Expression Affects Tocopherol Levels in Arabidopsis1[OPEN

PubMed Central

Zhang, Chunyu; Zhang, Wei; Ren, Guodong; Li, Delin; Cahoon, Rebecca E.; Chen, Ming; Zhou, Yongming; Yu, Bin

2015-01-01

Chlorophyll synthase catalyzes the final step in chlorophyll biosynthesis: the esterification of chlorophyllide with either geranylgeranyl diphosphate or phytyl diphosphate (PDP). Recent studies have pointed to the involvement of chlorophyll-linked reduction of geranylgeranyl by geranylgeranyl reductase as a major pathway for the synthesis of the PDP precursor of tocopherols. This indirect pathway of PDP synthesis suggests a key role of chlorophyll synthase in tocopherol production to generate the geranylgeranyl-chlorophyll substrate for geranylgeranyl reductase. In this study, contributions of chlorophyll synthase to tocopherol formation in Arabidopsis (Arabidopsis thaliana) were explored by disrupting and altering expression of the corresponding gene CHLOROPHYLL SYNTHASE (CHLSYN; At3g51820). Leaves from the homozygous chlysyn1-1 null mutant were nearly devoid of tocopherols, whereas seeds contained only approximately 25% of wild-type tocopherol levels. Leaves of RNA interference lines with partial suppression of CHLSYN displayed marked reductions in chlorophyll but up to a 2-fold increase in tocopherol concentrations. Cauliflower mosaic virus35S-mediated overexpression of CHLSYN unexpectedly caused a cosuppression phenotype at high frequencies accompanied by strongly reduced chlorophyll content and increased tocopherol levels. This phenotype and the associated detection of CHLSYN-derived small interfering RNAs were reversed with CHLSYN overexpression in rna-directed rna polymerase6 (rdr6), which is defective in RNA-dependent RNA polymerase6, a key enzyme in sense transgene-induced small interfering RNA production. CHLSYN overexpression in rdr6 had little effect on chlorophyll content but resulted in up to a 30% reduction in tocopherol levels in leaves. These findings show that altered CHLSYN expression impacts tocopherol levels and also, show a strong epigenetic surveillance of CHLSYN to control chlorophyll and tocopherol synthesis. PMID:26048882

Metabolomics Based Profiling of Dexamethasone Side Effects in Rats

PubMed Central

Malkawi, Abeer K.; Alzoubi, Karem H.; Jacob, Minnie; Matic, Goran; Ali, Asmaa; Al Faraj, Achraf; Almuhanna, Falah; Dasouki, Majed; Abdel Rahman, Anas M.

2018-01-01

Dexamethasone (Dex) is a synthetic glucocorticoid that has anti-inflammatory and immunosuppressant effects and is used in several conditions such as asthma and severe allergy. Patients receiving Dex, either at a high dose or for a long time, might develop several side effects such as hyperglycemia, weight change, or osteoporosis due to its in vivo non-selectivity. Herein, we used liquid chromatography-tandem mass spectrometry-based comprehensive targeted metabolomic profiling as well as radiographic imaging techniques to study the side effects of Dex treatment in rats. The Dex-treated rats suffered from a ∼20% reduction in weight gain, hyperglycemia (145 mg/dL), changes in serum lipids, and reduction in total serum alkaline phosphatase (ALP) (∼600 IU/L). Also, compared to controls, Dex-treated rats showed a distinctive metabolomics profile. In particular, serum amino acids metabolism showed six-fold reduction in phenylalanine, lysine, and arginine levels and upregulation of tyrosine and hydroxyproline reflecting perturbations in gluconeogenesis and protein catabolism which together lead to weight loss and abnormal bone metabolism. Sorbitol level was markedly elevated secondary to hyperglycemia and reflecting activation of the polyol metabolism pathway causing a decrease in the availability of reducing molecules (glutathione, NADPH, NAD+). Overexpression of succinylacetone (4,6-dioxoheptanoic acid) suggests a novel inhibitory effect of Dex on hepatic fumarylacetoacetate hydrolase. The acylcarnitines, mainly the very long chain species (C12, C14:1, C18:1) were significantly increased after Dex treatment which reflects degradation of the adipose tissue. In conclusion, long-term Dex therapy in rats is associated with a distinctive metabolic profile which correlates with its side effects. Therefore, metabolomics based profiling may predict Dex treatment-related side effects and may offer possible novel therapeutic interventions. PMID:29503615

Reappraisal of the diuretic effect of empagliflozin in the EMPA-REG OUTCOME trial: Comparison with classic diuretics.

PubMed

Scheen, A J

2016-09-01

Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has been associated with a remarkable reduction in cardiovascular and all-cause mortality in patients with type 2 diabetes and antecedents of cardiovascular disease. This effect was attributed to a diuretic (haemodynamic) rather than metabolic (antiatherogenic) effect. The aim of this review is to offer arguments that either support or challenge this 'diuretic hypothesis'. The literature was scrutinized to: (1) examine the diuretic effects of SGLT2 inhibitors vs. hydrochlorothiazide as the reference diuretic; (2) analyze the effects of classic diuretics on cardiovascular outcomes and mortality in diabetic patients; and (3) reconsider some of the specific analyses of the EMPA-REG OUTCOME trial possibly related to a diuretic effect. The diuretic effect of empagliflozin has so far been poorly investigated, although SGLT2 inhibitors have actions distinct from those of classic diuretics. The effects of thiazide-like diuretics on cardiovascular and overall mortality have been limited in diabetic patients with hypertension, whereas the effects of mineralocorticoid receptor antagonists in subgroups of diabetic patients with heart failure were more impressive, but still largely inferior to those reported in EMPA-REG, where relative reductions in mortality with empagliflozin were observed in diabetic patients with or without heart failure, arterial hypertension, renal impairment or diuretic background therapy. Although the diuretic hypothesis was put forward to explain the remarkable reduction in mortality with empagliflozin in EMPA-REG, the available results do not support a major contribution of this mechanism, unless the specific diuretic effect of SGLT2 inhibitors turns out to be markedly different from those of classic diuretics. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

L-asparaginase inhibits invasive and angiogenic activity and induces autophagy in ovarian cancer

PubMed Central

Yu, Minshu; Henning, Ryan; Walker, Amanda; Kim, Geoffrey; Perroy, Alyssa; Alessandro, Riccardo; Virador, Victoria; Kohn, Elise C

2012-01-01

Recent work identified L-asparaginase (L-ASP) as a putative therapeutic target for ovarian cancer. We suggest that L-ASP, a dysregulator of glycosylation, would interrupt the local microenvironment, affecting the ovarian cancer cell—endothelial cell interaction and thus angiogenesis without cytotoxic effects. Ovarian cancer cell lines and human microvascular endothelial cells (HMVEC) were exposed to L-ASP at physiologically attainable concentrations and subjected to analyses of endothelial tube formation, invasion, adhesion and the assessment of sialylated proteins involved in matrix-associated and heterotypic cell adhesion. Marked reduction in HMVEC tube formation in vitro, HMVEC and ovarian cancer cell invasion, and heterotypic cell-cell and cell-matrix adhesion was observed (P < 0.05–0.0001). These effects were associated with reduced binding to ß1integrin, activation of FAK, and cell surface sialyl LewisX (sLex) expression. No reduction in HMVEC E-selectin expression was seen consistent with the unidirectional inhibitory actions observed. L-ASP concentrations were non-toxic to either ovarian cancer or HMVEC lines in the time frame of the assays. However, early changes of autophagy were observed in both cell types with induction of ATG12, beclin-1, and cleavage of LC-3, indicating cell injury did occur. These data and the known mechanism of action of L-ASP on glycosylation of nascent proteins suggest that L-ASP reduces of ovarian cancer dissemination and progression through modification of its microenvironment. The reduction of ovarian cancer cell surface sLex inhibits interaction with HMVEC and thus HMVEC differentiation into tubes, inhibits interaction with the local matrix reducing invasive behaviour, and causes cell injury initiating autophagy in tumour and vascular cells. PMID:22333033

Effect of Probiotic Containing Ice-cream on Salivary Mutans Streptococci (SMS) Levels in Children of 6-12 Years of Age: A Randomized Controlled Double Blind Study with Six-months Follow Up.

PubMed

Ashwin, Devasya; Ke, Vijayaprasad; Taranath, Mahanthesh; Ramagoni, Naveen Kumar; Nara, Asha; Sarpangala, Mythri

2015-02-01

To evaluate the caries risk based on the salivary levels of streptococcus mutans in children of 6-12 years of age group before and after consuming probiotic ice-cream containing Bifidobacterium lactis Bb-12 and Lactobacillus acidophilus La-5. A double blind, placebo controlled trial was carried out in 60 children aged between 6 to 12 years with zero decayed, missing, and filled teeth (DMFT). They were randomly divided into two equal groups. Saliva sample were collected before the consumption of ice-cream and Streptococcus mutans count was calculated and recorded as baseline data. For the next seven days both the groups were given ice creams marked as A and B. Saliva samples were collected after ice-cream consumption at the end of study period and also after a washout period of 30 days and again after six months. Samples were inoculated and colonies were counted. On statistical evaluation by students paired t-test, probiotic ice-cream brought significant reduction in the Streptococcus mutans count after seven days of ice-cream ingestion (p<0.001) and also after 30 d of washout period (p<0.001). There was no significant reduction (p=0.076) by normal ice-cream consumption. After six months of the study period in both the groups the salivary levels of Streptococcus mutans was similar to the baseline. Probiotic ice-cream containing Bifidobacterium lactis Bb-12 and Lactobacillus acidophilus La-5 can cause reduction in caries causative organism. The dosage of the probiotic organisms for the long term or synergetic effect on the oral health are still needed to be explored.

High-protein diet differently modifies intestinal goblet cell characteristics and mucosal cytokine expression in ileum and colon.

PubMed

Lan, Annaïg; Andriamihaja, Mireille; Blouin, Jean-Marc; Liu, Xinxin; Descatoire, Véronique; Desclée de Maredsous, Caroline; Davila, Anne-Marie; Walker, Francine; Tomé, Daniel; Blachier, François

2015-01-01

We have previously shown that high-protein (HP) diet ingestion causes marked changes in the luminal environment of the colonic epithelium. This study aimed to evaluate the impact of such modifications on small intestinal and colonic mucosa, two segments with different transit time and physiological functions. Rats were fed with either normal protein (NP; 14% protein) or HP (53% protein) isocaloric diet for 2 weeks, and parameters related to intestinal mucous-secreting cells and to several innate/adaptive immune characteristics (myeloperoxidase activity, cytokine and epithelial TLR expression, proportion of immune cells in gut-associated lymphoid tissues) were measured in the ileum and colon. In ileum from HP animals, we observed hyperplasia of mucus-producing cells concomitant with an increased expression of Muc2 at both gene and protein levels, reduction of mucosal myeloperoxidase activity, down-regulation of Tlr4 gene expression in enterocytes and down-regulation of mucosal Th cytokines associated with CD4+ lymphocyte reduction in mesenteric lymph nodes. These changes coincided with an increased amount of acetate in the ileal luminal content. In colon, HP diet ingestion resulted in a lower number of goblet cells at the epithelial surface but increased goblet cell number in colonic crypts together with an increased Muc3 and a slight reduction of Il-6 gene expression. Our data suggest that HP diet modifies the goblet cell distribution in colon and, in ileum, increases goblet cell activity and decreases parameters related to basal gut inflammatory status. The impact of HP diet on intestinal mucosa in terms of beneficial or deleterious effects is discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

Chlorophyll Synthase under Epigenetic Surveillance Is Critical for Vitamin E Synthesis, and Altered Expression Affects Tocopherol Levels in Arabidopsis.

PubMed

Zhang, Chunyu; Zhang, Wei; Ren, Guodong; Li, Delin; Cahoon, Rebecca E; Chen, Ming; Zhou, Yongming; Yu, Bin; Cahoon, Edgar B

2015-08-01

Chlorophyll synthase catalyzes the final step in chlorophyll biosynthesis: the esterification of chlorophyllide with either geranylgeranyl diphosphate or phytyl diphosphate (PDP). Recent studies have pointed to the involvement of chlorophyll-linked reduction of geranylgeranyl by geranylgeranyl reductase as a major pathway for the synthesis of the PDP precursor of tocopherols. This indirect pathway of PDP synthesis suggests a key role of chlorophyll synthase in tocopherol production to generate the geranylgeranyl-chlorophyll substrate for geranylgeranyl reductase. In this study, contributions of chlorophyll synthase to tocopherol formation in Arabidopsis (Arabidopsis thaliana) were explored by disrupting and altering expression of the corresponding gene CHLOROPHYLL SYNTHASE (CHLSYN; At3g51820). Leaves from the homozygous chlysyn1-1 null mutant were nearly devoid of tocopherols, whereas seeds contained only approximately 25% of wild-type tocopherol levels. Leaves of RNA interference lines with partial suppression of CHLSYN displayed marked reductions in chlorophyll but up to a 2-fold increase in tocopherol concentrations. Cauliflower mosaic virus35S-mediated overexpression of CHLSYN unexpectedly caused a cosuppression phenotype at high frequencies accompanied by strongly reduced chlorophyll content and increased tocopherol levels. This phenotype and the associated detection of CHLSYN-derived small interfering RNAs were reversed with CHLSYN overexpression in rna-directed rna polymerase6 (rdr6), which is defective in RNA-dependent RNA polymerase6, a key enzyme in sense transgene-induced small interfering RNA production. CHLSYN overexpression in rdr6 had little effect on chlorophyll content but resulted in up to a 30% reduction in tocopherol levels in leaves. These findings show that altered CHLSYN expression impacts tocopherol levels and also, show a strong epigenetic surveillance of CHLSYN to control chlorophyll and tocopherol synthesis. © 2015 American Society of Plant Biologists. All Rights Reserved.

Reduction of eotaxin production and eosinophil recruitment by pulmonary autologous macrophage transfer in a cockroach allergen-induced asthma model.

PubMed

Beal, Dominic R; Stepien, David M; Natarajan, Sudha; Kim, Jiyoun; Remick, Daniel G

2013-12-01

We sought to investigate the effects of cockroach allergen (CRA) exposure on the lung macrophage population to determine how different macrophage phenotypes influence exacerbation of disease. CRA exposure caused significantly reduced expression of CD86 on lung macrophages. These effects were not systemic, as peritoneal macrophage CD86 expression was not altered. To investigate whether naïve macrophages could reduce asthma-like pulmonary inflammation, autologous peritoneal macrophages were instilled into the airways 24 h before the final CRA challenge. Pulmonary inflammation was assessed by measurement of airway hyperresponsiveness, mucin production, inflammatory cell recruitment, and cytokine production. Cell transfer did not have significant effects in control mice, nor did it affect pulmonary mucin production or airway hyperresponsiveness in control or CRA-exposed mice. However, there was significant reduction in the number of eosinophils recovered in the bronchoalveolar lavage (BAL) (5.8 × 10⁵ vs. 0.88 × 10⁵), and total cell recruitment to the airways of CRA-exposed mice was markedly reduced (1.1 × 10⁶ vs. 0.57 × 10⁶). The reduced eosinophil recruitment was reflected by substantially lower levels of eosinophil peroxidase in the lung and significantly lower concentrations of eotaxins in BAL (eotaxin 1: 3 pg/ml vs. undetectable; eotaxin 2: 2,383 vs. 131 pg/ml) and lung homogenate (eotaxin 1: 1,043 vs. 218 pg/ml; eotaxin 2: 10 vs. 1.5 ng/ml). We conclude that CRA decreases lung macrophage CD86 expression. Furthermore, supplementation of the lung cell population with peritoneal macrophages inhibits eosinophil recruitment, achieved through reduction of eotaxin production. These data demonstrate that transfer of naïve macrophages will reduce some aspects of asthma-like pulmonary inflammation in response to CRA.

Metabolomics Based Profiling of Dexamethasone Side Effects in Rats.

