Oral hypertonic saline causes transient fall of vasopressin in humans

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

Seckl, J.R.; Williams, D.M.; Lightman, S.L.

1986-08-01

After dehydration, oral rehydration causes a fall in plasma arginine vasopressin (AVP) that precedes changes in plasma osmolality. To investigate further the stimulus for this effect, its specificity, and association with thirst, six volunteers were deprived of water for 24 h and given a salt load on two separate occasions. On each study day they then drank rapidly 10 ml/kg of either tap water or hypertonic saline (360 mosmol/kg). There was a significant fall in plasma AVP from 2.0 +/- 0.3 to 1.2 +/- 0.4 pmol/l 5 min after drinking water and from 1.8 +/- 0.3 to 0.9 +/- 0.2more » pmol/l after hypertonic saline. Plasma osmolality fell 30-60 min after water and was unchanged after saline. Plasma renin activity, oxytocin, and total protein all remained unchanged. All subjects reported diminished thirst after hypertonic saline. Gargling with water reduced thirst but did not affect plasma AVP. There appears to be a drinking-mediated neuroendocrine reflex that decreases plasma AVP irrespective of the osmolality of the liquid consumed. The sensation of thirst did not correlate with plasma osmolality and was not always related to plasma AVP concentration. AVP was measured by radioimmunoassay.« less

Hypertonic Saline Suppresses NADPH Oxidase-Dependent Neutrophil Extracellular Trap Formation and Promotes Apoptosis.

PubMed

Nadesalingam, Ajantha; Chen, Jacky H K; Farahvash, Armin; Khan, Meraj A

2018-01-01

Tonicity of saline (NaCl) is important in regulating cellular functions and homeostasis. Hypertonic saline is administered to treat many inflammatory diseases, including cystic fibrosis. Excess neutrophil extracellular trap (NET) formation, or NETosis, is associated with many pathological conditions including chronic inflammation. Despite the known therapeutic benefits of hypertonic saline, its underlying mechanisms are not clearly understood. Therefore, we aimed to elucidate the effects of hypertonic saline in modulating NETosis. For this purpose, we purified human neutrophils and induced NETosis using agonists such as diacylglycerol mimetic phorbol myristate acetate (PMA), Gram-negative bacterial cell wall component lipopolysaccharide (LPS), calcium ionophores (A23187 and ionomycin from Streptomyces conglobatus ), and bacteria ( Pseudomonas aeruginosa and Staphylococcus aureus ). We then analyzed neutrophils and NETs using Sytox green assay, immunostaining of NET components and apoptosis markers, confocal microscopy, and pH sensing reagents. This study found that hypertonic NaCl suppresses nicotinamide adenine dinucleotide phosphate oxidase (NADPH2 or NOX2)-dependent NETosis induced by agonists PMA, Escherichia coli LPS (0111:B4 and O128:B12), and P. aeruginosa . Hypertonic saline also suppresses LPS- and PMA- induced reactive oxygen species production. It was determined that supplementing H 2 O 2 reverses the suppressive effect of hypertonic saline on NOX2-dependent NETosis. Many of the aforementioned suppressive effects were observed in the presence of equimolar concentrations of choline chloride and osmolytes (d-mannitol and d-sorbitol). This suggests that the mechanism by which hypertonic saline suppresses NOX2-dependent NETosis is via neutrophil dehydration. Hypertonic NaCl does not significantly alter the intracellular pH of neutrophils. We found that hypertonic NaCl induces apoptosis while suppressing NOX2-dependent NETosis. In contrast, hypertonic

Nebulized hypertonic-saline vs epinephrine for bronchiolitis; proof of concept study of cumulative sum (CUSUM) analysis.

PubMed

Gupta, Neeraj; Puliyel, Ashish; Manchanda, Ayush; Puliyel, Jacob

2012-07-01

To apply cumulative sum (CUSUM) to monitor a drug trial of nebulized hypertonic-saline in bronchiolitis. To test if monitoring with CUSUM control lines is practical and useful as a prompt to stop the drug trial early, if the study drug performs significantly worse than the comparator drug. Prospective, open label, controlled trial using standard therapy (epinephrine) and study drug (hypertonic-saline) sequentially in two groups of patients. Hospital offering tertiary-level pediatric care. Children, 2 months to 2 years, with first episode of bronchiolitis, excluding those with cardiac disease, immunodeficiency and critical illness at presentation. Nebulized epinephrine in first half of the bronchiolitis season (n = 35) and hypertonic saline subsequently (n = 29). Continuous monitoring of response to hypertonic-saline using CUSUM control charts developed with epinephrine-response data. Clinical score, tachycardia and total duration of hospital stay. In the epinephrine group, the maximum CUSUM was +2.25 (SD 1.34) and minimum CUSUM was -2.26 (SD 1.34). CUSUM score with hypertonic saline group stayed above the zero line throughout the study. There was no statistical difference in the post-treatment clinical score at 24 hours between the treatment groups {Mean (SD) 3.516 (2.816): 3.552 (2.686); 95% CI: -1.416 to 1.356}, heart rate {Mean (SD) 136 (44): 137(12); 95% CI: -17.849 to 15.849) or duration of hospital stay (Mean (SD) 96.029 (111.41): 82.914 (65.940); 95% CI: -33.888 to 60.128}. The software we developed allows for drawing of control lines to monitor study drug performance. Hypertonic saline performed as well or better than nebulized epinephrine in bronchiolitis.

Osmotherapy for intracranial hypertension: mannitol versus hypertonic saline.

PubMed

Fink, Matthew E

2012-06-01

Hyperosmolar therapy is one of the core medical treatments for brain edema and intracranial hypertension, but controversy exists regarding the use of the most common agents, mannitol, and hypertonic saline. This article describes the relative merits and adverse effects of these agents using the best available clinical evidence. Mannitol is effective and has been used for decades in the treatment of traumatic brain injury, but it may precipitate acute renal failure if serum osmolarity exceeds 320 mOsm/L. Hypertonic saline appears to be safe, and serum sodium has been elevated to as high as 180 mEq/L in clinical settings without significant neurologic, cardiac, or renal injury. In small comparative trials both agents are effective and no clinically significant difference has been noted, but a properly powered trial has not yet been performed. Both mannitol and hypertonic saline are effective and have an acceptable risk profile for use in the treatment of elevated intracranial pressure secondary to brain edema.

Intracellular Ca2+ release and Ca2+ influx during regulatory volume decrease in IMCD cells.

PubMed

Tinel, H; Wehner, F; Sauer, H

1994-07-01

Volume changes and cytosolic Ca2+ concentration ([Ca2+]i) of inner medullary collecting duct (IMCD) cells under hypotonic stress were monitored by means of confocal laser scanning microscopy and fura 2 fluorescence, respectively. Reduction of extracellular osmolality from 600 to 300 mosmol/kgH2O by omission of sucrose led to an increase in cell volume within 1 min to 135 +/- 3% (n = 9), followed by a partial regulatory volume decrease (RVD) to 109 +/- 2% (n = 9) within the ensuring 5 min. In parallel, [Ca2+]i rose from 145 +/- 9 to 433 +/- 16 nmol/l (n = 9) and thereafter reached a lower steady state of 259 +/- 9 nmol/l. Under low-Ca2+ conditions (10 nmol/l) RVD was not impeded and reduction of osmolality evoked only a transient increase of [Ca2+]i by 182 +/- 22 nmol/l (n = 6). Preincubation with 100 mumol/l 8-(N,N-diethylamino)octyl-3,4,5-trimethoxy-benzoate hydrochloride (TMB-8) or 20 mmol/l caffeine, both effective inhibitors of Ca2+ release from intracellular stores, in low Ca2+ as well as in high Ca2+, inhibited the Ca2+ response and abolished RVD. The temporal relationship between Ca2+ release from intracellular stores and Ca2+ entry was analyzed by determining fura 2 quenching, using Mn2+ as a substitute for external Ca2+. Intracellular Ca2+ release preceded Mn2+ influx by 17 +/- 3 s (n = 10). Mn2+ influx persisted during the whole period of exposure to hypotonicity, indicating that there is no time-dependent Ca2+ channel inactivation. Preincubation with TMB-8 or caffeine reduced Mn2+ influx to the control level, indicating that activation of Ca2+ channels in the plasma membrane occurs via intracellular Ca2+ release.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstracts of the International Conference on Hypertonic Resuscitation (5th) Held in Galveston, Texas on 3-5 June 1992

DTIC Science & Technology

1992-08-01

Dextran Metabolism in Dehydrated, Hemorrhaged Sheep Infused with Hypertonic Saline/Dextran (HSD). 3 J. Eaker (Davis, U.S.A.): Small Volume Intraosseous ...S. Majluf (Mexico City, Mexico): Eualuation of an Intraosseous Function versus Intrauenous and Central Catheter in Patients with Hemorrhagic Shock. W...between the traumatized brain parenchyma and the skull bone followed by closure of the cranium by dental cement. At 20 hrs later the animals were

Rejoining and misrejoining of radiation-induced chromatin breaks. III. Hypertonic treatment

NASA Technical Reports Server (NTRS)

Durante, M.; George, K.; Wu, H. L.; Yang, T. C.

1998-01-01

It has been shown that treatment in anisotonic medium modifies rejoining of radiation-induced breaks in interphase chromosomes. In previous work, we have demonstrated that formation of exchanges in human lymphocytes has a slow component (half-time of 1-2 h), but a fraction of exchanges are also observed in samples assayed soon after exposure. In this paper we studied the effect of hypertonic treatment on rejoining and misrejoining of radiation-induced breaks using fluorescence in situ hybridization of prematurely condensed chromosomes in human lymphocytes. Isolated lymphocytes were irradiated with 7 Gy gamma rays, fused to mitotic hamster cells and incubated in hypertonic solution (0.5 M NaCl) for the period normally allowed for interphase chromosome condensation to occur. The data from hypertonic treatment experiments indicate the presence of a class of interphase chromosome breaks that rejoin and misrejoin very quickly (half-time of 5-6 min). The fast misrejoining of these lesions is considered to be responsible for the initial level of exchanges which we reported previously. No significant effect of hypertonic treatment on the yield of chromosome aberrations scored at the first postirradiation mitosis was detected.

Pre-Exercise Ingestion of Pickle Juice, Hypertonic Saline, or Water and Aerobic Performance and Thermoregulation

PubMed Central

Peikert, Jarett; Miller, Kevin C.; Albrecht, Jay; Tucker, Jared; Deal, James

2014-01-01

Context: Ingesting high-sodium drinks pre-exercise can improve thermoregulation and performance. Athletic trainers (19%) give athletes pickle juice (PJ) prophylactically for cramping. No data exist on whether this practice affects aerobic performance or thermoregulation. Objective: To determine if drinking 2 mL/kg body mass of PJ, hypertonic saline, or deionized water (DIW) pre-exercise affects aerobic performance or thermoregulation. Design: Crossover study. Setting: Controlled laboratory study. Patients or Other Participants: Nine euhydrated men (age = 22 ± 3 years, height = 184.0 ± 8.2 cm, mass = 82.6 ± 16.0 kg) completed testing. Intervention(s): Participants rested for 65 minutes. During this period, they ingested 2 mL/kg of PJ, hypertonic saline, or DIW. Next, they drank 5 mL/kg of DIW. Blood was collected before and after ingestion of all fluids. Participants were weighed and ran in the heat (temperature = 38.3°C ± 1°C, relative humidity = 21.1% ± 4.7%) at increasing increments of maximal heart rate (50%, 60%, 70%, 80%, 90%, 95%) until exhaustion or until rectal temperature exceeded 39.5°C. Participants were weighed postexercise so we could calculate sweat volume. Main Outcome Measure(s): Time to exhaustion, rectal temperature, changes in plasma volume, and sweat volume. Results: Time to exhaustion did not differ among drinks (PJ = 77.4 ± 5.9 minutes, hypertonic saline = 77.4 ± 4.0 minutes, DIW = 75.7 ± 3.2 minutes; F2,16 = 1.1, P = .40). Core temperature of participants was similar among drinks (PJ = 38.7°C ± 0.3°C, hypertonic saline = 38.7°C ± 0.4°C, DIW = 38.8°C ± 0.4°C; P = .74) but increased from pre-exercise (36.7°C ± 0.2°C) to postexercise (38.7°C ± 0.4°C) (P < .05). No differences were observed for changes in plasma volume or sweat volume among drinks (P > .05). Conclusions: Ingesting small amounts of PJ or hypertonic saline with water did not affect performance or select thermoregulatory measures. Drinking larger volumes of

Pre-exercise ingestion of pickle juice, hypertonic saline, or water and aerobic performance and thermoregulation.

PubMed

Peikert, Jarett; Miller, Kevin C; Albrecht, Jay; Tucker, Jared; Deal, James

2014-01-01

Ingesting high-sodium drinks pre-exercise can improve thermoregulation and performance. Athletic trainers (19%) give athletes pickle juice (PJ) prophylactically for cramping. No data exist on whether this practice affects aerobic performance or thermoregulation. To determine if drinking 2 mL/kg body mass of PJ, hypertonic saline, or deionized water (DIW) pre-exercise affects aerobic performance or thermoregulation. Crossover study. Controlled laboratory study. Nine euhydrated men (age = 22 ± 3 years, height = 184.0 ± 8.2 cm, mass = 82.6 ± 16.0 kg) completed testing. Participants rested for 65 minutes. During this period, they ingested 2 mL/kg of PJ, hypertonic saline, or DIW. Next, they drank 5 mL/kg of DIW. Blood was collected before and after ingestion of all fluids. Participants were weighed and ran in the heat (temperature = 38.3°C ± 1°C, relative humidity = 21.1% ± 4.7%) at increasing increments of maximal heart rate (50%, 60%, 70%, 80%, 90%, 95%) until exhaustion or until rectal temperature exceeded 39.5°C. Participants were weighed postexercise so we could calculate sweat volume. Time to exhaustion, rectal temperature, changes in plasma volume, and sweat volume. Time to exhaustion did not differ among drinks (PJ = 77.4 ± 5.9 minutes, hypertonic saline = 77.4 ± 4.0 minutes, DIW = 75.7 ± 3.2 minutes; F2,16 = 1.1, P = .40). Core temperature of participants was similar among drinks (PJ = 38.7°C ± 0.3°C, hypertonic saline = 38.7°C ± 0.4°C, DIW = 38.8°C ± 0.4°C; P = .74) but increased from pre-exercise (36.7°C ± 0.2°C) to postexercise (38.7°C ± 0.4°C) (P < .05). No differences were observed for changes in plasma volume or sweat volume among drinks (P > .05). Ingesting small amounts of PJ or hypertonic saline with water did not affect performance or select thermoregulatory measures. Drinking larger volumes of PJ and water may be more effective at expanding the extracellular space.

Comparison of 20% mannitol and 3% hypertonic saline on intracranial pressure and systemic hemodynamics.

PubMed

Sokhal, Navdeep; Rath, Girija Prasad; Chaturvedi, Arvind; Singh, Manmohan; Dash, Hari Hara

2017-08-01

Mannitol and hypertonic saline (HS) are most commonly used hyperosmotic agents for intraoperative brain relaxation. We compared the changes in ICP and systemic hemodynamics after infusion of equiosmolar solutions of both agents in patients undergoing craniotomy for supratentorial tumors. Forty enrolled adults underwent a standard anesthetic induction. Apart from routine monitoring parameters, subdural ICP with Codmann catheter and cardiac indices by Vigileo monitor, were recorded. The patients were randomized to receive equiosmolar solutions of either 20% mannitol (5ml/kg) or 3% HS (5.35ml/kg) for brain relaxation. The time of placement of ICP catheter was marked as T 0 and baseline ICP and systemic hemodynamic variables were noted; it was followed by recording of the same parameters every 5min till 45min (Study Period). After the completion of study period, brain relaxation score as assessed by the neurosurgeon was recorded. Arterial blood gas (ABG) was analysed every 30min starting from T 0 upto one and half hours (T 90 ), and values of various parameters were recorded. Data was analysed using appropriate statistical methods. Both mannitol and HS significantly reduced the ICP; the values were comparable in between the two groups at most of the times. The brain relaxation score was comparable in both the groups. Urine output was significantly higher with mannitol. The perioperative complications, overall hospital stay, and Glasgow outcome score at discharge were comparable in between the two groups. To conclude, both mannitol and hypertonic saline in equiosmolar concentrations produced comparable effects on ICP reduction, brain relaxation, and systemic hemodynamics. Copyright © 2017 Elsevier Ltd. All rights reserved.

Black tea increases hypertonic stress resistance in C. elegans.

PubMed

Yuan, Pei; Pan, Lian-Yun; Xiong, Li-Gui; Tong, Jie-Wen; Li, Juan; Huang, Jian-An; Gong, Yu-Shun; Liu, Zhong-Hua

2018-06-22

Here we identified that BTE (black tea extract), within the studied concentration range, is more effective than GTE (green tea extract) in protecting C. elegans against hypertonic stress, by enhancing survival after exposure to various salts, and alleviating suffered motility loss and body shrinkage. The mechanism of such protection may be due to the ability of black tea to induce the conserved WNK/GCK signaling pathway and down-regulation of the expression levels of nlp-29. Intriguingly, black tea does not relieve hypertonicity-induced protein damage. The findings implicate the potential health benefits of black tea consumed worldwide.

Uterine injuries complicating hypertonic saline abortion

PubMed Central

Willems, J. J.

1974-01-01

Two cases of uterine injury complicating midtrimester abortion induced by hypertonic saline are described, one with an extensive laceration of the cervix and the other with a rupture of the lower uterine segment extending into the vault of the vagina. The etiology, diagnosis and possible obstetric sequelae are discussed. PMID:4434292

No increase in small-solute transport in peritoneal dialysis patients treated without hypertonic glucose for fifty-four months.

PubMed

Pagniez, Dominique; Duhamel, Alain; Boulanger, Eric; Lessore de Sainte Foy, Celia; Beuscart, Jean-Baptiste

2017-08-31

Glucose is widely used as an osmotic agent in peritoneal dialysis (PD), but exerts untoward effects on the peritoneum. The potential protective effect of a reduced exposure to hypertonic glucose has never been investigated. The cohort of PD patients attending our center which tackled the challenge of a restricted use of hypertonic glucose solutions has been prospectively followed since 1992. Small-solute transport was assessed using an equivalent of the glucose peritoneal equilibration test after 6 months, and then every year. Study was stopped on July 1st, 2008, before use of biocompatible solutions. Repeated measures in patients treated with PD for 54 months were analyzed by using (1) the slopes of the linear regression for D 4 /D 0 ratios over time computed for each individual, and (2) a linear mixed model. In the study period, 44 patients were treated for a total of 2376 months, 2058 without hypertonic glucose. There was one episode of peritoneal infection every 18 patient-months. The mean of slopes of the linear regression for D 4 /D 0 ratios was found to be significantly positive (Student's test, p < .001) and the results of the mixed model reflected a similar significant increase for D 4 /D 0 ratios over time. These results reflected a significant decrease of small-solute transport. In this large series, minimizing the use of hypertonic glucose solutions was associated in patients on long term PD with an overall decrease of small-solute transport within 54 months, despite a high rate of peritoneal infection.

The hypertonic environment differentially regulates wild-type CFTR and TNR-CFTR chloride channels.

PubMed

Lassance-Soares, Roberta M; Cheng, Jie; Krasnov, Kristina; Cebotaru, Liudmila; Cutting, Garry R; Souza-Menezes, Jackson; Morales, Marcelo M; Guggino, William B

2010-01-01

This study tested the hypotheses that the hypertonic environment of the renal medulla regulates the expression of cystic fibrosis transmembrane conductance regulator protein (CFTR) and its natural splice variant, TNR-CFTR. To accomplish this, Madin-Darby canine kidney (MDCK) stable cell lines expressing TNR-CFTR or CFTR were used. The cells were treated with hypertonic medium made with either NaCl or urea or sucrose (480 mOsm/kg or 560 mOsm/kg) to mimic the tonicity of the renal medulla environment. Western blot data showed that CFTR and TNR-CFTR total cell protein is increased by hypertonic medium, but using the surface biotinylation technique, only CFTR was found to be increased in cell plasma membrane. Confocal microscopy showed TNR-CFTR localization primarily at the endoplasmic reticulum and plasma membrane. In conclusion, CFTR and TNR-CFTR have different patterns of distribution in MDCK cells and they are modulated by a hypertonic environment, suggesting their physiological importance in renal medulla. Copyright © 2010 S. Karger AG, Basel.

Out-of-hospital Hypertonic Resuscitation After Traumatic Hypovolemic Shock

PubMed Central

Bulger, Eileen M.; May, Susanne; Kerby, Jeffery D.; Emerson, Scott; Stiell, Ian G.; Schreiber, Martin A.; Brasel, Karen J.; Tisherman, Samuel A.; Coimbra, Raul; Rizoli, Sandro; Minei, Joseph P.; Hata, J. Steven; Sopko, George; Evans, David C.; Hoyt, David B.

2011-01-01

Objective To determine whether out-of-hospital administration of hypertonic fluids would improve survival after severe injury with hemorrhagic shock. Background Hypertonic fluids have potential benefit in the resuscitation of severely injured patients because of rapid restoration of tissue perfusion, with a smaller volume, and modulation of the inflammatory response, to reduce subsequent organ injury. Methods Multicenter, randomized, blinded clinical trial, May 2006 to August 2008, 114 emergency medical services agencies in North America within the Resuscitation Outcomes Consortium. Inclusion criteria: injured patients, age ≥ 15 years with hypovolemic shock (systolic blood pressure ≤ 70 mm Hg or systolic blood pressure 71–90 mm Hg with heart rate ≥ 108 beats per minute). Initial resuscitation fluid, 250 mL of either 7.5% saline per 6% dextran 70 (hypertonic saline/dextran, HSD), 7.5% saline (hypertonic saline, HS), or 0.9% saline (normal saline, NS) administered by out-of-hospital providers. Primary outcome was 28-day survival. On the recommendation of the data and safety monitoring board, the study was stopped early (23% of proposed sample size) for futility and potential safety concern. Results A total of 853 treated patients were enrolled, among whom 62% were with blunt trauma, 38% with penetrating. There was no difference in 28-day survival—HSD: 74.5% (0.1; 95% confidence interval [CI], −7.5 to 7.8); HS: 73.0% (−1.4; 95% CI, −8.7–6.0); and NS: 74.4%, P = 0.91. There was a higher mortality for the postrandomization subgroup of patients who did not receive blood transfusions in the first 24 hours, who received hypertonic fluids compared to NS [28-day mortality—HSD: 10% (5.2; 95% CI, 0.4–10.1); HS: 12.2% (7.4; 95% CI, 2.5–12.2); and NS: 4.8%, P < 0.01]. Conclusion Among injured patients with hypovolemic shock, initial resuscitation fluid treatment with either HS or HSD compared with NS, did not result in superior 28-day survival. However

Hyaluronic acid improves "pleasantness" and tolerability of nebulized hypertonic saline in a cohort of patients with cystic fibrosis.

PubMed

Buonpensiero, Paolo; De Gregorio, Fabiola; Sepe, Angela; Di Pasqua, Antonio; Ferri, Pasqualina; Siano, Maria; Terlizzi, Vito; Raia, Valeria

2010-11-01

Inhaled hypertonic saline improves lung function and decreases pulmonary exacerbations in people with cystic fibrosis. However, side effects such as cough, narrowing of airways and saltiness cause intolerance of the therapy in 8% of patients. The aim of our study was to compare the effect of an inhaled solution of hyaluronic acid and hypertonic saline with hypertonic solution alone on safety and tolerability. A total of 20 patients with cystic fibrosis aged 6 years and over received a single treatment regimen of 7% hypertonic saline solution or hypertonic solution with 0.1% hyaluronate for 2 days nonconsecutively after a washout period in an open crossover study. Cough, throat irritation, and salty taste were evaluated by a modified ordinal score for assessing tolerability; "pleasantness" was evaluated by a five-level, Likert-type scale. Forced expiratory volume in 1 second was registered before and after the end of the saline inhalations. All 20 patients (nine males, 11 females, mean age 13 years, range 8.9-17.7) completed the study. The inhaled solution of 0.1% hyaluronic acid and hypertonic saline significantly improved tolerability and pleasantness compared to hypertonic saline alone. No major adverse effects were observed. No difference was documented in pulmonary function tests between the two treatments. Hyaluronic acid combined with hypertonic saline solution may contribute to improved adherence to hypertonic saline therapy. Further clinical trials are needed to confirm our findings. Considering the extraordinary versatility of hyaluronic acid in biological reactions, perspective studies could define its applicability to halting progression of lung disease in cystic fibrosis.

[The use of hypertonic sea-water solution in patients after surgery of the nose and paranasal sinuses].

PubMed

Rapiejko, Piotr; Jurkiewicz, Dariusz

2010-01-01

Surgical operations on the nose are very common otorhinolaryngological procedures. The surgical outcome depends not only on the performance of the procedure itself but also on the postoperative care of the nasal cavities. Clinicians continue their search for agents which would promote cleansing of the nasal cavities and regeneration of the nasal mucosa postoperatively. was a retrospective evaluation of the effect of the product Marimer Hypertonic on symptoms in patients who had undergone nasal surgery (septoplasty, functional endoscopic sinus surgery, surgical removal of nasal polyps). The medical records included details of full history and physical examination on postoperative days 1, 7 and 14.The medical records of 120 patients were randomly selected from all records. The records were consecutively selected using the following criteria: 1-Operation type; septoplasty group A and B, FESS group C and D or classical surgical removal of nasal polyps group E and F , 2- Use (group B, D, F) or non-use (group A, C, E) of the hypertonic sea water solution aerosol for nasal douching (Marimer Hypertonic 2.2% sea-water solution). All patients included in the postoperative follow-up at the ENT Outpatient Clinic assess their symptoms by completing a standard self-assessment chart. The symptoms include nasal obstruction, discharge and crusting in the nasal cavities, pain in the nose and paranasal sinuses, reduction of smell, and general health (disease severity) and are assessed on day 1 after removal of nasal packing and on treatment days 7 and 14. At the same time, a clinician assesses their condition, including general health, nasal blockage, discharge and crusting in the nasal cavities, appearance of the nasal mucosa, and sense of smell evaluated by a scratch test using a smell book and a felt-tip pen test. A statistically significance difference in the severity of disease between group A (control) and group B (using Marimer Hypertonic) indicates a statistically significant

Time-dependent expression of hypertonic effects on bullfrog taste nerve responses to salts and bitter substances.

PubMed

Mashiyama, Kazunori; Nozawa, Yuhei; Ohtubo, Yoshitaka; Kumazawa, Takashi; Yoshii, Kiyonori

2014-03-27

We previously showed that the hypertonicity of taste stimulating solutions modified tonic responses, the quasi-steady state component following the transient (phasic) component of each integrated taste nerve response. Here we show that the hypertonicity opens tight junctions surrounding taste receptor cells in a time-dependent manner and modifies whole taste nerve responses in bullfrogs. We increased the tonicity of stimulating solutions with non-taste substances such as urea or ethylene glycol. The hypertonicity enhanced phasic responses to NaCl>0.2M, and suppressed those to NaCl<0.1M, 1mM CaCl2, and 1mM bitter substances (quinine, denatonium and strychnine). The hypertonicity also enhanced the phasic responses to a variety of 0.5M salts such as LiCl and KCl. The enhancing effect was increased by increasing the difference between the ionic mobilities of the cations and anions in the salt. A preincubation time >20s in the presence of 1M non-taste substances was needed to elicit both the enhancing and suppressing effects. Lucifer Yellow CH, a paracellular marker dye, diffused into bullfrog taste receptor organs in 30s in the presence of hypertonicity. These results agreed with our proposed mechanism of hypertonic effects that considered the diffusion potential across open tight junctions. Copyright © 2014 Elsevier B.V. All rights reserved.

Complication Rates of 3% Hypertonic Saline Infusion Through Peripheral Intravenous Access.

PubMed

Perez, Claudia Andira; Figueroa, Stephen A

2017-06-01

Hyperosmolar therapy with hypertonic saline (HTS) is a cornerstone in the management of intracranial hypertension and hyponatremia in the neurological intensive care unit. Theoretical safety concerns remain for infiltration, thrombophlebitis, tissue ischemia, and venous thrombosis associated with continuous 3% HTS administered via peripheral intravenous (pIV) catheters. It is common practice at many institutions to allow only central venous catheter infusion of 3% HTS. Hospital policy was changed to allow the administration of 3% HTS via 16- to 20-gauge pIVs to a maximum infusion rate of 50 mL/h in patients without central venous access. We prospectively monitored patients who received peripheral 3% HTS as part of a quality improvement project. We documented gauge, location, maximum infusion rate, and total hours of administration. Patients were assessed for infiltration, erythema, swelling, phlebitis, thrombosis, and line infection. There were 28 subjects across 34 peripheral lines monitored. Overall, subjects received 3% HTS for a duration between 1 and 124 hours with infusion rates of 30 to 50 mL/h. The rate of complications observed was 10.7% among all subjects. Documented complications included infiltration (n = 2), with an incidence of 6%, and thrombophlebitis (n = 1), with an incidence of 3%. There has been a long concern among healthcare providers, including nursing staff, in regard to pIV administration of prolonged 3% HTS infusion therapy. Our study indicates that peripheral administration of 3% HTS carries a low risk of minor, nonlimb, or life-threatening complications. Although central venous infusion may reduce the risk of these minor complications, it may increase the risk of more serious complications such as large vessel thrombosis, bloodstream infection, pneumothorax, and arterial injury. The concern regarding the risks of pIV administration of 3% HTS may be overstated and unfounded.

Efficacy and Safety of Continuous Micro-Pump Infusion of 3% Hypertonic Saline combined with Furosemide to Control Elevated Intracranial Pressure.

PubMed

Li, Yuqian; Li, Zhihong; Li, Min; Yang, Yanlong; Wang, Bao; Gao, Li; Zhang, Xingye; Cheng, Hongyu; Fang, Wei; Zhao, Bo; Wang, Boliang; Gao, Guodong; Li, Lihong

2015-06-17

Elevated intracranial pressure is one of the most common problems in patients with diverse intracranial disorders, leading to increased morbidity and mortality. Effective management for increased intracranial pressure is based mainly on surgical and medical techniques with hyperosmolar therapy as one of the core medical treatments. The study aimed to explore the effects of continuous micro-pump infusions of 3% hypertonic saline combined with furosemide on intracranial pressure control. We analyzed data on 56 eligible participants with intracranial pressure >20 mmHg from March 2013 to July 2014. The target was to increase and maintain plasma sodium to a level between 145 and 155 mmol/L and osmolarity to a level of 310 to 320 mOsmol/kg. Plasma sodium levels significantly increased from 138±5 mmol/L at admission to 151±3 mmol/L at 24 h (P<0.01). Osmolarity increased from 282±11 mOsmol/kg at baseline to 311±8 mOsmol/kg at 24 h (P<0.01). Intracranial pressure significantly decreased from 32±7 mmHg to 15±6 mmHg at 24 h (P<0.01). There was a significant improvement in CPP (P<0.01). Moreover, central venous pressure, mean arterial pressure, and Glasgow Coma Scale slightly increased. However, these changes were not statistically significant. Continuous infusion of 3% hypertonic saline + furosemide is effective and safe for intracranial pressure control.

Effect of Intravenous Small-Volume Hypertonic Sodium Bicarbonate, Sodium Chloride, and Glucose Solutions in Decreasing Plasma Potassium Concentration in Hyperkalemic Neonatal Calves with Diarrhea.

PubMed

Trefz, F M; Constable, P D; Lorenz, I

2017-05-01

Hyperkalemia is a frequently observed electrolyte imbalance in dehydrated neonatal diarrheic calves that can result in skeletal muscle weakness and life-threatening cardiac conduction abnormalities and arrhythmias. Intravenous administration of a small-volume hypertonic NaHCO 3 solution is clinically more effective in decreasing the plasma potassium concentration (cK) in hyperkalemic diarrheic calves than hypertonic NaCl or glucose solutions. Twenty-two neonatal diarrheic calves with cK >5.8 mmol/L. Prospective randomized clinical trial. Calves randomly received either 8.4% NaHCO 3 (6.4 mL/kg BW; n = 7), 7.5% NaCl (5 mL/kg BW; n = 8), or 46.2% glucose (5 mL/kg BW; n = 7) IV over 5 minutes and were subsequently allowed to suckle 2 L of an electrolyte solution. Infusions with NaHCO 3 and NaCl provided an identical sodium load of 6.4 mmol/kg BW. Hypertonic NaHCO 3 infusions produced an immediate and sustained decrease in plasma cK. Hypertonic glucose infusions resulted in marked hyperglycemia and hyperinsulinemia, but cK remained unchanged for 20 minutes. Between 30 and 120 minutes after initiation of treatment, the most marked decrements in cK from baseline occurred in group NaHCO 3 , which were significantly (P < .05) larger during this period of time than in calves in group NaCl, but not group glucose. After 120 minutes, the mean decrease in cK from baseline was -26 ± 10%, -9 ± 8%, and -22 ± 6% in groups NaHCO 3 , NaCl, and glucose, respectively. Small-volume hypertonic NaHCO 3 infusions appear to have clinical advantages for the rapid resuscitation of hyperkalemic diarrheic calves, compared to hypertonic NaCl or glucose solutions. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Dornase alpha compared to hypertonic saline for lung atelectasis in critically ill patients.

PubMed

Youness, Houssein A; Mathews, Kathryn; Elya, Marwan K; Kinasewitz, Gary T; Keddissi, Jean I

2012-12-01

Despite the lack of randomized trials, nebulized Dornase alpha and hypertonic saline are used empirically to treat atelectasis in mechanically ventilated patients. Our objective was to determine the clinical and radiological efficacy of these medications as an adjunct to standard therapy in critically ill patients. Mechanically ventilated patients with new onset (<48 h) lobar or multilobar atelectasis were randomized into three groups: nebulized Dornase alpha, hypertonic (7%) saline or normal saline every 12 h. All patients received standard therapy, including chest percussion therapy, kinetic therapy, and bronchodilators. The primary endpoint was the change in the daily chest X-ray atelectasis score. A total of 33 patients met the inclusion criteria and were randomized equally into the three groups. Patients in the Dornase alpha group showed a reduction of 2.18±1.33 points in the CXR score from baseline to day 7, whereas patients in the normal saline group had a reduction of 1.00±1.79 points, and patients in the hypertonic saline group showed a score reduction of 1.09±1.51 points. Pairwise comparison of the mean change of the CXR score showed no statistical difference between hypertonic saline, normal saline, and dornase alpha. Airway pressures as well as oxygenation, expressed as PaO(2)/F(I)O(2) and time to extubation also were similar among groups. During the study period the rate of extubation was 54% (6/11), 45% (5/11), and 63% (7/11) in the normal saline, hypertonic saline, and Dornase alpha groups, respectively (p=0.09). No treatment related complications were observed. There was no significant improvement in the chest X-ray atelectasis score in mechanically ventilated patients with new onset atelectasis who were nebulized with Dornase alpha twice a day. Hypertonic saline was no more effective than normal saline in this population. Larger randomized control trials are needed to confirm our results.

Current purpose and practice of hypertonic saline in neurosurgery: a review of the literature.

PubMed

Thongrong, Cattleya; Kong, Nicolas; Govindarajan, Barani; Allen, Duane; Mendel, Ehud; Bergese, Sergio D

2014-12-01

To review and summarize controversies and current concepts regarding the use of hypertonic saline during the perioperative period in neurosurgery. Relevant literature was searched on PubMed and Scopus electronic databases to identify all studies that have investigated the use of hypertonic saline in neurosurgery. Fluid management during the course of neurosurgical practice has been debated at length, especially strategies to control intracranial pressure and small volume resuscitation. The goal of fluid therapy includes minimizing cerebral edema, preserving intravascular volume, and maintaining cerebral perfusion pressure. Mannitol is widely recognized as the gold standard for treating intracranial hypertension but can result in systemic hypotension. Thus, hypertonic saline provides volume expansion and may improve cerebral and systemic hemodynamics. Recently published prospective data, however, regarding the use of osmotic agents fails to establish clear guidelines in neurosurgical patients. We suggest that hypertonic saline will emerge as an alternative to mannitol, especially for a long-term use or multiple doses are needed and lead to a great opportunity for collaborative research. Copyright © 2014 Elsevier Inc. All rights reserved.

INHALED HYPERTONIC SALINE IN INFANTS AND CHILDREN LESS THAN SIX YEARS OF AGE WITH CYSTIC FIBROSIS: THE ISIS RANDOMIZED TRIAL

PubMed Central

Rosenfeld, Margaret; Ratjen, Felix; Brumback, Lyndia; Daniel, Stephen; Rowbotham, Ron; McNamara, Sharon; Johnson, Robin; Kronmal, Richard; Davis, Stephanie D

2013-01-01

Context Inhaled hypertonic saline is recommended as therapy for cystic fibrosis (CF) patients 6 years of age and older, but its efficacy has never been evaluated in CF patients <6 years of age. Objective To determine if hypertonic saline reduces the rate of protocol-defined pulmonary exacerbations in CF patients <6 years of age. Design and Setting A multicenter, randomized, double-blind placebo-controlled trial was conducted from April 2009 to October 2011 at 30 CF care centers in the United States and Canada. Participants Participants had an established diagnosis of CF and were 4 to 60 months of age. A total of 344 patients were assessed for eligibility; 321 participants were randomized; 29 (9%) withdrew prematurely. Intervention The active group (n=158) received 7% hypertonic saline and the control group (n=163) received 0.9% isotonic saline nebulized twice daily for 48 weeks. Both groups received albuterol or levalbuterol prior to each study drug dose. Main Outcome Measures the rate of protocol-defined pulmonary exacerbations during the 48 week treatment period treated with oral, inhaled or intravenous antibiotics. Results The mean pulmonary exacerbation rate (events/person-year) was 2.3 (95% CI, 2.0, 2.5) in the hypertonic saline group and 2.3 (95% CI, 2.1, 2.6) in the isotonic saline group; the rate ratio was 0.98 (95% CI, 0.84, 1.14)). Among participants with pulmonary exacerbations, the mean number of total antibiotic treatment days for a pulmonary exacerbation was 60 (95% CI 49, 70) in the hypertonic saline group and 52 (95% CI 43, 61) in the isotonic saline group. There was no significant difference in secondary endpoints including height, weight, respiratory rate, oxygen saturation, cough or respiratory symptom scores. Infant pulmonary function testing performed as an exploratory outcome in a subgroup (N=73, with acceptable measurements at 2 visits in 45) did not demonstrate significant differences between groups except for the mean change in forced

Common toads (Bufo arenarum) learn to anticipate and avoid hypertonic saline solutions.

PubMed

Daneri, M Florencia; Papini, Mauricio R; Muzio, Rubén N

2007-11-01

Toads (Bufo arenarum) were exposed to pairings between immersion in a neutral saline solution (i.e., one that caused no significant variation in fluid balance), followed by immersion in a highly hypertonic saline solution (i.e., one that caused water loss). In Experiment 1, solutions were presented in a Pavlovian conditioning arrangement. A group receiving a single neutral-highly hypertonic pairing per day exhibited a greater conditioned increase in heart rate than groups receiving either the same solutions in an explicitly unpaired fashion, or just the neutral solution. Paired toads also showed a greater ability to compensate for water loss across trials than that of the explicitly unpaired group. Using the same reinforcers and a similar apparatus, Experiment 2 demonstrated that toads learn a one-way avoidance response motivated by immersion in the highly hypertonic solution. Cardiac and avoidance conditioning are elements of an adaptive system for confronting aversive situations involving loss of water balance. Copyright 2007 APA.

Molecular Mechanisms of Urea Transport in Health and Disease

PubMed Central

Klein, Janet D.; Blount, Mitsi A.; Sands, Jeff M.

2012-01-01

In the late 1980s, urea permeability measurements produced values that could not be explained by paracellular transport or lipid phase diffusion. The existence of urea transport proteins were thus proposed and less than a decade later, the first urea transporter was cloned. The SLC14A family of urea transporters has two major subgroups, designated SLC14A1 (or UT-B) and Slc14A2 (or UT-A). UT-B and UT-A gene products are glycoproteins located in various extra-renal tissues however, a majority of the resulting isoforms are found in the kidney. The UT-B (Slc14A1) urea transporter was originally isolated from erythrocytes and two isoforms have been reported. In kidney, UT-B is located primarily in the descending vasa recta. The UT-A (Slc14A2) urea transporter yields 6 distinct isoforms, of which 3 are found chiefly in the kidney medulla. UT-A1 and UT-A3 are found in the inner medullary collecting duct (IMCD), while UT-A2 is located in the thin descending limb. These transporters are crucial to the kidney’s ability to concentrate urine. The regulation of urea transporter activity in the IMCD involves acute modification through phosphorylation and subsequent movement to the plasma membrane. UT-A1 and UT-A3 accumulate in the plasma membrane in response to stimulation by vasopressin or hypertonicity. Long term regulation of the urea transporters in the IMCD involves altering protein abundance in response to changes in hydration status, low protein diets, or adrenal steroids. Urea transporters have been studied using animal models of disease including diabetes mellitus, lithium intoxication, hypertension, and nephrotoxic drug responses. Exciting new genetically engineered mouse models are being developed to study these transporters. PMID:23007461

A comparison of sputum induction methods: ultrasonic vs compressed-air nebulizer and hypertonic vs isotonic saline inhalation.

PubMed

Loh, L C; Eg, K P; Puspanathan, P; Tang, S P; Yip, K S; Vijayasingham, P; Thayaparan, T; Kumar, S

2004-03-01

Airway inflammation can be demonstrated by the modem method of sputum induction using ultrasonic nebulizer and hypertonic saline. We studied whether compressed-air nebulizer and isotonic saline which are commonly available and cost less, are as effective in inducing sputum in normal adult subjects as the above mentioned tools. Sixteen subjects underwent weekly sputum induction in the following manner: ultrasonic nebulizer (Medix Sonix 2000, Clement Clarke, UK) using hypertonic saline, ultrasonic nebulizer using isotonic saline, compressed-air nebulizer (BestNeb, Taiwan) using hypertonic saline, and compressed-air nebulizer using isotonic saline. Overall, the use of an ultrasonic nebulizer and hypertonic saline yielded significantly higher total sputum cell counts and a higher percentage of cell viability than compressed-air nebulizers and isotonic saline. With the latter, there was a trend towards squamous cell contaminations. The proportion of various sputum cell types was not significantly different between the groups, and the reproducibility in sputum macrophages and neutrophils was high (Intraclass correlation coefficient, r [95%CI]: 0.65 [0.30-0.91] and 0.58 [0.22-0.89], p < 0.001). Overall changes in median FEV, were small and comparable between all groups. Induction using ultrasonic nebulizers together with hypertonic saline was generally less well tolerated than compressed-air nebulizers and isotonic saline. We conclude that in normal subjects, although both nebulizers and saline types can induce sputum with reproducible cellular profile, ultrasonic nebulizers and hypertonic saline are more effective but less well tolerated.

What are the effects of hypertonic saline plus furosemide in acute heart failure?

PubMed

Zepeda, Patricio; Rain, Carmen; Sepúlveda, Paola

2015-08-27

In search of new therapies to solve diuretic resistance in acute heart failure, the addition of hypertonic saline has been proposed. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified two systematic reviews including nine pertinent randomized controlled trials. We combined the evidence and generated a summary of findings following the GRADE approach. We concluded hypertonic saline associated with furosemide probably decrease mortality, length of hospital stay and hospital readmission in patients with acute decompensated heart failure.

The presence of PHB granules in cytoplasm protects non-halophilic bacterial cells against the harmful impact of hypertonic environments.

PubMed

Obruca, Stanislav; Sedlacek, Petr; Mravec, Filip; Krzyzanek, Vladislav; Nebesarova, Jana; Samek, Ota; Kucera, Dan; Benesova, Pavla; Hrubanova, Kamila; Milerova, Miluse; Marova, Ivana

2017-10-25

Numerous prokaryotes accumulate polyhydroxybutyrate (PHB) intracellularly as a storage material. It has also been proposed that PHB accumulation improves bacterial stress resistance. Cupriavidus necator and its PHB non-accumulating mutant were employed to investigate the protective role of PHB under hypertonic conditions. The presence of PHB granules enhanced survival of the bacteria after exposure to hypertonic conditions. Surprisingly, when coping with such conditions, the bacteria did not utilize PHB to harvest carbon or energy, suggesting that, in the osmotic upshock of C. necator, the protective mechanism of PHB granules is not associated with their hydrolysis. The presence of PHB granules influenced the overall properties of the cells, since challenged PHB-free cells underwent massive plasmolysis accompanied by damage to the cell membrane and the leakage of cytoplasm content, while no such effects were observed in PHB containing bacteria. Moreover, PHB granules demonstrated "liquid-like" properties indicating that they can partially repair and stabilize cell membranes by plugging small gaps formed during plasmolysis. In addition, the level of dehydration and changes in intracellular pH in osmotically challenged cells were less pronounced for PHB-containing cultures, demonstrating the important role of PHB for bacterial survival under hyperosmotic conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular mechanisms of urea transport in health and disease.

PubMed

Klein, Janet D; Blount, Mitsi A; Sands, Jeff M

2012-12-01

In the late 1980s, urea permeability measurements produced values that could not be explained by paracellular transport or lipid phase diffusion. The existence of urea transport proteins were thus proposed and less than a decade later, the first urea transporter was cloned. The family of urea transporters has two major subgroups, designated SLC14A1 (or UT-B) and Slc14A2 (or UT-A). UT-B and UT-A gene products are glycoproteins located in various extra-renal tissues however, a majority of the resulting isoforms are found in the kidney. The UT-B (Slc14A1) urea transporter was originally isolated from erythrocytes and two isoforms have been reported. In kidney, UT-B is located primarily in the descending vasa recta. The UT-A (Slc14A2) urea transporter yields six distinct isoforms, of which three are found chiefly in the kidney medulla. UT-A1 and UT-A3 are found in the inner medullary collecting duct (IMCD), while UT-A2 is located in the thin descending limb. These transporters are crucial to the kidney's ability to concentrate urine. The regulation of urea transporter activity in the IMCD involves acute modification through phosphorylation and subsequent movement to the plasma membrane. UT-A1 and UT-A3 accumulate in the plasma membrane in response to stimulation by vasopressin or hypertonicity. Long-term regulation of the urea transporters in the IMCD involves altering protein abundance in response to changes in hydration status, low protein diets, or adrenal steroids. Urea transporters have been studied using animal models of disease including diabetes mellitus, lithium intoxication, hypertension, and nephrotoxic drug responses. Exciting new genetically engineered mouse models are being developed to study these transporters.

Hypertonic Saline for the Treatment of Bronchiolitis in Infants and Young Children: A Critical Review of the Literature

PubMed Central

Baron, Jeffrey

2016-01-01

Bronchiolitis, an infection of the lower respiratory tract, is the leading cause of infant and child hospitalization in the United States. Therapeutic options for management of bronchiolitis are limited. Hypertonic saline inhalation therapy has been studied in numerous clinical trials with mixed results. In 2014, the American Academy of Pediatrics (AAP) published updated guidelines on the diagnosis and management of bronchiolitis, which include new recommendations on the use of hypertonic saline. We reviewed all published clinical trials mentioned in the 2014 AAP guidelines, as well as additional trials published since the guidelines, and critically evaluated each trial to determine efficacy, safety, and expectations of hypertonic saline inhalation therapy. A total of 2682 infants were studied over the course of 22 clinical trials. Nine trials were carried out in the outpatient/clinic/emergency department and 13 in the inpatient setting. We agree with the AAP guidelines regarding the recommendation to use nebulized hypertonic saline for infants hospitalized with bronchiolitis, with the expectation of reducing bronchiolitis scores and length of stay when it is expected to last more than 72 hours. However, we also believe there might be an advantage for hypertonic saline in reducing admission rates from the emergency department, based on close examination of the results of recent trials. This review also highlights important gaps in the available literature that need to be addressed in order to define the role of inhaled hypertonic saline therapy. PMID:26997926

Maturation of the renal response to hypertonic sodium chloride loading in rats: micropuncture and clearance studies.

PubMed Central

Baker, J T; Solomon, S

1976-01-01

1. The ability of maturing rats to excrete a sodium load was studied by micropuncture and clearance procedures. 2. During control conditions, no change of glomerular filtration rate or sodium excretion was observed for the time period of the entire procedure (P greater than 0-20). During the infusion of hypertonic (4%) sodium chloride, fractional sodium excretion was 0-08 +/- 0-01 in rats 21-30 days old and 0-14 +/- 0-01 (P less than 0-01) in adults. However, the depression of proximal tubular water re-absorption was equal in both groups (P greater than 0-20). 3. Proximal glomerulotubular balance for water re-absorption was similar in all groups (P less than 0-20). Since end proximal tubular water excretion and depression of fractional water excretion were the same in all animals, differences of urinary sodium excretion during development are probably due to differences of function of segments beyond the proximal tubule during development. 4. Fractional potassium excretion was reduced in young rats (0-17 +/- 0-04) during hypertonic sodium chloride infusion, compared to adults (0-24 +/- 0-01, P less than 0-05). 5. Passage time of fast green through cortical segments in seconds is prolonged in young rats during control conditions. Similar decreases of passage time were seen in all groups during hypertonic sodium chloride infusion. No segmental differences of passage time were seen during developmental. 6. No difference in the relationship between fractional sodium and water excretion was seen during development of the renal response to hypertonic sodium chloride infusion. Thus, altered sensitivity to sodium chloride osmotic diuresis does not exist during maturation in rats. PMID:945839

Gap junctions favor normal rat kidney epithelial cell adaptation to chronic hypertonicity.

PubMed

Desforges, Bénédicte; Savarin, Philippe; Bounedjah, Ouissame; Delga, Stéphanie; Hamon, Loïc; Curmi, Patrick A; Pastré, David

2011-09-01

Upon hypertonic stress most often resulting from high salinity, cells need to balance their osmotic pressure by accumulating neutral osmolytes called compatible osmolytes like betaine, myo-inositol, and taurine. However, the massive uptake of compatible osmolytes is a slow process compared with other defense mechanisms related to oxidative or heat stress. This is especially critical for cycling cells as they have to double their volume while keeping a hospitable intracellular environment for the molecular machineries. Here we propose that clustered cells can accelerate the supply of compatible osmolytes to cycling cells via the transit, mediated by gap junctions, of compatible osmolytes from arrested to cycling cells. Both experimental results in epithelial normal rat kidney cells and theoretical estimations show that gap junctions indeed play a key role in cell adaptation to chronic hypertonicity. These results can provide basis for a better understanding of the functions of gap junctions in osmoregulation not only for the kidney but also for many other epithelia. In addition to this, we suggest that cancer cells that do not communicate via gap junctions poorly cope with hypertonic environments thus explaining the rare occurrence of cancer coming from the kidney medulla.

Subfornical organ disconnection and Fos-like immunoreactivity in hypothalamic nuclei after intragastric hypertonic saline.

PubMed

Starbuck, Elizabeth M; Fitts, Douglas A

2002-10-04

The subfornical organ (SFO) may act as a sodium- or osmoreceptor that drives hypothalamic and other nuclei to secrete vasopressin and to elicit drinking. However, in response to mild doses of hypertonic saline, Fos-like immunoreactivity (Fos-ir) is absent in the SFO whereas it is well expressed in the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei. This suggests that the hypothalamus may be activated in advance of the SFO. In this study, the fibers connecting the SFO and hypothalamus were disconnected by a wire knife cut so that Fos-ir could be examined in both the SFO and hypothalamus after an intragastric (ig) load of 0.5% of body weight of 0.6 M NaCl. Compared with Fos-ir in isotonic-loaded rats, Fos-ir after the hypertonic load was not significantly elevated in the SFO or median preoptic nucleus in sham-cut or knife-cut rats and was only slightly elevated in the OVLT in sham-cut rats. However, the hypertonic load in sham-cut rats greatly elevated Fos-ir in the SON and in the entire PVN, but this expression was reduced significantly by 30-50% in knife-cut rats. Thus, the connectivity between SFO and the hypothalamus is critical for the full expression of Fos-ir in the hypothalamus during moderate ig hypertonic saline loading even when the SFO itself does not yet express Fos-ir.

Hypertonic Glucose Combined with Negative Pressure Wound Therapy to Prepare Wounds with Pseudomonas aeruginosa Infection for Skin Grafting: A Report of 3 Cases.

PubMed

Zhao, Jing-Chun; Xian, Chun-Jing; Yu, Jia-Ao; Shi, Kai; Hong, Lei

2015-06-01

Soft tissue losses from acute or chronic trauma are a challenge for surgeons. To explore a method to expedite granulation tissue formation in preparation for a split-thickness skin graft (STSG), the medical records of 3 patients - 2 adult men with wounds related to trauma injury and 1 infant with necrotizing fasciitis, all infected with Pseudomonas aeruginosa - were reviewed. All wounds were surgically debrided and managed by applying gauze soaked in 50% glucose followed by continuous negative pressure wound therapy (NPWT) before definitive skin grafting. NPWT pressure was applied at -80 mm Hg for the 2 adult males (ages 39 and 25 years) and -50 mm Hg for the 7-month-old male infant. The dressings were changed every 2 to 3 days. No adverse events occurred, and wounds were successfully closed with a STSG after an average of 7 days. In 1 case, NPWT was able to help affix dressings in a difficult-to-dress area (genital region). The combination of hypertonic glucose and hand-made, gauze-based NPWT was found to be safe, well-tolerated, and effective in preparing the wound bed for grafting. Prospective, randomized, controlled clinical studies are needed to compare the safety, effectiveness, and efficacy of this method to other treatment approaches for P. aeruginosa-infected wounds.

Comparison of equimolar doses of mannitol and hypertonic saline for the treatment of elevated intracranial pressure after traumatic brain injury: a systematic review and meta-analysis.

PubMed

Li, Min; Chen, Tao; Chen, Shu-da; Cai, Jing; Hu, Ying-Hong

2015-05-01

The purpose of this meta-analysis was to compare the effectiveness of mannitol and hypertonic saline for reducing intracranial pressure (ICP) after traumatic brain injury (TBI).PubMed, Cochrane, Embase, and ISI Web of Knowledge databases were searched until July 3, 2014 using the terms intracranial hypertension, mannitol, and hypertonic saline. Randomized controlled trials and 2-arm prospective studies in which elevated ICP was present after TBI treated with mannitol or hypertonic saline were included. The primary outcome was the change of ICP from baseline to termination of the infusion, while the secondary outcomes were change from baseline to 30, 60, and 120 minutes after terminating the infusion and change of osmolarity from baseline to termination.A total 7 studies with 169 patients were included. The mean age of patients receiving mannitol ranged from 30.8 to 47 years, and for patients receiving hypertonic saline ranged from 35 to 47 years. A pooled difference in means = -1.69 (95% confidence interval [CI]: -2.95 to -0.44, P = 0.008) indicated that hypertonic saline reduced ICP more effectively than mannitol when compared from the baseline value to the last measurement after treatment. At 30 minutes after intervention, there was no difference in the mean ICP change between the groups, whereas at 60 minutes after intervention (pooled difference in means = -2.58, 95% CI: -4.37 to -0.80, P = .005) and 120 min after intervention (pooled difference in means = -4.04, 95% CI: -6.75 to -1.32, P = .004) hypertonic saline resulted in a significantly greater decrease in ICP. The pooled difference in means = 1.84 (95% CI: -1.64 to 5.31, P = .301) indicated no difference in serum osmolarity between patients treated with hypertonic saline or mannitol.Hypertonic saline is more effective than mannitol for reducing ICP in cases of TBI.

Nebulised 7% hypertonic saline improves lung function and quality of life in bronchiectasis.

PubMed

Kellett, Fiona; Robert, Niven M

2011-12-01

Sputum retention is a distressing feature of non-cystic fibrosis bronchiectasis and has been shown to contribute to the vicious cycle of infection seen in this disease. In a previous study we demonstrated that nebulised 7% hypertonic saline was both safe and effective in this patient population. Patients with a clinical diagnosis of non-cystic fibrosis bronchiectasis, confirmed by HRCT, were entered into a randomised single blind cross-over study to evaluate 0.9% sodium chloride (IS) and 7% hypertonic saline (HS). Following a 4 week run in patients received a random order active HS or IS daily for 3 months. A 4 week wash-out phase was included between phases. We report lung function, quality of life, and health care utilisation responses. 32 patients mean age 56.6 years (SD 14.6), 16 male, were recruited of which 28 were randomised and completed the study. Lung function (%change from baseline) improved in HS vs. IS (FEV(1): 15.1, 1.8 p<0.01; FVC: 11.2, 0.7 p<0.01. SGRQ improved significantly from baseline (HS 6.0, IS 1.2; p<0.05). There were reductions in annualised antibiotic usage (HS 2.4, IS 5.4 courses per patient per year), annualised emergency health care utilisation visits were reduced (HS 2.1, IS 4.9 events per patient per year). There were also improvements in sputum viscosity and ease of expectoration (visual analogue scale). Regular use of 7% hypertonic saline improves lung function, quality of life and health care utilisation in non-cystic fibrosis bronchiectasis patients. Copyright © 2011 Elsevier Ltd. All rights reserved.

[The role of arteriovenous interrelations in the formation of clinical-pathogenetic variants of hypertonic encephalopathy].

PubMed

Belova, L A

2012-01-01

We studied 209 patients with chronic brain ischemia due to arterial hypertension (hypertonic encephalopathy). 93 patients (44.5%) had clinical-anamnestic features of constitutional phlebopathy and 116 (55.5%) had not. Based on the conception of 5 functional-morphological levels of the vascular brain system, a complex ultrasound study was conducted. The control group included 30 people without cerebrovascular pathology. In hypertonic encephalopathy, pathological processes developing in the 1st and 2nd structural-functional levels (extra- and intracerebral arteries) correspond to remodeling, that is characteristic of arterial hypertension, and do not depend on the presence of the constitutional venous insufficiency. Changes in parameters of the blood flow in the 3rd, 4th and 5th structural-functional levels of the brain's blood supply (microcirculatory bed, head venous system, jugular and spine veins) form a dopplerographic pattern of the cerebral venous dyscirculation which is mostly pronounced in constitutional phlebopathy in patients with hypertonic encephalopathy. This pattern includes the reduction of linear blood flow velocity in nitroglycerine test, lower values of the resistance index and the increase in the linear blood flow velocity in the sinus transversus and Rosenthal vein, lack of ostial valves of the inner jugular veinas well as the decrease of linear and increase in the volume blood flow velocity along it. The methodology of the system approach based on using clinical and instrumental method in the study of cerebral hemodynamics is important for treatment optimization in patients with chronic brain ischemia.

