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Warner, Brian, and Patrick A. Woudt. "Dwarf Nova Oscillations and Quasi-Periodic Oscillations: Extension of the Two-QPO Diagram of X-Ray Binaries, and a new kind of DNO." International Astronomical Union Colloquium 190 (2004): 85–90. http://dx.doi.org/10.1017/s0252921100001895.
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AbstractSeventeen examples are given of Cataclysmic Variable (CV) stars possessing both Dwarf Nova Oscillations (DNOs) and Quasi-Periodic Oscillations (QPOs). These form an extension of the X-Ray Two-QPO correlation to frequencies three orders of magnitude lower. We draw attention to the existence of a second type of DNO in CVs, which is probably caused by magnetically channelled accretion onto the white dwarf.
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Then, Daniel, Patrick Hein, Tanja M. Kneiske, and Martin Braun. "Analysis of Dependencies between Gas and Electricity Distribution Grid Planning and Building Energy Retrofit Decisions." Sustainability 12, no. 13 (July 1, 2020): 5315. http://dx.doi.org/10.3390/su12135315.
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Most macroeconomic studies predict a decline in final energy demand and the use of natural gas in the heating sector in Europe. In the course of building retrofitting, gas-based heating systems are predominantly replaced by electricity-based solutions. This influences the business models of electricity and especially gas distribution network operators (DNOs), where grid charges tend to rise. The resulting feedback effect could accelerate the decrease of demand and finally lead to the defection of the gas grid—an effect that has been neglected in energy system analysis so far. We present a multi-agent simulation with a rule-based gas and electricity DNO model and a building retrofit optimization model to analyze these interdependencies during the transformation path, focusing on the role of different technical, economic, and regulatory triggers. Our case studies for a real grid area of a German city shows that an interplay of the gas and electricity DNO’s strategy, as well as the building-, heating system-, grid-, and trigger-configuration, determine the decision on the extension, continuation, or defection of the gas grid infrastructure. Finally, strategies for how to reduce the risk of a gas grid defection, which are relevant for DNOs, policy makers, and creators of macro-economic models, are discussed.
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Lee, Chanhee, Seon-Ho Kim, Karen Beauchemin, Pietro Celi, and Stéphane Duval. "Short-Term Eating Preference of Beef Cattle Fed High Forage or High Grain Diets Supplemented with 3-Nitrooxypropanol." Animals 10, no. 1 (December 30, 2019): 64. http://dx.doi.org/10.3390/ani10010064.
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Two experiments were conducted to examine eating preference of beef cattle for diets with or without the investigative enteric methane inhibitor 3-nitrooxypropanol (3-NOP). Nine beef steers were housed in individual stalls, each equipped with two feed bunks. The first experiment (Exp. 1) was conducted with a high forage diet and each animal received a diet without 3-NOP (CON) in one bunk and a diet with 3-NOP (dNOP) in the other bunk. The second study (Exp. 2) was conducted with the same animals about 6 months after Exp. 1 where a high grain diet without (CON) or with 3-NOP (dNOP) was offered. In Exp. 1, animals initially preferred CON compared with dNOP. Feed consumption from 0 to 3, 3 to 6, and 6 to 12 h after feeding was lower for dNOP compared with CON. However, dry matter intake (DMI) and feed consumption of dNOP gradually increased during Exp. 1 such that there was no preference between CON and dNOP on day 7. In Exp. 2, there was no preference for or against dNOP. Average DMI was greater for dNOP vs. CON, but interactions between diet and day for DMI and feed consumption rates indicated that daily preference between CON and dNOP was variable. In conclusion, beef steers initially detected a difference between CON and dNOP and selected in favor of CON rather than dNOP when they had not previously been exposed to 3-NOP. However, the animals rapidly acclimatized to a diet with 3-NOP (Exp. 1) and showed no eating preference between CON and dNOP within 7 days. This lack of preference was maintained throughout Exp. 2 when the same animals were fed a high grain diet.
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Korniłłowicz, Teresa. "Effect of dinitroorthocresol (DNOC) on physiology and morphology of soil fungi. II. Effect of DNOC on uptake of nitrate and contents of some N-organic fractions in the mycelium." Acta Mycologica 19, no. 2 (August 20, 2014): 297–307. http://dx.doi.org/10.5586/am.1983.023.
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The purpose of the investigation was to study the influence of nitrophenol pesticide (DNOC) on nitrogen metabolism measured by growth reduction in the presence of low doses of DNOC. It was established that DNOC (5; 10 mcg/ml) increased the uptake of nitrates from the culture medium which was connected with an increase of the total content of low molecular weight nitrogen compounds and the amine fraction. In the presence of DNOC the quality and quantity of free amino acids was changed On the other hand low concentrations of DNOC decreased the amount of high molecular weight compounds of nitrogen in the mycelium.
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Crapart, Camille, Tom Andersen, Dag Olav Hessen, Nicolas Valiente, and Rolf David Vogt. "Factors Governing Biodegradability of Dissolved Natural Organic Matter in Lake Water." Water 13, no. 16 (August 13, 2021): 2210. http://dx.doi.org/10.3390/w13162210.
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Dissolved Natural Organic Matter (DNOM) is a heterogeneous mixture of partly degraded, oxidised and resynthesised organic compounds of terrestrial or aquatic origin. In the boreal biome, it plays a central role in element cycling and practically all biogeochemical processes governing the physico-chemistry of surface waters. Because it plays a central role in multiple aquatic processes, especially microbial respiration, an improved understanding of the biodegradability of the DNOM in surface water is needed. Here the current study, we used a relatively cheap and non-laborious analytical method to determine the biodegradability of DNOM, based on the rate and the time lapse at which it is decomposed. This was achieved by monitoring the rate of oxygen consumption during incubation with addition of nutrients. A synoptic method study, using a set of lake water samples from southeast Norway, showed that the maximum respiration rate (RR) and the normalised RR (respiration rate per unit of carbon) of the DNOM in the lakes varied significantly. This RR is conceived as a proxy for the biodegradability of the DNOM. The sUVa of the DNOM and the C:N ratio were the main predictors of the RR. This implies that the biodegradability of DNOM in these predominantly oligotrophic and dystrophic lake waters was mainly governed by their molecular size and aromaticity, in addition to its C:N ratio in the same manner as found for soil organic matter. The normalised RR (independently of the overall concentration of DOC) was predicted by the molecular weight and by the origin of the organic matter. The duration of the first phase of rapid biodegradation of the DNOM (BdgT) was found to be higher in lakes with a mixture of autochthonous and allochthonous DNOM, in addition to the amount of biodegradable DNOM.
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Broderick, Kate E., Matthew R. MacPherson, Michael Regulski, Tim Tully, Julian A. T. Dow, and Shireen A. Davies. "Interactions between epithelial nitric oxide signaling and phosphodiesterase activity in Drosophila." American Journal of Physiology-Cell Physiology 285, no. 5 (November 2003): C1207—C1218. http://dx.doi.org/10.1152/ajpcell.00123.2003.
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Signaling by nitric oxide (NO) and guanosine 3′,5′-cyclic monophosphate (cGMP) modulates fluid transport in Drosophila melanogaster. Expression of an inducible transgene encoding Drosophila NO synthase ( dNOS) increases both NOS activity in Malpighian (renal) tubules and DNOS protein in both type I (principal) and type II (stellate) cells. However, cGMP content is increased only in principal cells. DNOS overexpression results in elevated basal rates of fluid transport in the presence of the phosphodiesterase (PDE) inhibitor, Zaprinast. Direct assay of tubule cGMP-hydrolyzing phosphodiesterase (cG-PDE) activity in wild-type and dNOS transgenic lines shows that cG-PDE activity is Zaprinast sensitive and is elevated upon dNOS induction. Zaprinast treatment increases cGMP content in tubules, particularly at the apical regions of principal cells, suggesting localization of Zaprinast-sensitive cG-PDE to these areas. Potential cross talk between activated NO/cGMP and calcium signaling was assessed in vivo with a targeted aequorin transgene. Activated DNOS signaling alone does not modify either neuropeptide (CAP2b)- or cGMP-induced increases in cytosolic calcium levels. However, in the presence of Zaprinast, both CAP2b-and cGMP-stimulated calcium levels are potentiated upon DNOS overexpression. Use of the calcium channel blocker, verapamil, abolishes the Zaprinast-induced transport phenotype in dNOS-overexpressing tubules. Molecular genetic intervention in the NO/cGMP signaling pathway has uncovered a pivotal role for cell-specific cG-PDE in regulating the poise of the fluid transporting Malpighian tubule via direct effects on intracellular cGMP concentration and localization and via interactions with calcium signaling mechanisms.
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Chou, S. Grace, Douglas T. Petkie, Rebecca A. H. Butler, and Charles E. Miller. "Rotational Spectroscopy of DNO3." Journal of Molecular Spectroscopy 211, no. 2 (February 2002): 284–85. http://dx.doi.org/10.1006/jmsp.2001.8482.
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Korniłłowicz, Teresa. "Influence of dinitroorthocresol (DNOC) on physiology and morphology of soil fungi. III. The effect of various concentrations of DNOC on spore germination activity and morphology of germ tubes." Acta Mycologica 20, no. 1 (August 20, 2014): 45–61. http://dx.doi.org/10.5586/am.1984.005.
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In the present paper low concentrations (l -10 mcg/ml) of DNOC, in general, were not found to restrain germination of fungal spores. High concentrations (25-200 mcg/ml) were sporostatic and sporocidal Disturbances of fungal spore germination in the presence of DNOC were often accompanied by morphological changes of spores and germ tubes, <i>Mucor mucedo</i> under the influence of DNOC developed budding cels besides hyphae.