PubMed

Malkawi, Abeer K; Alzoubi, Karem H; Jacob, Minnie; Matic, Goran; Ali, Asmaa; Al Faraj, Achraf; Almuhanna, Falah; Dasouki, Majed; Abdel Rahman, Anas M

2018-01-01

Dexamethasone (Dex) is a synthetic glucocorticoid that has anti-inflammatory and immunosuppressant effects and is used in several conditions such as asthma and severe allergy. Patients receiving Dex, either at a high dose or for a long time, might develop several side effects such as hyperglycemia, weight change, or osteoporosis due to its in vivo non-selectivity. Herein, we used liquid chromatography-tandem mass spectrometry-based comprehensive targeted metabolomic profiling as well as radiographic imaging techniques to study the side effects of Dex treatment in rats. The Dex-treated rats suffered from a ∼20% reduction in weight gain, hyperglycemia (145 mg/dL), changes in serum lipids, and reduction in total serum alkaline phosphatase (ALP) (∼600 IU/L). Also, compared to controls, Dex-treated rats showed a distinctive metabolomics profile. In particular, serum amino acids metabolism showed six-fold reduction in phenylalanine, lysine, and arginine levels and upregulation of tyrosine and hydroxyproline reflecting perturbations in gluconeogenesis and protein catabolism which together lead to weight loss and abnormal bone metabolism. Sorbitol level was markedly elevated secondary to hyperglycemia and reflecting activation of the polyol metabolism pathway causing a decrease in the availability of reducing molecules (glutathione, NADPH, NAD + ). Overexpression of succinylacetone (4,6-dioxoheptanoic acid) suggests a novel inhibitory effect of Dex on hepatic fumarylacetoacetate hydrolase. The acylcarnitines, mainly the very long chain species (C12, C14:1, C18:1) were significantly increased after Dex treatment which reflects degradation of the adipose tissue. In conclusion, long-term Dex therapy in rats is associated with a distinctive metabolic profile which correlates with its side effects. Therefore, metabolomics based profiling may predict Dex treatment-related side effects and may offer possible novel therapeutic interventions.

Effect of Probiotic Containing Ice-cream on Salivary Mutans Streptococci (SMS) Levels in Children of 6-12 Years of Age: A Randomized Controlled Double Blind Study with Six-months Follow Up

PubMed Central

KE, Vijayaprasad; Taranath, Mahanthesh; Ramagoni, Naveen Kumar; Nara, Asha; Sarpangala, Mythri

2015-01-01

Introduction: To evaluate the caries risk based on the salivary levels of streptococcus mutans in children of 6-12 years of age group before and after consuming probiotic ice-cream containing Bifidobacterium lactis Bb-12 and Lactobacillus acidophilus La-5. Materials and Methods: A double blind, placebo controlled trial was carried out in 60 children aged between 6 to 12 years with zero decayed, missing, and filled teeth (DMFT). They were randomly divided into two equal groups. Saliva sample were collected before the consumption of ice-cream and Streptococcus mutans count was calculated and recorded as baseline data. For the next seven days both the groups were given ice creams marked as A and B. Saliva samples were collected after ice-cream consumption at the end of study period and also after a washout period of 30 days and again after six months. Samples were inoculated and colonies were counted. Results: On statistical evaluation by students paired t-test, probiotic ice-cream brought significant reduction in the Streptococcus mutans count after seven days of ice-cream ingestion (p<0.001) and also after 30 d of washout period (p<0.001). There was no significant reduction (p=0.076) by normal ice-cream consumption. After six months of the study period in both the groups the salivary levels of Streptococcus mutans was similar to the baseline. Conclusion: Probiotic ice-cream containing Bifidobacterium lactis Bb-12 and Lactobacillus acidophilus La-5 can cause reduction in caries causative organism. The dosage of the probiotic organisms for the long term or synergetic effect on the oral health are still needed to be explored. PMID:25859515

Lipido-sterolic extract of Serenoa repens (LSESr, Permixon) treatment affects human prostate cancer cell membrane organization.

PubMed

Petrangeli, E; Lenti, L; Buchetti, B; Chinzari, P; Sale, P; Salvatori, L; Ravenna, L; Lococo, E; Morgante, E; Russo, A; Frati, L; Di Silverio, F; Russo, M A

2009-04-01

The molecular mechanism by which the lipido-sterolic extract of Serenoa repens (LSESr, Permixon) affects prostate cells remains to be fully elucidated. In androgen-independent PC3 prostate cancer cells, the LSESr-induced effects on proliferation and apoptosis were evaluated by counting cells and using a FACScan cytofluorimeter. PC3 cells were stained with JC-1 dye to detect mitochondrial membrane potential. Cell membrane lipid composition was evaluated by thin layer chromatography and gas chromatographic analysis. Akt phosphorylation was analyzed by Western blotting and cellular ultrastructure through electron microscopy. LSESr (12.5 and 25 microg/ml) administration exerted a biphasic action by both inhibiting proliferation and stimulating apoptosis. After 1 h, it caused a marked reduction in the mitochondrial potential, decreased cholesterol content and modified phospholipid composition. A decrease in phosphatidylinositol-4,5-bisphosphate (PIP2) level was coupled with reduced Akt phosphorylation. After 24 h, all of these effects were restored to pre-treatment conditions; however, the saturated (SFA)/unsaturated fatty acid (UFA) ratio increased, mainly due to a significant decrease in omega 6 content. The reduction in cholesterol content could be responsible for both membrane raft disruption and redistribution of signaling complexes, allowing for a decrease of PIP2 levels, reduction of Akt phosphorylation and apoptosis induction. The decrease in omega 6 content appears to be responsible for the prolonged and more consistent increase in the apoptosis rate and inhibition of proliferation observed after 2-3 days of LSESr treatment. In conclusion, LSESr administration results in complex changes in cell membrane organization and fluidity of prostate cancer cells that have progressed to hormone-independent status. (c) 2008 Wiley-Liss, Inc.

Microstructural Damage During High-Strain Torsion Experiments on Calcite-Anhydrite Aggregates

NASA Astrophysics Data System (ADS)

Cross, A. J.; Skemer, P. A.

2016-12-01

Ductile shear zones play a critical role in localising deformation in the Earth's crust and mantle. Severe grain size reduction - a ubiquitous feature of natural mylonites - is commonly thought to cause strain weakening via a transition to grain size sensitive deformation mechanisms. Although grain size reduction is modulated by grain growth in single-phase aggregates, grain boundary pinning in well-mixed poly-phase composites can inhibit grain growth, leading to microstructural `damage' which is likely a critical element of strain localization in the lithosphere. While dynamic recrystallization has been widely explored in rock mechanics and materials science, the mechanisms behind phase-mixing remain poorly understood. In this contribution we present results from high-strain, deformation experiments on calcite-anhydrite composites. Experiments were conducted in torsion at T = 500-700°C and P 1.5 GPa, using the new Large Volume Torsion (LVT) solid-medium apparatus, to shear strains of 0.5-30. As shear strain increases, progressive thinning and necking of initially large (≤ 1 mm) calcite domains is observed, resulting in an increase in the proportion of interphase boundaries. Grain-size is negatively correlated with the fraction of interphase boundaries, such that calcite grains in well-mixed regions are significantly smaller than those in single-phase domains. Crucially, progressive deformation leads to a reduction in grain-size beyond the lower limit established by the grain size piezometer for mono-phase calcite, implying microstructural damage. These data therefore demonstrate continued microstructural evolution in two-phase composites that is not possible in single-phase aggregates. These observations mark a new `geometric' mechanism for phase mixing, complementing previous models for phase mixing involving chemical reactions, material diffusion, and/or grain boundary sliding.

Effect of gamma irradiation on commercial eggs experimentally inoculated with Salmonella enteritidis

NASA Astrophysics Data System (ADS)

Tellez, I. G.; Trejo, R. M.; Sanchez, R. E.; Ceniceros, R. M.; Luna, Q. P.; Zazua, P.; Hargis, B. M.

1995-02-01

Using intact, fresh shell eggs, inoculated with 10 8 colony-forming units (cfu) of S. enteritidis, the effect of three doses of gamma irradiation on bacteriologic population and physical characteristics (Haugh units and yolk color) of the eggs was determinated. Penetration test area was picked at random just off the air cell of each egg. Aluminum cylinders were attached to the egg surface with a rim of molten paraffin, and 10 8S. enteritidis was then applied to inoculate the egg. Eggs were then irradiated within 2 hours using a Cobalt-60 gamma source at either 1, 2, or 3 kGy. A second set of inoculated, non-irradiated was used as controls. Following irradiation, eggs were maintained at 4°C for 42 hours prior culture. Irradiation with 1 kGy resulted in a significant (P < .05), 3.9 log reduction in detectable S. enteritidis in the shell and a higly significant (P < .025) 95% reduction in detectable S. enteritidis in the internal shell membranes. Irradiation of eggs with either 2 or 3 kGy reduced bacterial contamination to non-detectable levels in both the shell and internal membranes. However, irradiation at either 1, 2 or 3 kGy resulted in a significant (P <- .05) decrease (approximately 50%) in Haugh units. Additionally, irradiation of intact shell eggs at 2 or 3 Kgy significantly (P ≤ .05) reduced yolk color regardless of the level of irradiation exposure implemented. This data indicates that gamma irradiation of intact raw eggs is effective in reducing (1 kGy) or eliminating (2 or more kGy) S. enteritidis contamination. However, each of the levels of irradiation used in the present experiments caused marked reduction of selected measures of egg quality.

Notch3 protein expression in skin fibroblasts from CADASIL patients.

PubMed

Qualtieri, Antonio; Ungaro, Carmine; Bagalà, Angelo; Bianchi, Silvia; Pantoni, Leonardo; Moccia, Marcello; Mazzei, Rosalucia

2018-07-15

CADASIL is an inherited cerebrovascular disease caused by mutations in the NOTCH3 gene. Notch signaling is involved in a broad spectrum of function, from the cell proliferation to apoptosis. Thus far, because the molecular mechanism underlying the pathological alterations remains unclear and taking into account that fibroblasts contribute to the integrity of the vasculature, our aims was to establish whether fibroblasts, in subjects carrying different NOTCH3 mutations, show abnormalities in the protein expression. We performed the investigation on skin fibroblasts in culture obtained from three CADASIL patients and normal subjects. The patients were genetically characterized, and carried a p.R61W, a p.C174T, and p.R103X, mutation respectively. Notch3 expression was first evaluated on fibroblasts by immunofluorescence analysis, then western blot on cellular extract was utilized to validate the immunofluorescence results. The Notch3 immunoreactivity was clearly detected along the cellular body and in the cellular nuclei of the control fibroblasts. We observed a marked, statistically significant, reduction of the fluorescence immunoreactivity in the fibroblasts from patient with the classical C174T cysteine mutation and a less pronounced reduction in the other two subject's samples with respect to the normal controls. These data were confirmed by the immunoblot analysis. Our results show that the investigated three NOTCH3 mutations are associated with a reduction of the levels of Notch3 expression in vitro. Because the smooth muscle cells appear to be predominantly involved in this cerebrovascular disease, our result, despite the limitation of the sample size examinated, clearly suggest that also fibroblasts, directly involved in making the vascular basal lamina and in maintaining the vascular integrity, may play an important role in the mechanism responsible for the disease. Copyright © 2018 Elsevier B.V. All rights reserved.

Genomic analysis of wig-1 pathways.

PubMed

Sedaghat, Yalda; Mazur, Curt; Sabripour, Mahyar; Hung, Gene; Monia, Brett P

2012-01-01

Wig-1 is a transcription factor regulated by p53 that can interact with hnRNP A2/B1, RNA Helicase A, and dsRNAs, which plays an important role in RNA and protein stabilization. in vitro studies have shown that wig-1 binds p53 mRNA and stabilizes it by protecting it from deadenylation. Furthermore, p53 has been implicated as a causal factor in neurodegenerative diseases based in part on its selective regulatory function on gene expression, including genes which, in turn, also possess regulatory functions on gene expression. In this study we focused on the wig-1 transcription factor as a downstream p53 regulated gene and characterized the effects of wig-1 down regulation on gene expression in mouse liver and brain. Antisense oligonucleotides (ASOs) were identified that specifically target mouse wig-1 mRNA and produce a dose-dependent reduction in wig-1 mRNA levels in cell culture. These wig-1 ASOs produced marked reductions in wig-1 levels in liver following intraperitoneal administration and in brain tissue following ASO administration through a single striatal bolus injection in FVB and BACHD mice. Wig-1 suppression was well tolerated and resulted in the reduction of mutant Htt protein levels in BACHD mouse brain but had no effect on normal Htt protein levels nor p53 mRNA or protein levels. Expression microarray analysis was employed to determine the effects of wig-1 suppression on genome-wide expression in mouse liver and brain. Reduction of wig-1 caused both down regulation and up regulation of several genes, and a number of wig-1 regulated genes were identified that potentially links wig-1 various signaling pathways and diseases. Antisense oligonucleotides can effectively reduce wig-1 levels in mouse liver and brain, which results in specific changes in gene expression for pathways relevant to both the nervous system and cancer.

Genomic Analysis of wig-1 Pathways

PubMed Central

Sedaghat, Yalda; Mazur, Curt; Sabripour, Mahyar; Hung, Gene; Monia, Brett P.

2012-01-01

Background Wig-1 is a transcription factor regulated by p53 that can interact with hnRNP A2/B1, RNA Helicase A, and dsRNAs, which plays an important role in RNA and protein stabilization. in vitro studies have shown that wig-1 binds p53 mRNA and stabilizes it by protecting it from deadenylation. Furthermore, p53 has been implicated as a causal factor in neurodegenerative diseases based in part on its selective regulatory function on gene expression, including genes which, in turn, also possess regulatory functions on gene expression. In this study we focused on the wig-1 transcription factor as a downstream p53 regulated gene and characterized the effects of wig-1 down regulation on gene expression in mouse liver and brain. Methods and Results Antisense oligonucleotides (ASOs) were identified that specifically target mouse wig-1 mRNA and produce a dose-dependent reduction in wig-1 mRNA levels in cell culture. These wig-1 ASOs produced marked reductions in wig-1 levels in liver following intraperitoneal administration and in brain tissue following ASO administration through a single striatal bolus injection in FVB and BACHD mice. Wig-1 suppression was well tolerated and resulted in the reduction of mutant Htt protein levels in BACHD mouse brain but had no effect on normal Htt protein levels nor p53 mRNA or protein levels. Expression microarray analysis was employed to determine the effects of wig-1 suppression on genome-wide expression in mouse liver and brain. Reduction of wig-1 caused both down regulation and up regulation of several genes, and a number of wig-1 regulated genes were identified that potentially links wig-1 various signaling pathways and diseases. Conclusion Antisense oligonucleotides can effectively reduce wig-1 levels in mouse liver and brain, which results in specific changes in gene expression for pathways relevant to both the nervous system and cancer. PMID:22347364

Reductions in cardiovascular, cerebrovascular, and respiratory mortality following the national irish smoking ban: interrupted time-series analysis.

PubMed

Stallings-Smith, Sericea; Zeka, Ariana; Goodman, Pat; Kabir, Zubair; Clancy, Luke

2013-01-01

Previous studies have shown decreases in cardiovascular mortality following the implementation of comprehensive smoking bans. It is not known whether cerebrovascular or respiratory mortality decreases post-ban. On March 29, 2004, the Republic of Ireland became the first country in the world to implement a national workplace smoking ban. The aim of this study was to assess the effect of this policy on all-cause and cause-specific, non-trauma mortality. A time-series epidemiologic assessment was conducted, utilizing Poisson regression to examine weekly age and gender-standardized rates for 215,878 non-trauma deaths in the Irish population, ages ≥35 years. The study period was from January 1, 2000, to December 31, 2007, with a post-ban follow-up of 3.75 years. All models were adjusted for time trend, season, influenza, and smoking prevalence. Following ban implementation, an immediate 13% decrease in all-cause mortality (RR: 0.87; 95% CI: 0.76-0.99), a 26% reduction in ischemic heart disease (IHD) (RR: 0.74; 95% CI: 0.63-0.88), a 32% reduction in stroke (RR: 0.68; 95% CI: 0.54-0.85), and a 38% reduction in chronic obstructive pulmonary disease (COPD) (RR: 0.62; 95% CI: 0.46-0.83) mortality was observed. Post-ban reductions in IHD, stroke, and COPD mortalities were seen in ages ≥65 years, but not in ages 35-64 years. COPD mortality reductions were found only in females (RR: 0.47; 95% CI: 0.32-0.70). Post-ban annual trend reductions were not detected for any smoking-related causes of death. Unadjusted estimates indicate that 3,726 (95% CI: 2,305-4,629) smoking-related deaths were likely prevented post-ban. Mortality decreases were primarily due to reductions in passive smoking. The national Irish smoking ban was associated with immediate reductions in early mortality. Importantly, post-ban risk differences did not change with a longer follow-up period. This study corroborates previous evidence for cardiovascular causes, and is the first to demonstrate reductions in cerebrovascular and respiratory causes.