Tyrosine kinase inhibitors and immunosuppressants perturb the myo-inositol but not the betaine cotransporter in isotonic and hypertonic MDCK cells

PubMed Central

Atta, Mohamed G.; Dahl, Stephen C.; Kwon, H. Moo; Handler, Joseph S.

2008-01-01

Background The sodium/myo-inositol cotransporter (SMIT) and the betaine cotransporter (BGT1) are essential for the accumulation of myo-inositol and betaine, and hence cell survival in a hypertonic environment. The underlying molecular mechanism involves an increase in transcription of the SMIT and BGT1 genes through binding of a trans-acting factor to enhancer elements in the 5′ flanking region of both genes, resulting in increased mRNA abundance and increased activity of the cotransporters. Current evidence regarding transcriptional and post-transcriptional regulation indicates that both cotransporters are regulated in parallel. Methods To investigate the signal transduction of hypertonic stress, we examined the effect of tyrosine kinase inhibitors and immunosuppressants on the hypertonicity-induced activity of the two cotransporters in Madin-Darby canine kidney (MDCK) cells. Results None of the agents studied affected BGT1 activity in isotonic or hypertonic conditions. Treatment of MDCK cells with genistein, a tyrosine kinase inhibitor, increased SMIT activity in hypertonic but not isotonic conditions. The stimulation of SMIT by genistein was accompanied by a parallel increase in mRNA abundance. In contrast, treating cells with tyrphostin A23, another tyrosine kinase inhibitor, or cyclosporine A, an immunosuppressant, inhibited SMIT activity in hypertonic cells. FK506, another immunosuppressant, increased SMIT activity, but only in isotonic conditions. Conclusions These results provide the first evidence of divergent regulatory pathways modulating SMIT and BGT activity. PMID:10027932

Cap-independent protein synthesis is enhanced by betaine under hypertonic conditions.

PubMed

Carnicelli, Domenica; Arfilli, Valentina; Onofrillo, Carmine; Alfieri, Roberta R; Petronini, Pier Giorgio; Montanaro, Lorenzo; Brigotti, Maurizio

2017-02-12

Protein synthesis is one of the main cellular functions inhibited during hypertonic challenge. The subsequent accumulation of the compatible osmolyte betaine during the later adaptive response allows not only recovery of translation but also its stimulation. In this paper, we show that betaine modulates translation by enhancing the formation of cap-independent 48 S pre-initiation complexes, leaving cap-dependent 48 S pre-initiation complexes basically unchanged. In the presence of betaine, CrPV IRES- and sodium-dependent neutral amino acid transporter-2 (SNAT2) 5'-UTR-driven translation is 2- and 1.5-fold stimulated in MCF7 cells, respectively. Thus, betaine could provide an advantage in translation of messengers coding for proteins implicated in the response of cells to different stressors, which are often recognized by ribosomal 40 S subunit through simplified cap-independent mechanisms. Copyright © 2017 Elsevier Inc. All rights reserved.

Urinary composition predicts diuretic efficiency of hypertonic saline solution with furosemide therapy and heart failure prognosis.

PubMed

Ando, Tomotaka; Okuhara, Yoshitaka; Orihara, Yoshiyuki; Nishimura, Koichi; Yamamoto, Kyoko; Masuyama, Tohru; Hirotani, Shinichi

2018-03-19

Recently, we and other group have reported that furosemide administration along with hypertonic saline solution enhanced diuretic efficiency of furosemide. However, little is known about factors which associated with high diuretic efficiency by hypertonic saline solution with furosemide therapy. To identify predictors of diuretic efficiency in the hypertonic saline solution with furosemide therapy, we recruited 30 consecutive hospitalized heart failure (HF) patients with volume overload (77 ± 10 years, systolic blood pressure > 90 mmHg, and estimated glomerular filtration rate > 15 ml/min/1.73 m 2 ). Hypertonic saline with furosemide solution, consisting of 500 ml of 1.7% hypertonic saline solution with 40 mg of furosemide, was administered continuously over 24 h. The patients were divided into two groups on the basis of 24-h urine volume (UV) after initiation of diuretic treatment ≥ 2000 ml (high urine volume: HUV) and < 2000 ml (low urine volume: LUV). The basal clinical characteristics of both groups were analyzed and the predictors of HUV after receiving the treatment were identified. There were not significant differences between two groups in baseline clinical characteristics and medication. Univariate logistic analysis revealed that blood urea nitrogen/creatinine ratio, urine urea nitrogen/creatinine ratio (UUN/UCre), fractional excretion of sodium, and tricuspid annular plane systolic excursion positively associated with HUV. Multivariate logistic regression analysis revealed that UUN/UCre at baseline was independently associated with HUV, and UUN/UCre best predicts HUV by the therapy with a cut-off value of 6.16 g/dl/g Cre (AUC 0.910, 95% CI 0.696-0.999, sensitivity 80%, specificity 87%). The Kaplan-Meier curves revealed significant difference for HF rehospitalization and death rate at 180 days between patients with UUN/UCre ≥ 6.16 g/dl/g Cre and those with UUN/UCre < 6.16 g/dl/g Cre (log-rank P = 0

Comparison of the effects of intravenous administration of isotonic and hypertonic sodium bicarbonate solutions on venous acid-base status in dehydrated calves with strong ion acidosis.

PubMed

Coskun, Alparslan; Sen, Ismail; Guzelbektes, Hasan; Ok, Mahmut; Turgut, Kursat; Canikli, Sebnem

2010-05-15

OBJECTIVE-To compare the effects of IV administration of isotonic (1.3%) and hypertonic (8.4%) sodium bicarbonate (NaHCO(3)) solutions on acid-base status in dehydrated calves with strong ion (metabolic) acidosis. DESIGN-Randomized controlled clinical trial. ANIMALS-50 calves with diarrhea and severe dehydration. PROCEDURES-Calves were randomly assigned to receive isotonic NaHCO(3) solution (65 mL/kg [29.5 mL/lb], IV) over 3 hours (n = 30) or hypertonic NaHCO(3) solution (10 mL/kg [4.5 mL/lb], IV) over 20 minutes (20). Blood samples were collected at 0 hours (immediately prior to solution administration) and at 0.5, 1, 2, and 4 hours after administration began. Samples were submitted for blood gas analysis, serum biochemical analysis, and determination of blood Na(+), K(+), and Cl(-) concentrations and percentage change in plasma volume. RESULTS-Calves that received isotonic NaHCO(3) solution had an increase in venous blood pH, HCO(3) concentration, and base excess; a small, transient increase in Po(2); and no change in Pco(2) within 4 hours after administration began. Calves that received hypertonic NaHCO(3) solution had an immediate increase in venous blood pH, HCO(3) concentration, and base excess; a small, transient increase Pco(2); and no change in Po(2) within 0.5 hours after treatment began. Plasma volume increased to a greater extent following administration of isotonic solution than after administration of hypertonic solution. CONCLUSIONS AND CLINICAL RELEVANCE-IV administration of 8.4% NaHCO(3) solution in small volumes provided fast and effective improvement of severe acid-base abnormalities in calves with severe strong ion acidosis but did not improve hydration status as well as administration of a larger volume of isotonic NaHCO(3) solution.

Agreement of measured and calculated serum osmolality during the infusion of mannitol or hypertonic saline in patients after craniotomy: a prospective, double-blinded, randomised controlled trial.

PubMed

Li, Qian; Chen, Han; Hao, Jing-Jing; Yin, Ning-Ning; Xu, Ming; Zhou, Jian-Xin

2015-10-07

Mannitol and hypertonic saline are used to ameliorate brain edema and intracranial hypertension during and after craniotomy. We hypothesized that the agreement of measured and calculated serum osmolality during the infusion of hypertonic saline would be better than mannitol. The objective was to determine the accuracy of serum osmolality estimation by different formulas during the administration of hyperosmolar agent. A prospective, randomized, double-blinded, controlled trial was conducted in a 30-bed neurosurgical intensive care unit at a university hospital. Thirty-five adult patients requiring the use of hyperosmolar agents for prevention or treatment of brain edema after elective craniotomy were enrolled, and randomly assigned 1:1 to receive 125 mL of either 20 % mannitol (mannitol group) or 3.1 % sodium chloride solution (hypertonic saline group) in 15 min. Serum osmolality, serum sodium and potassium concentration, blood urea nitrogen and blood glucose concentration were measured during the study period. The primary outcome was the agreement of measured and estimated serum osmolality during the infusion of the two experimental agents. We used Bland and Altman's limits of agreement analysis to clarify the accuracy of estimated serum osmolality. Bias and upper and lower limits of agreement of bias were calculated. For each formula, the bias was statistically lower in hypertonic saline group than mannitol group (p < 0.001). Within group comparison showed that the lowest bias (6.0 [limits of agreement: -18.2 to 30.2] and 0.8 [-12.9 to 14.5] mOsml/kg in mannitol group and hypertonic saline group, respectively) was derived from the formula '2 × ([serum sodium] + [serum potassium]) + [blood urea nitrogen] + [blood glucose]'. Compared to mannitol, a better agreement between measured and estimated serum osmolality was found during the infusion of hypertonic saline. This result indicates that, if hypertonic saline is chosen to prevent or treat brain edema

Hypertonic enhancement of transmitter release from frog motor nerve terminals: Ca2+ independence and role of integrins

NASA Technical Reports Server (NTRS)

Kashani, A. H.; Chen, B. M.; Grinnell, A. D.

2001-01-01

Hyperosmotic solutions cause markedly enhanced spontaneous quantal release of neurotransmitter from many nerve terminals. The mechanism of this enhancement is unknown. We have investigated this phenomenon at the frog neuromuscular junction with the aim of determining the degree to which it resembles the modulation of release by stretch, which has been shown to be mediated by mechanical tension on integrins.The hypertonicity enhancement, like the stretch effect, does not require Ca2+ influx or release from internal stores, although internal release may contribute to the effect. The hypertonicity effect is sharply reduced (but not eliminated) by peptides containing the RGD sequence, which compete with native ligands for integrin bonds.There is co-variance in the magnitude of the stretch and osmotic effects; that is, individual terminals exhibiting a large stretch effect also show strong enhancement by hypertonicity, and vice versa. The stretch and osmotic enhancements also can partially occlude each other.There remain some clear-cut differences between osmotic and stretch forms of modulation: the larger range of enhancement by hypertonic solutions, the relative lack of effect of osmolarity on evoked release, and the reported higher temperature sensitivity of osmotic enhancement. Nevertheless, our data strongly implicate integrins in a significant fraction of the osmotic enhancement, possibly acting via the same mechanism as stretch modulation.

The selective cyclooxygenase-2 inhibitor parecoxib markedly improves the ability of the duodenum to regulate luminal hypertonicity in anaesthetized rats.

PubMed

Sedin, J; Sjöblom, M; Nylander, O

2012-07-01

To examine whether the prevention of post-operative duodenal ileus by treatment with parecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, affects the ability of the duodenum to respond to luminal hypertonicity. The proximal duodenums of anaesthetized rats were perfused with hypertonic NaCl solutions with osmolalities of 400, 500, 600 or 700 mOsm kg(-1) , and the effects on mucosal permeability, motility, transepithelial net fluid flux and effluent osmolality were assessed in the absence (control) and presence of parecoxib. Parecoxib-treated, but not control animals, exhibited duodenal contractions, which were reduced by the nicotinic receptor antagonists mecamylamine and hexamethonium and by perfusion with 700 mOsm kg(-1) . All animals responded to luminal hypertonicity with induction of net fluid secretion, which peaked at an osmolality of 500 mOsm kg(-1) . The hypertonicity-induced increases in fluid secretion were twofold greater in parecoxib-treated than in control rats and attenuated by nicotinic receptor blockade. The decrease in luminal osmolality correlated with the osmolality of the perfusion solution in both control and parecoxib-treated animals but the osmolality-adjusting capability was markedly better in the latter group. Rats exposed to duodenal luminal distension responded to hypertonicity with a greater fluid secretion and a larger decrease in luminal osmolality than control rats. Perfusion with 700 mOsm kg(-1) increased mucosal permeability in parecoxib-treated animals only, an effect abolished by nicotinic receptor blockade. Parecoxib markedly improved the ability of the duodenum to sense and to decrease luminal hypertonicity by a mechanism most probably involving inhibition of COX-2 and stimulation of nicotinic acetylcholine receptors. © 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society.

Hypertonicity-induced transmitter release at Drosophila neuromuscular junctions is partly mediated by integrins and cAMP/protein kinase A

NASA Technical Reports Server (NTRS)

Suzuki, Kazuhiro; Grinnell, Alan D.; Kidokoro, Yoshiaki

2002-01-01

The frequency of quantal transmitter release increases upon application of hypertonic solutions. This effect bypasses the Ca(2+) triggering step, but requires the presence of key molecules involved in vesicle fusion, and hence could be a useful tool for dissecting the molecular process of vesicle fusion. We have examined the hypertonicity response at neuromuscular junctions of Drosophila embryos in Ca(2+)-free saline. Relative to wild-type, the response induced by puff application of hypertonic solution was enhanced in a mutant, dunce, in which the cAMP level is elevated, or in wild-type embryos treated with forskolin, an activator of adenylyl cyclase, while protein kinase A (PKA) inhibitors decreased it. The response was also smaller in a mutant, DC0, which lacks the major subunit of PKA. Thus the cAMP/PKA cascade is involved in the hypertonicity response. Peptides containing the sequence Arg-Gly-Asp (RGD), which inhibit binding of integrins to natural ligands, reduced the response, whereas a peptide containing the non-binding sequence Arg-Gly-Glu (RGE) did not. A reduced response persisted in a mutant, myospheroid, which expresses no integrins, and the response in DC0 was unaffected by RGD peptides. These data indicate that there are at lease two components in the hypertonicity response: one that is integrin mediated and involves the cAMP/PKA cascade, and another that is not integrin mediated and does not involve the cAMP/PKA cascade.

Effect of different concentrations of hypertonic saline at different times on protoscoleces of hydatid cyst isolated from liver and lung.

PubMed

Tappeh, Khosrow Hazreti; Einshaei, Ali; Mahmudloo, Rahim; Mohammadzadeh, Habib; Tahermaram, Mansoor; Mousavi, Seyed Javad

2011-01-01

Most surgeons inject scoloidal materials into the cyst before or after its removal, since any contamination to normal sites will cause re-growth of the same cyst. The aim of this study was to determine the lethal effect of hypertonic saline at different doses and different times on protoscolexes of lung and liver. The livers and lungs of killed animals with hydatid cyst disease were gathered from Urmia Industrial Abattoirs. They were transferred to the university parasitological lab immediately. The hydatid cyst fluid was aspirated with a 10 mm syringe and poured into a 15 cc tubes. The movement of protoscoleces and staining with 0.1% eosin was the test to determine viability of protoscoleces. Those with color absorption were those which were not viable. Different concentrations of hypertonic saline were given at different time. The results showed that in 20% of hypertonic saline in the 4th minute, 80% of protoscoleces were alive while in the 5th minute 50% were alive, in the 7th minute 20% and 8th minute 5%, 9th minute all of them were dead. In the 10% concentration, at up to 9 minutes 50% were alive, in the 18th minute 20% and in 30 minutes 10% of protoscoleces were alive. In the 5% concentration at up to 10 minutes 90% were alive while in the 22nd minute 80% and in 30 minutes 70% of protoscoleces were alive. When we inject 20% hypertonic saline into the cyst cavity there is aprobability that the cyst contaminates the bile duct and liver through the small hole we made. This material may cause widespread necrosis of the liver. We should use 10% hypertonic saline minimally for 45 minute before surgery and after cyst removal, since the hypertonic saline itself may cause injury to the biliary system.

In vitro impairment of whole blood coagulation and platelet function by hypertonic saline hydroxyethyl starch.

PubMed

Hanke, Alexander A; Maschler, Stephanie; Schöchl, Herbert; Flöricke, Felix; Görlinger, Klaus; Zanger, Klaus; Kienbaum, Peter

2011-02-10

Hypertonic saline hydroxyethyl starch (HH) has been recommended for first line treatment of hemorrhagic shock. Its effects on coagulation are unclear. We studied in vitro effects of HH dilution on whole blood coagulation and platelet function. Furthermore 7.2% hypertonic saline, 6% hydroxyethylstarch (as ingredients of HH), and 0.9% saline solution (as control) were tested in comparable dilutions to estimate specific component effects of HH on coagulation. The study was designed as experimental non-randomized comparative in vitro study. Following institutional review board approval and informed consent blood samples were taken from 10 healthy volunteers and diluted in vitro with either HH (HyperHaes, Fresenius Kabi, Germany), hypertonic saline (HT, 7.2% NaCl), hydroxyethylstarch (HS, HAES6%, Fresenius Kabi, Germany) or NaCl 0.9% (ISO) in a proportion of 5%, 10%, 20% and 40%. Coagulation was studied in whole blood by rotation thrombelastometry (ROTEM) after thromboplastin activation without (ExTEM) and with inhibition of thrombocyte function by cytochalasin D (FibTEM), the latter was performed to determine fibrin polymerisation alone. Values are expressed as maximal clot firmness (MCF, [mm]) and clotting time (CT, [s]). Platelet aggregation was determined by impedance aggregrometry (Multiplate) after activation with thrombin receptor-activating peptide 6 (TRAP) and quantified by the area under the aggregation curve (AUC [aggregation units (AU)/min]). Scanning electron microscopy was performed to evaluate HyperHaes induced cell shape changes of thrombocytes. 2-way ANOVA for repeated measurements, Bonferroni post hoc test, p < 0.01. Dilution impaired whole blood coagulation and thrombocyte aggregation in all dilutions in a dose dependent fashion. In contrast to dilution with ISO and HS, respectively, dilution with HH as well as HT almost abolished coagulation (MCFExTEM from 57.3 ± 4.9 mm (native) to 1.7 ± 2.2 mm (HH 40% dilution; p < 0.0001) and to 6.6 ± 3.4 mm (HT

[Changes induced by hypertonic solutions in the transportation of calcium by the cardiac reticular sarcoplasma].

PubMed

Sierra, M; Holguín, J A

1979-01-01

In the sarcoplasmic reticulum of the myocardium, celular organell which function is to regulate the cytoplasmic concentration of calcium in contraction and relaxation, we have studied the effect of hypertonic solutions of sucrose between 1 and 6.96 times the normal tonicity in order to observe the behavior of the internal linked or free calcium of this structure, as well as to prove the hypothesis that hypertonic solutions encourage the calcium exit of the sarcoplasmatic reticulum with the resulting signs of contractures. The following results were obtained: 1. The ATP hydrolisis and calcium transport rate are 14% and 90% respectively of the maximum speeds of 10(-5) M in calcium, while for concentrations of 10(-7) M or ess of the said cation, the transport rates and the ATPase do not reach 5% of the maximum values. 2. Between 1 and 2.54 times of the normal tonicity the calcium uptake remains between 400 and 500 nmoles of calcium/mg protein/min, the transported amount of calcium varies between 14 and 16 nmoles/mg protein and the rate of the ATP hydrolysis increases a 37% to 0.4 M in sucrose. 3. Between 0.4 and 1.2 M in sucrose of 2.54 to 6.96 times the isotonicity, the calcium transport rate velocity as well as the ATP hydrolisis are strongly inhibited. The vesicles volume minimizes and the amount of linked calcium remains within the control values, proving that the capacity of linking this cathion is independent from sarcoplasmic reticulum volume. These results show that the sarcoplasmic reticulum is involved in the contractures induced by hypertonic solutions in intact cells, since the osmolarity increase produces changes of volume which results in a decrease of the calcium transportation velocity or in an increase of the exit of said cathion.

Hypertonic saline or mannitol for treating elevated intracranial pressure in traumatic brain injury: a meta-analysis of randomized controlled trials.

PubMed

Gu, Jiajie; Huang, Haoping; Huang, Yuejun; Sun, Haitao; Xu, Hongwu

2018-06-15

Hyperosmolar therapy is regarded as the mainstay for treatment of elevated intracranial pressure (ICP) in traumatic brain injury (TBI). This still has been disputed as application of hypertonic saline (HS) or mannitol for treating patients with severe TBI. Thus, this meta-analysis was performed to further compare the advantages and disadvantages of mannitol with HS for treating elevated ICP after TBI. We conducted a systematic search on PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Wan Fang Data, VIP Data, SinoMed, and China National Knowledge Infrastructure (CNKI) databases. Studies were included or not based on the quality assessment by the Jadad scale and selection criteria. Twelve RCTs with 438 patients were enrolled for the meta-analysis. The comparison of HS and mannitol indicated that they were close in field of improving function outcome (RR = 1.17, 95% CI 0.89 to 1.54, p = 0.258) and reducing intracranial pressure (MD = - 0.16, 95% CI: - 0.59 to 0.27, p = 0.473) and mortality (RR = 0.78, 95% CI 0.53 to 1.16, p = 0.216). The pooled relative risk of successful ICP control was 1.06 (95% CI: 1.00 to 1.13, p = 0.044), demonstrating that HS was more effective than mannitol in ICP management. Both serum sodium (WMD = 5.30, 95% CI: 4.37 to 6.22, p < 0.001) and osmolality (WMD = 3.03, 95% CI: 0.18 to 5.88, p = 0.037) were increased after injection of hypertonic saline. The results do not lend a specific recommendation to select hypertonic saline or mannitol as a first-line for the patients with elevated ICP caused by TBI. However, for the refractory intracranial hypertension, hypertonic saline seems to be preferred.

Intratesticular hypertonic sodium chloride solution treatment as a method of chemical castration in cattle.

PubMed

Neto, Olmiro Andrade; Gasperin, Bernardo G; Rovani, Monique T; Ilha, Gustavo F; Nóbrega, Janduí E; Mondadori, Rafael G; Gonçalves, Paulo B D; Antoniazzi, Alfredo Q

2014-10-15

Castration of male calves is necessary for trading to facilitate handling and prevent reproduction. However, some methods of castration are traumatic and lead to economic losses because of infection and myiasis. The objective of the present study was to evaluate the efficiency of intratesticular injection (ITI) of hypertonic sodium chloride (NaCl; 20%) solution in male calf castration during the first weeks of life. Forty male calves were allocated to one of the following experimental groups: negative control-surgically castrated immediately after birth; positive control -intact males; G1-ITI from 1- to 5-day old; G2-ITI from 15- to 20-day old; and G3-ITI from 25- to 30-day old. Intratesticular injection induced coagulative necrosis of Leydig cells and seminiferous tubules leading to extensive fibrosis. Testosterone secretion and testicular development were severely impaired in 12-month-old animals from G1 and G2 groups (P<0.05), in which no testicular structure and sperm cells were observed during breeding soundness evaluation. Rectal and scrotal temperatures were not affected by different procedures. In conclusion, ITI of hypertonic NaCl solution induces sterility and completely suppresses testosterone secretion when performed during the first 20 days of life. Copyright © 2014 Elsevier Inc. All rights reserved.

In Vitro impairment of whole blood coagulation and platelet function by hypertonic saline hydroxyethyl starch

PubMed Central

2011-01-01

Background Hypertonic saline hydroxyethyl starch (HH) has been recommended for first line treatment of hemorrhagic shock. Its effects on coagulation are unclear. We studied in vitro effects of HH dilution on whole blood coagulation and platelet function. Furthermore 7.2% hypertonic saline, 6% hydroxyethylstarch (as ingredients of HH), and 0.9% saline solution (as control) were tested in comparable dilutions to estimate specific component effects of HH on coagulation. Methods The study was designed as experimental non-randomized comparative in vitro study. Following institutional review board approval and informed consent blood samples were taken from 10 healthy volunteers and diluted in vitro with either HH (HyperHaes®, Fresenius Kabi, Germany), hypertonic saline (HT, 7.2% NaCl), hydroxyethylstarch (HS, HAES6%, Fresenius Kabi, Germany) or NaCl 0.9% (ISO) in a proportion of 5%, 10%, 20% and 40%. Coagulation was studied in whole blood by rotation thrombelastometry (ROTEM) after thromboplastin activation without (ExTEM) and with inhibition of thrombocyte function by cytochalasin D (FibTEM), the latter was performed to determine fibrin polymerisation alone. Values are expressed as maximal clot firmness (MCF, [mm]) and clotting time (CT, [s]). Platelet aggregation was determined by impedance aggregrometry (Multiplate) after activation with thrombin receptor-activating peptide 6 (TRAP) and quantified by the area under the aggregation curve (AUC [aggregation units (AU)/min]). Scanning electron microscopy was performed to evaluate HyperHaes induced cell shape changes of thrombocytes. Statistics: 2-way ANOVA for repeated measurements, Bonferroni post hoc test, p < 0.01. Results Dilution impaired whole blood coagulation and thrombocyte aggregation in all dilutions in a dose dependent fashion. In contrast to dilution with ISO and HS, respectively, dilution with HH as well as HT almost abolished coagulation (MCFExTEM from 57.3 ± 4.9 mm (native) to 1.7 ± 2.2 mm (HH 40

SABRE: a multicentre randomised control trial of nebulised hypertonic saline in infants hospitalised with acute bronchiolitis.

PubMed

Everard, Mark L; Hind, Daniel; Ugonna, Kelechi; Freeman, Jennifer; Bradburn, Mike; Cooper, Cindy L; Cross, Elizabeth; Maguire, Chin; Cantrill, Hannah; Alexander, John; McNamara, Paul S

2014-12-01

Acute bronchiolitis is the commonest cause for hospitalisation in infancy. Supportive care remains the cornerstone of current management and no other therapy has been shown to influence the course of the disease. It has been suggested that adding nebulised hypertonic saline to usual care may shorten the duration of hospitalisation. To determine whether hypertonic saline does have beneficial effects we undertook an open, multi-centre parallel-group, pragmatic RCT in ten UK hospitals. Infants admitted to hospital with a clinical diagnosis of acute bronchiolitis and requiring oxygen therapy were randomised to receive usual care alone or nebulised 3% hypertonic saline (HS) administered 6-hourly. Randomisation was within 4 h of admission. The primary outcome was time to being assessed as 'fit' for discharge with secondary outcomes including time to discharge, incidence of adverse events together with follow up to 28 days assessing patient centred health related outcomes. A total of 317 infants were recruited to the study. 158 infants were randomised to HS (141 analysed) and 159 to standard care (149 analysed). There was no difference between the two arms in time to being declared fit for discharge (hazard ratio: 0-95, 95% CI: 0.75-1.20) nor to actual discharge (hazard ratio: 0.97, 95% CI: 0.76-1.23). There was no difference in adverse events. One infant in the HS group developed bradycardia with desaturation. This study does not support the use of nebulised HS in the treatment of acute bronchiolitis over usual care with minimal handlings. NCT01469845. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Comparison of hypertonic saline versus normal saline on cytokine profile during CABG.

PubMed

Mazandarani, Mahnaz; Yousefshahi, Fardin; Abdollahi, Mohammad; Hamishehkar, Hadi; Barkhordari, Khosro; Boroomand, Mohammad Ali; Jalali, Arash; Ahmadi, Arezoo; Moharari, Reza Shariat; Bashirzadeh, Mona; Mojtahedzadeh, Mojtaba

2012-10-08

Blood contact with artificial surfaces of the extracorporeal circuit and ischemia-reperfusion injury in CABG with CPB, may lead to a systemic inflammatory response. Hypertonic saline have been recently investigated as a fluid in order to decrease inflammatory response and cytokines generation in patients undergo cardiac operations. Our purpose is to study the prophylactic effect of HS 5% infusion versus NS on serum IL-6 as an inflammatory & IL-10 as an anti-inflammatory biomarker in CABG patients. The present study is a randomized double-blinded clinical trial. 40 patients undergoing CABG were randomized to receive HS 5% or NS before operation. Blood samples were obtained after receiving HS or NS, just before operation, 24 and 48 hours post-operatively. Plasma levels of IL-6 and IL-10 were measured by ELISA. Patients received HS had lower levels of IL-6 and higher level of IL-10 compared with NS group, however these differences were not statistically significant. Results of this study suggest that pre-treatment with small volume hypertonic saline 5% may have beneficial effects on inflammatory response following CABG operation.

Sequence of Fibrinogen Proteolysis and Platelet Release after Intrauterine Infusion of Hypertonic Saline

PubMed Central

Nossel, H. L.; Wasser, J.; Kaplan, K. L.; Lagamma, K. S.; Yudelman, I.; Canfield, R. E.

1979-01-01

Plasma fibrinopeptide B (Bβ1-14 or FPB) immunoreactivity was studied by radioimmunoassay in patients who received intrauterine infusion of hypertonic saline to terminate pregnancy. FPB immunoreactivity increased with thrombin treatment (TIFPB) suggesting the presence of a larger FPB-containing peptide, since purified FPB is not altered by thrombin, whereas thrombin increases the immunoreactivity of Bβ1-42 (which includes FPB) 10-fold. TIFPB immunoreactivity in plasma, drawn 4 h after hypertonic saline infusion eluted from Sephadex G-50 similarly to isolated Bβ1-42. Streptokinase, incubated with normal plasma progressively generated TIFPB immunoreactivity, which showed a major component which eluted from Sephadex G-50 similarly to Bβ1-42. Streptokinase generated TIFPB much more rapidly in reptilase-treated plasma that contains fibrin I, (which still includes FPB), indicating that fibrin I is preferred over fibrinogen as a substrate for plasmin cleavage of arginine (Bβ42)-alanine (Bβ43). Serial studies were then made in 10 patients receiving intrauterine hypertonic saline. Fibrinopeptide A (FPA) levels rose immediately, reached a peak between 1 and 2 h, were declining at 4 h, and were normal at 24 and 48 h. TIFPB levels rose slightly in the 1st h, reached a peak at 4 h, and had returned to base-line values at 24 h. Serum fibrinogen degradation product levels were unchanged at 1 h, reached their highest level at 4 h, and were still markedly elevated at 24 and 48 h. Fibrinogen levels dropped slightly being lowest at 4 and 24 h. Platelet counts declined in parallel with the fibrinogen levels over the first 4 h, but continued to decrease through 48 h. Beta thromboglobulin (βTG) levels generally paralleled FPA levels whereas platelet factor 4 (PF4) levels showed only slight changes. The data indicate that immediately after intrauterine hypertonic saline infusion thrombin is formed that cleaves FPA from fibrinogen to produce fibrin I and releases βTG and PF4 from

Induction of the high-affinity Na(+)-dependent glutamate transport system XAG- by hypertonic stress in the renal epithelial cell line NBL-1.

PubMed Central

Ferrer-Martinez, A; Felipe, A; Nicholson, B; Casado, J; Pastor-Anglada, M; McGivan, J

1995-01-01

The high-affinity Na(+)-dependent glutamate transport system XAG- is induced (threefold increase in Vmax. with no change in Km) by hypertonicity in the renal epithelial cell line NBL-1. This effect is dependent on protein synthesis and glycosylation and is accompanied by an increase in EAAC1 mRNA levels. Other Na(+)-dependent transport systems in this cell line do not respond to hypertonic stress. In contrast to recent findings [Ruiz-Montasell, Gomez-Angelats, Casado, Felipe, McGivan and Pastor-Anglada (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 9569-9573] showing that increased system A activity after hyperosmotic shock results from induction of a regulatory protein, this is the first demonstration that hypertonicity may increase the expression of the gene for an amino acid transport protein itself. Images Figure 4 PMID:7654212

Comparison of hypertonic saline versus normal saline on cytokine profile during CABG

PubMed Central

2012-01-01

Background and the purpose of the study Blood contact with artificial surfaces of the extracorporeal circuit and ischemia-reperfusion injury in CABG with CPB, may lead to a systemic inflammatory response. Hypertonic saline have been recently investigated as a fluid in order to decrease inflammatory response and cytokines generation in patients undergo cardiac operations. Our purpose is to study the prophylactic effect of HS 5% infusion versus NS on serum IL-6 as an inflammatory & IL-10 as an anti-inflammatory biomarker in CABG patients. Methods The present study is a randomized double-blinded clinical trial. 40 patients undergoing CABG were randomized to receive HS 5% or NS before operation. Blood samples were obtained after receiving HS or NS, just before operation, 24 and 48 hours post-operatively. Plasma levels of IL-6 and IL-10 were measured by ELISA. Results and major conclusion Patients received HS had lower levels of IL-6 and higher level of IL-10 compared with NS group, however these differences were not statistically significant. Results of this study suggest that pre-treatment with small volume hypertonic saline 5% may have beneficial effects on inflammatory response following CABG operation. PMID:23351427

Modulation of jaw muscle spindle afferent activity following intramuscular injections with hypertonic saline.

PubMed

Ro, J Y; Capra, N F

2001-05-01

Transient noxious chemical stimulation of small diameter muscle afferents modulates jaw movement-related responses of caudal brainstem neurons. While it is likely that the effect is mediated from the spindle afferents in the mesencephalic nucleus (Vmes) via the caudally projecting Probst's tract, the mechanisms of pain induced modulations of jaw muscle spindle afferents is not known. In the present study, we tested the hypothesis that jaw muscle nociceptors gain access to muscle spindle afferents in the same muscle via central mechanisms and alter their sensitivity. Thirty-five neurons recorded from the Vmes were characterized as muscle spindle afferents based on their responses to passive jaw movements, muscle palpation, and electrical stimulation of the masseter nerve. Each cell was tested by injecting a small volume (250 microl) of either 5% hypertonic and/or isotonic saline into the receptor-bearing muscle. Twenty-nine units were tested with 5% hypertonic saline, of which 79% (23/29) showed significant modulation of mean firing rates (MFRs) during one or more phases of ramp-and-hold movements. Among the muscle spindle primary-like units (n = 12), MFRs of 4 units were facilitated, five reduced, two showed mixed responses and one unchanged. In secondary-like units (n = 17), MFRs of 9 were facilitated, three reduced and five unchanged. Thirteen units were tested with isotonic saline, of which 77% showed no significant changes of MFRs. Further analysis revealed that the hypertonic saline not only affected the overall output of muscle spindle afferents, but also increased the variability of firing and altered the relationship between afferent signal and muscle length. These results demonstrated that activation of muscle nociceptors significantly affects proprioceptive properties of jaw muscle spindles via central neural mechanisms. The changes can have deleterious effects on oral motor function as well as kinesthetic sensibility.

Hypertonic Saline Resuscitation Restores Inflammatory Cytokine Balance in Post-Traumatic Hemorrhagic Shock Patients

DTIC Science & Technology

2004-09-01

hypertonic saline with 6% dextran-70 (HSD) has been shown in experimental studies to reduce shock/resuscitation-induced inflammatory reactions and...hemodynamics and reestablishing inflammatory equilibrium [12]. Various immunoinflammatory alterations have been described in clinical and experimental ...ultimately causing greater morbidity and mortality [4]. Moreover, convincing experimental evidence indicates that conventional large-volume fluid

Nebulized hypertonic saline and recombinant human DNase in the treatment of pulmonary atelectasis in newborns.

PubMed

Dilmen, Ugur; Karagol, Belma Saygili; Oguz, Serife Suna

2011-06-01

The aim of this study was to compare and evaluate the efficacy of nebulized 3% hypertonic saline (HS) and recombinant human DNase (rhDNase) treatment for resolution of persistent atelectasis in newborns. Forty newborns (38 preterms) who did not respond to conventional treatment were enrolled to receive either nebulized 3% HS solution (n = 20) or rhDNase (n = 20) between September 2007 and March 2008. Clinical parameters, oxygen saturation and radiological response (chest X-ray scoring) were analyzed before and after administration of 3% HS or rhDNase. The patients of the nebulized 3% HS solution group improved better chest X-ray scores parameters than the patients of the rhDNase group: chest X-ray scores were 5.1 ± 1.9 vs 4.8 ± 1.7 before treatment and 1.0 ± 0.8 vs 2.1 ± 1.4 after treatment (P < 0.001). Resolution time of atelectasis did not differ between the two groups after whole treatment but the percentage of atelectasis resolution after 3 days treatment were 90% (18/20) in the 3% HS group and 70% (14/20) in the rhDNase group. The patients in the 3% HS group improved better also in clinical parameters in comparison to the rhDNase treatment. The difference of oxygen saturation before and after the treatment was 4.6 ± 0.8 in 3% HS group in comparison to 2.6 ± 0.1 in the rhDNase group (P < 0.05). All serum sodium levels were normal in two groups before and after the treatment modalities. This is the first study on the usefulness of nebulized 3% hypertonic saline solution in treating newborns with pulmonary atelectasis. In addition, 3% HS solution was a more effective therapeutic option on the basis of clinical and radiological improvement compared to rhDNase treatment in newborns with pulmonary atelectasis. © 2011 The Authors. Pediatrics International © 2011 Japan Pediatric Society.

Hypertonic Saline Resuscitation Restores Inflammatory Cytokine Balance in Post-Traumatic Hemorrhagic Shock Patients

DTIC Science & Technology

2004-08-01

immunocompetant cells experience bidirectional communication with hormones and cytokines [35,40]. Thus, despite compelling experimental findings, HSD has not...hypertonic saline with 6% dextran-70 (HSD) has been shown in experimental studies to reduce shock/resuscitation-induced inflammatory reactions and...alterations have been described in clinical and experimental investigations of post-traumatic hemorrhagic shock [13]. The initial immunological

Determination of fluid extraction and osmotic conductance sigma K in the lung with hypertonic NaCl infusion. I. Theory.

PubMed

Hunter, M; Lee, J

1992-11-01

A dispersion and extraction model of the lung is developed to assess how the infusion of hypertonic saline into the pulmonary artery changes the gravimetric density of pulmonary venous blood. The dispersion analysis is built on the indicator dilution curve measured for the pulmonary circulation. The extraction model consists of microvascular and interstitial compartments separated by a permeable pulmonary endothelium. Because the density of fluid extracted by the hypertonic disturbance is lower than the blood density, the extraction leads to a decrease in blood density. Two cases of fluid extraction are analyzed, a hypertonic infusion to elevate the osmotic pressure in the pulmonary arterial blood in the form of a step function and an infusion performed over a period of 1 sec. Both cases show that the dispersion significantly attenuates the changes in osmotic pressure and density as they are transported by the blood along the pulmonary vasculature. Because the model has taken into account the effect of dispersion and pulmonary blood flow, the equations developed here provide the basis to calculate from the density change in pulmonary venous blood the characteristics of osmotic extraction intrinsic to the lung.

Effect of Hypertonic Saline Infusion versus Normal Saline on Serum NGAL and Cystatin C Levels in Patients Undergoing Coronary Artery Bypass Graft

PubMed Central

Yousefshahi, Fardin; Bashirzadeh, Mona; Abdollahi, Mohammad; Mojtahedzadeh, Mojtaba; Salehiomran, Abbass; Jalali, Arash; Mazandarani, Mahnaz; Zaare, Elmira; Ahadi, Mehdi

2013-01-01

Background: Acute kidney injury (AKI) is a common and life-threatening complication following coronary artery bypass graft (CABG). Neutrophil gelatinase-associated lipocalin (NGAL) and Cystatin C have shown to be good predictive factors for AKI. Recently, there has been a growing interest in the use of hypertonic saline in cardiac operations. The purpose of this study was to evaluate the prophylactic anti-inflammatory effect of hypertonic saline (Group A) infusion versus normal saline (Group B) on serum NGAL and Cystatin C levels as the two biomarkers of AKI in CABG patients. Methods: This randomized double-blinded clinical trial recruited 40 patients undergoing CABG in Tehran Heart Center, Tehran, Iran. After applying exclusion criteria, the effects of preoperative hypertonic saline (294 meq Na) versus normal saline (154 meq Na) infusion on serum NGAL and Cystatin C levels were investigated in three intervals: before surgery and 24 and 48 hours postoperatively. The probable intraoperative or postoperative confounders, including pump time, cross-clamp time, heart rate, systolic and diastolic blood pressures, central venous pressure, arterial pH, partial pressure of arterial oxygen, fraction of inspired oxygen, blood sugar, Na, K, Mg, hemoglobins, white blood cells, hematocrits, and platelets, were recorded and compared between the two groups of study. Results: The study population comprised 40 patients, including 25 (62.5%) males, at a, mean age ± SD of 61.75 ± 8.13 years. There were no statistically significant differences between the patients’ basic, intraoperative, and postoperative characteristics, including intraoperative and postoperative hemodynamic variables and supports such as inotropic use. Intra-aortic balloon pump use and mortality were not seen in our cases. Three patients in the normal saline group and one patient in the hypertonic saline group had serum NGAL levels greater than 400 ng/ml. Moreover, 10 patients in Group A and 17 patients in group

Effect of Hypertonic Saline Infusion versus Normal Saline on Serum NGAL and Cystatin C Levels in Patients Undergoing Coronary Artery Bypass Graft.

PubMed

Yousefshahi, Fardin; Bashirzadeh, Mona; Abdollahi, Mohammad; Mojtahedzadeh, Mojtaba; Salehiomran, Abbass; Jalali, Arash; Mazandarani, Mahnaz; Zaare, Elmira; Ahadi, Mehdi

2013-01-01

Acute kidney injury (AKI) is a common and life-threatening complication following coronary artery bypass graft (CABG). Neutrophil gelatinase-associated lipocalin (NGAL) and Cystatin C have shown to be good predictive factors for AKI. Recently, there has been a growing interest in the use of hypertonic saline in cardiac operations. The purpose of this study was to evaluate the prophylactic anti-inflammatory effect of hypertonic saline (Group A) infusion versus normal saline (Group B) on serum NGAL and Cystatin C levels as the two biomarkers of AKI in CABG patients. This randomized double-blinded clinical trial recruited 40 patients undergoing CABG in Tehran Heart Center, Tehran, Iran. After applying exclusion criteria, the effects of preoperative hypertonic saline (294 meq Na) versus normal saline (154 meq Na) infusion on serum NGAL and Cystatin C levels were investigated in three intervals: before surgery and 24 and 48 hours postoperatively. The probable intraoperative or postoperative confounders, including pump time, cross-clamp time, heart rate, systolic and diastolic blood pressures, central venous pressure, arterial pH, partial pressure of arterial oxygen, fraction of inspired oxygen, blood sugar, Na, K, Mg, hemoglobins, white blood cells, hematocrits, and platelets, were recorded and compared between the two groups of study. The study population comprised 40 patients, including 25 (62.5%) males, at a, mean age ± SD of 61.75 ± 8.13 years. There were no statistically significant differences between the patients' basic, intraoperative, and postoperative characteristics, including intraoperative and postoperative hemodynamic variables and supports such as inotropic use. Intra-aortic balloon pump use and mortality were not seen in our cases. Three patients in the normal saline group and one patient in the hypertonic saline group had serum NGAL levels greater than 400 ng/ml. Moreover, 10 patients in Group A and 17 patients in group B showed a rise in serum

Clinical and pathological characteristics of HIV- and HHV-8–negative Castleman disease

PubMed Central

Yu, Li; Tu, Meifeng; Cortes, Jorge; Xu-Monette, Zijun Y.; Miranda, Roberto N.; Zhang, Jun; Orlowski, Robert Z.; Neelapu, Sattva; Boddu, Prajwal C.; Akosile, Mary A.; Uldrick, Thomas S.; Yarchoan, Robert; Medeiros, L. Jeffrey; Li, Yong; Fajgenbaum, David C.

2017-01-01

Castleman disease (CD) comprises 3 poorly understood lymphoproliferative variants sharing several common histopathological features. Unicentric CD (UCD) is localized to a single region of lymph nodes. Multicentric CD (MCD) manifests with systemic inflammatory symptoms and organ dysfunction due to cytokine dysregulation and involves multiple lymph node regions. Human herpesvirus 8 (HHV-8) causes MCD (HHV-8–associated MCD) in immunocompromised individuals, such as HIV-infected patients. However, >50% of MCD cases are HIV and HHV-8 negative (defined as idiopathic [iMCD]). The clinical and biological behavior of CD remains poorly elucidated. Here, we analyzed the clinicopathologic features of 74 patients (43 with UCD and 31 with iMCD) and therapeutic response of 96 patients (43 with UCD and 53 with iMCD) with HIV-/HHV-8–negative CD compared with 51 HIV-/HHV-8–positive patients. Systemic inflammatory symptoms and elevated inflammatory factors were more common in iMCD patients than UCD patients. Abnormal bone marrow features were more frequent in iMCD (77.0%) than UCD (45%); the most frequent was plasmacytosis, which was seen in 3% to 30.4% of marrow cells. In the lymph nodes, higher numbers of CD3+ lymphocytes (median, 58.88 ± 20.57) and lower frequency of CD19+/CD5+ (median, 5.88 ± 6.52) were observed in iMCD patients compared with UCD patients (median CD3+ cells, 43.19 ± 17.37; median CD19+/CD5+ cells, 17.37 ± 15.80). Complete surgical resection is a better option for patients with UCD. Siltuximab had a greater proportion of complete responses and longer progression-free survival (PFS) for iMCD than rituximab. Centricity, histopathological type, and anemia significantly impacted PFS. This study reveals that CD represents a heterogeneous group of diseases with differential immunophenotypic profiling and treatment response. PMID:28100459

Aldosterone does not alter endothelin B receptor signaling in the inner medullary collecting duct.

PubMed

Ramkumar, Nirupama; Stuart, Deborah; Yang, Tianxin; Kohan, Donald E

2017-03-01

Recent studies suggest that aldosterone-mediated sulfenic acid modification of the endothelin B receptor (ETB) promotes renal injury in an ischemia/reperfusion model through reduced ETB-stimulated nitric oxide production. Similarly, aldosterone inactivation of ETB signaling promotes pulmonary artery hypertension. Consequently, we asked whether aldosterone inhibits collecting duct ETB signaling; this could promote fluid retention since CD ETB exerts natriuretic and diuretic effects. A mouse inner medullary collecting duct cell line (IMCD3) was treated with aldosterone for 48 h followed by sarafotoxin-6c, an ETB-selective agonist, and extracellular signal-related kinase 1/2 (ERK) phosphorylation assessed. S6c increased the phospho/total-ERK ratio similarly in control and aldosterone-treated cells (aldosterone alone increased phospho/total-ERK). Since cultured IMCD cell lines lack ETB inhibited AVP signaling, the effect of S6c on AVP-stimulated cAMP in acutely isolated IMCD was assessed. Rats (have much higher CD ETB expression than mice) were exposed to 3 days of a normal or low Na + diet, or low Na + diet + desoxycorticosterone acetate. S6c inhibited AVP-stimulated cAMP in rat IMCD by the same degree in the high mineralocorticoid groups compared to controls. Finally, S6c-stimulated cGMP accumulation in cultured IMCD, or S6c-stimulated nitric oxide or cGMP in acutely isolated IMCD, was not affected by prior aldosterone exposure. These findings provide evidence that aldosterone does not modify ETB effects on ERK phosphorylation, AVP-dependent cAMP inhibition, or NO/cGMP accumulation in the IMCD Thus, while aldosterone can inhibit endothelial cell ETB activity to promote hypertension and injury, this response does not appear to occur in the IMCD. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Urinary concentrating defect in mice with selective deletion of phloretin-sensitive urea transporters in the renal collecting duct

PubMed Central

Fenton, Robert A.; Chou, Chung-Lin; Stewart, Gavin S.; Smith, Craig P.; Knepper, Mark A.

2004-01-01

To investigate the role of inner medullary collecting duct (IMCD) urea transporters in the renal concentrating mechanism, we deleted 3 kb of the UT-A urea transporter gene containing a single 140-bp exon (exon 10). Deletion of this segment selectively disrupted expression of the two known IMCD isoforms of UT-A, namely UT-A1 and UT-A3, producing UT-A1/3-/- mice. In isolated perfused IMCDs from UT-A1/3-/- mice, there was a complete absence of phloretin-sensitive or vasopressin-stimulated urea transport. On a normal protein intake (20% protein diet), UT-A1/3-/- mice had significantly greater fluid consumption and urine flow and a reduced maximal urinary osmolality relative to wild-type controls. These differences in urinary concentrating capacity were nearly eliminated when urea excretion was decreased by dietary protein restriction (4% by weight), consistent with the 1958 Berliner hypothesis stating that the chief role of IMCD urea transport in the concentrating mechanism is the prevention of urea-induced osmotic diuresis. Analysis of inner medullary tissue after water restriction revealed marked depletion of urea in UT-A1/3-/- mice, confirming the concept that phloretin-sensitive IMCD urea transporters play a central role in medullary urea accumulation. However, there were no significant differences in mean inner medullary Na+ or Cl- concentrations between UT-A1/3-/- mice and wild-type controls, indicating that the processes that concentrate NaCl were intact. Thus, these results do not corroborate the predictions of passive medullary concentrating models stating that NaCl accumulation in the inner medulla depends on rapid vasopressin-regulated urea transport across the IMCD epithelium. PMID:15123796

Hypertonic sodium lactate reverses brain oxygenation and metabolism dysfunction after traumatic brain injury.

PubMed

Millet, A; Cuisinier, A; Bouzat, P; Batandier, C; Lemasson, B; Stupar, V; Pernet-Gallay, K; Crespy, T; Barbier, E L; Payen, J F

2018-06-01

The mechanisms by which hypertonic sodium lactate (HSL) solution act in injured brain are unclear. We investigated the effects of HSL on brain metabolism, oxygenation, and perfusion in a rodent model of diffuse traumatic brain injury (TBI). Thirty minutes after trauma, anaesthetised adult rats were randomly assigned to receive a 3 h infusion of either a saline solution (TBI-saline group) or HSL (TBI-HSL group). The sham-saline and sham-HSL groups received no insult. Three series of experiments were conducted up to 4 h after TBI (or equivalent) to investigate: 1) brain oedema using diffusion-weighted magnetic resonance imaging and brain metabolism using localized 1 H-magnetic resonance spectroscopy (n = 10 rats per group). The respiratory control ratio was then determined using oxygraphic analysis of extracted mitochondria, 2) brain oxygenation and perfusion using quantitative blood-oxygenation-level-dependent magnetic resonance approach (n = 10 rats per group), and 3) mitochondrial ultrastructural changes (n = 1 rat per group). Compared with the TBI-saline group, the TBI-HSL and the sham-operated groups had reduced brain oedema. Concomitantly, the TBI-HSL group had lower intracellular lactate/creatine ratio [0.049 (0.047-0.098) vs 0.097 (0.079-0.157); P < 0.05], higher mitochondrial respiratory control ratio, higher tissue oxygen saturation [77% (71-79) vs 66% (55-73); P < 0.05], and reduced mitochondrial cristae thickness in astrocytes [27.5 (22.5-38.4) nm vs 38.4 (31.0-47.5) nm; P < 0.01] compared with the TBI-saline group. Serum sodium and lactate concentrations and serum osmolality were higher in the TBI-HSL than in the TBI-saline group. These findings indicate that the hypertonic sodium lactate solution can reverse brain oxygenation and metabolism dysfunction after traumatic brain injury through vasodilatory, mitochondrial, and anti-oedema effects. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Intravenous hypertonic saline solution (7.5%) and oral electrolytes to treat of calves with noninfectious diarrhea and metabolic acidosis.

PubMed

Leal, M L R; Fialho, S S; Cyrillo, F C; Bertagnon, H G; Ortolani, E L; Benesi, F J

2012-01-01

The aim of this study was to compare the efficacy of treating osmotic diarrhea and dehydration in calves with hypertonic saline solution (HSS) IV, isotonic electrolyte solution (IES) PO, and a combination of these 2 solutions (HSS + IES). Eighteen male calves 8-30 days of age were used to evaluate the efficacy of 3 methods of fluid therapy after induction of osmotic diarrhea and dehydration. The diarrhea and dehydration were induced by administration of saccharose, spironolactone, and hydrochlorothiazide for 48 hours. The animals were randomly divided into 3 experimental groups: Group 1: 7.2% hypertonic saline solution-HSS (5 mL/kg IV); Group 2: oral isotonic electrolyte solution IES (60 mL/kg PO); or Group 3: HSS+IES. Clinical signs and laboratory finding observed 48 hours post-induction (Time 0) included diarrhea, dehydration, lethargy, and metabolic acidosis. Calves treated with HSS + IES experienced decreases in hematocrit, total protein concentration, albumin concentration, urea nitrogen concentration, and plasma volume as well as increases in blood pH, blood bicarbonate concentration, and central venous pressure between 1 and 3 hours post-treatment. These findings also were observed in animals treated with IES, however, at a slower rate than in the HSS + IES-treated animals. Animals treated with HSS continued to display signs of dehydration, lethargy, and metabolic acidosis 24 hours post-treatment. Treatment with a combination of HSS and IES produced rapid and sustainable correction of hypovolemia and metabolic acidosis in calves with noninfections diarrhea and dehydration. Copyright © 2012 by the American College of Veterinary Internal Medicine.

Axial hypertonicity in Parkinson’s disease: Direct measurements of trunk and hip torque

PubMed Central

Wright, W.G.; Gurfinkel, V.S.; Nutt, J.; Horak, F.B.; Cordo, P.J.

2007-01-01

A cardinal feature of Parkinson’s disease (PD) is muscle hypertonicity, i.e. rigidity. Little is known about the axial tone in PD or the relation of hypertonia to functional impairment. We quantified axial rigidity to assess its relation to motor symptoms as measured by UPDRS and determine whether rigidity is affected by levodopa treatment. Axial rigidity was measured in 12 PD and 14 age-matched controls by directly measuring torsional resistance of the longitudinal axis to twisting (±10°). Feet were rotated relative to fixed hips (Hip Tone) or feet and hips were rotated relative to fixed shoulders (Trunk Tone). To assess tonic activity only, low constant velocity rotation (1°/s) and low acceleration (<12°/s2) were used to avoid eliciting phasic sensorimotor responses. Subjects stood during testing without changing body orientation relative to gravity. Body parts fixed against rotation could translate laterally within the boundaries of normal postural sway, but could not rotate. PD OFF-medication had higher axial rigidity (p<0.05) in hips (5.07 Nm) and trunk (5.30 Nm) than controls (3.51 Nm and 4.46 Nm, respectively), which didn’t change with levodopa (p>0.10). Hip-to-trunk torque ratio was greater in PD than controls (p<0.05) and unchanged by levodopa (p=0.28). UPDRS scores were significantly correlated with hip rigidity for PD OFF-medication (r=0.73, p<0.05). Torsional resistance to clockwise versus counter-clockwise axial rotation was more asymmetrical in PD than controls (p<0.05), however, there was no correspondence between direction of axial asymmetry and side of disease onset. In conclusion, these findings concerning hypertonicity may underlie functional impairments of posture and locomotion in PD. The absence of a levodopa effect on axial tone suggests axial and appendicular tone are controlled by separate neural circuits. PMID:17692315

Generating chimeric mice from embryonic stem cells via vial coculturing or hypertonic microinjection.

PubMed

Lee, Kun-Hsiung

2014-01-01

The generation of a fertile embryonic stem cell (ESC)-derived or F0 (100 % coat color chimerism) mice is the final criterion in proving that the ESC is truly pluripotent. Many methods have been developed to produce chimeric mice. To date, the most popular methods for generating chimeric embryos is well sandwich aggregation between zona pellucida (ZP) removed (denuded) 2.5-day post-coitum (dpc) embryos and ESC clumps, or direct microinjection of ESCs into the cavity (blastocoel) of 3.5-dpc blastocysts. However, due to systemic limitations and the disadvantages of conventional microinjection, aggregation, and coculturing, two novel methods (vial coculturing and hypertonic microinjection) were developed in recent years at my laboratory.Coculturing 2.5-dpc denuded embryos with ESCs in 1.7-mL vials for ~3 h generates chimeras that have significantly high levels of chimerism (including 100 % coat color chimerism) and germline transmission. This method has significantly fewer instrumental and technological limitations than existing methods, and is an efficient, simple, inexpensive, and reproducible method for "mass production" of chimeric embryos. For laboratories without a microinjection system, this is the method of choice for generating chimeric embryos. Microinjecting ESCs into a subzonal space of 2.5-dpc embryos can generate germline-transmitted chimeras including 100 % coat color chimerism. However, this method is adopted rarely due to the very small and tight space between ZP and blastomeres. Using a laser pulse or Piezo-driven instrument/device to help introduce ESCs into the subzonal space of 2.5-dpc embryos demonstrates the superior efficiency in generating ESC-derived (F0) chimeras. Unfortunately, due to the need for an expensive instrument/device and extra fine skill, not many studies have used either method. Recently, ESCs injected into the large subzonal space of 2.5-dpc embryos in an injection medium containing 0.2-0.3 M sucrose very efficiently generated

The UT-A Urea Transporter Promoter, UT-Aα, Targets Principal Cells of the Renal Inner Medullary Collecting Duct

PubMed Central

Fenton, Robert A.; Shodeinde, Adetola; Knepper, Mark A.

2006-01-01

The urea transporters, UT-A1 and UT-A3, two members of the UT-A gene family, are localized to the terminal portion of the inner medullary collecting duct (IMCD). In this manuscript, we demonstrate that 4.2-kb of the 5′-flanking region of the UT-A gene (UT-Aα promoter) is sufficient to drive the IMCD-specific expression of a heterologous reporter gene, β-galactosidase (β-Gal), in transgenic mice. RT-PCR, immunoblotting and immunohistochemistry demonstrate that within the kidney, transgene expression is confined to the terminal portion of the IMCD. Co-localization studies with aquaporin 2 show that expression is localized to the principal cells of the IMCD2 and IMCD3 regions. Utilizing β-Gal activity assays, we further show that within the kidney, the β-Gal transgene can be regulated by both water restriction and glucocorticoids, similar to the regulation of the endogenous UT-A gene. These results demonstrate that 4.2-kb of the UT-Aα promoter is sufficient to drive expression of a heterologous reporter gene in a tissue-specific and cell-specific fashion in transgenic mice PMID:16091580

The transport systems of Ventricaria ventricosa: hypotonic and hypertonic turgor regulation.