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Silva, Fabio Henrique, Serkan Karakus, Biljana Musicki, Hotaka Matsui, Trinity J. Bivalacqua, Jean L. dos Santos, Arthut L. Burnett, and Fernando F. Costa. "Treatment with a New Nitric Oxide Donor, a Hybrid Derived from Thalidomide and Hydroxycarbamide 3-(1,3-dioxoisoindolin-2-yl)Benzyl Nitrate, Reverses Priapism in the Sickle Cell Mouse and the Nitric Oxide-Deficient Mouse." Blood 128, no. 22 (December 2, 2016): 3634. http://dx.doi.org/10.1182/blood.v128.22.3634.3634.
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Abstract Introduction: Sickle cell disease (SCD) men display priapism. Previous studies showed that endothelial nitric oxide synthase (eNOS) gene-deficient mice and combined eNOS and neuronal nitric oxide synthase double gene-deficient mice (dNOS-/-) display a priapism phenotype associated with phosphodiesterase-5 (PDE5) downregulation. The Berkeley SCD transgenic mice display features of priapism, and, as in SCD human, this appears to be due to decreased nitric oxide (NO) signaling, which leads to lower PDE5 in the penis. Thus, when an erectile stimulus occurs in vivo, cGMP accumulates into the cavernosal smooth muscle cells, rendering the penile vasculature uncontrollably dilated, penile erection persists (i.e. priapism) as cGMP is not degraded as a consequence of PDE5 downregulation. Moreover, oxidative/nitrosative stress have been associated with priapism in SCD mice. In this study, since decreased NO bioavailability leads to lower PDE5 in penis, we aimed to evaluate the effects of new NO donor, a hybrid derived from thalidomide and hydroxycarbamide, 3-(1,3-dioxoisoindolin-2-yl)benzyl nitrate (4C), on functional and molecular alterations of erectile function in SCD and dNOS-/- mice. We have focused on the dysregulated NO-cGMP-PDE5 pathway and oxidative/nitrosative stress in erectile tissue of SCD and dNOS-/-mice. Methods: Wild type (WT, C57BL/6), Berkeley SCD transgenic and dNOS-/-male mice (3-5 mo old) were treated with compound 4C (100 µmol/kg/day) or its vehicle (20% Cremophor) daily for 3 weeks via intraperitoneal injection. The intracavernous pressure (ICP) was assessed following electrical stimulation of cavernous nerve (CN) in anaesthetized mice. ICP were normalized per mean arterial pressure (MAP). In separate protocols, corpus cavernosum (CC) strips were mounted in isolated organ baths, and the relaxing responses to acetylcholine (ACh; endothelium-dependent response) and sodium nitroprusside (SNP; endothelium-independent response), as well as electrical-field stimulation (EFS; nitrergic relaxation) were obtained in CC strips precontracted with the α1-adrenergic receptor agonist phenylephrine (10 µM). Results: The CN stimulation (4 V) caused increases of ICP/MAP ratio in WT, SCD and dNOS-/- mice. However, half detumescence time (sec) and poststimulated ICP/MAP ratio values after 9 min were (P<0.05) higher in SCD compared to the WT group, indicating that SCD mice display priapism. In dNOS-/- group, maximal ICP/MAP ratio values were higher (P<0.05) compared to WT mice, indicating that dNOS-/- mice also display priapism. Compound 4C treatment reversed the priapism in SCD and dNOS-/- mice. The cumulative addition of ACh (0.001-10 µM) produced concentration-dependent CC relaxations in WT and SCD groups, but the ACh potency (pEC50) value was higher (P<0.05) in CC of SCD compared to WT mice, which was reversed by 4C. Likewise, the nitrergic relaxation induced by EFS was also higher (P<0.05) in SCD mice compared to control mice (2 Hz: 12 ± 3 and 37 ± 9 %, respectively; n=5), which was reversed by 4C treatment. Similarly, SNP (0.01- 10 µM) produced concentration-dependent CC relaxations in WT, SCD and dNOS-/- groups, but, again, the maximal relaxations elicited by this agent were higher (P<0.05) in SCD (93 ± 7%) and dNOS-/- (105 ± 1%) groups compared to WT mice (72 ± 4%), which were fully restored to WT values with compound 4C treatment (n=5-9). PDE5 protein expressions were reduced (P<0.05) by approximately 48% and 35% in penile tissues from SCD and dNOS-/- compared to the WT group, respectively. Compound 4C treatment restored (P<0.05) the protein levels of PDE5 in the penises from SCD and dNOS-/- group. The protein expressions for gp91phox and 3-NT were significantly higher (P<0.05) in erectile tissues from SCD and dNOS-/- compared to the WT group, which were reduced (P<0.05) by 4C treatment (n=5-9). In WT mice, PDE5, gp91phox and 3-NT protein expressions were not affected by 4C, as well as CC relaxations induced by ACh, SNP and EFS. Conclusion: Compound 4C treatment reversed the priapism, as well as enhanced NO-mediated CC relaxations and normalized PDE5 expressions in the penises from SCD and dNOS-/- mice. Moreover, increased gp91phox and 3-nitrotyrosine protein expressions were also decreased by 4C in SCD and dNOS-/-mice. Compound 4C may constitute an additional strategy to prevent priapism in SCD, since SCD-related priapism therapies are few. Financial Support: FAPESP Disclosures No relevant conflicts of interest to declare.
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Blinkova, Alexandra, Mary Jo Hermandson, and James R. Walker. "Suppression of Temperature-Sensitive Chromosome Replication of an Escherichia coli dnaX(Ts) Mutant by Reduction of Initiation Efficiency." Journal of Bacteriology 185, no. 12 (June 15, 2003): 3583–95. http://dx.doi.org/10.1128/jb.185.12.3583-3595.2003.
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ABSTRACT Temperature sensitivity of DNA polymerization and growth of a dnaX(Ts) mutant is suppressible at 39 to 40°C by mutations in the initiator gene, dnaA. These suppressor mutations concomitantly cause initiation inhibition at 20°C and have been designated Cs,Sx to indicate both phenotypic characteristics of cold-sensitive initiation and suppression of dnaX(Ts). One dnaA(Cs,Sx) mutant, A213D, has reduced affinity for ATP, and two mutants, R432L and T435K, have eliminated detectable DnaA box binding in vitro. Two models have explained dnaA(Cs,Sx) suppression of dnaX, which codes for both the τ and γ subunits of DNA polymerase III. The initiation deficiency model assumes that reducing initiation efficiency allows survival of the dnaX(Ts) mutant at the somewhat intermediate temperature of 39 to 40°C by reducing chromosome content per cell, thus allowing partially active DNA polymerase III to complete replication of enough chromosomes for the organism to survive. The stabilization model is based on the idea that DnaA interacts, directly or indirectly, with polymerization factors during replication. We present five lines of evidence consistent with the initiation deficiency model. First, a dnaA(Cs,Sx) mutation reduced initiation frequency and chromosome content (measured by flow cytometry) and origin/terminus ratios (measured by real-time PCR) in both wild-type and dnaX(Ts) strains growing at 39 and 34°C. These effects were shown to result specifically from the Cs,Sx mutations, because the dnaX(Ts) mutant is not defective in initiation. Second, reduction of the number of origins and chromosome content per cell was common to all three known suppressor mutations. Third, growing the dnaA(Cs,Sx) dnaX(Ts) strain on glycerol-containing medium reduced its chromosome content to one per cell and eliminated suppression at 39°C, as would be expected if the combination of poor carbon source, the Cs,Sx mutation, the Ts mutation, and the 39°C incubation reduced replication to the point that growth (and, therefore, suppression) was not possible. However, suppression was possible on glycerol medium at 38°C. Fourth, the dnaX(Ts) mutation can be suppressed also by introduction of oriC mutations, which reduced initiation efficiency and chromosome number per cell, and the degree of suppression was proportional to the level of initiation defect. Fifth, introducing a dnaA(Cos) allele, which causes overinitiation, into the dnaX(Ts) mutant exacerbated its temperature sensitivity.
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Machado, Benedito H., Jaci A. Castania, Leni G. H. Bonagamba, and Hélio C. Salgado. "Neurotransmission of autonomic components of aortic baroreceptor afferents in the NTS of awake rats." American Journal of Physiology-Heart and Circulatory Physiology 279, no. 1 (July 1, 2000): H67—H75. http://dx.doi.org/10.1152/ajpheart.2000.279.1.h67.
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The effect of sequential blockade of N-methyl-d-aspartic acid (NMDA) receptors with dl-2-amino-5-phosphonopentanoic acid (AP-5) and non-NMDA receptors with 6,7-dinitroquinoxaline-2,3 dione (DNQX) in the nucleus tractus solitarii (NTS) on the cardiovascular responses to electrical stimulation (ES) of the aortic depressor nerve (ADN) was evaluated in awake rats. Two protocols were used. In protocol 1, bilateral microinjection of AP-5 into the NTS ( n = 7) reduced the hypotensive response to ES of the ADN; subsequent microinjection of DNQX produced additional reduction in this response. AP-5 reduced the bradycardic response, and DNQX almost abolished this response. In protocol 2, bilateral microinjection of DNQX into the NTS ( n = 6) reduced the hypotensive response, and subsequent microinjection of AP-5 significantly reduced this response. DNQX produced a significant reduction in bradycardic response, and AP-5 abolished this response. The data indicate that processing of the parasympathetic component of the NTS aortic baroreceptor afferents is mediated by both NMDA and non-NMDA receptors, whereas processing of the sympathoinhibitory component seems to be only partially mediated by ionotropic receptors.
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Pascal, Jean, and Radovan Popovic. "Mécanismes de toxicité du dinitro-o-crésol dans les chloroplastes." Water Quality Research Journal 28, no. 4 (November 1, 1993): 687–96. http://dx.doi.org/10.2166/wqrj.1993.036.