Reductions in Cardiovascular, Cerebrovascular, and Respiratory Mortality following the National Irish Smoking Ban: Interrupted Time-Series Analysis

PubMed Central

Stallings-Smith, Sericea; Zeka, Ariana; Goodman, Pat; Kabir, Zubair; Clancy, Luke

2013-01-01

Background Previous studies have shown decreases in cardiovascular mortality following the implementation of comprehensive smoking bans. It is not known whether cerebrovascular or respiratory mortality decreases post-ban. On March 29, 2004, the Republic of Ireland became the first country in the world to implement a national workplace smoking ban. The aim of this study was to assess the effect of this policy on all-cause and cause-specific, non-trauma mortality. Methods A time-series epidemiologic assessment was conducted, utilizing Poisson regression to examine weekly age and gender-standardized rates for 215,878 non-trauma deaths in the Irish population, ages ≥35 years. The study period was from January 1, 2000, to December 31, 2007, with a post-ban follow-up of 3.75 years. All models were adjusted for time trend, season, influenza, and smoking prevalence. Results Following ban implementation, an immediate 13% decrease in all-cause mortality (RR: 0.87; 95% CI: 0.76–0.99), a 26% reduction in ischemic heart disease (IHD) (RR: 0.74; 95% CI: 0.63–0.88), a 32% reduction in stroke (RR: 0.68; 95% CI: 0.54–0.85), and a 38% reduction in chronic obstructive pulmonary disease (COPD) (RR: 0.62; 95% CI: 0.46–0.83) mortality was observed. Post-ban reductions in IHD, stroke, and COPD mortalities were seen in ages ≥65 years, but not in ages 35–64 years. COPD mortality reductions were found only in females (RR: 0.47; 95% CI: 0.32–0.70). Post-ban annual trend reductions were not detected for any smoking-related causes of death. Unadjusted estimates indicate that 3,726 (95% CI: 2,305–4,629) smoking-related deaths were likely prevented post-ban. Mortality decreases were primarily due to reductions in passive smoking. Conclusions The national Irish smoking ban was associated with immediate reductions in early mortality. Importantly, post-ban risk differences did not change with a longer follow-up period. This study corroborates previous evidence for cardiovascular causes, and is the first to demonstrate reductions in cerebrovascular and respiratory causes. PMID:23637964

Balancing medicine prices and business sustainability: analyses of pharmacy costs, revenues and profit shed light on retail medicine mark-ups in rural Kyrgyzstan

PubMed Central

2010-01-01

Background Numerous not-for-profit pharmacies have been created to improve access to medicines for the poor, but many have failed due to insufficient financial planning and management. These pharmacies are not well described in health services literature despite strong demand from policy makers, implementers, and researchers. Surveys reporting unaffordable medicine prices and high mark-ups have spurred efforts to reduce medicine prices, but price reduction goals are arbitrary in the absence of information on pharmacy costs, revenues, and profit structures. Health services research is needed to develop sustainable and "reasonable" medicine price goals and strategic initiatives to reach them. Methods We utilized cost accounting methods on inventory and financial information obtained from a not-for-profit rural pharmacy network in mountainous Kyrgyzstan to quantify costs, revenues, profits and medicine mark-ups during establishment and maintenance periods (October 2004-December 2007). Results Twelve pharmacies and one warehouse were established in remote Kyrgyzstan with < US $25,000 due to governmental resource-sharing. The network operated at break-even profit, leaving little room to lower medicine prices and mark-ups. Medicine mark-ups needed for sustainability were greater than originally envisioned by network administration. In 2005, 55%, 35%, and 10% of the network's top 50 products revealed mark-ups of < 50%, 50-99% and > 100%, respectively. Annual mark-ups increased dramatically each year to cover increasing recurrent costs, and by 2007, only 19% and 46% of products revealed mark-ups of < 50% and 50-99%, respectively; while 35% of products revealed mark-ups > 100%. 2007 medicine mark-ups varied substantially across these products, ranging from 32% to 244%. Mark-ups needed to sustain private pharmacies would be even higher in the absence of government subsidies. Conclusion Pharmacy networks can be established in hard-to-reach regions with little funding using public-private partnership, resource-sharing models. Medicine prices and mark-ups must be interpreted with consideration for regional costs of business. Mark-ups vary dramatically across medicines. Some mark-ups appear "excessive" but are likely necessary for pharmacy viability. Pharmacy financial data is available in remote settings and can be used towards determination of "reasonable" medicine price goals. Health systems researchers must document the positive and negative financial experiences of pharmacy initiatives to inform future projects and advance access to medicines goals. PMID:20626904

Balancing medicine prices and business sustainability: analyses of pharmacy costs, revenues and profit shed light on retail medicine mark-ups in rural Kyrgyzstan.

PubMed

Waning, Brenda; Maddix, Jason; Soucy, Lyne

2010-07-13

Numerous not-for-profit pharmacies have been created to improve access to medicines for the poor, but many have failed due to insufficient financial planning and management. These pharmacies are not well described in health services literature despite strong demand from policy makers, implementers, and researchers. Surveys reporting unaffordable medicine prices and high mark-ups have spurred efforts to reduce medicine prices, but price reduction goals are arbitrary in the absence of information on pharmacy costs, revenues, and profit structures. Health services research is needed to develop sustainable and "reasonable" medicine price goals and strategic initiatives to reach them. We utilized cost accounting methods on inventory and financial information obtained from a not-for-profit rural pharmacy network in mountainous Kyrgyzstan to quantify costs, revenues, profits and medicine mark-ups during establishment and maintenance periods (October 2004-December 2007). Twelve pharmacies and one warehouse were established in remote Kyrgyzstan with < US $25,000 due to governmental resource-sharing. The network operated at break-even profit, leaving little room to lower medicine prices and mark-ups. Medicine mark-ups needed for sustainability were greater than originally envisioned by network administration. In 2005, 55%, 35%, and 10% of the network's top 50 products revealed mark-ups of < 50%, 50-99% and > 100%, respectively. Annual mark-ups increased dramatically each year to cover increasing recurrent costs, and by 2007, only 19% and 46% of products revealed mark-ups of < 50% and 50-99%, respectively; while 35% of products revealed mark-ups > 100%. 2007 medicine mark-ups varied substantially across these products, ranging from 32% to 244%. Mark-ups needed to sustain private pharmacies would be even higher in the absence of government subsidies. Pharmacy networks can be established in hard-to-reach regions with little funding using public-private partnership, resource-sharing models. Medicine prices and mark-ups must be interpreted with consideration for regional costs of business. Mark-ups vary dramatically across medicines. Some mark-ups appear "excessive" but are likely necessary for pharmacy viability. Pharmacy financial data is available in remote settings and can be used towards determination of "reasonable" medicine price goals. Health systems researchers must document the positive and negative financial experiences of pharmacy initiatives to inform future projects and advance access to medicines goals.

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.

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

Protein phosphatase 2A mediates JS-K-induced apoptosis by affecting Bcl-2 family proteins in human hepatocellular carcinoma HepG2 cells.

PubMed

Liu, Ling; Huang, Zile; Chen, Jingjing; Wang, Jiangang; Wang, Shuying

2018-04-25

Protein phosphatase 2A (PP2A) is an important enzyme within various signal transduction pathways. The present study was investigated PP2A mediates JS-K-induced apoptosis by affecting Bcl-2 family protein. JS-K showed diverse inhibitory effects in five HCC cell lines, especially HepG2 cells. JS-K caused a dose- and time-dependent reduction in cell viability and increased in levels of LDH release. Meanwhile, JS-K- induced apoptosis was characterized by mitochondrial membrane potential reduction, Hoechst 33342 + /PI + dual staining, release of cytochrome c (Cyt c), and activation of cleaved caspase-9/3. Moreover, JS-K-treatment could lead to the activation of protein phosphatase 2A-C (PP2A-C), decrease of anti-apoptotic Bcl-2 family-protein expression including p-Bcl-2 (Ser70), Bcl-2, Bcl-xL, and Mcl-1 as well as the increase of pro-apoptosis Bcl-2 family-protein including Bim, Bad, Bax, and Bak. Furthermore, JS-K caused a marked increase of intracellular NO levels while pre-treatment with Carboxy-PTIO (a NO scavenger) reduced the cytotoxicity effects and the apoptosis rate. Meanwhile, pre-treatment with Carboxy-PTIO attenuated the JS-K-induced up-regulation of PP2A, Cyt c, and cleaved-caspase-9/3 activation. The silencing PP2A-C by siRNA could abolish the activation of PP2A-C, down-regulation of anti-apoptotic Bcl-2 family-protein (p-Bcl-2, Bcl-2, Bcl-xL, and Mcl-1), increase of pro-apoptosis Bcl-2 family-protein (Bim, Bad, Bax, and Bak) and apoptotic-related protein (Cyt c, cleaved caspase-9/3) that were caused by JS-K in HepG2 cells. In addition, pre-treatment with OA (a PP2A inhibitor) also attenuated the above effects induced by JS-K. In summary, NO release from JS-K induces apoptosis through PP2A activation, which contributed to the regulation of Bcl-2 family proteins. © 2018 Wiley Periodicals, Inc.

Defects of Lipid Synthesis Are Linked to the Age-Dependent Demyelination Caused by Lamin B1 Overexpression

PubMed Central

Rolyan, Harshvardhan; Tyurina, Yulia Y.; Hernandez, Marylens; Amoscato, Andrew A.; Sparvero, Louis J.; Nmezi, Bruce C.; Lu, Yue; Estécio, Marcos R. H.; Lin, Kevin; Chen, Junda; He, Rong-Rong; Gong, Pin; Rigatti, Lora H.; Dupree, Jeffrey; Bayır, Hülya; Kagan, Valerian E.; Casaccia, Patrizia

2015-01-01

Lamin B1 is a component of the nuclear lamina and plays a critical role in maintaining nuclear architecture, regulating gene expression and modulating chromatin positioning. We have previously shown that LMNB1 gene duplications cause autosomal dominant leukodystrophy (ADLD), a fatal adult onset demyelinating disease. The mechanisms by which increased LMNB1 levels cause ADLD are unclear. To address this, we used a transgenic mouse model where Lamin B1 overexpression is targeted to oligodendrocytes. These mice showed severe vacuolar degeneration of the spinal cord white matter together with marked astrogliosis, microglial infiltration, and secondary axonal damage. Oligodendrocytes in the transgenic mice revealed alterations in histone modifications favoring a transcriptionally repressed state. Chromatin changes were accompanied by reduced expression of genes involved in lipid synthesis pathways, many of which are known to play important roles in myelin regulation and are preferentially expressed in oligodendrocytes. Decreased lipogenic gene expression resulted in a significant reduction in multiple classes of lipids involved in myelin formation. Many of these gene expression changes and lipid alterations were observed even before the onset of the phenotype, suggesting a causal role. Our findings establish, for the first time, a link between LMNB1 and lipid synthesis in oligodendrocytes, and provide a mechanistic framework to explain the age dependence and white matter involvement of the disease phenotype. These results have implications for disease pathogenesis and may also shed light on the regulation of lipid synthesis pathways in myelin maintenance and turnover. SIGNIFICANCE STATEMENT Autosomal dominant leukodystrophy (ADLD) is fatal neurological disorder caused by increased levels of the nuclear protein, Lamin B1. The disease is characterized by an age-dependent loss of myelin, the fatty sheath that covers nerve fibers. We have studied a mouse model where Lamin B1 level are increased in oligodendrocytes, the cell type that produces myelin in the CNS. We demonstrate that destruction of myelin in the spinal cord is responsible for the degenerative phenotype in our mouse model. We show that this degeneration is mediated by reduced expression of lipid synthesis genes and the subsequent reduction in myelin enriched lipids. These findings provide a mechanistic framework to explain the age dependence and tissue specificity of the ADLD disease phenotype. PMID:26311780

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...

Decreased number of steroid receptors of circulating lymphocytes in Crohn's disease and ulcerative colitis.

PubMed

Krasznai, A; Krajcsi, P; Arányi, P; Mészáros, K; Horváth, I

1986-01-01

The number of steroid receptors of circulating lymphocytes was determined in 13 patients with inflammatory bowel disease and in controls. Marked reduction of the number of receptors was observed both in Crohn's disease and in ulcerative colitis; no receptors were detected by radioactive hormone binding assay in 4 cases.

A Triumph of Hope over Reason? Aid Accords and Education Policy in Kenya

ERIC Educational Resources Information Center

Colclough, Christopher; Webb, Andrew

2012-01-01

Despite a long history of post-independence aid to education, Kenya's relationships with overseas donors have, until recently, been markedly fractious. Donors' concerns about transparency and corruption, in the context of a political regime which became increasingly authoritarian, led to sharp reductions in aid to Kenyan education during the…

High-density lipoprotein particles, coronary heart disease, and niacin

USDA-ARS?s Scientific Manuscript database

In clinical trials, the use of statins in patients with high risk for cardiovascular disease (CVD) has resulted in a 25% to 40% decrease in major clinical events. However, despite a marked reduction (up to 60%) in LDL-C, approximately 50% (or more) of patients continue to have CVD events. This high ...

How to Identify Lead-Free Certification Marks for Drinking Water System & Plumbing Materials

EPA Science Inventory

In 2011, Congress passed the “Reduction of Lead in Drinking Water Act,” which effectively reduces the lead content allowed in material used for potable water plumbing. The Act, which will go into effect on January 4, 2014, changes the definition of “lead-free” by reducing allowed...

How to Identify Lead-Free Certification Marks for Drinking Water System & Plumbing Materials - Presentation

EPA Science Inventory

In 2011, Congress passed the “Reduction of Lead in Drinking Water Act,” which effectively reduces the lead content allowed in material used for potable water plumbing. The Act, which will go into effect on January 4, 2014, changes the definition of “lead-free” by reducing allowed...

Virtue, Practical Wisdom and Character in Teaching

ERIC Educational Resources Information Center

Cooke, Sandra; Carr, David

2014-01-01

Recent reflection on the professional knowledge of teachers has been marked by a shift away from more reductive competence and skill-focused models of teaching towards a view of teacher expertise as involving complex context-sensitive deliberation and judgement. Much of this shift has been inspired by an Aristotelian conception of practical wisdom…

Galantamine Facilitates Acquisition of Hippocampus-Dependent Trace Eyeblink Conditioning in Aged Rabbits

ERIC Educational Resources Information Center

Weible, Aldis P.; Oh, M. Matthew; Lee, Grace; Disterhoft, John F.

2004-01-01

Cholinergic systems are critical to the neural mechanisms mediating learning. Reduced nicotinic cholinergic receptor (nAChR) binding is a hallmark of normal aging. These reductions are markedly more severe in some dementias, such as Alzheimer's disease. Pharmacological central nervous system therapies are a means to ameliorate the cognitive…

The Effects on Monopsony on Strategy and Leadership in Ontario Colleges. Professional File. Number 28

ERIC Educational Resources Information Center

Cooke, Michael

2008-01-01

The period 1995 to 2005 was one of significant turbulence for Ontario colleges, marked by increasing globalization, immigration, disruptions in the labour market, new technologies and dramatic reductions in government operating grants. This study examines how colleges and their leaders responded to those strategic challenges in their official…

Preparation and physicochemical properties of surfactant-free emulsions using electrolytic-reduction ion water containing lithium magnesium sodium silicate.

PubMed

Okajima, Masahiro; Wada, Yuko; Hosoya, Takashi; Hino, Fumio; Kitahara, Yoshiyasu; Shimokawa, Ken-ichi; Ishii, Fumiyoshi

2013-04-01

Surfactant-free emulsions by adding jojoba oil, squalane, olive oil, or glyceryl trioctanoate (medium chain fatty acid triglycerides, MCT) to electrolytic-reduction ion water containing lithium magnesium sodium silicate (GE-100) were prepared, and their physiochemical properties (thixotropy, zeta potential, and mean particle diameter) were evaluated. At an oil concentration of 10%, the zeta potential was ‒22.3 ‒ ‒26.8 mV, showing no marked differences among the emulsions of various types of oil, but the mean particle diameters in the olive oil emulsion (327 nm) and MCT emulsion (295 nm) were smaller than those in the other oil emulsions (452-471 nm). In addition, measurement of the hysteresis loop area of each type of emulsion revealed extremely high thixotropy of the emulsion containing MCT at a low concentration and the olive emulsion. Based on these results, since surfactants and antiseptic agents markedly damage sensitive skin tissue such as that with atopic dermatitis, surfactant- and antiseptic-free emulsions are expected to be new bases for drugs for external use.

Marked Decline in Malaria Prevalence among Pregnant Women and Their Offspring from 1996 to 2010 on the South Kenyan Coast

PubMed Central

Kalayjian, Benjamin C.; Malhotra, Indu; Mungai, Peter; Holding, Penny; King, Christopher L.