PubMed

Bisson, M A; Beilby, M J

2002-11-01

The time course of hypertonic and hypotonic turgor regulation was studied in Ventricaria (Valonia) using pressure probe and I/V(current-voltage) analysis. Of 11 cells, 9 exhibited hypertonic turgor regulation, ranging from 100% regulation in 150 min to 14% regulation (14% recovery of the decrease in turgor) in 314 min. Some cells began regulating immediately, others took up to 90 min to begin. The resting PD (potential difference) became more positive in most cells. The I/V characteristics became more nonlinear with high resistance between -150 and -20 mV and negative conductance region near -70 mV. Prolonged (16 sec) voltage clamps to negative levels (-100 to -150 mV) showed progressively more rapid current turn-off, but subsequent I/V characteristics were not affected. Clamping to +150 mV, however, abolished the high conductance between -50 and +100 mV to yield a uniform high resistance I/V characteristic, similar to that in high [K+]o. Decreasing illumination from 2.02 micromol sec(-1) m(-2) to 0.5 micromol sec(-1)1 m(-2) had a similar effect. Two out of a total of three cells exhibited hypotonic turgor regulation. Both cells started regulating within minutes and achieved near 50% regulation within 50 min. The PD became more negative. The I/V curves exhibited high resistance between +50 and +150 mV. The characteristics were similar to those in cells exposed to low [K+]o. Prolonged voltage clamps to both negative and positive levels showed slow current increase. Decreased illumination increased the membrane resistance.

Small-volume fluid resuscitation with hypertonic saline prevents inflammation but not mortality in a rat model of hemorrhagic shock.

PubMed

Bahrami, Soheyl; Zimmermann, Klaus; Szelényi, Zoltán; Hamar, János; Scheiflinger, Friedrich; Redl, Heinz; Junger, Wolfgang G

2006-03-01

Hemorrhage remains a primary cause of death in civilian and military trauma. Permissive hypotensive resuscitation is a possible approach to reduce bleeding in patients until they can be stabilized in an appropriate hospital setting. Small-volume resuscitation with hypertonic saline (HS) is of particular interest because it allows one to modulate the inflammatory response to hemorrhage and trauma. Here, we tested the utility of permissive hypotensive resuscitation with hypertonic fluids in a rat model of hemorrhagic shock. Animals were subjected to massive hemorrhage [mean arterial pressure (MAP) = 30 - 35 mmHg for 2 h until decompensation] and partially resuscitated with a bolus dose of 4 mL/kg of 7.5% NaCl (HS), hypertonic hydroxyl ethyl starch (HHES; hydroxyl ethyl starch + 7.5% NaCl), or normal saline (NS) followed by additional infusion of Ringer solution to maintain MAP at 40 to 45 mmHg for 40 min (hypotensive state). Finally, animals were fully resuscitated with Ringer solution and the heparinized shed blood. Hypotensive resuscitation with NS caused a significant increase in plasma interleukin (IL)-1beta, IL-6, IL-2, interferon gamma (IFNgamma), IL-10, and granulocyte-macrophage colony stimulating factor (GM-CSF). This increase was blocked by treatment with HS. HHES treatment significantly reduced the increase of IL-1beta and IL-2 but not that of the other cytokines studied. Despite the strong effects of HS and HHES on cytokine production, both treatments had little effect on plasma lactate, base excess (BE), white blood cell (WBC) count, myeloperoxidase (MPO) content, and the wet/dry weight ratio of the lungs. Moreover, on day 7 after shock, the survival rate in rats treated with HS was markedly, but not significantly, lower than that of NS-treated animals (47% vs. 63%, respectively). In summary, hypotensive resuscitation with hypertonic fluids reduces the inflammatory response but not lung tissue damage or mortality after severe hemorrhagic shock.

Fourteen-Day Subacute Intravenous Toxicity Study of Hypertonic Saline/ Dextran 70 (Trade name) and its Constituents in New Zealand White Rabbits

DTIC Science & Technology

1989-11-01

of Hypertonic Saline/Dextran 70C and its Constituents in New Zealand White Rabbits," Toxicology Series 248, was audited on 20 October 1989. CAROLYNM...at tA "e a .6 L C C o L a L Lm .. .. a. a4 1 . . ao 3.&ow2 aCCa .0 00 c -C a- 4;. *; a 0O .. t x.T 2Cu u . u uu0 0 Uc L 01 2.:4A.1 4xa&C -I - -N .CA -e

Airway inflammation and mannitol challenge test in COPD

PubMed Central

2011-01-01

Background Eosinophilic airway inflammation has successfully been used to tailor anti-inflammatory therapy in chronic obstructive pulmonary disease (COPD). Airway hyperresponsiveness (AHR) by indirect challenges is associated with airway inflammation. We hypothesized that AHR to inhaled mannitol captures eosinophilia in induced sputum in COPD. Methods Twenty-eight patients (age 58 ± 7.8 yr, packyears 40 ± 15.5, post-bronchodilator FEV1 77 ± 14.0%predicted, no inhaled steroids ≥4 wks) with mild-moderate COPD (GOLD I-II) completed two randomized visits with hypertonic saline-induced sputum and mannitol challenge (including sputum collection). AHR to mannitol was expressed as response-dose-ratio (RDR) and related to cell counts, ECP, MPO and IL-8 levels in sputum. Results There was a positive correlation between RDR to mannitol and eosinophil numbers (r = 0.47, p = 0.03) and level of IL-8 (r = 0.46, p = 0.04) in hypertonic saline-induced sputum. Furthermore, significant correlations were found between RDR and eosinophil numbers (r = 0.71, p = 0.001), level of ECP (r = 0.72, p = 0.001), IL-8 (r = 0.57, p = 0.015) and MPO (r = 0.64, p = 0.007) in sputum collected after mannitol challenge. ROC-curves showed 60% sensitivity and 100% specificity of RDR for >2.5% eosinophils in mannitol-induced sputum. Conclusions In mild-moderate COPD mannitol hyperresponsiveness is associated with biomarkers of airway inflammation. The high specificity of mannitol challenge suggests that the test is particularly suitable to exclude eosinophilic airways inflammation, which may facilitate individualized treatment in COPD. Trial registration Netherlands Trial Register (NTR): NTR1283 PMID:21241520

Comparison of different drying methods on Chinese ginger (Zingiber officinale Roscoe): Changes in volatiles, chemical profile, antioxidant properties, and microstructure.

PubMed

An, Kejing; Zhao, Dandan; Wang, Zhengfu; Wu, Jijun; Xu, Yujuan; Xiao, Gengsheng

2016-04-15

Nowadays, food industry is facing challenges in preserving better quality of fruit and vegetable products after processing. Recently, many attentions have been drawn to ginger rhizome processing due to its numerous health promoting properties. In our study, ginger rhizome slices were subjected to air-drying (AD), freeze drying (FD), infrared drying (IR), microwave drying (MD) and intermittent microwave & convective drying (IM&CD). Quality attributes of the dried samples were compared in terms of volatile compounds, 6, 8, 10-gingerols, 6-shogaol, antioxidant activities and microstructure. Results showed that AD and IR were good drying methods to preserve volatiles. FD, IR and IM&CD led to higher retention of gingerols, TPC, TFC and better antioxidant activities. However, FD and IR had relative high energy consumption and drying time. Therefore, considering about the quality retention and energy consumption, IM&CD would be very promising for thermo sensitive material. Copyright © 2015 Elsevier Ltd. All rights reserved.

Trehalose metabolism genes of Aphelenchoides besseyi (Nematoda: Aphelenchoididae) in hypertonic osmotic pressure survival

PubMed Central

Chen, Qiaoli; Li, Danlei; Zhang, Ruizhi; Ling, Yaming

2017-01-01

ABSTRACT Some organisms can survive extreme desiccation caused by hypertonic osmotic pressure by entering a state of suspended animation known as osmobiosis. The free-living mycophagous nematode Aphelenchoides besseyi can be induced to enter osmobiosis by soaking in osmolytes. It is assumed that sugars (in particular trehalose) are instrumental for survival under environmental stress. In A. besseyi, two putative trehalose-6-phosphate synthase genes (TPS) encoding enzymes catalyzing trehalose synthesis, and a putative trehalase gene (TRE) encoding enzymes that catalyze hydrolysis of trehalose were identified and then characterized based on their transcriptome. RT-qPCR analyses showed that each of these genes is expressed as mRNA when A. besseyi is entering in, during and recovering from osmobiosis, but only for certain periods. The changes of TRE activity were consistent with the transcript level changes of the TRE gene, and the trehalose level declined at certain periods when the nematodes were in, as well as recovering from, osmobiosis; this suggested that the hydrolysis of threhalose is essential. The feeding method of RNA interference (RNAi) was used to temporarily knock down the expression of each of the TPS and TRE genes. No obviously different phenotype was observed from any of the genes silenced individually or simultaneously, but the survival under hypertonic osmotic pressure reduced significantly and the recovery was delayed. These results indicated that trehalose metabolism genes should play a role in osmobiosis regulation and function within a restricted time frame. PMID:28396490

CNS sites activated by renal pelvic epithelial sodium channels (ENaCs) in response to hypertonic saline in awake rats.

PubMed

Goodwill, Vanessa S; Terrill, Christopher; Hopewood, Ian; Loewy, Arthur D; Knuepfer, Mark M

2017-05-01

In some patients, renal nerve denervation has been reported to be an effective treatment for essential hypertension. Considerable evidence suggests that afferent renal nerves (ARN) and sodium balance play important roles in the development and maintenance of high blood pressure. ARN are sensitive to sodium concentrations in the renal pelvis. To better understand the role of ARN, we infused isotonic or hypertonic NaCl (308 or 500mOsm) into the left renal pelvis of conscious rats for two 2hours while recording arterial pressure and heart rate. Subsequently, brain tissue was analyzed for immunohistochemical detection of the protein Fos, a marker for neuronal activation. Fos-immunoreactive neurons were identified in numerous sites in the forebrain and brainstem. These areas included the nucleus tractus solitarius (NTS), the lateral parabrachial nucleus, the paraventricular nucleus of the hypothalamus (PVH) and the supraoptic nucleus (SON). The most effective stimulus was 500mOsm NaCl. Activation of these sites was attenuated or prevented by administration of benzamil (1μM) or amiloride (10μM) into the renal pelvis concomitantly with hypertonic saline. In anesthetized rats, infusion of hypertonic saline but not isotonic saline into the renal pelvis elevated ARN activity and this increase was attenuated by simultaneous infusion of benzamil or amiloride. We propose that renal pelvic epithelial sodium channels (ENaCs) play a role in activation of ARN and, via central visceral afferent circuits, this system modulates fluid volume and peripheral blood pressure. These pathways may contribute to the development of hypertension. Copyright © 2016 Elsevier B.V. All rights reserved.

Hypertonic saline in paediatric traumatic brain injury: a review of nine years' experience with 23.4% hypertonic saline as standard hyperosmolar therapy.

PubMed

Piper, B J; Harrigan, P W

2015-03-01

We describe the protocolised use of 23.4% hypertonic saline solution (HTS) for intracranial hypertension in the context of traumatic brain injury in the paediatric population. This study represents the largest published data on the use of 23.4% HTS in the paediatric population. In this retrospective cohort, we focus on the efficacy, biochemical and metabolic consequences of 23.4% HTS administration in a Level 1 paediatric trauma centre. Mortality in the first seven days was 6% (2/32) with a mean intensive care unit length-of-stay of ten days (range 2 to 25, standard deviation [SD] 6). All-cause hospital mortality was 6%, with no deaths after the seven-day study period. Mean intracranial pressure (ICP) response to HTS was 10 mmHg (range 1 to 30, SD 8). For biochemistry data, the mean highest daily serum sodium was 148 mmol/l (139 to 161, SD 6), mean highest serum chloride was 115 mmol/l (range 101 to 132, SD 8) with matched mean serum base excess of -1.5 mmol/l (range 2 to -8, SD 3) and mean peak serum creatinine was 73 mmol/l (range 32 to 104, SD 32). Glasgow outcome scores of >3 (independent function) were achieved in 74% of patients. We describe the use of 23.4% HTS, demonstrating it to be a practical and efficacious method of delivering osmoles and may be advantageous in minimising total fluid volume. Thus, the bolus versus infusion debate may best be served via combining both approaches.

Hypertonic Saline Reduces Vascular Leakage in a Mouse Model of Severe Dengue

PubMed Central

Tan, Kar Wai; Angeli, Veronique; Moochhala, Shabbir; Ooi, Eng Eong; Alonso, Sylvie

2013-01-01

Dengue (DEN) is a mosquito-borne viral disease and represents a serious public health threat and an economical burden throughout the tropics. Dengue clinical manifestations range from mild acute febrile illness to severe DEN hemorrhagic fever/DEN shock syndrome (DHF/DSS). Currently, resuscitation with large volumes of isotonic fluid remains the gold standard of care for DEN patients who develop vascular leakage and shock. Here, we investigated the ability of small volume of hypertonic saline (HTS) suspensions to control vascular permeability in a mouse model of severe DEN associated with vascular leakage. Several HTS treatment regimens were considered and our results indicated that a single bolus of 7.5% NaCl at 4 mL per kg of body weight administered at the onset of detectable vascular leakage rapidly and significantly reduced vascular leak for several days after injection. This transient reduction of vascular leakage correlated with reduced intestine and liver damage with restoration of the hepatic functions, and resulted in delayed death of the infected animals. Mechanistically, we showed that HTS did not directly impact on the viral titers but resulted in lower immune cells counts and decreased systemic levels of soluble mediators involved in vascular permeability. In addition, we demonstrated that neutrophils do not play a critical role in DEN-associated vascular leakage and that the therapeutic effect of HTS is not mediated by its impact on the neutrophil counts. Together our data indicate that HTS treatment can transiently but rapidly reduce dengue-associated vascular leakage, and support the findings of a recent clinical trial which evaluated the efficacy of a hypertonic suspension to impact on vascular permeability in DSS children. PMID:23637867

Integrin linked kinase regulates the transcription of AQP2 by NFATC3.

PubMed

Hatem-Vaquero, Marco; Griera, Mercedes; Giermakowska, Wieslawa; Luengo, Alicia; Calleros, Laura; Gonzalez Bosc, Laura V; Rodríguez-Puyol, Diego; Rodríguez-Puyol, Manuel; De Frutos, Sergio

2017-09-01

Two processes are associated with progressive loss of renal function: 1) decreased aquaporin-2 (AQP2) expression and urinary concentrating capacity (Nephrogenic Diabetes Insipidus, NDI); and 2) changes in extracellular matrix (ECM) composition, e.g. increased collagen I (Col I) deposition, characteristic of tubule-interstitial fibrosis. AQP2 expression is regulated by both the ECM-to-intracellular scaffold protein integrin-linked kinase (ILK) by NFATc/AP1 and other transcription factors. In the present work, we used in vivo and in vitro approaches to examine ILK participation in NFATc3/AP-1-mediated increases in AQP2 gene expression. Both NFATc3 knock-out mice and ILK conditional-knockdown mice (cKD-ILK) display symptoms of NDI (polyuria and reduced AQP2 expression). NFATc3 is upregulated in the renal medulla tubular cells of cKD-ILK mice but with reduced nuclear localization. Inner medullary collecting duct mIMCD3 cells were subjected to ILK depletion and transfected with reporter plasmids. Pharmacological activators or inhibitors determined the effect of ILK activity on NFATc/AP-1-dependent increases in transcription of AQP2. Finally, mIMCD3 cultured on Col I showed reduced activity of the ILK/GSK3β/NFATc/AQP2 axis, suggesting this pathway is a potential target for therapeutic treatment of NDI. Copyright © 2017 Elsevier B.V. All rights reserved.

[Intra-amniotic administration of prostaglandin F 2 alpha, 12-methyl-prostaglandin F 2 alpha and hypertonic sodium chloride solution for induction of abortion in second-trimester pregnancy].

PubMed

Persianinov, L S; Chernukha, E A

1975-01-01

The authors had performed comperative studies of the effect of the induction of abortion in late pregnancy according to the medical indications by intra-amniotic injection of 20% hypertonic NaCl saline in 26 pregnant patients, of 25 mg prostaglandin F2alpha with 6 hours' intervals in 25 patients, a single dose injection of 40 mg PGF2alpha in 27 cases and single dose injection of 2,5 mg 15-me-PGF2alpha given to 25 patients. The highest success rate was obtained with the single dose injection of 2,5 mg 15-me-PGF2alpha and the lowest success rate was obtained with 25 mg prostaglandin F2alpha with 6 hours' intervals. Despite of rather high procentage of success rate in using the hypertonic NaCl saline, this method is more dangerous in the moment of the injection of saline and complications during the abortion (water intoxication, necrosis of tissue, coagulation defects and other). The most frequently incountered side-effects in using PGs were vomiting and diarhea. Histologic examinations of the placenta revealed massive bleedings, at frequency rate being the same for prostaglandins and the hypertonic saline. The degree of isoimmunisation was lower with prostaglandins than with hypertonic NaCl saline, despite of the late dates of pregnancy termination. The intro-amniotic injection of the small volume solution of 15-me-PGF2alpha or PGF2alpha is more simpler and easier from the technical point of view than any methodic recommended for using saline and at the same time it is more effective.

Acute and Subacute Toxicity of 7.5% Hypertonic Saline/6% Dextran-70 (HSD) in Dogs

DTIC Science & Technology

1991-11-18

7.5% hypertonic saline/6% Dextran-70 in dogs . 1. Serum immunoglobulin and complement responses. J. Appl. Toxicol., in press. 26. G.M. Zaucha, D.F...Dextran-70 (HSD) in Dogs . I PuoiL UM. aucna, DW. Korte, Jr., CE. Wade 13a. TYPE OF REPORT 113b. TIME COVERED 114. DATE OF REPORT (Year, Month, Day) 15...dehydrogenase dogs . 19. ABSTRACT (Continue on reverse if necessary and identify by block number) HSD is currently being evaluated in our laboratory as

Histochemical carbonic anhydrase in rat inner medullary collecting duct

NASA Technical Reports Server (NTRS)

Kleinman, J. G.; Bain, J. L.; Fritsche, C.; Riley, D. A.

1992-01-01

Rat inner medullary collecting duct (IMCD) secretes substantial amounts of H+. However, carbonic anhydrase (CA), a concomitant of H+ secretion, has been generally reported absent in this segment. To reexamine this problem, we investigated CA and the morphological phenotypes of cells comprising the IMCD by CA histochemistry, using a modified Hansson technique with light and electron microscopy. Throughout the medulla, tubule cells exhibit histochemical CA activity. In the initial third of the inner medulla, a small proportion have features of intercalated cells and demonstrate some degree of CA activity. However, the majority population in the early portions of the IMCD appears to consist of principal cells. These also show CA staining of widely variable intensity, both among and within cells. A third cell type, previously called "IMCD cells", appears in the middle portion of the IMCD and is the only cell type present near the papilla tip. In contrast to previous reports, these "IMCD cells" have histochemical CA staining, also of highly variable intensity. These results demonstrate that stainable carbonic anhydrase to support acidification is present throughout the rat IMCD, both in intercalated cells and in some cells clearly not of this type. Therefore, the presence of CA is not specific for the intercalated cell type and suggests that other cell types may participate in acid secretion in IMCD.

Taking Control of Castleman Disease: Leveraging Precision Medicine Technologies to Accelerate Rare Disease Research.

PubMed

Newman, Samantha Kass; Jayanthan, Raj K; Mitchell, Grant W; Carreras Tartak, Jossie A; Croglio, Michael P; Suarez, Alexander; Liu, Amy Y; Razzo, Beatrice M; Oyeniran, Enny; Ruth, Jason R; Fajgenbaum, David C

2015-12-01

Castleman disease (CD) is a rare and heterogeneous disorder characterized by lymphadenopathy that may occur in a single lymph node (unicentric) or multiple lymph nodes (multicentric), the latter typically occurring secondary to excessive proinflammatory hypercytokinemia. While a cohort of multicentric Castleman disease (MCD) cases are caused by Human Herpes Virus-8 (HHV-8), the etiology of HHV-8 negative, idiopathic MCD (iMCD), remains unknown. Breakthroughs in "omics" technologies that have facilitated the development of precision medicine hold promise for elucidating disease pathogenesis and identifying novel therapies for iMCD. However, in order to leverage precision medicine approaches in rare diseases like CD, stakeholders need to overcome several challenges. To address these challenges, the Castleman Disease Collaborative Network (CDCN) was founded in 2012. In the past 3 years, the CDCN has worked to transform the understanding of the pathogenesis of CD, funded and initiated genomics and proteomics research, and united international experts in a collaborative effort to accelerate progress for CD patients. The CDCN's collaborative structure leverages the tools of precision medicine and serves as a model for both scientific discovery and advancing patient care.

Transgenic Restoration of Urea Transporter A1 Confers Maximal Urinary Concentration in the Absence of Urea Transporter A3.

PubMed

Klein, Janet D; Wang, Yanhua; Mistry, Abinash; LaRocque, Lauren M; Molina, Patrick A; Rogers, Richard T; Blount, Mitsi A; Sands, Jeff M

2016-05-01

Urea has a critical role in urinary concentration. Mice lacking the inner medullary collecting duct (IMCD) urea transporter A1 (UT-A1) and urea transporter A3 (UT-A3) have very low levels of urea permeability and are unable to concentrate urine. To investigate the role of UT-A1 in the concentration of urine, we transgenically expressed UT-A1 in knockout mice lacking UT-A1 and UT-A3 using a construct with a UT-A1 gene that cannot be spliced to produce UT-A3. This construct was inserted behind the original UT-A promoter to yield a mouse expressing only UT-A1 (UT-A1(+/+)/UT-A3(-/-)). Western blot analysis demonstrated UT-A1 in the inner medulla of UT-A1(+/+)/UT-A3(-/-) and wild-type mice, but not in UT-A1/UT-A3 knockout mice, and an absence of UT-A3 in UT-A1(+/+)/UT-A3(-/-) and UT-A1/UT-A3 knockout mice. Immunohistochemistry in UT-A1(+/+)/UT-A3(-/-) mice also showed negative UT-A3 staining in kidney and other tissues and positive UT-A1 staining only in the IMCD. Urea permeability in isolated perfused IMCDs showed basal permeability in the UT-A1(+/+)/UT-A3(-/-) mice was similar to levels in wild-type mice, but vasopressin stimulation of urea permeability in wild-type mice was significantly greater (100% increase) than in UT-A1(+/+)/UT-A3(-/-) mice (8% increase). Notably, basal urine osmolalities in both wild-type and UT-A1(+/+)/UT-A3(-/-) mice increased upon overnight water restriction. We conclude that transgenic expression of UT-A1 restores basal urea permeability to the level in wild-type mice but does not restore vasopressin-stimulated levels of urea permeability. This information suggests that transgenic expression of UT-A1 alone in mice lacking UT-A1 and UT-A3 is sufficient to restore urine-concentrating ability. Copyright © 2016 by the American Society of Nephrology.

Transgenic Restoration of Urea Transporter A1 Confers Maximal Urinary Concentration in the Absence of Urea Transporter A3

PubMed Central

Wang, Yanhua; Mistry, Abinash; LaRocque, Lauren M.; Molina, Patrick A.; Rogers, Richard T.; Blount, Mitsi A.; Sands, Jeff M.

2016-01-01

Urea has a critical role in urinary concentration. Mice lacking the inner medullary collecting duct (IMCD) urea transporter A1 (UT-A1) and urea transporter A3 (UT-A3) have very low levels of urea permeability and are unable to concentrate urine. To investigate the role of UT-A1 in the concentration of urine, we transgenically expressed UT-A1 in knockout mice lacking UT-A1 and UT-A3 using a construct with a UT-A1 gene that cannot be spliced to produce UT-A3. This construct was inserted behind the original UT-A promoter to yield a mouse expressing only UT-A1 (UT-A1+/+/UT-A3−/−). Western blot analysis demonstrated UT-A1 in the inner medulla of UT-A1+/+/UT-A3−/− and wild-type mice, but not in UT-A1/UT-A3 knockout mice, and an absence of UT-A3 in UT-A1+/+/UT-A3−/− and UT-A1/UT-A3 knockout mice. Immunohistochemistry in UT-A1+/+/UT-A3−/− mice also showed negative UT-A3 staining in kidney and other tissues and positive UT-A1 staining only in the IMCD. Urea permeability in isolated perfused IMCDs showed basal permeability in the UT-A1+/+/UT-A3−/− mice was similar to levels in wild-type mice, but vasopressin stimulation of urea permeability in wild-type mice was significantly greater (100% increase) than in UT-A1+/+/UT-A3−/− mice (8% increase). Notably, basal urine osmolalities in both wild-type and UT-A1+/+/UT-A3−/− mice increased upon overnight water restriction. We conclude that transgenic expression of UT-A1 restores basal urea permeability to the level in wild-type mice but does not restore vasopressin-stimulated levels of urea permeability. This information suggests that transgenic expression of UT-A1 alone in mice lacking UT-A1 and UT-A3 is sufficient to restore urine-concentrating ability. PMID:26407594

[Some mechanisms of pathogenesis of hypertonic type neurocirculatory dystonia in flying personnel].

PubMed

Denisov, S L; Koroleva, L V; Lairov, I A

1996-01-01

Cytochemical analysis was used to compare the activities of hyaloplasmatic and mitochondrial glycerophosphate dehydrogenase, and succinate dehydrogenase in lymphocytes of peripheral blood taken from 14 aviators with the diagnose of hypertonic neurocirculatory dystonia, and 18 healthy aviators. Significantly higher activity of these enzymes in patients is assumed to signify intensification of metabolism and cellular respiration bearing the forced adaptive character. On this evidence, an attempt is made to interpret earlier discovered changes in the immunobiochemical status of these patients and plausible mechanisms of progressive arterial hypertension are hypothesized. Emphasis is laid on the necessity to direct secondary preventive measures at the early phases of hypertension not only on reduction of the vascular tone and correction of the immunobiochemical status but on building-up of cell's functional reserves.

High salt induces autocrine actions of ET-1 on inner medullary collecting duct NO production via upregulated ETB receptor expression.

PubMed

Hyndman, Kelly Anne; Dugas, Courtney; Arguello, Alexandra M; Goodchild, Traci T; Buckley, Kathleen M; Burch, Mariah; Yanagisawa, Masashi; Pollock, Jennifer S

2016-08-01

The collecting duct endothelin-1 (ET-1), endothelin B (ETB) receptor, and nitric oxide synthase-1 (NOS1) pathways are critical for regulation of fluid-electrolyte balance and blood pressure control during high-salt feeding. ET-1, ETB receptor, and NOS1 are highly expressed in the inner medullary collecting duct (IMCD) and vasa recta, suggesting that there may be cross talk or paracrine signaling between the vasa recta and IMCD. The purpose of this study was to test the hypothesis that endothelial cell-derived ET-1 (paracrine) and collecting duct-derived ET-1 (autocrine) promote IMCD nitric oxide (NO) production through activation of the ETB receptor during high-salt feeding. We determined that after 7 days of a high-salt diet (HS7), there was a shift to 100% ETB expression in IMCDs, as well as a twofold increase in nitrite production (a metabolite of NO), and this increase could be prevented by acute inhibition of the ETB receptor. ETB receptor blockade or NOS1 inhibition also prevented the ET-1-dependent decrease in ion transport from primary IMCDs, as determined by transepithelial resistance. IMCD were also isolated from vascular endothelial ET-1 knockout mice (VEETKO), collecting duct ET-1 KO (CDET-1KO), and flox controls. Nitrite production by IMCD from VEETKO and flox mice was similarly increased twofold with HS7. However, IMCD NO production from CDET-1KO mice was significantly blunted with HS7 compared with flox control. Taken together, these data indicate that during high-salt feeding, the autocrine actions of ET-1 via upregulation of the ETB receptor are critical for IMCD NO production, facilitating inhibition of ion reabsorption. Copyright © 2016 the American Physiological Society.

Autophagic degradation of aquaporin-2 is an early event in hypokalemia-induced nephrogenic diabetes insipidus.

PubMed

Khositseth, Sookkasem; Uawithya, Panapat; Somparn, Poorichaya; Charngkaew, Komgrid; Thippamom, Nattakan; Hoffert, Jason D; Saeed, Fahad; Michael Payne, D; Chen, Shu-Hui; Fenton, Robert A; Pisitkun, Trairak

2015-12-17

Hypokalemia (low serum potassium level) is a common electrolyte imbalance that can cause a defect in urinary concentrating ability, i.e., nephrogenic diabetes insipidus (NDI), but the molecular mechanism is unknown. We employed proteomic analysis of inner medullary collecting ducts (IMCD) from rats fed with a potassium-free diet for 1 day. IMCD protein quantification was performed by mass spectrometry using a label-free methodology. A total of 131 proteins, including the water channel AQP2, exhibited significant changes in abundance, most of which were decreased. Bioinformatic analysis revealed that many of the down-regulated proteins were associated with the biological processes of generation of precursor metabolites and energy, actin cytoskeleton organization, and cell-cell adhesion. Targeted LC-MS/MS and immunoblotting studies further confirmed the down regulation of 18 selected proteins. Electron microscopy showed autophagosomes/autophagolysosomes in the IMCD cells of rats deprived of potassium for only 1 day. An increased number of autophagosomes was also confirmed by immunofluorescence, demonstrating co-localization of LC3 and Lamp1 with AQP2 and several other down-regulated proteins in IMCD cells. AQP2 was also detected in autophagosomes in IMCD cells of potassium-deprived rats by immunogold electron microscopy. Thus, enhanced autophagic degradation of proteins, most notably including AQP2, is an early event in hypokalemia-induced NDI.

Autophagic degradation of aquaporin-2 is an early event in hypokalemia-induced nephrogenic diabetes insipidus

PubMed Central

Khositseth, Sookkasem; Uawithya, Panapat; Somparn, Poorichaya; Charngkaew, Komgrid; Thippamom, Nattakan; Hoffert, Jason D.; Saeed, Fahad; Michael Payne, D.; Chen, Shu-Hui; Fenton, Robert A.; Pisitkun, Trairak

2015-01-01

Hypokalemia (low serum potassium level) is a common electrolyte imbalance that can cause a defect in urinary concentrating ability, i.e., nephrogenic diabetes insipidus (NDI), but the molecular mechanism is unknown. We employed proteomic analysis of inner medullary collecting ducts (IMCD) from rats fed with a potassium-free diet for 1 day. IMCD protein quantification was performed by mass spectrometry using a label-free methodology. A total of 131 proteins, including the water channel AQP2, exhibited significant changes in abundance, most of which were decreased. Bioinformatic analysis revealed that many of the down-regulated proteins were associated with the biological processes of generation of precursor metabolites and energy, actin cytoskeleton organization, and cell-cell adhesion. Targeted LC-MS/MS and immunoblotting studies further confirmed the down regulation of 18 selected proteins. Electron microscopy showed autophagosomes/autophagolysosomes in the IMCD cells of rats deprived of potassium for only 1 day. An increased number of autophagosomes was also confirmed by immunofluorescence, demonstrating co-localization of LC3 and Lamp1 with AQP2 and several other down-regulated proteins in IMCD cells. AQP2 was also detected in autophagosomes in IMCD cells of potassium-deprived rats by immunogold electron microscopy. Thus, enhanced autophagic degradation of proteins, most notably including AQP2, is an early event in hypokalemia-induced NDI. PMID:26674602

Requirement for the eIF4E binding proteins for the synergistic down-regulation of protein synthesis by hypertonic conditions and mTOR inhibition.

PubMed

Clemens, Michael J; Elia, Androulla; Morley, Simon J

2013-01-01

The protein kinase mammalian target of rapamycin (mTOR) regulates the phosphorylation and activity of several proteins that have the potential to control translation, including p70S6 kinase and the eIF4E binding proteins 4E-BP1 and 4E-BP2. In spite of this, in exponentially growing cells overall protein synthesis is often resistant to mTOR inhibitors. We report here that sensitivity of wild-type mouse embryonic fibroblasts (MEFs) to mTOR inhibitors can be greatly increased when the cells are subjected to the physiological stress imposed by hypertonic conditions. In contrast, protein synthesis in MEFs with a double knockout of 4E-BP1 and 4E-BP2 remains resistant to mTOR inhibitors under these conditions. Phosphorylation of p70S6 kinase and protein kinase B (Akt) is blocked by the mTOR inhibitor Ku0063794 equally well in both wild-type and 4E-BP knockout cells, under both normal and hypertonic conditions. The response of protein synthesis to hypertonic stress itself does not require the 4E-BPs. These data suggest that under certain stress conditions: (i) translation has a greater requirement for mTOR activity and (ii) there is an absolute requirement for the 4E-BPs for regulation by mTOR. Importantly, dephosphorylation of p70S6 kinase and Akt is not sufficient to affect protein synthesis acutely.

Ouabain-insensitive salt and water movements in duck red cells. I. Kinetics of cation transport under hypertonic conditions

PubMed Central

Schmidt III, WF; McManus, TJ

1977-01-01

Duck red cells in hypertonic media experience rapid osmotic shrinkage followed by gradual reswelling back toward their original volume. This uptake of salt and water is self limiting and demands a specific ionic composition of the external solution. Although ouabain (10(-4)M) alters the pattern of cation accumulation from predominantly potassium to sodium, it does not affect the rate of the reaction, or the total amount of salt or water taken up. To study the response without the complications of active Na-K transport, ouabain was added to most incubations. All water accumulated by the cells can be accounted for by net salt uptake. Specific external cation requirements for reswelling include: sufficient sodium (more than 23 mM), and elevated potassium (more than 7 mM). In the absence of external potassium cells lose potassium without gaining sodium and continue to shrink instead of reswelling. Adding rubidium to the potassium- free solution promotes an even greater loss of cell potassium, yet causes swelling due to a net uptake of sodium and rubidium followed by chloride. The diuretic furosemide (10(-3)M) inhibits net sodium uptake which depends on potassium (or rubidium), as well as inhibits net sodium uptake which depends on sodium. As a result, cell volume is stabilized in the presence of this drug by inhibition of shrinkage, at low, and of swelling at high external potassium. The response has a high apparent energy of activation (15-20 kcal/mol). We propose that net salt and water movements in hypertonic solutions containing ouabain are mediated by direct coupling or cis-interaction, between sodium and potassium so that the uphill movement of one is driven by the downhill movement of the other in the same direction. PMID:894251

Hypertonic 15% sodium pyruvate offers no initial resuscitation advantage compared with 8% hypertonic NACl in sheep with multiple hemorrhages.

PubMed

do Nascimento, Paulo; Vaid, Sumreen U; Hoskins, Stephen L; Espana, Jonathan M; Kinsky, Michael P; Kramer, George C

2007-05-01

Initial fluid resuscitation of hemorrhagic shock might be enhanced by the infusion of monocarboxylate-energy substrates. We evaluated hemodynamics, metabolism, and fluid dynamics for initial resuscitation of hemorrhage using small volume 15% sodium pyruvate solution (HPY) compared with osmotically matched 8% hypertonic saline (HS). Instrumented conscious sheep were hemorrhaged 25 mL/kg at time zero through 15 min (T0-T15) and 5 mL/kg for 5 min at T50 to T55 and T70 to T75. Fluid resuscitation from T30 to T180 was performed by a computer-controlled closed-loop system, which titrated infusion rate to a mean arterial pressure of 90 mmHg. Initial infusion was 4 mL/kg of either HPY or HS, followed by the administration of lactated Ringer. Both HPY and HS restored cardiac index similarly. The lactate/pyruvate ratio was used to assess metabolic debt and was significantly higher (T180), whereas oxygen delivery was significantly lower (T120) with HPY versus HS. Total fluid administered was similar, with 43.7 +/- 6.2 mL/kg for HPY and 39.4 +/- 6.8 mL/kg for HS. Plasma volume was similarly increased and approached baseline values for both groups. Initial resuscitation with small volume HPY offered no hemodynamic or metabolic advantage compared with small volume HS when the fluids were infused to an end point pressure.

H+, Water and Urea Transport in the Inner Medullary Collecting Duct and Their Role in the Prevention and Pathogenesis of Renal Stone Disease

NASA Astrophysics Data System (ADS)

Wall, Susan M.; Klein, Janet D.

2008-09-01

The inner medullary collecting duct (IMCD) is the final site within the kidney for the reabsorption of urea, water and electrolytes and for the secretion of H+ before the luminal fluid becomes the final urine. Transporters expressed in the IMCD contribute to the generation of the large ion gradients that exist between the interstitium and the collecting duct lumen. Thus, the luminal fluid within the human IMCD can reach an osmolality of 1200 mOsm/kg H2O and a pH of 4. This ability of the human nephron to concentrate and acidify the urine might predispose to stone formation. However, under treatment conditions that predispose to stone formation, such as during hypercalciuria, the kidney mitigates stone formation by reducing solute concentration by reducing H2O reabsorption. Moreover, the kidney attenuates stone formation by tightly controlling acid-base balance, which prevents the bone loss, hypocitraturia and hypercalciuria observed during metabolic acidosis by augmenting net H+ excretion by tightly regulating H+ transporter function and through luminal buffering, particularly with NH3. This article will review the ion transporters present in the mammalian IMCD and their role in the prevention and in the pathogenesis of renal stone formation.

In vitro effects of 3% hypertonic saline and 20% mannitol on canine whole blood coagulation and platelet function.

PubMed

Adamik, Katja-Nicole; Butty, Emmanuelle; Howard, Judith

2015-09-24

Hyperosmolar therapy, using either mannitol or hypertonic saline (HTS), is considered the treatment of choice for intracranial hypertension. However, hyperosmolar agents may impair coagulation and platelet function, limiting their use in patients at risk for hemorrhage. Despite this, studies evaluating the effects of mannitol compared to other hyperosmolar agents in dogs are largely lacking. The aim of this study was to compare the in vitro effects on global hemostasis and platelet function of 20% mannitol and 3% HTS on canine blood. Citrated whole blood from 15 healthy dogs was diluted with 0.9% saline, 20% mannitol and 3% HTS in ratios of 1:16 and 1:8. Rotational thromboelastometry (ROTEM) was used to assess clotting time (CT), clot formation time (CFT) and maximal clot firmness (MCF) following extrinsic activation (Ex-tem) and after platelet inhibition (Fib-tem). A platelet function analyzer (PFA-100) was used to assess closure time (Ct(PFA)). No significant differences were observed between untreated whole blood and samples diluted with saline. Samples diluted with both mannitol and HTS were hypocoagulable compared to untreated whole blood samples. At a dilution of 1:16, no significant differences were found between any measured parameter in samples diluted with saline compared to mannitol or HTS. At a 1:8 dilution, Ct(PFA) was prolonged in samples diluted with mannitol and HTS compared to saline, and Ct(PFA) was prolonged more with mannitol than HTS. Ex-tem CT was increased at a 1:8 dilution with mannitol compared to HTS. Ex-tem CFT was prolonged at a 1:8 dilution with both agents compared to saline, and was prolonged more with mannitol than HTS. Ex-tem MCF was reduced at a 1:8 dilution with both agents compared to saline. Data in this study indicate that both mannitol and HTS affect canine platelet function and whole blood coagulation in vitro in a dose-dependent fashion. The most pronounced effects were observed after high dilutions with mannitol, which

[Effect of hypertonic-hyperoncotic solution infusion on tissue perfusion during surgical treatment of the abdominal aorta].

PubMed

Soskić, Ljiljana; Davidović, Lazar; Milicić, Biljana; Kocica, Mladen; Kovacević, Natasa; Simić, Tijana

2007-10-01

Decreasing of arterial flow below the critical level leads to capillary endothelium edema and to further worsening of tissue perfusion. Hypertonic solution infusion provides mild and short plasma osmolality increasing, while colloidal solutions intensify that effect. The aim of this study was to investigate the effect of hypertonic-hyperoncotic solution (HH) on the organs perfusion during reconstructive surgical procedure on the abdominal aorta (AA). The study included 40 patients submitted to AA reconstruction due to aneurysm or Leriche's syndrome. A clamp was put transversally to the aorta, under the outlets of the renal arterias. According to the solution received when a clamp was on the aorta, the patients were divided into two groups containing 20 patients each: the tested group (A) which received 4 ml/kg of the solution (7.2% NaCl/10% dextran), and the control group (B) which received 0.9% NaCl. The study excluded the patients with the preoperative creatinine level more than 139 micromol/l, and ejection heart fraction less than 40%. The mixed venous blood oxygen saturation increased from 73.3+/-7.33 to 74.95+/-6.19% in the group A, while it decreased from 65.35+/-10.39 to 62.65+/-10.42% in the group B (p = 0.001). The quantity of the provided oxygen in the group A increased significantly from 684.44+/-244.34 to 1362.45+/-2351.01 ml/min, while it decreased from 668.2+/-382.12 to 651.7+/-313.98 ml/min in the group B (p = 0.016). Alveolo-arterial difference in oxygen decreased from 23.12+/-14.74 to 21.1+/-10 mmHg in the group A, while it increased from 23.79+/-15.22 to 26.33+/-13.78 mmHg in the group B (p = 0.05). Satisfactory perfusion of organs during the AA surgery is obtained by using both HH and an isotonic solution. Due to maintaining the optimal values of the minute heart volume, saturation of vein blood blended with oxygen, and al-veolo-arterial difference in oxygen, it is recommended to use HH solution for reanimation of patients in declamping shock.

Body water handling in response to hypertonic-saline induced diuresis in fasting northern elephant seal pups (Mirounga angustirostris)

NASA Technical Reports Server (NTRS)

Ortiz, Rudy M.; Wade, Charles E.; Ortiz, C. Leo

2003-01-01

During natural fasting conditions in postweaned northern elephant seal (NES) (Mirounga angustirostris) pups, urinary water loss is minimized and percent total body water (TBW) is maintained constant. However, following infusion of hypertonic saline, glomerular filtration rate (GFR) and urine output increased in fasting pups. Therefore, we quantified the magnitude of the hypernatremia-induced diuresis relative to the animal's total body water (TBW) pool and the percentage of filtered water reabsorbed. Following a 24 h control period, naturally fasting NES pups (n=7) were infused (4 ml min(-1)) with hypertonic saline (16.7%) at a dose of 3 mmol NaCl kg(-1) body mass. Total body water was estimated prior to infusion by tritium dilution, GFR was estimated by standard creatinine clearance, and urine output (V) was measured for 24 h during the control and post infusion periods. Percentage of filtered water reabsorbed was calculated as (1-(V/GFR))x100. Twenty-four hours following the infusion, GFR (control: 69+/-12 ml min(-1) and post-infusion: 118+/-19 ml min(-1); mean+/-S.E.) increased 77+/-28% above control and the percentage of filtered water reabsorbed was decreased 0.4+/-0.1%. The increase in urine output (control: 218+/-47 ml d(-1) and post-infusion: 883+/-92 ml d(-1)) accounted for 1.7+/-0.2% of the pups' TBW. The hypernatremia-induced diuresis was accompanied by the loss of body water indicating the lack of water retention. Although the 77% increase in GFR was only associated with a 0.4% decrease in the percentage of filtered water reabsorbed, this decrease was significant enough to result in a 4-fold increase in urine output. Despite the observed diuresis, fasting NES pups appear to possess an efficient water recycling mechanism requiring only a small percentage of body water to excrete an excess salt load. This water recycling mechanism may allow pups to avoid negative perturbations in body water as they initiate feeding in a marine environment following the

The Effects of Hypertonic Dextrose Injection on Connective Tissue and Nerve Conduction through the Rabbit Carpal Tunnel

PubMed Central

Yoshii, Yuichi; Zhao, Chunfeng; Schmelzer, James D.; Low, Phillip A.; An, Kai-Nan; Amadio, Peter C.

2009-01-01

Objective To investigate the effects of hypertonic dextrose injection on the subsynovial connective tissue (SSCT) in a rabbit model. We hypothesized that dextrose injection would induce proliferation of the SSCT, hinder median nerve conduction, and alter SSCT mechanical properties similar to what is observed in patients with carpal tunnel syndrome (CTS). Design Randomized, controlled prospective study. Setting Not applicable. Participants New Zealand white rabbits (N=28) weighing 4.0 to 4.5kg. Intervention One fore paw was randomly injected with 0.1ml of 10% dextrose solution. The contralateral paw was injected with a similar amount of 0.9% saline solution as a control. Animals were sacrificed at 12 weeks after injection. Main Outcome Measures Animals were evaluated by electrophysiology (EP), mechanical testing, and histology. EP was evaluated by distal motor latency and amplitude. Shear force was evaluated when the middle digit flexor digitorum superficialis tendon was pulled out from the carpal tunnel. The ultimate tensile load and the energy absorption were also measured. Tissue for histology was evaluated qualitatively. Results EP demonstrated significant prolongation of distal motor latency. The energy absorption and stiffness were also significantly increased in the dextrose group. Histologically, the dextrose group showed thickening of the collagen bundles and vascular proliferation within the SSCT compared to the saline group. Conclusions These results are consistent with the findings in CTS patients and suggest that hypertonic dextrose injection has the potential to create a novel animal model in which to study the evolution of CTS. PMID:19236989

Oral Hypertonic Saline Is Effective in Reversing Acute Mild-to-Moderate Symptomatic Exercise -Associated Hyponatremia.

PubMed

Bridges, Eileen; Altherwi, Tawfeeq; Correa, José A; Hew-Butler, Tamara

2018-01-23

To determine whether oral administration of 3% hypertonic saline (HTS) is as efficacious as intravenous (IV) 3% saline in reversing symptoms of mild-to-moderate symptomatic exercise-associated hyponatremia (EAH) in athletes during and after a long-distance triathlon. Noninferiority, open-label, parallel-group, randomized control trial to IV or oral HTS. We used permuted block randomization with sealed envelopes, containing the word either "oral" or "IV." Annual long-distance triathlon (3.8-km swim, 180-km bike, and 42-km run) at Mont-Tremblant, Quebec, Canada. Twenty race finishers with mild to moderately symptomatic EAH. Age, sex, race finish time, and 9 clinical symptoms. Time from treatment to discharge. We successfully randomized 20 participants to receive either an oral (n = 11) or IV (n = 9) bolus of HTS. We performed venipuncture to measure serum sodium (Na) at presentation to the medical clinic and at time of symptom resolution after the intervention. The average time from treatment to discharge was 75.8 minutes (SD 29.7) for the IV treatment group and 50.3 minutes (SD 26.8) for the oral treatment group (t test, P = 0.02). Serum Na before and after treatment was not significantly different in both groups. There was no difference on presentation between groups in age, sex, or race finish time, both groups presented with an average of 6 symptoms. Oral HTS is effective in reversing symptoms of mild-to-moderate hyponatremia in EAH.

[Effect of hypertonic saline solution on the viscoelasticities of erythrocyte membrane in rats subjected to hemorrhagic shock].

PubMed

Zhou, X; Hu, D; Liu, L; Wu, Z; Qin, J; Cai, S

2001-12-01

We have studied the effect of hypertonic saline solution on the viscoelasticities of erythrocyte membrane in hemorrhage-shocked rats using micropippette aspiration technique. Wistar rats were randomly divided into three groups of 0.9% NaCl(NS), 7.5% NaCl (HS) and 5% NaCl-3.5% NaAc (HSA), respectively. The animals were bled to reach a mean arterial pressure of 5.3 kPa in 10 minutes and maintained in shock for 90 minutes. 4 ml/kg NS, HS and HSA was given intravenously and respectively in 5 minutes following hemorrhagic shock. The blood was collected to determine the viscoelasticities of erythrocyte membrane at baseline, shock and after treatment. The results showed that the elastic moduli and viscous coefficients of erythrocyte membrane were increased obviously following hemorrhagic shock. HS raised elastic moduli and reduced viscous coefficients significantly compared with NS after treatment. The elastic moduli and viscous coefficients of erythrocyte membrane were decreased remarkably in HSA group than in NS and HS group. These data suggested that HSA could improve the viscoelasticities of erythrocyte membrane significantly in rats subjected to hemorrhagic shock.

Synovitis induced by joint lavage with hypertonic saline solutions in healthy dairy calves

PubMed Central

Achard, Damien; Francoz, David; Desrochers, André; Girard, Christiane; Piché, Caroline

2012-01-01

The objective of this study was to evaluate the effect of a single joint lavage with 7.2% or 15% hypertonic saline solutions (HSS) on the tarsocrural joints of healthy calves. The tarsi of 10 calves were randomly lavaged with 7.2% HSS, 15% HSS, or isotonic saline. Synovial fluid samples were collected aseptically on days 1 (before joint lavage), 2, 3, 4, and 8 for complete cytological analysis. Lameness, joint swelling, and pain were recorded daily. Calves were euthanized on day 8 for gross and histological analyses of synovial membranes and articular cartilage. Synovitis was evaluated using a scoring system reflecting inflammatory changes in synovial membranes. Joints irrigated with HSS were more distended and painful compared with isotonic control joints. Swelling decreased consistently in the joints lavaged with 7.2% HSS, whereas it remained unchanged in joints lavaged with 15% HSS. Slight to moderate lameness was observed in the joints lavaged with 15% HSS. In comparison to isotonic saline joints, total protein concentration was significantly increased on day 2 and 3 for the joints lavaged with 7.2% HSS (P ≤ 0.01) and on days 2, 3, and 4 in the joints lavaged with 15% HSS (P ≤ 0.0006). Gross and histological findings revealed that synovitis was more severe in the joints lavaged with 15% HSS but variable in the joints lavaged with 7.2% HSS. No significant differences were observed for the articular cartilage. Fifteen percent HSS is not recommended for joint lavage. Although irrigation with 7.2% HSS may induce a variable synovitis, it was found appropriate for joint lavage. Its effects on septic joints remain undetermined. PMID:23024450

[Preliminary establishment of cytological examination and the normal reference values for hypertonic saline solution-induced sputum of healthy children in Guangzhou].

PubMed

Chen, De-hui; Zhong, Guo-yu; Luo, Wei; Chen, Qiao-li; Chen, Ru-chong; Lin, Yu-neng; Pan, Xiao-an; Li, Jin-ying; Wu, Shang-zhi; Lai, Ke-fang; Zhong, Nan-shan

2012-07-01

To establish the method of cytological examination and the normal reference values for hypertonic saline solution-induced sputum of healthy children (age range from 5 to 15 years) with physical examination in Guangzhou. A total of 352 children, 5 to 15 years old, were enrolled from primary school and middle school in Guangzhou from January to December, 2010. All subjects completed a standardized questionnaire on the presence of respiratory, allergic symptoms and family history, the medical history and the physical examination was performed by doctors, lung function (forced expiratory volume at 1 s in predicted normal, FEV(1)%) was determined. There were 266 healthy children (137 males, 129 females) who were selected and undergone hypertonic saline solution induction of sputum, and cytological examination was performed. Hypertonic saline (5%) was nebulized and inhaled for 15 - 30 min. No expectoration within 30 min was defined as failure, and the procedure was terminated. The part of opaque and higher density sputum samples was detected by cytology. The proportion of neutrophils, lymphocytes, eosinophils, macrophages and monocytes was calculated. This study was approved by the institutional Ethics Review Committee of First Affiliated Hospital of Guangzhou Medical College. Informed consent was obtained from the legal guardians of all participants following a detailed description of the purpose and potential benefits of the study. There were 175 subjects' induced sputum specimens (175/266, 65.8%), non-qualified sputum samples were obtained from 16 of the subjects. The proportions of median (IQR) of lymphocytes were 0.012 (0.020), 95%CI were ranged from 0.015 to 0.022; neutrophils 0.207 (0.330), 95%CI 0.266 - 0.356 macrophages 0.761 (0.327), 95%CI 0.607 - 0.699; eosinophils 0.004 (0.019), 95%CI 0.013 - 0.022. There were no significant differences in proportions of cytological findings of female or male, different age groups and second-hand smoking or not (all P > 0

Glycogen Synthase Kinase-3 Modulates Hyperosmotic-Induced Urea Transporter A1 Relocation in the Inner Medullary Collecting Duct Cells.

PubMed

Li, Yong-Xia; Huang, Yun; Liu, Song; Mao, Yan; Yuan, Cheng-Yan; Yang, Xiao; Yao, Li-Jun

2016-01-01

Glycogen synthase kinase 3 (GSK3) regulates urine concentration by mediating the vasopressin-induced aquaporin 2 expression and water permeability, although it is unknown whether GSK3 also mediates the accumulation of the urea transporter A1 (UT-A1). The aim of this study is to investigate the effect of GSK3 on UT-A1 distribution. Mouse inner medullary collecting duct 3 cells were transfected with UT-A1-GFP construct. The stable transfected cells were cultured under hypertonic conditions, treated with GSK3 inhibitor lithium chloride, GSK3 activator, lysosome or proteasome inhibitor. The expression levels of UT-A1, GSK3, and phospho-GSK3 were analyzed using western blot. The interaction between UT-A1 and the Golgi apparatus was examined using confocal immunofluorescence microscope. The UT-A1 trafficking was examined using the biotinylation of surface membranes. UT-A1 dissociated away from the Golgi apparatus and translocated to the plasma membrane under hypertonic-NaCl and NaCl plus urea stimulation. This movement was accompanied by the increased phosphorylation of GSK3 and its localization on the cellular membrane. Moreover, these results were duplicated by treating the cells with the GSK3 inhibitor, and by contrast, were partially reversed by the GSK3 activator. Treating cells with a lysosome or proteasome inhibitor failed to attenuate the effects of hypertonic stimulus, indicating that the loss of UT-A1 from the Golgi was not due to degradation. Our results suggest that GSK3 may in part modulate the hypertonic-induced intracellular UT-A1 redistribution and its accumulation on the plasma membrane, which may constitute another mechanism by which GSK3 modulates urine concentration. © 2016 S. Karger AG, Basel.

Equiosmolar Solutions of Hypertonic Saline and Mannitol Do Not Impair Blood Coagulation During Elective Intracranial Surgery.

PubMed

Hernández-Palazón, Joaquín; Fuentes-García, Diego; Doménech-Asensi, Paloma; Piqueras-Pérez, Claudio; Falcón-Araña, Luis; Burguillos-López, Sebastián

2017-01-01

The authors investigated the effect of equiosmolar, equivolemic solutions of 3% hypertonic saline (HS) and 20% mannitol on blood coagulation assessed by rotational thromboelastometry (ROTEM) and standard coagulation tests during elective craniotomy. In a prospective, randomized, double-blind trial, 40 patients undergoing elective craniotomy were randomized to receive 5 mL/kg of either 20% mannitol or 3% HS for intraoperative brain relaxation. Fibrinogen, activated partial thromboplastin time, prothrombin time, hemoglobin, hematocrit, and platelet count were simultaneously measured intraoperatively with ROTEM for EXTEM, INTEM, and FIBTEM analysis. ROTEM parameters were: clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), and α-angle. No significant differences between groups were found in ROTEM variables CT, CFT, MCF, α-angle (EXTEM and INTEM), and MCF (FIBTEM) nor standard coagulation tests. ROTEM parameters did not show changes after administration of hyperosmolar solutions relating to basal values, except for an increase of CFT EXTEM (118±28 vs. 128±26 s) and decrease of CT INTEM (160±18 vs. 148±15 s) with values within normal range. Significant decreases from baseline levels were observed for hematocrit (-7%), platelet count (-10%), and fibrinogen (-13%) after HS infusion, and hematocrit (-9%), platelet count (-13%), and fibrinogen (-9%) after mannitol infusion, but remaining normal. The use of 5 mL/kg of equiosmolar solutions of 3% HS and 20% mannitol applied to reach a brain relaxation during elective craniotomy does not induce coagulation impairment as evidenced by ROTEM and standard coagulation tests.

Different mechanisms may generate sustained hypertonic and rhythmic bursting muscle activity in idiopathic dystonia.

PubMed

Liu, Xuguang; Yianni, John; Wang, Shouyan; Bain, Peter G; Stein, John F; Aziz, Tipu Z

2006-03-01

Despite that deep brain stimulation (DBS) of the globus pallidus internus (GPi) is emerging as the favored intervention for patients with medically intractable dystonia, the pathophysiological mechanisms of dystonia are largely unclear. In eight patients with primary dystonia who were treated with bilateral chronic pallidal stimulation, we correlated symptom-related electromyogram (EMG) activity of the most affected muscles with the local field potentials (LFPs) recorded from the globus pallidus electrodes. In 5 dystonic patients with mobile involuntary movements, rhythmic EMG bursts in the contralateral muscles were coherent with the oscillations in the pallidal LFPs at the burst frequency. In contrast, no significant coherence was seen between EMG and LFPs either for the sustained activity separated out from the compound EMGs in those 5 cases, or in the EMGs in 3 other cases without mobile involuntary movements and rhythmic EMG bursts. In comparison with the resting condition, in both active and passive movements, significant modulation in the GPi LFPs was seen in the range of 8-16 Hz. The finding of significant coherence between GPi oscillations and rhythmic EMG bursts but not sustained tonic EMG activity suggests that the synchronized pallidal activity may be directly related to the rhythmic involuntary movements. In contrast, the sustained hypertonic muscle activity may be represented by less synchronized activity in the pallidum. Thus, the pallidum may play different roles in generating different components of the dystonic symptom complex.

Baclofen into the lateral parabrachial nucleus induces hypertonic sodium chloride intake during cell dehydration

PubMed Central

2013-01-01

Background Activation of GABAB receptors with baclofen into the lateral parabrachial nucleus (LPBN) induces ingestion of water and 0.3 M NaCl in fluid replete rats. However, up to now, no study has investigated the effects of baclofen injected alone or combined with GABAB receptor antagonist into the LPBN on water and 0.3 M NaCl intake in rats with increased plasma osmolarity (rats treated with an intragastric load of 2 M NaCl). Male Wistar rats with stainless steel cannulas implanted bilaterally into the LPBN were used. Results In fluid replete rats, baclofen (0.5 nmol/0.2 μl), bilaterally injected into the LPBN, induced ingestion of 0.3 M NaCl (14.3 ± 4.1 vs. saline: 0.2 ± 0.2 ml/210 min) and water (7.1 ± 2.9 vs. saline: 0.6 ± 0.5 ml/210 min). In cell-dehydrated rats, bilateral injections of baclofen (0.5 and 1.0 nmol/0.2 μl) into the LPBN induced an increase of 0.3 M NaCl intake (15.6 ± 5.7 and 21.5 ± 3.5 ml/210 min, respectively, vs. saline: 1.7 ± 0.8 ml/210 min) and an early inhibition of water intake (3.5 ± 1.4 and 6.7 ± 2.1 ml/150 min, respectively, vs. saline: 9.2 ± 1.4 ml/150 min). The pretreatment of the LPBN with 2-hydroxysaclofen (GABAB antagonist, 5 nmol/0.2 μl) potentiated the effect of baclofen on 0.3 M NaCl intake in the first 90 min of test and did not modify the inhibition of water intake induced by baclofen in cell-dehydrated rats. Baclofen injected into the LPBN did not affect blood pressure and heart rate. Conclusions Thus, injection of baclofen into the LPBN in cell-dehydrated rats induced ingestion of 0.3 M NaCl and inhibition of water intake, suggesting that even in a hyperosmotic situation, the blockade of LPBN inhibitory mechanisms with baclofen is enough to drive rats to drink hypertonic NaCl, an effect independent of changes in blood pressure. PMID:23642235

Dragon (repulsive guidance molecule RGMb) inhibits E-cadherin expression and induces apoptosis in renal tubular epithelial cells.