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Résumé L’inhibition du transport d’électron photosynthétique des plantes d’orge (Hordeum vulgarae) par un herbicide phénolique (DNOC) a été étudié. Ces expériences ont été réalisées afin de pouvoir mieux connaître les sites d’inhibition ainsi que les principaux modes d’action de cet herbicide. Les résultats ont démontré que le DNOC agit en inhibant au contact, du côté donneur et accepteur du PSII simultanément. L’inhibition du côté oxydant, via le complexe de dégagement d’oxygène, est partielle (70%) et semble affecter les PSII situés dans les empilements granaires. Du côté réducteur, l’action du DNOC est plus complexes. Ainsi, à faibles concentration (<10 µM), le DNOC agit comme un accepteur d’électron au niveau de QA. A de plus fortes concentrations, cet herbicide inhibe la chaîne de transport d’électron au niveau du même site ainsi que du côté accepteur du PSII.
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Schiller, Alicia M., Karla K. V. Haack, Peter R. Pellegrino, Pamela L. Curry, and Irving H. Zucker. "Unilateral renal denervation improves autonomic balance in conscious rabbits with chronic heart failure." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 305, no. 8 (October 15, 2013): R886—R892. http://dx.doi.org/10.1152/ajpregu.00269.2013.
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A hallmark of chronic heart failure (CHF) is an increased sympathetic tone resulting in autonomic imbalance. Renal denervation (DNx) in CHF patients has resulted in symptomatic improvement, but the protective mechanisms remain unclear. We hypothesized in CHF, unilateral renal DNx would improve cardiac autonomic balance. The present study used conscious, chronically instrumented New Zealand White rabbits undergoing renal DNx prior to pacing-induced CHF. Four treatment groups were used: nonpace, non-DNx [Sham-Innervated (Sham-INV)], nonpace DNx (sham-DNx), pace non-DNx (CHF-INV) or pace DNx (CHF-DNx). We examined several markers indicative of autonomic balance. Baroreflex sensitivity and time domain heart rate variability (HRV) were both decreased in the CHF-INV group compared with sham-INV and were restored to sham levels by renal DNx. Power spectral analysis indicated an increase in low-frequency/high-frequency (LF/HF) ratio in the CHF-INV compared with the sham-INV, which was normalized to sham levels by DNx. To assess whether this was due to a withdrawal of sympathetic tone or an increase in parasympathetic tone, the heart rate response was measured after an intravenous bolus of metoprolol or atropine. Bradycardia induced by intravenous metoprolol (indicative of cardiac sympathetic tone) was exacerbated in CHF-INV rabbits compared with sham-INV but was normalized in CHF-DNx. Conversely, the tachycardia in response to intravenous atropine (indicative of cardiac vagal tone) was not improved in CHF-DNx vs. CHF-INV animals. Renal DNx also prevented the increase in circulating plasma NE seen in CHF-INV rabbits. These results suggest renal DNx improves cardiac autonomic balance in CHF by a reduction of sympathetic tone.
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De Leon, H., and R. Garcia. "Regulation of glomerular atrial natriuretic factor receptor subtypes by renal sympathetic nerves." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 260, no. 6 (June 1, 1991): R1043—R1050. http://dx.doi.org/10.1152/ajpregu.1991.260.6.r1043.
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The modulation of glomerular atrial natriuretic factor (ANF) receptors (ANF-R1 and ANF-R2) was examined in rats after unilateral (Uni-DNx), bilateral (Bil-DNx), and sham renal denervation (Sham-DNx). Glomerular ANF receptor density was higher in both left and right kidneys (1,138 +/- 73 and 952 +/- 100 fmol/mg protein, respectively) of Bil-DNx rats than in Sham-DNx animals (302 +/- 9 and 328 +/- 13 fmol/mg protein, respectively). The denervated (left) kidney from Uni-DNx rats also showed higher ANF receptor density (1,146 +/- 68 fmol/mg protein) than the contralateral untouched kidney (602 +/- 34 fmol/mg protein). Plasma ANF-(99-126) and ANF-(1-98) levels were significantly lower in the Bil-DNx group than in either Uni-DNx or Sham-DNx animals. Affinity cross-linking studies followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography demonstrated that both ANF-R1 and ANF-R2 receptors were upregulated in the same proportion in denervated kidneys. Guanosine 3',5'-cyclic monophosphate production by isolated glomeruli from denervated kidneys of either Bil-DNx or Uni-DNx rats was significantly higher than that of Sham-DNx controls. We conclude that renal sympathetic nerves regulate both glomerular ANF-R1 and ANF-R2-receptor subtypes.
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Klausner, Arthur. "DNAX Keeps a Scholar's Focus." Nature Biotechnology 6, no. 4 (April 1988): 373–78. http://dx.doi.org/10.1038/nbt0488-373.
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Lee, Sang-Hun, G. Govindaiah, and Charles L. Cox. "Selective Excitatory Actions of DNQX and CNQX in Rat Thalamic Neurons." Journal of Neurophysiology 103, no. 4 (April 2010): 1728–34. http://dx.doi.org/10.1152/jn.00540.2009.
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The thalamic reticular nucleus (TRN) consists of GABA-containing neurons that form reciprocal synaptic connections with thalamic relay nuclei. Excitatory synaptic innervation of TRN neurons arises from glutamatergic afferents from thalamocortical relay neurons and deep layer corticothalamic neurons, and they produce excitation via both N-methyl-d-aspartate (NMDA) and non-NMDA receptors. Quinoxaline derivatives [e.g., 6,7-dinitroquinoxaline-2,3-dione (DNQX), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)] have routinely been used as non-NMDA receptor antagonists over the last two decades. In this study, we examined whether quinoxaline derivatives alter the intrinsic properties of thalamic neurons in light of recent findings indicating that these compounds can alter neuronal excitability in hippocampal and cerebellar neurons via transmembrane AMPA receptor (AMPAR) regulatory proteins (TARPs). Whole cell recordings were obtained from TRN and ventrobasal (VB) thalamic relay neurons in vitro. DNQX and CNQX produced a consistent depolarization in all TRN neurons tested. The depolarization persisted in tetrodotoxin and low Ca2+/high Mg2+ conditions, suggesting a postsynaptic site of action. In contrast, DNQX and CNQX produced little or no change in VB thalamocortical relay neurons. The nonspecific ionotropic glutamate receptor antagonist, kynurenic acid, and the selective AMPAR antagonist, 4-(8-methyl-9H-1,3-dioxolo[4,5-h][2,3]benzodiazepin-5-y l)-benzenamine hydrochloride, blocked the DNQX-mediated depolarizations. Our results indicate that the DNQX- and CNQX-mediated depolarizations are mediated by AMPAR but not kainate receptors in TRN neurons. The AMPAR-positive allosteric modulator, trichloromethiazide, potentiated the DNQX-mediated depolarization in TRN neurons but did not unmask any excitatory actions of DNQX/CNQX in relay neurons. This selective action may not only reveal a differential TARP distribution among thalamic neurons but also may provide insight into distinct characteristics of AMPA receptors of thalamic neurons that could be exploited by future pharmacological development. Furthermore, these data suggest that quinoxaline derivatives could modulate synaptic transmission and alter neuronal excitability.
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Manor, Meghan L., Theodore J. Derksen, Andrew D. Magnuson, Fahad Raza, and Xin Gen Lei. "Inclusion of Dietary Defatted Microalgae Dose-Dependently Enriches ω-3 Fatty Acids in Egg Yolk and Tissues of Laying Hens." Journal of Nutrition 149, no. 6 (April 22, 2019): 942–50. http://dx.doi.org/10.1093/jn/nxz032.
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ABSTRACT Background The potential for dietary microalgae to enrich eggs of laying hens with ω-3 (n–3) fatty acids, and the mechanisms involved, are unclear. Objectives The aim of this study was to determine the effects and molecular regulation of a defatted Nannochloropsis oceanica microalgae (DNOM) biomass on the enrichment of the eggs and tissues of laying hens with ω-3 fatty acids. Methods Fifty Shaver-White Leghorn hens (46 wk of age, body weight: 1.70 ± 0.27 kg) were individually caged (n = 10) and fed a corn-soy–based diet supplemented with DNOM at 0% (control), 2.86%, 5.75%, 11.5%, and 23% for 6 wk. Fatty acid profiles, health status, and related gene expression in eggs, blood, and tissues were performed at weeks 0, 2, 4, and 6. Data were analyzed by a combination of 1-factor ANOVA and correlation between DNOM doses and measures. Results The DNOM produced linear (P < 0.01) enrichments of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and total ω-3 fatty acids in the egg yolk (R2 > 0.9) and of DHA in the liver, breast, and thigh (R2 = 0.66–0.82). Concentrations of EPA + DHA in the egg yolk and these 3 tissues of hens fed 11.5% and 23% DNOM were 1.4–2.1, 0.6–1, 3.3–5.3, and 6–7 times greater (P < 0.001) than those in the controls, respectively. The DNOM caused dose-dependent elevations (P < 0.01) of malic enzyme and elongases 3, 4, and 5 mRNA levels (R2 = 0.97, 0.78, 0.97, and 0.86, respectively), along with increased (P < 0.01) Δ5- and Δ6-desaturases and decreased (P < 0.01) Δ9-desaturase and acyl-coenzyme A thioesterase 4 mRNA levels in the liver. Conclusions Feeding DNOM to laying hens produced dose-dependent enrichments of DHA in their eggs, liver, and muscles by regulating key genes involved in the elongation and desaturation of polyunsaturated fatty acids. Our findings will help produce DHA-enriched eggs.
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Gopakumar, Sricharan, Joy Gumin, Marc Daou, Daniel Ledbetter, Malcolm McDonald, Anwar Hossain, Shawn Hingtgen, Matthew Ewend, and Frederick Lang. "EXTH-62. STEM CELL DELIVERY OF ONCOLYTIC ADENOVIRUS DNX-2401 FOLLOWING SURGICAL RESECTION FOR THE TREATMENT OF GLIOBLASTOMA." Neuro-Oncology 21, Supplement_6 (November 2019): vi95. http://dx.doi.org/10.1093/neuonc/noz175.392.