2013-01-01

Expanded malaria control in Kenya since the early 2000s has resulted in marked reduction in hospital admissions for malaria; however, no studies have reported changes in malaria infection rates in the same population over this period. Randomly selected archived blood samples from four cohorts of pregnant women and their children from 1996 to 2010 in Kwale District, Coast Province, Kenya, were examined for Plasmodium falciparum (Pf), P. malariae, P. ovale, and Plasmodium vivax by quantitative polymerase chain reaction (PCR) and microscopy. Maternal delivery Pf prevalence by PCR declined from 40% in 2000–2005 to 1% in 2009–2010, concordant with increased bed net and malaria chemoprophylaxis use. Individual risk of Pf infection in children from birth to 3 years in serial longitudinal cohort studies declined from almost 100% in 1996–1999 to 15% in 2006–2010. Declines in P. malariae and P. ovale infections rates were also observed. These results show a profound reduction in malaria transmission in coastal Kenya. PMID:24080635

Early trends in N-terminal pro-brain natriuretic peptide values after left ventricular assist device implantation for chronic heart failure.

PubMed

Hasin, Tal; Kushwaha, Sudhir S; Lesnick, Timothy G; Kremers, Walter; Boilson, Barry A; Schirger, John A; Clavell, Alfredo L; Rodeheffer, Richard J; Frantz, Robert P; Edwards, Brooks S; Pereira, Naveen L; Stulak, John M; Joyce, Lyle; Daly, Richard; Park, Soon J; Jaffe, Allan S

2014-10-15

Left ventricular assist devices (LVADs) acutely decrease left ventricular wall stress. Thus, early postoperative levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) should decrease. This study investigated postoperative changes in NT-proBNP levels, the parameters related to changes, and the possible association with complications by performing a retrospective analysis of changes in daily NT-proBNP (pg/ml) levels from admission to discharge both before and after LVAD implantation in a tertiary referral center. For 72 patients implanted with HeartMate II LVADs, baseline NT-proBNP levels were elevated at 3,943 ng/ml (interquartile range 1,956 to 12,964). Preoperative stabilization led to marked decreases in NT-proBNP. Levels peaked 3 days after surgery and subsequently decreased. Patients with complicated postoperative courses had higher early postoperative elevations. By discharge, NT-proBNP decreased markedly but was still 2.83 (1.60 to 5.76) times the age-based upper limit of normal. The 26% reduction in NT-proBNP between admission and discharge was due mostly to the preoperative reductions and not those induced by the LVAD itself. The decrease was not associated with decreases in LV volume. In conclusion, preoperative treatment reduces NT-proBNP values. The magnitude of early postoperative changes is related to the clinical course. Levels at discharge remain markedly elevated and similar to values after preoperative stabilization despite presumptive acute LV unloading. Copyright © 2014 Elsevier Inc. All rights reserved.

Curcumin synergizes the growth inhibitory properties of Indian toad (Bufo melanostictus Schneider) skin-derived factor (BM-ANF1) in HCT-116 colon cancer cells.

PubMed

Giri, Biplab; Gomes, Antony; Sengupta, Radha; Banerjee, Sanjeev; Nautiyal, Jyoti; Sarkar, Fazlul H; Majumdar, Adhip P N

2009-01-01

Curcumin, an active ingredient of turmeric with no discernable toxicity, inhibits the growth of transformed cells and the development and progression of colon carcinogenesis in experimental animals. Recent data from one of our laboratories demonstrated that a crude skin extract or a purified crystalline compound (Bufo melanostictus-antineoplastic factor 1, BM-ANF1) from Indian common toad (Bufo melanostictus, Schneider) skin inhibits the growth of human leukemic cells. The present investigation was undertaken to determine whether combining BM-ANF1 with curcumin would be a better therapeutic strategy for colon cancer. Colon cancer HCT-116 cells were used. Changes in growth, apoptosis, growth factor receptor signaling and events of the cell cycle were analyzed. Curcumin together with BM-ANF1 produced a greater inhibition of HCT-116 cells growth than either agent alone, attributable to the inhibition of proliferation and stimulation of apoptosis, as evidenced by suppression of proliferating cell nuclear antigen (PCNA) expression, cell cycle arrest at the G2/M-phase and caspase-3 activation. There was also a marked reduction of cyclin-dependent kinase (CDK)2, CDK4 and cyclin B expression and up-regulation of CDK inhibitors (p21, p27) and p53, accompanied by attenuation of Akt signaling and nuclear factor-kappa B (NF-kappaB) activation. BM-ANF1 in combination with curcumin causes a marked inhibition of growth of colon cancer cells and could be an effective therapeutic strategy for colon cancer.

Did Photosymbiont Bleaching Lead to the Demise of Planktic Foraminifer Morozovella at the Early Eocene Climatic Optimum?

PubMed

Luciani, Valeria; D'Onofrio, Roberta; Dickens, Gerald R; Wade, Bridget S

2017-11-01

The symbiont-bearing mixed-layer planktic foraminiferal genera Morozovella and Acarinina were among the most important calcifiers of early Paleogene tropical-subtropical oceans. A marked and permanent switch in the abundance of these genera is known to have occurred at low-latitude sites at the beginning of the Early Eocene Climatic Optimum (EECO), such that the relative abundance of Morozovella permanently and significantly decreased along with a progressive reduction in the number of species; concomitantly, the genus Acarinina almost doubled its abundance and diversified. Here we examine planktic foraminiferal assemblages and stable isotope compositions of their tests at Ocean Drilling Program Site 1051 (northwest Atlantic) to detail the timing of this biotic event, to document its details at the species level, and to test a potential cause: the loss of photosymbionts (bleaching). We also provide stable isotope measurements of bulk carbonate to refine the stratigraphy at Site 1051 and to determine when changes in Morozovella species composition and their test size occurred. We demonstrate that the switch in Morozovella and Acarinina abundance occurred rapidly and in coincidence with a negative carbon isotope excursion known as the J event (~53 Ma), which marks the start of the EECO. We provide evidence of photosymbiont loss after the J event from a size-restricted δ 13 C analysis. However, such inferred bleaching was transitory and also occurred in the acarininids. The geologically rapid switch in planktic foraminiferal genera during the early Eocene was a major evolutionary change within marine biota, but loss of photosymbionts was not the primary causal mechanism.

Pro-arrhythmic effects of low plasma [K+] in human ventricle: An illustrated review.

PubMed

Trenor, Beatriz; Cardona, Karen; Romero, Lucia; Gomez, Juan F; Saiz, Javier; Rajamani, Sridharan; Belardinelli, Luiz; Giles, Wayne

2018-05-01

Potassium levels in the plasma, [K + ] o , are regulated precisely under physiological conditions. However, increases (from approx. 4.5 to 8.0mM) can occur as a consequence of, e.g., endurance exercise, ischemic insult or kidney failure. This hyperkalemic modulation of ventricular electrophysiology has been studied extensively. Hypokalemia is also common. It can occur in response to diuretic therapy, following renal dialysis, or during recovery from endurance exercise. In the human ventricle, clinical hypokalemia (e.g., [K + ] o levels of approx. 3.0mM) can cause marked changes in both the resting potential and the action potential waveform, and these may promote arrhythmias. Here, we provide essential background information concerning the main K + -sensitive ion channel mechanisms that act in concert to produce prominent short-term ventricular electrophysiological changes, and illustrate these by implementing recent mathematical models of the human ventricular action potential. Even small changes (~1mM) in [K + ] o result in significant alterations in two different K + currents, I K1 and HERG. These changes can markedly alter in resting membrane potential and/or action potential waveform in human ventricle. Specifically, a reduction in net outward transmembrane K + currents (repolarization reserve) and an increased substrate input resistance contribute to electrophysiological instability during the plateau of the action potential and may promote pro-arrhythmic early after-depolarizations (EADs). Translational settings where these insights apply include: optimal diuretic therapy, and the interpretation of data from Phase II and III trials for anti-arrhythmic drug candidates. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

Alterations in mitochondrial respiratory functions, redox metabolism and apoptosis by oxidant 4-hydroxynonenal and antioxidants curcumin and melatonin in PC12 cells

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

Raza, Haider; John, Annie; Brown, Eric M.

Cellular oxidative stress and alterations in redox metabolisms have been implicated in the etiology and pathology of many diseases including cancer. Antioxidant treatments have been proven beneficial in controlling these diseases. We have recently shown that 4-hydroxynonenal (4-HNE), a by-product of lipid peroxidation, induces oxidative stress in PC12 cells by compromising the mitochondrial redox metabolism. In this study, we have further investigated the deleterious effects of 4-HNE on mitochondrial respiratory functions and apoptosis using the same cell line. In addition, we have also compared the effects of two antioxidants, curcumin and melatonin, used as chemopreventive agents, on mitochondrial redox metabolismmore » and respiratory functions in these cells. 4-HNE treatment has been shown to cause a reduction in glutathione (GSH) pool, an increase in reactive oxygen species (ROS), protein carbonylation and apoptosis. A marked inhibition in the activities of the mitochondrial respiratory enzymes, cytochrome c oxidase and aconitase was observed after 4-HNE treatment. Increased nuclear translocation of NF-kB/p65 protein was also observed after 4-HNE treatment. Curcumin and melatonin treatments, on the other hand, maintained the mitochondrial redox and respiratory functions without a marked effect on ROS production and cell viability. These results suggest that 4-HNE-induced cytotoxicity may be associated, at least in part, with the altered mitochondrial redox and respiratory functions. The alterations in mitochondrial energy metabolism and redox functions may therefore be critical in determining the difference between cell death and survival.« less

Did Photosymbiont Bleaching Lead to the Demise of Planktic Foraminifer Morozovella at the Early Eocene Climatic Optimum?

PubMed Central

D'Onofrio, Roberta; Dickens, Gerald R.; Wade, Bridget S.

2017-01-01

Abstract The symbiont‐bearing mixed‐layer planktic foraminiferal genera Morozovella and Acarinina were among the most important calcifiers of early Paleogene tropical–subtropical oceans. A marked and permanent switch in the abundance of these genera is known to have occurred at low‐latitude sites at the beginning of the Early Eocene Climatic Optimum (EECO), such that the relative abundance of Morozovella permanently and significantly decreased along with a progressive reduction in the number of species; concomitantly, the genus Acarinina almost doubled its abundance and diversified. Here we examine planktic foraminiferal assemblages and stable isotope compositions of their tests at Ocean Drilling Program Site 1051 (northwest Atlantic) to detail the timing of this biotic event, to document its details at the species level, and to test a potential cause: the loss of photosymbionts (bleaching). We also provide stable isotope measurements of bulk carbonate to refine the stratigraphy at Site 1051 and to determine when changes in Morozovella species composition and their test size occurred. We demonstrate that the switch in Morozovella and Acarinina abundance occurred rapidly and in coincidence with a negative carbon isotope excursion known as the J event (~53 Ma), which marks the start of the EECO. We provide evidence of photosymbiont loss after the J event from a size‐restricted δ13C analysis. However, such inferred bleaching was transitory and also occurred in the acarininids. The geologically rapid switch in planktic foraminiferal genera during the early Eocene was a major evolutionary change within marine biota, but loss of photosymbionts was not the primary causal mechanism. PMID:29398777

Neuroprotective efficacy of a combination of fish oil and ferulic acid against 3-nitropropionic acid-induced oxidative stress and neurotoxicity in rats: behavioural and biochemical evidence.

PubMed

K M, Denny Joseph; Muralidhara

2014-04-01

The beneficial effects of fish oil (FO) supplements on the central nervous system have been adequately demonstrated. However, FO supplementation at higher doses for longer duration is likely to cause oxidative stress in vivo. To overcome this, attempts have been made to enrich FO with known antioxidants/phytochemicals. In the present study, we examined the hypothesis that a combination of FO with ferulic acid (FA), a naturally occurring phenolic compound, is likely to provide higher degree of neuroprotection. This was examined by employing 3-nitropropionic acid (NPA), a well-known neurotoxin used to mimic behavioural and neurochemical features of Huntington's disease. Growing male rats administered with NPA (25 mg/kg of body weight (bw) for 4 days) were provided with either FO (2 mL/kg bw), FA (50 mg/kg bw) or FO+FA for 2 weeks. Interestingly, FO+FA not only offered significant protection against NPA-induced behavioural impairments, but also markedly attenuated oxidative stress in brain regions (striatum/cerebellum) as evidenced by the reduction in reactive species, malondialdehyde, hydroperoxides and nitric oxide (NO) levels. Further, FO+FA combination restored the activities of various antioxidant enzymes and the levels of cytosolic calcium. In striatum, activity levels of acetylcholinesterase enzyme and dopamine levels were markedly restored among FO+FA rats. Interestingly, NPA-induced mitochondrial dysfunctions were also attenuated among FO+FA rats. Collectively, our findings suggest the advantage of co-treatment of FO with known antioxidants to achieve a higher therapeutic benefit in the treatment of oxidative stress-mediated neurodegenerative conditions.

THE EFFICACY OF THREE MEDICINAL PLANTS; GARLIC, GINGER AND MIRAZID AND A CHEMICAL DRUG METRONIDAZOLE AGAINST CRYPTOSPORIDIUM PARVUM: II-HISTOLOGICAL CHANGES.

PubMed

Abouel-Nour, Mohamed F; El-Shewehy, Dina Magdy M; Hamada, Shadia F; Morsy, Tosson A

2016-04-01

Cryptosporidiosis parvum is a zoonotic protozoan parasite infects intestinal epithelial cells of man and animals causing a major health problem. This study was oriented to evaluate the protective and curative capacity of garlic, ginger and mirazid in comparison with metronidazole drug (commercially known) against Cryptosporidium in experimental mice. Male Swiss Albino mice experimentally infected with C. parvum were treated with medicinal plants extracts (Ginger, Mirazid, and Garlic) as compared to chemical drug Metronidazole. Importantly, C. parvum-infected mice treated with ginger, Mirazid, garlic and metronidazole showed a complete elimination in shedding oocysts by 9th day PI. The reduction and elimination of shedding oocysts in response to the treatments might be attributable to a direct effect on parasite growth in intestines, sexual phases production and/or the formation of oocysts. The results were evaluated histopathological examination of ideum section of control mice (uninfected, untreated) displayed normal architecture of the villi. Examiination of infected mice ileum section (infected, untreated) displayed histopathological alterations from uninfected groups. Examination of ileum section prepared from mice treated with garlic, ginger, mirazid, and metronidazole displayed histopathological alterations from that of the control groups, and showed marked histologic correction in the pattern with the four regimes used in comparison to control mice. Garlic successfully eradicated oocysts of infected mice from stool and intestine. Supplementation of ginger to infected mice markedly corrected elevation in the inflammatory risk factors and implied its potential antioxidant, anti-inflammatory and immunomodulatory capabilities. Infected mice treated with ginger, mirazid, garlic and metronidazole showed significant symptomatic improvements during treatment.

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

Linagliptin plus metformin in patients with newly diagnosed type 2 diabetes and marked hyperglycemia.

PubMed

Ross, Stuart A; Caballero, A Enrique; Del Prato, Stefano; Gallwitz, Baptist; Lewis-D'Agostino, Diane; Bailes, Zelie; Thiemann, Sandra; Patel, Sanjay; Woerle, Hans-Juergen; von Eynatten, Maximilian

2016-11-01

Few studies of oral glucose-lowering drugs exist in newly diagnosed type 2 diabetes (T2D) patients with marked hyperglycemia, and insulin is often proposed as initial treatment. We evaluated the oral initial combination of metformin and linagliptin, a dipeptidyl peptidase-4 inhibitor, in this population. We performed a pre-specified subgroup analysis of a randomized study in which newly diagnosed T2D patients with glycated hemoglobin A1c (HbA1c) 8.5%-12.0% received linagliptin/metformin or linagliptin monotherapy. Subgroups of baseline HbA1c, age, body-mass index (BMI), renal function, race, and ethnicity were evaluated, with efficacy measured by HbA1c change from baseline after 24 weeks. HbA1c reductions from baseline (mean 9.7%) at week 24 in the overall population were an adjusted mean -2.81% ± 0.12% with linagliptin/metformin (n = 132) and -2.02% ± 0.13% with linagliptin (n = 113); treatment difference -0.79% (95% CI -1.13 to -0.46, P < 0.0001). In patients with baseline HbA1c ≥9.5%, HbA1c reduction was -3.37% with linagliptin/metformin (n = 76) and -2.53% with linagliptin (n = 61); difference -0.84% (95% CI -1.32 to -0.35). In those with baseline HbA1c <9.5%, HbA1c reduction was -2.08% with linagliptin/metformin (n = 56) and -1.39% with linagliptin (n = 52); difference -0.69% (95% CI -1.23 to -0.15). Changes in HbA1c and treatment differences between the linagliptin/metformin and linagliptin groups were of similar magnitudes to the overall population across patient subgroups based on age, BMI, renal function, and race. Drug-related adverse events occurred in 8.8% and 5.7% of linagliptin/metformin and linagliptin patients, respectively; no severe hypoglycemia occurred. Linagliptin/metformin combination in newly diagnosed T2D patients with marked hyperglycemia was well tolerated and elicited substantial improvements in glycemic control regardless of baseline HbA1c, age, BMI, renal function, or race. Thus, newly diagnosed, markedly hyperglycemic patients may be effectively treated by combinations of oral agents. www.clinicaltrials.gov identifier is NCT01512979.