PubMed

Liu, Wenjing; Li, Xiaoling; Zhao, Yueshui; Meng, Xiao-Ming; Wan, Chao; Yang, Baoxue; Lan, Hui-Yao; Lin, Herbert Y; Xia, Yin

2013-11-01

Dragon is one of the three members of the repulsive guidance molecule (RGM) family, i.e. RGMa, RGMb (Dragon), and RGMc (hemojuvelin). We previously identified the RGM members as bone morphogenetic protein (BMP) co-receptors that enhance BMP signaling. Our previous studies found that Dragon is highly expressed in the tubular epithelial cells of mouse kidneys. However, the roles of Dragon in renal epithelial cells are yet to be defined. We now show that overexpression of Dragon increased cell death induced by hypoxia in association with increased cleaved poly(ADP-ribose) polymerase and cleaved caspase-3 levels in mouse inner medullary collecting duct (IMCD3) cells. Dragon also inhibited E-cadherin expression but did not affect epithelial-to-mesenchymal transition induced by TGF-β in IMCD3 cells. Previous studies suggest that the three RGM members can function as ligands for the receptor neogenin. Interestingly, our present study demonstrates that the Dragon actions on apoptosis and E-cadherin expression in IMCD3 cells were mediated by the neogenin receptor but not through the BMP pathway. Dragon expression in the kidney was up-regulated by unilateral ureteral obstruction in mice. Compared with wild-type mice, heterozygous Dragon knock-out mice exhibited 45-66% reduction in Dragon mRNA expression, decreased epithelial apoptosis, and increased tubular E-cadherin expression and had attenuated tubular injury after unilateral ureteral obstruction. Our results suggest that Dragon may impair tubular epithelial integrity and induce epithelial apoptosis both in vitro and in vivo.

A Systematic Review of Randomized Controlled Trials Comparing Hypertonic Sodium Solutions and Mannitol for Traumatic Brain Injury: Implications for Emergency Department Management.

PubMed

Burgess, Sarah; Abu-Laban, Riyad B; Slavik, Richard S; Vu, Erik N; Zed, Peter J

2016-04-01

To comparatively evaluate hypertonic sodium (HTS) and mannitol in patients following acute traumatic brain injury (TBI) on the outcomes of all-cause mortality, neurological disability, intracranial pressure (ICP) change from baseline, ICP treatment failure, and serious adverse events. PubMed, EMBASE, CENTRAL, Cochrane Database of Systematic Reviews, ClinicalTrials.gov, and WHO ICTRP (World Health Organization International Clinical Trials Registry Platform) were searched (inception to November 2015) using hypertonic saline solutions, sodium chloride, mannitol, osmotic diuretic, traumatic brain injury, brain injuries, and head injury. Searches were limited to humans. Clinical practice guidelines and bibliographies were reviewed. Prospective, randomized trials comparing HTS and mannitol in adults (≥16 years) with severe TBI (Glasgow Coma Scale score ≤8) and elevated ICP were included. ICP elevation, ICP reduction, and treatment failure were defined using study definitions. Of 326 articles screened, 7 trials enrolling a total of 191 patients met inclusion criteria. Studies were underpowered to detect a significant difference in mortality or neurological outcomes. Due to significant heterogeneity and differences in reporting ICP change from baseline, this outcome was not meta-analyzed. No difference between HTS and mannitol was observed for mean ICP reduction; however, risk of ICP treatment failure favored HTS (risk ratio [RR] = 0.39; 95% CI = 0.18-0.81). Serious adverse events were not reported. Based on limited data, clinically important differences in mortality, neurological outcomes, and ICP reduction were not observed between HTS or mannitol in the management of severe TBI. HTS appears to lead to fewer ICP treatment failures. © The Author(s) 2016.

Two Sulfur Glycoside Compounds Isolated from Lepidium apetalum Willd Protect NRK52e Cells against Hypertonic-Induced Adhesion and Inflammation by Suppressing the MAPK Signaling Pathway and RAAS.

PubMed

Yuan, Peipei; Zheng, Xiaoke; Li, Meng; Ke, Yingying; Fu, Yang; Zhang, Qi; Wang, Xiaolan; Feng, Weisheng

2017-11-12

Lepidium apetalum Willd has been used to reduce edema and promote urination. Cis -desulfoglucotropaeolin ( cis -DG) and trans -desulfoglucotropaeolin ( trans -DG) were isolated from Lepidium apetalum Willd, and caused a significant increase in cell viability in a hypertonic model in NRK52e cells. In the hypertonic model, cis -DG and trans -DG significantly promoted the cell viability of NRK52e cells and inhibited the elevation of Na⁺ in the supernatant, inhibited the renin-angiotensin-aldosterone (RAAS) system, significantly reduced the levels of angiotensin II (Ang II) and aldosterone (ALD), and lowered aquaporin-2 (AQP2) and Na⁺-K⁺ ATP content in renal medulla. After treatment with cis -DG and trans -DG, expression of calcineurin (CAN) and Ca/calmodulin-dependent protein kinase II (CaMK II) was decreased in renal tissue and Ca 2+ influx was inhibited, thereby reducing the secretion of transforming growth factor-β (TGFβ), reversing the increase in adhesion and inflammatory factor E-selectin and monocyte chemotactic protein 1 (MCP-1) induced by high NaCl, while reducing oxidative stress status and decreasing the expression of cyclooxygenase-2 (COX2). Furthermore, inhibition of protein kinase C (PKC) expression also contributed to these improvements. The cis -DG and trans -DG reduced the expression of p-p44/42 MAPK, p-JNK and p-p38, inhibited the phosphorylation of the MAPK signaling pathway in NRN52e cells induced by high salt, decreased the overexpression of p-p38 and p-HSP27, and inhibited the overactivation of the p38-MAPK signaling pathway, suggesting that the p38-MAPK pathway may play a vital role in the hypertonic-induced adhesion and inflammatory response. From the results of this study, it can be concluded that the mechanism of cis -DG and trans -DG may mainly be through inhibiting the p38-MAPK signaling pathway, inhibiting the excessive activation of the RAAS system, and thereby reducing adhesion and inflammatory factors.

A successful combined treatment with dermal substitutes and products of regenerative medicine in a patient affected by extravasation injury from hypertonic solution.

PubMed

Onesti, Maria Giuseppina; Carella, Sara; Maruccia, Michele; Marchese, Cinzia; Fino, Pasquale; Scuderi, Nicolò

2012-01-01

In neonatal intensive care units, extravasation is one of the most common injuries occurring in infants as a complication of infusion therapy. These very preterm infants have immature skin which is easily damaged. They often require a longer duration of intravenous therapy, and obtaining intravenous access can be difficult. An invasive treatment should be avoided, whenever possible, particularly for very immature infants. In our Special Operative Unit for ulcers and difficult-to-heal wounds, University of Rome, we successfully treated a premature neonate, who experienced extravasation of hypertonic fluid, using dermal substitutes and products of regenerative medicine.

Osmolality and respiratory regulation in humans: respiratory compensation for hyperchloremic metabolic acidosis is absent after infusion of hypertonic saline in healthy volunteers.

PubMed

Moen, Vibeke; Brudin, Lars; Rundgren, Mats; Irestedt, Lars

2014-10-01

Several animal studies show that changes in plasma osmolality may influence ventilation. Respiratory depression caused by increased plasma osmolality is interpreted as inhibition of water-dependent thermoregulation because conservation of body fluid predominates at the cost of increased core temperature. Respiratory alkalosis, on the other hand, is associated with a decrease in plasma osmolality and strong ion difference (SID) during human pregnancy. We investigated the hypothesis that osmolality would influence ventilation, so that increased osmolality will decrease ventilation and decreased osmolality will stimulate ventilation in both men and women. Our study participants were healthy volunteers of both sexes (ASA physical status I). Ten men (mean 28 years; range 20-40) and 9 women (mean 33 years; range 22-43) were included. All women participated in both the follicular and luteal phases of the menstrual cycle. Hyperosmolality was induced by IV infusion of hypertonic saline 3%, and hypoosmolality by drinking tap water. Arterial blood samples were collected for analysis of electrolytes, osmolality, and blood gases. Sensitivity to CO2 was determined by rebreathing tests performed before and after the fluid-loading procedures. Infusion of hypertonic saline caused hyperchloremic metabolic acidosis with decreased SID in all subjects. Analysis of pooled data showed absence of respiratory compensation. Baseline arterial PCO2 (PaCO2) mean (SD) 37.8 (2.9) mm Hg remained unaltered, with lowest PaCO2 37.8 (2.9) mm Hg after 100 minutes, P = 0.70, causing a decrease in pH from mean (SD) 7.42 (0.02) to 7.38 (0.02), P < 0.001. Metabolic acidosis was also observed during water loading. Pooled results show that PaCO2 decreased from 38.2 (3.3) mm Hg at baseline to 35.7 (2.8) mm Hg after 80 minutes of drinking water, P = 0.002, and pH remained unaltered: pH 7.43 (0.02) at baseline to pH 7.42 (0.02), P = 0.14, mean difference (confidence interval) = pH -0.007 (-0.017 to 0.003). Our

A comparison of equivolume, equiosmolar solutions of hypertonic saline and mannitol for brain relaxation during elective supratentorial craniotomy.

PubMed

Hernández-Palazón, Joaquín; Fuentes-García, Diego; Doménech-Asensi, Paloma; Piqueras-Pérez, Claudio; Falcón-Araña, Luis; Burguillos-López, Sebastián

2016-01-01

Hyperosmolar solutions have been used in neurosurgery to reduce brain volume and facilitate surgical exposure. The purpose of this study was to compare the effects of equivolume, equiosmolar solutions of mannitol and hypertonic saline (HS) on brain relaxation, intensive care unit (ICU) and hospital stay, postoperative outcomes and incidence of side-effects in patients undergoing elective supratentorial craniotomy. In a randomised, prospective, double-blind study, 60 patients undergoing elective supratentorial craniotomy were randomised 1:1 to receive 3 ml/kg of either 20% mannitol or 3% HS. The primary outcome was the surgical condition of the brain assessed by the neurosurgeon using a 4-point scale after opening the dura (1 = relaxed, 2 = satisfactory, 3 = firm and 4 = bulging). Secondary outcomes were electrolytes, blood gases, plasma osmolality and haemodynamic variables measured at 0 min, 30 min, 2 h and 6 h after infusion. Also, predefined postoperative complications, length of ICU and hospital stay were recorded. Appropriate statistical tests were used for comparison; p < 0.05 was considered significant. There was no difference in brain relaxation [mannitol, 1(1-3) versus HS, 1(1.4) points; p = 0.55]. Patients with brain midline shift showed a worse response to hyperosmolar solutions than those without midline shift: 37% versus 8%, respectively; OR = 6.6 (95% CI, 1.54-28.83); p = 0.006. Plasma osmolality increased during the study period (6 h) in both the groups (p < 0.05 compared with baseline). No significant differences in postoperative complications or length of ICU and hospital stay were observed between the groups. Single doses of 3 ml/kg of 20% mannitol and 3% HS are safe and effective for intraoperative brain debulking during elective supratentorial craniotomy, but less effective in patients with pre-existing mass effect and midline shift.

Treatment of reticular and telangiectatic leg veins: double-blind, prospective comparative trial of polidocanol and hypertonic saline.

PubMed

Peterson, Jennifer D; Goldman, Mitchel P; Weiss, Robert A; Duffy, David M; Fabi, Sabrina G; Weiss, Margaret A; Guiha, Isabella

2012-08-01

Sixty-three subjects' legs were randomized to receive treatment with polidocanol (POL) or hypertonic saline (HS) for telangiectasias and reticular leg veins. To compare the safety and efficacy of two sclerosing agents in three dermatologic surgery practices. After exclusion of saphenofemoral junction incompetence, each subject's veins were categorized (telangiectasias <1 mm and reticular veins 1-3 mm) and randomized. Telangiectasias were treated with POL 0.5% or 11.7% HS and reticular veins with POL 1% or 23.4% HS. An independent, blinded physician determined efficacy and adverse events. Subject satisfaction questionnaires were administered and global clinical improvement assessments performed. All patients completed four visits at 0, 1, 4, and 12 weeks. Patients reported significantly greater pain during treatment with HS (2.42) than POL (1.03) (p < .001). There were no significant differences in physician-assessed improvement of reticular leg veins or telangiectasias; subject- or physician-assessed overall improvement; or physician-assessed phlebitis, pigmentation, edema, or matting in either of the three practices or the entire cohort. Two subjects developed ulcerations with HS. No ulcerations or allergic reactions developed after POL injections. Both agents provided effective treatment, but HS caused 2.35 times as much pain during injections and resulted in two episodes of tissue necrosis. © 2012 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

Prevention of duodenal ileus reveals functional differences in the duodenal response to luminal hypertonicity in Sprague-Dawley and Dark Agouti rats.

PubMed

Sedin, J; Sjöblom, M; Nylander, O

2014-03-01

The mechanism by which the duodenum adjusts the luminal osmolality remains unclear. The aim was to compare the duodenal osmoregulation in response to different hyperosmolar solutions in Sprague-Dawley and Dark Agouti rats and to elucidate whether cyclooxygenase-2 inhibition affects these responses. The duodenum was perfused in situ with a 700-milliosmolar solution (NaCl alone, D-glucose ± NaCl, D-mannitol ± NaCl or orange juice), and the effects on the duodenal motility, mucosal permeability, luminal alkalinization, fluid flux and osmoregulation were assessed in anaesthetized rats. The change in net fluid flux and luminal osmolality, in response to a given hyperosmolar solution, was almost identical in control rats of both strains. In control rats, hypertonic D-glucose-NaCl induced fluid secretion only in the presence of phlorizin, an inhibitor of SGLT1. Cyclooxygenase-2 inhibition potentiated the hypertonicity-induced fluid secretion and increased the osmolality-adjusting capability in both strains, but the responses were greater in Dark Agouti rats. While cyclooxygenase-2-inhibited Dark Agouti rats responded to the hyperosmolar solutions with depression of motility and increased mucosal permeability, these effects were absent or smaller in the Sprague-Dawley strain. In contrast, orange juice induced the same duodenal responses in cyclooxygenase-2-inhibited Dark Agouti and Sprague-Dawley rats. The duodenum possesses the ability to absorb fluid despite a very high luminal osmolality. Inhibition of cyclooxygenase-2 markedly enhanced the capability of the duodenum to secrete fluid and to decrease luminal osmolality, irrespective of the hyperosmolar solution or the rat strain used, and revealed notable differences between the two strains with regard to their osmolality-adjusting capability. © 2013 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Dragon (Repulsive Guidance Molecule RGMb) Inhibits E-cadherin Expression and Induces Apoptosis in Renal Tubular Epithelial Cells*

PubMed Central

Liu, Wenjing; Li, Xiaoling; Zhao, Yueshui; Meng, Xiao-Ming; Wan, Chao; Yang, Baoxue; Lan, Hui-Yao; Lin, Herbert Y.; Xia, Yin

2013-01-01

Dragon is one of the three members of the repulsive guidance molecule (RGM) family, i.e. RGMa, RGMb (Dragon), and RGMc (hemojuvelin). We previously identified the RGM members as bone morphogenetic protein (BMP) co-receptors that enhance BMP signaling. Our previous studies found that Dragon is highly expressed in the tubular epithelial cells of mouse kidneys. However, the roles of Dragon in renal epithelial cells are yet to be defined. We now show that overexpression of Dragon increased cell death induced by hypoxia in association with increased cleaved poly(ADP-ribose) polymerase and cleaved caspase-3 levels in mouse inner medullary collecting duct (IMCD3) cells. Dragon also inhibited E-cadherin expression but did not affect epithelial-to-mesenchymal transition induced by TGF-β in IMCD3 cells. Previous studies suggest that the three RGM members can function as ligands for the receptor neogenin. Interestingly, our present study demonstrates that the Dragon actions on apoptosis and E-cadherin expression in IMCD3 cells were mediated by the neogenin receptor but not through the BMP pathway. Dragon expression in the kidney was up-regulated by unilateral ureteral obstruction in mice. Compared with wild-type mice, heterozygous Dragon knock-out mice exhibited 45–66% reduction in Dragon mRNA expression, decreased epithelial apoptosis, and increased tubular E-cadherin expression and had attenuated tubular injury after unilateral ureteral obstruction. Our results suggest that Dragon may impair tubular epithelial integrity and induce epithelial apoptosis both in vitro and in vivo. PMID:24052264

Aldosterone alters the chromatin structure of the murine endothelin-1 gene.

PubMed

Welch, Amanda K; Jeanette Lynch, I; Gumz, Michelle L; Cain, Brian D; Wingo, Charles S

2016-08-15

Aldosterone increases sodium reabsorption in the renal collecting duct and systemic blood pressure. Paradoxically, aldosterone also induces transcription of the endothelin-1 (Edn1) gene to increase protein (ET-1) levels, which inhibits sodium reabsorption. Here we investigated changes in the chromatin structure of the Edn1 gene of collecting duct cell lines in response to aldosterone treatment. The Edn1 gene has a CpG island that encompasses the transcription start site and four sites in the 5' regulatory region previously linked to transcriptional regulation. The chromatin structure of the Edn1 gene was investigated using a quantitative PCR-based DNaseI hypersensitivity assay in murine hepatocyte (AML12), renal cortical collecting duct (mpkCCDC14), outer medullary collecting duct1 (OMCD1), and inner medullary collecting duct-3 (IMCD-3) cell lines. The CpG island was uniformly accessible. One calcium-responsive NFAT element remained at low chromatin accessibility in all cell lines under all conditions tested. However, the second calcium responsive NFAT element located at -1563bp upstream became markedly more accessible in IMCD-3 cells exposed to aldosterone. Importantly, one established aldosterone hormone response element HRE at -671bp relative to the transcription start site was highly accessible, and another HRE (-551bp) became more accessible in aldosterone-treated IMCD-3 and OMCD1 cells. The evidence supports a model in which aldosterone activation of the mineralocorticoid receptor (MR) results in the MR-hormone complex binding at HRE at -671bp to open chromatin structure around other regulatory elements in the Edn1 gene. Published by Elsevier Inc.

Hypertonic lactated saline resuscitation reduces the risk of abdominal compartment syndrome in severely burned patients.

PubMed

Oda, Jun; Ueyama, Masashi; Yamashita, Katsuyuki; Inoue, Takuya; Noborio, Mitsuhiro; Ode, Yasumasa; Aoki, Yoshiki; Sugimoto, Hisashi

2006-01-01

Secondary abdominal compartment syndrome is a lethal complication after resuscitation from burn shock. Hypertonic lactated saline (HLS) infusion reduces early fluid requirements in burn shock, but the effects of HLS on intraabdominal pressure have not been clarified. Patients admitted to our burn unit between 2002 and 2004 with burns > or =40% of the total body surface area without severe inhalation injury were entered into a fluid resuscitation protocol using HLS (n = 14) or lactated Ringer's solution (n = 22). Urine output was monitored hourly with a goal of 0.5 to 1.0 mL/kg per hour. Hemodynamic parameters, blood gas analysis, intrabladder pressure as an indicator of intraabdominal pressure (IAP), and the peak inspiratory pressure were recorded. Pulmonary compliance and the abdominal perfusion pressure were also calculated. In the HLS group, the amount of intravenous fluid volume needed to maintain adequate urine output was less at 3.1 +/- 0.9 versus 5.2 +/- 1.2 mL/24 h per kg per percentage of total body surface area, and the peak IAP and peak inspiratory pressure at 24 hours after injury were significantly lower than those in the lactated Ringer's group. Two of 14 patients (14%) in the HLS group and 11 of 22 patients (50%) developed IAH within 20.8 +/- 7.2 hours after injury. In patients with severe burn injury, a large intravenous fluid volume decreases abdominal perfusion during the resuscitative period because of increased IAP. Our data suggest that HLS resuscitation could reduce the risk of secondary abdominal compartment syndrome with lower fluid load in burn shock patients.

Challenges to the successful implementation of 3-D sound

NASA Astrophysics Data System (ADS)

Begault, Durand R.

1991-11-01

The major challenges for the successful implementation of 3-D audio systems involve minimizing reversals, intracranially heard sound, and localization error for listeners. Designers of 3-D audio systems are faced with additional challenges in data reduction and low-frequency response characteristics. The relationship of the head-related transfer function (HRTF) to these challenges is shown, along with some preliminary psychoacoustic results gathered at NASA-Ames.

ARL and Association 3.0: Ten Management Challenges

ERIC Educational Resources Information Center

Funk, Carla J.

2009-01-01

Association management in today's "association 3.0" environment presents some new challenges and new perspectives on old ones. This paper summarizes 10 such challenges including collaboration, diversity, innovation, transparency, financial stability, member benefits, knowledge-based decision-making, a demand-driven association model, pro-activity…

The PPARδ ligand GW501516 reduces growth but not apoptosis in mouse inner medullary collecting duct cells.

PubMed

Clark, Jordan; Nasrallah, Rania; Hébert, Richard L

2009-01-01

The collecting duct (CD) expresses considerable amounts of PPARδ. While its role is unknown in the CD, in other renal cells it has been shown to regulate both growth and apoptosis. We thus hypothesized that PPARδ reduces apoptotic responses and stimulates cell growth in the mouse CD, and examined the effect of GW501516, a synthetic PPARδ ligand, on these responses in mouse IMCD-K2 cells. High doses of GW501516 decreased both DNA and protein synthesis in these cells by 80%, but had no overall effect on cell viability. Although anisomycin treatment resulted in an increase of caspase-3 levels of about 2.59-fold of control, GW501516 did not affect anisomycin-induced changes in active caspase-3 levels. These results show that a PPARδ ligand inhibits growth but does not affect anisomycin-apoptosis in a mouse IMCD cell line. This could have therapeutic implications for renal diseases associated with increased CD growth responses.

The Challenge. Volume 14, Number 3

ERIC Educational Resources Information Center

US Department of Education, 2007

2007-01-01

"The Challenge" provides information and resources to help schools create safe and healthy learning environments for students. Articles in this issue include: (1) Research Shows Consequences of Drug Abuse on the Teenage Brain (Don Vereen); (2) Interview: NIDA [National Institute on Drug Abuse] Director Discusses Drug Abuse among Teens; (3) Know…

Thienoquinolins exert diuresis by strongly inhibiting UT-A urea transporters

PubMed Central

Ren, Huiwen; Wang, Yanhua; Xing, Yongning; Ran, Jianhua; Liu, Ming; Lei, Tianluo; Zhou, Hong; Li, Runtao; Sands, Jeff M.

2014-01-01

Urea transporters (UT) play an important role in the urine concentration mechanism by mediating intrarenal urea recycling, suggesting that UT inhibitors could have therapeutic use as a novel class of diuretic. Recently, we found a thienoquinolin UT inhibitor, PU-14, that exhibited diuretic activity. The purpose of this study was to identify more potent UT inhibitors that strongly inhibit UT-A isoforms in the inner medullary collecting duct (IMCD). Efficient thienoquinolin UT inhibitors were identified by structure-activity relationship analysis. Urea transport inhibition activity was assayed in perfused rat terminal IMCDs. Diuretic activity of the compound was determined in rats and mice using metabolic cages. The results show that the compound PU-48 exhibited potent UT-A inhibition activity. The inhibition was 69.5% with an IC50 of 0.32 μM. PU-48 significantly inhibited urea transport in perfused rat terminal IMCDs. PU-48 caused significant diuresis in UT-B null mice, which indicates that UT-A is the target of PU-48. The diuresis caused by PU-48 did not change blood Na+, K+, or Cl− levels or nonurea solute excretion in rats and mice. No toxicity was detected in cells or animals treated with PU-48. The results indicate that thienoquinolin UT inhibitors induce a diuresis by inhibiting UT-A in the IMCD. This suggests that they may have the potential to be developed as a novel class of diuretics with fewer side effects than classical diuretics. PMID:25298523

Production of consistent pain by intermittent infusion of sterile 5% hypertonic saline, followed by decrease of pain with cryotherapy.

PubMed

Long, Blaine C; Knight, Kenneth L; Hopkins, Ty; Parcell, Allen C; Feland, J Brent

2012-08-01

It is suggested that postinjury pain is difficult to examine; thus, investigators have developed experimental pain models. To minimize pain, cryotherapy (cryo) is applied, but reports on its effectiveness are limited. To investigate a pain model for the anterior knee and examine cryo in reducing the pain. Controlled laboratory study. Therapeutic modality laboratory. 30 physically active healthy male subjects who were free from any lower extremity orthopedic, neurological, cardiovascular, or endocrine pathologies. Perceived pain was measured every minute. Surface temperature was also assessed in the center of the patella and the popliteal fossa. There was a significant interaction between group and time (F68,864 = 3.0, P = .0001). At the first minute, there was no difference in pain between the 3 groups (saline/cryo = 4.80 ± 4.87 mm, saline/sham = 2.80 ± 3.55 mm, no saline/cryo = 4.00 ± 3.33 mm). During the first 5 min, pain increased from 4.80 ± 4.87 to 45.90 ± 21.17 mm in the saline/cryo group and from 2.80 ± 3.55 to 31.10 ± 20.25 mm in the saline/sham group. Pain did not change within the no-saline/cryo group, 4.00 ± 3.33 to 1.70 ± 1.70 mm. Pain for the saline/sham group remained constant for 17 min. Cryo decreased pain for 16 min in the saline/cryo group. There was no difference in preapplication surface temperature between or within each group. No change in temperature occurred within the saline/sham. Cooling and rewarming were similar in both cryo groups. Ambient temperature fluctuated less than 1°C during data collection. Intermittent infusion of sterile 5% hypertonic saline may be a useful experimental pain model in establishing a constant level of pain in a controlled laboratory setting. Cryotherapy decreased the induced anterior knee pain for 16 min.

Responses of magnocellular neurons to osmotic stimulation involves coactivation of excitatory and inhibitory input: an experimental and theoretical analysis.

PubMed

Leng, G; Brown, C H; Bull, P M; Brown, D; Scullion, S; Currie, J; Blackburn-Munro, R E; Feng, J; Onaka, T; Verbalis, J G; Russell, J A; Ludwig, M

2001-09-01

How does a neuron, challenged by an increase in synaptic input, display a response that is independent of the initial level of activity? Here we show that both oxytocin and vasopressin cells in the supraoptic nucleus of normal rats respond to intravenous infusions of hypertonic saline with gradual, linear increases in discharge rate. In hyponatremic rats, oxytocin and vasopressin cells also responded linearly to intravenous infusions of hypertonic saline but with much lower slopes. The linearity of response was surprising, given both the expected nonlinearity of neuronal behavior and the nonlinearity of the oxytocin secretory response to such infusions. We show that a simple computational model can reproduce these responses well, but only if it is assumed that hypertonic infusions coactivate excitatory and inhibitory synaptic inputs. This hypothesis was tested first by applying the GABA(A) antagonist bicuculline to the dendritic zone of the supraoptic nucleus by microdialysis. During local blockade of GABA inputs, the response of oxytocin cells to hypertonic infusion was greatly enhanced. We then went on to directly measure GABA release in the supraoptic nucleus during hypertonic infusion, confirming the predicted rise. Together, the results suggest that hypertonic infusions lead to coactivation of excitatory and inhibitory inputs and that this coactivation may confer appropriate characteristics on the output behavior of oxytocin cells. The nonlinearity of oxytocin secretion that accompanies the linear increase in oxytocin cell firing rate reflects frequency-facilitation of stimulus-secretion coupling at the neurohypophysis.

combination effect of hypertonic disease with chronic pancreatitis on the processes maintain homeostasis.

PubMed

Babinets, Liliya S; Medvid, Igor I; Herasymets, Iryna I; Borovyk, Iryna O; Migenko, Liudmyla M; Migenko, Bogdan O; Ryabokon, Svitlana S; Korylchuk, Neonila I; Botcyk, Natalia E; Tvorko, Vadym M

Introduction: Abnormalities comorbidity - a frequent phenomenon in medical practice. This determines the relevance of research processes maintaining homeostasis with a combination of various diseases. The aim of this study was to examine and compare the character of vegetative, antioxidant, kallikrein-kinin system and parameters of endogenous intoxication disorders in the patients with isolated essential hypertension and with combination of hypertonic disease and chronic pancreatitis. Materials and Methods: Cardiointervalography was used in the research with definition of standard statistical and spectral heart rate variability. Determination of superoxide dismutase, glutathione, catalase, middle molecular peptides, total proteolytic activity of plasma by the hydrolysis of protamine sulfate, prekallikrein, kallikrein, α1 -proteinase inhibitor, α2 -macroglobulin and kininase II was conducted by laboratory methods. Results: Sympathicotonia with the moderate tension of adaptation processes, violation of antioxidant protection, kallikrein-kinin system and displays of endogenous intoxication were found in the patients with isolated hypertension. Reduction of sympathicotonia, reducing total power spectrum, increasing the share of humoral-metabolic effects on heart rate, tendency to asympathicotonia autonomic reactivity, lower levels of superoxide dismutase, glutathione, prekallikrein, α2 -macroglobulin, kininase II, higher levels of catalase, middle molecular peptides, total proteolytic activity of plasma kallikrein were observed upon accession the concomitant chronic pancreatitis. Conclusions: The signs of compensatory mechanisms disruption and increased autonomic nervous system imbalance with a decrease in ductility autonomous processes in the load were determined upon accession the concomitant chronic pancreatitis. The combination of pathologies also accompanied by more severe manifestations of endogenous intoxication, significant violations of antioxidant and

Hypertonic Saline as a Useful Tool for Sputum Induction and Pathogen Detection in Cystic Fibrosis.

PubMed

Ferreira, Adriana Carolina Marques; Marson, Fernando Augusto Lima; Cohen, Milena Antonelli; Bertuzzo, Carmen Silvia; Levy, Carlos Emilio; Ribeiro, Antonio Fernando; Ribeiro, Jose Dirceu

2017-08-01

The aim of this study was to compare the qualitative and semi-quantitative detection of pathogens in the airway secretions of patients with cystic fibrosis (CF) and the sputum induction capacity before and after inhalation of 7% hypertonic saline solution (HSS). The study enrolled 64 patients with CF. Airway secretions were collected from all enrolled patients with CF before and after inhalation of 7% HSS, and the samples were screened for pathogens. Inhalation of 7% HSS increased the probability of producing sputum from 36 to 52% (p = 0.002) in children with CF. The effect was most in children under 11 years. Inhalation of 7% HSS improved qualitative pathogen identification (p = 0.008). Inhalation of 7% HSS increased the mucoid Pseudomonas aeruginosa (p = 0.002) and non-mucoid P. aeruginosa in the semi-quantitative analysis (p = 0.035). Four new pathogens (Aspergillus fumigatus, Achromobacter xylosoxidans, Ochrobactrum anthropi, and Elizabethkingia meningoseptica) were identified in the sputum samples collected from the airways of patients with CF following 7% HSS. Inhalation of 7% HSS increased sputum production and pathogen identification in children with CF. The inhalation of 7% HSS was feasible and should be implemented for routine pathogen detection in the airways of patients with CF, particularly in those patients who do not produce sputum.

Regulation of Renal Urea Transport by Vasopressin

PubMed Central

Sands, Jeff M.; Blount, Mitsi A.; Klein, Janet D.

2011-01-01

Terrestrial life would be miserable without the ability to concentrate urine. Production of concentrated urine requires complex interactions among the nephron segments and vasculature in the kidney medulla. In addition to water channels (aquaporins) and sodium transporters, urea transporters are critically important to the theories proposed to explain the physiologic processes occurring when urine is concentrated. Vasopressin (anti-diuretic hormone) is the key hormone regulating the production of concentrated urine. Vasopressin rapidly increases water and urea transport in the terminal inner medullary collecting duct (IMCD). Vasopressin rapidly increases urea permeability in the IMCD through increases in phosphorylation and apical plasma-membrane accumulation of the urea transporter A1 (UT-A1). Vasopressin acts through two cAMP-dependent signaling pathways in the IMCD: protein kinase A and exchange protein activated by cAMP Epac. Protein kinase A phosphorylates UT-A1 at serines 486 and 499. In summary, vasopressin regulates urea transport acutely by increasing UT-A1 phosphorylation and the apical plasma-membrane accumulation of UT-A1 through two cAMP-dependent pathways. PMID:21686211

Regulation of renal urea transport by vasopressin.

PubMed

Sands, Jeff M; Blount, Mitsi A; Klein, Janet D

2011-01-01

Terrestrial life would be miserable without the ability to concentrate urine. Production of concentrated urine requires complex interactions among the nephron segments and vasculature in the kidney medulla. In addition to water channels (aquaporins) and sodium transporters, urea transporters are critically important to the theories proposed to explain the physiologic processes occurring when urine is concentrated. Vasopressin (anti-diuretic hormone) is the key hormone regulating the production of concentrated urine. Vasopressin rapidly increases water and urea transport in the terminal inner medullary collecting duct (IMCD). Vasopressin rapidly increases urea permeability in the IMCD through increases in phosphorylation and apical plasma-membrane accumulation of the urea transporter A1 (UT-A1). Vasopressin acts through two cAMP-dependent signaling pathways in the IMCD: protein kinase A and exchange protein activated by cAMP Epac. Protein kinase A phosphorylates UT-A1 at serines 486 and 499. In summary, vasopressin regulates urea transport acutely by increasing UT-A1 phosphorylation and the apical plasma-membrane accumulation of UT-A1 through two cAMP-dependent pathways.

An equiosmolar study on early intracranial physiology and long term outcome in severe traumatic brain injury comparing mannitol and hypertonic saline.

PubMed

Jagannatha, Aniruddha Tekkatte; Sriganesh, Kamath; Devi, Bhagavatula Indira; Rao, Ganne Sesha Umamaheswara

2016-05-01

The impact of hypertonic saline (HTS) on long term control of intracranial hypertension (ICH) is yet to be established. The current prospective randomized controlled study was carried out in 38 patients with severe traumatic brain injury (TBI). Over 450 episodes of refractory ICH were treated with equiosmolar boluses of 20% mannitol in 20 patients and 3.0% HTS in 18 subjects. Intracranial pressure (ICP) was monitored for 6days. ICP and cerebral perfusion pressure (CPP) were comparable between the groups. The mannitol group had a progressive increase in the ICP over the study period (p=0.01). A similar increase was not seen in the HTS group (p=0.1). The percentage time for which the ICP remained below a threshold of 20 mmHg on day6 was higher in the HTS group (63% versus 49%; p=0.3). The duration of inotrope requirement in the HTS group was less compared to the mannitol group (p=0.06). The slope of fall in ICP in response to a bolus dose at a given baseline value of ICP was higher with HTS compared to mannitol (p=0.0001). In-hospital mortality tended to be lower in the HTS group (3 versus 10; p=0.07) while mortality at 6 months was not different between the groups (6 versus 10; p=0.41). Dichotomized Glasgow Outcome Scale scores at 6months were comparable between the groups (p=0.21). To conclude, immediate physiological advantages seen with HTS over mannitol did not translate into long term benefit on ICP/CPP control or mortality of patients with TBI. Copyright © 2015 Elsevier Ltd. All rights reserved.

Thienoquinolins exert diuresis by strongly inhibiting UT-A urea transporters.

PubMed

Ren, Huiwen; Wang, Yanhua; Xing, Yongning; Ran, Jianhua; Liu, Ming; Lei, Tianluo; Zhou, Hong; Li, Runtao; Sands, Jeff M; Yang, Baoxue

2014-12-15

Urea transporters (UT) play an important role in the urine concentration mechanism by mediating intrarenal urea recycling, suggesting that UT inhibitors could have therapeutic use as a novel class of diuretic. Recently, we found a thienoquinolin UT inhibitor, PU-14, that exhibited diuretic activity. The purpose of this study was to identify more potent UT inhibitors that strongly inhibit UT-A isoforms in the inner medullary collecting duct (IMCD). Efficient thienoquinolin UT inhibitors were identified by structure-activity relationship analysis. Urea transport inhibition activity was assayed in perfused rat terminal IMCDs. Diuretic activity of the compound was determined in rats and mice using metabolic cages. The results show that the compound PU-48 exhibited potent UT-A inhibition activity. The inhibition was 69.5% with an IC50 of 0.32 μM. PU-48 significantly inhibited urea transport in perfused rat terminal IMCDs. PU-48 caused significant diuresis in UT-B null mice, which indicates that UT-A is the target of PU-48. The diuresis caused by PU-48 did not change blood Na(+), K(+), or Cl(-) levels or nonurea solute excretion in rats and mice. No toxicity was detected in cells or animals treated with PU-48. The results indicate that thienoquinolin UT inhibitors induce a diuresis by inhibiting UT-A in the IMCD. This suggests that they may have the potential to be developed as a novel class of diuretics with fewer side effects than classical diuretics. Copyright © 2014 the American Physiological Society.

Expansions of the Neurovascular Scleral Canal and Contained Optic Nerve Occur Early in the Hypertonic Saline Rat Experimental Glaucoma Model

PubMed Central

Pazos, Marta; Yang, Hongli; Gardiner, Stuart K.; Cepurna, W.O.; Johnson, E.C.; Morrison, J.C.; Burgoyne, Claude F.

2015-01-01

Purpose To characterize early optic nerve head (ONH) structural change in rat experimental glaucoma (EG). Methods Unilateral intraocular pressure (IOP) elevation was induced in Brown Norway rats by hypertonic saline injection into the episcleral veins and animals were sacrificed 4 weeks later by perfusion fixation. Optic nerve cross-sections were graded from 1 (normal) to 5 (extensive injury) by 5 masked observers. ONH’s with peripapillary retina and sclera were embedded, serial sectioned, 3-D reconstructed, delineated, and quantified. Overall and animal-specific EG versus Control eye ONH parameter differences were assessed globally and regionally by linear mixed effect models with significance criteria adjusted for multiple comparisons. Results Expansions of the optic nerve and surrounding anterior scleral canal opening achieved statistical significance overall (p<.0022), and in 7 of 8 EG eyes (p<.005). In at least 5 EG eyes, significant expansions (p<.005) in Bruch’s membrane opening (range 3–10%), the anterior and posterior scleral canal openings (8–21% and 5–21%, respectively), and the optic nerve at the anterior and posterior scleral canal openings (11–30% and 8–41%, respectively) were detected. Optic nerve expansion was greatest within the superior and inferior quadrants. Optic nerve expansion at the posterior scleral canal opening was significantly correlated to optic nerve damage (R= 0.768, P=.042). Conclusion In the rat ONH, the optic nerve and surrounding Bruch’s membrane opening and neurovascular scleral canal expand early in their response to chronic experimental IOP elevation. These findings provide phenotypic landmarks and imaging targets for detecting the development of experimental glaucomatous optic neuropathy in the rat eye. PMID:26500195

Expansions of the neurovascular scleral canal and contained optic nerve occur early in the hypertonic saline rat experimental glaucoma model.

PubMed

Pazos, Marta; Yang, Hongli; Gardiner, Stuart K; Cepurna, William O; Johnson, Elaine C; Morrison, John C; Burgoyne, Claude F

2016-04-01

To characterize early optic nerve head (ONH) structural change in rat experimental glaucoma (EG). Unilateral intraocular pressure (IOP) elevation was induced in Brown Norway rats by hypertonic saline injection into the episcleral veins and animals were sacrificed 4 weeks later by perfusion fixation. Optic nerve cross-sections were graded from 1 (normal) to 5 (extensive injury) by 5 masked observers. ONHs with peripapillary retina and sclera were embedded, serial sectioned, 3-D reconstructed, delineated, and quantified. Overall and animal-specific EG versus Control eye ONH parameter differences were assessed globally and regionally by linear mixed effect models with significance criteria adjusted for multiple comparisons. Expansions of the optic nerve and surrounding anterior scleral canal opening achieved statistical significance overall (p < 0.0022), and in 7 of 8 EG eyes (p < 0.005). In at least 5 EG eyes, significant expansions (p < 0.005) in Bruch's membrane opening (BMO) (range 3-10%), the anterior and posterior scleral canal openings (8-21% and 5-21%, respectively), and the optic nerve at the anterior and posterior scleral canal openings (11-30% and 8-41%, respectively) were detected. Optic nerve expansion was greatest within the superior and inferior quadrants. Optic nerve expansion at the posterior scleral canal opening was significantly correlated to optic nerve damage (R = 0.768, p = 0.042). In the rat ONH, the optic nerve and surrounding BMO and neurovascular scleral canal expand early in their response to chronic experimental IOP elevation. These findings provide phenotypic landmarks and imaging targets for detecting the development of experimental glaucomatous optic neuropathy in the rat eye. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hypertonic saline alleviates experimentally induced cerebral oedema through suppression of vascular endothelial growth factor and its receptor VEGFR2 expression in astrocytes.

PubMed

Huang, Linqiang; Cao, Wei; Deng, Yiyu; Zhu, Gaofeng; Han, Yongli; Zeng, Hongke

2016-10-13

Cerebral oedema is closely related to the permeability of blood-brain barrier, vascular endothelial growth factor (VEGF) and its receptor vascular endothelial growth factor receptor 2 (VEGFR2) all of which are important blood-brain barrier (BBB) permeability regulatory factors. Zonula occludens 1 (ZO-1) and claudin-5 are also the key components of BBB. Hypertonic saline is widely used to alleviate cerebral oedema. This study aimed to explore the possible mechanisms underlying hypertonic saline that ameliorates cerebral oedema effectively. Middle cerebral artery occlusion (MCAO) model in Sprague-Dawley (SD) rats and of oxygen-glucose deprivation model in primary astrocytes were used in this study. The brain water content (BWC) was used to assess the effect of 10 % HS on cerebral oedema. The assessment of Evans blue (EB) extravasation was performed to evaluate the protective effect of 10 % HS on blood-brain barrier. The quantification of VEGF, VEGFR2, ZO-1 and claudin-5 was used to illustrate the mechanism of 10 % HS ameliorating cerebral oedema. BWC was analysed by wet-to-dry ratios in the ischemic hemisphere of SD rats; it was significantly decreased after 10 % HS treatment (P < 0.05). We also investigated the blood-brain barrier protective effect by 10 % HS which reduced EB extravasation effectively in the peri-ischemic brain tissue. In parallel to the above notably at 24 h following MCAO, mRNA and protein expression of VEGF and VEGFR2 in the peri-ischemic brain tissue was down-regulated after 10 % HS treatment (P < 0.05). Along with this, in vitro studies showed increased VEGF and VEGFR2 mRNA and protein expression in primary astrocytes under hypoxic condition (P < 0.05), but it was suppressed after HS treatment (P < 0.05). In addition, HS inhibited the down-regulation of ZO-1, claudin-5 effectively. The results suggest that 10 % HS could alleviate cerebral oedema possibly through reducing the ischemia induced BBB permeability as a consequence of

Role of medullary progenitor cells in epithelial cell migration and proliferation

PubMed Central

Chen, Dong; Chen, Zhiyong; Zhang, Yuning; Park, Chanyoung; Al-Omari, Ahmed

2014-01-01

This study is aimed at characterizing medullary interstitial progenitor cells and to examine their capacity to induce tubular epithelial cell migration and proliferation. We have isolated a progenitor cell side population from a primary medullary interstitial cell line. We show that the medullary progenitor cells (MPCs) express CD24, CD44, CXCR7, CXCR4, nestin, and PAX7. MPCs are CD34 negative, which indicates that they are not bone marrow-derived stem cells. MPCs survive >50 passages, and when grown in epithelial differentiation medium develop phenotypic characteristics of epithelial cells. Inner medulla collecting duct (IMCD3) cells treated with conditioned medium from MPCs show significantly accelerated cell proliferation and migration. Conditioned medium from PGE2-treated MPCs induce tubule formation in IMCD3 cells grown in 3D Matrigel. Moreover, most of the MPCs express the pericyte marker PDGFR-b. Our study shows that the medullary interstitium harbors a side population of progenitor cells that can differentiate to epithelial cells and can stimulate tubular epithelial cell migration and proliferation. The findings of this study suggest that medullary pericyte/progenitor cells may play a critical role in collecting duct cell injury repair. PMID:24808539

Magnolol attenuates the lung injury in hypertonic saline treatment from mesenteric ischemia reperfusion through diminishing iNOS.

PubMed

Shih, Hsin-Chin; Huang, Mu-Shun; Lee, Chen-Hsen

2012-06-15

Hypertonic saline (HTS) administration can decrease the inflammation following ischemia reperfusion. Magnolol is a potent antioxidant. The present study investigated whether combined treatment of magnolol and HTS could provide further protection in mesenteric ischemia reperfusion injury. Male C3H/HeOuJ mice were randomly segregated into the following groups: sham-operated (sham), vehicle treatment and mesenteric ischemia reperfusion (MSIR) (vehicle-treated), magnolol treatment and MSIR (magnolol-treated), HTS treatment and MSIR (HTS-treated), as well as co-administration of magnolol plus HTS and MSIR (combined-treated). In MSIR, mice were subjected to mesenteric ischemia for 60 min followed by reperfusion for 30 min. Lung injury was evaluated by lung edema (water ratio) and myeloperoxide (MPO) activity; RNA expression of inducible nitric oxide synthetase (iNOS), TNF-α, and IL-6 were assayed by real time RT-PCR. The formation of peroxynitrite in plasma was assayed by the peroxynitrite-dependent oxidation of dihydrorhodamine 123 (DHR 123) to rhodamine. Compared with those in the sham-treated group, lung edema and MPO activity, expressions of iNOS, TNF-α and IL-6, and plasma peroxynitrite were significantly increased in the vehicle-treated group. Significant attenuations of these parameters were found in the magnolol-treated or HTS-treated animals. Combined treatment of magnolol and HTS further suppressed the lung edema, iNOS, and TNF-α expressions, and plasma peroxynitrite, compared with the results of a single treatment of magnolol or HTS. Compared with single-agent use, co-administration of magnolol and HTS further decreases iNOS expression and plasma peroxynitrite as well as the degree of lung injury from MISR. These results may provide another treatment measure for post-injury immunomodulation. Copyright © 2012 Elsevier Inc. All rights reserved.

Hypertonic dextrose injections (prolotherapy) in the treatment of symptomatic knee osteoarthritis: A systematic review and meta-analysis

PubMed Central

Sit, Regina WS; Chung, Vincent CH; Reeves, Kenneth D.; Rabago, David; Chan, Keith KW; Chan, Dicken CC; Wu, Xinyin; Ho, Robin ST; Wong, Samuel YS

2016-01-01

Hypertonic dextrose injections (prolotherapy) is an emerging treatment for symptomatic knee osteoarthritis (OA) but its efficacy is uncertain. We conducted a systematic review with meta-analysis to synthesize clinical evidence on the effect of prolotherapy for knee OA. Fifteen electronic databases were searched from their inception to September 2015. The primary outcome of interest was score change on the Western Ontario and McMaster Universities Arthritis Index (WOMAC). Three randomized controlled trials (RCTs) of moderate risk of bias and one quasi–randomized trial were included, with data from a total of 258 patients. In the meta-analysis of two eligible studies, prolotherapy is superior to exercise alone by a standardized mean difference (SMD) of 0.81 (95% CI: 0.18 to 1.45, p = 0.012), 0.78 (95% CI: 0.25 to 1.30, p = 0.001) and 0.62 (95% CI: 0.04 to 1.20, p = 0.035) on the WOMAC composite scale; and WOMAC function and pain subscale scores respectively. Moderate heterogeneity exists in all cases. Overall, prolotherapy conferred a positive and significant beneficial effect in the treatment of knee OA. Adequately powered, longer-term trials with uniform end points are needed to better elucidate the efficacy of prolotherapy. PMID:27146849

The Role of Cell Swelling in Ischemic Renal Damage and the Protective Effect of Hypertonic Solute

PubMed Central

Flores, Jorge; DiBona, Donald R.; Beck, Clyde H.; Leaf, Alexander

1972-01-01

The failure of blood flow to return to the kidney following a transient period of ischemia has long been recognized. The cause of this “no-reflow” has been investigated in the rat after a transient period of total obstruction of the renal arteries. The vascular pattern of the kidneys as visualized with silicone rubber injection shows a diffuse patchy ischemia throughout the kidney, which persists after release of the obstructed renal artery. Electron microscopic studies of ischemic kidneys showed that all cellular elements were swollen and limiting the available vascular space. Functional studies revealed an increase in plasma urea nitrogen and creatinine after 1 hr or longer ischemic periods. The ischemia, cell swelling, “no-reflow,” and subsequent renal dysfunction occurring after obstruction to the renal arteries were corrected by the administration of hypertonic mannitol, but were unaffected by an equivalent expansion of the extracellular fluid volume either with isotonic saline or isotonic mannitol, showing that the osmotic effect was primary. The hypothesis is presented that ischemic swelling of cells may occlude small blood vessels so that recirculation does not resume even after the initial cause of the ischemia is no longer present; solutes which do not penetrate cell membranes are able to shrink swollen cells, increase the available vascular space and thus permit reflow of blood to the ischemic organ. Images PMID:5007042

Roles of basolateral solute uptake via NKCC1 and of myosin II in vasopressin-induced cell swelling in inner medullary collecting duct.

PubMed

Chou, Chung-Lin; Yu, Ming-Jiun; Kassai, Eliza M; Morris, Ryan G; Hoffert, Jason D; Wall, Susan M; Knepper, Mark A

2008-07-01

Collecting duct cells swell when exposed to arginine vasopressin (AVP) in the presence of a transepithelial osmolality gradient. We investigated the mechanisms of AVP-induced cell swelling in isolated, perfused rat inner medullary collecting ducts (IMCDs) using quantitative video microscopy and fluorescence-based measurements of transepithelial water transport. We tested the roles of transepithelial water flow, basolateral solute entry, and the cytoskeleton (actomyosin). When a transepithelial osmolality gradient was imposed by addition of NaCl to the bath, AVP significantly increased both water flux and cell height. When the osmolality gradient was imposed by addition of mannitol, AVP increased water flux but not cell height, suggesting that AVP-induced cell swelling requires a NaCl gradient and is not merely dependent on the associated water flux. Bumetanide (Na-K-2Cl cotransporter inhibitor) added to the bath markedly diminished the AVP-induced cell height increase. AVP-induced cell swelling was absent in IMCDs from NKCC1-knockout mice. In rat IMCDs, replacement of Na, K, or Cl in the peritubular bath caused significant cell shrinkage, consistent with a basolateral solute transport pathway dependent on all three ions. Immunocytochemistry using an antibody to NKCC1 confirmed basolateral expression in IMCD cells. The conventional nonmuscle myosin II inhibitor blebbistatin also diminished the AVP-induced cell height increase and cell shape change, consistent with a role for the actin cytoskeleton and myosin II. We conclude that the AVP-induced cell height increase is dependent on basolateral solute uptake via NKCC1 and changes in actin organization via myosin II, but is not dependent specifically on increased apical water entry.

The Effects of Stereotactic Cerebroventricular Administration of Albumin, Mannitol, Hypertonic Sodium Chloride, Glycerin and Dextran in Rats with Experimental Brain Edema.

PubMed

Ates, Tuncay; Gezercan, Yurdal; Menekse, Guner; Turkoz, Yusuf; Parlakpinar, Hakan; Okten, Ali Ihsan; Akyuva, Yener; Onal, Selami Cagatay

2017-01-01

To evaluate the effects of cerebroventricular administration of hyperoncotic/hyperosmotic agents on edematous brain tissue in rats with experimental head trauma. The study included 54 female Sprague-Dawley rats with weights ranging between 200 and 250 g. Six experimental groups were examined with each group containing 9 rats. All rats were exposed to head trauma, and treatment groups were administered 2 µl of one of the drugs (albumin, mannitol, hypertonic sodium chloride (NaCl), glycerin and dextran) 6, 12 and 24 hours after the trauma via the cerebroventricular route and using a stereotactic device. Rats were sacrificed 48 hours after the trauma, and brain tissues were extracted without damage. Biochemical analyses including reduced glutathione (GSH), nitric oxide (NO), malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1β) were performed on the injured left hemisphere. Compared with the control group, the albumin, mannitol, 3% NaCl and glycerin treatment groups revealed dramatic increases in GSH levels (p < 0.001). Levels of MDA, which is the end-product of brain edema and lipid peroxidation, failed to show a statistically significant decrease, but there was a decreasing trend observed in the inter-group comparisons. NO levels were also decreased in the 3% NaCl treatment group. An analysis of TNF-α and IL-1β, two proinflammatory cytokines associated with the trauma, revealed that IL-1β decreased significantly in all treatment groups (p=0.001), whereas no significant difference was detected in TNF-α levels. Cerebroventricular administration of hyperoncotic/hyperosmotic agents provides substantial effects on the treatment of brain edema.

Systems-level analysis of cell-specific AQP2 gene expression in renal collecting duct.

PubMed

Yu, Ming-Jiun; Miller, R Lance; Uawithya, Panapat; Rinschen, Markus M; Khositseth, Sookkasem; Braucht, Drew W W; Chou, Chung-Lin; Pisitkun, Trairak; Nelson, Raoul D; Knepper, Mark A

2009-02-17

We used a systems biology-based approach to investigate the basis of cell-specific expression of the water channel aquaporin-2 (AQP2) in the renal collecting duct. Computational analysis of the 5'-flanking region of the AQP2 gene (Genomatix) revealed 2 conserved clusters of putative transcriptional regulator (TR) binding elements (BEs) centered at -513 bp (corresponding to the SF1, NFAT, and FKHD TR families) and -224 bp (corresponding to the AP2, SRF, CREB, GATA, and HOX TR families). Three other conserved motifs corresponded to the ETS, EBOX, and RXR TR families. To identify TRs that potentially bind to these BEs, we carried out mRNA profiling (Affymetrix) in mouse mpkCCDc14 collecting duct cells, revealing expression of 25 TRs that are also expressed in native inner medullary collecting duct. One showed a significant positive correlation with AQP2 mRNA abundance among mpkCCD subclones (Ets1), and 2 showed a significant negative correlation (Elf1 and an orphan nuclear receptor Nr1h2). Transcriptomic profiling in native proximal tubules (PT), medullary thick ascending limbs (MTAL), and IMCDs from kidney identified 14 TRs (including Ets1 and HoxD3) expressed in the IMCD but not PT or MTAL (candidate AQP2 enhancer roles), and 5 TRs (including HoxA5, HoxA9 and HoxA10) expressed in PT and MTAL but not in IMCD (candidate AQP2 repressor roles). In luciferase reporter assays, overexpression of 3 ETS family TRs transactivated the mouse proximal AQP2 promoter. The results implicate ETS family TRs in cell-specific expression of AQP2 and point to HOX, RXR, CREB and GATA family TRs as playing likely additional roles.

Hypercalcemia induces targeted autophagic degradation of aquaporin-2 at the onset of nephrogenic diabetes insipidus.

PubMed

Khositseth, Sookkasem; Charngkaew, Komgrid; Boonkrai, Chatikorn; Somparn, Poorichaya; Uawithya, Panapat; Chomanee, Nusara; Payne, D Michael; Fenton, Robert A; Pisitkun, Trairak

2017-05-01

Hypercalcemia can cause renal dysfunction such as nephrogenic diabetes insipidus (NDI), but the mechanisms underlying hypercalcemia-induced NDI are not well understood. To elucidate the early molecular changes responsible for this disorder, we employed mass spectrometry-based proteomic analysis of inner medullary collecting ducts (IMCD) isolated from parathyroid hormone-treated rats at onset of hypercalcemia-induced NDI. Forty-one proteins, including the water channel aquaporin-2, exhibited significant changes in abundance, most of which were decreased. Bioinformatic analysis revealed that many of the downregulated proteins were associated with cytoskeletal protein binding, regulation of actin filament polymerization, and cell-cell junctions. Targeted LC-MS/MS and immunoblot studies confirmed the downregulation of 16 proteins identified in the initial proteomic analysis and in additional experiments using a vitamin D treatment model of hypercalcemia-induced NDI. Evaluation of transcript levels and estimated half-life of the downregulated proteins suggested enhanced protein degradation as the possible regulatory mechanism. Electron microscopy showed defective intercellular junctions and autophagy in the IMCD cells from both vitamin D- and parathyroid hormone-treated rats. A significant increase in the number of autophagosomes was confirmed by immunofluorescence labeling of LC3. Colocalization of LC3 and Lamp1 with aquaporin-2 and other downregulated proteins was found in both models. Immunogold electron microscopy revealed aquaporin-2 in autophagosomes in IMCD cells from both hypercalcemia models. Finally, parathyroid hormone withdrawal reversed the NDI phenotype, accompanied by termination of aquaporin-2 autophagic degradation and normalization of both nonphoshorylated and S256-phosphorylated aquaporin-2 levels. Thus, enhanced autophagic degradation of proteins plays an important role in the initial mechanism of hypercalcemic-induced NDI. Copyright © 2016

Hypertonic saline for brain relaxation and intracranial pressure in patients undergoing neurosurgical procedures: a meta-analysis of randomized controlled trials.