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Abstract BACKGROUND The oncolytic virus DNX-2401 (Delta-24-RGD) is a novel treatment of GBM. While prior studies have examined intratumoral injection of DNX-2401 into recurrent GBM, the potential of delivering DNX-2401 into the surgical resection cavity using tumor-tropic human mesenchymal stem cells (MSCs) has not been evaluated. We hypothesize that exploiting a fibrin-based scaffold for transplanting MSCs loaded with DNX-2401 (MSCs-DNX-2401) into the resection cavity will improve viral delivery, decrease GBM recurrence, and extend overall survival. METHODS MSCs-DNX-2401 were seeded in a fibrin matrix or suspended in PBS and placed in the upper wells of transwell plates with U87 cells placed below. After one week, U87 cells were counted to compare rates of cellular killing and confirm release of DNX-2401 from fibrin-seeded MSCs. U87 cells were transduced with mCherry-Luciferase and implanted into the brains of athymic mice (N=16). After fluorescence-guided surgical resection of glioma xenografts, MSCs (control) or MSCs-DNX-2401 were delivered in the resection cavity using a fibrin scaffold. Serial bioluminescence imaging (BLI) was used to monitor tumor recurrence. RESULTS In transwell experiments, MSCs-DNX-2401 seeded in fibrin were as effective as MSCs-DNX-2401 without the scaffold, indicating that fibrin did not negatively impact cell viability or viral release. In in vivo studies mimicking residual tumor after surgical resection, treatment of the post-resection cavity with MSCs-DNX-2401 suspended in fibrin permitted retention of MSCs-DNX-2401 within the tumor bed. Kaplan-Meier survival analyses revealed statistically significant improved survival after treatment with MSC-DNX-2401 in fibrin compared to controls with 50% of animals demonstrating complete responses according to BLI (p < 0.05). CONCLUSION Delivering DNX-2401 into the post-resection surgical cavity using MSCs seeded in fibrin is capable of eradicating residual GBM and prolonging overall survival. These studies support the clinical translation of this approach in newly diagnosed patients undergoing surgical resection of GBM.
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Korniłłowicz, Teresa. "Effects of dtnitroorthocresol (DNOC) on physiology and morphology of soil fungi. IV. The effect of various concentrations of DNOC on morphology of developing hyphae and colonies." Acta Mycologica 21, no. 1 (August 20, 2014): 3–12. http://dx.doi.org/10.5586/am.1985.001.
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Low doses of DNOC (l -10 mcg/ml) caused morphological and anatomical changes of vegetative hyphae and conidiophores of some soil fungi. These changes in hyphae were connected with changes in structure of fungi colonies. Sporulation of fungi was stopped in the presence of low DNOC concentrations — approached to field doses.
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Rodionova, Kristina, Christian Fiedler, Franziska Guenther, Eric Grouzmann, Winfried Neuhuber, Michael J. M. Fischer, Christian Ott, et al. "Complex reinnervation pattern after unilateral renal denervation in rats." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 310, no. 9 (May 1, 2016): R806—R818. http://dx.doi.org/10.1152/ajpregu.00227.2014.
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Renal denervation (DNX) is a treatment for resistant arterial hypertension. Efferent sympathetic nerves regrow, but reinnervation by renal afferent nerves has only recently been shown in the renal pelvis of rats after unilateral DNX. We examined intrarenal perivascular afferent and sympathetic efferent nerves after unilateral surgical DNX. Tyrosine hydroxylase (TH), CGRP, and smooth muscle actin were identified in kidney sections from 12 Sprague-Dawley rats, to distinguish afferents, efferents, and vasculature. DNX kidneys and nondenervated kidneys were examined 1, 4, and 12 wk after DNX. Tissue levels of CGRP and norepinephrine (NE) were measured with ELISA and mass spectrometry, respectively. DNX decreased TH and CGRP labeling by 90% and 95%, respectively ( P < 0.05) within 1 wk. After 12 wk TH and CGRP labeling returned to baseline with a shift toward afferent innervation ( P < 0.05). Nondenervated kidneys showed a doubling of both labels within 12 wk ( P < 0.05). CGRP content decreased by 72% [3.2 ± 0.3 vs. 0.9 ± 0.2 ng/gkidney; P < 0.05] and NA by 78% [1.1 ± 0.1 vs. 0.2 ± 0.1 pmol/mgkidney; P < 0.05] 1 wk after DNX. After 12 wk, CGRP, but not NE, content in DNX kidneys was fully recovered, with no changes in the nondenervated kidneys. The use of phenol in the DNX procedure did not influence this result. We found morphological reinnervation and transmitter recovery of afferents within 12 wk after DNX. Despite morphological evidence of sympathetic regrowth, NE content did not fully recover. These results suggest a long-term net surplus of afferent influence on the DNX kidney may be contributing to the blood pressure lowering effect of DNX.
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Wollina, Uwe, Jacqueline Schönlebe, Georgi Georgi Tchernev, and Torello Lotti. "Diffuse Normolipemic Plane Xanthoma (DNPX) of the Neck without Xanthelasma Palpebrum." Open Access Macedonian Journal of Medical Sciences 6, no. 1 (January 10, 2018): 123–25. http://dx.doi.org/10.3889/oamjms.2018.037.
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Diffuse normolipemic plane xanthoma (DNPX) is an uncommon subtype of non-Langerhans histiocytosis. DNPX is characterised by xanthelasma palpebrarum, diffuse plane xanthoma of the head, neck, trunk, or extremities, and normal plasma lipid levels. The neck is the most common site. We report about a 62-year-old female Caucasian patient, who developed an asymptomatic fine wrinkling and loose skin on the neck and décolleté about three years ago. The skin colour became yellowish. Xanthelasma was absent. Histopathology of a skin biopsy confirmed the diagnosis of DNPX. The patient had a medical history of chronic myeloblastic leukaemia. No other laboratory abnormalities were found. Laser treatment was offered but opposed by the patient.
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Rossi, Noreen F., Russell Pajewski, Haiping Chen, Peter J. Littrup, and Maria Maliszewska-Scislo. "Hemodynamic and neural responses to renal denervation of the nerve to the clipped kidney by cryoablation in two-kidney, one-clip hypertensive rats." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 310, no. 2 (January 15, 2016): R197—R208. http://dx.doi.org/10.1152/ajpregu.00331.2015.
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Renal artery stenosis is increasing in prevalence. Angioplasty plus stenting has not proven to be better than medical management. There has been a reluctance to use available denervation methodologies in this condition. We studied conscious, chronically instrumented, two-kidney, one-clip (2K-1C) Goldblatt rats, a model of renovascular hypertension, to test the hypothesis that renal denervation by cryoablation (cryo-DNX) of the renal nerve to the clipped kidney decreases mean arterial pressure (MAP), plasma and tissue ANG II, and contralateral renal sympathetic nerve activity (RSNA). Five-week-old male Sprague-Dawley rats underwent sham (ShC) or right renal artery clipping (2K-1C), placement of telemetry transmitters, and pair-feeding with a 0.4% NaCl diet. After 6 wk, rats were randomly assigned to cryo-DNX or sham cryotreatment (sham DNX) of the renal nerve to the clipped kidney. MAP was elevated in 2K-1C and decreased significantly in both ShC cryo-DNX and 2K-1C cryo-DNX. Tissue norepinephrine was ∼85% lower in cryo-DNX kidneys. Plasma ANG II was higher in 2K-1C sham DNX but not in 2K-1C cryo-DNX vs ShC. Renal tissue ANG II in the clipped kidney decreased after cryo-DNX. Baseline integrated RSNA of the unclipped kidney was threefold higher in 2K-1C versus ShC and decreased in 2K-1C cryo-DNX to values similar to ShC. Maximum reflex response of RSNA to baroreceptor unloading in 2K-1C was lower after cryo-DNX. Thus, denervation by cryoablation of the renal nerve to the clipped kidney decreases not only MAP but also plasma and renal tissue ANG II levels and RSNA to the contralateral kidney in conscious, freely moving 2K-1C rats.
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Grigoraș, Gheorghe, Bogdan-Constantin Neagu, Mihai Gavrilaș, Ion Triștiu, and Constantin Bulac. "Optimal Phase Load Balancing in Low Voltage Distribution Networks Using a Smart Meter Data-Based Algorithm." Mathematics 8, no. 4 (April 8, 2020): 549. http://dx.doi.org/10.3390/math8040549.
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In the electric distribution systems, the “Smart Grid” concept is implemented to encourage energy savings and integration of the innovative technologies, helping the distribution network operators (DNOs) in choosing the investment plans which lead to the optimal operation of the networks and increasing the energy efficiency. In this context, a new phase load balancing algorithm was proposed to be implemented in the low voltage distribution networks with hybrid structures of the consumption points (switchable and non-switchable consumers). It can work in both operation modes (real-time and off-line), uploading information from different databases of the DNO which contain: The consumers’ characteristics, the real loads of the consumers integrated into the smart metering system (SMS), and the typical load profiles for the consumers non-integrated in the SMS. The algorithm was tested in a real network, having a hybrid structure of the consumption points, on a by 24-h interval. The obtained results were analyzed and compared with other algorithms from the heuristic (minimum count of loads adjustment algorithm) and the metaheuristic (particle swarm optimization and genetic algorithms) categories. The best performances were provided by the proposed algorithm, such that the unbalance coefficient had the smallest value (1.0017). The phase load balancing led to the following technical effects: decrease of the average current in the neutral conductor and the energy losses with 94%, respectively 61.75%, and increase of the minimum value of the phase voltage at the farthest pillar with 7.14%, compared to the unbalanced case.
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Grigoraș, Gheorghe, Bogdan-Constantin Neagu, Florina Scarlatache, Livia Noroc, and Ecaterina Chelaru. "Bi-Level Phase Load Balancing Methodology with Clustering-Based Consumers’ Selection Criterion for Switching Device Placement in Low Voltage Distribution Networks." Mathematics 9, no. 5 (March 4, 2021): 542. http://dx.doi.org/10.3390/math9050542.