The sounds of sarcasm in English and Cantonese: A cross-linguistic production and perception study

NASA Astrophysics Data System (ADS)

Cheang, Henry S.

Three studies were conducted to examine the acoustic markers of sarcasm in English and in Cantonese, and the manner in which such markers are perceived across these languages. The first study consisted of acoustic analyses of sarcastic utterances spoken in English to verify whether particular prosodic cues correspond to English sarcastic speech. Native English speakers produced utterances expressing sarcasm, sincerity, humour, or neutrality. Measures taken from each utterance included fundamental frequency (F0), amplitude, speech rate, harmonics-to-noise ratio (HNR, to probe voice quality), and one-third octave spectral values (to probe resonance). The second study was conducted to ascertain whether specific acoustic features marked sarcasm in Cantonese and how such features compare with English sarcastic prosody. The elicitation and acoustic analysis methods from the first study were applied to similarly-constructed Cantonese utterances spoken by native Cantonese speakers. Direct acoustic comparisons between Cantonese and English sarcasm exemplars were also made. To further test for cross-linguistic prosodic cues of sarcasm and to assess whether sarcasm could be conveyed across languages, a cross-linguistic perceptual study was then performed. A subset of utterances from the first two studies was presented to naive listeners fluent in either Cantonese or English. Listeners had to identify the attitude in each utterance regardless of language of presentation. Sarcastic utterances in English (regardless of text) were marked by lower mean F0 and reductions in HNR and F0 standard deviation (relative to comparison attitudes). Resonance changes, reductions in both speech rate and F0 range signalled sarcasm in conjunction with some vocabulary terms. By contrast, higher mean F0, amplitude range reductions, and F0 range restrictions corresponded with sarcastic utterances spoken in Cantonese regardless of text. For Cantonese, reduced speech rate and higher HNR interacted with certain vocabulary to mark sarcasm. Sarcastic prosody was most distinguished from acoustic features corresponding to sincere utterances in both languages. Direct English-Cantonese comparisons between sarcasm tokens confirmed cross-linguistic differences in sarcastic prosody. Finally, Cantonese and English listeners could identify sarcasm in their native languages but identified sarcastic utterances spoken in the unfamiliar language at chance levels. It was concluded that particular acoustic cues marked sarcastic speech in Cantonese and English, and these patterns of sarcastic prosody were specific to each language.

Time dependent reduction in platelet aggregation using the multiplate analyser and hirudin blood due to platelet clumping.

PubMed

Chapman, Kent; Favaloro, Emmanuel J

2018-05-01

The Multiplate is a popular instrument that measures platelet function using whole blood. Potentially considered a point of care instrument, it is also used by hemostasis laboratories. The instrument is usually utilized to assess antiplatelet medication or as a screen of platelet function. According to the manufacturer, testing should be performed within 0.5-3 hours of blood collection, and preferably using manufacturer provided hirudin tubes. We report time-associated reduction in platelet aggregation using the Multiplate and hirudin blood collection tubes, for all the major employed agonists. Blood for Multiplate analysis was collected into manufacturer supplied hirudin tubes, and 21 consecutive samples assessed using manufacturer supplied agonists (ADP, arachidonic acid, TRAP, collagen and ristocetin), at several time-points post-sample collection within the recommended test time period. Blood was also collected into EDTA as a reference method for platelet counts, with samples collected into sodium citrate and hirudin used for comparative counts. All platelet agonists showed a diminution of response with time. Depending on the agonist, the reduction caused 5-20% and 22-47% of responses initially in the normal reference range to fall below the reference range at 120min and 180min, respectively. Considering any agonist, 35% and 67% of initially "normal" responses became 'abnormal' at 120 min and 180 min, respectively. Platelet counts showed generally minimal changes in EDTA blood, but were markedly reduced over time in both citrate and hirudin blood, with up to 40% and 60% reduction, respectively, at 240 min. The presence of platelet clumping (micro-aggregate formation) was also observed in a time dependent manner, especially for hirudin. In conclusion, considering any platelet agonist, around two-thirds of samples can, within the recommended 0.5-3 hour testing window post-blood collection, yield a reduction in platelet aggregation that may lead to a change in interpretation (i.e., normal to reduced). Thus, the stability of Multiplate testing can more realistically be considered as being between 30-120 min of blood collection for samples collected into hirudin.

Wire Marking Results in a Small but Significant Reduction in Avian Mortality at Power Lines: A BACI Designed Study

PubMed Central

Barrientos, Rafael; Ponce, Carlos; Palacín, Carlos; Martín, Carlos A.; Martín, Beatriz; Alonso, Juan Carlos

2012-01-01

Background Collision with electric power lines is a conservation problem for many bird species. Although the implementation of flight diverters is rapidly increasing, few well-designed studies supporting the effectiveness of this costly conservation measure have been published. Methodology/Principal Findings We provide information on the largest worldwide marking experiment to date, including carcass searches at 35 (15 experimental, 20 control) power lines totalling 72.5 km, at both transmission (220 kV) and distribution (15 kV–45 kV) lines. We found carcasses of 45 species, 19 of conservation concern. Numbers of carcasses found were corrected to account for carcass losses due to removal by scavengers or being overlooked by researchers, resulting in an estimated collision rate of 8.2 collisions per km per month. We observed a small (9.6%) but significant decrease in the number of casualties after line marking compared to before line marking in experimental lines. This was not observed in control lines. We found no influence of either marker size (large vs. small spirals, sample of distribution lines only) or power line type (transmission vs. distribution, sample of large spirals only) on the collision rate when we analyzed all species together. However, great bustard mortality was slightly lower when lines were marked with large spirals and in transmission lines after marking. Conclusions Our results confirm the overall effectiveness of wire marking as a way to reduce, but not eliminate, bird collisions with power lines. If raw field data are not corrected by carcass losses due to scavengers and missed observations, findings may be biased. The high cost of this conservation measure suggests a need for more studies to improve its application, including wire marking with non-visual devices. Our findings suggest that different species may respond differently to marking, implying that species-specific patterns should be explored, at least for species of conservation concern. PMID:22396776

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.

Comparative assessment of onion and garlic extracts on endogenous hepatic and renal antioxidant status in rat.

PubMed

Suru, Stephen M; Ugwu, Chidiebere E

2015-07-01

Despite growing claims of functional health benefits in folkloric medicine, the safety of chronic/elevated intakes of onion and garlic cannot be assumed. Therefore, this study assesses oral administration of varied doses of onion and garlic on some biomarkers of hepatic and renal functions in rats. Animals were divided into five groups: control group received vehicle and extract-treated groups received varied doses of onion or garlic extract (0.5 mL and 1.0 mL/100 g bwt/day) for 6 weeks. Both doses of onion caused marked (p<0.05) increase in hepatic and renal levels of glutathione (GSH), glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT) and marked (p<0.05) decrease in malondialdehyde (MDA). Treatment with low dose of garlic elicited similar trend except in hepatic CAT, renal SOD and GST levels. A high dose of garlic only caused marked (p<0.05) increase in hepatic GST, renal GST, and SOD. Both doses of onion and low dose of garlic significantly (p<0.05) enhanced renal Na+/K+-ATPase activity. Only a high dose of onion caused significant (p<0.05) increase in hepatic aspartate transaminase (AST), alkaline phosphatase (ALP), and decrease in plasma AST activities. These findings suggest antioxidant enhancing capability for both doses of onion and low dose of garlic, while high dose of garlic elicited pro-oxidant conditions.

Acid reflux directly causes sleep disturbances in rat with chronic esophagitis.

PubMed

Nakahara, Kenichi; Fujiwara, Yasuhiro; Tsukahara, Takuya; Yamagami, Hirokazu; Tanigawa, Tetsuya; Shiba, Masatsugu; Tominaga, Kazunari; Watanabe, Toshio; Urade, Yoshihiro; Arakawa, Tetsuo

2014-01-01

Gastroesophageal reflux disease (GERD) is strongly associated with sleep disturbances. Proton pump inhibitor (PPI) therapy improves subjective but not objective sleep parameters in patients with GERD. This study aimed to investigate the association between GERD and sleep, and the effect of PPI on sleep by using a rat model of chronic acid reflux esophagitis. Acid reflux esophagitis was induced by ligating the transitional region between the forestomach and the glandular portion and then wrapping the duodenum near the pylorus. Rats underwent surgery for implantation of electrodes for electroencephalogram and electromyogram recordings, and they were transferred to a soundproof recording chamber. Polygraphic recordings were scored by using 10-s epochs for wake, rapid eye movement sleep, and non-rapid eye movement (NREM) sleep. To examine the role of acid reflux, rats were subcutaneously administered a PPI, omeprazole, at a dose of 20 mg/kg once daily. Rats with reflux esophagitis presented with several erosions, ulcers, and mucosal thickening with basal hyperplasia and marked inflammatory infiltration. The reflux esophagitis group showed a 34.0% increase in wake (232.2±11.4 min and 173.3±7.4 min in the reflux esophagitis and control groups, respectively; p<0.01) accompanied by a reduction in NREM sleep during light period, an increase in sleep fragmentation, and more frequent stage transitions. The use of omeprazole significantly improved sleep disturbances caused by reflux esophagitis, and this effect was not observed when the PPI was withdrawn. Acid reflux directly causes sleep disturbances in rats with chronic esophagitis.

Acid Reflux Directly Causes Sleep Disturbances in Rat with Chronic Esophagitis

PubMed Central

Nakahara, Kenichi; Fujiwara, Yasuhiro; Tsukahara, Takuya; Yamagami, Hirokazu; Tanigawa, Tetsuya; Shiba, Masatsugu; Tominaga, Kazunari; Watanabe, Toshio; Urade, Yoshihiro; Arakawa, Tetsuo

2014-01-01

Background & Aims Gastroesophageal reflux disease (GERD) is strongly associated with sleep disturbances. Proton pump inhibitor (PPI) therapy improves subjective but not objective sleep parameters in patients with GERD. This study aimed to investigate the association between GERD and sleep, and the effect of PPI on sleep by using a rat model of chronic acid reflux esophagitis. Methods Acid reflux esophagitis was induced by ligating the transitional region between the forestomach and the glandular portion and then wrapping the duodenum near the pylorus. Rats underwent surgery for implantation of electrodes for electroencephalogram and electromyogram recordings, and they were transferred to a soundproof recording chamber. Polygraphic recordings were scored by using 10-s epochs for wake, rapid eye movement sleep, and non-rapid eye movement (NREM) sleep. To examine the role of acid reflux, rats were subcutaneously administered a PPI, omeprazole, at a dose of 20 mg/kg once daily. Results Rats with reflux esophagitis presented with several erosions, ulcers, and mucosal thickening with basal hyperplasia and marked inflammatory infiltration. The reflux esophagitis group showed a 34.0% increase in wake (232.2±11.4 min and 173.3±7.4 min in the reflux esophagitis and control groups, respectively; p<0.01) accompanied by a reduction in NREM sleep during light period, an increase in sleep fragmentation, and more frequent stage transitions. The use of omeprazole significantly improved sleep disturbances caused by reflux esophagitis, and this effect was not observed when the PPI was withdrawn. Conclusions Acid reflux directly causes sleep disturbances in rats with chronic esophagitis. PMID:25215524

Protection against MPP(+)-induced neurotoxicity in SH-SY5Y cells by tormentic acid via the activation of PI3-K/Akt/GSK3β pathway.

PubMed

Zhao, Qing; Ye, Junli; Wei, Na; Fong, Chichun; Dong, Xiaoli

2016-07-01

The cause of Parkinson's disease (PD) could be ascribed to the progressive and selective loss of dopaminergic neurons in the substantia nigra pars compacta, and thus molecules with neuroprotective ability may have therapeutic value against PD. In the current study, the neuroprotective effects and underlying mechanisms of tormentic acid (TA), a naturally occurring triterpene extracted from medicinal plants such as Rosa rugosa and Potentilla chinensis, were evaluated in a widely used cellular PD model in which neurotoxicity was induced by MPP(+) in cultured SH-SY5Y cells. We found that TA at 1-30 μM substantially protected against MPP(+)-induced neurotoxicity, as evidenced by the increase in cell viability, decrease in lactate dehydrogenase release and the reduction in apoptotic nuclei. Moreover, TA effectively inhibited the elevated intracellular accumulation of reactive oxygen species as well as Bax/Bcl-2 ratio caused by MPP(+). Most importantly, TA markedly reversed the inhibition of protein expression of phosphorylated Akt (Ser 473) and phosphorylated GSK3β (Ser 9) caused by MPP(+). LY294002, the specific inhibitor of PI3-K, significantly abrogated the up-regulated phosphorylated Akt and phosphorylated GSK3β offered by TA, suggesting that the neuroprotection of TA was mainly dependent on the activation of PI3-K/Akt/GSK3β signaling pathway. The results taken together indicate that TA may be a potential candidate for further preclinical study aimed at the prevention and treatment of PD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Oenothera paradoxa defatted seeds extract containing pentagalloylglucose and procyanidins potentiates the cytotoxicity of vincristine.

PubMed

Jaszewska, E; Kosmider, A; Kiss, A K; Naruszewicz, M

2010-10-01

The purpose of the study was a comparison of Oenothera paradoxa Hudziok defatted seeds extract (EPE) effect with the activity of individual constituents of the extract: pentagalloylglucose (PGG), gallic acid, (+)-catechin and the procyanidin fraction, as well as an assessment of the combined effect of EPE and vincristine (VCR) in the absence or presence of MRP1 (indomethacin) and P-glycoprotein (verapamil) inhibitors, on two human cancer cell lines, metastatic melanoma (HTB-140) and hepatoma (HepG2). The presence of EPE, PGG and procyanidins caused a marked reduction in viability (MTT assay) and rise in mortality (LDH release assay) of HTB-140 cells. The combined use of EPE (25 μg/mL) and VCR (1 μM) in HTB-140 and HepG2 cells produced an increased cytotoxicity as compared to vincristine alone - by more than 4 and 1.5 times, respectively. In HTB-140 cells, the level of intracellular ATP (measured by bioluminescence) was lowered over 7-fold as a result of exposure to the combination of EPE and VCR, while the addition of MRP-1 inhibitor did not cause an increased cytotoxicity or further lowering of the ATP level. Our results demonstrate that EPE, containing PGG and procyanidins, significantly increased the sensitivity of cancer cells, particularly the melanoma cells, to the action of vincristine.

Mechanisms Underlying the Anti-Tumoral Effects of Citrus bergamia Juice

PubMed Central

Delle Monache, Simona; Sanità, Patrizia; Trapasso, Elena; Ursino, Maria Rita; Dugo, Paola; Russo, Marina; Ferlazzo, Nadia; Calapai, Gioacchino; Angelucci, Adriano; Navarra, Michele

2013-01-01

Based on the growing deal of data concerning the biological activity of flavonoid-rich natural products, the aim of the present study was to explore in vitro the potential anti-tumoral activity of Citrus Bergamia (bergamot) juice (BJ), determining its molecular interaction with cancer cells. Here we show that BJ reduced growth rate of different cancer cell lines, with the maximal growth inhibition observed in neuroblastoma cells (SH-SY5Y) after 72 hs of exposure to 5% BJ. The SH-SY5Y antiproliferative effect elicited by BJ was not due to a cytotoxic action and it did not induce apoptosis. Instead, BJ stimulated the arrest in the G1 phase of cell cycle and determined a modification in cellular morphology, causing a marked increase of detached cells. The inhibition of adhesive capacity on different physiologic substrates and on endothelial cells monolayer were correlated with an impairment of actin filaments, a reduction in the expression of the active form of focal adhesion kinase (FAK) that in turn caused inhibition of cell migration. In parallel, BJ seemed to hinder the association between the neural cell adhesion molecule (NCAM) and FAK. Our data suggest a mechanisms through which BJ can inhibit important molecular pathways related to cancer-associated aggressive phenotype and offer new suggestions for further studies on the role of BJ in cancer treatment. PMID:23613861

Morphometric changes in the aortic arch with advancing age in fetal to mature thoroughbred horses.