PubMed

Shao, Liujiazi; Hong, Fangxiao; Zou, Yi; Hao, Xiaofang; Hou, Haijun; Tian, Ming

2015-01-01

A wealth of evidence from randomized controlled trials (RCTs) has indicated that hypertonic saline (HS) is at least as effective as, if not better than, mannitol in the treatment of increased intracranial pressure(ICP). However, there is little known about the effects of HS in patients during neurosurgery. Thus, this meta-analysis was performed to compare the intraoperative effects of HS with mannitol in patients undergoing craniotomy. According to the research strategy, we searched PUBMED, EMBASE and Cochrane Central Register of Controlled Trials. Other sources such as the internet-based clinical trial registries and conference proceedings were also searched. After literature searching, two investigators independently performed literature screening, quality assessment of the included trials and data extraction. The outcomes included intraoperative brain relaxation, intraoperative ICP, total volume of fluid required, diuresis, hemodynamic parameters, electrolyte level, mortality or dependence and adverse events. Seven RCTs with 468 participants were included. The quality of the included trials was acceptable. HS could significantly increase the odds of satisfactory intraoperative brain relaxation (OR: 2.25, 95% CI: 1.32-3.81; P = 0.003) and decrease the mean difference (MD) of maximal ICP (MD: -2.51 mmHg, 95% CI: -3.39--1.93 mmHg; P<0.00001) in comparison with mannitol with no significant heterogeneity among the study results. Compared with HS, mannitol had a more prominent diuretic effect. And patients treated with HS had significantly higher serum sodium than mannitol-treated patients. Considering that robust outcome measures are absent because brain relaxation and ICP can be influenced by several factors except for the hyperosmotic agents, the results of present meta-analysis should be interpreted with cautions. Well-designed RCTs in the future are needed to further test the present results, identify the impact of HS on the clinically relevant outcomes and

A fragment-based approach to the SAMPL3 Challenge

NASA Astrophysics Data System (ADS)

Kulp, John L.; Blumenthal, Seth N.; Wang, Qiang; Bryan, Richard L.; Guarnieri, Frank

2012-05-01

The success of molecular fragment-based design depends critically on the ability to make predictions of binding poses and of affinity ranking for compounds assembled by linking fragments. The SAMPL3 Challenge provides a unique opportunity to evaluate the performance of a state-of-the-art fragment-based design methodology with respect to these requirements. In this article, we present results derived from linking fragments to predict affinity and pose in the SAMPL3 Challenge. The goal is to demonstrate how incorporating different aspects of modeling protein-ligand interactions impact the accuracy of the predictions, including protein dielectric models, charged versus neutral ligands, ΔΔGs solvation energies, and induced conformational stress. The core method is based on annealing of chemical potential in a Grand Canonical Monte Carlo (GC/MC) simulation. By imposing an initially very high chemical potential and then automatically running a sequence of simulations at successively decreasing chemical potentials, the GC/MC simulation efficiently discovers statistical distributions of bound fragment locations and orientations not found reliably without the annealing. This method accounts for configurational entropy, the role of bound water molecules, and results in a prediction of all the locations on the protein that have any affinity for the fragment. Disregarding any of these factors in affinity-rank prediction leads to significantly worse correlation with experimentally-determined free energies of binding. We relate three important conclusions from this challenge as applied to GC/MC: (1) modeling neutral ligands—regardless of the charged state in the active site—produced better affinity ranking than using charged ligands, although, in both cases, the poses were almost exactly overlaid; (2) simulating explicit water molecules in the GC/MC gave better affinity and pose predictions; and (3) applying a ΔΔGs solvation correction further improved the ranking of the

4-PBA improves lithium-induced nephrogenic diabetes insipidus by attenuating ER stress.

PubMed

Zheng, Peili; Lin, Yu; Wang, Feifei; Luo, Renfei; Zhang, Tiezheng; Hu, Shan; Feng, Pinning; Liang, Xinling; Li, Chunling; Wang, Weidong

2016-10-01

Endoplasmic reticulum (ER) stress has been implicated in some types of glomerular and tubular disorders. The objectives of this study were to elucidate the role of ER stress in lithium-induced nephrogenic diabetes insipidus (NDI) and to investigate whether attenuation of ER stress by 4-phenylbutyric acid (4-PBA) improves urinary concentrating defect in lithium-treated rats. Wistar rats received lithium (40 mmol/kg food), 4-PBA (320 mg/kg body wt by gavage every day), or no treatment (control) for 2 wk, and they were dehydrated for 24 h before euthanasia. Lithium treatment resulted in increased urine output and decreased urinary osmolality, which was significantly improved by 4-PBA. 4-PBA also prevented reduced protein expression of aquaporin-2 (AQP2), pS256-AQP2, and pS261-AQP2 in the inner medulla of kidneys from lithium-treated rats after 24-h dehydration. Lithium treatment resulted in increased expression of ER stress markers in the inner medulla, which was associated with dilated cisternae and expansion of ER in the inner medullary collecting duct (IMCD) principal cells. Confocal immunofluorescence studies showed colocalization of a molecular chaperone, binding IgG protein (BiP), with AQP2 in principal cells. Immunohistochemistry demonstrated increased intracellular expression of BiP and decreased AQP2 expression in IMCD principal cells of kidneys from lithium-treated rats. 4-PBA attenuated expression of ER stress markers and recovered ER morphology. In IMCD suspensions isolated from lithium-treated rats, 4-PBA incubation was also associated with increased AQP2 expression and ameliorated ER stress. In conclusion, in experimental lithium-induced NDI, 4-PBA improved the urinary concentrating defect and increased AQP2 expression, likely via attenuating ER stress in IMCD principal cells. Copyright © 2016 the American Physiological Society.

Immunohistochemical localization of luteinizing hormone-releasing hormone (LHRH) in the hypothalamus of adult female hamsters treated neonatally with monosodium glutamate or hypertonic saline.

PubMed

Lamperti, A A; Pickard, G E

1984-05-01

The immunohistochemical localization of luteinizing hormone-releasing hormone (LHRH) was studied in paraffin and vibratome-sectioned tissue from adult female hamsters that were treated neonatally with monosodium glutamate (MSG) or hypertonic saline. There appeared to be a reduction in LHRH-positive fibers in the median eminence of animals with an MSG-induced lesion of the arcuate nucleus in paraffin-embedded tissue. However, when unembedded tissue was cut on a vibratome, the distribution of LHRH-positive fibers and perikarya was similar in both groups of animals. Fibers were seen coursing through the periventricular area and lateral hypothalamus to the median eminence. In addition, LHRH-positive fibers were seen in the organum vasculosum of the lamina terminalis, subfornical organ, septal and preoptic areas, fasciculus retroflexus, habenular complex, and several regions in the basal forebrain. Animals that were pretreated with colchicine had LHRH-positive perikarya in the medial habenular nucleus, diagonal band of Broca, and the medial olfactory tract.

Advantage and Challenges of $$Nb_3Sn$$ Superconducting Undulators

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

Zlobin, A. V.; Barzi, E.; Turrinoni, D.

Utilization of Nb3Sn superconducting wires offers the possibility to increase undulators’ nominal operation field and temperature margin, but requires overcoming chal-lenges that are described in this paper. The achievable field levels for a Nb3Sn version of superconducting undulators being developed at APS-ANL and the conductor choice are also presented and discussed.

Improvement of Neuroenergetics by Hypertonic Lactate Therapy in Patients with Traumatic Brain Injury Is Dependent on Baseline Cerebral Lactate/Pyruvate Ratio

PubMed Central

Quintard, Hervé; Patet, Camille; Zerlauth, Jean-Baptiste; Suys, Tamarah; Bouzat, Pierre; Pellerin, Luc; Meuli, Reto; Magistretti, Pierre J.

2016-01-01

Abstract Energy dysfunction is associated with worse prognosis after traumatic brain injury (TBI). Recent data suggest that hypertonic sodium lactate infusion (HL) improves energy metabolism after TBI. Here, we specifically examined whether the efficacy of HL (3h infusion, 30–40 μmol/kg/min) in improving brain energetics (using cerebral microdialysis [CMD] glucose as a main therapeutic end-point) was dependent on baseline cerebral metabolic state (assessed by CMD lactate/pyruvate ratio [LPR]) and cerebral blood flow (CBF, measured with perfusion computed tomography [PCT]). Using a prospective cohort of 24 severe TBI patients, we found CMD glucose increase during HL was significant only in the subgroup of patients with elevated CMD LPR >25 (n = 13; +0.13 [95% confidence interval (CI) 0.08–0.19] mmol/L, p < 0.001; vs. +0.04 [–0.05–0.13] in those with normal LPR, p = 0.33, mixed-effects model). In contrast, CMD glucose increase was independent from baseline CBF (coefficient +0.13 [0.04–0.21] mmol/L when global CBF was <32.5 mL/100 g/min vs. +0.09 [0.04–0.14] mmol/L at normal CBF, both p < 0.005) and systemic glucose. Our data suggest that improvement of brain energetics upon HL seems predominantly dependent on baseline cerebral metabolic state and support the concept that CMD LPR – rather than CBF – could be used as a diagnostic indication for systemic lactate supplementation following TBI. PMID:26421521

The Mock LISA Data Challenge Round 3: New and Improved Sources

NASA Technical Reports Server (NTRS)

Baker, John

2008-01-01

The Mock LISA Data Challenges are a program to demonstrate and encourage the development of data-analysis capabilities for LISA. Each round of challenges consists of several data sets containing simulated instrument noise and gravitational waves from sources of undisclosed parameters. Participants are asked to analyze the data sets and report the maximum information they can infer about the source parameters. The challenges are being released in rounds of increasing complexity and realism. Challenge 3. currently in progress, brings new source classes, now including cosmic-string cusps and primordial stochastic backgrounds, and more realistic signal models for supermassive black-hole inspirals and galactic double white dwarf binaries.

NFAT5 Is Activated by Hypoxia: Role in Ischemia and Reperfusion in the Rat Kidney

PubMed Central

Villanueva, Sandra; Suazo, Cristian; Santapau, Daniela; Pérez, Francisco; Quiroz, Mariana; Carreño, Juan E.; Illanes, Sebastián; Lavandero, Sergio; Michea, Luis; Irarrazabal, Carlos E.

2012-01-01

The current hypothesis postulates that NFAT5 activation in the kidney's inner medulla is due to hypertonicity, resulting in cell protection. Additionally, the renal medulla is hypoxic (10–18 mmHg); however there is no information about the effect of hypoxia on NFAT5. Using in vivo and in vitro models, we evaluated the effect of reducing the partial pressure of oxygen (PO2) on NFAT5 activity. We found that 1) Anoxia increased NFAT5 expression and nuclear translocation in primary cultures of IMCD cells from rat kidney. 2) Anoxia increased transcriptional activity and nuclear translocation of NFAT5 in HEK293 cells. 3) The dose-response curve demonstrated that HIF-1α peaked at 2.5% and NFAT5 at 1% of O2. 4) At 2.5% of O2, the time-course curve of hypoxia demonstrated earlier induction of HIF-1α gene expression than NFAT5. 5) siRNA knockdown of NFAT5 increased the hypoxia-induced cell death. 6) siRNA knockdown of HIF-1α did not affect the NFAT5 induction by hypoxia. Additionally, HIF-1α was still induced by hypoxia even when NFAT5 was knocked down. 7) NFAT5 and HIF-1α expression were increased in kidney (cortex and medulla) from rats subjected to an experimental model of ischemia and reperfusion (I/R). 7) Experimental I/R increased the NFAT5-target gene aldose reductase (AR). 8) NFAT5 activators (ATM and PI3K) were induced in vitro (HEK293 cells) and in vivo (I/R kidneys) with the same timing of NFAT5. 8) Wortmannin, which inhibits ATM and PI3K, reduces hypoxia-induced NFAT5 transcriptional activation in HEK293 cells. These results demonstrate for the first time that NFAT5 is induced by hypoxia and could be a protective factor against ischemic damage. PMID:22768306

NASA Centennial Challenge: Three Dimensional (3D) Printed Habitat, Phase 2

NASA Technical Reports Server (NTRS)

Mueller, Robert P.; Roman, Monserrate C.; Kim, Hong S.

2017-01-01

The NASA Centennial Challenges: 3D-Printed Habitat Challenge seeks to develop the fundamental technologies necessary to manufacture an off-world habitat using mission recycled materials andor local indigenous materials. The vision is that autonomous habitat manufacturing machines will someday be deployed to the Moon or Mars to construct shelters for human habitation.NASA and Bradley University, are holding a new US$ 2.5 million competition to design and build a 3-D printed habitat for deep space exploration, including the agencys journey to Mars.The multi-phase 3-D Printed Habitat Challenge, part of NASA's Centennial Challenges program, is designed to advance the additive construction technology needed to create sustainable housing solutions for Earth and beyond.The first phase of the competition ran through Sept. 27, 2015. This phase, a design competition, called on participants to develop state-of-the-art architectural concepts that take advantage of the unique capabilities 3-D printing offers. The top 3 prizes with a prize purse of $40,000 were awarded at the 2015 World Maker Faire in New York.The second phase of the competition is called the Structural Member Competition and it is divided into three levels happening in the spring and summer of 2017. The Compression Test Competition (Level 1) focuses on the fabrication technologies needed to manufacture structural components from a combination of indigenous materials and recyclables, or indigenous materials alone. For Level 1, teams will develop 3D printable materials, build a 3D printing machine, and print two specimens: a truncated cone and a cylinder. The Level 2 Beam Member Competition is the second of three sub-competitions within the overall Structural Member Competition. For Level 2, teams will print a beam that will be tested.The Level 3 Head to Head Competition is the third of three sub-competitions within the overall Structural Member Competition. For Level 3, teams will develop 3D printable materials

Osmotic tolerance of avian spermatozoa: Influence of time, temperature, cryoprotectant and membrane ion pump function on sperm viability

USGS Publications Warehouse

Blanco, J.M.; Long, J.A.; Gee, G.; Donoghue, A.M.; Wildt, D.E.

2008-01-01

Potential factors influencing sperm survival under hypertonic conditions were evaluated in the Sandhill crane (Grus canadensis) and turkey (Meleagridis gallopavo). Sperm osmotolerance (300-3000 mOsm/kg) was evaluated after: (1) equilibration times of 2, 10, 45 and 60 min at 4 ?C versus 21 ?C; (2) pre-equilibrating with dimethylacetamide (DMA) or dimethylsulfoxide (Me2SO) at either 4 ?C or 21 ?C; and (3) inhibition of the Na+/K+ and the Na+/H+ antiporter membrane ionic pumps. Sperm viability was assessed using the eosin-nigrosin live/dead stain. Species-specific differences occurred in response to hypertonic conditions with crane sperm remaining viable under extreme hypertonicity (3000 mOsm/kg), whereas turkey sperm viability was compromised with only slightly hypertonic (500 mOsm/kg) conditions. The timing of spermolysis under hypertonic conditions was also species-specific, with a shorter interval for turkey (2 min) than crane (10 min) sperm. Turkey sperm osmotolerance was slightly improved by lowering the incubation temperature from 21 to 4 ?C. Pre-equilibrating sperm with DMA reduced the incidence of hypertonic spermolysis only in the crane, at both room and refrigeration temperature. Inhibiting the Na+/K+ and the Na+/H+ antiporter membrane ion pumps did not impair resistance of crane and turkey spermatozoa to hypertonic stress; pump inhibition actually increased turkey sperm survival compared to control sperm. Results demonstrate marked species specificity in osmotolerance between crane and turkey sperm, as well as in the way temperature and time of exposure affect sperm survival under hypertonic conditions. Differences are independent of the role of osmotic pumps in these species.

[Effect of compound hypertonic saline solution on septic rats].

PubMed

Dong, Fang; Xu, Liang; Xu, Gang; Wang, Huabing; Lu, Huizhi; Cai, Liping

2015-01-01

To study the effect of compound hypertonic saline solution ( HSD ) on sepsis. 133 male Wistar rats were divided into four groups, sham operation group ( n = 15 ), cecal ligation and puncture ( CLP ) group ( n = 45 ), CLP plus normal saline ( NS ) group ( n = 45 ), and CLP plus HSD group ( n = 28 ). A rat model of sepsis was reproduced by CLP, and the rats in sham operation group received celiotomy without ligation and puncture. All rats in four groups received subcutaneous injection of 30 mL/kg 0.9% sodium chloride after laparotomy. The rats in CLP plus NS group and CLP plus HSD group received infusion of 5 mL/kg 0.9% sodium chloride or 7.5% sodium chloride/6% dextran post CLP via jugular vein for 3 hours, with the infusion rate of 0.4 mL×kg(-1)×min(-1). The survival rate of each group was observed 9 hours and 18 hours after laparotomy. Mean arterial pressure ( MAP ) at 0, 9, 18 hours were monitored. Blood specimens were collected from all rats 0, 9 and 18 hours after laparotomy, respectively, for measurement of the plasma levels of tumor necrosis factor-α ( TNF-α), interleukin-1β ( IL-1β ), and procalcitonin ( PCT ). The rats were all sacrificed, and their lung tissues were harvested for the neutrophil count in bronchoalveolar lavage fluid ( BALF ), myeloperoxidase ( MPO ) activity in lung tissue, wet/dry weight ratio ( W/D ) of lung, and pathological changes in lung tissue. There was no death in the sham operation group. The survival rates at 9 hours and 18 hours were 62.2% and 31.1% in the CLP group, 57.8% and 35.6% in the CLP plus NS group, 85.7% and 64.3% in the CLP plus HSD group, and they were all significantly higher compared with those of the CLP group and the CLP plus NS group ( P<0.05 or P<0.01 ). MAP levels in the CLP group and the CLP plus NS group were significantly lower than those in sham operation group, and the plasma levels of TNF-α, IL-1β and PCT were significantly higher compared with those of sham operation group, while there was no

The HYSLAR trial: a prospective randomized controlled trial of the use of a restrictive fluid regimen with 3% hypertonic saline versus lactated Ringers in patients undergoing pancreaticoduodenectomy.

PubMed

Lavu, Harish; Sell, Naomi M; Carter, Timothy I; Winter, Jordan M; Maguire, David P; Gratch, David M; Berman, Richard A; Feil, Marian G; Grunwald, Zvi; Leiby, Benjamin E; Pequignot, Edward C; Rosato, Ernest L; Yeo, Charles J

2014-09-01

This study was designed to determine whether the volume and type of fluid administered for pancreaticoduodenectomy impacts postoperative outcomes. Three percent hypertonic saline (HYS) has been suggested as a means of reducing the volume of fluid required to sustain tissue perfusion in the perioperative period. Between May 2011 and November 2013, patients undergoing pancreaticoduodenectomy were enrolled in an institutional review board-approved, single-center, prospective, parallel, randomized controlled trial (NCT 01428050), comparing lactated Ringers (LAR) (15 mL/kg/hr LAR intraoperation, 2 mL/kg/hr LAR postoperation) with HYS (9 mL/kg/hr LAR and 1 mL/kg/hr HYS intraoperation, 1 mL/kg/hr HYS postoperation). A total of 264 patients were randomized. Demographic variables between groups were similar. The HYS patients had a significantly reduced net fluid balance (65 vs 91 mL/kg, P = 0.02). The overall complication rate was reduced in the HYS group (43% vs 54%), with a relative risk of 0.79 [95% confidence interval (CI), 0.62-1.02; P = 0.073], factoring stratification for pancreas texture. After adjustment for age and weight, the relative risk was 0.75 [95% CI (0.58-0.96); P = 0.023]. The total number of complications was significantly reduced in the HYS group (93 vs 123), with an incidence rate ratio of 0.74 [95% CI (0.56-0.97); P = 0.027]. After adjustment for age and weight, the incidence rate ratio was 0.69 [95% CI (0.52-0.90); P = 0.0068]. Reoperations, length of stay, readmissions, and 90-day mortality were similar between groups. A moderately restrictive fluid regimen with HYS resulted in a statistically significant 25% reduction in complications when adjusted for age, weight, and pancreatic texture.

Ad libitum fluid intake and plasma responses after pickle juice, hypertonic saline, or deionized water ingestion.

PubMed

Allen, Scott; Miller, Kevin C; Albrecht, Jay; Garden-Robinson, Julie; Blodgett-Salafia, Elizabeth

2013-01-01

Adding sodium (Na(+)) to drinks improves rehydration and ad libitum fluid consumption. Clinicians (∼25%) use pickle juice (PJ) to treat cramping. Scientists warn against PJ ingestion, fearing it will cause rapid plasma volume restoration and thereby decrease thirst and delay rehydration. Advice about drinking PJ has been developed but never tested. To determine if drinking small volumes of PJ, hypertonic saline (HS), or deionized water (DIW) affects ad libitum DIW ingestion, plasma variables, or perceptual indicators. Crossover study. Laboratory. Fifteen, euhydrated (urine specific gravity ≤ 1.01) men (age = 22 ± 2 years, height = 178 ± 6 cm, mass = 82.9 ± 8.4 kg). Participants completed 3 testing days (≥ 72 hours between days). After a 30-minute rest, a blood sample was collected. Participants completed 60 minutes of hard exercise (temperature = 36 ± 2°C, relative humidity = 16 ± 1%). Postexercise, they rested for 30 minutes; had a blood sample collected; rated thirst, fullness, and nausea; and ingested 83 ± 8 mL of PJ, HS, or DIW. They rated drink palatability (100-mm visual analog scale) and were allowed to drink DIW ad libitum for 60 minutes. Blood samples and thirst, fullness, and nausea ratings (100-mm visual analog scales) were collected at 15, 30, 45, and 60 minutes posttreatment drink ingestion. Ad libitum DIW volume, percentage change in plasma volume, plasma osmolality (OSMp,) plasma sodium concentration ([Na(+)]p), and thirst, fullness, nausea, and palatability ratings. Participants consumed more DIW ad libitum after HS (708.03 ± 371.03 mL) than after DIW (532.99 ± 337.14 mL, P < .05). Ad libitum DIW ingested after PJ (700.35 ± 366.15 mL) was similar to that after HS and DIW (P > .05). Plasma sodium concentration, OSMp, percentage change in plasma volume, thirst, fullness, and nausea did not differ among treatment drinks over time (P > .05). Deionized water (73 ± 14 mm) was more palatable than HS (17 ± 13 mm) or PJ (26 ± 16 mm, P

Emergence of 3D Printed Dosage Forms: Opportunities and Challenges.

PubMed

Alhnan, Mohamed A; Okwuosa, Tochukwu C; Sadia, Muzna; Wan, Ka-Wai; Ahmed, Waqar; Arafat, Basel

2016-08-01

The recent introduction of the first FDA approved 3D-printed drug has fuelled interest in 3D printing technology, which is set to revolutionize healthcare. Since its initial use, this rapid prototyping (RP) technology has evolved to such an extent that it is currently being used in a wide range of applications including in tissue engineering, dentistry, construction, automotive and aerospace. However, in the pharmaceutical industry this technology is still in its infancy and its potential yet to be fully explored. This paper presents various 3D printing technologies such as stereolithographic, powder based, selective laser sintering, fused deposition modelling and semi-solid extrusion 3D printing. It also provides a comprehensive review of previous attempts at using 3D printing technologies on the manufacturing dosage forms with a particular focus on oral tablets. Their advantages particularly with adaptability in the pharmaceutical field have been highlighted, which enables the preparation of dosage forms with complex designs and geometries, multiple actives and tailored release profiles. An insight into the technical challenges facing the different 3D printing technologies such as the formulation and processing parameters is provided. Light is also shed on the different regulatory challenges that need to be overcome for 3D printing to fulfil its real potential in the pharmaceutical industry.

3D bioprinting for reconstructive surgery: Principles, applications and challenges.

PubMed

Jessop, Zita M; Al-Sabah, Ayesha; Gardiner, Matthew D; Combellack, Emman; Hawkins, Karl; Whitaker, Iain S

2017-09-01

Despite the increasing laboratory research in the growing field of 3D bioprinting, there are few reports of successful translation into surgical practice. This review outlines the principles of 3D bioprinting including software and hardware processes, biocompatible technological platforms and suitable bioinks. The advantages of 3D bioprinting over traditional tissue engineering techniques in assembling cells, biomaterials and biomolecules in a spatially controlled manner to reproduce native tissue macro-, micro- and nanoarchitectures are discussed, together with an overview of current progress in bioprinting tissue types relevant for plastic and reconstructive surgery. If successful, this platform technology has the potential to biomanufacture autologous tissue for reconstruction, obviating the need for donor sites or immunosuppression. The biological, technological and regulatory challenges are highlighted, with strategies to overcome these challenges by using an integrated approach from the fields of engineering, biomaterial science, cell biology and reconstructive microsurgery. Copyright © 2017. Published by Elsevier Ltd.

The comparative effects of 3% saline and 0.5M sodium lactate on cardiac function:a randomised, crossover study in volunteers.

PubMed

Nalos, Marek; Kholodniak, Euguenia; Smith, Louise; Orde, Sam; Ting, Iris; Slama, Michel; Seppelt, Ian; McLean, Anthony S; Huang, Stephen

2018-06-01

To investigate the metabolic and cardiac effects of intravenous administration of two hypertonic solutions - 3% saline (SAL) and 0.5M sodium lactate (LAC). A randomised, doubleblind, crossover study in ten human volunteers. Intravenous bolus of either SAL or LAC at 3 mL/kg over 20 min followed by a 2 mL/kg infusion over 60 min. Acid base parameters and echocardiographic indices of cardiac function, cardiac output (CO), left ventricular ejection fraction (LVEF) and mitral annular peak systolic velocity (Sm) before and after infusion of SAL or LAC. Despite haemodilution, we observed an increase in sodium (139 ± 2 mmol/L to 142 ± 2 mmol/L in both groups) and respective anions, chloride (106 ± 2 mmol/L to 112 ± 3 mmol/L) and lactate (1.01 ± 0.28 mmol/L to 2.38 ± 0.38 mmol/L) with SAL and LAC, respectively. The pH (7.37 ± 0.03 to 7.45 ± 0.03; P < 0.01) and simplified strong ion difference (SID) (36.3 ± 4.6 mmol/L to 39.2 ± 3.6 mmol/L; P < 0.01) increased during the LAC infusion. The pH was unchanged, but SID decreased during SAL infusion (36.3 ± 2.5 mmol/L to 33.9 ± 3.1 mmol/L; P = 0.01). Both solutions led to an increase in preload and cardiac function, CO (4.36 ± 0.79 L/min to 4.98 ± 1.37 L/ min v 4.62 ± 1.30 L/min to 5.13 ± 1.44 L/min), LVEF (61 ± 6% to 63 ± 8% v 64 ± 6% to 68 ± 7%). The averaged Sm improved in the LAC group as compared with the SAL group (0.088 ± 0.008 to 0.096 ± 0.016 v 0.086 ± 0.012 to 0.082 ± 0.012; P = 0.032). The administration of SAL or LAC has opposing effects on acid base variables such as SID. Hypertonic fluid infusion lead to increased cardiac preload and performance with Sm, suggesting better left ventricular systolic function during LAC as compared with SAL. Lactated hypertonic solutions should be evaluated as resuscitation fluids.

Dragon enhances BMP signaling and increases transepithelial resistance in kidney epithelial cells.

PubMed

Xia, Yin; Babitt, Jodie L; Bouley, Richard; Zhang, Ying; Da Silva, Nicolas; Chen, Shanzhuo; Zhuang, Zhenjie; Samad, Tarek A; Brenner, Gary J; Anderson, Jennifer L; Hong, Charles C; Schneyer, Alan L; Brown, Dennis; Lin, Herbert Y

2010-04-01

The neuronal adhesion protein Dragon acts as a bone morphogenetic protein (BMP) coreceptor that enhances BMP signaling. Given the importance of BMP signaling in nephrogenesis and its putative role in the response to injury in the adult kidney, we studied the localization and function of Dragon in the kidney. We observed that Dragon localized predominantly to the apical surfaces of tubular epithelial cells in the thick ascending limbs, distal convoluted tubules, and collecting ducts of mice. Dragon expression was weak in the proximal tubules and glomeruli. In mouse inner medullary collecting duct (mIMCD3) cells, Dragon generated BMP signals in a ligand-dependent manner, and BMP4 is the predominant endogenous ligand for the Dragon coreceptor. In mIMCD3 cells, BMP4 normally signaled through BMPRII, but Dragon enhanced its signaling through the BMP type II receptor ActRIIA. Dragon and BMP4 increased transepithelial resistance (TER) through the Smad1/5/8 pathway. In epithelial cells isolated from the proximal tubule and intercalated cells of collecting ducts, we observed coexpression of ActRIIA, Dragon, and BMP4 but not BMPRII. Taken together, these results suggest that Dragon may enhance BMP signaling in renal tubular epithelial cells and maintain normal renal physiology.

Hypertonic saline-epinephrine local injection therapy for post-endoscopic sphincterotomy bleeding: removal of blood clots using pure ethanol local injection.

PubMed

Sakai, Yuji; Tsuyuguchi, Toshio; Sugiyama, Harutoshi; Nishikawa, Takao; Kurosawa, Jo; Saito, Masayoshi; Tawada, Katsunobu; Mikata, Rintaro; Tada, Motohisa; Ishihara, Takeshi; Yokosuka, Osamu

2013-08-01

Bleeding following endoscopic sphincterotomy (EST) is a rare but unavoidable complication of the procedure. We routinely perform local injection of hypertonic saline-epinephrine (HSE) for the treatment of post-EST bleeding. Any blood clot is removed only by irrigation with water after local injection of pure ethanol into the blood clot to cause crusting. We evaluated the usefulness of this treatment method. Subjects were 8 patients (1.2%) with post-EST bleeding requiring hemostatic intervention among 682 patients undergoing EST. After determination of the bleeding point, local injection of HSE was performed. When an adherent blood clot was present, pure ethanol was injected into the blood clot and then irrigation with water was performed to remove the blood clot. Endoscopic hemostasis was successfully achieved in all the 8 patients (100%). In 4 patients (50%), the adherent blood clots were successfully removed only with pure ethanol local injection into the blood clot followed by irrigation with water. No complications of the hemostatic procedure occurred in any patients. This study indicated that hemostasis with HSE local injection can be safe and useful for the treatment of post-EST bleeding, and also that blood clot removal with pure ethanol local injection can be useful.

The effect of topical treatments for CRS on the sinonasal epithelial barrier.

PubMed

Ramezanpour, M; Rayan, A; Smith, J L P; Vreugde, S

2017-06-01

Several topical treatments are used in the management of Chronic Rhinosinusitis (CRS), some of which the safety and efficacy has yet to be determined. The purpose of this study was to investigate the effect of commonly used topical treatments on the sinonasal epithelial barrier. Normal saline (0.9% Sodium Chloride), hypertonic saline (3% Sodium Chloride), FESS Sinu-Cleanse Hypertonic, FLO Sinus Care and Budesonide 1 mg/ 2 ml were applied to the apical side of air-liquid interface (ALI) cultures of primary human nasal epithelial cells (HNECs) from CRS patients (n=3) and non-CRS controls (n=3) for 24 hours. Epithelial barrier structure and function was assessed using trans-epithelial electrical resistance (TEER), measuring the passage of Fluorescein Isothiocyanate labelled Dextrans (FITC-Dextrans) and assessing the expression of the tight junction protein Zona Occludens-1 (ZO-1) using immunofluorescence. Toxicity was assessed using a Lactate Dehydrogenase (LDH) assay. Data was analysed using ANOVA, followed by Tukey HSD post hoc test. Hypertonic solution and budesonide significantly increased TEER values in CRS derived HNECs. In contrast, FESS Sinu-Cleanse Hypertonic significantly reduced TEER 5 minutes after application of the solution followed by an increase in paracellular permeability of FITC-Dextrans (30 minutes) and increased LDH levels 6 hours after application of the solution. Our findings confirm that isotonic and hypertonic saline solutions do not compromise epithelial barrier function in vitro but underscore the importance of examining safety and efficacy of over-the-counter wash solutions.

The Effects of Three Nebulized Osmotic Agents in the Dry Larynx

ERIC Educational Resources Information Center

Tanner, Kristine; Roy, Nelson; Merrill, Ray M.; Elstad, Mark

2007-01-01

Purpose: This investigation examined the effects of nebulized hypertonic saline, isotonic saline (IS), and sterile (hypotonic) water on phonation threshold pressure (PTP) and self-perceived phonatory effort (PPE) following a surface laryngeal dehydration challenge. Method: In a double-blind, randomized experimental trial, 60 vocally healthy women…

K(+) channels of squid giant axons open by an osmotic stress in hypertonic solutions containing nonelectrolytes.

PubMed

Kukita, Fumio

2011-08-01

In hypertonic solutions made by adding nonelectrolytes, K(+) channels of squid giant axons opened at usual asymmetrical K(+) concentrations in two different time courses; an initial instantaneous activation (I (IN)) and a sigmoidal activation typical of a delayed rectifier K(+) channel (I (D)). The current-voltage relation curve for I (IN) was fitted well with Goldman equation described with a periaxonal K(+) concentration at the membrane potential above -10 mV. Using the activation-voltage curve obtained from tail currents, K(+) channels for I (IN) are confirmed to activate at the membrane potential that is lower by 50 mV than those for I (D). Both I (IN) and I (D) closed similarly at the holding potential below -100 mV. The logarithm of I (IN)/I (D) was linearly related with the osmolarity for various nonelectrolytes. Solute inaccessible volumes obtained from the slope increased with the nonelectrolyte size from 15 to 85 water molecules. K(+) channels representing I (D) were blocked by open channel blocker tetra-butyl ammonium (TBA) more efficiently than in the absence of I (IN), which was explained by the mechanism that K(+) channels for I (D) were first converted to those for I (IN) by the osmotic pressure and then blocked. So K(+) channels for I (IN) were suggested to be derived from the delayed rectifier K(+) channels. Therefore, the osmotic pressure is suggested to exert delayed-rectifier K(+) channels to open in shrinking rather hydrophilic flexible parts outside the pore than the pore itself, which is compatible with the recent structure of open K(+) channel pore.

Towards a Rigorous Assessment of Systems Biology Models: The DREAM3 Challenges

PubMed Central

Prill, Robert J.; Marbach, Daniel; Saez-Rodriguez, Julio; Sorger, Peter K.; Alexopoulos, Leonidas G.; Xue, Xiaowei; Clarke, Neil D.; Altan-Bonnet, Gregoire; Stolovitzky, Gustavo

2010-01-01

Background Systems biology has embraced computational modeling in response to the quantitative nature and increasing scale of contemporary data sets. The onslaught of data is accelerating as molecular profiling technology evolves. The Dialogue for Reverse Engineering Assessments and Methods (DREAM) is a community effort to catalyze discussion about the design, application, and assessment of systems biology models through annual reverse-engineering challenges. Methodology and Principal Findings We describe our assessments of the four challenges associated with the third DREAM conference which came to be known as the DREAM3 challenges: signaling cascade identification, signaling response prediction, gene expression prediction, and the DREAM3 in silico network challenge. The challenges, based on anonymized data sets, tested participants in network inference and prediction of measurements. Forty teams submitted 413 predicted networks and measurement test sets. Overall, a handful of best-performer teams were identified, while a majority of teams made predictions that were equivalent to random. Counterintuitively, combining the predictions of multiple teams (including the weaker teams) can in some cases improve predictive power beyond that of any single method. Conclusions DREAM provides valuable feedback to practitioners of systems biology modeling. Lessons learned from the predictions of the community provide much-needed context for interpreting claims of efficacy of algorithms described in the scientific literature. PMID:20186320

Increased long-latency reflex activity as a sufficient explanation for childhood hypertonic dystonia: a neuromorphic emulation study

NASA Astrophysics Data System (ADS)

Sohn, Won J.; Niu, Chuanxin M.; Sanger, Terence D.

2015-06-01

Objective. Childhood dystonia is a movement disorder that interferes with daily movements and can have a devastating effect on quality of life for children and their families. Although injury to basal ganglia is associated with dystonia, the neurophysiological mechanisms leading to the clinical manifestations of dystonia are not understood. Previous work suggested that long-latency stretch reflex (LLSR) is hyperactive in children with hypertonia due to secondary dystonia. We hypothesize that abnormal activity in motor cortices may cause an increase in the LLSR leading to hypertonia. Approach. We modeled two possibilities of hyperactive LLSR by either creating a tonic involuntary drive to cortex, or increasing the synaptic gain in cortical neurons. Both models are emulated using programmable very-large-scale-integrated-circuit hardware to test their sufficiency for producing dystonic symptoms. The emulation includes a joint with two Hill-type muscles, realistic muscle spindles, and 2,304 Izhikevich-type spiking neurons. The muscles are regulated by a monosynaptic spinal pathway with 32 ms delay and a long-latency pathway with 64 ms loop-delay representing transcortical/supra-spinal connections. Main results. When the limb is passively stretched, both models produce involuntary resistance with increased antagonist EMG responses similar to human data; also the muscle relaxation is delayed similar to human data. Both models predict reduced range of motion in voluntary movements. Significance. Although our model is a highly simplified and limited representation of reflex pathways, it shows that increased activity of the LLSR is by itself sufficient to cause many of the features of hypertonic dystonia.

Computational fragment-based screening using RosettaLigand: the SAMPL3 challenge

NASA Astrophysics Data System (ADS)

Kumar, Ashutosh; Zhang, Kam Y. J.

2012-05-01

SAMPL3 fragment based virtual screening challenge provides a valuable opportunity for researchers to test their programs, methods and screening protocols in a blind testing environment. We participated in SAMPL3 challenge and evaluated our virtual fragment screening protocol, which involves RosettaLigand as the core component by screening a 500 fragments Maybridge library against bovine pancreatic trypsin. Our study reaffirmed that the real test for any virtual screening approach would be in a blind testing environment. The analyses presented in this paper also showed that virtual screening performance can be improved, if a set of known active compounds is available and parameters and methods that yield better enrichment are selected. Our study also highlighted that to achieve accurate orientation and conformation of ligands within a binding site, selecting an appropriate method to calculate partial charges is important. Another finding is that using multiple receptor ensembles in docking does not always yield better enrichment than individual receptors. On the basis of our results and retrospective analyses from SAMPL3 fragment screening challenge we anticipate that chances of success in a fragment screening process could be increased significantly with careful selection of receptor structures, protein flexibility, sufficient conformational sampling within binding pocket and accurate assignment of ligand and protein partial charges.

PI3K and Cancer: Lessons, Challenges and Opportunities

PubMed Central

Fruman, David A.; Rommel, Christian

2014-01-01

Summary The central role of phosphoinositide 3-kinase (PI3K) activation in tumor cell biology has prompted a sizeable effort to target PI3K and/or downstream kinases such as AKT and mTOR in cancer. However, emerging clinical data show limited single agent activity of PI3K/AKT/mTOR inhibitors at tolerated doses. One exception is the response to PI3Kδ inhibitors in chronic lymphocytic leukemia, where a combination of cell-intrinsic and -extrinsic activities drive efficacy. Here we review key challenges and opportunities for clinical development of PI3K/AKT/mTOR inhibitors. Through a greater focus on patient selection, increased understanding of immune modulation, and strategic application of rational combinations, it should be possible to realize the potential of this promising class of targeted anti-cancer agents. PMID:24481312

Hextend and 7.5% hypertonic saline with Dextran are equivalent to Lactated Ringer's in a swine model of initial resuscitation of uncontrolled hemorrhagic shock.

PubMed

Riha, Gordon M; Kunio, Nicholas R; Van, Philbert Y; Hamilton, Gregory J; Anderson, Ross; Differding, Jerome A; Schreiber, Martin A

2011-12-01

The optimal fluid strategy for the early treatment of trauma patients remains highly debated. Our objective was to determine the efficacy of an initial bolus of resuscitative fluids used in military and civilian settings on the physiologic response to uncontrolled hemorrhagic shock in a prospective, randomized, blinded animal study. Fifty anesthetized swine underwent central venous and arterial catheterization followed by celiotomy. Grade V liver injury was performed, followed by 30 minutes of uncontrolled hemorrhage. Then, liver packing was completed, and fluid resuscitation was initiated over 12 minutes with 2 L normal saline (NS), 2 L Lactated Ringer's (LR), 250 mL 7.5% hypertonic saline with 3% Dextran (HTS), 500 mL Hextend (HEX), or no fluid (NF). Animals were monitored for 2 hours postinjury. Blood loss after initial hemorrhage, mean arterial pressure (MAP), tissue oxygen saturation (StO2), hematocrit, pH, base excess, and lactate were measured at baseline, 1 hour, and 2 hours. NF group had less post-treatment blood loss compared with other groups. MAP and StO2 for HEX, HTS, and LR at 1 hour and 2 hours were similar and higher than NF. MAP and StO2 did not differ between NS and NF, but NS resulted in decreased pH and base excess. Withholding resuscitative fluid results in the least amount of posttreatment blood loss. In clinically used volumes, HEX and HTS are equivalent to LR with regard to physiologic outcomes and superior to NF. NS did not provide a measurable improvement in outcome compared with NF and resulted in increased acidosis.

Salt appetite is reduced by a single experience of drinking hypertonic saline in the adult rat.

PubMed

Greenwood, Michael P; Greenwood, Mingkwan; Paton, Julian F R; Murphy, David

2014-01-01

Salt appetite, the primordial instinct to favorably ingest salty substances, represents a vital evolutionary important drive to successfully maintain body fluid and electrolyte homeostasis. This innate instinct was shown here in Sprague-Dawley rats by increased ingestion of isotonic saline (IS) over water in fluid intake tests. However, this appetitive stimulus was fundamentally transformed into a powerfully aversive one by increasing the salt content of drinking fluid from IS to hypertonic saline (2% w/v NaCl, HS) in intake tests. Rats ingested HS similar to IS when given no choice in one-bottle tests and previous studies have indicated that this may modify salt appetite. We thus investigated if a single 24 h experience of ingesting IS or HS, dehydration (DH) or 4% high salt food (HSD) altered salt preference. Here we show that 24 h of ingesting IS and HS solutions, but not DH or HSD, robustly transformed salt appetite in rats when tested 7 days and 35 days later. Using two-bottle tests rats previously exposed to IS preferred neither IS or water, whereas rats exposed to HS showed aversion to IS. Responses to sweet solutions (1% sucrose) were not different in two-bottle tests with water, suggesting that salt was the primary aversive taste pathway recruited in this model. Inducing thirst by subcutaneous administration of angiotensin II did not overcome this salt aversion. We hypothesised that this behavior results from altered gene expression in brain structures important in thirst and salt appetite. Thus we also report here lasting changes in mRNAs for markers of neuronal activity, peptide hormones and neuronal plasticity in supraoptic and paraventricular nuclei of the hypothalamus following rehydration after both DH and HS. These results indicate that a single experience of drinking HS is a memorable one, with long-term changes in gene expression accompanying this aversion to salty solutions.

Salt Appetite Is Reduced by a Single Experience of Drinking Hypertonic Saline in the Adult Rat

PubMed Central

Greenwood, Michael P.; Greenwood, Mingkwan; Paton, Julian F. R.; Murphy, David

2014-01-01

Salt appetite, the primordial instinct to favorably ingest salty substances, represents a vital evolutionary important drive to successfully maintain body fluid and electrolyte homeostasis. This innate instinct was shown here in Sprague-Dawley rats by increased ingestion of isotonic saline (IS) over water in fluid intake tests. However, this appetitive stimulus was fundamentally transformed into a powerfully aversive one by increasing the salt content of drinking fluid from IS to hypertonic saline (2% w/v NaCl, HS) in intake tests. Rats ingested HS similar to IS when given no choice in one-bottle tests and previous studies have indicated that this may modify salt appetite. We thus investigated if a single 24 h experience of ingesting IS or HS, dehydration (DH) or 4% high salt food (HSD) altered salt preference. Here we show that 24 h of ingesting IS and HS solutions, but not DH or HSD, robustly transformed salt appetite in rats when tested 7 days and 35 days later. Using two-bottle tests rats previously exposed to IS preferred neither IS or water, whereas rats exposed to HS showed aversion to IS. Responses to sweet solutions (1% sucrose) were not different in two-bottle tests with water, suggesting that salt was the primary aversive taste pathway recruited in this model. Inducing thirst by subcutaneous administration of angiotensin II did not overcome this salt aversion. We hypothesised that this behavior results from altered gene expression in brain structures important in thirst and salt appetite. Thus we also report here lasting changes in mRNAs for markers of neuronal activity, peptide hormones and neuronal plasticity in supraoptic and paraventricular nuclei of the hypothalamus following rehydration after both DH and HS. These results indicate that a single experience of drinking HS is a memorable one, with long-term changes in gene expression accompanying this aversion to salty solutions. PMID:25111786

Repurposing tromethamine as inhaled therapy to treat CF airway disease

PubMed Central

Alaiwa, Mahmoud H. Abou; Launspach, Janice L.; Sheets, Kelsey A.; Rivera, Jade A.; Gansemer, Nicholas D.; Taft, Peter J.; Thorne, Peter S.; Welsh, Michael J.; Stoltz, David A.

2016-01-01

In cystic fibrosis (CF), loss of CF transmembrane conductance regulator (CFTR) anion channel activity causes airway surface liquid (ASL) pH to become acidic, which impairs airway host defenses. One potential therapeutic approach is to correct the acidic pH in CF airways by aerosolizing HCO3– and/or nonbicarbonate pH buffers. Here, we show that raising ASL pH with inhaled HCO3– increased pH. However, the effect was transient, and pH returned to baseline values within 30 minutes. Tromethamine (Tham) is a buffer with a long serum half-life used as an i.v. formulation to treat metabolic acidosis. We found that Tham aerosols increased ASL pH in vivo for at least 2 hours and enhanced bacterial killing. Inhaled hypertonic saline (7% NaCl) is delivered to people with CF in an attempt to promote mucus clearance. Because an increased ionic strength inhibits ASL antimicrobial factors, we added Tham to hypertonic saline and applied it to CF sputum. We found that Tham alone and in combination with hypertonic saline increased pH and enhanced bacterial killing. These findings suggest that aerosolizing the HCO3–-independent buffer Tham, either alone or in combination with hypertonic saline, might be of therapeutic benefit in CF airway disease. PMID:27390778

Transcriptional responses of the rat vasopressin gene to acute and repeated acute osmotic stress.

PubMed

Zemo, David A; McCabe, Joseph T

2002-09-01

To determine the impact of hypertonic saline administration upon rat arginine vasopressin (AVP) gene transcription in supraoptic nucleus neurons, a probe complementary to the first intron (AVP1) of AVP was used to measure changes in AVP heteronuclear RNA (hnRNA) levels. Animals that received hypertonic saline had increases in AVP1 after 15 and 30 min, with a return to baseline levels by 180 min. In a double injection paradigm, animals were given an injection of normal or hypertonic saline followed 180 min later by a second injection of normal or hypertonic saline and sacrificed 30 min later. When both injections were hypertonic saline (H-H), AVP1 levels were greater than levels seen after a single hypertonic saline injection, or after an injection of normal saline followed by a second injection of hypertonic saline (N-H). This study shows acute, repeated exposure to hypertonic saline causes a robust increase in vasopressin gene transcription. Since a second hyperosmotic stimulus is known to increase neuronal firing rate and activity, our results suggest that a correlation exists with intracellular mechanisms regulating vasopressin gene transcription.

Challenges in Flying Quadrotor Unmanned Aerial Vehicle for 3d Indoor Reconstruction

NASA Astrophysics Data System (ADS)

Yan, J.; Grasso, N.; Zlatanova, S.; Braggaar, R. C.; Marx, D. B.

2017-09-01

Three-dimensional modelling plays a vital role in indoor 3D tracking, navigation, guidance and emergency evacuation. Reconstruction of indoor 3D models is still problematic, in part, because indoor spaces provide challenges less-documented than their outdoor counterparts. Challenges include obstacles curtailing image and point cloud capture, restricted accessibility and a wide array of indoor objects, each with unique semantics. Reconstruction of indoor environments can be achieved through a photogrammetric approach, e.g. by using image frames, aligned using recurring corresponding image points (CIP) to build coloured point clouds. Our experiments were conducted by flying a QUAV in three indoor environments and later reconstructing 3D models which were analysed under different conditions. Point clouds and meshes were created using Agisoft PhotoScan Professional. We concentrated on flight paths from two vantage points: 1) safety and security while flying indoors and 2) data collection needed for reconstruction of 3D models. We surmised that the main challenges in providing safe flight paths are related to the physical configuration of indoor environments, privacy issues, the presence of people and light conditions. We observed that the quality of recorded video used for 3D reconstruction has a high dependency on surface materials, wall textures and object types being reconstructed. Our results show that 3D indoor reconstruction predicated on video capture using a QUAV is indeed feasible, but close attention should be paid to flight paths and conditions ultimately influencing the quality of 3D models. Moreover, it should be decided in advance which objects need to be reconstructed, e.g. bare rooms or detailed furniture.

Biochemical properties of urea transporters.

PubMed

Chen, Guangping

2014-01-01

Urea and urea transporters (UT) are critical to the production of concentrated urine and hence in maintaining body fluid balance. The UT-A1 urea transporter is the major and most important UT isoform in the kidney. Native UT-A1, expressed in the terminal inner medullary collecting duct (IMCD) epithelial cells, is a glycosylated protein with two glycoforms of 117 and 97 kDa. Vasopressin is the major hormone in vivo that rapidly increases urea permeability in the IMCD through increases in phosphorylation and apical plasma-membrane accumulation of UT-A1. The cell signaling pathway for vasopressin-mediated UT-A1 phosphorylation and activity involves two cAMP-dependent signaling pathways: protein kinase A (PKA) and exchange protein activated by cAMP (Epac). In this chapter, we will discuss UT-A1 regulation by phosphorylation, ubiquitination, and glycosylation.

A Case of 3,4-Dimethoxyamphetamine (3,4-DMA) and 3,4-Methylenedioxymethamphetamine (MDMA) Toxicity with Possible Metabolic Interaction.

PubMed

Darracq, Michael A; Thornton, Stephen L; Minns, Alicia B; Gerona, Roy R

2016-01-01

We present a case of "ecstasy" ingestion revealing 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-dimethoxyamphetamine (3,4-DMA) and absence of cytochrome P450 (CYP)-2D6 MDMA metabolites. A 19-year-old presented following a seizure. Initial vital signs were normal. Laboratories were normal with the exception of sodium 127 mEq/L and urine drugs of abuse screen positive for amphetamines. Twelve hours later, serum sodium was 114 mEq/L and a second seizure occurred. After receiving hypertonic saline (3%), the patient had improvement in mental status and admitted to taking "ecstasy" at a rave prior to her initial presentation. Liquid chromatography-time-of-flight mass spectrometry (LC-TOF/MS) of serum and urine revealed MDMA, 3,4-DMA, and the CYP-2B6 MDMA metabolites 3,4-methylendioxyamphetamine (MDA) and 4-hydroxy-3-methoxyamphetamine (HMA). The CYP2D6 metabolites of MDMA, 3,4-dihydromethamphetamine (HHMA) and 4-hydroxy-3-methoxymethamphetamine (HMMA), were detected at very low levels. This case highlights the polypharmacy which may exist among users of psychoactive illicit substances and demonstrates that concurrent use of MDMA and 3,4-DMA may predispose patients to severe toxicity. Toxicologists and other healthcare providers should be aware of this potential toxicity.

Osmolar Therapy in Pediatric Traumatic Brain Injury

PubMed Central

Bennett, Tellen D.; Statler, Kimberly D.; Korgenski, E. Kent; Bratton, Susan L.

2011-01-01

Objectives To describe patterns of use for mannitol and hypertonic saline in children with traumatic brain injury (TBI), to evaluate any potential associations between hypertonic saline and mannitol use and patient demographic, injury, and treatment hospital characteristics, and to determine if the 2003 guidelines for severe pediatric TBI impacted clinical practice regarding osmolar therapy. Design Retrospective cohort study Setting Pediatric Health Information System (PHIS) database, January, 2001 to December, 2008 Patients Children (age < 18 years) with TBI and head/neck Abbreviated Injury Scale (AIS) score ≥ 3 who received mechanical ventilation and intensive care Interventions None Measurements and Main Results The primary outcome was hospital billing for parenteral hypertonic saline and mannitol use, by day of service. Overall, 33% (2,069 of 6,238) of the patients received hypertonic saline and 40% (2,500 of 6,238) received mannitol. Of the 1,854 patients who received hypertonic saline or mannitol for ≥ 2 days in the first week of therapy, 29% did not have ICP monitoring. After adjustment for hospital-level variation, primary insurance payer, and overall injury severity, use of both drugs was independently associated with older patient age, intracranial hemorrhage (other than epidural), skull fracture, and higher head/neck injury severity. Hypertonic saline use increased and mannitol use decreased with publication of the 2003 guidelines, and these trends continued through 2008. Conclusions Hypertonic saline and mannitol are used less in infants than in older children. The patient-level and hospital-level variation in osmolar therapy use and the substantial amount of sustained osmolar therapy without ICP monitoring suggest opportunities to improve the quality of pediatric TBI care. With limited high-quality evidence available, published expert guidelines appear to significantly impact clinical practice in this area. PMID:21926592

Females have stronger neurogenic response than males after non-specific nasal challenge in patients with seasonal allergic rhinitis.

PubMed

Tomljenovic, Dejan; Baudoin, Tomislav; Megla, Zeljka Bukovec; Geber, Goran; Scadding, Glenis; Kalogjera, Livije

2018-07-01

Epidemiological studies show female predominance in the prevalence of non- allergic rhinitis (NAR) and local allergic rhinitis (LAR). Experimental studies show female patients with allergic rhinitis (AR) demonstrate higher levels of sensitivity to irritants and airway hyperresponsiveness than males. Bronchial asthma shows female predominance in post-puberty patients, and gender interaction with severe asthma endotypes. Fibromyalgia, chronic fatigue syndrome, migraine and chronic cough, syndromes, which are commonly related to neurokinin substance P (SP) in the literature, also show strong female predominance. Studies have demonstrated that sex hormones, primarily oestrogens, affect mast cell activation. Mast cell proteases can amplify neurogenic inflammatory responses including the release of SP. Based on human epidemiological data and animal experimental data we hypothesized that female patients have different interaction between mast cell activation and neurogenic inflammation, i.e. substance P release, resulting in a different nasal symptom profile. To test the hypothesis we performed allergen and non-specific nasal challenges in patients with seasonal allergic rhinitis (SAR) out of season and looked for gender differences in subjective and objective responses. The interaction between subjective and objective reactivity was evaluated through the comparison of subjective symptom scores, concentrations of neurokinin substance P (SP) and cellular markers in nasal lavages after low doses of nasal allergen challenges. Female allergic subjects tended to have higher substance P (SP) concentrations both before and after non-specific challenges. The difference between post-allergen and post - hypertonic saline (HTS) challenge was highly significant in female patients (p = 0.001), while insignificant in male subjects (p = 0.14). Female patients had significantly stronger burning sensation after HTS challenge than male. These data indicate difference in the

3 CFR - Designation of Officers of the Millennium Challenge Corporation To Act as Chief Executive Officer...

Code of Federal Regulations, 2013 CFR

2013-01-01

... 3 The President 1 2013-01-01 2013-01-01 false Designation of Officers of the Millennium Challenge Corporation To Act as Chief Executive Officer of the Millennium Challenge Corporation Presidential Documents... an acting CEO of the MCC. Sec. 3. Judicial Review. This memorandum is not intended to, and does not...

Effects of hypertonic saline (7.5%) on extracellular fluid volumes compared with normal saline (0.9%) and 6% hydroxyethyl starch after aortocoronary bypass graft surgery.

PubMed

Järvelä, K; Koskinen, M; Kaukinen, S; Kööbi, T

2001-04-01

To compare the effects of hypertonic (7.5%) saline (HS), normal (0.9%) saline (NS), and 6% hydroxyethyl starch (HES) on extracellular fluid volumes in the early postoperative period after cardiopulmonary bypass. A prospective, randomized, double-blind study. University teaching hospital. Forty-eight patients scheduled for elective coronary artery bypass graft surgery. Patients were randomly allocated to receive 4 mL/kg of HS, NS, or HES during 30 minutes when volume loading was needed during the postoperative rewarming period in the intensive care unit. Plasma volume was measured using a dilution of iodine-125-labeled human serum albumin. Extracellular water and cardiac output were measured by whole-body impedance cardiography. Plasma volume had increased by 19 +/- 7% in the HS group and by 10 +/- 3% in the NS group (p = 0.001) at the end of the study fluid infusion. After 1-hour follow-up time, the plasma volume increase was greatest (23 +/- 8%) in the group receiving HES (p < 0.001). The increase of extracellular water was greater than the infused volume in the HS and HES groups at the end of the infusion. One-hour diuresis after the study infusion was greater in the HS group (536 +/- 280 mL) than in the NS (267 +/- 154 mL, p = 0.006) and HES groups (311 +/- 238 mL, p = 0.025). The effect of HS on plasma volume was short-lasting, but it stimulated excretion of excess body fluid accumulated during cardiopulmonary bypass and cardiac surgery. HS may be used in situations in which excess free water administration is to be avoided but the intravascular volume needs correction. Copyright 2001 by W.B. Saunders Company

Effect of peritoneal cavity lavage with 0.9% and 3.0% saline solution in the lung and spleen of gerbils with induced peritonitis.

PubMed

Nunes, Vinícius Rodrigues Taranto; Barbuto, Rafael Calvão; Vidigal, Paula Vieira Teixeira; Pena, Guilherme Nogueira; Rocha, Silvia Lunardi; de Siqueira, Lucas Tourinho; Caliari, Marcelo Vidigal; de Araujo, Ivana Duval

2014-04-01

Peritoneal cavity lavage is used widely in the treatment of peritonitis. Nonetheless, some studies question its rationale and prove it to be deleterious to the mesothelium. The present study aims to determine whether 0.9% and 3.0% saline lavage of the peritoneal cavity have an effect on the early systemic inflammatory response, namely, in the lung injury and splenic cellularity of gerbils with induced peritonitis. Thirty-four male gerbils were divided into four groups: Control (n=9), submitted to laparotomy at time zero, re-laparotomy after 2 h, and sacrificed after a total of 6 h from start; untreated (n=8), submitted to peritonitis induction through cecal ligation and puncture (CLP) at time zero, re-laparotomy intended for drying of abdominal cavity and resection of the ischemic cecum after 2 h, and sacrifice after a total of 6 h from start; saline (n=8), submitted to peritonitis induction through CLP at time zero, re-laparotomy intended for warm 0.9% saline lavage of the abdominal cavity and resection of the ischemic cecum after 2 h, and sacrificed after a total of 6 h from start; and hypertonic (n=9), submitted to peritonitis induction through CLP at time zero, re-laparotomy intended for warm hypertonic saline (3.0%) lavage of the abdominal cavity and resection of the ischemic cecum after 2 h, and sacrificed after a total of 6 h from start. After sacrifice, we collected the left lung and the spleen for morphometric analysis. In the both the saline and hypertonic groups, there was significant decrease in the mean nuclei count in the lungs, compared with the untreated group (p<0.01). There was no difference in terms of nuclei count in the spleen among groups (p>0.05). The present study demonstrated that the peritoneal lavage with large volumes of warm 0.9% and 3.0% saline has a beneficial effect on the early systemic inflammatory response in infected animals, modulating and reducing the lung injury but having no effect on splenic cell count.