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In the last years, the distribution network operators (DNOs) assumed transition strategies of the electric distribution networks (EDNs) towards the active areas of the microgrids where, regardless of the operating regimes, flexibility, economic efficiency, low power losses, and high power quality are ensured. Artificial intelligence techniques, combined with the smart devices and real-time remote communication solutions of the enormous data amounts, can represent the starting point in establishing decision-making strategies to solve one of the most important challenges related to phase load balancing (PLB). In this context, the purpose of the paper is to prove that a decision-making strategy based on a limited number of PLB devices installed at the consumers (small implementation degree) leads to similar technical benefits as in the case of full implementation in the EDNs. Thus, an original bi-level PLB methodology, considering a clustering-based selection criterion of the consumers for placement of the switching devices, was proposed. A real EDN from a rural area belonging to a Romanian DNO has been considered in testing the proposed methodology. An implementation degree of the PLB devices in the EDN by 17.5% represented the optimal solution, leading to a faster computational time with 43% and reducing the number of switching operations by 92%, compared to a full implementation degree (100%). The performance indicators related to the unbalance factor and energy-saving highlighted the efficiency of the proposed methodology.
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Lang, Frederick F., Nam D. Tran, Vinay K. Puduvalli, J. Bradley Elder, Karen L. Fink, Charles A. Conrad, W. K. Alfred Yung, et al. "Phase 1b open-label randomized study of the oncolytic adenovirus DNX-2401 administered with or without interferon gamma for recurrent glioblastoma." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 2002. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.2002.
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2002 Background: DNX-2401 is a replication-competent, tumor-selective, oncolytic adenovirus with enhanced infectivity that causes durable tumor control by killing tumor cells and eliciting antitumor immunity. To increase immune activation, a phase 1b randomized study of intratumoral DNX-2401 alone versus DNX-2401 with interferon gamma (IFN) was conducted. Methods: A total of 27 patients with biopsy-confirmed glioblastoma at first or second recurrence received a single intratumoral injection of 3e10 vp DNX-2401. Patients were randomized in a 2:1 ratio to receive 50 mcg/m2 of subcutaneous IFN (Actimmune) Q3W initiated 14 days after DNX-2401 or to be followed without further treatment for safety and survival. Results: Twenty-seven (27) patients were enrolled following first (59%) or second (41%) recurrence having previously failed surgery, radiation, and temozolomide (100%). The median longest tumor diameter was 40 mm (range 20-77 mm). Patients were randomized to DNX-2401 followed by IFN (n = 18) or to DNX-2401 alone (n = 9). Due to the poor tolerability of IFN, the median duration of treatment was only 6 weeks (range 0-30 weeks), and two patients did not initiate treatment as scheduled due to early clinical deterioration. The most frequent grade 3-4 AEs across treatment groups were fatigue, headache, and seizures consistent with pre-existing symptoms, underlying disease and/or surgery. Based upon a preliminary intent-to-treat analysis, IFN did not appear to provide additional benefit. However, OS-12 and OS-18 for all patients enrolled was 33% and 22%, respectively regardless of treatment assignment. Three patients remain alive at 19, 21, and 22 months (DNX-2401, n = 1; DNX-2401 + IFN, n = 2). Interestingly, 50% of patients with a baseline tumor diameter of ≤ 42 mm survived beyond 12 months, potentially identifying a sub-population of patients that may live longer following intratumoral DNX-2401. Conclusions: DNX-2401 was well tolerated as monotherapy. Although the addition of IFN did not improve survival, clinical activity following a single injection of DNX-2401 is encouraging and supports an ongoing Phase II study of DNX-2401 for recurrent glioblastoma. Clinical trial information: NCT02197169.
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Awazu, M., V. Kon, R. C. Harris, T. Imada, T. Inagami, and I. Ichikawa. "Renal sympathetic nerves modulate glomerular ANP receptors and filtration." American Journal of Physiology-Renal Physiology 261, no. 1 (July 1, 1991): F29—F35. http://dx.doi.org/10.1152/ajprenal.1991.261.1.f29.
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We examined characteristics of atrial natriuretic peptide (ANP) receptors in glomeruli isolated from subacutely (3-5 days) denervated (DNX) and contralateral nondenervated (non-DNX) kidneys of normal rats (NL) and rats subjected to water deprivation for 48 h (WD). Total ANP receptor density in DNX kidneys of WD rats, measured by competitive inhibition binding between 125I-labeled ANP and ANP, was twofold higher than non-DNX kidneys (726 +/- 96 vs. 384 +/- 32 fmol/mg protein, P less than 0.05). Equilibrium association constant (Ka) was not significantly different (2.33 +/- 0.43 vs. 3.34 +/- 0.78 x 10(9) M-1). In NL rats, there was no difference in ANP receptor density between DNX and non-DNX kidneys (244 +/- 20 and 264 +/- 16 fmol/mg protein). Production of guanosine 3',5'-cyclic monophosphate (cGMP), a putative second messenger of ANP, in response to ANP (10(-7) M) in glomeruli isolated from DNX was significantly larger than non-DNX kidneys of WD rats. To determine whether these changes in ANP receptors have functional consequences in vivo, glomerular capillary ultrafiltration coefficient (Kf) was assessed by micropuncture technique in WD Munich-Wistar rats. In DNX kidneys, ANP infusion (4 micrograms.kg-1.h-1) significantly increased whole kidney glomerular filtration rate (GFR) and single-nephron (SN) GFR (0.64 +/- 0.06 to 0.89 +/- 0.17 ml/min and 25 +/- 2 to 33 +/- 2 nl/min, respectively; n = 7) and Kf (1.26 +/- 0.29 to 2.18 +/- 0.41 nl.min-1.mmHg-1).(ABSTRACT TRUNCATED AT 250 WORDS)
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Karler, Ralph, Larry D. Calder, and Stuart A. Turkanis. "DNQX blockade of amphetamine behavioral sensitization." Brain Research 552, no. 2 (June 1991): 295–300. http://dx.doi.org/10.1016/0006-8993(91)90095-d.
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Rudd, M. A., R. S. Grippo, and W. J. Arendshorst. "Acute renal denervation produces a diuresis and natriuresis in young SHR but not WKY rats." American Journal of Physiology-Renal Physiology 251, no. 4 (October 1, 1986): F655—F661. http://dx.doi.org/10.1152/ajprenal.1986.251.4.f655.
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Clearance experiments were conducted to determine the effect of acute unilateral renal denervation (DNX) on renal hemodynamics and salt and water excretion in anesthetized 6-wk-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto genetic control rats (WKY). Before DNX, SHR had higher mean arterial pressure (33%) and renal vascular resistance (RVR) (57%) and lower glomerular filtration rate (GFR) (10%); urine flow and sodium excretion were similar. Following DNX in SHR, sodium and water excretion increased by 138 and 62%, respectively (P less than 0.001); GFR and RVR were unchanged. In contrast, DNX in WKY did not affect urine flow (0%) or sodium excretion (-21%). These strain differences were observed in Okamoto-Aoki rats from two sources. Effective DNX was indicated by 95% reduction of norepinephrine content 3 days after DNX in both strains. Six-week-old Sprague-Dawley and Munich-Wistar rats, in contrast to WKY, responded to DNX with a natriuresis (+182%) and diuresis (+95%) (P less than 0.001). Renal function was unaffected by sham DNX in SHR. Our results indicate that efferent renal nerve activity has little tonic influence on the renal vasculature in these young rats. Augmented neurotransmitter release and/or tubular responsiveness may be involved in fluid and electrolyte retention and the pathogenesis of hypertension in SHR. Conversely, blunted renal neuroeffector responses may prevent WKY from developing hypertension.
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Petersen, J. C. "Doppler-limited dye laser excitation spectroscopy of DNO: Predissociation of DNO." Journal of Molecular Spectroscopy 110, no. 2 (April 1985): 277–300. http://dx.doi.org/10.1016/0022-2852(85)90295-4.
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Tran, Oanh Thi Kieu, Ton Trong Luong, Hoa Ngoc Tran, and Trang Minh Pham. "Determination of phthalate esters in children’s toys." Science and Technology Development Journal 19, no. 3 (September 30, 2016): 79–88. http://dx.doi.org/10.32508/stdj.v19i3.539.
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A validated analytical method for the determination of phthalates (DBP, BBP, DEHP, DNOP, DINP and DIDP) in plastics was described and applied to 20 toys in Ho Chi Minh city, Vietnam. Phthalates in the sample were extracted in a mixture of acetone and hexane and analyzed by GC-FID. Limits of detection (LOD) and limits of quantification (LOQ) of the analysis method for DBP, BBP, DEHP và DNOP in the PVC plastic were from 0.0011% to 0.0014% and from 0.0028 to 0.0046%, respectively. Recoveries of DBP, BBP, DEHP và DNOP in PVC and PP at two spiked concentrations (0.1% and 0.01%) ranged from 86.6% to 91.7% with the relative standard deviation (%RSD) were from 2.5% to 8.7%. Wide ranges of linearity of standard curves were obtained from 0.5 mg/L to 100 mg/L for DBP, BBP, DEHP and DNOP and from 25 mg/L to 1000 mg/L for DINP and DIDP with R2 > 0.999. The studied method was a reliable, rapid, easy and cheap method and permitted to determine the restricted phthalates in plastic toys in compliance with European Regulation (No 1907/2006). The method was applied to determine phthalates in 20 toys in HoChiMinh city, Vietnam. Phthalates were found in almost soft PVC toys with high concentrations.
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Soffiati, Arthur. "DNOS: uma instituição mítica da República Brasileira." Revista Brasileira de Estudos Urbanos e Regionais 7, no. 2 (November 30, 2005): 61. http://dx.doi.org/10.22296/2317-1529.2005v7n2p61.