PubMed

Endoh, Chihiro; Matsuda, Kazuya; Okamoto, Minoru; Tsunoda, Nobuo; Taniyama, Hiroyuki

2017-03-28

Aortic rupture is a well recognized cause of sudden death in thoroughbred horses. Some microscopic lesions, such as those caused by cystic medial necrosis and medionecrosis, can lead to aortic rupture. However, these microscopic lesions are also observed in normal horses. On the other hand, a previous study of aortic rupture suggested that underlying elastin and collagen deposition disorders might be associated with aortic rupture. Therefore, the purpose of this study was to compare the structural components of the tunica media of the aortic arch, which is composed of elastin, collagen, smooth muscle cells and mucopolysaccharides (MPS), in fetal to mature thoroughbred horses. The percentage area of elastin was greatest in the young horses and subsequently decreased with aging. The percentage area of collagen increased with aging, and the elderly horses (aged ≥20) exhibited significantly higher percentage areas of collagen than the young horses. The percentage area of smooth muscle cells did not change with age. The percentage area of MPS was inversely proportional to the percentage area of elastin. The fetuses exhibited a markedly larger percentage area of MPS than the mature horses. We concluded that the medial changes seen in the aortic arch, which included a reduction in the amount of elastin and increases in the amounts of collagen and MPS, were age-related variations.

Loss of p300 and CBP disrupts histone acetylation at the mouse Sry promoter and causes XY gonadal sex reversal

PubMed Central

Carré, Gwenn-Aël; Siggers, Pam; Xipolita, Marilena; Brindle, Paul; Lutz, Beat; Wells, Sara; Greenfield, Andy

2018-01-01

Abstract CREB-binding protein (CBP, CREBBP, KAT3A) and its closely related paralogue p300 (EP300, KAT3B), together termed p300/CBP, are histone/lysine acetyl-transferases that control gene expression by modifying chromatin-associated proteins. Here, we report roles for both of these chromatin-modifying enzymes in mouse sex determination, the process by which the embryonic gonad develops into a testis or an ovary. By targeting gene ablation to embryonic gonadal somatic cells using an inducible Cre line, we show that gonads lacking either gene exhibit major abnormalities of XY gonad development at 14.5 dpc, including partial sex reversal. Embryos lacking three out of four functional copies of p300/Cbp exhibit complete XY gonadal sex reversal and have greatly reduced expression of the key testis-determining genes Sry and Sox9. An analysis of histone acetylation at the Sry promoter in mutant gonads at 11.5 dpc shows a reduction in levels of the positive histone mark H3K27Ac. Our data suggest a role for CBP/p300 in testis determination mediated by control of histone acetylation at the Sry locus and reveal a novel element in the epigenetic control of Sry and mammalian sex determination. They also suggest possible novel causes of human disorders of sex development (DSD). PMID:29145650

Decrease in Adult Neurogenesis and Neuroinflammation Are Involved in Spatial Memory Impairment in the Streptozotocin-Induced Model of Sporadic Alzheimer's Disease in Rats.

PubMed

Bassani, Taysa Bervian; Bonato, Jéssica M; Machado, Meira M F; Cóppola-Segovia, Valentín; Moura, Eric L R; Zanata, Silvio M; Oliveira, Rúbia M M W; Vital, Maria A B F

2018-05-01

Early impairments in cerebral glucose metabolism and insulin signaling pathways may participate in the pathogenesis of the sporadic form of Alzheimer's disease (sAD). Intracerebroventricular (ICV) injections of low doses of streptozotocin (STZ) are used to mimic sAD and study these alterations in rodents. Streptozotocin causes impairments in insulin signaling and has been reported to trigger several alterations in the brain, such as oxidative stress, neuroinflammation, and dysfunctions in adult neurogenesis, which may be involved in cognitive decline and are features of human AD. The aim of the present study was to assess the influence of neuroinflammation on the process of adult neurogenesis and consequent cognitive deficits in the STZ-ICV model of sAD in Wistar rats. Streptozotocin caused an acute and persistent neuroinflammatory response, reflected by reactive microgliosis and astrogliosis in periventricular areas and the dorsal hippocampus, accompanied by a marked reduction of the proliferation of neural stem cells in the dentate gyrus of the hippocampus and subventricular zone. Streptozotocin also reduced the survival, differentiation, and maturation of newborn neurons, resulting in impairments in short-term and long-term spatial memory. These results support the hypothesis that neuroinflammation has a detrimental effect on neurogenesis, and both neuroinflammation and impairments in neurogenesis contribute to cognitive deficits in the STZ-ICV model of sAD.

[Blood flow analysis in the left coronary artery in a patient with annulo-aortic-ectasia before and after Bentall's operation].

PubMed

Kondo, Y; Hanya, S; Hiyama, T; Ishihara, A

1990-12-01

It has not been established that Bentall's operation induces beneficial effect on a coronary circulation in a patient with Annulo-Aortic-Ectasia. Availability of a small subselective coronary Doppler catheter makes it possible to study the effects of the operation on coronary circulation. In a 49 year old man with Annulo-Aortic-Ectasia, phasic coronary flow velocity in the left main truncus was measured using a 3F steerable Doppler catheter (DC-101, Millar Inc.) pre- and postoperatively with assessment of vasodilator reserve capacity of individual coronary arteries. After the operation, the velocity wave form in the LMT changed to a diastolic-predominant normal pattern with a relatively small systolic component. That is, Bentall's operation caused a marked reduction of systolic- to diastolic flow component ratio from 0.32 to 0.19. The postoperative coronary flow configuration in the LMT was characterized by the presence of predominant diastolic spike. It coincided with "Water hammer wave" in the aortic pressure tracings caused by sudden closing of mechanical valve leaflets. Preoperative intracoronary papaverine increased the ratio of peak to resting velocity (coronary flow reserve) to 2.0 times at the rest, and 3.0 times after the operation. These results suggest that Bentall's operation seems to induce beneficial effect on the myocardial coronary circulation.

20 CFR 404.403 - Reduction where total monthly benefits exceed maximum family benefits payable.

Code of Federal Regulations, 2010 CFR

2010-04-01

.... This causes a reduction in the benefit to child one to 0.00 and the benefit to child two to $30.00... is entitled to $280.00 monthly. This causes a reduction in the benefit to child one to $0.00 and the... and child are entitled to benefits. The wage earner's primary insurance amount is $600.00. His maximum...

Evaluation of lamprey larvicides in the Big Garlic River and Saux Head Lake

USGS Publications Warehouse

Manion, Patrick J.

1969-01-01

Bayluscide (5,2'-dichloro-4'-nitrosalicylanilide) and TFM (3-trifluoromethyl-4-nitrophenol) were evaluated as selective larvicides for control of the sea lamprey, Petromyzon marinus, in the Big Garlic River and Saux Head Lake in Marquette County, Michigan. Population estimates and movement of ammocetes were determined from the recapture of marked ammocetes released before chemical treatment. In 1966 the estimated population of 3136 ammocetes off the stream mouth in Saux Head Lake was reduced 89% by treatment with granular Bayluscide; this percentage was supported by a population estimate of 120 ammocetes in 1967, an indicated reduction of 96% from 1966. Post-marking movement of ammocetes was greater upstream than downstream.

Reduction in all-cause otitis media-related outpatient visits in children after PCV10 introduction in Brazil

PubMed Central

Sartori, Ana L.; Minamisava, Ruth; Bierrenbach, Ana L.; Toscano, Cristiana M.; Afonso, Eliane T.; Morais-Neto, Otaliba L.; Antunes, José L. F.; Cristo, Elier B.

2017-01-01

Few studies have reported the effect of 10-valent pneumococcal conjugate vaccine (PCV10) on otitis media (OM) in infants. In particular, no population-based study in upper-middle income countries is available. In 2010, Brazil introduced PCV10 into its routine National Immunization Program using a 3+1 schedule. We measured the impact of PCV10 on all-cause OM in children. An interrupted time-series analysis was conducted in Goiânia/Brazil considering monthly rates (per 100,000) of all-cause OM outpatient visits in children aged 2–23 months. We used case-based data from the Outpatient Visits Information System of the Unified Health System coded for ICD-10 diagnosis for the period of August/2008 to July/2015. As a comparator, we used rates of outpatient visits due to all-other causes. The relative reduction of all-cause OM and all-other causes of outpatient visits were calculated as the difference between the predicted and observed cumulative rates of the PCV10 post-vaccination period. We then subtracted the relative reduction of all-other causes of outpatient visits from all-cause OM to obtain the impact of PCV10 on OM. In total, 6,401 OM outpatient visits were recorded in 4,793 children aged 2–23 months. Of these, 922 (19.2%) children had more than one OM episode. A significant reduction in all-cause OM visits was observed (50.7%; 95%CI: 42.2–59.2%; p = 0.013), while the reduction in visits due to all-other causes was 7.7% (95% CI 0.8–14.7%; p<0.001). The impact of PCV10 on all-cause OM was thus estimated at 43.0% (95%CI 41.4–44.5). This is the first study to show significant PCV10 impact on OM outpatient visits in infants in a developing country. Our findings corroborate the available evidence from developed countries. PMID:28594913

Reduction in all-cause otitis media-related outpatient visits in children after PCV10 introduction in Brazil.

PubMed

Sartori, Ana L; Minamisava, Ruth; Bierrenbach, Ana L; Toscano, Cristiana M; Afonso, Eliane T; Morais-Neto, Otaliba L; Antunes, José L F; Cristo, Elier B; Andrade, Ana Lucia

2017-01-01

Few studies have reported the effect of 10-valent pneumococcal conjugate vaccine (PCV10) on otitis media (OM) in infants. In particular, no population-based study in upper-middle income countries is available. In 2010, Brazil introduced PCV10 into its routine National Immunization Program using a 3+1 schedule. We measured the impact of PCV10 on all-cause OM in children. An interrupted time-series analysis was conducted in Goiânia/Brazil considering monthly rates (per 100,000) of all-cause OM outpatient visits in children aged 2-23 months. We used case-based data from the Outpatient Visits Information System of the Unified Health System coded for ICD-10 diagnosis for the period of August/2008 to July/2015. As a comparator, we used rates of outpatient visits due to all-other causes. The relative reduction of all-cause OM and all-other causes of outpatient visits were calculated as the difference between the predicted and observed cumulative rates of the PCV10 post-vaccination period. We then subtracted the relative reduction of all-other causes of outpatient visits from all-cause OM to obtain the impact of PCV10 on OM. In total, 6,401 OM outpatient visits were recorded in 4,793 children aged 2-23 months. Of these, 922 (19.2%) children had more than one OM episode. A significant reduction in all-cause OM visits was observed (50.7%; 95%CI: 42.2-59.2%; p = 0.013), while the reduction in visits due to all-other causes was 7.7% (95% CI 0.8-14.7%; p<0.001). The impact of PCV10 on all-cause OM was thus estimated at 43.0% (95%CI 41.4-44.5). This is the first study to show significant PCV10 impact on OM outpatient visits in infants in a developing country. Our findings corroborate the available evidence from developed countries.

Measles mortality reduction contributes substantially to reduction of all cause mortality among children less than five years of age, 1990-2008.

PubMed

van den Ent, Maya M V X; Brown, David W; Hoekstra, Edward J; Christie, Athalia; Cochi, Stephen L

2011-07-01

The Millennium Development Goal 4 (MDG4) to reduce mortality in children aged <5 years by two-thirds from 1990 to 2015 has made substantial progress. We describe the contribution of measles mortality reduction efforts, including those spearheaded by the Measles Initiative (launched in 2001, the Measles Initiative is an international partnership committed to reducing measles deaths worldwide and is led by the American Red Cross, the Centers for Disease Control and Prevention, UNICEF, the United Nations Foundation, and the World Health Organization). We used published data to assess the effect of measles mortality reduction on overall and disease-specific global mortality rates among children aged <5 years by reviewing the results from studies with the best estimates on causes of deaths in children aged 0-59 months. The estimated measles-related mortality among children aged <5 years worldwide decreased from 872,000 deaths in 1990 to 556,000 in 2001 (36% reduction) and to 118,000 in 2008 (86% reduction). All-cause mortality in this age group decreased from >12 million in 1990 to 10.6 million in 2001 (13% reduction) and to 8.8 million in 2008 (28% reduction). Measles accounted for about 7% of deaths in this age group in 1990 and 1% in 2008, equal to 23% of the global reduction in all-cause mortality in this age group from 1990 to 2008. Aggressive efforts to prevent measles have led to this remarkable reduction in measles deaths. The current funding gap and insufficient political commitment for measles control jeopardizes these achievements and presents a substantial risk to achieving MDG4. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

A One-Step, Solvothermal Reduction Method for Producing Reduced Graphene Oxide Dispersions in Organic Solvents

PubMed Central

Dubin, Sergey; Gilje, Scott; Wang, Kan; Tung, Vincent C.; Cha, Kitty; Hall, Anthony S.; Farrar, Jabari; Varshneya, Rupal; Yang, Yang; Kaner, Richard B.

2014-01-01

Refluxing graphene oxide (GO) in N-methyl-2-pyrrolidinone (NMP) results in deoxygenation and reduction to yield a stable colloidal dispersion. The solvothermal reduction is accompanied by a color change from light brown to black. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) images of the product confirm the presence of single sheets of the solvothermally reduced graphene oxide (SRGO). X-ray photoelectron spectroscopy (XPS) of SRGO indicates a significant increase in intensity of the C=C bond character, while the oxygen content decreases markedly after the reduction is complete. X-ray diffraction analysis of SRGO shows a single broad peak at 26.24° 2θ (3.4 Å), confirming the presence of graphitic stacking of reduced sheets. SRGO sheets are redispersible in a variety of organic solvents, which may hold promise as an acceptor material for bulk heterojunction photovoltaic cells, or electromagnetic interference shielding applications. PMID:20586422

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.

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 - ...

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…

Prevention and Treatment of Cardiovascular Disease in Adolescents and Adults through the Transcendental Meditation(®) Program: A Research Review Update.

PubMed

Barnes, Vernon A; Orme-Johnson, David W

2012-08-01

The pathogenesis and progression of cardiovascular diseases are thought to be exacerbated by stress. Basic research indicates that the Transcendental Meditation(®) technique produces acute and longitudinal reductions in sympathetic tone and stress reactivity. In adolescents at risk for hypertension, the technique has been found to reduce resting and ambulatory blood pressure, left ventricular mass, cardiovascular reactivity, and to improve school behavior. Research on adults with mild or moderate essential hypertension has reported decreased blood pressure and reduced use of anti-hypertensive medication. The technique has also been reported to decrease symptoms of angina pectoris and carotid atherosclerosis, to reduce cardiovascular risk factors, including alcohol and tobacco use, to markedly reduce medical care utilization for cardiovascular diseases, and to significantly decrease cardiovascular and all-cause morbidity and mortality. These findings have important implications for inclusion of the Transcendental Meditation program in efforts to prevent and treat cardiovascular diseases and their clinical consequences.(®)Transcendental Meditation and TM are trademarks registered in the US. Patent and Trademark Office, licensed to Maharishi Vedic Education Development Corporation and are used with permission.

Gas cluster ion beam surface treatments for reducing field emission and breakdown of electrodes and SRF cavities

NASA Astrophysics Data System (ADS)

Swenson, D. R.; Wu, A. T.; Degenkolb, E.; Insepov, Z.

2007-08-01

Sub-micron-scale surface roughness and contamination cause field emission that can lead to high-voltage breakdown of electrodes, and these are limiting factors in the development of high gradient RF technology. We are studying various Gas Cluster Ion Beam (GCIB) treatments to smooth, clean, etch and/or chemically alter electrode surfaces to allow higher fields and accelerating gradients, and to reduce the time and cost of conditioning high-voltage electrodes. For this paper, we have processed Nb, stainless steel and Ti electrode materials using beams of Ar, O2, or NF3 + O2 clusters with accelerating potentials up to 35 kV. Using a scanning field emission microscope (SFEM), we have repeatedly seen a dramatic reduction in the number of field emission sites on Nb coupons treated with GCIB. Smoothing effects on stainless steel and Ti substrates, evaluated using SEM and AFM imaging, show that 200-nm-wide polishing scratch marks are greatly attenuated. A 150-mm diameter GCIB-treated stainless steel electrode has shown virtually no DC field emission current at gradients over 20 MV/m.