3D Laser Triangulation for Plant Phenotyping in Challenging Environments

PubMed Central

Kjaer, Katrine Heinsvig; Ottosen, Carl-Otto

2015-01-01

To increase the understanding of how the plant phenotype is formed by genotype and environmental interactions, simple and robust high-throughput plant phenotyping methods should be developed and considered. This would not only broaden the application range of phenotyping in the plant research community, but also increase the ability for researchers to study plants in their natural environments. By studying plants in their natural environment in high temporal resolution, more knowledge on how multiple stresses interact in defining the plant phenotype could lead to a better understanding of the interaction between plant responses and epigenetic regulation. In the present paper, we evaluate a commercial 3D NIR-laser scanner (PlantEye, Phenospex B.V., Herleen, The Netherlands) to track daily changes in plant growth with high precision in challenging environments. Firstly, we demonstrate that the NIR laser beam of the scanner does not affect plant photosynthetic performance. Secondly, we demonstrate that it is possible to estimate phenotypic variation amongst the growth pattern of ten genotypes of Brassica napus L. (rapeseed), using a simple linear correlation between scanned parameters and destructive growth measurements. Our results demonstrate the high potential of 3D laser triangulation for simple measurements of phenotypic variation in challenging environments and in a high temporal resolution. PMID:26066990

Renal Phenotype of UT-A Urea Transporter Knockout Mice

PubMed Central

Fenton, Robert A.; Flynn, Anneliese; Shodeinde, Adetola; Smith, Craig P.; Schnermann, Jurgen; Knepper, Mark A.

2006-01-01

The urea transporters UT-A1 and UT-A3 mediate rapid transepithelial urea transport across the inner medullary collecting duct (IMCD). In a previous study, using a new mouse model in which both UT-A1 and UT-A3 were genetically deleted from the IMCD (UT-A1/3−/− mice), we investigated the role of these transporters in the function of the renal inner medulla. Here we report a series of studies investigating more generally the renal phenotype of UT-A1/3−/− mice. Pathological screening revealed abnormalities in both the testis (increased size) and kidney (decreased size and vascular congestion) of UT-A1/3−/− mice. Total urinary nitrate and nitrite excretion rates in UT-A1/3−/− mice were more than double those in wildtype mice. Total renal blood flow was not different between UT-A1/3−/− and wildtype mice, but underwent a greater percentage decrease in response to NG-Nitro-L-arginine Methyl Ester Hydrochloride (L-NAME) infusion. Whole kidney glomerular filtration rate was not different in UT-A1/3−/− mice compared to controls and underwent a similar increase in response to a greater dietary protein intake. Fractional urea excretion was markedly elevated in UT-A1/3−/− mice on a 40% protein diet, reaching 102.4 ± 8.8% of the filtered load, suggesting that there may be active urea secretion along the renal tubule. Although there was a marked urinary concentrating defect in UT-A1/3−/− mice, there was no decrease in aquaporin-2 or -3 expression. Furthermore, although urea accumulation in the inner medulla was markedly attenuated, there was no decrease in NaCl concentration in tissue from outer medulla or 2 levels of the inner medulla. PMID:15829709

Clinical 3T MR imaging: mastering the challenges.

PubMed

Tanenbaum, Lawrence N

2006-02-01

3T MRI is ready to meet the needs of clinical practice. SAR limitations are minimized by technical advances and surface coils are available for all core applications. With appropriate adjustments to scanning protocols, one can master the challenges of scanning at 3T; studies of the brain, spine, chest, abdomen, pelvis, vasculature, and extremities can be consistently higher in quality than are those obtained at 1.5T. The superior studies that are obtainable at 3T have great appeal to clinicians who are sophisticated about MR technology in areas, such as neurology, orthopedics, vascular surgery, and oncology,and encourage a shift in referrals toward practices that invest in higher field technology. The greater sensitivity to magnetic susceptibility offers unique benefits in functional neuroimaging, and available software/hardware packages enhance clinical setting feasibility, which adds a source of new referrals. The greater overall signal of 3T can be manipulated to make scanning more comfortable and with less motion artifact because scan times could be half as long. Spectacular anatomic delineation that is provided by high-definition scanning at true 1024 resolution can improve preoperative assessment and may improve sensitivity to smaller lesions. 3T provides practices with an advantage that is sought increasingly by high field strength purchasers in a competitive market. Only cost considerations stand in the way of the eventual domination of 3T systems in the high field strength market.

Transport systems of Ventricaria ventricosa: asymmetry of the hyper- and hypotonic regulation mechanisms.

PubMed

Bisson, M A; Beilby, M J

2008-01-01

Hyper- and hypotonic stresses elicit apparently symmetrical responses in the alga Ventricaria. With hypertonic stress, membrane potential difference (PD) between the vacuole and the external medium becomes more positive, conductance at positive PDs (Gmpos) increases and KCl is actively taken up to increase turgor. With hypotonic stress, the membrane PD becomes more negative, conductance at negative PDs (Gmneg) increases and KCl is lost to decrease turgor. We used inhibitors that affect active transport to determine whether agents that inhibit the K(+) pump and hypertonic regulation also inhibit hypotonic regulatory responses. Cells whose turgor pressure was held low by the pressure probe (turgor-clamped) exhibited the same response as cells challenged by hyperosmotic medium, although the response was maintained longer than in osmotically challenged cells, which regulate turgor. The role of active K(+) transport was confirmed by the effects of decreased light, dichlorophenyldimethyl urea and diethylstilbestrol, which induced a uniformly low conductance (quiet state). Cells clamped to high turgor exhibited the same response as cells challenged by hypo-osmotic medium, but the response was similarly transient, making effects of inhibitors hard to determine. Unlike clamped cells, cells challenged by hypo-osmotic medium responded to inhibitors with rapid, transient, negative-going PDs, with decreased Gmneg and increased Gmpos (linearized I-V), achieving the quiet state as PD recovered. These changes are different from those exerted on the pump state, indicating that different transport systems are responsible for turgor regulation in the two cases.

NaCl and osmolarity produce different responses in organum vasculosum of the lamina terminalis neurons, sympathetic nerve activity and blood pressure.

PubMed

Kinsman, Brian J; Browning, Kirsteen N; Stocker, Sean D

2017-09-15

Changes in extracellular osmolarity stimulate thirst and vasopressin secretion through a central osmoreceptor; however, central infusion of hypertonic NaCl produces a greater sympathoexcitatory and pressor response than infusion of hypertonic mannitol/sorbitol. Neurons in the organum vasculosum of the lamina terminalis (OVLT) sense changes in extracellular osmolarity and NaCl. In this study, we discovered that intracerebroventricular infusion or local OVLT injection of hypertonic NaCl increases lumbar sympathetic nerve activity, adrenal sympathetic nerve activity and arterial blood pressure whereas equi-osmotic mannitol/sorbitol did not alter any variable. In vitro whole-cell recordings demonstrate the majority of OVLT neurons are responsive to hypertonic NaCl or mannitol. However, hypertonic NaCl stimulates a greater increase in discharge frequency than equi-osmotic mannitol. Intracarotid or intracerebroventricular infusion of hypertonic NaCl evokes a greater increase in OVLT neuronal discharge frequency than equi-osmotic sorbitol. Collectively, these novel data suggest that subsets of OVLT neurons respond differently to hypertonic NaCl versus osmolarity and subsequently regulate body fluid homeostasis. These responses probably reflect distinct cellular mechanisms underlying NaCl- versus osmo-sensing. Systemic or central infusion of hypertonic NaCl and other osmolytes readily stimulate thirst and vasopressin secretion. In contrast, central infusion of hypertonic NaCl produces a greater increase in arterial blood pressure (ABP) than equi-osmotic mannitol/sorbitol. Although these responses depend on neurons in the organum vasculosum of the lamina terminalis (OVLT), these observations suggest OVLT neurons may sense or respond differently to hypertonic NaCl versus osmolarity. The purpose of this study was to test this hypothesis in Sprague-Dawley rats. First, intracerebroventricular (icv) infusion (5 μl/10 min) of 1.0 m NaCl produced a significantly greater

Prior infection of pigs with a genotype 3 swine hepatitis E virus (HEV) protects against subsequent challenges with homologous and heterologous genotypes 3 and 4 human HEV

PubMed Central

Sanford, Brenton J.; Dryman, Barbara A.; Huang, Yao-Wei; Feagins, Alicia R.; LeRoith, Tanya; Meng, Xiang-Jin

2011-01-01

Hepatitis E virus (HEV) is an important human pathogen. At least four recognized and two putative genotypes of mammalian HEV have been reported: genotypes 1 and 2 are restricted to humans whereas genotypes 3 and 4 are zoonotic. The current experimental vaccines are all based on a single strain of HEV, even though multiple genotypes of HEV are co-circulating in some countries and thus an individual may be exposed to more than one genotype. Genotypes 3 and 4 swine HEV is widespread in pigs and known to infect humans. Therefore, it is important to know if prior infection with a genotype 3 swine HEV will confer protective immunity against subsequent exposure to genotypes 3 and 4 human and swine HEV. In this study, specific-pathogen-free pigs were divided into 4 groups of 6 each. Pigs in the three treatment groups were each inoculated with a genotype 3 swine HEV, and 12 weeks later, challenged with the same genotype 3 swine HEV, a genotype 3 human HEV, and a genotype 4 human HEV, respectively. The control group was inoculated and challenged with PBS buffer. Weekly sera from all pigs were tested for HEV RNA and IgG anti-HEV, and weekly fecal samples were also tested for HEV RNA. The pigs inoculated with swine HEV became infected as evidenced by fecal virus shedding and viremia, and the majority of pigs also developed IgG anti-HEV prior to challenge at 12 weeks post-inoculation. After challenge, viremia and fecal virus shedding of challenge viruses were not detected, suggesting that prior infection with a genotype 3 swine HEV prevented pigs from developing viremia and fecal virus shedding after challenges with homologous and heterologous genotypes 3 and 4 HEV. The results from this study have important implications for future development of an effective HEV vaccine. PMID:21536085

Elevated extracellular glucose and uncontrolled type 1 diabetes enhance NFAT5 signaling and disrupt the transverse tubular network in mouse skeletal muscle

PubMed Central

Hernández-Ochoa, Erick O; Robison, Patrick; Contreras, Minerva; Shen, Tiansheng; Zhao, Zhiyong; Schneider, Martin F

2012-01-01

The transcription factor nuclear factor of activated T-cells 5 (NFAT5) is a key protector from hypertonic stress in the kidney, but its role in skeletal muscle is unexamined. Here, we evaluate the effects of glucose hypertonicity and hyperglycemia on endogenous NFAT5 activity, transverse tubular system morphology and Ca2+ signaling in adult murine skeletal muscle fibers. We found that exposure to elevated glucose (25–50 mmol/L) increased NFAT5 expression and nuclear translocation, and NFAT-driven transcriptional activity. These effects were insensitive to the inhibition of calcineurin A, but sensitive to both p38a mitogen-activated protein kinases and phosphoinositide 3-kinase-related kinase inhibition. Fibers exposed to elevated glucose exhibited disrupted transverse tubular morphology, characterized by swollen transverse tubules and an increase in longitudinal connections between adjacent transverse tubules. Ca2+ transients elicited by a single, brief electric field stimuli were increased in amplitude in fibers challenged by elevated glucose. Muscle fibers from type 1 diabetic mice exhibited increased NFAT5 expression and transverse tubule disruptions, but no differences in electrically evoked Ca2+ transients. Our results suggest the hypothesis that these changes in skeletal muscle could play a role in the pathophysiology of acute and severe hyperglycemic episodes commonly observed in uncontrolled diabetes. PMID:22966145

Challenges and complexity of functionality evaluation of flavan-3-ol derivatives.

PubMed

Saito, Akiko

2017-06-01

Flavan-3-ol derivatives are common plant-derived bioactive compounds. In particular, (-)-epigallocatechin-3-O-gallate shows various moderate biological activities without severe toxicity, and its health-promoting effects have been widely studied because it is a main ingredient in green tea and is commercially available at low cost. Although various biologically active flavan-3-ol derivatives are present as minor constituents in plants as well as in green tea, their biological activities have yet to be revealed, mainly due to their relative unavailability. Here, I outline the major factors contributing to the complexity of functionality studies of flavan-3-ol derivatives, including proanthocyanidins and oligomeric flavan-3-ols. I emphasize the importance of conducting structure-activity relationship studies using synthesized flavan-3-ol derivatives that are difficult to obtain from plant extracts in pure form to overcome this challenge. Further discovery of these minor constituents showing strong biological activities is expected to produce useful information for the development of functional health foods.

Rational drug use for acute bronchiolitis in emergency care.

PubMed

Uysalol, Metin; Haşlak, Fatih; Özünal, Zeynep Güneş; Vehid, Hayriye; Uzel, Nedret

2017-01-01

Uysalol M, Haşlak F, Özünal ZG, Vehid H, Uzel N. Rational drug use for acute bronchiolitis in emergency care. Turk J Pediatr 2017; 59: 155-161. Despite the large variety of inhaled treatment options of acute bronchiolitis, there is no generally agreed treatment regime. This study aimed to determine the most appropriate treatment option. This was a double-blind randomized prospective clinical trial and has been performed in emergency department. The mean age of the 378 infants included in the study was 7.63 ± 4.6 months, and 54.8% (207) were boys. Patients were randomized by using the lottery method for simple random sample into 5 different treatment options; 3% hypertonic saline, nebulized adrenaline, nebulized adrenaline mixed with 3% hypertonic saline, nebulized salbutamol, and as control group; normal saline (0.9% NaCl). From the first treatment time until discharge time; treatment durations, adverse events and readmission rates within the first fifteen days were recorded for each patient. Nebulized adrenaline mixed with 3% hypertonic saline, as compared with other options, were associated with a significantly higher discharge rate at 4th hours (p < 0.001) and shorter length of hospital stay (p=0.039). However, there was no significant difference between options with regard to adverse events, discharge rates at 24th hours, and readmission rates within the first fifteen days. The superiority of discharge rates at 4 hours of nebulized adrenaline mixed with 3% hypertonic saline, was evaluated as `better acute response` and can be helpful to reduce hospitalization needs. Additionally, this option seems to be more effective to reduce length of hospital stay.

3D and 4D Bioprinting of the Myocardium: Current Approaches, Challenges, and Future Prospects

PubMed Central

Ong, Chin Siang; Nam, Lucy; Ong, Kingsfield; Krishnan, Aravind; Huang, Chen Yu; Fukunishi, Takuma

2018-01-01

3D and 4D bioprinting of the heart are exciting notions in the modern era. However, myocardial bioprinting has proven to be challenging. This review outlines the methods, materials, cell types, issues, challenges, and future prospects in myocardial bioprinting. Advances in 3D bioprinting technology have significantly improved the manufacturing process. While scaffolds have traditionally been utilized, 3D bioprinters, which do not require scaffolds, are increasingly being employed. Improved understanding of the cardiac cellular composition and multiple strategies to tackle the issues of vascularization and viability had led to progress in this field. In vivo studies utilizing small animal models have been promising. 4D bioprinting is a new concept that has potential to advance the field of 3D bioprinting further by incorporating the fourth dimension of time. Clinical translation will require multidisciplinary collaboration to tackle the pertinent issues facing this field. PMID:29850546

GCN-2 dependent inhibition of protein synthesis activates osmosensitive gene transcription via WNK and Ste20 kinase signaling

PubMed Central

Lee, Elaine Choung-Hee

2012-01-01

Increased gpdh-1 transcription is required for accumulation of the organic osmolyte glycerol and survival of Caenorhabditis elegans during hypertonic stress. Our previous work has shown that regulators of gpdh-1 (rgpd) gene knockdown constitutively activates gpdh-1 expression. Fifty-five rgpd genes play essential roles in translation suggesting that inhibition of protein synthesis is an important signal for regulating osmoprotective gene transcription. We demonstrate here that translation is reduced dramatically by hypertonic stress or knockdown of rgpd genes encoding aminoacyl-tRNA synthetases and eukaryotic translation initiation factors (eIFs). Toxin-induced inhibition of translation also activates gpdh-1 expression. Hypertonicity-induced translation inhibition is mediated by general control nonderepressible (GCN)-2 kinase signaling and eIF-2α phosphoryation. Loss of gcn-1 or gcn-2 function prevents eIF-2α phosphorylation, completely blocks reductions in translation, and inhibits gpdh-1 transcription. gpdh-1 expression is regulated by the highly conserved with-no-lysine kinase (WNK) and Ste20 kinases WNK-1 and GCK-3, which function in the GCN-2 signaling pathway downstream from eIF-2α phosphorylation. Our previous work has shown that hypertonic stress causes rapid and dramatic protein damage in C. elegans and that inhibition of translation reduces this damage. The current studies demonstrate that reduced translation also serves as an essential signal for activation of WNK-1/GCK-3 kinase signaling and subsequent transcription of gpdh-1 and possibly other osmoprotective genes. PMID:23076791

Long-term hand tele-rehabilitation on the PlayStation 3: benefits and challenges.

PubMed

Burdea, Grigore C; Jain, Abhishek; Rabin, Bryan; Pellosie, Richard; Golomb, Meredith

2011-01-01

Rehabilitation interventions for the hand have shown benefits for children with Hemiplegia due to cerebral palsy or traumatic brain injury. Longer interventions are facilitated if training is provided in the patient's home, due to easier access to care and reduced impact on school or work activities. Providing remote rehabilitation over lengthy periods of time has however its own challenges. This paper presents two pediatric patients with hemiplegia, who practiced virtual hand rehabilitation games using a modified PlayStation 3 and 5DT sensing gloves. Despite severe initial hand spasticity, and occasional technology shortcomings, the subjects practiced for about 14 months, and 6 months, respectively. Game performance data for the second patient is presented. Follow-up evaluations 14 months from the removal of the PlayStation 3 from the home of the child with cerebral palsy showed that the patient had good retention in terms of grasp strength, hand function and bone health. Challenges of long-term home tele-rehabilitation are also discussed.

Prior infection of pigs with a genotype 3 swine hepatitis E virus (HEV) protects against subsequent challenges with homologous and heterologous genotypes 3 and 4 human HEV.

PubMed

Sanford, Brenton J; Dryman, Barbara A; Huang, Yao-Wei; Feagins, Alicia R; Leroith, Tanya; Meng, Xiang-Jin

2011-07-01

Hepatitis E virus (HEV) is an important human pathogen. At least four recognized and two putative genotypes of mammalian HEV have been reported: genotypes 1 and 2 are restricted to humans whereas genotypes 3 and 4 are zoonotic. The current experimental vaccines are all based on a single strain of HEV, even though multiple genotypes of HEV are co-circulating in some countries and thus an individual may be exposed to more than one genotype. Genotypes 3 and 4 swine HEV is widespread in pigs and known to infect humans. Therefore, it is important to know if prior infection with a genotype 3 swine HEV will confer protective immunity against subsequent exposure to genotypes 3 and 4 human and swine HEV. In this study, specific-pathogen-free pigs were divided into 4 groups of 6 each. Pigs in the three treatment groups were each inoculated with a genotype 3 swine HEV, and 12 weeks later, challenged with the same genotype 3 swine HEV, a genotype 3 human HEV, and a genotype 4 human HEV, respectively. The control group was inoculated and challenged with PBS buffer. Weekly sera from all pigs were tested for HEV RNA and IgG anti-HEV, and weekly fecal samples were also tested for HEV RNA. The pigs inoculated with swine HEV became infected as evidenced by fecal virus shedding and viremia, and the majority of pigs also developed IgG anti-HEV prior to challenge at 12 weeks post-inoculation. After challenge, viremia was not detected and only two pigs challenged with swine HEV had 1-week fecal virus shedding, suggesting that prior infection with a genotype 3 swine HEV prevented pigs from developing viremia and fecal virus shedding after challenges with homologous and heterologous genotypes 3 and 4 HEV. The results from this study have important implications for future development of an effective HEV vaccine. Copyright © 2011 Elsevier B.V. All rights reserved.

Changes in translation rate modulate stress-induced damage of diverse proteins

PubMed Central

Kim, Heejung

2013-01-01

Proteostasis is the maintenance of the proper function of cellular proteins. Hypertonic stress disrupts proteostasis and causes rapid and widespread protein aggregation and misfolding in the nematode Caenorhabditis elegans. Optimal survival in hypertonic environments requires degradation of damaged proteins. Inhibition of protein synthesis occurs in response to diverse environmental stressors and may function in part to minimize stress-induced protein damage. We recently tested this idea directly and demonstrated that translation inhibition by acute exposure to cycloheximide suppresses hypertonicity-induced aggregation of polyglutamine::YFP (Q35::YFP) in body wall muscle cells. In this article, we further characterized the relationship between protein synthesis and hypertonic stress-induced protein damage. We demonstrate that inhibition of translation reduces hypertonic stress-induced formation and growth of Q35::YFP, Q44::YFP, and α-synuclein aggregates; misfolding of paramyosin and ras GTPase; and aggregation of multiple endogenous proteins expressed in diverse cell types. Activation of general control nonderepressible-2 (GCN-2) kinase signaling during hypertonic stress inhibits protein synthesis via phosphorylation of eukaryotic initiation factor-2α (eIF-2α). Inhibition of GCN-2 activation prevents the reduction in translation rate and greatly exacerbates the formation and growth of Q35::YFP aggregates and the aggregation of endogenous proteins. The current studies together with our previous work provide the first direct demonstration that hypertonic stress-induced reduction in protein synthesis minimizes protein aggregation and misfolding. Reduction in translation rate also serves as a signal that activates osmoprotective gene expression. The cellular proteostasis network thus plays a critical role in minimizing hypertonic stress-induced protein damage, in degrading stress-damaged proteins, and in cellular osmosensing and signaling. PMID:24153430

Innovations in College Access: Challenges and Lessons Learned from Investing in Innovation (i3) Grantees

ERIC Educational Resources Information Center

Murthy, Carrie, Comp.

2017-01-01

In May 2017, the Investing in Innovation Fund (i3) College Access and Success community embarked on a project to compile shared challenges and lessons learned as a resource for fellow i3 College Access and Success grantees, the larger community of i3 grantees, and the broader field of college access. Through this project, the authors discovered…

Fluid resuscitation with isotonic or hypertonic saline solution avoids intraneural calcium influx after traumatic brain injury associated with hemorrhagic shock.

PubMed

Balbino, Marcos; Capone Neto, Antonio; Prist, Ricardo; Ferreira, Alice Teixeira; Poli-de-Figueiredo, Luiz F

2010-04-01

Calcium is one of the triggers involved in ischemic neuronal death. Because hypotension is a strong predictor of outcome in traumatic brain injury (TBI), we tested the hypothesis that early fluid resuscitation blunts calcium influx in hemorrhagic shock associated to TBI. Fifteen ketamine-halothane anesthetized mongrel dogs (18.7 kg +/- 1.4 kg) underwent unilateral cryogenic brain injury. Blood was shed in 5 minutes to a target mean arterial pressure of 40 mm Hg to 45 mm Hg and maintained at these levels for 20 minutes (shed blood volume = 26 mL/kg +/- 7 mL/kg). Animals were then randomized into three groups: CT (controls, no fluid resuscitation), HS (7.5% NaCl, 4 mL/kg, in 5 minutes), and LR (lactate Ringer's, 33 mL/kg, in 15 minutes). Twenty minutes later, a craniotomy was performed and cerebral biopsies were obtained next to the lesion ("clinical penumbra") and from the corresponding contralateral side ("lesion's mirror") to determine intracellular calcium by fluorescence signals of Fura-2-loaded cells. Controls remained hypotensive and in a low-flow state, whereas fluid resuscitation improved hemodynamic profile. There was a significant increase in intracellular calcium in the injured hemisphere in CT (1035 nM +/- 782 nM), compared with both HS (457 nM +/- 149 nM, p = 0.028) and LR (392 nM +/- 178 nM, p = 0.017), with no differences between HS and LR (p = 0.38). Intracellular calcium at the contralateral, uninjured hemisphere was 438 nM +/- 192 nM in CT, 510 nM +/- 196 nM in HS, and 311 nM +/- 51 nM in LR, with no significant differences between them. Both small volume hypertonic saline and large volume lactated Ringer's blunts calcium influx in early stages of TBI associated to hemorrhagic shock. No fluid resuscitation strategy promotes calcium influx and further neural damage.

The Expression of Fos, Jun and AP-1 DNA Binding Activity in Rat Supraoptic Nucleus Neurons Following Acute Versus Repeated Osmotic Stimulation

DTIC Science & Technology

1995-06-22

heterodimers with each other, they may have very different effects upon gene expression (Mellstrom et al., 1991). Hypertonic saline injections may induce...1, fra 2, Jun-B and Jun-D, that in turn have dramatic effects upon hormone synthesis. How one should view hypertonic saline as an experimental...treatment is also a complex issue. Hypertonic saline administration has at least three effects upon an animal: it is an osmotic stimulus (dramatically

A comparative study of charge movement in rat and frog skeletal muscle fibres.

PubMed

Hollingworth, S; Marshall, M W

1981-12-01

1. The middle of the fibre voltage--clamp technique (Adrian & Marshall, 1977), modified where necessary for electrically short muscle fibres, has been used to measure non-linear charge movements in mammalian fast twitch (rat extensor digitorum longus), mammalian slow twitch (rat soleus) and frog (sartorius) muscles. 2. The maximum amount of charge moved in mammalian fast twitch muscle at 2 degrees C in hypertonic solution, was 3--5 times greater than in slow twitch muscle. The voltage distribution of fast twitch charge was 10--15 mV more positive when compared to slow twitch. 3. In both mammalian muscle types hypertonic Ringer solution negatively shifted the voltage distribution of charge some 6 mV. The steepness of charge moved around mechanical threshold was unaffected by hypertonicity. 4. The amount of charge in frog sartorius fibres at 2 degrees C in hypertonic solution was about half of that in rat fast twitch muscle; the voltage distribution of the frog charge was similar to rat soleus muscle. 5. Warming between 2 and 15 degrees C had no effect on either the amount of steady-state distribution of charge in mammalian or frog muscles. 6. At 2 degrees C, the kinetics of charge movement in fast and slow twitch mammalian muscles were similar and 2--3 times faster than frog muscle at the same temperature. In fast and slow mammalian fibres at 2 degrees C similar times were taken to shift the same fractions of the total amount of charge. The Q10 of charge movement kinetics was between 1.2 and 2.0 in the three muscles studied.

D3R Grand Challenge 2015: Evaluation of Protein-Ligand Pose and Affinity Predictions

PubMed Central

Gathiaka, Symon; Liu, Shuai; Chiu, Michael; Yang, Huanwang; Stuckey, Jeanne A; Kang, You Na; Delproposto, Jim; Kubish, Ginger; Dunbar, James B.; Carlson, Heather A.; Burley, Stephen K.; Walters, W. Patrick; Amaro, Rommie E.; Feher, Victoria A.; Gilson, Michael K.

2017-01-01

The Drug Design Data Resource (D3R) ran Grand Challenge 2015 between September 2015 and February 2016. Two targets served as the framework to test community docking and scoring methods: (i) HSP90, donated by AbbVie and the Community Structure Activity Resource (CSAR), and (ii) MAP4K4, donated by Genentech. The challenges for both target datasets were conducted in two stages, with the first stage testing pose predictions and the capacity to rank compounds by affinity with minimal structural data; and the second stage testing methods for ranking compounds with knowledge of at least a subset of the ligand-protein poses. An additional sub-challenge provided small groups of chemically similar HSP90 compounds amenable to alchemical calculations of relative binding free energy. Unlike previous blinded Challenges, we did not provide cognate receptors or receptors prepared with hydrogens and likewise did not require a specified crystal structure to be used for pose or affinity prediction in Stage 1. Given the freedom to select from over 200 crystal structures of HSP90 in the PDB, participants employed workflows that tested not only core docking and scoring technologies, but also methods for addressing water-mediated ligand-protein interactions, binding pocket flexibility, and the optimal selection of protein structures for use in docking calculations. Nearly 40 participating groups submitted over 350 prediction sets for Grand Challenge 2015. This overview describes the datasets and the organization of the challenge components, summarizes the results across all submitted predictions, and considers broad conclusions that may be drawn from this collaborative community endeavor. PMID:27696240

D3R grand challenge 2015: Evaluation of protein-ligand pose and affinity predictions

NASA Astrophysics Data System (ADS)

Gathiaka, Symon; Liu, Shuai; Chiu, Michael; Yang, Huanwang; Stuckey, Jeanne A.; Kang, You Na; Delproposto, Jim; Kubish, Ginger; Dunbar, James B.; Carlson, Heather A.; Burley, Stephen K.; Walters, W. Patrick; Amaro, Rommie E.; Feher, Victoria A.; Gilson, Michael K.

2016-09-01

The Drug Design Data Resource (D3R) ran Grand Challenge 2015 between September 2015 and February 2016. Two targets served as the framework to test community docking and scoring methods: (1) HSP90, donated by AbbVie and the Community Structure Activity Resource (CSAR), and (2) MAP4K4, donated by Genentech. The challenges for both target datasets were conducted in two stages, with the first stage testing pose predictions and the capacity to rank compounds by affinity with minimal structural data; and the second stage testing methods for ranking compounds with knowledge of at least a subset of the ligand-protein poses. An additional sub-challenge provided small groups of chemically similar HSP90 compounds amenable to alchemical calculations of relative binding free energy. Unlike previous blinded Challenges, we did not provide cognate receptors or receptors prepared with hydrogens and likewise did not require a specified crystal structure to be used for pose or affinity prediction in Stage 1. Given the freedom to select from over 200 crystal structures of HSP90 in the PDB, participants employed workflows that tested not only core docking and scoring technologies, but also methods for addressing water-mediated ligand-protein interactions, binding pocket flexibility, and the optimal selection of protein structures for use in docking calculations. Nearly 40 participating groups submitted over 350 prediction sets for Grand Challenge 2015. This overview describes the datasets and the organization of the challenge components, summarizes the results across all submitted predictions, and considers broad conclusions that may be drawn from this collaborative community endeavor.

Predicted consequences of diabetes and SGLT inhibition on transport and oxygen consumption along a rat nephron

PubMed Central

Vallon, Volker; Edwards, Aurélie

2016-01-01

Diabetes increases the reabsorption of Na+ (TNa) and glucose via the sodium-glucose cotransporter SGLT2 in the early proximal tubule (S1-S2 segments) of the renal cortex. SGLT2 inhibitors enhance glucose excretion and lower hyperglycemia in diabetes. We aimed to investigate how diabetes and SGLT2 inhibition affect TNa and sodium transport-dependent oxygen consumption QO2active along the whole nephron. To do so, we developed a mathematical model of water and solute transport from the Bowman space to the papillary tip of a superficial nephron of the rat kidney. Model simulations indicate that, in the nondiabetic kidney, acute and chronic SGLT2 inhibition enhances active TNa in all nephron segments, thereby raising QO2active by 5–12% in the cortex and medulla. Diabetes increases overall TNa and QO2active by ∼50 and 100%, mainly because it enhances glomerular filtration rate (GFR) and transport load. In diabetes, acute and chronic SGLT2 inhibition lowers QO2active in the cortex by ∼30%, due to GFR reduction that lowers proximal tubule active TNa, but raises QO2active in the medulla by ∼7%. In the medulla specifically, chronic SGLT2 inhibition is predicted to increase QO2active by 26% in late proximal tubules (S3 segments), by 2% in medullary thick ascending limbs (mTAL), and by 9 and 21% in outer and inner medullary collecting ducts (OMCD and IMCD), respectively. Additional blockade of SGLT1 in S3 segments enhances glucose excretion, reduces QO2active by 33% in S3 segments, and raises QO2active by <1% in mTAL, OMCD, and IMCD. In summary, the model predicts that SGLT2 blockade in diabetes lowers cortical QO2active and raises medullary QO2active, particularly in S3 segments. PMID:26764207

Microscale screening systems for 3D cellular microenvironments: platforms, advances, and challenges

PubMed Central

Montanez-Sauri, Sara I.; Beebe, David J.; Sung, Kyung Eun

2015-01-01

The increasing interest in studying cells using more in vivo-like three-dimensional (3D) microenvironments has created a need for advanced 3D screening platforms with enhanced functionalities and increased throughput. 3D screening platforms that better mimic in vivo microenvironments with enhanced throughput would provide more in-depth understanding of the complexity and heterogeneity of microenvironments. The platforms would also better predict the toxicity and efficacy of potential drugs in physiologically relevant conditions. Traditional 3D culture models (e.g. spinner flasks, gyratory rotation devices, non-adhesive surfaces, polymers) were developed to create 3D multicellular structures. However, these traditional systems require large volumes of reagents and cells, and are not compatible with high throughput screening (HTS) systems. Microscale technology offers the miniaturization of 3D cultures and allows efficient screening of various conditions. This review will discuss the development, most influential works, and current advantages and challenges of microscale culture systems for screening cells in 3D microenvironments. PMID:25274061

Fludrocortisone therapy in cerebral salt wasting.

PubMed

Taplin, Craig E; Cowell, Christopher T; Silink, Martin; Ambler, Geoffrey R

2006-12-01

Cerebral salt wasting is an increasingly recognized condition in pediatrics and is characterized by inappropriate natriuresis and volume contraction in the presence of cerebral pathology. Diagnosis can be difficult and therapy challenging. A few single case reports of the successful use of fludrocortisone exist. We report 4 patients with cerebral salt wasting, all of whom presented with hyponatremia in the presence of known intracerebral pathology. All had clinically significant hyponatremia, and 3 had hyponatremic seizures. Two of the patients also satisfied clinical criteria for diabetes insipidus. They all were treated with regimens using increased sodium and fluid administration but experienced ongoing salt wasting. Fludrocortisone was instituted in all 4 patients and in 3 resulted in rapid improvement in net sodium balance, enabling the weaning of hypertonic fluids and stabilization of serum electrolytes. In 3 patients, fludrocortisone treatment was complicated by hypokalemia, and in 1 patient by hypertension, which necessitated a dose reduction or brief cessation of therapy. Duration of therapy was 4 to 125 days. Cerebral salt wasting presents considerable management challenges; however, fludrocortisone therapy can be an effective adjunct to treatment.

Less impairment of hemostasis and reduced blood loss in pigs after resuscitation from hemorrhagic shock using the small-volume concept with hypertonic saline/hydroxyethyl starch as compared to administration of 4% gelatin or 6% hydroxyethyl starch solution.

PubMed

Haas, Thorsten; Fries, Dietmar; Holz, Carmen; Innerhofer, Petra; Streif, Werner; Klingler, Anton; Hanke, Alexander; Velik-Salchner, Corinna

2008-04-01

Small-volume resuscitation using hypertonic saline/hydroxyethyl starch 200/0.62 (HS-HES) has been shown to be an effective alternative to the administration of crystalloids or colloids in trauma patients. All i.v. fluids cause dose-related dilutional coagulopathy and show intrinsic effects on the hemostatic system, but only few data refer to functional consequences after small-volume resuscitation. Using thrombelastometry (ROTEM), we studied 30 pigs (weighing 35-45 kg) after withdrawal of 60% of blood volume [1484 mL (1369-1624 mL)] and receiving 4 mL/kg HS-HES for compensation of blood loss or 4% gelatin or 6% HES 130/0.4 in a 1:1 ratio to lost blood volume. To compare the ROTEM variables (coagulation time, clot formation time, alpha angle, clot firmness, and fibrinogen polymerization) with bleeding tendency, a hepatic incision was made and blood loss was measured. Median (25th, 75th percentile) fibrinogen polymerization was significantly higher after HS-HES infusion [11 mm (10, 11), P = 0.0034] when compared with administration of 4% gelatin [4.5 mm (3.0, 5.8)] or HES 130/0.4 [3.5 mm (2.3, 4.0)]. Median blood loss after liver incision was 725 mL (900, 375) after HS-HES, 1625 mL (1275, 1950) after 4% gelatin, and 1600 mL (1500, 1800) after 6% HES 130/0.4 (P = 0.004). Hemodynamic stabilization was traceable in all groups but showed differences regarding filling pressures. Resuscitation from hemorrhagic shock with HS-HES 200/0.62 results in less impairment of clot formation when compared with compensation of blood loss by administering 6% HES 130/0.4 or 4% gelatin.

The longstanding challenge of the nanocrystallization of 1,3,5-trinitroperhydro-1,3,5-triazine (RDX)

PubMed Central

Spitzer, Denis

2017-01-01

Research efforts for realizing safer and higher performance energetic materials are continuing unabated all over the globe. While the thermites – pyrotechnic compositions of an oxide and a metal – have been finely tailored thanks to progress in other sectors, organic high explosives are still stagnating. The most symptomatic example is the longstanding challenge of the nanocrystallization of 1,3,5-trinitroperhydro-1,3,5-triazine (RDX). Recent advances in crystallization processes and milling technology mark the beginning of a new area which will hopefully lead the pyroelectric industry to finally embrace nanotechnology. This work reviews the previous and current techniques used to crystallize RDX at a submicrometer scale or smaller. Several key points are highlighted then discussed, such as the smallest particle size and its morphology, and the scale-up capacity and the versatility of the process. PMID:28326236

Role of NH3 and NH4+ transporters in renal acid-base transport.

PubMed

Weiner, I David; Verlander, Jill W

2011-01-01

Renal ammonia excretion is the predominant component of renal net acid excretion. The majority of ammonia excretion is produced in the kidney and then undergoes regulated transport in a number of renal epithelial segments. Recent findings have substantially altered our understanding of renal ammonia transport. In particular, the classic model of passive, diffusive NH3 movement coupled with NH4+ "trapping" is being replaced by a model in which specific proteins mediate regulated transport of NH3 and NH4+ across plasma membranes. In the proximal tubule, the apical Na+/H+ exchanger, NHE-3, is a major mechanism of preferential NH4+ secretion. In the thick ascending limb of Henle's loop, the apical Na+-K+-2Cl- cotransporter, NKCC2, is a major contributor to ammonia reabsorption and the basolateral Na+/H+ exchanger, NHE-4, appears to be important for basolateral NH4+ exit. The collecting duct is a major site for renal ammonia secretion, involving parallel H+ secretion and NH3 secretion. The Rhesus glycoproteins, Rh B Glycoprotein (Rhbg) and Rh C Glycoprotein (Rhcg), are recently recognized ammonia transporters in the distal tubule and collecting duct. Rhcg is present in both the apical and basolateral plasma membrane, is expressed in parallel with renal ammonia excretion, and mediates a critical role in renal ammonia excretion and collecting duct ammonia transport. Rhbg is expressed specifically in the basolateral plasma membrane, and its role in renal acid-base homeostasis is controversial. In the inner medullary collecting duct (IMCD), basolateral Na+-K+-ATPase enables active basolateral NH4+ uptake. In addition to these proteins, several other proteins also contribute to renal NH3/NH4+ transport. The role and mechanisms of these proteins are discussed in depth in this review.

Relative binding affinity prediction of farnesoid X receptor in the D3R Grand Challenge 2 using FEP+

NASA Astrophysics Data System (ADS)

Schindler, Christina; Rippmann, Friedrich; Kuhn, Daniel

2018-01-01

Physics-based free energy simulations have increasingly become an important tool for predicting binding affinity and the recent introduction of automated protocols has also paved the way towards a more widespread use in the pharmaceutical industry. The D3R 2016 Grand Challenge 2 provided an opportunity to blindly test the commercial free energy calculation protocol FEP+ and assess its performance relative to other affinity prediction methods. The present D3R free energy prediction challenge was built around two experimental data sets involving inhibitors of farnesoid X receptor (FXR) which is a promising anticancer drug target. The FXR binding site is predominantly hydrophobic with few conserved interaction motifs and strong induced fit effects making it a challenging target for molecular modeling and drug design. For both data sets, we achieved reasonable prediction accuracy (RMSD ≈ 1.4 kcal/mol, rank 3-4 according to RMSD out of 20 submissions) comparable to that of state-of-the-art methods in the field. Our D3R results boosted our confidence in the method and strengthen our desire to expand its applications in future in-house drug design projects.

Relative binding affinity prediction of farnesoid X receptor in the D3R Grand Challenge 2 using FEP.

PubMed

Schindler, Christina; Rippmann, Friedrich; Kuhn, Daniel

2018-01-01

Physics-based free energy simulations have increasingly become an important tool for predicting binding affinity and the recent introduction of automated protocols has also paved the way towards a more widespread use in the pharmaceutical industry. The D3R 2016 Grand Challenge 2 provided an opportunity to blindly test the commercial free energy calculation protocol FEP+ and assess its performance relative to other affinity prediction methods. The present D3R free energy prediction challenge was built around two experimental data sets involving inhibitors of farnesoid X receptor (FXR) which is a promising anticancer drug target. The FXR binding site is predominantly hydrophobic with few conserved interaction motifs and strong induced fit effects making it a challenging target for molecular modeling and drug design. For both data sets, we achieved reasonable prediction accuracy (RMSD ≈ 1.4 kcal/mol, rank 3-4 according to RMSD out of 20 submissions) comparable to that of state-of-the-art methods in the field. Our D3R results boosted our confidence in the method and strengthen our desire to expand its applications in future in-house drug design projects.

Intravenous administration of hypertonic sodium chloride solution with dextran or isotonic sodium chloride solution for treatment of septic shock secondary to pyometra in dogs.

PubMed

Fantoni, D T; Auler Junior, J O; Futema, F; Cortopassi, S R; Migliati, E R; Faustino, M; de Oliveira, C M

1999-11-01

To determine effects of i.v. administration of hypertonic saline (7.5% NaCl) solution with 6% dextran 70 (HSSD) or isotonic saline (0.9% NaCl) solution (ISS) to dogs with septic shock secondary to pyometra. Prospective, randomized, clinical study. 14 client-owned dogs with septic shock secondary to pyometra. Prior to emergency ovariohysterectomy, catheters were placed in pulmonary and femoral arteries of each dog to evaluate hemodynamic and oxygenation status. Immediately prior to surgery, 7 dogs received HSSD (4 ml/kg [1.82 ml/lb] of body weight, i.v.) and 7 dogs received ISS (32 ml/kg [14.54 ml/lb], i.v.) during a 5-minute period. Measurements of hemodynamic and oxygenation variables were obtained before and 5 and 20 minutes after administration of fluids. Mean arterial pressure (MAP) increased significantly 5 and 20 minutes after administration of HSSD, whereas ISS did not affect MAP. However, cardiac output, cardiac index, and oxygen delivery increased and hematocrit decreased after both treatments. Oxygen consumption and extraction rate and degree of acidosis did not improve after either treatment. Intravenous administration of small volumes of HSSD to dogs with septic shock secondary to pyometra resulted in improvement of hemodynamic and oxygenation status. Although cardiac output, cardiac index, and oxygen delivery improved after administration of a volume of ISS equal to 8 times that of HSSD, MAP increased to > 80 mm Hg only after treatment with HSSD. Administration of HSSD may be an effective treatment for septic shock in dogs.

Adaptation of the nematode Caenorhabditis elegans to extreme osmotic stress.

PubMed

Lamitina, S Todd; Morrison, Rebecca; Moeckel, Gilbert W; Strange, Kevin

2004-04-01

The ability to control osmotic balance is essential for cellular life. Cellular osmotic homeostasis is maintained by accumulation and loss of inorganic ions and organic osmolytes. Although osmoregulation has been studied extensively in many cell types, major gaps exist in our molecular understanding of this essential process. Because of its numerous experimental advantages, the nematode Caenorhabditis elegans provides a powerful model system to characterize the genetic basis of animal cell osmoregulation. We therefore characterized the ability of worms to adapt to extreme osmotic stress. Exposure of worms to high-salt growth agar causes rapid shrinkage. Survival is normal on agar containing up to 200 mM NaCl. When grown on 200 mM NaCl for 2 wk, worms are able to survive well on agar containing up to 500 mM NaCl. HPLC analysis demonstrated that levels of the organic osmolyte glycerol increase 15- to 20-fold in nematodes grown on 200 mM NaCl agar. Accumulation of glycerol begins 3 h after exposure to hypertonic stress and peaks by 24 h. Glycerol accumulation is mediated primarily by synthesis from metabolic precursors. Consistent with this finding, hypertonicity increases transcriptional expression of glycerol 3-phosphate dehydrogenase, an enzyme that is rate limiting for hypertonicity-induced glycerol synthesis in yeast. Worms adapted to high salt swell and then return to their initial body volume when exposed to low-salt agar. During recovery from hypertonic stress, glycerol levels fall rapidly and glycerol excretion increases approximately fivefold. Our studies provide the first description of osmotic adaptation in C. elegans and provide the foundation for genetic and functional genomic analysis of animal cell osmoregulation.

Limited treatment with beta-1,3/1,6-glucan improves production values of broiler chickens challenged with Escherichia coli.

PubMed

Huff, G R; Huff, W E; Rath, N C; Tellez, G

2006-04-01

The development of antibiotic-resistant bacteria has led to a need for alternatives to antibiotics for growth promotion and disease prevention in poultry production. The helical polysaccharide beta-1,3/1,6-glucan is derived from the cell wall of Saccharomyces cervisiae and has immunomodulating activities. The objective of this study was to determine the ability of 2 supplementation programs with a commercial beta-1,3/1,6-glucan product to protect broiler chicks from experimental respiratory challenge with Escherichia coli. Chicks were housed in battery-brooders from 1 d of age and fed a standard starter diet or the same diet containing 20 g/ton (22 ppm) of purified beta-1,3/1,6-glucan either continuously (BG25d) or for only the first 7 d prior to challenge (BG7d). At d 7 one-half of the birds were inoculated in the thoracic air sac with 800 cfu of a serotype O2, nonmotile strain of E. coli. All surviving birds were necropsied at d 25. Body weight of survivors and feed conversion efficiency were protected from the adverse effects of E. coli challenge by BG7d but not by BG25d. Mortality was nominally decreased from 63% (control) to 53% in BG25d and 47% in BG7d, but these decreases were not significant. The relative weights of the liver and heart were increased, and the bursa of Fabricius relative weights were decreased by E. coli challenge, and these effects were modulated by beta-glucan treatment. Despite positive effects of BG7d in E. coli-challenged birds, the BW of nonchallenged birds was decreased by BG7d and BG25d. These results suggest that supplementation of broiler diets with beta-1,3/1,6-glucan may be valuable for decreasing production losses due to E. coli respiratory disease, but that the immune stimulation provided may also result in decreased production values under experimental battery conditions or for birds raised in an environment with minimal disease challenges.

Modulation of kidney urea transporter UT-A3 activity by alpha2,6-sialylation

PubMed Central

Qian, Xiaoqian; Sands, Jeff M.; Song, Xiang; Chen, Guangping

2016-01-01

Two urea transporters, UT-A1 and UT-A3, are expressed in the kidney terminal inner medullary collecting duct (IMCD) and are important for the production of concentrated urine. UT-A1, as the largest isoform of all UT-A urea transporters, has gained much attention and been extensively studied; however the role and the regulation of UT-A3 are less explored. In this study, we investigated UT-A3 regulation by glycosylation modification. A site-directed mutagenesis verified a single glycosylation site in UT-A3 at Asn279. Loss of the glycosylation reduced forskolin-stimulated UT-A3 cell membrane expression and urea transport activity. UT-A3 has two glycosylation forms, 45 kDa and 65 kDa. Using sugar specific-binding lectins, the UT-A3 glycosylation profile was examined. The 45 kDa form was pulled down by lectin Con A and GNL, indicating an immature glycan with a high amount of mannose (Man); whereas the 65 kDa form is a mature glycan composed of acetylglucosamine (GlcNAc), poly-N-acetyllactosame (poly-LacNAc) that was pulled down by WGA and tomato lectin, respectively. Interestingly, the mature form of UT-A3 glycan contains significant amounts of sialic acid. We explored the enzymes responsible for directing UT-A3 sialylation. Sialyltransferase ST6GalI, but not ST3GalIV, catabolizes UT-A3 α2, 6-sialylation. Activation of PKC by PDB treatment promoted UT-A3 glycan sialylation and membrane surface expression. PKC inhibitor chelerythrine blocks ST6GalI-induced UT-A3 sialylation. Increased sialylation by ST6GalI increased UT-A3 protein stability and urea transport activity. Collectively, our study reveals a novel mechanism of UT-A3 regulation by ST6GalI-mediated sialylation modification that may play an important in kidney urea reabsorption and the urinary concentrating mechanism. PMID:26972907

Modulation of kidney urea transporter UT-A3 activity by alpha2,6-sialylation.

PubMed

Qian, Xiaoqian; Sands, Jeff M; Song, Xiang; Chen, Guangping

2016-07-01

Two urea transporters, UT-A1 and UT-A3, are expressed in the kidney terminal inner medullary collecting duct (IMCD) and are important for the production of concentrated urine. UT-A1, as the largest isoform of all UT-A urea transporters, has gained much attention and been extensively studied; however, the role and the regulation of UT-A3 are less explored. In this study, we investigated UT-A3 regulation by glycosylation modification. A site-directed mutagenesis verified a single glycosylation site in UT-A3 at Asn279. Loss of the glycosylation reduced forskolin-stimulated UT-A3 cell membrane expression and urea transport activity. UT-A3 has two glycosylation forms, 45 and 65 kDa. Using sugar-specific binding lectins, the UT-A3 glycosylation profile was examined. The 45-kDa form was pulled down by lectin concanavalin A (Con A) and Galant husnivalis lectin (GNL), indicating an immature glycan with a high amount of mannose (Man), whereas the 65-kDa form is a mature glycan composed of acetylglucosamine (GlcNAc) and poly-N-acetyllactosame (poly-LacNAc) that was pulled down by wheat germ agglutinin (WGA) and tomato lectin, respectively. Interestingly, the mature form of UT-A3 glycan contains significant amounts of sialic acid. We explored the enzymes responsible for directing UT-A3 sialylation. Sialyltransferase ST6GalI, but not ST3GalIV, catabolizes UT-A3 α2,6-sialylation. Activation of protein kinase C (PKC) by PDB treatment promoted UT-A3 glycan sialylation and membrane surface expression. The PKC inhibitor chelerythrine blocks ST6GalI-induced UT-A3 sialylation. Increased sialylation by ST6GalI increased UT-A3 protein stability and urea transport activity. Collectively, our study reveals a novel mechanism of UT-A3 regulation by ST6GalI-mediated sialylation modification that may play an important role in kidney urea reabsorption and the urinary concentrating mechanism.

Evaluation and comparison of 3D intervertebral disc localization and segmentation methods for 3D T2 MR data: A grand challenge.

PubMed

Zheng, Guoyan; Chu, Chengwen; Belavý, Daniel L; Ibragimov, Bulat; Korez, Robert; Vrtovec, Tomaž; Hutt, Hugo; Everson, Richard; Meakin, Judith; Andrade, Isabel Lŏpez; Glocker, Ben; Chen, Hao; Dou, Qi; Heng, Pheng-Ann; Wang, Chunliang; Forsberg, Daniel; Neubert, Aleš; Fripp, Jurgen; Urschler, Martin; Stern, Darko; Wimmer, Maria; Novikov, Alexey A; Cheng, Hui; Armbrecht, Gabriele; Felsenberg, Dieter; Li, Shuo

2017-01-01

The evaluation of changes in Intervertebral Discs (IVDs) with 3D Magnetic Resonance (MR) Imaging (MRI) can be of interest for many clinical applications. This paper presents the evaluation of both IVD localization and IVD segmentation methods submitted to the Automatic 3D MRI IVD Localization and Segmentation challenge, held at the 2015 International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI2015) with an on-site competition. With the construction of a manually annotated reference data set composed of 25 3D T2-weighted MR images acquired from two different studies and the establishment of a standard validation framework, quantitative evaluation was performed to compare the results of methods submitted to the challenge. Experimental results show that overall the best localization method achieves a mean localization distance of 0.8 mm and the best segmentation method achieves a mean Dice of 91.8%, a mean average absolute distance of 1.1 mm and a mean Hausdorff distance of 4.3 mm, respectively. The strengths and drawbacks of each method are discussed, which provides insights into the performance of different IVD localization and segmentation methods. Copyright © 2016 Elsevier B.V. All rights reserved.

β-1,3/1,6-Glucan alleviated intestinal mucosal barrier impairment of broiler chickens challenged with Salmonella enterica serovar Typhimurium.

PubMed

Shao, Yujing; Guo, Yuming; Wang, Zhong

2013-07-01

This study investigated the protective effect of β-1,3/1,6-glucan on gut morphology, intestinal epithelial tight junctions, and bacterial translocation of broiler chickens challenged with Salmonella enterica serovar Typhimurium. Ninety Salmonella-free Arbor Acre male broiler chickens were randomly divided into 3 groups: negative control group (NC), Salmonella Typhimurium-infected positive group (PC), and the Salmonella Typhimurium-infected group with dietary 100 mg/kg of β-1,3/1,6-glucan supplementation (T) to determine the effect of β-1,3/1,6-glucan on intestinal barrier function. Salmonella Typhimurium challenge alone significantly decreased villus height (P < 0.001), villus height/crypt depth ratio (P < 0.05), and the number of goblet cells (P < 0.001) in the jejunum at 14 d postinfection (dpi), but significantly increased the number of intestinal secretory IgA (sIgA)-expressing cells at 14 dpi (P < 0.01) and total sIgA levels in the jejunum at 7 (P < 0.05) and 14 dpi (P < 0.01) compared with the unchallenged birds (NC). Dietary β-1,3/1,6-glucan supplementation not only significantly increased villus height, villus height/crypt depth ratio, and the number of goblet cells (P < 0.01), but also increased the number of sIgA-expressing cells (P < 0.05) and sIgA content in the jejunum at 14 dpi (P < 0.01) in birds challenged with Salmonella Typhimurium in comparison with Salmonella Typhimurium challenge alone. β-1,3/1,6-Glucan addition had significant inhibitory effects (P < 0.05) on cecal Salmonella colonization levels and liver Salmonella invasion of the Salmonella Typhimurium-infected birds compared with the PC group. Intestinal tight junction proteins claudin-1, claudin-4, and occludin mRNA expression in the jejunum at 14 dpi was significantly decreased by Salmonella Typhimurium challenge alone (P < 0.01) compared with that of the NC group, whereas β-1,3/1,6-glucan supplementation significantly increased claudin-1 and occludin mRNA expression (P < 0.01) at

Aquatic rehabilitation for the treatment of neurological disorders.

PubMed

Morris, D M

1994-01-01

Patients with neurological disorders present therapists with complex challenges for treatment, including weakness, hypertonicity, voluntary movement deficit, limited range of motion, sensory loss, incoordination, and postural instability. The presence of one or more of these impairments negatively influences these patients by contributing to problems in walking, transferring, and reaching. Aquatic rehabilitation offers a unique, versatile approach to the treatment of these disabilities. This article examines the problems encountered by patients with neurological disorders, general principles guiding neurotreatment, and aquatic neurorehabilitation approaches.

Long noncoding RNA Hoxb3os is dysregulated in autosomal dominant polycystic kidney disease and regulates mTOR signaling.

PubMed

Aboudehen, Karam; Farahani, Shayan; Kanchwala, Mohammed; Chan, Siu Chiu; Avdulov, Svetlana; Mickelson, Alan; Lee, Dayeon; Gearhart, Micah D; Patel, Vishal; Xing, Chao; Igarashi, Peter

2018-06-15

Autosomal dominant polycystic kidney disease (ADPKD) is a debilitating disease that is characterized by the accumulation of numerous fluid-filled cysts in the kidney. ADPKD is primarily caused by mutations in two genes, PKD1 and PKD2 Long noncoding RNAs (lncRNA), defined by a length >200 nucleotides and absence of a long ORF, have recently emerged as epigenetic regulators of development and disease; however, their involvement in PKD has not been explored previously. Here, we performed deep RNA-Seq to identify lncRNAs that are dysregulated in two orthologous mouse models of ADPKD (kidney-specific Pkd1 and Pkd2 mutant mice). We identified a kidney-specific, evolutionarily conserved lncRNA called Hoxb3os that was down-regulated in cystic kidneys from Pkd1 and Pkd2 mutant mice. The human ortholog HOXB3-AS1 was down-regulated in cystic kidneys from ADPKD patients. Hoxb3os was highly expressed in renal tubules in adult WT mice, whereas its expression was lost in the cyst epithelium of mutant mice. To investigate the function of Hoxb3os , we utilized CRISPR/Cas9 to knock out its expression in mIMCD3 cells. Deletion of Hoxb3os resulted in increased phosphorylation of mTOR and its downstream targets, including p70 S6 kinase, ribosomal protein S6, and the translation repressor 4E-BP1. Consistent with activation of mTORC1 signaling, Hoxb3os mutant cells displayed increased mitochondrial respiration. The Hoxb3os mutant phenotype was partially rescued upon re-expression of Hoxb3os in knockout cells. These findings identify Hoxb3os as a novel lncRNA that is down-regulated in ADPKD and regulates mTOR signaling and mitochondrial respiration. © 2018 Aboudehen et al.

Effect of melatonin supplementation on plasma vasopressin response to different conditions in rats with hyperthyroidism induced by L-thyroxine.

PubMed

Mogulkoc, Rasim; Baltaci, Abdulkerim Kasim

2010-04-09

The present study was performed to determine how basal, isotonic, hypertonic and hypovolemic conditions affect fluid-electrolyte balance and plasma arginine vasopressin (AVP) levels in rats with experimental hyperthyroidism supplemented with melatonin. The rats were divided into four groups of twenty-four subjects each kept under the following treatments during one month: (1) Controls; (2) treated with L-thyroxine; (3) treated with L-thyroxine and sham melatonin and (4) treated with L-thyroxine and melatonin. After this each group was further subdivided into subgroups that were subject to normal, isotonic, hypertonic and hypovolemic conditions. The plasma AVP, total triiodothyronine (TT(3)), total thyroxine (TT(4)) and melatonin levels were measured in plasma by means of a Phoenix Pharmaceutical RIA test kit. Hematocrit and osmolality levels were also determined. There were significant increases of total T3 and T4 levels in the L-thyroxine treated groups, p<0.001. The AVP levels were also increased in groups 2 and 3, but not so in the rats treated with melatonin (p<0.001), which also showed increased plasma melatonin levels (p<0.001). These results indicate that treatment with L-thyroxine increases stimulated and non-stimulated AVP release that are inhibited by melatonin supplementation. It was also shown that AVP response to hypertonic and hypovolemic conditions was not affected by L-thyroxine treatment and/or L-thyroxine+melatonin treatment. Copyright 2009 Elsevier B.V. All rights reserved.

The Challenge. Volume 13, Number 3, Spring 2005

ERIC Educational Resources Information Center

US Department of Education, 2005

2005-01-01

"The Challenge", a publication of the US Department of Education's office of Safe and Drug-Free Schools, provides critical information and resources to assist schools in creating safe and healthy environments for young people. This issue addresses the following topics: (1) Prevention Programs with Staying Power: What Makes Good Prevention Programs…

Challenges and Opportunities in Gen3 Embedded Cooling with High-Quality Microgap Flow

NASA Technical Reports Server (NTRS)

Bar-Cohen, Avram; Robinson, Franklin L.; Deisenroth, David C.