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Tomando por base o conceito de mito histórico, amplamente estudado por Raoul Girardet e José Murilo de Carvalho, pretende-se, neste artigo, examinar a trajetória do Departamento Nacional de Obras e Saneamento (DNOS) – principalmente na Baixada dos Goytacazes (RJ), onde sua atuação foi mais intensa que em outras partes do país –, em consonância com os fundamentos teóricos dos autores citados. Assim, são identificadas quatro fases no mito do DNOS: tempo do apelo e da espera, tempo da presença, tempo da crise e tempo da lembrança. Para concluir, aborda-se o período posterior à extinção ao órgão, em plena fase do neoliberalismo.Palavras-chave: mito histórico; Departamento Nacional de Obras e Saneamento; saneamento. Abstract: Considering the concept of historical myth largely discussed byauthors as Raoul Girardet and José Murilo de Carvalho, this article examines the trajectory of the National Department of Works and Sanitation (DNOS), mainly in Baixada dos Goytacazes (Rio de Janeiro state), where its action was greater than in other regions of the country. Four phases are identified in this mythical institution experience: time of appeal and expectation, time of presence, time of crisis and remembrance. In conclusion, some comments are made on the period that followed DNOS extinction, in a full phase of neoliberalism.Keywords: historical myth; sanitation; environmental agencies.
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Islam, Md Rashedul, Osamu Ichii, Teppei Nakamura, Takao Irie, Akio Shinohara, Md Abdul Masum, Yuki Otani, et al. "Comparison of Ovarian Morphology and Follicular Disturbances between Two Inbred Strains of Cotton Rats (Sigmodon hispidus)." Animals 11, no. 6 (June 12, 2021): 1768. http://dx.doi.org/10.3390/ani11061768.
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Most mammalian ovarian follicles contain only a single oocyte having a single nucleus. However, two or more oocytes and nuclei are observed within one follicle and one oocyte, respectively, in several species, including cotton rat (CR, Sigmodon hispidus). The present study compared ovarian histology, focusing on folliculogenesis, between two inbred CR strains, HIS/Hiph and HIS/Mz. At 4 weeks of age, ovarian sections from both the strains were analyzed histologically. Multi-oocyte follicles (MOFs) and double-nucleated oocytes (DNOs) were observed in all stages of developing follicles in HIS/Hiph, whereas HIS/Mz had MOFs up to secondary stages and lacked DNOs. The estimated total follicles in HIS/Mz were almost half that of HIS/Hiph, but interstitial cells were well developed in HIS/Mz. Furthermore, immunostaining revealed no clear strain differences in the appearance of oocytes positive for Ki67, PCNA, and p63 in MOF or DNOs; no cell death was observed in these oocytes. Ultrastructural analysis revealed more abundant mitochondrial clouds in oocytes of HIS/Hiph than HIS/Mz. Thus, we clarified the strain differences in the CR ovary. These findings indicate that early events during folliculogenesis affect the unique ovarian phenotypes found in CRs, including MOFs or DNOs, and their strain differences.
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Borland, Colin, Helen Dunningham, Fiona Bottrill, and Alain Vuylsteke. "Can a membrane oxygenator be a model for lung NO and CO transfer?" Journal of Applied Physiology 100, no. 5 (May 2006): 1527–38. http://dx.doi.org/10.1152/japplphysiol.00949.2005.
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To model lung nitric oxide (NO) and carbon monoxide (CO) uptake, a membrane oxygenator circuit was primed with horse blood flowing at 2.5 l/min. Its gas channel was ventilated with 5 parts/million NO, 0.02% CO, and 22% O2 at 5 l/min. NO diffusing capacity (Dno) and CO diffusing capacity (Dco) were calculated from inlet and outlet gas concentrations and flow rates: Dno = 13.45 ml·min−1·Torr−1 (SD 5.84) and Dco = 1.22 ml·min−1·Torr−1 (SD 0.3). Dno and Dco increased ( P = 0.002) with blood volume/surface area. 1/Dno ( P < 0.001) and 1/Dco ( P < 0.001) increased with 1/Hb. Dno ( P = 0.01) and Dco ( P = 0.004) fell with increasing gas flow. Dno but not Dco increased with hemolysis ( P = 0.001), indicating Dno dependence on red cell diffusive resistance. The posthemolysis value for membrane diffusing capacity = 41 ml·min−1·Torr−1 is the true membrane diffusing capacity of the system. No change in Dno or Dco occurred with changing blood flow rate. 1/Dco increased ( P = 0.009) with increasing Po2. Dno and Dco appear to be diffusion limited, and Dco reaction limited. In this apparatus, the red cell and plasma offer a significant barrier to NO but not CO diffusion. Applying the Roughton-Forster model yields similar specific transfer conductance of blood per milliliter for NO and CO to previous estimates. This approach allows alteration of membrane area/blood volume, blood flow, gas flow, oxygen tension, red cell integrity, and hematocrit (over a larger range than encountered clinically), while keeping other variables constant. Although structurally very different, it offers a functional model of lung NO and CO transfer.
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Kim, Seon-Ho, Chanhee Lee, Heather A. Pechtl, Jade M. Hettick, Magnus R. Campler, Monique D. Pairis-Garcia, Karen A. Beauchemin, Pietro Celi, and Stephane M. Duval. "Effects of 3-nitrooxypropanol on enteric methane production, rumen fermentation, and feeding behavior in beef cattle fed a high-forage or high-grain diet1." Journal of Animal Science 97, no. 7 (May 17, 2019): 2687–99. http://dx.doi.org/10.1093/jas/skz140.
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AbstractThe objective of the study was to determine whether feeding a diet supplemented with 3-nitrooxypropanol (3-NOP) affects feeding behavior altering intake and rumen fermentation. Two experiments were conducted with 9 rumen-cannulated beef steers in a replicated 3 × 3 Latin square design where animals received a high-forage or high-grain diet. Treatments were 1) a basal diet (CON), the CON diet supplemented with 3-NOP (dNOP; 100 mg/kg in dietary DM or 1 g/d), or the CON diet with 3-NOP (1 g/d) infused into the rumen (infNOP). Each experimental period consisted of 14-d diet adaptation and 7-d sample collection. A 7-d washout period was provided between experiment periods. All data were analyzed as a Latin square design using Mixed Procedure of SAS. In Exp. 1 (high-forage diet), methane yield (measured by the Greenfeed system) was lowered by 18% (18.6 vs. 22.7 g/kg DMI; P < 0.01) by dNOP compared with CON. Rumen fermentation was altered similarly by both NOP treatments compared with CON where dNOP and infNOP increased (P < 0.01) rumen pH at 3 h and decreased (P < 0.01) proportion of acetate in total VFA. However, DMI, feed consumption rate (0 to 3, 3 to 6, 6 to 12, and 12 to 24 h after feeding), particle size distribution of orts, and feeding behavior (videotaped for individual animals over 48 h) were not affected by dNOP and infNOP compared with CON. In Exp. 2 (high-grain diet), methane production was not affected by dNOP or infNOP compared with CON. Dry matter intake, feed consumption rate, particle size distribution of orts, and feeding behavior were not altered by dNOP and infNOP compared with CON. However, both dNOP and infNOP affected rumen fermentation where total VFA decreased (P = 0.04) and acetate proportion in total VFA tended to decrease (P = 0.07) compared with CON. In conclusion, dietary supplementation of 3-NOP did not affect feeding behavior of beef steers fed a high-forage or high-grain diet. However, rumen fermentation was similarly changed when 3-NOP was provided in the diet or directly infused in the rumen. Thus, observed changes in rumen fermentation with 3-NOP were not due to changes in feeding behavior indicating no effects on the organoleptic property of the diets. In addition, according to small or no changes in DMI in both experiments and relatively small changes in rumen fermentation in Exp. 2, a greater dosage level of 3-NOP than 100 mg/kg (dietary DM) may need further examination of its effects on feeding behavior of beef cattle.
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Bartoli, Fiona, Marc A. Bailey, Baptiste Rode, Philippe Mateo, Fabrice Antigny, Kaveen Bedouet, Pascale Gerbaud, et al. "Orai1 Channel Inhibition Preserves Left Ventricular Systolic Function and Normal Ca 2+ Handling After Pressure Overload." Circulation 141, no. 3 (January 21, 2020): 199–216. http://dx.doi.org/10.1161/circulationaha.118.038891.
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Background: Orai1 is a critical ion channel subunit, best recognized as a mediator of store-operated Ca 2+ entry (SOCE) in nonexcitable cells. SOCE has recently emerged as a key contributor of cardiac hypertrophy and heart failure but the relevance of Orai1 is still unclear. Methods: To test the role of these Orai1 channels in the cardiac pathophysiology, a transgenic mouse was generated with cardiomyocyte-specific expression of an ion pore-disruptive Orai1 R91W mutant (C-dnO1). Synthetic chemistry and channel screening strategies were used to develop 4-(2,5-dimethoxyphenyl)-N-[(pyridin-4-yl)methyl]aniline (hereafter referred to as JPIII), a small-molecule Orai1 channel inhibitor suitable for in vivo delivery. Results: Adult mice subjected to transverse aortic constriction (TAC) developed cardiac hypertrophy and reduced ventricular function associated with increased Orai1 expression and Orai1-dependent SOCE (assessed by Mn 2+ influx). C-dnO1 mice displayed normal cardiac electromechanical function and cellular excitation-contraction coupling despite reduced Orai1-dependent SOCE. Five weeks after TAC, C-dnO1 mice were protected from systolic dysfunction (assessed by preserved left ventricular fractional shortening and ejection fraction) even if increased cardiac mass and prohypertrophic markers induction were observed. This is correlated with a protection from TAC-induced cellular Ca 2+ signaling alterations (increased SOCE, decreased [Ca 2+ ] i transients amplitude and decay rate, lower SR Ca 2+ load and depressed cellular contractility) and SERCA2a downregulation in ventricular cardiomyocytes from C-dnO1 mice, associated with blunted Pyk2 signaling. There was also less fibrosis in heart sections from C-dnO1 mice after TAC. Moreover, 3 weeks treatment with JPIII following 5 weeks of TAC confirmed the translational relevance of an Orai1 inhibition strategy during hypertrophic insult. Conclusions: The findings suggest a key role of cardiac Orai1 channels and the potential for Orai1 channel inhibitors as inotropic therapies for maintaining contractility reserve after hypertrophic stress.