Biologically mediated isotope fractionations - Biochemistry, geochemical significance and preservation in the earth's oldest sediments

NASA Technical Reports Server (NTRS)

Schidlowski, M.

1983-01-01

Preferential metabolization of isotopically light carbon and sulfur has resulted in a fractionation of the stable isotopes of these elements on a global scale, with the light species (C-12, S-32) markedly concentrated in biogenic materials. Since the biological effects are basically retained when carbon and sulfur are incorporated in sediments, the respective fractionations are propagated into the rock section of the geochemical cycle, this having consequently caused a characteristic bipartition of both elements between 'light' and 'heavy' crustal reservoirs. Preservation of the biological isotope effects in sedimentary rocks makes it possible to trace the underlying biochemical processes back over most of the geological record. According to the available evidence, biological (autotrophic) carbon fixation arose prior to 3.5(if not 3.8) billion years ago, while the emergence of dissimilatory sulfate reduction antedates the appearance of the oldest presumably bacteriogenic sulfur isotope patterns in rocks between 2.7 and 2.8 billion years old. Hence, biological control of the terrestrial carbon and sulfur cycles has been established very early in the earth's history.

Adverse effects of the anabolic steroid, boldenone undecylenate, on reproductive functions of male rabbits.

PubMed

Oda, Samah S; El-Ashmawy, Ibrahim M

2012-06-01

This study was conducted to evaluate the adverse effects of the anabolic steroid, boldenone undecylenate (BOL) on reproductive functions of male rabbits. Thirty white New Zealand mature male rabbits were divided into three groups (10 rabbits each). Group A rabbits served as a control group. Group B rabbits received 4.4 mg/kg body weight (bwt) BOL 5% oily solution. Group C rabbits received 8.8 mg/kg bwt BOL. Rabbits were injected intramuscularly twice weekly for two months. BOL had no significant effect on the bwt and bwt gain. Testes and epididymis weights were decreased significantly in the BOL-treated groups. BOL caused significant reduction in serum testosterone level, seminal volume, sperm motility, and sperm count. No abnormalities were detected in the sperm morphology of the BOL-treated groups. Histopathological alterations in the testes and epididymis were marked in the group C rabbits. These results indicate that administration of BOL exerts a significant harmful effect on the reproductive functions of male rabbits. © 2012 The Authors. International Journal of Experimental Pathology © 2012 International Journal of Experimental Pathology.

An Activity Switch in Human Telomerase Based on RNA Conformation and Shaped by TCAB1.

PubMed

Chen, Lu; Roake, Caitlin M; Freund, Adam; Batista, Pedro J; Tian, Siqi; Yin, Yi A; Gajera, Chandresh R; Lin, Shengda; Lee, Byron; Pech, Matthew F; Venteicher, Andrew S; Das, Rhiju; Chang, Howard Y; Artandi, Steven E

2018-05-18

Ribonucleoprotein enzymes require dynamic conformations of their RNA constituents for regulated catalysis. Human telomerase employs a non-coding RNA (hTR) with a bipartite arrangement of domains-a template-containing core and a distal three-way junction (CR4/5) that stimulates catalysis through unknown means. Here, we show that telomerase activity unexpectedly depends upon the holoenzyme protein TCAB1, which in turn controls conformation of CR4/5. Cells lacking TCAB1 exhibit a marked reduction in telomerase catalysis without affecting enzyme assembly. Instead, TCAB1 inactivation causes unfolding of CR4/5 helices that are required for catalysis and for association with the telomerase reverse-transcriptase (TERT). CR4/5 mutations derived from patients with telomere biology disorders provoke defects in catalysis and TERT binding similar to TCAB1 inactivation. These findings reveal a conformational "activity switch" in human telomerase RNA controlling catalysis and TERT engagement. The identification of two discrete catalytic states for telomerase suggests an intramolecular means for controlling telomerase in cancers and progenitor cells. Copyright © 2018 Elsevier Inc. All rights reserved.

Involvement of up-regulated Necl-5/Tage4/PVR/CD155 in the loss of contact inhibition in transformed NIH3T3 cells

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

Minami, Yukiko; Department of Surgery and Clinical Oncology, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Osaka; Ikeda, Wataru

2007-01-26

Normal cells show contact inhibition of cell movement and proliferation, but this is lost following transformation. We found that Necl-5, originally identified as a poliovirus receptor and up-regulated in many cancer cells, enhances growth factor-induced cell movement and proliferation. We showed that when cells contact other cells, Necl-5 interacts in trans with nectin-3 and is removed by endocytosis from the cell surface, resulting in a reduction of cell movement and proliferation. We show here that up-regulation of the gene encoding Necl-5 by the oncogene V12-Ki-Ras causes enhanced cell movement and proliferation. Upon cell-cell contact, de novo synthesis of Necl-5 exceedsmore » the rate of Necl-5 endocytosis, eventually resulting in a net increase in the amount of Necl-5 at the cell surface. In addition, expression of the gene encoding nectin-3 is markedly reduced in transformed cells. Thus, up-regulation of Necl-5 following transformation contributes to the loss of contact inhibition in transformed cells.« less

On the critical parameters that regulate the deformation behaviour of tooth enamel.

PubMed

Xie, Zonghan; Swain, Michael; Munroe, Paul; Hoffman, Mark

2008-06-01

Tooth enamel is the hardest tissue in the human body with a complex hierarchical structure. Enamel hypomineralisation--a developmental defect--has been reported to cause a marked reduction in the mechanical properties of enamel and loss of dental function. We discover a distinctive difference in the inelastic deformation mechanism between sound and hypomineralised enamels that is apparently controlled by microstructural variation. For sound enamel, when subjected to mechanical forces the controlling deformation mechanism was distributed shearing within nanometre thick protein layer between its constituent mineral crystals; whereas for hypomineralised enamel microcracking and subsequent crack growth were more evident in its less densely packed microstructure. We develop a mechanical model that not only identifies the critical parameters, i.e., the thickness and shear properties of enamels, that regulate the mechanical behaviour of enamel, but also explains the degradation of hypomineralised enamel as manifested by its lower resistance to deformation and propensity for catastrophic failure. With support of experimental data, we conclude that for sound enamel an optimal microstructure has been developed that endows enamel with remarkable structural integrity for durable mechanical function.

The brain-specific double-stranded RNA-binding protein Staufen2 is required for dendritic spine morphogenesis.

PubMed

Goetze, Bernhard; Tuebing, Fabian; Xie, Yunli; Dorostkar, Mario M; Thomas, Sabine; Pehl, Ulrich; Boehm, Stefan; Macchi, Paolo; Kiebler, Michael A

2006-01-16

Mammalian Staufen2 (Stau2) is a member of the double-stranded RNA-binding protein family. Its expression is largely restricted to the brain. It is thought to play a role in the delivery of RNA to dendrites of polarized neurons. To investigate the function of Stau2 in mature neurons, we interfered with Stau2 expression by RNA interference (RNAi). Mature neurons lacking Stau2 displayed a significant reduction in the number of dendritic spines and an increase in filopodia-like structures. The number of PSD95-positive synapses and miniature excitatory postsynaptic currents were markedly reduced in Stau2 down-regulated neurons. Akin effects were caused by overexpression of dominant-negative Stau2. The observed phenotype could be rescued by overexpression of two RNAi cleavage-resistant Stau2 isoforms. In situ hybridization revealed reduced expression levels of beta-actin mRNA and fewer dendritic beta-actin mRNPs in Stau2 down-regulated neurons. Thus, our data suggest an important role for Stau2 in the formation and maintenance of dendritic spines of hippocampal neurons.

The brain-specific double-stranded RNA-binding protein Staufen2 is required for dendritic spine morphogenesis

PubMed Central

Goetze, Bernhard; Tuebing, Fabian; Xie, Yunli; Dorostkar, Mario M.; Thomas, Sabine; Pehl, Ulrich; Boehm, Stefan; Macchi, Paolo; Kiebler, Michael A.

2006-01-01

Mammalian Staufen2 (Stau2) is a member of the double-stranded RNA-binding protein family. Its expression is largely restricted to the brain. It is thought to play a role in the delivery of RNA to dendrites of polarized neurons. To investigate the function of Stau2 in mature neurons, we interfered with Stau2 expression by RNA interference (RNAi). Mature neurons lacking Stau2 displayed a significant reduction in the number of dendritic spines and an increase in filopodia-like structures. The number of PSD95-positive synapses and miniature excitatory postsynaptic currents were markedly reduced in Stau2 down-regulated neurons. Akin effects were caused by overexpression of dominant-negative Stau2. The observed phenotype could be rescued by overexpression of two RNAi cleavage-resistant Stau2 isoforms. In situ hybridization revealed reduced expression levels of β-actin mRNA and fewer dendritic β-actin mRNPs in Stau2 down-regulated neurons. Thus, our data suggest an important role for Stau2 in the formation and maintenance of dendritic spines of hippocampal neurons. PMID:16418534

miR-137 and miR-491 Negatively Regulate Dopamine Transporter Expression and Function in Neural Cells.

PubMed

Jia, Xiaojian; Wang, Feng; Han, Ying; Geng, Xuewen; Li, Minghua; Shi, Yu; Lu, Lin; Chen, Yun

2016-12-01

The dopamine transporter (DAT) is involved in the regulation of extracellular dopamine levels. A 40-bp variable-number tandem repeat (VNTR) polymorphism in the 3'-untranslated region (3'UTR) of the DAT has been reported to be associated with various phenotypes that are involved in the aberrant regulation of dopaminergic neurotransmission. In the present study, we found that miR-137 and miR-491 caused a marked reduction of DAT expression, thereby influencing neuronal dopamine transport. Moreover, the regulation of miR-137 and miR-491 on this transport disappeared after the DAT was silenced. The miR-491 seed region that is located on the VNTR sequence in the 3'UTR of the DAT and the regulatory effect of miR-491 on the DAT depended on the VNTR copy-number. These data indicate that miR-137 and miR-491 regulate DAT expression and dopamine transport at the post-transcriptional level, suggesting that microRNA may be targeted for the treatment of diseases associated with DAT dysfunction.

External Nasal Neuralgia: A Neuropathic Pain Within the Territory of the External Nasal Nerve.

PubMed

García-Moreno, Héctor; Aledo-Serrano, Ángel; Gimeno-Hernández, Jesús; Cuadrado, María-Luz

2015-10-01

Nasal pain is a challenging diagnosis and very little has been reported in the neurological literature. The nose is a sophisticated structure regarding its innervation, which is supplied by the first and second divisions of the trigeminal nerve. Painful cranial neuropathies are an important group in the differential diagnosis, although they have been described only scarcely. Here, we report a case that can conform a non-traumatic external nasal nerve neuralgia. A 76-year-old woman was referred to our office due to pain in her left nose. She was suffering from daily excruciating attacks, which were strictly limited to the territory supplied by her left external nasal nerve (left ala nasi and apex nasi). She denied previous traumatisms and the ancillary tests did not yield any underlying pathology. An anesthetic blockade of her left external nasal nerve achieved a marked reduction of the number of episodes as well as their intensity. External nasal neuralgia seems a specific neuralgia causing nasal pain. Anesthetic blockades of the external nasal nerve may be a valid treatment for this condition. © 2015 American Headache Society.

Cellular and Molecular Mechanisms of Alveolar Destruction in Emphysema

PubMed Central

Tuder, Rubin M.; Yoshida, Toshinori; Arap, Wadih; Pasqualini, Renata; Petrache, Irina

2006-01-01

Emphysema consists of a unique pattern of alveolar destruction, resulting in marked airspace enlargement with reduction of alveolar capillary exchange area. Classical concepts of the pathogenesis of emphysema have relied on the paradigm set by the inflammation and protease/antiprotease imbalance. We propose herein that cigarette smoke constitutes an environmental hazard that causes alveolar destruction by the interaction of apoptosis, oxidative stress, and protease/antiprotease imbalance. We draw a parallel between organismal aging, organ structural maintenance, and the damage resulting from chronic cigarette smoke inhalation. The stochastic interaction between environmental hazards and the effort of an organism or a particular organ to fend off these hazards results in the accumulation of cellular damage and features characteristic of aging. Inflammation follows as the result of the multiplication of injuries. We highlight the importance of understanding the biology of the interaction of alveolar cells in homeostasis and in alveolar destruction, and the potential role of novel processes related to senescence and stress response. An evolutionary perspective of emphysema that incorporates mechanisms related to aging may lead to important advances in the understanding and therapeutic targeting of chronic obstructive pulmonary disease. PMID:16921129

Deregulation of calcium fluxes in HTLV-I infected CD4-positive T-cells plays a major role in malignant transformation.

PubMed

Akl, Haidar; Badran, Bassam; El Zein, Nabil; Dobirta, Gratiela; Burny, Arsene; Martiat, Philippe

2009-01-01

The CD4+ T-cell malignancy induced by human T-cell leukemia virus type 1 (HTLV-I) infection and termed; Adult T-cell Leukemia lymphoma (ATLL), is caused by defects in the mechanisms underlying cell proliferation and cell death. In the CD4+ T-cells, calcium ions are central for both phenomena. ATLL is associated with a marked hypercalcemia in many patients. The consequence of a defect in the Ca2+ signaling pathway for lymphocyte activation is characterized by an impaired NFAT activation and transcription of cytokines, chemokines and many other NFAT target genes whose transcription is essential for productive immune defense. Fresh ATLL cells lack the TCR/CD3 and CD7 molecules on their surface. Whereas CD7 is a calcium transporter, reduction in calcium influx in response to T-cell activation was reported as a functional consequence of TCR/CD3 expression deficiency. Understanding these changes and identifying the molecular players involved might provide further insights on how to improve ATLL treatment.

Chronic alcohol binging injures the liver and other organs by reducing NAD⁺ levels required for sirtuin's deacetylase activity.

PubMed

French, Samuel W

2016-04-01

NAD(+) levels are markedly reduced when blood alcohol levels are high during binge drinking. This causes liver injury to occur because the enzymes that require NAD(+) as a cofactor such as the sirtuin de-acetylases cannot de-acetylate acetylated proteins such as acetylated histones. This prevents the epigenetic changes that regulate metabolic processes and which prevent organ injury such as fatty liver in response to alcohol abuse. Hyper acetylation of numerous regulatory proteins develops. Systemic multi-organ injury occurs when NAD(+) is reduced. For instance the Circadian clock is altered if NAD(+) is not available. Cell cycle arrest occurs due to up regulation of cell cycle inhibitors leading to DNA damage, mutations, apoptosis and tumorigenesis. NAD(+) is linked to aging in the regulation of telomere stability. NAD(+) is required for mitochondrial renewal. Alcohol dehydrogenase is present in every visceral organ in the body so that there is a systemic reduction of NAD(+) levels in all of these organs during binge drinking. Copyright © 2016. Published by Elsevier Inc.

Formation of Nanocones on Highly Oriented Pyrolytic Graphite by Oxygen Plasma

PubMed Central

Vesel, Alenka; Eleršič, Kristina; Modic, Martina; Junkar, Ita; Mozetič, Miran

2014-01-01

Improvement in hemocompatibility of highly oriented pyrolytic graphite (HOPG) by formation of nanostructured surface by oxygen plasma treatment is reported. We have showed that by appropriate fine tuning of plasma and discharge parameters we are able to create nanostructured surface which is densely covered with nanocones. The size of the nanocones strongly depended on treatment time. The optimal results in terms of material hemocompatibility were obtained after treatment with oxygen plasma for 15 s, when both the nanotopography and wettability were the most favorable, since marked reduction in adhesion and activation of platelets was observed on this surface. At prolonged treatment times, the rich surface topography was lost and thus also its antithrombogenic properties. Chemical composition of the surface was always more or less the same, regardless of its morphology and height of the nanocones. Namely, on all plasma treated samples, only a few atomic percent of oxygen was found, meaning that plasma caused mostly etching, leading to changes in the surface morphology. This indicates that the main preventing mechanism against platelets adhesion was the right surface morphology. PMID:28788553

Strong metal-support interactions

NASA Technical Reports Server (NTRS)

Vannice, M. Albert

1987-01-01

It has been demonstrated that synergistic metal-support effects can occur which markedly enhance specific activity and alter selectivity in certain reactions. Because of the presence of such effects in certain reactions conducted under reducing conditions (that is, under H2 pressure), but not others, the creation of unique sites at the metal-support interface seems to be the best model at the present time to explain this behavior. The postulation of these sites, which are specific for a certain reactant such as CO, provides an effective explanation for the higher methanation rates that have been reported over some catalysts. The creation of these sites in the adlineation zone is facilitated by hydrogen spillover from the metal surface, and this same process can also enhance the reduction of many oxide supports. Although oxygen spillover is much less probable due to its higher heat of adsorption, it is much less well understood and the possibility of rate enhancements in CO oxidation caused by special interface sites cannot be discounted at the present time. Consequently, this seems to be an important area of future research.