2018-01-01

Gen3, Embedded Cooling, promises to revolutionize thermal management of advanced microelectronic systems by eliminating the sequential conductive and interfacial thermal resistances which dominate the present 'remote cooling' paradigm. Single-phase interchip microfluidic flow with high thermal conductivity chips and substrates has been used successfully to cool single transistors dissipating more than 40kW/sq cm, but efficient heat removal from transistor arrays, larger chips, and chip stacks operating at these prodigious heat fluxes would require the use of high vapor fraction (quality), two-phase cooling in intra- and inter-chip microgap channels. The motivation, as well as the challenges and opportunities associated with evaporative embedded cooling in realistic form factors, is the focus of this paper. The paper will begin with a brief review of the history of thermal packaging, reflecting the 70-year 'inward migration' of cooling technology from the computer-room, to the rack, and then to the single chip and multichip module with 'remote' or attached air- and liquid-cooled coldplates. Discussion of the limitations of this approach and recent results from single-phase embedded cooling will follow. This will set the stage for discussion of the development challenges associated with application of this Gen3 thermal management paradigm to commercial semiconductor hardware, including dealing with the effects of channel length, orientation, and manifold-driven centrifugal acceleration on the governing behavior.

Closing the Gap: The Challenges of Treating Hepatitis C Virus Genotype 3 Infection.

PubMed

Martin, Michelle T; Deming, Paulina

2017-06-01

The efficacy of hepatitis C virus (HCV) treatment has increased over the last 5 years to nearly 100% for many patient groups. Patients with genotype (GT) 3 HCV infection, however, and specifically cirrhotic or treatment-experienced patients, have lower sustained virologic response (SVR) rates than patients with other GTs. Because GT 3 presents more clinical challenges than other GTs, this review focuses on the evolution and efficacy of direct-acting antiviral (DAA) treatment options for HCV GT 3 infection after the historical standard of care with pegylated interferon and ribavirin. Our objective was to review the SVR rates with available and late-pipeline DAAs for HCV GT 3 infection and discuss challenges with successful GT 3 treatment. Authors performed a literature search of the PubMed/MEDLINE database (inception to March 27, 2017) and narrowed the field to clinical trials published in English. Trials that evaluated alternative treatments, non-DAA historical treatment, and DAAs not currently indicated for HCV were excluded. Trials only involving patients with human immunodeficiency virus/HCV coinfection were also excluded. Additional trials were identified from a review of the ClinicalTrials.gov database. Authors further identified references from a review of literature citations and reviewed annual meeting abstracts from the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver for pipeline and real-world GT 3 data. Phase III trial data were not available to support all GT 3 treatment recommendations found in the guidelines. The SVR rates were lower in treatment-experienced and cirrhotic patients with GT 3 than other HCV populations. Treatment failure was associated with resistance to current treatment regimens. Clinical studies included patients with various levels of advanced liver disease, but few patients with decompensated cirrhosis were represented. Recent advances in pharmacologic treatment with DAAs

Transcriptional Activation of c3 and hsp70 as Part of the Immune Response of Acropora millepora to Bacterial Challenges

PubMed Central

Brown, Tanya; Bourne, David; Rodriguez-Lanetty, Mauricio

2013-01-01

The impact of disease outbreaks on coral physiology represents an increasing concern for the fitness and resilience of reef ecosystems. Predicting the tolerance of corals to disease relies on an understanding of the coral immune response to pathogenic interactions. This study explored the transcriptional response of two putative immune genes (c3 and c-type lectin) and one stress response gene (hsp70) in the reef building coral, Acropora millepora challenged for 48 hours with bacterial strains, Vibrio coralliilyticus and Alteromonas sp. at concentrations of 106 cells ml-1. Coral fragments challenged with V. coralliilyticus appeared healthy while fragments challenged with Alteromonas sp. showed signs of tissue lesions after 48 hr. Coral-associated bacterial community profiles assessed using denaturing gradient gel electrophoresis changed after challenge by both bacterial strains with the Alteromonas sp. treatment demonstrating the greatest community shift. Transcriptional profiles of c3 and hsp70 increased at 24 hours and correlated with disease signs in the Alteromonas sp. treatment. The expression of hsp70 also showed a significant increase in V. coralliilyticus inoculated corals at 24 h suggesting that even in the absence of disease signs, the microbial inoculum activated a stress response in the coral. C-type lectin did not show a response to any of the bacterial treatments. Increase in gene expression of c3 and hsp70 in corals showing signs of disease indicates their potential involvement in immune and stress response to microbial challenges. PMID:23861754

Classroom Challenge: A 3D Snapshot of Student Learning in Mathematics

ERIC Educational Resources Information Center

Wilder, Sandra

2015-01-01

This article aims to describe a type of formative assessment, MAP Classroom Challenge, which has been introduced in mathematics classrooms in recent years. MAP, or the Mathematics Assessment Project Classroom Challenges (formerly known as Formative Assessment Lessons), are developed by teams of math educators from the Shell Centre for Mathematical…

Characterization of constitutive and acid-induced outwardly rectifying chloride currents in immortalized mouse distal tubular cells.

PubMed

Valinsky, William C; Touyz, Rhian M; Shrier, Alvin

2017-08-01

Thiazides block Na + reabsorption while enhancing Ca 2+ reabsorption in the kidney. As previously demonstrated in immortalized mouse distal convoluted tubule (MDCT) cells, chlorothiazide application induced a robust plasma membrane hyperpolarization, which increased Ca 2+ uptake. This essential thiazide-induced hyperpolarization was prevented by the Cl - channel inhibitor 5-Nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), implicating NPPB-sensitive Cl - channels, however the nature of these Cl - channels has been rarely described in the literature. Here we show that MDCT cells express a dominant, outwardly rectifying Cl - current at extracellular pH7.4. This constitutive Cl - current was more permeable to larger anions (Eisenman sequence I; I - >Br - ≥Cl - ) and was substantially inhibited by >100mM [Ca 2+ ] o , which distinguished it from ClC-K2/barttin. Moreover, the constitutive Cl - current was blocked by NPPB, along with other Cl - channel inhibitors (4,4'-diisothiocyanatostilbene-2,2'-disulfonate, DIDS; flufenamic acid, FFA). Subjecting the MDCT cells to an acidic extracellular solution (pH<5.5) induced a substantially larger outwardly rectifying NPPB-sensitive Cl - current. This acid-induced Cl - current was also anion permeable (I - >Br - >Cl - ), but was distinguished from the constitutive Cl - current by its rectification characteristics, ion sensitivities, and response to FFA. In addition, we have identified similar outwardly rectifying and acid-sensitive currents in immortalized cells from the inner medullary collecting duct (mIMCD-3 cells). Expression of an acid-induced Cl - current would be particularly relevant in the acidic IMCD (pH<5.5). To our knowledge, the properties of these Cl - currents are unique and provide the mechanisms to account for the Cl - efflux previously speculated to be present in MDCT cells. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

3D Virtual Worlds as Art Media and Exhibition Arenas: Students' Responses and Challenges in Contemporary Art Education

ERIC Educational Resources Information Center

Lu, Lilly

2013-01-01

3D virtual worlds (3D VWs) are considered one of the emerging learning spaces of the 21st century; however, few empirical studies have investigated educational applications and student learning aspects in art education. This study focused on students' responses to and challenges with 3D VWs in both aspects. The findings show that most participants…

Urea transporter knockout mice and their renal phenotypes.

PubMed

Fenton, Robert A; Yang, Baoxue

2014-01-01

Urea transporter gene knockout mice have been created for the study of the urine-concentrating mechanism. The major findings in studies of the renal phenotype of these mice are as follows: (1) Urea accumulation in the inner medullary interstitium is dependent on intrarenal urea recycling mediated by urea transporters; (2) urea transporters are essential for preventing urea-induced osmotic diuresis and thus for water conservation; (3) NaCl concentration in the inner medullary interstitium is not significantly affected by the absence of IMCD, descending limb of Henle and descending vasa recta urea transporters. Studies in urea transporter knockout mouse models have highlighted the essential role of urea for producing maximally concentrated urine.

[3D bioprinting of cartilage: challenges concerning the reconstruction of a burned ear].

PubMed

Visscher, Dafydd O; Bos, Ernst J; van Zuijlen, Paul P M

2015-01-01

Reconstruction of a severely maimed ear is a major challenge. The ear is highly flexible yet tough, and has a very complex three-dimensional shape. Reconstruction of a patient's burned ear is even more complex due to surrounding tissue damage. Not only does this hamper reconstruction options, it also increases the likelihood of issues when using synthetic implant materials. In such cases, rib cartilage is the preferred option, but this tissue has practical limitations too. For these reasons, tissue engineering and 3D bioprinting may have the potential to create personalized cartilage implants for burns patients. However, 3D bioprinting is a tool to facilitate the reconstruction, and not by itself the Holy Grail. The clinical application of this technique is still at a very early stage. Nevertheless, we expect that 3D bioprinting can be utilised for facial reconstruction following burns come 2020.

Regulatory impairments following selective 6-OHDA lesions of the neostriatum.

PubMed

Dunnett, S B; Iversen, S D

1982-02-01

6-Hydroxydopamine lesions of the ventrolateral (VLC) but not anteromedial (AMC) caudate-putamen in rats resulted in a greater post-operative reduction in body weight and water intake than seen in animals with sham lesions. Once animals had fully resumed spontaneous food and water intake, a series of regulatory challenges were administered, and the AMC rats showed a reduced enhancement of drinking following injection of hypertonic saline. The results are interpreted in terms of a heterogeneous striatal convergence of nigrostriatal and cortical regulatory mechanisms.

Saline in acute bronchiolitis RCT and economic evaluation: hypertonic saline in acute bronchiolitis - randomised controlled trial and systematic review.

PubMed

Everard, Mark L; Hind, Daniel; Ugonna, Kelechi; Freeman, Jennifer; Bradburn, Mike; Dixon, Simon; Maguire, Chin; Cantrill, Hannah; Alexander, John; Lenney, Warren; McNamara, Paul; Elphick, Heather; Chetcuti, Philip Aj; Moya, Eduardo F; Powell, Colin; Garside, Jonathan P; Chadha, Lavleen Kumar; Kurian, Matthew; Lehal, Ravinderjit S; MacFarlane, Peter I; Cooper, Cindy L; Cross, Elizabeth

2015-08-01

Acute bronchiolitis is the most common cause of hospitalisation in infancy. Supportive care and oxygen are the cornerstones of management. A Cochrane review concluded that the use of nebulised 3% hypertonic saline (HS) may significantly reduce the duration of hospitalisation. To test the hypothesis that HS reduces the time to when infants were assessed as being fit for discharge, defined as in air with saturations of > 92% for 6 hours, by 25%. Parallel-group, pragmatic randomised controlled trial, cost-utility analysis and systematic review. Ten UK hospitals. Infants with acute bronchiolitis requiring oxygen therapy were allocated within 4 hours of admission. Supportive care with oxygen as required, minimal handling and fluid administration as appropriate to the severity of the disease, 3% nebulised HS every ± 6 hours. The trial primary outcome was time until the infant met objective discharge criteria. Secondary end points included time to discharge and adverse events. The costs analysed related to length of stay (LoS), readmissions, nebulised saline and other NHS resource use. Quality-adjusted life-years (QALYs) were estimated using an existing utility decrement derived for hospitalisation in children, together with the time spent in hospital in the trial. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and other databases from inception or from 2010 onwards, searched ClinicalTrials.gov and other registries and hand-searched Chest, Paediatrics and Journal of Paediatrics to January 2015. We included randomised/quasi-randomised trials which compared HS versus saline (± adjunct treatment) or no treatment. We used a fixed-effects model to combine mean differences for LoS and assessed statistical heterogeneity using the I (2) statistic. The trial randomised 158 infants to HS (n = 141 analysed) and 159 to standard care (n = 149 analysed). There was no difference between the two arms in the time to being declared fit for

Differential requirements of arrestin-3 and clathrin for ligand-dependent and -independent internalization of human G protein-coupled receptor 40.

PubMed

Qian, Jing; Wu, Chun; Chen, Xiaopan; Li, Xiangmei; Ying, Guoyuan; Jin, Lili; Ma, Qiang; Li, Guo; Shi, Ying; Zhang, Guozheng; Zhou, Naiming

2014-11-01

G protein-coupled receptor 40 (GPR40) is believed to be an attractive target to enhance insulin secretion in patients with type 2 diabetes. GPR40 has been found to couple to Gq protein, leading to the activation of phospholipase C and subsequent increases in the intracellular Ca(2+) level. However, the underlying mechanisms that regulate the internalization and desensitization of GPR40 remain to be elucidated. In the present study, a construct of GPR40 fused with enhanced green fluorescent protein (EGFP) at its C-terminus was constructed for direct imaging of the localization and internalization of GPR40 by confocal microscopy. In stably transfected HEK-293 cells, GPR40 receptors underwent rapid agonist-induced internalization and constitutive ligand-independent internalization. Our data demonstrated that the agonist-mediated internalization of GPR40 was significantly blocked by hypertonic sucrose treatment and by siRNA mediated depletion of the heavy chain of clathrin. In contrast, constitutive GPR40 internalization was not affected by hypertonic sucrose or by knock-down of clathrin expression, but it was affected by treatment with methyl-β-cyclodextrin (MβCD) and nystatin. Furthermore, our results using an arrestin-3-EGFP redistribution assay and siRNA-mediated knock-down of arrestin-3 and GRK2 expression revealed that arrestin-3 and GRK2 play an essential role in the regulation of agonist-mediated GPR40 internalization, but are not involved in the regulation of constitutive GPR40 internalization. Additionally, our observation showed that upon activation by agonist, the internalized GPR40 receptors were rapidly recycled back to the plasma membrane via Rab4/Rab5 positive endosomes, whereas the constitutively internalized GPR40 receptors were recycled back to the cell surface through Rab5 positive endosomes. Because FFA receptors exhibit a high level of homology, our observations could be applicable to other members of this family. Copyright © 2014 Elsevier Inc

Manufacturing and Security Challenges in 3D Printing

NASA Astrophysics Data System (ADS)

Zeltmann, Steven Eric; Gupta, Nikhil; Tsoutsos, Nektarios Georgios; Maniatakos, Michail; Rajendran, Jeyavijayan; Karri, Ramesh

2016-07-01

As the manufacturing time, quality, and cost associated with additive manufacturing (AM) continue to improve, more and more businesses and consumers are adopting this technology. Some of the key benefits of AM include customizing products, localizing production and reducing logistics. Due to these and numerous other benefits, AM is enabling a globally distributed manufacturing process and supply chain spanning multiple parties, and hence raises concerns about the reliability of the manufactured product. In this work, we first present a brief overview of the potential risks that exist in the cyber-physical environment of additive manufacturing. We then evaluate the risks posed by two different classes of modifications to the AM process which are representative of the challenges that are unique to AM. The risks posed are examined through mechanical testing of objects with altered printing orientation and fine internal defects. Finite element analysis and ultrasonic inspection are also used to demonstrate the potential for decreased performance and for evading detection. The results highlight several scenarios, intentional or unintentional, that can affect the product quality and pose security challenges for the additive manufacturing supply chain.

Regulatory impairments following selective kainic acid lesions of the neostriatum.

PubMed

Dunnett, S B; Iversen, S D

1980-12-01

Kainic acid lesions were made to the anteromedial (AMC) or ventrolateral (VLC) caudate nucleus and the projection areas of medial and sulcal prefrontal cortex (PFC), respectively. By the second day following lesion, all control and AMC rats had recovered normal food and water intake. By contrast, VLC lesions resulted in severe aphagia and adipsia lasting 3-15 days, accompanied by a rapid loss in weight. Animals were kept alive by palatable food supplement and force-feeding as required. Once all animals had recovered normal food and water intake (3-5 weeks) drinking to various physiological challenges--5% hypertonic saline s.c., food deprivation, quinine adulteration of water and 40% polyethylene glycol--were found to be normal in both lesion groups. By 3 months after lesion the groups did not differ in weight. Acute aphagia and adipsia had been reported following ablation of the sulcal but not the medial PFC in rats. The present experiment obtains parallel results in the PFC projection areas within the neostriatum.

Hindbrain serotonin and the rapid induction of sodium appetite

NASA Technical Reports Server (NTRS)

Menani, J. V.; De Luca, L. A. Jr; Thunhorst, R. L.; Johnson, A. K.

2000-01-01

Both systemically administered furosemide and isoproterenol produce water intake (i.e., thirst). Curiously, however, in light of the endocrine and hemodynamic effects produced by these treatments, they are remarkably ineffective in eliciting intake of hypertonic saline solutions (i.e., operationally defined as sodium appetite). Recent work indicates that bilateral injections of the serotonin receptor antagonist methysergide into the lateral parabrachial nuclei (LPBN) markedly enhance a preexisting sodium appetite. The present studies establish that a de novo sodium appetite can be induced with LPBN-methysergide treatment under experimental conditions in which only water is typically ingested. The effects of bilateral LPBN injections of methysergide were studied on the intake of water and 0. 3 M NaCl following acute (beginning 1 h after treatment) diuretic (furosemide)-induced sodium and water depletion and following subcutaneous isoproterenol treatment. With vehicle injected into the LPBN, furosemide treatment and isoproterenol injection both caused water drinking but essentially no intake of hypertonic saline. In contrast, bilateral treatment of the LPBN with methysergide induced the intake of 0.3 M NaCl after subcutaneous furosemide and isoproterenol. Water intake induced by subcutaneous furosemide or isoproterenol was not changed by LPBN-methysergide injections. The results indicate that blockade of LPBN-serotonin receptors produces a marked intake of hypertonic NaCl (i.e., a de novo sodium appetite) after furosemide treatment as well as subcutaneous isoproterenol.

Regulation of cytochrome P-450 4A activity by peroxisome proliferator-activated receptors in the rat kidney.

PubMed

Ishizuka, Tsuneo; Ito, Osamu; Tan, Liping; Ogawa, Susumu; Kohzuki, Masahiro; Omata, Ken; Takeuchi, Kazuhisa; Ito, Sadayoshi

2003-11-01

The localization of cytochrome P-450 4A, peroxisome proliferator-activated receptor (PPAR) alpha, and PPARgamma proteins, and the inducibility of P-450 4A expression and activity by PPAR agonists were determined in the rat kidney. The expressions of these proteins in isolated nephron segments were evaluated by immunoblot analysis, and the production of 20-hydroxyeicosatetraenoic acid (20-HETE) was measured as P-450 4A activity. P-450 4A proteins were expressed predominantly in the proximal tubule (PT), with lower expression in the preglomerular arteriole (Art), glomerulus (Glm), and medullary thick ascending limb (mTAL), but their expression was not detected in the inner medullary collecting duct (IMCD). PPARalpha protein was expressed in the PT and mTAL, and PPARgamma protein was expressed in the IMCD and mTAL. Treatment with clofibrate, the PPARalpha agonist, increased P-450 4A protein levels and the production of 20-HETE in microsomes prepared from the renal cortex, whereas treatment with pioglitazone, the PPARgamma agonist, affected neither of them. These results indicate that PPARalpha and PPARgamma proteins are localized in different nephron segments and the inducibility of P-450 4A expression and activity by the PPAR agonists correlates with the nephron-specific localization of the respective PPAR isoforms.

Performance of multiple docking and refinement methods in the pose prediction D3R prospective Grand Challenge 2016

NASA Astrophysics Data System (ADS)

Fradera, Xavier; Verras, Andreas; Hu, Yuan; Wang, Deping; Wang, Hongwu; Fells, James I.; Armacost, Kira A.; Crespo, Alejandro; Sherborne, Brad; Wang, Huijun; Peng, Zhengwei; Gao, Ying-Duo

2018-01-01

We describe the performance of multiple pose prediction methods for the D3R 2016 Grand Challenge. The pose prediction challenge includes 36 ligands, which represent 4 chemotypes and some miscellaneous structures against the FXR ligand binding domain. In this study we use a mix of fully automated methods as well as human-guided methods with considerations of both the challenge data and publicly available data. The methods include ensemble docking, colony entropy pose prediction, target selection by molecular similarity, molecular dynamics guided pose refinement, and pose selection by visual inspection. We evaluated the success of our predictions by method, chemotype, and relevance of publicly available data. For the overall data set, ensemble docking, visual inspection, and molecular dynamics guided pose prediction performed the best with overall mean RMSDs of 2.4, 2.2, and 2.2 Å respectively. For several individual challenge molecules, the best performing method is evaluated in light of that particular ligand. We also describe the protein, ligand, and public information data preparations that are typical of our binding mode prediction workflow.

Comparison of 7.2% hypertonic saline - 6% hydroxyethyl starch solution and 6% hydroxyethyl starch solution after the induction of anesthesia in patients undergoing elective neurosurgical procedures.

PubMed

Shao, Liujiazi; Wang, Baoguo; Wang, Shuangyan; Mu, Feng; Gu, Ke

2013-01-01

The ideal solution for fluid management during neurosurgical procedures remains controversial. The aim of this study was to compare the effects of a 7.2% hypertonic saline - 6% hydroxyethyl starch (HS-HES) solution and a 6% hydroxyethyl starch (HES) solution on clinical, hemodynamic and laboratory variables during elective neurosurgical procedures. Forty patients scheduled for elective neurosurgical procedures were randomly assigned to the HS-HES group orthe HES group. Afterthe induction of anesthesia, patients in the HS-HES group received 250 mL of HS-HES (500 mL/h), whereas the patients in the HES group received 1,000 mL of HES (1000 mL/h). The monitored variables included clinical, hemodynamic and laboratory parameters. Chictr.org: ChiCTR-TRC-12002357 The patients who received the HS-HES solution had a significant decrease in the intraoperative total fluid input (p<0.01), the volume of Ringer's solution required (p<0.05), the fluid balance (p<0.01) and their dural tension scores (p<0.05). The total urine output, blood loss, bleeding severity scores, operation duration and hemodynamic variables were similar in both groups (p>0.05). Moreover, compared with the HES group, the HS-HES group had significantly higher plasma concentrations of sodium and chloride, increasing the osmolality (p<0.01). Our results suggest that HS-HES reduced the volume of intraoperative fluid required to maintain the patients undergoing surgery and led to a decrease in the intraoperative fluid balance. Moreover, HS-HES improved the dural tension scores and provided satisfactory brain relaxation. Our results indicate that HS-HES may represent a new avenue for volume therapy during elective neurosurgical procedures.

Astrocytic and neuronal accumulation of elevated extracellular K+ with a 2/3 K+/Na+ flux ratio—consequences for energy metabolism, osmolarity and higher brain function

PubMed Central

Hertz, Leif; Xu, Junnan; Song, Dan; Yan, Enzhi; Gu, Li; Peng, Liang

2013-01-01

Brain excitation increases neuronal Na+ concentration by 2 major mechanisms: (i) Na+ influx caused by glutamatergic synaptic activity; and (ii) action-potential-mediated depolarization by Na+ influx followed by repolarizating K+ efflux, increasing extracellular K+ concentration. This review deals mainly with the latter and it concludes that clearance of extracellular K+ is initially mainly effectuated by Na+,K+-ATPase-mediated K+ uptake into astrocytes, at K+ concentrations above ~10 mM aided by uptake of Na+,K+ and 2 Cl− by the cotransporter NKCC1. Since operation of the astrocytic Na+,K+-ATPase requires K+-dependent glycogenolysis for stimulation of the intracellular ATPase site, it ceases after normalization of extracellular K+ concentration. This allows K+ release via the inward rectifying K+ channel Kir4.1, perhaps after trans-astrocytic connexin- and/or pannexin-mediated K+ transfer, which would be a key candidate for determination by synchronization-based computational analysis and may have signaling effects. Spatially dispersed K+ release would have little effect on extracellular K+ concentration and allow K+ accumulation by the less powerful neuronal Na+,K+-ATPase, which is not stimulated by increases in extracellular K+. Since the Na+,K+-ATPase exchanges 3 Na+ with 2 K+, it creates extracellular hypertonicity and cell shrinkage. Hypertonicity stimulates NKCC1, which, aided by β-adrenergic stimulation of the Na+,K+-ATPase, causes regulatory volume increase, furosemide-inhibited undershoot in [K+]e and perhaps facilitation of the termination of slow neuronal hyperpolarization (sAHP), with behavioral consequences. The ion transport processes involved minimize ionic disequilibria caused by the asymmetric Na+,K+-ATPase fluxes. PMID:23986689

Pain referral and regional deep tissue hyperalgesia in experimental human hip pain models.

PubMed

Izumi, Masashi; Petersen, Kristian Kjær; Arendt-Nielsen, Lars; Graven-Nielsen, Thomas

2014-04-01

Hip disorder patients typically present with extensive pain referral and hyperalgesia. To better understand underlying mechanisms, an experimental hip pain model was established in which pain referrals and hyperalgesia could be studied under standardized conditions. In 16 healthy subjects, pain was induced by hypertonic saline injection into the gluteus medius tendon (GMT), adductor longus tendon (ALT), or gluteus medius muscle (GMM). Isotonic saline was injected contralaterally as control. Pain intensity was assessed on a visual analogue scale (VAS), and subjects mapped the pain distribution. Before, during, and after injections, passive hip joint pain provocation tests were completed, together with quantitative sensory testing as follows: pressure pain thresholds (PPTs), cuff algometry pain thresholds (cuff PPTs), cutaneous pin-prick sensitivity, and thermal pain thresholds. Hypertonic saline injected into the GMT resulted in higher VAS scores than hypertonic injections into the ALT and GMM (P<.05). Referred pain areas spread to larger parts of the leg after GMT and GMM injections compared with more regionalized pain pattern after ALT injections (P<.05). PPTs at the injection site were decreased after hypertonic saline injections into GMT and GMM compared with baseline, ALT injections, and isotonic saline. Cuff PPTs from the thigh were decreased after hypertonic saline injections into the ALT compared with baseline, GMT injections, and isotonic saline (P<.05). More subjects had positive joint pain provocation tests after hypertonic compared with isotonic saline injections (P<.05), indicating that this provocation test also assessed hyperalgesia in extra-articular soft tissues. The experimental models may open for better understanding of pain mechanisms associated with painful hip disorders. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Motile activities of Dictyostelium discoideum differ from those in Protista or vertebrate animal cells.

PubMed

Waligórska, Agnieszka; Wianecka-Skoczeń, Magdalena; Korohoda, Włodzimierz

2007-01-01

Cell movement in the amoebae Dictyostelium discoideum has been examined in media differing in monovalent cation concentration (i.e. Na+ and K+). Under isotonic or even slightly hypertonic conditions, the cells move equally well in solutions in which either potassium or sodium ions dominate. However, in strongly hypertonic solutions the amoebae showed motility in a 2% potassium chloride solution, but remained motionless in a hypertonic 2% sodium chloride solution. This inhibition of D. discoideum amoebae movement in a hypertonic sodium chloride solution was fully reversible. Such behaviour corresponds to that of plant, fungi, and some invertebrate animal cells rather than protozoan or vertebrate cells. These observations suggest that studies using D. discoideum as a model for cell motility in vertebrate animal tissue cells should be considered with caution, and would seem to confirm the classification of cellular slime moulds as related rather to Fungi than to Protista. This also shows that the cell membrane models should consider the asymmetry in sodium/potassium ion concentrations found in vertebrate animal cells as one of various possibilities.

Divergent Effects of Hypertonic Fluid Resuscitation on Renal Pathophysiological and Structural Parameters in Rat Model of Lower Body Ischemia/Reperfusion-Induced Sterile Inflammation.

PubMed

Ergin, Bulent; Zuurbier, Coert J; Kapucu, Aysegul; Ince, Can

2017-12-27

The pathogenesis of acute kidney injury (AKI) is characterized by the deterioration of tissue perfusion and oxygenation and enhanced inflammation. The purpose of this study was to investigate whether or not the hemodynamic and inflammatory effects of hypertonic saline (HS) protect the kidney by promoting renal microcirculatory oxygenation and possible deleterious effects of HS due to its high sodium content on renal functional and structural injury following ischemia/reperfusion. Mechanically ventilated and anesthetized rats were randomly divided into four groups (n = 6 per group): a sham-operated control group; a group subjected to renal ischemia for 45 min by supra-aortic occlusion followed by 2 h of reperfusion (I/R); and I/R group treated with a continuous i.v. infusion (5 mL/kg/h) of either % 0.9 NaCl (IR+NS) or %10 NaCl (I/R+HS) after releasing the clamp. Systemic and renal hemodynamic, renal cortical (CμPO2), and medullar microcirculatory pO2 (MμPO2) are measured by the oxygen-dependent quenching of the phosphorescence lifetime technique. Renal functional, inflammatory, and tissues damage parameters were also assessed. HS, but not NS, treatment restored I/R-induced reduced mean arterial pressure, CμPO2, renal oxygen deliver (DO2ren), and consumption (VO2ren). HS caused a decrease in tubular sodium reabsorption (TNa) that correlated with an elevation of fractional sodium excretion (EFNa) and urine output. HS had an anti-inflammatory effect by reducing the levels TNF-α, IL-6, and hyaluronic acid in the renal tissue samples as compared with the I/R and I/R+NS groups (P < 0.05). HS treatment was also associated with mild acidosis and an increased renal tubular damage. Despite HS resuscitation improving the systemic hemodynamics, microcirculatory oxygenation, and renal oxygen consumption as well as inflammation, it should be limited or strictly controlled for long-term use because of provoking widespread renal structural damage.

Green Flight Challenge

NASA Image and Video Library

2011-10-03

Pipistrel-USA Team Lead Jack Langelaan talks after his team won the 2011 Green Flight Challenge, sponsored by Google, on Monday, Oct. 3, 2011 at the NASA Ames Research Center, Mountain View, Calif. The all electric Taurus G4 aircraft achieved the equivalency of more than 400 miles per gallon. NASA and CAFE Foundation held the challenge to advance technologies in fuel efficiency and reduced emissions with cleaner renewable fuels and electric aircraft. Photo Credit: (NASA/Bill Ingalls)

A case-cohort study with propensity score matching to evaluate the effects of mannitol on venous thromboembolism.

PubMed

Fletcher, Jeffrey J; Kade, Allison M; Sheehan, Kyle M; Wilson, Thomas J

2014-08-01

Mannitol has been shown to damage endothelial cells and activate coagulation pathways leading to intravascular thrombosis. Dehydration and hemagglutination have also been associated with mannitol use, although the risk of clinically evident venous thromboembolism (VTE) disease is not well-defined. The aim of this study was to compare the risk of VTE in critically ill neurological patients who received mannitol compared to only hypertonic saline. A case-cohort study design with propensity score matching was used to evaluate the risk of VTE among patients who received mannitol compared to those who received hypertonic saline alone. The odds of thrombosis were evaluated by the Cochran-Mantel-Haenszel method and conditional logistic regression was used to adjust for year of treatment. Ninety-one of 330 patients (27.6%; 95% confidence interval [CI] 23-33%) developed a VTE; however, the yearly proportion remained unchanged over the 8 year study period. Cumulative use of mannitol declined and use of hypertonic saline increased significantly. The odds of thrombosis for those exposed to mannitol compared to hypertonic saline alone was 1.11 (95% CI 0.65-1.73; p=0.75). This remained insignificant after adjusting for year of injury. In conclusion, despite a significant change in the pattern of osmotic therapy used at our institution, the proportion of patients with VTE remained unchanged. We found no evidence that mannitol use was associated with VTE compared to hypertonic saline alone. Copyright © 2014. Published by Elsevier Ltd.

Evaluation of Newly Developed Chemical Castration Method: Changes in Hormone Gene Expression of Hypothalamic-Pituitary Axis

PubMed Central

Kwak, Byung Kuk; Lee, Sung-Ho

2017-01-01

ABSTRACT Surgical castration (also known as orchidectomy, ORX) has been frequently performed to avoid uncontrolled breeding. However, it has some serious disadvantages. Several laboratories have developed chemical castration methods, using bilateral intratesticular injection (BITI) of simple chemical solutions. The present study was undertaken to compare the effects of ORX and of hypertonic saline BITI on the androgen-sensitive tissues such as pituitary and hypothalamus. Serum testosterone (T) levels of ORX animals and hypertonic saline BITI animals (SAL) after 4 weeks of the manipulations exhibited significantly drops as compared with the levels of intact animals (Intact:ORX:SAL = 7.74± 1.31:1.34±0.19:1.28±0.18 ng/ml, p<0.001). Both ORX and BITI method induced similar stimulatory effects on the pituitary gonadotropin subunits and hypothalamic KiSS-1 gene expressions. In contrast, the effects of ORX and hypertonic saline BITI on hypothalamic GnRH gene expression were different from these gene expressions, shown an inverse relationship between the two groups (Intact:ORX:SAL = 1:0.45±0.06:1:2.07±0.41:1.51±0.37 AU; ORX, p<0.001; SAL, p<0.05). In conclusion, we provided evidence that hypertonic saline BITI method has equivalent efficacy of T depletion to surgical castration in rats. The present study suggests the hypertonic saline BITI could be a promising substitute to conventional surgical castration. PMID:29082346

The effects of tetracaine on charge movement in fast twitch rat skeletal muscle fibres.

PubMed

Hollingworth, S; Marshall, M W; Robson, E

1990-02-01

1. The effects of tetracaine, a local anaesthetic that inhibits muscle contraction, on membrane potential and intramembrane charge movements were investigated in fast twitch rat muscle fibres (extensor digitorum longus). 2. The resting membrane potentials of surface fibres from muscles bathed in isotonic Ringer solution containing 2 mM-tetracaine were well maintained, but higher concentrations of tetracaine caused a time-dependent fall of potential. Muscle fibres bathed in hypertonic solutions containing 2 mM-tetracaine were rapidly depolarized. In both isotonic and hypertonic solutions, the depolarizing effect of tetracaine could not be reversed. 3. Charge movement measurements were made using the middle-of-the-fibre voltage clamp technique. The voltage dependence of charge movements measured in cold isotonic solutions was well fitted by a Boltzmann distribution (Q(V) = Qmax/(1 + exp(-(V-V)/k] where Qmax = 37.3 +/- 2.8 nC muF-1, V = -17.9 +/- 1.2 mV and k = 12.6 +/- 0.8 mV (n = 6, 2 degrees C; means +/- S.E. of means). Similar values were obtained when 2 mM-tetracaine was added to the isotonic bathing fluid (Qmax = 40.6 +/- 2.3 nC microF-1, V = -14.1 +/- 1.3 mV, k = 15.3 +/- 0.8 mV; n = 8, 2 degrees C). 4. Charge movements measured around mechanical threshold in muscle fibres bathed in hypertonic solutions were reduced when 2 mM-tetracaine was added to the bathing fluid. The tetracaine-sensitive component of charge was well fitted with an unconstrained Boltzmann distribution which gave: Qmax = 7.5 nC microF-1, V = -46.5 mV, k = 5.5 mV. The e-fold rise of the foot of the curve was 9.3 mV.

The effects of tetracaine on charge movement in fast twitch rat skeletal muscle fibres.

PubMed Central

Hollingworth, S; Marshall, M W; Robson, E

1990-01-01

1. The effects of tetracaine, a local anaesthetic that inhibits muscle contraction, on membrane potential and intramembrane charge movements were investigated in fast twitch rat muscle fibres (extensor digitorum longus). 2. The resting membrane potentials of surface fibres from muscles bathed in isotonic Ringer solution containing 2 mM-tetracaine were well maintained, but higher concentrations of tetracaine caused a time-dependent fall of potential. Muscle fibres bathed in hypertonic solutions containing 2 mM-tetracaine were rapidly depolarized. In both isotonic and hypertonic solutions, the depolarizing effect of tetracaine could not be reversed. 3. Charge movement measurements were made using the middle-of-the-fibre voltage clamp technique. The voltage dependence of charge movements measured in cold isotonic solutions was well fitted by a Boltzmann distribution (Q(V) = Qmax/(1 + exp(-(V-V)/k] where Qmax = 37.3 +/- 2.8 nC muF-1, V = -17.9 +/- 1.2 mV and k = 12.6 +/- 0.8 mV (n = 6, 2 degrees C; means +/- S.E. of means). Similar values were obtained when 2 mM-tetracaine was added to the isotonic bathing fluid (Qmax = 40.6 +/- 2.3 nC microF-1, V = -14.1 +/- 1.3 mV, k = 15.3 +/- 0.8 mV; n = 8, 2 degrees C). 4. Charge movements measured around mechanical threshold in muscle fibres bathed in hypertonic solutions were reduced when 2 mM-tetracaine was added to the bathing fluid. The tetracaine-sensitive component of charge was well fitted with an unconstrained Boltzmann distribution which gave: Qmax = 7.5 nC microF-1, V = -46.5 mV, k = 5.5 mV. The e-fold rise of the foot of the curve was 9.3 mV. PMID:2348406

Osmotic Compounds Enhance Antibiotic Efficacy against Acinetobacter baumannii Biofilm Communities

PubMed Central

Falghoush, Azeza; Beyenal, Haluk; Besser, Thomas E.; Omsland, Anders

2017-01-01

ABSTRACT Biofilm-associated infections are a clinical challenge, in part because a hydrated matrix protects the bacterial community from antibiotics. Herein, we evaluated how different osmotic compounds (maltodextrin, sucrose, and polyethylene glycol [PEG]) enhance antibiotic efficacy against Acinetobacter baumannii biofilm communities. Established (24-h) test tube biofilms (strain ATCC 17978) were treated with osmotic compounds in the presence or absence of 10× the MIC of different antibiotics (50 μg/ml tobramycin, 20 μg/ml ciprofloxacin, 300 μg/ml chloramphenicol, 30 μg/ml nalidixic acid, or 100 μg/ml erythromycin). Combining antibiotics with hypertonic concentrations of the osmotic compounds for 24 h reduced the number of biofilm bacteria by 5 to 7 log (P < 0.05). Increasing concentrations of osmotic compounds improved the effect, but there was a trade-off with increasing solution viscosity, whereby low-molecular-mass compounds (sucrose, 400-Da PEG) worked better than higher-mass compounds (maltodextrin, 3,350-Da PEG). Ten other A. baumannii strains were similarly treated with 400-Da PEG and tobramycin, resulting in a mean 2.7-log reduction in recoverable bacteria compared with tobramycin treatment alone. Multivariate regression models with data from different osmotic compounds and nine antibiotics demonstrated that the benefit from combining hypertonic treatments with antibiotics is a function of antibiotic mass and lipophilicity (r2 > 0.82; P < 0.002), and the relationship was generalizable for biofilms formed by A. baumannii and Escherichia coli K-12. Augmenting topical antibiotic therapies with a low-mass hypertonic treatment may enhance the efficacy of antibiotics against wound biofilms, particularly when using low-mass hydrophilic antibiotics. IMPORTANCE Biofilms form a barrier that protects bacteria from environmental insults, including exposure to antibiotics. We demonstrated that multiple osmotic compounds can enhance antibiotic efficacy against

Minocycline Prevents Muscular Pain Hypersensitivity and Cutaneous Allodynia Produced by Repeated Intramuscular Injections of Hypertonic Saline in Healthy Human Participants.

PubMed

Samour, Mohamad Samir; Nagi, Saad Saulat; Shortland, Peter John; Mahns, David Anthony

2017-08-01

Minocycline, a glial suppressor, prevents behavioral hypersensitivities in animal models of peripheral nerve injury. However, clinical trials of minocycline in human studies have produced mixed results. This study addressed 2 questions: can repeated injections of hypertonic saline (HS) in humans induce persistent hypersensitivity? Can pretreatment with minocycline, a tetracycline antibiotic with microglial inhibitory effects, prevent the onset of hypersensitivity? Twenty-seven healthy participants took part in this double-blind, placebo-controlled study, consisting of 6 test sessions across 2 weeks. At the beginning of every session, pressure-pain thresholds of the anterior muscle compartment of both legs were measured to determine the region distribution and intensity of muscle soreness. To measure changes in thermal sensitivity in the skin overlying the anterior muscle compartment of both legs, quantitative sensory testing was used to measure the cutaneous thermal thresholds (cold sensation, cold pain, warm sensation, and heat pain) and a mild cooling stimulus was applied to assess the presence of cold allodynia. To induce ongoing hypersensitivity, repeated injections of HS were administered into the right tibialis anterior muscle at 48-hour intervals. In the final 2 sessions (days 9 and 14), only sensory assessments were done to plot the recovery after cessation of HS administrations and drug washout. By day 9, nontreated participants experienced a significant bilateral increase in muscle soreness (P < .0001), accompanied by the emergence of bilateral cold allodynia in 44% of participants, thus confirming the effectiveness of the model. Placebo-treated participants experienced a bilateral 35% alleviation in muscle soreness (P < .0001), with no changes to the prevalence of cold allodynia. In contrast, minocycline-treated participants experienced a bilateral 70% alleviation in muscle soreness (P < .0001), additionally, only 10% of minocycline

Predicting motor outcomes with 3 month prone hip angles in premature infants.

PubMed

Shehee, Lindsey; Coker-Bolt, Patty; Barbour, Andrew; Moss, Hunter; Brown, Truman; Jenkins, Dorothea

2016-09-02

This study used kinematic analysis to identify a reliable and rapid assessment method for abnormal patterns of motor development in preterm infants. In a retrospective analysis, we examined video of n= 35 preterm infants at 3mo corrected age (CA) who had concurrent Test of Infant Motor Performance (TIMP) scores. Hyperflexion at the hip produces common gait anomalies seen in children with CP, therefore we analyzed hip angle in the prone head lift position at 3 months CA. Magnetic Resonance Spectroscopy (MRS) was performed at term equivalent (n= 23) and Bayley-III neurodevelopmental tests were performed at 1 year (n= 28). We correlated hip angles with TIMP and Bayley-III scores, and MRS neuronal metabolites. Hip angle positively correlated with TIMP at 3 months (r= 0.642, p≤ 0.001), but not with Bayley-III at 1 year (r= 0.122, p= 0.529). Hip angle correlated negatively with myo-inositol (mI) ratios in frontal white matter tracts (mI/Cr r= -0.520, p= 0.011). These results suggest prone hip angle may be a quantitative proxy for the 42-item TIMP at 3 months, and that hypertonicity in the hip flexor musculature is a manifestation of white matter metabolic abnormalities (elevated mI ratios) that may indicate occult white matter injury.

Long-term culture of bovine nucleus pulposus explants in a native environment.

PubMed

van Dijk, Bart G M; Potier, Esther; Ito, Keita

2013-04-01

Chronic low back pain is a disease with tremendous financial and social implications, and it is often caused by intervertebral disc degeneration. Regenerative therapies for disc repair are promising treatments, but they need to be tested in physiological models. To develop a physiological in vitro explant model that incorporates the native environment of the intervertebral disc, for example, hypoxia, low glucose, and high tissue osmolarity. Bovine nucleus pulposus (NP) explants were cultured for 42 days in conditions mimicking the native physiological environment. Two different approaches were used to balance the swelling pressure of the NP: raised medium osmolarity or an artificial annulus. Bovine NP explants were either cultured in media with osmolarity balanced at isotonic and hypertonic levels compared with the native tissue or cultured inside a fiber jacket used as an artificial annulus. Oxygen and glucose levels were set at either standard (21% O2 and 4.5 g/L glucose) or physiological (5% O2 and 1 g/L glucose) levels. Samples were analyzed at Day 0, 3, and 42 for tissue composition (water, sulfated glycosaminoglycans, DNA, and hydroxyproline contents and fixed charge density), tissue histology, cell viability, and cellular behavior with messenger RNA (mRNA) expression. Both the hypertonic culture and the artificial annulus approach maintained the tissue matrix composition for 42 days. At Day 3, mRNA expressions of aggrecan, collagen Type I, and collagen Type II in both hypertonic and artificial annulus cultures were not different from Day 0; however, at Day 42, the artificial annulus preserved the mRNA expression closer to Day 0. Gene expressions of matrix metalloprotease 13, tissue inhibitor of matrix metalloprotease 1, and tissue inhibitor of matrix metalloprotease 2 were downregulated under physiological O2 and glucose levels, whereas the other parameters analyzed were not affected. Although the hypertonic culture and the artificial annulus approach are

Opportunities and challenges for 3D printing of solid-state lighting systems

NASA Astrophysics Data System (ADS)

Narendran, Nadarajah; Perera, Indika U.; Mou, Xi; Thotagamuwa, Dinusha R.

2017-09-01

Low energy use and reduced maintenance have made the LED, a solid-state light (SSL) source, the preferred technology for many lighting applications. With the explosion of products in the marketplace and subsequent price erosion, manufacturers are looking for lower cost materials and manufacturing methods. 3-D printing, also known as additive manufacturing, could be a potential solution. Recently, manufacturers in the automotive, aerospace, and medical industries have embraced 3-D printing for manufacturing parts and systems. This could pave the way for the lighting industry to produce lower cost, custom lighting systems that are 3-D printed on-site to achieve on-time and on-demand manufacturing. One unique aspect of LED fixture manufacturing is that it requires thermo-mechanical, electrical, and optical components. The goal of our investigation was to understand if current 3-D printing technologies and materials can be used to manufacture functional thermo-mechanical, electrical, and optical components for SSL fixtures. We printed heat sink components and electrical traces using an FFF-type 3-D printer with different filaments. The results showed that the printed heat sinks achieved higher thermal conductivity values compared to components made with plastic materials. For electrical traces, graphene-infused PLA showed low resistivity but it is much higher than bulk copper resistivity. For optics, SLA-printed optical components showed that print resolution, print orientation, and postprocessing affect light transmission and light scatter properties. Overall, 3-D printing offers an opportunity for mass customization of SSL fixtures and changing architectural lighting practice, but several challenges in terms of process and materials still have to be overcome.

Hypertonic saline in the treatment of corneal jellyfish stings.

PubMed

Yu Yao, Hsin; Cho, Ta Hsiung; Lu, Ching Hsiang; Lin, Feng Chi; Horng, Chi Ting

2016-02-01

A 20-year-old male soldier was hit by the jellyfish. The ophthalmic examination revealed that epithelial keratitis and corneal oedema in the right eye. We prescribed 3% NaCl eyedrops and 0.3% Norfloxacin eyedrops in the treatment of the corneal jellyfish stings. Two weeks later, the cornea in the right eye healed. In this case report, 3% NaCl eyedrops was effective in the treatment of acute phase of jellyfish stings of the cornea. © International Society of Travel Medicine, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

β3-Adrenergic receptors, adipokines and neuroendocrine activation during stress induced by repeated immune challenge in male and female rats.

PubMed

Csanova, Agnesa; Hlavacova, Natasa; Hasiec, Malgorzata; Pokusa, Michal; Prokopova, Barbora; Jezova, Daniela

2017-05-01

The main hypothesis of the study is that stress associated with repeated immune challenge has an impact on β 3 -adrenergic receptor gene expression in the brain. Sprague-Dawley rats were intraperitoneally injected with increasing doses of lipopolysaccharide (LPS) for five consecutive days. LPS treatment was associated with body weight loss and increased anxiety-like behavior. In LPS-treated animals of both sexes, β 3 -receptor gene expression was increased in the prefrontal cortex but not the hippocampus. LPS treatment decreased β 3 -receptor gene expression in white adipose tissue with higher values in males compared to females. In the adipose tissue, LPS reduced peroxisome proliferator-activated receptor-gamma, leptin and adiponectin gene expression, but increased interleukin-6 expression, irrespective of sex. Repeated immune challenge resulted in increased concentrations of plasma aldosterone and corticosterone with higher values of corticosterone in females compared to males. Concentrations of dehydroepiandrosterone (DHEA) in plasma were unaffected by LPS, while DHEA levels in the frontal cortex were lower in the LPS-treated animals compared to the controls. Thus, changes of DHEA levels in the brain take place irrespective of the changes of this neurosteroid in plasma. We have provided the first evidence on stress-induced increase in β 3 -adrenergic receptor gene expression in the brain. Greater reduction of β 3 -adrenergic receptor expression in the adipose tissue and of the body weight gain by repeated immune challenge in male than in female rats suggests sex differences in the role of β 3 -adrenergic receptors in the metabolic functions. LPS-induced changes in adipose tissue regulatory factors and hormone concentrations might be important for coping with chronic infections.

Challenges and limitations of patient-specific vascular phantom fabrication using 3D Polyjet printing.

PubMed

Ionita, Ciprian N; Mokin, Maxim; Varble, Nicole; Bednarek, Daniel R; Xiang, Jianping; Snyder, Kenneth V; Siddiqui, Adnan H; Levy, Elad I; Meng, Hui; Rudin, Stephen

2014-03-13

Additive manufacturing (3D printing) technology offers a great opportunity towards development of patient-specific vascular anatomic models, for medical device testing and physiological condition evaluation. However, the development process is not yet well established and there are various limitations depending on the printing materials, the technology and the printer resolution. Patient-specific neuro-vascular anatomy was acquired from computed tomography angiography and rotational digital subtraction angiography (DSA). The volumes were imported into a Vitrea 3D workstation (Vital Images Inc.) and the vascular lumen of various vessels and pathologies were segmented using a "marching cubes" algorithm. The results were exported as Stereo Lithographic (STL) files and were further processed by smoothing, trimming, and wall extrusion (to add a custom wall to the model). The models were printed using a Polyjet printer, Eden 260V (Objet-Stratasys). To verify the phantom geometry accuracy, the phantom was reimaged using rotational DSA, and the new data was compared with the initial patient data. The most challenging part of the phantom manufacturing was removal of support material. This aspect could be a serious hurdle in building very tortuous phantoms or small vessels. The accuracy of the printed models was very good: distance analysis showed average differences of 120 μm between the patient and the phantom reconstructed volume dimensions. Most errors were due to residual support material left in the lumen of the phantom. Despite the post-printing challenges experienced during the support cleaning, this technology could be a tremendous benefit to medical research such as in device development and testing.

Microgravity, stem cells, and embryonic development: challenges and opportunities for 3D tissue generation

NASA Astrophysics Data System (ADS)

Andreazzoli, Massimiliano; Angeloni, Debora; Broccoli, Vania; Demontis, Gian C.

2017-04-01

Space is a challenging environment for the human body, due to the combined effects of reduced gravity (microgravity) and cosmic radiation. Known effects of microgravity range from the blood redistribution that affects the cardiovascular system and the eye to muscle wasting, bone loss, anemia and immune depression. About cosmic radiation, the shielding provided by the spaceship hull is far less efficient than that afforded at ground level by the combined effects of the Earth atmosphere and magnetic field. The eye and its nervous layer (the retina) are affected by both microgravity and heavy ions exposure. Considering the importance of sight for long-term manned flights, visual research aimed at devising measures to protect the eye from environmental conditions of the outer space represents a special challenge to meet. In this review we focus on the impact of microgravity on embryonic development, discussing the roles of mechanical forces in the context of the neutral buoyancy the embryo experiences in the womb. At variance with its adverse effects on the adult human body, simulated microgravity may provide a unique tool for understanding the biomechanical events involved in the development and assembly in vitro of three-dimensional (3D) ocular tissues. Prospective benefits are the development of novel safety measures to protect the human eye from cosmic radiation in microgravity during long-term manned spaceflights in the outer space, as well as the generation of human 3D-retinas with its supporting structures to develop innovative and effective therapeutic options for degenerative eye diseases.

Challenges and limitations of patient-specific vascular phantom fabrication using 3D Polyjet printing

NASA Astrophysics Data System (ADS)

Ionita, Ciprian N.; Mokin, Maxim; Varble, Nicole; Bednarek, Daniel R.; Xiang, Jianping; Snyder, Kenneth V.; Siddiqui, Adnan H.; Levy, Elad I.; Meng, Hui; Rudin, Stephen

2014-03-01

Additive manufacturing (3D printing) technology offers a great opportunity towards development of patient-specific vascular anatomic models, for medical device testing and physiological condition evaluation. However, the development process is not yet well established and there are various limitations depending on the printing materials, the technology and the printer resolution. Patient-specific neuro-vascular anatomy was acquired from computed tomography angiography and rotational digital subtraction angiography (DSA). The volumes were imported into a Vitrea 3D workstation (Vital Images Inc.) and the vascular lumen of various vessels and pathologies were segmented using a "marching cubes" algorithm. The results were exported as Stereo Lithographic (STL) files and were further processed by smoothing, trimming, and wall extrusion (to add a custom wall to the model). The models were printed using a Polyjet printer, Eden 260V (Objet-Stratasys). To verify the phantom geometry accuracy, the phantom was reimaged using rotational DSA, and the new data was compared with the initial patient data. The most challenging part of the phantom manufacturing was removal of support material. This aspect could be a serious hurdle in building very tortuous phantoms or small vessels. The accuracy of the printed models was very good: distance analysis showed average differences of 120 μm between the patient and the phantom reconstructed volume dimensions. Most errors were due to residual support material left in the lumen of the phantom. Despite the post-printing challenges experienced during the support cleaning, this technology could be a tremendous benefit to medical research such as in device development and testing.

Effect of sodium and calcium ingestion on thermoregulation during exercise in man

NASA Technical Reports Server (NTRS)

Greenleaf, J. E.; Brock, P. J.; Morse, J. T.; Van Beaumont, W.; Montgomery, L. D.; Convertino, V. A.; Mangseth, G. R.

1978-01-01

The effects of hypertonic sodium and calcium ingestion on body temperature during exercise in cool and hot environments are investigated. Rectal and mean skin temperatures, sweat rates and arm and leg total blood flows were measured in men during periods of rest, submaximal exercise and recovery at temperatures of 26.5 C and 39.4 C after ingestion of NaCl and CaCl2 solutions. In both environments, higher rectal temperatures are observed after hypertonic sodium ingestion, which is also associated with attenuated blood flow in the extremities, lower sweat rates and slightly higher skin temperature in the heat, indicating significant thermoregulatory responses. Hypertonic calcium and isotonic sodium cause no temperature change, although calcium caused a reduction of blood flow in the extremities.

Immunization of African Indigenous Pigs with Attenuated Genotype I African Swine Fever Virus OURT88/3 Induces Protection Against Challenge with Virulent Strains of Genotype I.

PubMed

Mulumba-Mfumu, L K; Goatley, L C; Saegerman, C; Takamatsu, H-H; Dixon, L K

2016-10-01

The attenuated African swine fever virus genotype I strain OURT88/3 has previously been shown to induce protection of European breeds of domestic pigs against challenge with virulent isolates. To determine whether protective immune responses could also be induced in indigenous breeds of pigs from the Kinshassa region in Democratic Republic of Congo, we immunized a group of eight pigs with OURT88/3 strain and challenged the pigs 3 weeks later with virulent genotype I strain OURT88/1. Four of the pigs were protected against challenge. Three of the eight pigs died from African swine fever virus and a fourth from an unknown cause. The remaining four pigs all survived challenge with a recent virulent genotype I strain from the Democratic Republic of Congo, DRC 085/10. Control groups of non-immune pigs challenged with OURT88/1 or DRC 085/10 developed signs of acute ASFV as expected and had high levels of virus genome in blood. © 2015 Blackwell Verlag GmbH.

Comparison of 7.2% hypertonic saline - 6% hydroxyethyl starch solution and 6% hydroxyethyl starch solution after the induction of anesthesia in patients undergoing elective neurosurgical procedures

PubMed Central

Shao, Liujiazi; Wang, Baoguo; Wang, Shuangyan; Mu, Feng; Gu, Ke

2013-01-01

OBJECTIVE: The ideal solution for fluid management during neurosurgical procedures remains controversial. The aim of this study was to compare the effects of a 7.2% hypertonic saline - 6% hydroxyethyl starch (HS-HES) solution and a 6% hydroxyethyl starch (HES) solution on clinical, hemodynamic and laboratory variables during elective neurosurgical procedures. METHODS: Forty patients scheduled for elective neurosurgical procedures were randomly assigned to the HS-HES group or the HES group. After the induction of anesthesia, patients in the HS-HES group received 250 mL of HS-HES (500 mL/h), whereas the patients in the HES group received 1,000 mL of HES (1000 mL/h). The monitored variables included clinical, hemodynamic and laboratory parameters. Chictr.org: ChiCTR-TRC-12002357 RESULTS: The patients who received the HS-HES solution had a significant decrease in the intraoperative total fluid input (p<0.01), the volume of Ringer's solution required (p<0.05), the fluid balance (p<0.01) and their dural tension scores (p<0.05). The total urine output, blood loss, bleeding severity scores, operation duration and hemodynamic variables were similar in both groups (p>0.05). Moreover, compared with the HES group, the HS-HES group had significantly higher plasma concentrations of sodium and chloride, increasing the osmolality (p<0.01). CONCLUSION: Our results suggest that HS-HES reduced the volume of intraoperative fluid required to maintain the patients undergoing surgery and led to a decrease in the intraoperative fluid balance. Moreover, HS-HES improved the dural tension scores and provided satisfactory brain relaxation. Our results indicate that HS-HES may represent a new avenue for volume therapy during elective neurosurgical procedures. PMID:23644851

BIOPSY PROVEN MEDULLARY SPONGE KIDNEY: Clinical findings, histopathology, and role of osteogenesis in stone and plaque formation

PubMed Central

Evan, Andrew P.; Worcester, Elaine M.; Williams, James C.; Sommer, Andre J.; Lingeman, James E.; Phillips, Carrie L.; Coe, Fredric L.