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Nicholls, David P., and Fernando Reitich. "A new approach to analyticity of Dirichlet-Neumann operators." Proceedings of the Royal Society of Edinburgh: Section A Mathematics 131, no. 6 (December 2001): 1411–33. http://dx.doi.org/10.1017/s0308210500001463.
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This paper outlines the theoretical background of a new approach towards an accurate and well-conditioned perturbative calculation of Dirichlet-Neumann operators (DNOs) on domains that are perturbations of simple geometries. Previous work on the analyticity of DNOs has produced formulae that, as we have found, are very ill-conditioned. We show how a simple change of variables can lead to recursions that satisfy analyticity estimates without relying on subtle cancellation properties at the heart of previous formulae.
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Lomovskaya, Natalie, Sharee L. Otten, Yukiko Doi-Katayama, Leonid Fonstein, Xiao-Chun Liu, Toshio Takatsu, Augusto Inventi-Solari, et al. "Doxorubicin Overproduction in Streptomyces peucetius: Cloning and Characterization of the dnrU Ketoreductase anddnrV Genes and the doxA Cytochrome P-450 Hydroxylase Gene." Journal of Bacteriology 181, no. 1 (1999): 305–18. http://dx.doi.org/10.1128/jb.181.1.305-318.1999.
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Doxorubicin-overproducing strains of Streptomyces peucetius ATCC 29050 can be obtained through manipulation of the genes in the region of the doxorubicin (DXR) gene cluster that containsdpsH, the dpsG polyketide synthase gene, the putative dnrU ketoreductase gene, dnrV, and thedoxA cytochrome P-450 gene. These five genes were characterized by sequence analysis, and the effects of replacingdnrU, dnrV, doxA, ordpsH with mutant alleles and of doxAoverexpression on the production of the principal anthracycline metabolites of S. peucetius were studied. The exact roles of dpsH and dnrV could not be established, although dnrV is implicated in the enzymatic reactions catalyzed by DoxA, but dnrU appears to encode a ketoreductase specific for the C-13 carbonyl of daunorubicin (DNR) and DXR or their biosynthetic precursors. The highest DXR titers were obtained in a dnrX dnrU (N. Lomovskaya, Y. Doi-Katayama, S. Filippini, C. Nastro, L. Fonstein, M. Gallo, A. L. Colombo, and C. R. Hutchinson, J. Bacteriol. 180:2379–2386, 1998) double mutant and a dnrX dnrU dnrH (C. Scotti and C. R. Hutchinson, J. Bacteriol. 178:7316–7321, 1996) triple mutant. Overexpression of doxA in adoxA::aphII mutant resulted in the accumulation of DXR precursors instead of in a notable increase in DXR production. In contrast, overexpression of dnrV and doxAjointly in the dnrX dnrU double mutant or the dnrX dnrU dnrH triple mutant increased the DXR titer 36 to 86%.
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Cauley, Christy E., Areej R. El-Jawahri, Juliet C. Jacobsen, Brooks V. Udelsman, Vicki A. Jackson, Jennifer S. Temel, and Motaz Qadan. "DNR, DNI, and DNO?" Journal of Palliative Medicine 23, no. 6 (June 1, 2020): 829–31. http://dx.doi.org/10.1089/jpm.2019.0486.
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Gabbai, F. B., S. C. Thomson, O. Peterson, L. Wead, K. Malvey, and R. C. Blantz. "Glomerular and tubular interactions between renal adrenergic activity and nitric oxide." American Journal of Physiology-Renal Physiology 268, no. 6 (June 1, 1995): F1004—F1008. http://dx.doi.org/10.1152/ajprenal.1995.268.6.f1004.
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Endothelium-dependent nitric oxide (EDNO) exerts control over the processes of glomerular filtration and tubular reabsorption. The importance of the renal nerves to the tonic influence of EDNO in the glomerular microcirculation and proximal tubule was tested by renal micropuncture in euvolemic adult male Munich-Wistar rats. The physical determinants of glomerular filtration and proximal reabsorption were assessed before and during administration of the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA), in control animals and in animals 5–9 days after either ipsilateral surgical renal denervation (DNX) or after either sham surgery (SHX). L-NMMA caused single-nephron glomerular filtration rate to decline in control and SHX animals but not in DNX rats. L-NMMA caused a reduction in proximal reabsorption in control and SHX rats, which was prevented by prior DNX. DNX did not alter urinary guanosine 3',5'-cyclic monophosphate excretion, and, although DNX upregulates glomerular angiotensin II (ANG II) receptors, prior DNX did not alter intrarenal ANG II content as evaluated by radioimmunoassay. Some component of renal adrenergic activity is required for the full expression of the glomerular and tubular effects of blockade of nitric oxide synthase.
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Lacombe, A. M., and D. R. Jones. "Role of adrenal catecholamines during forced submergence in ducks." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 261, no. 6 (December 1, 1991): R1364—R1372. http://dx.doi.org/10.1152/ajpregu.1991.261.6.r1364.
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Maximum underwater tolerance (UTmax) of chronically adrenalectomized ducks (ADX, 5.3 +/- 0.3 min) and chronically adrenal-denervated ducks (DNX, 7.2 +/- 0.2 min) was significantly lower than sham-operated controls (SH-ADX, 10 +/- 0.8 min; SH-DNX, 12.2 +/- 0.5 min). After 4 min forced submergence, heart rates of ADX (62 +/- 16 beats/min) and DNX (31 +/- 2 beats/min) ducks were significantly higher than in their respective sham-operated controls (23 +/- 3 and 17 +/- 2 beats/min), although their blood pressure was significantly lower. Arterial partial pressure of O2, arterial O2 content, arterial pH, and lactate levels in DNX ducks (42 +/- 2 mmHg, 4.5 +/- 0.8 ml O2/100 ml blood, 7.233 +/- 0.016, 3.1 +/- 0.3 mM, respectively) were significantly lower than in SH-DNX ducks after 5 min forced submergence (53 +/- 1 mmHg, 6.8 +/- 0.4 ml O2/100 ml blood, 7.301 +/- 0.007, 4.8 +/- 0.4 mM, respectively). Venous infusion of catecholamines in ADX and DNX ducks during forced submergence significantly increased UTmax. It is suggested that adrenal catecholamines increase tolerance to underwater submersion by enhancing peripheral vasoconstriction, thus preserving the O2 stores for the heart and brain. Other adrenal products could also be involved.
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Schneider, Florian, Michael Klinge, Jannik Brodthuhn, Tino Peplau, and Daniela Sauer. "Hydrological soil properties control tree regrowth after forest disturbance in the forest steppe of central Mongolia." SOIL 7, no. 2 (August 30, 2021): 563–84. http://dx.doi.org/10.5194/soil-7-563-2021.
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Abstract. The central Mongolian forest steppe forms a transition between different ecozones and is as such particularly sensitive to environmental changes. It is commonly affected by disturbances such as logging and forest fires. Intensified drought events aggravate stress on the trees that are anyway at their drier limit in the forest steppe. Climate change increases evapotranspiration and reduces the distribution of discontinuous permafrost, which leads to drier soil conditions. The motivation for this study came about through our previous observation that forest stands show great differences with respect to their recovery after disturbance by fire or logging. Sometimes, no regrowth of trees takes place at all. As water availability is the main limiting factor of forest growth in this region, we hypothesised that differences in soil hydrology control the forest recovery pattern. To test this hypothesis, we analysed soil properties under forests, predominantly consisting of Siberian larch (Larix sibirica Ledeb.), in the forest steppe of the northern Khangai Mountains, central Mongolia. We distinguished the following four vegetation categories: (1) near-natural forest (FOR), (2) steppe close to the forest (STE), (3) disturbed forest with regrowth of trees (DWIR), and (4) disturbed forest showing no regrowth of trees (DNOR). A total of 54 soil profiles were described in the field and sampled for soil chemical, physical, and hydrological analysis. We found a significant difference in soil texture between soils under DWIR and DNOR. Sand generally dominated the soil texture, but soils under DWIR had more silt and clay compared to soils under DNOR. Soil pF curves showed that soils under DWIR had higher plant-available field capacity in their uppermost parts than soils under DNOR. In addition, hydraulic conductivity tended to be higher in the uppermost horizons of soils under DWIR compared to their counterparts under DNOR. Chemical properties of the soils under DWIR and DNOR showed no significant differences. We conclude that the differences in post-disturbance tree regrowth are mainly caused by different soil hydrology. High plant-available field capacity is the key factor for forest recovery under semi-arid conditions. High hydraulic conductivity in the uppermost soil horizons can further support tree regrowth because it reduces the evaporation loss and the competition of larch saplings with grasses and herbs for water. Another important factor is human impact, particularly grazing livestock on cleared forest sites, which often keeps seedlings from growing and, thus, inhibits forest recovery. None of the disturbed sites (DWIR and DNOR) had permafrost. We, thus, conclude that permafrost is no major factor for the post-disturbance tree regrowth pattern, although it generally supports tree growth in the forest steppe by preventing meltwater from seasonal ice from seeping below the root zone, thus increasing the water supply in summer.
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DiBona, G. F., and L. L. Sawin. "Role of renal nerves in sodium retention of cirrhosis and congestive heart failure." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 260, no. 2 (February 1, 1991): R298—R305. http://dx.doi.org/10.1152/ajpregu.1991.260.2.r298.