Functional enrichment of mannanase-treated spent brewer yeast.

PubMed

Cao, Ruge; Yang, Xingyue; Shang, Wenting; Zhou, Zhongkai; Strappe, Padraig; Blanchard, Chris

2017-09-14

In this study, the effect of Bacillus amyloliquefaciens-produced β-mannanase on the nutrient diffusion (release) and antioxidant activity of spent brewer yeast (SBY) was investigated. Three pretreatments were performed: (1) autolysis at 50°C for 24 h; (2) autolysis at 50°C for 24 h, with the addition of β-mannanase during the autolysis; (3) autolysis at 50°C for 24 h, and the β-mannanase was added for another 12 h treatment. The pretreatments with the addition of β-mannanase caused significant cell wall degradation, markedly increased the yield of SBY extracts. More importantly, this study found that polysaccharides were degraded to be oligosaccharides with a considerable reduction in molecular weights. Meanwhile, pretreatment with the enzyme also exhibited a higher antioxidant activity in SBY extract compared to autolysis itself. The current study indicated that pretreatment (3) had a better effect than pretreatment (2) in terms of improving in antioxidant activity in SBY extract. These improved characteristics of SBY extracts isolated through enzymatic treatment appear to show promising features for their prospective use as natural functional agents.

Ebf2 is required for development of dopamine neurons in the midbrain periaqueductal gray matter of mouse.

PubMed

Yang, Qiaoqiao; Liu, Shuxi; Yin, Min; Yin, Yanqing; Zhou, Guomin; Zhou, Jiawei

2015-11-01

Dopaminergic (DA) neurons in the midbrain ventral periaqueductal gray matter (PAG) play critical roles in various physiological and pathophysiological processes including sleep-wake rhyme, antinociception, and drug addiction. However, the molecular mechanisms underlying their development are poorly understood. Here, we showed that PAG DA neurons arose as early as E15.5 in mouse embryos. During the prenatal period, the majority of PAG DA neurons was distributed in the intermediate and caudal regions of the PAG. In the postnatal brain, ∼50% of PAG DA neurons were preferentially located in the caudal portion of the PAG. Moreover, transcription factor early B-cell factor 2 (Ebf2) was transiently expressed in a subset of DA neurons in embryonic ventral mesencephalon. Functional analysis revealed that loss of Ebf2 in vivo caused a marked reduction in the number of DA neurons in the midbrain PAG but not in the substantia nigra and ventral tegmental area. Thus, Ebf2 is identified as a novel and important regulator selectively required for midbrain PAG DA neuron development. © 2015 Wiley Periodicals, Inc.

Arbuscular mycorrhiza effects on plant performance under osmotic stress.

PubMed

Santander, Christian; Aroca, Ricardo; Ruiz-Lozano, Juan Manuel; Olave, Jorge; Cartes, Paula; Borie, Fernando; Cornejo, Pablo

2017-10-01

At present, drought and soil salinity are among the most severe environmental stresses that affect the growth of plants through marked reduction of water uptake which lowers water potential, leading to osmotic stress. In general, osmotic stress causes a series of morphological, physiological, biochemical, and molecular changes that affect plant performance. Several studies have found that diverse types of soil microorganisms improve plant growth, especially when plants are under stressful conditions. Most important are the arbuscular mycorrhizal fungi (AMF) which form arbuscular mycorrhizas (AM) with approximately 80% of plant species and are present in almost all terrestrial ecosystems. Beyond the well-known role of AM in improving plant nutrient uptake, the contributions of AM to plants coping with osmotic stress merit analysis. With this review, we describe the principal direct and indirect mechanisms by which AM modify plant responses to osmotic stress, highlighting the role of AM in photosynthetic activity, water use efficiency, osmoprotectant production, antioxidant activities, and gene expression. We also discuss the potential for using AMF to improve plant performance under osmotic stress conditions and the lines of research needed to optimize AM use in plant production.

Anti-tumour efficacy of etoposide alone and in combination with piroxicam against canine osteosarcoma in a xenograft model.

PubMed

Ong, S M; Saeki, K; Kok, M K; Tanaka, Y; Choisunirachon, N; Yoshitake, R; Nishimura, R; Nakagawa, T

2017-08-01

Osteosarcoma (OSA) in dogs is locally invasive and highly malignant. Distant metastasis is the most common cause of death. To date, the survival rate in dogs with OSA remains poor. The cytotoxic effects of etoposide against canine OSA cell lines, either alone or in combination with piroxicam, have been previously demonstrated in vitro. The aim of this study was to evaluate the anti-tumour effect of etoposide alone and in combination with piroxicam on canine OSA using murine models. Etoposide single agent treatment significantly delayed tumour progression with a marked reduction in Ki-67 immunoreactivity in tumour tissue. Concomitant treatment with piroxicam did not enhance the anti-tumour efficacy of etoposide. Etoposide single agent treatment and combination treatment with piroxicam down-regulated survivin expression, but was not followed by increased apoptotic activity. These findings indicate that etoposide might be a promising novel therapeutic for canine OSA. Further investigations into its potential for clinical application in veterinary oncology are warranted. Copyright © 2017 Elsevier Ltd. All rights reserved.

Are MAO-A deficiency states in the general population and in putative high-risk populations highly uncommon?

PubMed

Murphy, D L; Sims, K; Eisenhofer, G; Greenberg, B D; George, T; Berlin, F; Zametkin, A; Ernst, M; Breakefield, X O

1998-01-01

Lack of monoamine oxidase A (MAO-A) due to either Xp chromosomal deletions or alterations in the coding sequence of the gene for this enzyme are associated with marked changes in monoamine metabolism and appear to be associated with variable cognitive deficits and behavioral changes in humans and in transgenic mice. In mice, some of the most marked behavioral changes are ameliorated by pharmacologically-induced reductions in serotonin synthesis during early development, raising the question of possible therapeutic interventions in humans with MAO deficiency states. At the present time, only one multi-generational family and a few other individuals with marked MAO-A deficiency states have been identified and studied in detail. Although MAO deficiency states associated with Xp chromosomal deletions were identified by distinct symptoms (including blindness in infancy) produced by the contiguous Norrie disease gene, the primarily behavioral phenotype of individuals with the MAO mutation is less obvious. This paper reports a sequential research design and preliminary results from screening several hundred volunteers in the general population and from putative high-risk groups for possible MAO deficiency states. These preliminary results suggest that marked MAO deficiency states are very rare.

Clinical, cellular, microscopic, and ultrastructural studies of a case of fibrogenesis imperfecta ossium

PubMed Central

Barron, Melissa L; Rybchyn, Mark S; Ramesh, Sutharshani; Mason, Rebecca S; Fiona Bonar, S; Stalley, Paul; Khosla, Sundeep; Hudson, Bernie; Arthur, Christopher; Kim, Edward; Clifton-Bligh, Roderick J; Clifton-Bligh, Phillip B

2017-01-01

Fibrogenesis imperfecta ossium is a rare disorder of bone usually characterized by marked osteopenia and associated with variable osteoporosis and osteosclerosis, changing over time. Histological examination shows that newly formed collagen is abnormal, lacking birefringence when examined by polarized light. The case presented demonstrates these features and, in addition, a previously undocumented finding of a persistent marked reduction of the serum C3 and C4. Osteoblasts established in culture from a bone biopsy showed abnormal morphology on electron microscopy and increased proliferation when cultured with benzoylbenzoyl-ATP and 1,25-dihydroxyvitamin D, contrasting with findings in normal osteoblasts in culture. A gene microarray study showed marked upregulation of the messenger RNA (mRNA) for G-protein-coupled receptor 128 (GPR 128), an orphan receptor of unknown function and also of osteoprotegerin in the patient’s osteoblasts in culture. When normal osteoblasts were cultured with the patient’s serum, there was marked upregulation of the mRNA for aquaporin 1. A single pathogenetic factor to account for the features of this disorder has not been defined, but the unique findings described here may facilitate more definitive investigation of the abnormal bone cell function. PMID:28326223

How to Identify Lead Free Certification Marks for Drinking Water System & Plumbing Products

EPA Science Inventory

The Reduction of Lead in Drinking Water Act went into effect on January 4, 2014. The Act has reduced the lead content allowed in water system and plumbing products by changing the definition of lead free in Section 1417 of the Safe Drinking Water Act (SDWA) from not more than 8% ...

An Assessment of Prison-Based Drug Treatment; Texas' In-Prison Therapeutic Community Program.

ERIC Educational Resources Information Center

Knight, Kevin; Simpson, D. Dwayne; Chatham, Lois R.; Camacho, L. Mabel

1997-01-01

Provides an overview of a comprehensive, prison-based treatment assessment, including a six-month follow-up study. Results show that 80% of the inmates referred to the program graduated. Graduates demonstrated marked reductions in criminal and drug-use activity and had lower relapse and recidivism rates when compared to other parolees. (RJM)

Between History and Apocalypse: Stumbling

ERIC Educational Resources Information Center

Lalu, Premesh

2016-01-01

Apartheid rested on a division of the senses as much as it did on a reductive politics of racial subjection and its accompanying violence. As an instance of the division of the senses, it produced a condition of stasis in which history and a post-apartheid future were increasingly marked by a politico-religious discourse of apocalypse, and a moral…

Consistent improvement in the nutritional status of Colombian children between 1965 and 1989.

PubMed

Mora, J O; de Paredes, B; de Navarro, L; Rodríguez, E

1992-01-01

Three national anthropometric surveys carried out in Colombia in 1965-1966, 1977-1980, and 1986-1989 provide a reasonably standardized basis for comparing the nutritional status of infants and young children in those years. That comparison, presented here together with appropriate socioeconomic data, indicates marked reduction of malnutrition paralleling strong socioeconomic gains.

Analysis of FY 1990 Budget Proposals and Their Impact on Low Income Programs.

ERIC Educational Resources Information Center

Center on Budget and Policy Priorities, Washington, DC.

Despite claims that benefits for the needy have not been reduced, the Reagan Administration's final budget for fiscal year 1990 is marked by substantial reductions in programs for the poor. Actual spending for low-income programs would be sliced $6.75 billion below current levels. Medicaid, which provides health care coverage for poor families…

A black female with the 48, XXXX chromosome constitution.

PubMed

Hara, S; Haywood, B D; Davis, K K; Sherrill, M V; Blackshear, A; Crump, E P

1975-01-01

The case of a 19-year-old severly mentally retarded Black female with a 48,XXXX chromosome constitution is reported. She had low-set ears, minimum webbing of the neck, small inverted nipples, and tapering of the extremities. All ten digital patterns of the fingers were ulnar loops, resulting in a marked reduction of dermal ridge counts.

Dissonant health transition in the states of Mexico, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.

PubMed

Gómez-Dantés, Héctor; Fullman, Nancy; Lamadrid-Figueroa, Héctor; Cahuana-Hurtado, Lucero; Darney, Blair; Avila-Burgos, Leticia; Correa-Rotter, Ricardo; Rivera, Juan A; Barquera, Simon; González-Pier, Eduardo; Aburto-Soto, Tania; de Castro, Elga Filipa Amorin; Barrientos-Gutiérrez, Tonatiuh; Basto-Abreu, Ana C; Batis, Carolina; Borges, Guilherme; Campos-Nonato, Ismael; Campuzano-Rincón, Julio C; de Jesús Cantoral-Preciado, Alejandra; Contreras-Manzano, Alejandra G; Cuevas-Nasu, Lucia; de la Cruz-Gongora, Vanessa V; Diaz-Ortega, Jose L; de Lourdes García-García, María; Garcia-Guerra, Armando; de Cossío, Teresita González; González-Castell, Luz D; Heredia-Pi, Ileana; Hijar-Medina, Marta C; Jauregui, Alejandra; Jimenez-Corona, Aida; Lopez-Olmedo, Nancy; Magis-Rodríguez, Carlos; Medina-Garcia, Catalina; Medina-Mora, Maria E; Mejia-Rodriguez, Fabiola; Montañez, Julio C; Montero, Pablo; Montoya, Alejandra; Moreno-Banda, Grea L; Pedroza-Tobías, Andrea; Pérez-Padilla, Rogelio; Quezada, Amado D; Richardson-López-Collada, Vesta L; Riojas-Rodríguez, Horacio; Ríos Blancas, Maria J; Razo-Garcia, Christian; Mendoza, Martha P Romero; Sánchez-Pimienta, Tania G; Sánchez-Romero, Luz M; Schilmann, Astrid; Servan-Mori, Edson; Shamah-Levy, Teresa; Téllez-Rojo, Martha M; Texcalac-Sangrador, José L; Wang, Haidong; Vos, Theo; Forouzanfar, Mohammad H; Naghavi, Mohsen; Lopez, Alan D; Murray, Christopher J L; Lozano, Rafael

2016-11-12

Child and maternal health outcomes have notably improved in Mexico since 1990, whereas rising adult mortality rates defy traditional epidemiological transition models in which decreased death rates occur across all ages. These trends suggest Mexico is experiencing a more complex, dissonant health transition than historically observed. Enduring inequalities between states further emphasise the need for more detailed health assessments over time. The Global Burden of Diseases, Injuries, and Risk Factors Study 2013 (GBD 2013) provides the comprehensive, comparable framework through which such national and subnational analyses can occur. This study offers a state-level quantification of disease burden and risk factor attribution in Mexico for the first time. We extracted data from GBD 2013 to assess mortality, causes of death, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) in Mexico and its 32 states, along with eight comparator countries in the Americas. States were grouped by Marginalisation Index scores to compare subnational burden along a socioeconomic dimension. We split extracted data by state and applied GBD methods to generate estimates of burden, and attributable burden due to behavioural, metabolic, and environmental or occupational risks. We present results for 306 causes, 2337 sequelae, and 79 risk factors. From 1990 to 2013, life expectancy from birth in Mexico increased by 3·4 years (95% uncertainty interval 3·1-3·8), from 72·1 years (71·8-72·3) to 75·5 years (75·3-75·7), and these gains were more pronounced in states with high marginalisation. Nationally, age-standardised death rates fell 13·3% (11·9-14·6%) since 1990, but state-level reductions for all-cause mortality varied and gaps between life expectancy and years lived in full health, as measured by HALE, widened in several states. Progress in women's life expectancy exceeded that of men, in whom negligible improvements were observed since 2000. For many states, this trend corresponded with rising YLL rates from interpersonal violence and chronic kidney disease. Nationally, age-standardised YLL rates for diarrhoeal diseases and protein-energy malnutrition markedly decreased, ranking Mexico well above comparator countries. However, amid Mexico's progress against communicable diseases, chronic kidney disease burden rapidly climbed, with age-standardised YLL and DALY rates increasing more than 130% by 2013. For women, DALY rates from breast cancer also increased since 1990, rising 12·1% (4·6-23·1%). In 2013, the leading five causes of DALYs were diabetes, ischaemic heart disease, chronic kidney disease, low back and neck pain, and depressive disorders; the latter three were not among the leading five causes in 1990, further underscoring Mexico's rapid epidemiological transition. Leading risk factors for disease burden in 1990, such as undernutrition, were replaced by high fasting plasma glucose and high body-mass index by 2013. Attributable burden due to dietary risks also increased, accounting for more than 10% of DALYs in 2013. Mexico achieved sizeable reductions in burden due to several causes, such as diarrhoeal diseases, and risks factors, such as undernutrition and poor sanitation, which were mainly associated with maternal and child health interventions. Yet rising adult mortality rates from chronic kidney disease, diabetes, cirrhosis, and, since 2000, interpersonal violence drove deteriorating health outcomes, particularly in men. Although state inequalities from communicable diseases narrowed over time, non-communicable diseases and injury burdens varied markedly at local levels. The dissonance with which Mexico and its 32 states are experiencing epidemiological transitions might strain health-system responsiveness and performance, which stresses the importance of timely, evidence-informed health policies and programmes linked to the health needs of each state. Bill & Melinda Gates Foundation, Instituto Nacional de Salud Pública. Copyright © 2016 Elsevier Ltd. All rights reserved.