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To define the role of renal nerves in renal Na retention of cirrhosis and congestive heart failure (CHF), experiments were done in rats with cirrhosis due to common bile duct ligation (CBDL) and CHF due to myocardial infarction from left coronary artery ligation. Two weeks after induction of CBDL or CHF, diseased and sham diseased (Sham) rats were subjected to bilateral renal denervation (DNX) or sham renal denervation (innervated, INN). Five days after DNX or INN, 26-day metabolic balance studies were carried out in all rats. Daily dietary Na intake averaged 2.0-3.0 meq/day on days 1-6 and 22-26 and averaged 0.120 meq/day on days 7-21. Cumulative Na balance was greater in CBDL and CHF rats, INN or DNX, than in Sham/CBDL or CHF rats throughout the study. On day 6 at the end of the normal dietary Na intake period (days 0-6), cumulative Na balance was not affected by renal denervation in Sham/CBDL or CHF rats (INN, 2.02 +/- 0.19 meq, n = 10; DNX, 2.04 +/- 0.17 meq, n = 11), CBDL rats (INN, 4.21 +/- 0.39 meq, n = 10; DNX, 3.78 +/- 0.37 meq, n = 10), or CHF rats (INN, 3.74 +/- 0.72 meq, n = 9; DNX, 3.22 +/- 0.55 meq, n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)
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Jose, P. A., R. A. Felder, R. R. Holloway, and G. M. Eisner. "Dopamine receptors modulate sodium excretion in denervated kidney." American Journal of Physiology-Renal Physiology 250, no. 6 (June 1, 1986): F1033—F1038. http://dx.doi.org/10.1152/ajprenal.1986.250.6.f1033.
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Dopamine (DA) modulates sodium excretion by the innervated kidney. To examine the role of DA in the denervated (DNX) kidney the effects of the DA1/DA2 antagonist cis-flupenthixol (group 2, n = 7) (10 nmol X kg-1 X min-1), given intravenously in saline-loaded Wistar-Kyoto rats after acute unilateral left DNX, were compared with a placebo group (group 1, n = 7) and a group that received the DA1 antagonist SCH 23390 (group 3, n = 7) at 2.5 nmol X kg-1 X min-1. Pentobarbital sodium anesthesia was employed. Adequacy of DNX was assessed by a natriuresis and decrease in renal norepinephrine content in the DNX kidney and an antinatriuresis in the innervated right kidney. Mean arterial pressure slightly decreased in the placebo group (group 1, 106.7 +/- 2.2 vs. 99.3 +/- 2.4 mmHg) and after cis-flupenthixol (group 2, 108.8 +/- 2.7 vs. 92.8 +/- 1.8 mmHg) but not after SCH 23390 (group 3, 105.6 +/- 1.6 vs. 103 +/- 1.1 mmHg). Glomerular filtration rate was not affected by placebo or SCH 23390 in the DNX or innervated kidney but did slightly decrease after cis-flupenthixol in the DNX kidney. Sodium and water excretion after drug administration differed among the groups. In the DNX kidney urine flow decreased only in group 2, whereas fractional sodium excretion decreased modestly (P less than 0.05 paired t test) with SCH 23390 (3.53 +/- 0.34 vs. 2.89 +/- 0.20%) markedly with cis-flupenthixol (3.18 +/- 0.50 vs. 1.21 +/- 0.18%) and was unchanged in the placebo group (3.25 +/- 0.61 vs. 3.45 +/- 0.45%).(ABSTRACT TRUNCATED AT 250 WORDS)
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Chen, K. S., P. Saxena, and J. R. Walker. "Expression of the Escherichia coli dnaX gene." Journal of Bacteriology 175, no. 20 (1993): 6663–70. http://dx.doi.org/10.1128/jb.175.20.6663-6670.1993.
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Winzeler, E., and L. Shapiro. "Translation of the leaderless Caulobacter dnaX mRNA." Journal of bacteriology 179, no. 12 (1997): 3981–88. http://dx.doi.org/10.1128/jb.179.12.3981-3988.1997.
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Dallmann, H. Garry, Roberta L. Thimmig, and Charles S. McHenry. "DnaX Complex ofEscherichia coliDNA Polymerase III Holoenzyme." Journal of Biological Chemistry 270, no. 49 (December 8, 1995): 29555–62. http://dx.doi.org/10.1074/jbc.270.49.29555.
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Dallmann, H. Garry, and Charles S. McHenry. "DnaX Complex ofEscherichia coliDNA Polymerase III Holoenzyme." Journal of Biological Chemistry 270, no. 49 (December 8, 1995): 29563–69. http://dx.doi.org/10.1074/jbc.270.49.29563.
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Patel, K. P., P. L. Zhang, and P. K. Carmines. "Neural influences on renal responses to acute volume expansion in rats with heart failure." American Journal of Physiology-Heart and Circulatory Physiology 271, no. 4 (October 1, 1996): H1441—H1448. http://dx.doi.org/10.1152/ajpheart.1996.271.4.h1441.
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Experiments were performed to test the postulate that neural influences underlie the suppressed excretory response to acute volume expansion (VE) typically observed 3-4 wk after myocardial infarction to induce chronic heart failure (CHF). Responses to VE were assessed in innervated (intact) and denervated (DNX) kidneys of anesthetized CHF rats and sham-operated controls. CHF rats exhibited blunted natriuretic responses to VE in both intact kidneys (35% of sham response) and DNX kidneys (55% of sham DNX response). CHF rats also displayed suppressed excretory responses to atrial natriuretic factor (0.25 microgram.kg-1.min-1 iv) in both intact kidneys (74% of sham response) and DNX kidneys (63% of sham DNX response). Additional experiments confirmed that the compliance of the venoatrial junction did not differ between sham rats (52 +/- 2 mmHg/microliter) and CHF rats (54-2 mmHg/microliter). The observations support the contention that both tonic renal sympathetic renal nerve activity and suppressed renal atrial natriuretic factor responsiveness likely contribute to the blunted excretory response to VE during CHF.
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Greenberg, S. G., S. Tershner, and J. L. Osborn. "Neurogenic regulation of rate of achieving sodium balance after increasing sodium intake." American Journal of Physiology-Renal Physiology 261, no. 2 (August 1, 1991): F300—F307. http://dx.doi.org/10.1152/ajprenal.1991.261.2.f300.
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Evidence that the renal sympathetic nerves have direct effects on renal tubular function suggests that neurogenic mechanisms may play an important role in the daily regulation of sodium balance. We evaluated the influence of the renal nerves on the rate of elevating urinary sodium excretion (UNaV) after a step increase in fixed sodium intake. Conscious rats with innervated (INN) or denervated (DNX) kidneys were placed on low-sodium intake (LNa = 0.3 meq/day) or a normal sodium intake (NNa = 1.0 meq/day) by intravenous infusion. Hourly changes in UNaV were determined 24 h before and 72 h after increasing sodium intake to either NNa or high-sodium intake (HNa = 5.0 meq/day). Switching from LNa to NNa, INN rats increased UNaV within 24 h; however, DNX rats did not begin to increase UNaV until hour 60. Cumulative sodium balance over 72 h was more positive in DNX rats (INN = 1.29 +/- 0.29 meq; DNX = 2.06 +/- 0.21 meq, P less than 0.05). During the LNa-to-HNa switch, both INN and DNX rats increased UNaV equally for 12 h; however, at this time INN rats continued to increase UNaV, whereas DNX rats did not. DNX rats had a net accumulation of 2.54 meq more sodium than INN rats over 72 h. Significant inhibition of plasma renin activity within the first 24 h occurred only in rats receiving the LNa-to-HNa switch in sodium intake, and this response was not different between rats with innervated and denervated kidneys. These data suggest that the renal nerves provide a rapid sodium excretory response to step increases in sodium intake.(ABSTRACT TRUNCATED AT 250 WORDS)
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Aiken, Robert, Clark Chen, Timothy Cloughesy, Howard Colman, Mariza Daras, Morris Groves, Simon Khagi, et al. "ATIM-33. INTERIM RESULTS OF A PHASE II MULTI-CENTER STUDY OF ONCOLYTIC ADENOVIRUS DNX-2401 WITH PEMBROLIZUMAB FOR RECURRENT GLIOBLASTOMA; CAPTIVE STUDY (KEYNOTE-192)." Neuro-Oncology 21, Supplement_6 (November 2019): vi8—vi9. http://dx.doi.org/10.1093/neuonc/noz175.032.
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Abstract BACKGROUND DNX-2401 (tasadenoturev) is a replication-competent, tumor-selective, oncolytic adenovirus. Phase I studies in adults with recurrent glioblastoma (rGBM) have demonstrated safety and encouraging clinical activity. A Phase II open-label, dose-escalating multi-center study in rGBM was initiated to evaluate DNX-2401 with pembrolizumab. Planned enrollment of 48 subjects is complete. METHODS Subjects ≥ 18 years, with a single tumor, KPS ≥ 70% and adequate organ function were enrolled sequentially into 3 cohorts of DNX-2401 (5e8vp, 5e9vp, 5e10vp). A single intratumoral injection of DNX-2401 was administered followed 7 days later by pembrolizumab (200 mg IV). Thereafter, pembrolizumab was infused Q3wks up to 24 months until progression or toxicity. 5e10vp was determined as the optimal dose and this cohort was expanded. Safety monitoring, assessments of response and survival follow-up are ongoing. RESULTS Nine subjects were treated in the escalation phase; 42 subjects received 5e10vp. No dose-limiting toxicity or unexpected safety issues were identified by an independent review committee, and there were no treatment-related deaths. Adverse events were primarily consistent with underlying disease, effects of the neuro-procedure, expected effects of pembrolizumab, and concomitant use of steroids/anticonvulsants per the standard of care. The majority of events were mild to moderate, and unrelated to DNX-2401. Headache and manageable vasogenic edema were the most common events related to DNX-2401 with pembrolizumab. For the 48 subjects who received pembrolizumab (median 6 cycles), median OS from DNX-2401 administration was 12 months (95% CI, 10.6–14.7), OS6 was 91%, and 47% experienced clinical benefit (stable disease or better). Four subjects (5e10) had a partial response (two with > 94% regression of tumor), and three (5e8; 5e10[2]) are alive > 20 months. Updated safety and efficacy results will be presented. CONCLUSIONS The data continue to demonstrate that DNX-2401 administered with pembrolizumab has an acceptable safety profile. Long-term survival and clinical benefit remain compelling.