2015-01-01

Medullary sponge kidney (MSK) is associated with recurrent stone formation, but the clinical phenotype is unclear because patients with other disorders may be incorrectly labeled MSK. We studied 12 patients with histologic findings pathognomonic of MSK. All patients had an endoscopically recognizable pattern of papillary malformation, which may be segmental or diffuse. Affected papillae are enlarged and billowy, due to markedly enlarged inner medullary collecting ducts (IMCD), which contain small, mobile ductal stones. Patients had frequent dilation of Bellini ducts, with occasional mineral plugs. Stones may form over white (Randall’s) plaque, but most renal pelvic stones are not attached, and have a similar morphology as ductal stones, which are a mixture of calcium oxalate and apatite. Patients had no abnormalities of urinary acidification or acid excretion; the most frequent metabolic abnormality was idiopathic hypercalciuria. Although both Runx2 and Osterix are expressed in papillae of MSK patients, no mineral deposition was seen at the sites of gene expression, arguing against a role of these genes in this process. Similar studies in idiopathic calcium stone formers showed no expression of these genes at sites of Randall’s plaque. The most likely mechanism for stone formation in MSK appears to be crystallization due to urinary stasis in dilated IMCD with subsequent passage of ductal stones into the renal pelvis where they may serve as nuclei for stone formation. PMID:25615853

Operation Brain Trauma Therapy Extended Studies

DTIC Science & Technology

2015-05-01

peaks in the TBI models. It is also possible that the use of a craniotomy in all 3 models results in an under- estimation of the potential benefit of...traditional strategies, namely, osmolar therapy (mannitol or hypertonic saline administration), CSF drainage , craniectomy, limitation of fluid administration

Green Flight Challenge

NASA Image and Video Library

2011-10-03

Team Lead Jack Langelaan poses for a photograph next to the Pipistrel-USA, Taurus G4, aircraft prior to winning the 2011 Green Flight Challenge, sponsored by Google, on Monday, Oct. 3, 2011 at the NASA Ames Research Center, Mountain View, Calif. The all electric Taurus G4 aircraft achieved the equivalency of more than 400 miles per gallon. NASA and CAFE held the challenge to advance technologies in fuel efficiency and reduced emissions with cleaner renewable fuels and electric aircraft. Photo Credit: (NASA/Bill Ingalls)

Heterogenous patterns of recovery of thirst in adult patients with adipsic diabetes insipidus.

PubMed

Cuesta, M; Gupta, S; Salehmohamed, R; Dineen, R; Hannon, M J; Tormey, W; Thompson, C J

2016-05-01

The natural history of adipsic diabetes insipidus (ADI) is not well described, and reports of recovery of thirst are rare. Case histories presentation. ADI was identified by demonstrating absent thirst and arginine vasopressin (AVP) responses to hypertonic saline infusion. Twelve patients with ADI were identified (craniopharyngioma 5, anterior communicating artery aneurysm (ACOM) repair 4, congenital 1, neurosarcoidosis 1, prolactinoma 1). Three patients died. Six patients had permanent ADI. Three patients had recovery of thirst, with a heterogenous pattern of recovery. In the first case, ADI had developed after clipping of an ACOM aneurysm. Ten years after surgery; he sensed the return of thirst; repeated hypertonic saline infusion showed recovery of thirst and AVP secretion. In the second case, a 41-year-old female with an intrasellar craniopharyngioma developed post-operative ADI with persistent hypernatremia. Two years post-operatively, she complained of thirst, and hypertonic saline infusion showed normalization of thirst but absent AVP responses, confirming recovery of thirst, but with persistent diabetes insipidus (DI). In the third case, a 29-year-old Caucasian had craniotomy and radiotherapy for craniopharyngioma and developed ADI post-operatively. Eight years post-op, she presented with thirst, seizures and pNa of 112 mmol/l. Hypertonic saline infusion showed persistent DI but thirst responses typical of compulsive water drinking; she has had recurrent hyponatraemia since then. We report that 3/12 patients with ADI recovered thirst after longstanding adipsia with heterogenous pattern of recovery. Both the mortality of 25% and the recovery rate of 25% should be considered when planning long-term surveillance. © The Author 2015. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effect of apical hyperosmotic sodium challenge and amiloride on sodium transport in human bronchial epithelial cells from cystic fibrosis donors.

PubMed

Rasgado-Flores, Hector; Krishna Mandava, Vamsi; Siman, Homayoun; Van Driessche, Willy; Pilewski, Joseph M; Randell, Scott H; Bridges, Robert J

2013-12-01

Hypertonic saline (HS) inhalation therapy benefits cystic fibrosis (CF) patients [Donaldson SH, Bennet WD, Zeman KL, Knowles MR, Tarran R, Boucher RC. N Engl J Med 354: 241-250, 2006; Elkins MR, Robinson M, Rose BR, Harbour C, Moriarty CP, Marks GB, Belousova EG, Xuan W, Bye PT; the National Hypertonic Saline in Cystic Fibrosis (NHSCF) Study Group. N Engl J Med 354: 229-240, 2006]. Surprisingly, these benefits are long-lasting and are diminished by the epithelial Na(+) channel blocker amiloride (Donaldson SH, Bennet WD, Zeman KL, Knowles MR, Tarran R, Boucher RC. N Engl J Med 354: 241-250, 2006). Our aim was to explain these effects. Human bronchial epithelial (hBE) cells from CF lungs were grown in inserts and were used in three experimental approaches: 1) Ussing chambers to measure amiloride-sensitive short-circuit currents (INa); 2) continuous perfusion Ussing chambers; and 3) near "thin-film" conditions in which the airway surface of the inserts was exposed to a small volume (30 μl) of isosmotic or HS solution as the inserts were kept in their incubation tray and were subsequently used to measure INa under isosmotic conditions (near thin-film experiments; Tarran R, Boucher RC. Methods Mol Med 70: 479-492, 2002). HS solutions (660 mosmol/kgH2O) were prepared by adding additional NaCl to the isosmotic buffer. The transepithelial short-circuit current (ISC), conductance (GT), and capacitance (CT) were measured by transepithelial impedance analysis (Danahay H, Atherton HC, Jackson AD, Kreindler JL, Poll CT, Bridges RJ. Am J Physiol Lung Cell Mol Physiol 290: L558-L569, 2006; Singh AK, Singh S, Devor DC, Frizzell RA, van Driessche W, Bridges RJ. Methods Mol Med 70: 129-142, 2002). Exposure to apical HS inhibited INa, GT, and CT. The INa inhibition required 60 min of reexposure to the isosmotic solution to recover 75%. The time of exposure to HS required to inhibit INa was <2.5 min. Under near thin-film conditions, apical exposure to HS inhibited INa, but as

New autosomal recessive mutations in aquaporin-2 causing nephrogenic diabetes insipidus through deficient targeting display normal expression in Xenopus oocytes

PubMed Central

Leduc-Nadeau, Alexandre; Lussier, Yoann; Arthus, Marie-Françoise; Lonergan, Michèle; Martinez-Aguayo, Alejandro; Riveira-Munoz, Eva; Devuyst, Olivier; Bissonnette, Pierre; Bichet, Daniel G

2010-01-01

Aquaporin-2 (AQP2), located at the luminal side of the collecting duct principal cells, is a water channel responsible for the final concentration of urine. Lack of function, often occurring through mistargeting of mutated proteins, induces nephrogenic diabetes insipidus (NDI), a condition characterized by large urinary volumes. In the present study, two new mutations (K228E and V24A) identified in NDI-affected individuals from distinct families along with the already reported R187C were analysed in comparison to the wild-type protein (AQP2-wt) using Xenopus laevis oocytes and a mouse collecting duct cell-line (mIMCD-3). Initial data in oocytes showed that all mutations were adequately expressed at reduced levels when compared to AQP2-wt. K228E and V24A were found to be properly targeted at the plasma membrane and exhibited adequate functionality similar to AQP2-wt, as opposed to R187C which was retained in internal stores and was thus inactive. In coexpression studies using oocytes, R187C impeded the functionality of all other AQP2 variants while combinations with K228E, V24A and AQP2-wt only showed additive functionalities. When expressed in mIMCD-3 cells, forskolin treatment efficiently promoted the targeting of AQP2-wt at the plasma membrane (>90%) while K228E only weakly responded to the same treatment (∼20%) and both V24A and R187C remained completely insensitive to the treatment. We concluded that both V24A and K228E are intrinsically functional water channels that lack a proper response to vasopressin, which leads to NDI as found in both compound mutations studied (K228E + R187C and V24A + R187C). The discrepancies in plasma membrane targeting response found in both expression systems stress the need to evaluate such data using mammalian cell systems. PMID:20403973

HSR Aerodynamic Performance Status and Challenges

NASA Technical Reports Server (NTRS)

Gilbert, William P.; Antani, Tony; Ball, Doug; Calloway, Robert L.; Snyder, Phil

1999-01-01

This paper describes HSR (High Speed Research) Aerodynamic Performance Status and Challenges. The topics include: 1) Aero impact on HSR; 2) Goals and Targets; 3) Progress and Status; and 4) Remaining Challenges. This paper is presented in viewgraph form.

Interoperable Acquisition for Systems of Systems: The Challenges

DTIC Science & Technology

2006-09-01

Interoperable Acquisition for Systems of Systems: The Challenges James D. Smith II D. Mike Phillips September 2006 TECHNICAL NOTE...Failure of Program-Centric Risk Management 10 3.3.2 Absence of System-of-Systems Engineering 12 3.3.3 Disconnect Between System-of-Systems...SOFTWARE ENGINEERING INSTITUTE | vii viii | CMU/SEI-2006-TN-034 Abstract Large, complex systems development has always been challenging , even when the

Vitamin E and omega-3 fatty acids independently attenuate plasma concentrations of proinflammatory cytokines and prostaglandin E3 in Escherichia coli lipopolysaccharide-challenged growing-finishing pigs.

PubMed

Upadhaya, S D; Kim, J C; Mullan, B P; Pluske, J R; Kim, I H

2015-06-01

This study tested the hypothesis that vitamin E (Vit E) and omega-3 fatty acids will additively attenuate the production of proinflammatory cytokines and PGE2 in immune system–stimulated growing–finishing pigs. A total of 80 mixed sex pigs weighing 50.7 ± 0.76 kg (mean ± SE) were blocked and stratified based on sex and BW to a 2 × 2 factorial design with the respective factors being 1) without and with 300 IU Vit E and 2) without and with 25% replacement of tallow to linseed oil as a source of n-3 fatty acids. Each treatment consisted of 4 replicate pens with 5 pigs (3 barrows and 2 gilts) per pen. All pigs were challenged with an intramuscular injection of Escherichia coli lipopolysaccharide (LPS; O111:B4) twice weekly over the 6-wk experiment. After LPS challenge, pigs fed a diet supplemented with n-3 fatty acids had fewer (P < 0.05) white blood cells and tended to show both a reduced (P < 0.10) proportion of lymphocytes and IgG concentration compared with pigs fed a diet without any supplements. Supplementation of n-3 fatty acids reduced (P < 0.01 and P < 0.05) serum concentrations of cortisol and tumor necrosis factor α (TNF-α), respectively. The serum concentration of PGE2 was decreased (P < 0.05) with supplementation of both Vit E and n-3 fatty acids; however, the extent of the reduction was greater (P < 0.001) in pigs fed an n-3 fatty acid–supplemented diet. However, there were no additive effects of the combined supplementation of Vit E and n-3 fatty acids on serum concentrations of proinflammatory cytokines and PGE2. The results suggest that n-3 fatty acids independently attenuate production of TNF-α and PGE2 in immune system–stimulated growing–finishing pigs.

IT Challenges for Space Medicine

NASA Technical Reports Server (NTRS)

Johnson-Throop, Kathy

2010-01-01

This viewgraph presentation reviews the various Information Technology challenges for aerospace medicine. The contents include: 1) Space Medicine Activities; 2) Private Medical Information; 3) Lifetime Surveillance of Astronaut Health; 4) Mission Medical Support; 5) Data Repositories for Research; 6) Data Input and Output; 7) Finding Data/Information; 8) Summary of Challenges; and 9) Solutions and questions.

VAST Challenge 2014: The Kronos Incident

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

Whiting, Mark A.; Cook, Kristin A.; Grinstein, Georges

2014-10-31

The 2014 IEEE Visual Analytics Science and Technology (VAST) Challenge presented researchers with a single fictitious scenario: the disappearance of staff members of the GASTech oil and gas company on location on the island of Kronos. A group named the Protectors of Kronos (POK) was the prime suspect in the disappearance. Three mini-challenges and a grand challenge were offered. Mini-challenge 1 included multiple types of text data for participants to provide a timeline of key events and characterize the POK, mini-challenge 2 focused on individuals’ movement and financial data for participants to provide patterns of daily life, and mini-challenge 3more » featured real-time streaming social media and emergency service data for participants to provide hostage and kidnapper information. The grand challenge asked the participants to integrate results and generate a synopsis of events. The VAST Challenge received 73 submissions from 13 countries« less

Binding pose and affinity prediction in the 2016 D3R Grand Challenge 2 using the Wilma-SIE method

NASA Astrophysics Data System (ADS)

Hogues, Hervé; Sulea, Traian; Gaudreault, Francis; Corbeil, Christopher R.; Purisima, Enrico O.

2018-01-01

The Farnesoid X receptor (FXR) exhibits significant backbone movement in response to the binding of various ligands and can be a challenge for pose prediction algorithms. As part of the D3R Grand Challenge 2, we tested Wilma-SIE, a rigid-protein docking method, on a set of 36 FXR ligands for which the crystal structures had originally been blinded. These ligands covered several classes of compounds. To overcome the rigid protein limitations of the method, we used an ensemble of publicly available structures for FXR from the PDB. The use of the ensemble allowed Wilma-SIE to predict poses with average and median RMSDs of 2.3 and 1.4 Å, respectively. It was quite clear, however, that had we used a single structure for the receptor the success rate would have been much lower. The most successful predictions were obtained on chemical classes for which one or more crystal structures of the receptor bound to a molecule of the same class was available. In the absence of a crystal structure for the class, observing a consensus binding mode for the ligands of the class using one or more receptor structures of other classes seemed to be indicative of a reasonable pose prediction. Affinity prediction proved to be more challenging with generally poor correlation with experimental IC50s (Kendall tau 0.3). Even when the 36 crystal structures were used the accuracy of the predicted affinities was not appreciably improved. A possible cause of difficulty is the internal energy strain arising from conformational differences in the receptor across complexes, which may need to be properly estimated and incorporated into the SIE scoring function.

Prospective evaluation of shape similarity based pose prediction method in D3R Grand Challenge 2015

NASA Astrophysics Data System (ADS)

Kumar, Ashutosh; Zhang, Kam Y. J.

2016-09-01

Evaluation of ligand three-dimensional (3D) shape similarity is one of the commonly used approaches to identify ligands similar to one or more known active compounds from a library of small molecules. Apart from using ligand shape similarity as a virtual screening tool, its role in pose prediction and pose scoring has also been reported. We have recently developed a method that utilizes ligand 3D shape similarity with known crystallographic ligands to predict binding poses of query ligands. Here, we report the prospective evaluation of our pose prediction method through the participation in drug design data resource (D3R) Grand Challenge 2015. Our pose prediction method was used to predict binding poses of heat shock protein 90 (HSP90) and mitogen activated protein kinase kinase kinase kinase (MAP4K4) ligands and it was able to predict the pose within 2 Å root mean square deviation (RMSD) either as the top pose or among the best of five poses in a majority of cases. Specifically for HSP90 protein, a median RMSD of 0.73 and 0.68 Å was obtained for the top and the best of five predictions respectively. For MAP4K4 target, although the median RMSD for our top prediction was only 2.87 Å but the median RMSD of 1.67 Å for the best of five predictions was well within the limit for successful prediction. Furthermore, the performance of our pose prediction method for HSP90 and MAP4K4 ligands was always among the top five groups. Particularly, for MAP4K4 protein our pose prediction method was ranked number one both in terms of mean and median RMSD when the best of five predictions were considered. Overall, our D3R Grand Challenge 2015 results demonstrated that ligand 3D shape similarity with the crystal ligand is sufficient to predict binding poses of new ligands with acceptable accuracy.

Challenges faced by multidisplinary new investigators on addressing grand challenges in global health

PubMed Central

2014-01-01

Background The grand challenges approach aims to spark innovative and transformative strategies to overcome barriers to significant global health issues. Grand Challenges Canada endorses an ‘Integrated Innovation™’ approach that focuses on the intersection of scientific/technological, social and business innovation. In this article we explore themes emerging from a dialogue between the authors, who are multidisciplinary recipients of the ‘Rising Stars in Global Health’ award from Grand Challenges Canada, regarding benefits of engaging in integrated innovation research, and recommendations for how this approach may develop in the future. Discussion Our dialogue followed a semi-structured interview format that addressed three topics: 1) reflections on applying an Integrated Innovation™ approach for global health; 2) thoughts on participation in the Grand Challenges 2012 meeting; and 3) authors’ visions of Grand Challenges Canada and the Grand Challenge movement towards 2020. The dialogue was transcribed verbatim and we used thematic analysis techniques to identify, analyze and report themes in the data. Benefits of working using the Grand Challenges approach centered on two themes: a) the potential for scientific breakthrough and b) building interdisciplinary collaborations and a community of scholars. Challenges and opportunities for Grand Challenges in moving forward included: a) capacity building, particularly regarding Integrated Innovation™ and scale-up planning; b) interdisciplinary and international mentorship for new investigators; and c) potential for future commercialization. Conclusions Our discussion highlighted that Integrated Innovation™ offers the opportunity to develop new theories, methods and approaches to global health while simultaneously fostering a collaborative spirit grounded in international, interdisciplinary collaborations. However, the arguable over-emphasis on corporatization poses a major challenge for new investigators

Challenges faced by multidisplinary new investigators on addressing grand challenges in global health.

PubMed

Logie, Carmen; Dimaras, Helen; Fortin, Anny; Ramón-García, Santiago

2014-04-15

The grand challenges approach aims to spark innovative and transformative strategies to overcome barriers to significant global health issues. Grand Challenges Canada endorses an 'Integrated Innovation™' approach that focuses on the intersection of scientific/technological, social and business innovation. In this article we explore themes emerging from a dialogue between the authors, who are multidisciplinary recipients of the 'Rising Stars in Global Health' award from Grand Challenges Canada, regarding benefits of engaging in integrated innovation research, and recommendations for how this approach may develop in the future. Our dialogue followed a semi-structured interview format that addressed three topics: 1) reflections on applying an Integrated Innovation™ approach for global health; 2) thoughts on participation in the Grand Challenges 2012 meeting; and 3) authors' visions of Grand Challenges Canada and the Grand Challenge movement towards 2020. The dialogue was transcribed verbatim and we used thematic analysis techniques to identify, analyze and report themes in the data. Benefits of working using the Grand Challenges approach centered on two themes: a) the potential for scientific breakthrough and b) building interdisciplinary collaborations and a community of scholars. Challenges and opportunities for Grand Challenges in moving forward included: a) capacity building, particularly regarding Integrated Innovation™ and scale-up planning; b) interdisciplinary and international mentorship for new investigators; and c) potential for future commercialization. Our discussion highlighted that Integrated Innovation™ offers the opportunity to develop new theories, methods and approaches to global health while simultaneously fostering a collaborative spirit grounded in international, interdisciplinary collaborations. However, the arguable over-emphasis on corporatization poses a major challenge for new investigators. We propose a more balanced way forward

Increasing Fruit, Vegetable and Water Consumption in Summer Day Camps-3-Year Findings of the Healthy Lunchbox Challenge

ERIC Educational Resources Information Center

Beets, Michael W.; Tilley, Falon; Weaver, Robert G.; Turner-McGrievy, Gabrielle M.; Moore, Justin B.

2014-01-01

The objective of this study was to describe the 3-year outcomes (2011-2013) from the healthy lunchbox challenge (HLC) delivered in the US-based summer day camps (SDC) (8-10 hours day-1, 10-11 weeks summer-1, SDC) to increase children and staff bringing fruit, vegetables and water (FVW) each day. A single group pre- with multiple post-test design…

The Terawatt Challenge

NASA Astrophysics Data System (ADS)

Haegel, Nancy

In response to concerns about accelerating climate change, the world is uniting to both envision and enable a global energy system that supports a sustainable environment and broad economic prosperity. Growth in the technology and the deployment of renewable energy has been dramatic. Evidence can be seen in the growth of photovoltaics (PV) and wind as contributors to worldwide electricity production over the last decade. PV and wind provided 1.2% and 3.7% of global electricity production in 2015, compared to 0.1% and 1.3% respectively in 2005. These numbers indicate both the rapid increase in the rate of deployment, as well as the remaining work to be done to extend this trend to transform a massive energy system and provide a significant fraction of the world's future energy demand with renewable energy. Based on recent trends, it is highly likely that global cumulative PV installation will reach terawatt scale in the next few decades. The challenges, as well as the resulting impact, vary greatly depending on whether we envision 1 TW ( 15% of 2015 global electricity capacity), 3 TW ( 50% of 2015 global electricity capacity) or 10 TW, a level that could drive electrification of transportation and industrial sectors and production of solar fuels. This presentation will draw upon the work of the 2016 GA-SERI (Global Alliance of Solar Energy Research Institutes) Terawatt Workshop to assess the feasibility and summarize the challenges for PV as a primary energy source. These challenges include the continuing demand for improved efficiency and reliability, the required magnitude of capital expenditure, the need for a sustainable industry (both financially and environmentally), as well as needs for grid modernization and consistent policies that support global climate goals. Physicists can play important roles in addressing this full range of challenges, from materials science to public policy, as well as in education of the public and its future leaders.

THE FREEZING POINT DEPRESSION OF MAMMALIAN TISSUES AFTER SUDDEN HEATING IN BOILING DISTILLED WATER

PubMed Central

Appelboom, Johannes W. Th.; Brodsky, William A.; Tuttle, William S.; Diamond, Israel

1958-01-01

The calculated freezing point depression of freshly excised boiled mammalian tissue is approximately the same as that of plasma. The boiling procedure was chosen to eliminate the influence of metabolism on the level of the freezing point depression. Problems created by the boiling, such as equilibrium between tissue and diluent, change in activity coefficient by dilution, and loss of CO2 content, are discussed. A frozen crushed tissue homogenate is hypertonic to plasma. Boiling and dilution of such hypertonic homogenate exposed to room temperature for 5 to 15 minutes did not produce significant or unexplicable decreases in its osmotic activity. Moreover, freezing and crushing of a boiled diluted tissue did not produce any increase of the isoosmotic level of freezing point depression. It is possible to explain these data either with the hypothesis of hypertonic cell fluid or with that of isotonic cell fluid. In the case of an assumed isotonic cell fluid, data can be explained with one assumption, experimentally backed. In the case of an assumed hypertonic theory data can be explained only with the help of at least three ad hoc postulates. The data support the validity of the classical concept which holds that cell fluid is isotonic to extracellular fluid. PMID:13563805

Large scale free energy calculations for blind predictions of protein-ligand binding: the D3R Grand Challenge 2015.

PubMed

Deng, Nanjie; Flynn, William F; Xia, Junchao; Vijayan, R S K; Zhang, Baofeng; He, Peng; Mentes, Ahmet; Gallicchio, Emilio; Levy, Ronald M

2016-09-01

We describe binding free energy calculations in the D3R Grand Challenge 2015 for blind prediction of the binding affinities of 180 ligands to Hsp90. The present D3R challenge was built around experimental datasets involving Heat shock protein (Hsp) 90, an ATP-dependent molecular chaperone which is an important anticancer drug target. The Hsp90 ATP binding site is known to be a challenging target for accurate calculations of ligand binding affinities because of the ligand-dependent conformational changes in the binding site, the presence of ordered waters and the broad chemical diversity of ligands that can bind at this site. Our primary focus here is to distinguish binders from nonbinders. Large scale absolute binding free energy calculations that cover over 3000 protein-ligand complexes were performed using the BEDAM method starting from docked structures generated by Glide docking. Although the ligand dataset in this study resembles an intermediate to late stage lead optimization project while the BEDAM method is mainly developed for early stage virtual screening of hit molecules, the BEDAM binding free energy scoring has resulted in a moderate enrichment of ligand screening against this challenging drug target. Results show that, using a statistical mechanics based free energy method like BEDAM starting from docked poses offers better enrichment than classical docking scoring functions and rescoring methods like Prime MM-GBSA for the Hsp90 data set in this blind challenge. Importantly, among the three methods tested here, only the mean value of the BEDAM binding free energy scores is able to separate the large group of binders from the small group of nonbinders with a gap of 2.4 kcal/mol. None of the three methods that we have tested provided accurate ranking of the affinities of the 147 active compounds. We discuss the possible sources of errors in the binding free energy calculations. The study suggests that BEDAM can be used strategically to discriminate

Large scale free energy calculations for blind predictions of protein-ligand binding: the D3R Grand Challenge 2015

NASA Astrophysics Data System (ADS)

Deng, Nanjie; Flynn, William F.; Xia, Junchao; Vijayan, R. S. K.; Zhang, Baofeng; He, Peng; Mentes, Ahmet; Gallicchio, Emilio; Levy, Ronald M.

2016-09-01

We describe binding free energy calculations in the D3R Grand Challenge 2015 for blind prediction of the binding affinities of 180 ligands to Hsp90. The present D3R challenge was built around experimental datasets involving Heat shock protein (Hsp) 90, an ATP-dependent molecular chaperone which is an important anticancer drug target. The Hsp90 ATP binding site is known to be a challenging target for accurate calculations of ligand binding affinities because of the ligand-dependent conformational changes in the binding site, the presence of ordered waters and the broad chemical diversity of ligands that can bind at this site. Our primary focus here is to distinguish binders from nonbinders. Large scale absolute binding free energy calculations that cover over 3000 protein-ligand complexes were performed using the BEDAM method starting from docked structures generated by Glide docking. Although the ligand dataset in this study resembles an intermediate to late stage lead optimization project while the BEDAM method is mainly developed for early stage virtual screening of hit molecules, the BEDAM binding free energy scoring has resulted in a moderate enrichment of ligand screening against this challenging drug target. Results show that, using a statistical mechanics based free energy method like BEDAM starting from docked poses offers better enrichment than classical docking scoring functions and rescoring methods like Prime MM-GBSA for the Hsp90 data set in this blind challenge. Importantly, among the three methods tested here, only the mean value of the BEDAM binding free energy scores is able to separate the large group of binders from the small group of nonbinders with a gap of 2.4 kcal/mol. None of the three methods that we have tested provided accurate ranking of the affinities of the 147 active compounds. We discuss the possible sources of errors in the binding free energy calculations. The study suggests that BEDAM can be used strategically to discriminate

Cyber Intelligence: Challenges and Best Practices

DTIC Science & Technology

2015-01-15

2015 2 . REPORT TYPE N/A 3. DATES COVERED 4. TITLE AND SUBTITLE Cyber Intelligence Challenges and Best Practices 5a. CONTRACT NUMBER 5b...ANSI Std Z39-18 2 Cyber Intel – Challenges and Best Practices January 2015 © 2015 Carnegie Mellon University Copyright 2015 Carnegie Mellon University...University Reporting timelines Gov’t Agency 1 Gov’t Agency 2 Gov’t Agency 3 Gov’t Agency 4 Urgent Normal Strategic 2 -4 Hours 1 Day 1 Month 1 Day 2

Lessons learned from participating in D3R 2016 Grand Challenge 2: compounds targeting the farnesoid X receptor

NASA Astrophysics Data System (ADS)

Duan, Rui; Xu, Xianjin; Zou, Xiaoqin

2018-01-01

D3R 2016 Grand Challenge 2 focused on predictions of binding modes and affinities for 102 compounds against the farnesoid X receptor (FXR). In this challenge, two distinct methods, a docking-based method and a template-based method, were employed by our team for the binding mode prediction. For the new template-based method, 3D ligand similarities were calculated for each query compound against the ligands in the co-crystal structures of FXR available in Protein Data Bank. The binding mode was predicted based on the co-crystal protein structure containing the ligand with the best ligand similarity score against the query compound. For the FXR dataset, the template-based method achieved a better performance than the docking-based method on the binding mode prediction. For the binding affinity prediction, an in-house knowledge-based scoring function ITScore2 and MM/PBSA approach were employed. Good performance was achieved for MM/PBSA, whereas the performance of ITScore2 was sensitive to ligand composition, e.g. the percentage of carbon atoms in the compounds. The sensitivity to ligand composition could be a clue for the further improvement of our knowledge-based scoring function.

D3R Grand Challenge 2: blind prediction of protein-ligand poses, affinity rankings, and relative binding free energies

NASA Astrophysics Data System (ADS)

Gaieb, Zied; Liu, Shuai; Gathiaka, Symon; Chiu, Michael; Yang, Huanwang; Shao, Chenghua; Feher, Victoria A.; Walters, W. Patrick; Kuhn, Bernd; Rudolph, Markus G.; Burley, Stephen K.; Gilson, Michael K.; Amaro, Rommie E.

2018-01-01

The Drug Design Data Resource (D3R) ran Grand Challenge 2 (GC2) from September 2016 through February 2017. This challenge was based on a dataset of structures and affinities for the nuclear receptor farnesoid X receptor (FXR), contributed by F. Hoffmann-La Roche. The dataset contained 102 IC50 values, spanning six orders of magnitude, and 36 high-resolution co-crystal structures with representatives of four major ligand classes. Strong global participation was evident, with 49 participants submitting 262 prediction submission packages in total. Procedurally, GC2 mimicked Grand Challenge 2015 (GC2015), with a Stage 1 subchallenge testing ligand pose prediction methods and ranking and scoring methods, and a Stage 2 subchallenge testing only ligand ranking and scoring methods after the release of all blinded co-crystal structures. Two smaller curated sets of 18 and 15 ligands were developed to test alchemical free energy methods. This overview summarizes all aspects of GC2, including the dataset details, challenge procedures, and participant results. We also consider implications for progress in the field, while highlighting methodological areas that merit continued development. Similar to GC2015, the outcome of GC2 underscores the pressing need for methods development in pose prediction, particularly for ligand scaffolds not currently represented in the Protein Data Bank (http://www.pdb.org), and in affinity ranking and scoring of bound ligands.

N-domain angiotensin-I converting enzyme is expressed in immortalized mesangial, proximal tubule and collecting duct cells.

PubMed

Mei Wang, Pamella Huey; Andrade, Maria Claudina; Quinto, Beata Marie Redublo; Di Marco, Giovana; Mortara, Renato Arruda; Vio, Carlos P; Casarini, Dulce Elena

2015-01-01

Somatic ACE (sACE) is found in glomerulus, proximal tubule and excreted in urine. We hypothesized that N-domain ACE can also be found at these sites. ACE profile was analyzed in mesangial (IMC), proximal (LLC-PK1), distal tubule (MDCK) and collecting duct (IMCD) cells. Cell lysate and culture medium were submitted to gel filtration chromatography, which separated two peaks with ACE activity from cells and medium, except from distal tubule. The first had a high molecular weight and the second, a lower one (65 kDa; N-domain ACE). We focused on N-domain ACE purification and characterization from LLC-PK1. Total LLC-PK1 N-domain ACE purification was achieved by ion-exchange chromatography, which presented only one peak with ACE activity, denominated ACE(int2A). ACE(int2A) activity was influenced by pH, NaCl and temperature. The purified enzyme was inhibited by Captopril and hydrolyzed AngI, Ang1-7 and AcSDKP. Its ability to hydrolyze AcSDKP characterized it as an N-domain ACE. ACE(int2A) also presented high amino acid sequence homology with the N-terminal part of sACE from mouse, rat, human and rabbit. The presence of secreted and intracellular N-domain ACE and sACE in IMC, LLC-PK1 and IMCD cells confirmed our studies along the nephron. We identified, purified and characterized N-domain ACE from LLC-PK1. Copyright © 2014 Elsevier B.V. All rights reserved.

Apical P2XR contribute to [Ca2+]i signaling and Isc in mouse renal MCD.

PubMed

Li, Liuzhe; Lynch, I Jeanette; Zheng, Wencui; Cash, Melanie N; Teng, Xueling; Wingo, Charles S; Verlander, Jill W; Xia, Shen-Ling

2007-08-03

We examined P2X receptor expression and distribution in the mouse collecting duct (CD) and their functional role in Ca(2+) signaling. Both P2X(1) and P2X(4) were detected by RT-PCR and Western blot. Immunohistochemistry demonstrated apical P2X(1) and P2X(4) immunoreactivity in principal cells in the outer medullary CD (OMCD) and inner medullary CD (IMCD). Luminal ATP induced an increase in Ca(2+) signaling in native medullary CD (MCD) as measured by fluorescence imaging. ATP also induced an increase in Ca(2+) signaling in MCD cells grown in primary culture but not in the presence of P2XR antagonist PPNDS. Short circuit current (I(sc)) measurement with mouse IMCD cells showed that P2XR agonist BzATP induced a larger I(sc) than did P2YR agonist UTP in the apical membrane. Our data reveal for the first time that P2X(1) and P2X(4) are cell-specific with prominent immunoreactivity in the apical area of MCD cells. The finding that P2XR blockade inhibits ATP-induced Ca(2+) signaling suggests that activation of P2XR is a key step in Ca(2+)-dependent purinergic signaling. The result that activation of P2XR produces large I(sc) indicates the necessity of P2XR in renal CD ion transport.

Expression of peroxisomal proliferator-activated receptors and retinoid X receptors in the kidney.

PubMed

Yang, T; Michele, D E; Park, J; Smart, A M; Lin, Z; Brosius, F C; Schnermann, J B; Briggs, J P

1999-12-01

The discovery that 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) is a ligand for the gamma-isoform of peroxisome proliferator-activated receptor (PPAR) suggests nuclear signaling by prostaglandins. Studies were undertaken to determine the nephron localization of PPAR isoforms and their heterodimer partners, retinoid X receptors (RXR), and to evaluate the function of this system in the kidney. PPARalpha mRNA, determined by RT-PCR, was found predominately in cortex and further localized to proximal convoluted tubule (PCT); PPARgamma was abundant in renal inner medulla, localized to inner medullary collecting duct (IMCD) and renal medullary interstitial cells (RMIC); PPARbeta, the ubiquitous form of PPAR, was abundant in all nephron segments examined. RXRalpha was localized to PCT and IMCD, whereas RXRbeta was expressed in almost all nephron segments examined. mRNA expression of acyl-CoA synthase (ACS), a known PPAR target gene, was stimulated in renal cortex of rats fed with fenofibrate, but the expression was not significantly altered in either cortex or inner medulla of rats fed with troglitazone. In cultured RMIC cells, both troglitazone and 15d-PGJ2 significantly inhibited cell proliferation and dramatically altered cell shape by induction of cell process formation. We conclude that PPAR and RXR isoforms are expressed in a nephron segment-specific manner, suggesting distinct functions, with PPARalpha being involved in energy metabolism through regulating ACS in PCT and with PPARgamma being involved in modulating RMIC growth and differentiation.

Transplantology: Challenges for Today.

PubMed

Boratyńska, Maria; Patrzałek, Dariusz

2016-12-01

Clinical transplantology in Poland had its 50th anniversary this year. With the early and long results comparable to the best achieved in the world leading centers, we face old and completely new challenges for this medical speciality. Main and growing challenge is insufficient number of available organs. With less than 15 donors/mln population/year Poland stay in the lower row of European countries in this measurement of transplant activity. Donation system is not efficient enough and we lose a big number of potential donors still. Living donation (with the exception for the fragments of the liver) remains low despite of different initiatives made so far on the national and local levels. Donation after cardiac death is possible from the point of Polish juridical regulations, but since last 3 years had not showed real impact on country donation rates (only three procedures done). Methods of tissue typing remain slow and cause relatively long times of cold ischemia for kidney programs. Second main challenge is chronic rejection causing loss of organs in the long-term follow-up and no efficient treatment employed. The emerging possibility of tolerance induction despite of plenty of new protocols proposition in the publications does not show up a clinical everyday practice in work. The same is with xenotransplantation promises; even we were informed recently that till 2030 such genetically modified porcine organs will be available. The next challenge is production of organs and tissues from own recipients cells installed on the different scaffolds or 3D printed. Other challenge is the personnel working in this field. We observe like in the other European countries lack of new candidates for work in this field together with serious problems of nursing staff, being a catastrophic perspective in country medical service in general, not only in transplant centers. The last but not least challenge is financial side of transplant programs.

Meeting the Energy-Climate Challenge

DTIC Science & Technology

2010-04-21

e.g., cogeneration , wind, some biofuels incl waste-to- energy . • The “win-win” approaches will not be enough. Adequate mitigation will...Meeting the  Energy ‐Climate Challenge John P. Holdren Science and Technology Advisor to President Obama and Director...DATE 2010 2. REPORT TYPE 3. DATES COVERED 00-00-2010 to 00-00-2010 4. TITLE AND SUBTITLE Meeting the Energy -Climate Challenge 5a. CONTRACT

Vagal afferents contribute to exacerbated airway responses following ozone and allergen challenge

PubMed Central

Schelegle, Edward S.; Walby, William F.

2012-01-01

Brown-Norway rats (n = 113) sensitized and challenged with nDer f 1 allergen were used to examine the contribution of lung sensory nerves to ozone (O3) exacerbation of asthma. Prior to their third challenge rats inhaled 1.0 ppm O3 for 8 hours. There were three groups: 1) control; 2) vagus perineural capsaicin treatment (PCT) with or without hexamethonium; and 3) vagotomy. O3 inhalation resulted in a significant increase in lung resistance (RL) and an exaggerated response to subsequent allergen challenge. PCT abolished the O3-induced increase in RL and significantly reduced the increase in RL induced by a subsequent allergen challenge, while hexamethonium treatment reestablished bronchoconstriction induced by allergen challenge. Vagotomy resulted in a significant increase in the bronchoconstriction induced by O3 inhalation and subsequent challenge with allergen. In this model of O3 exacerbation of asthma, vagal C-fibers initiate reflex bronchoconstriction, vagal myelinated fibers initiate reflex bronchodilation, and mediators released within the airway initiate bronchoconstriction. PMID:22525484

Receptor-mediated internalization of [3H]-neurotensin in synaptosomal preparations from rat neostriatum.

PubMed

Nguyen, Ha Minh Ky; Cahill, Catherine M; McPherson, Peter S; Beaudet, Alain

2002-06-01

Following its binding to somatodendritic receptors, the neuropeptide neurotensin (NT) internalizes via a clathrin-mediated process. In the present study, we investigated whether NT also internalizes presynaptically using synaptosomes from rat neostriatum, a region in which NT1 receptors are virtually all presynaptic. Binding of [(3)H]-NT to striatal synaptosomes in the presence of levocabastine to block NT2 receptors is specific, saturable, and has NT1 binding properties. A significant fraction of the bound radioactivity is resistant to hypertonic acid wash indicating that it is internalized. Internalization of [(3)H]-NT, like that of [(125)I]-transferrin, is blocked by sucrose and low temperature, consistent with endocytosis occurring via a clathrin-dependent pathway. However, contrary to what was reported at the somatodendritic level, neither [(3)H]-NT nor [(125)I]-transferrin internalization in synaptosomes is sensitive to the endocytosis inhibitor phenylarsine oxide. Moreover, treatment of synaptosomes with monensin, which prevents internalized receptors from recycling to the plasma membrane, reduces [(3)H]-NT binding and internalization, suggesting that presynaptic NT1 receptors, in contrast to somatodendritic ones, are recycled back to the plasma membrane. Taken together, these results suggest that NT internalizes in nerve terminals via an endocytic pathway that is related to, but is mechanistically distinct from that responsible for NT internalization in nerve cell bodies.

Influence of Polymorphisms in the HTR3A and HTR3B Genes on Experimental Pain and the Effect of the 5-HT3 Antagonist Granisetron.

PubMed

Louca Jounger, Sofia; Christidis, Nikolaos; Hedenberg-Magnusson, Britt; List, Thomas; Svensson, Peter; Schalling, Martin; Ernberg, Malin

2016-01-01

The aim of this study was to investigate experimentally if 5-HT3 single nucleotide polymorphisms (SNP) contribute to pain perception and efficacy of the 5-HT3-antagonist granisetron and sex differences. Sixty healthy participants were genotyped regarding HTR3A (rs1062613) and HTR3B (rs1176744). First, pain was induced by bilateral hypertonic saline injections (HS, 5.5%, 0.2 mL) into the masseter muscles. Thirty min later the masseter muscle on one side was pretreated with 0.5 mL granisetron (1 mg/mL) and on the other side with 0.5 mL placebo (isotonic saline) followed by another HS injection (0.2 mL). Pain intensity, pain duration, pain area and pressure pain thresholds (PPTs) were assessed after each injection. HS evoked moderate pain, with higher intensity in the women (P = 0.023), but had no effect on PPTs. None of the SNPs influenced any pain variable in general, but compared to men, the pain area was larger in women carrying the C/C (HTR3A) (P = 0.015) and pain intensity higher in women with the A/C alleles (HTR3B) (P = 0.019). Pre-treatment with granisetron reduced pain intensity, duration and area to a lesser degree in women (P < 0.05), but the SNPs did not in general influence the efficacy of granisetron. Women carrying the C/T & T/T (HTR3A) genotype had less reduction of pain intensity (P = 0.041) and area (P = 0.005), and women with the C/C genotype (HTR3B) had less reduction of pain intensity (P = 0.030), duration (P = 0.030) and area compared to men (P = 0.017). In conclusion, SNPs did not influence experimental muscle pain or the effect of granisetron on pain variables in general, but there were some sex differences in pain variables that seem to be influenced by genotypes. However, due to the small sample size further research is needed before any firm conclusions can be drawn.

Influence of Polymorphisms in the HTR3A and HTR3B Genes on Experimental Pain and the Effect of the 5-HT3 Antagonist Granisetron

PubMed Central

Hedenberg-Magnusson, Britt; List, Thomas; Svensson, Peter; Schalling, Martin

2016-01-01

The aim of this study was to investigate experimentally if 5-HT3 single nucleotide polymorphisms (SNP) contribute to pain perception and efficacy of the 5-HT3-antagonist granisetron and sex differences. Sixty healthy participants were genotyped regarding HTR3A (rs1062613) and HTR3B (rs1176744). First, pain was induced by bilateral hypertonic saline injections (HS, 5.5%, 0.2 mL) into the masseter muscles. Thirty min later the masseter muscle on one side was pretreated with 0.5 mL granisetron (1 mg/mL) and on the other side with 0.5 mL placebo (isotonic saline) followed by another HS injection (0.2 mL). Pain intensity, pain duration, pain area and pressure pain thresholds (PPTs) were assessed after each injection. HS evoked moderate pain, with higher intensity in the women (P = 0.023), but had no effect on PPTs. None of the SNPs influenced any pain variable in general, but compared to men, the pain area was larger in women carrying the C/C (HTR3A) (P = 0.015) and pain intensity higher in women with the A/C alleles (HTR3B) (P = 0.019). Pre-treatment with granisetron reduced pain intensity, duration and area to a lesser degree in women (P < 0.05), but the SNPs did not in general influence the efficacy of granisetron. Women carrying the C/T & T/T (HTR3A) genotype had less reduction of pain intensity (P = 0.041) and area (P = 0.005), and women with the C/C genotype (HTR3B) had less reduction of pain intensity (P = 0.030), duration (P = 0.030) and area compared to men (P = 0.017). In conclusion, SNPs did not influence experimental muscle pain or the effect of granisetron on pain variables in general, but there were some sex differences in pain variables that seem to be influenced by genotypes. However, due to the small sample size further research is needed before any firm conclusions can be drawn. PMID:28002447

Restructuring Principal Preparation in Illinois: Perspectives on Implementation Successes, Challenges, and Future Outlook. IERC 2015-3

ERIC Educational Resources Information Center

Klostermann, Brenda K.; Pareja, Amber Stitziel; Hart, Holly; White, Bradford R.; Huynh, Michelle Hanh

2015-01-01

The goals of the current mixed methods study--the Illinois Principal Preparation Implementation Review Project (I-PREP)--are to describe how the new policy is being implemented, learning which aspects of the implementation have been challenging and why they present challenges, and how programs are addressing challenges and realizing improvements…

Vaccine-induced protection from egg production losses in commercial turkey breeder hens following experimental challenge with a triple-reassortant H3N2 avian influenza virus.

PubMed

Kapczynski, Darrell R; Gonder, Eric; Liljebjelke, Karen; Lippert, Ron; Petkov, Daniel; Tilley, Becky

2009-03-01

Infections of avian influenza virus (AIV) in turkey breeder hens can cause a decrease in both egg production and quality, resulting in significant production losses. In North Carolina in 2003, a triple-reassortant H3N2 AIV containing human, swine, and avian gene segments was isolated from turkey breeder hens (A/turkey/NC/16108/03). This viral subtype was subsequently isolated from both turkeys and swine in Ohio in 2004, and in Minnesota in 2005, and was responsible for significant losses in turkey production. The objective of this study was to determine if currently available commercial, inactivated avian influenza H3 subtype oil-emulsion vaccines would protect laying turkey hens from egg production losses following challenge with the 2003 H3N2 field virus isolate from North Carolina. Laying turkey hens were vaccinated in the field with two injections of either a commercial monovalent (A/duck/Minnesota/79/79 [H3N4]) or autogenous bivalent (A/turkey/North Carolina/05 (H3N2)-A/turkey/North Carolina/88 [H1N1]) vaccine, at 26 and 30 wk of age, and subsequently challenged under BSL 3-Ag conditions at 32 wk of age. Vaccine-induced efficacy was determined as protection from a 50% decrease in egg production and from a decrease in egg quality within 21 days postchallenge. Results indicate that, following a natural route of challenge (eye drop and intranasal), birds vaccinated with the 2005 North Carolina H3N2 subtype were significantly protected from the drop in egg production observed in both the H3N4 vaccinated and sham-vaccinated hens. The results demonstrate that groups receiving vaccines containing either H3 subtype had a decreased number of unsettable eggs, increased hemagglutination inhibition titers following challenge, and decreased virus isolations from cloacal swabs as compared to the sham-vaccinated group. Phylogenetic analysis of the nucleotide sequence of the HA1 gene segment from the three H3 viruses used in these studies indicated that the two North Carolina

Green Flight Challenge

NASA Image and Video Library

2011-10-03

Comparative Aircraft Flight Efficiency (CAFE) Foundation President Brien A. Seeley M.D., left, NASA Acting Chief Technologist Joe Parrish, 2nd from left, and Pipistrel-USA Team Lead Jack Langelaan, center with suit, and the entire Pipistrel-USA, Taurus G4 aircraft team pose for a photograph shortly after winning the 2011 Green Flight Challenge, sponsored by Google, on Monday, Oct. 3, 2011 at the NASA Ames Research Center, Mountain View, Calif. The all electric Taurus G4 aircraft achieved the equivalency of more than 400 miles per gallon. NASA and CAFE held the challenge to advance technologies in fuel efficiency and reduced emissions with cleaner renewable fuels and electric aircraft. Photo Credit: (NASA/Bill Ingalls)

Life Support Systems Microbial Challenges

NASA Technical Reports Server (NTRS)

Roman, Monserrate C.

2009-01-01

This viewgraph presentation reviews the current microbial challenges of environmental control and life support systems. The contents include: 1) Environmental Control and Life Support Systems (ECLSS) What is it?; 2) A Look Inside the International Space Station (ISS); 3) The Complexity of a Water Recycling System; 4) ISS Microbiology Acceptability Limits; 5) Overview of Current Microbial Challenges; 6) In a Perfect World What we Would like to Have; and 7) The Future.

Collider Bias in Trauma Comparative Effectiveness Research: The Stratification Blues for Systematic Reviews

DTIC Science & Technology

2015-05-01

of treatment and outcome, plagues randomised and observational trauma research. Of the seven trials of prehospital hypertonic saline in dextran (HSD...hypertonic saline in dextran (HSD) for hypovolaemic trauma patients [11–17] evaluated in systematic reviews [18–26], none found an overall between-group...containing either HSD (7.5% NaCl with 6% dextran -70) or the standard-of-care, i.e., lactated Ringer’s in the pilot [11]; normal saline (0.9%) in the pivotal

Challenges in the development of dopamine D2- and D3-selective radiotracers for PET imaging studies.

PubMed

Mach, Robert H; Luedtke, Robert R

2018-03-01

The dopamine D2-like receptors (ie, D2/3 receptors) have been the most extensively studied CNS receptor with Positron Emission Tomography (PET). The 3 different radiotracers that have been used in these studies are [ 11 C]raclopride, [ 18 F]fallypride, and [ 11 C]PHNO. Because these radiotracers have a high affinity for both dopamine D2 and D3 receptors, the density of dopamine receptors in the CNS is reported as the D2/3 binding potential, which reflects a measure of the density of both receptor subtypes. Although the development of D2- and D3-selective PET radiotracers has been an active area of research for many years, this by and large presents an unmet need in the area of translational PET imaging studies. This article discusses some of the challenges that have inhibited progress in this area of research and the current status of the development of subtype selective radiotracers for imaging D3 and D2 dopamine receptors with PET. Copyright © 2017 John Wiley & Sons, Ltd.

Experimental muscle pain produces central modulation of proprioceptive signals arising from jaw muscle spindles.

PubMed

Capra, N F; Ro, J Y

2000-05-01

The aim of the present study was to investigate the effects of intramuscular injection with hypertonic saline, a well-established experimental model for muscle pain, on central processing of proprioceptive input from jaw muscle spindle afferents. Fifty-seven cells were recorded from the medial edge of the subnucleus interpolaris (Vi) and the adjacent parvicellular reticular formation from 11 adult cats. These cells were characterized as central units receiving jaw muscle spindle input based on their responses to electrical stimulation of the masseter nerve, muscle palpation and jaw stretch. Forty-five cells, which were successfully tested with 5% hypertonic saline, were categorized as either dynamic-static (DS) (n=25) or static (S) (n=20) neurons based on their responses to different speeds and amplitudes of jaw movement. Seventy-six percent of the cells tested with an ipsilateral injection of hypertonic saline showed a significant modulation of mean firing rates (MFRs) during opening and/or holding phases. The most remarkable saline-induced change was a significant reduction of MFR during the hold phase in S units (100%, 18/18 modulated). Sixty-nine percent of the DS units (11/16 modulated) also showed significant changes in MFRs limited to the hold phase. However, in the DS neurons, the MFRs increased in seven units and decreased in four units. Finally, five DS neurons showed significant changes of MFRs during both opening and holding phases. Injections of isotonic saline into the ipsilateral masseter muscle had little effect, but hypertonic saline injections made into the contralateral masseter muscle produced similar results to ipsilateral injections with hypertonic saline. These results unequivocally demonstrate that intramuscular injection with an algesic substance, sufficient to produce muscle pain, produces significant changes in the proprioceptive properties of the jaw movement-related neurons. Potential mechanisms involved in saline-induced changes in the

Lack of UCP3 does not affect skeletal muscle mitochondrial function under lipid-challenged conditions, but leads to sudden cardiac death.

PubMed

Nabben, Miranda; van Bree, Bianca W J; Lenaers, Ellen; Hoeks, Joris; Hesselink, Matthijs K C; Schaart, Gert; Gijbels, Marion J J; Glatz, Jan F C; da Silva, Gustavo J J; de Windt, Leon J; Tian, Rong; Mike, Elise; Skapura, Darlene G; Wehrens, Xander H T; Schrauwen, Patrick

2014-01-01

UCP3's exact physiological function in lipid handling in skeletal and cardiac muscle remains unknown. Interestingly, etomoxir, a fat oxidation inhibitor and strong inducer of UCP3, is proposed for treating both diabetes and heart failure. We hypothesize that the upregulation of UCP3 upon etomoxir serves to protect mitochondria against lipotoxicity. To evaluate UCP3's role in skeletal muscle (skm) and heart under lipid-challenged conditions, the effect of UCP3 ablation was examined in a state of dysbalance between fat availability and oxidative capacity. Wild type (WT) and UCP3(-/-) mice were subjected to high-fat feeding for 14 days. From day 6 onwards, they were given either saline or etomoxir. Etomoxir treatment induced an increase in markers of lipotoxicity in skm compared to saline. This increase upon etomoxir was similar for both, WT and UCP3(-/-) mice, suggesting that UCP3 does not play a role in protection against lipotoxicity. Interestingly, we observed 25 % mortality in UCP3(-/-)s upon etomoxir administration vs. 11 % in WTs. This increased mortality in UCP3(-/-) compared to WT mice could not be explained by differences in cardiac lipotoxicity, apoptosis, fibrosis (histology, immunohistochemistry), oxidative capacity (respirometry) or function (echocardiography). Electrophysiology demonstrated, however, prolonged QRS and QTc intervals and greater susceptibility to ventricular tachycardia upon programmed electrical stimulation in etomoxir-treated UCP3(-/-)s versus WTs. Isoproterenol administration after pacing resulted in 75 % mortality in UCP3(-/-)s vs. 14 % in WTs. Our results argue against a protective role for UCP3 on skm metabolism under lipid overload, but suggest UCP3 to be crucial in prevention of arrhythmias upon lipid-challenged conditions.

Predicting the affinity of Farnesoid X Receptor ligands through a hierarchical ranking protocol: a D3R Grand Challenge 2 case study

NASA Astrophysics Data System (ADS)

Réau, Manon; Langenfeld, Florent; Zagury, Jean-François; Montes, Matthieu

2018-01-01

The Drug Design Data Resource (D3R) Grand Challenges are blind contests organized to assess the state-of-the-art methods accuracy in predicting binding modes and relative binding free energies of experimentally validated ligands for a given target. The second stage of the D3R Grand Challenge 2 (GC2) was focused on ranking 102 compounds according to their predicted affinity for Farnesoid X Receptor. In this task, our workflow was ranked 5th out of the 77 submissions in the structure-based category. Our strategy consisted in (1) a combination of molecular docking using AutoDock 4.2 and manual edition of available structures for binding poses generation using SeeSAR, (2) the use of HYDE scoring for pose selection, and (3) a hierarchical ranking using HYDE and MM/GBSA. In this report, we detail our pose generation and ligands ranking protocols and provide guidelines to be used in a prospective computer aided drug design program.

Challenges Facing 3-D Audio Display Design for Multimedia

NASA Technical Reports Server (NTRS)

Begault, Durand R.; Null, Cynthia H. (Technical Monitor)

1998-01-01

The challenges facing successful multimedia presentation depend largely on the expectations of the designer and end user for a given application. Perceptual limitations in distance, elevation and azimuth sound source simulation differ significantly between headphone and cross-talk cancellation loudspeaker listening and therefore must be considered. Simulation of an environmental context is desirable but the quality depends on processing resources and lack of interaction with the host acoustical environment. While techniques such as data reduction of head-related transfer functions have been used widely to improve simulation fidelity, another approach involves determining thresholds for environmental acoustic events. Psychoacoustic studies relevant to this approach are reviewed in consideration of multimedia applications

Docking pose selection by interaction pattern graph similarity: application to the D3R grand challenge 2015.

PubMed

Slynko, Inna; Da Silva, Franck; Bret, Guillaume; Rognan, Didier

2016-09-01

High affinity ligands for a given target tend to share key molecular interactions with important anchoring amino acids and therefore often present quite conserved interaction patterns. This simple concept was formalized in a topological knowledge-based scoring function (GRIM) for selecting the most appropriate docking poses from previously X-rayed interaction patterns. GRIM first converts protein-ligand atomic coordinates (docking poses) into a simple 3D graph describing the corresponding interaction pattern. In a second step, proposed graphs are compared to that found from template structures in the Protein Data Bank. Last, all docking poses are rescored according to an empirical score (GRIMscore) accounting for overlap of maximum common subgraphs. Taking the opportunity of the public D3R Grand Challenge 2015, GRIM was used to rescore docking poses for 36 ligands (6 HSP90α inhibitors, 30 MAP4K4 inhibitors) prior to the release of the corresponding protein-ligand X-ray structures. When applied to the HSP90α dataset, for which many protein-ligand X-ray structures are already available, GRIM provided very high quality solutions (mean rmsd = 1.06 Å, n = 6) as top-ranked poses, and significantly outperformed a state-of-the-art scoring function. In the case of MAP4K4 inhibitors, for which preexisting 3D knowledge is scarce and chemical diversity is much larger, the accuracy of GRIM poses decays (mean rmsd = 3.18 Å, n = 30) although GRIM still outperforms an energy-based scoring function. GRIM rescoring appears to be quite robust with comparison to the other approaches competing for the same challenge (42 submissions for the HSP90 dataset, 27 for the MAP4K4 dataset) as it ranked 3rd and 2nd respectively, for the two investigated datasets. The rescoring method is quite simple to implement, independent on a docking engine, and applicable to any target for which at least one holo X-ray structure is available.

Docking pose selection by interaction pattern graph similarity: application to the D3R grand challenge 2015

NASA Astrophysics Data System (ADS)

Slynko, Inna; Da Silva, Franck; Bret, Guillaume; Rognan, Didier

2016-09-01

High affinity ligands for a given target tend to share key molecular interactions with important anchoring amino acids and therefore often present quite conserved interaction patterns. This simple concept was formalized in a topological knowledge-based scoring function (GRIM) for selecting the most appropriate docking poses from previously X-rayed interaction patterns. GRIM first converts protein-ligand atomic coordinates (docking poses) into a simple 3D graph describing the corresponding interaction pattern. In a second step, proposed graphs are compared to that found from template structures in the Protein Data Bank. Last, all docking poses are rescored according to an empirical score (GRIMscore) accounting for overlap of maximum common subgraphs. Taking the opportunity of the public D3R Grand Challenge 2015, GRIM was used to rescore docking poses for 36 ligands (6 HSP90α inhibitors, 30 MAP4K4 inhibitors) prior to the release of the corresponding protein-ligand X-ray structures. When applied to the HSP90α dataset, for which many protein-ligand X-ray structures are already available, GRIM provided very high quality solutions (mean rmsd = 1.06 Å, n = 6) as top-ranked poses, and significantly outperformed a state-of-the-art scoring function. In the case of MAP4K4 inhibitors, for which preexisting 3D knowledge is scarce and chemical diversity is much larger, the accuracy of GRIM poses decays (mean rmsd = 3.18 Å, n = 30) although GRIM still outperforms an energy-based scoring function. GRIM rescoring appears to be quite robust with comparison to the other approaches competing for the same challenge (42 submissions for the HSP90 dataset, 27 for the MAP4K4 dataset) as it ranked 3rd and 2nd respectively, for the two investigated datasets. The rescoring method is quite simple to implement, independent on a docking engine, and applicable to any target for which at least one holo X-ray structure is available.

Vagal afferents contribute to exacerbated airway responses following ozone and allergen challenge.

PubMed

Schelegle, Edward S; Walby, William F

2012-05-31

Brown-Norway rats (n=113) sensitized and challenged with nDer f 1 allergen were used to examine the contribution of lung sensory nerves to ozone (O(3)) exacerbation of asthma. Prior to their third challenge rats inhaled 1.0ppm O(3) for 8h. There were three groups: (1) control; (2) vagus perineural capsaicin treatment (PCT) with or without hexamethonium; and (3) vagotomy. O(3) inhalation resulted in a significant increase in lung resistance (R(L)) and an exaggerated response to subsequent allergen challenge. PCT abolished the O(3)-induced increase in R(L) and significantly reduced the increase in R(L) induced by a subsequent allergen challenge, while hexamethonium treatment reestablished bronchoconstriction induced by allergen challenge. Vagotomy resulted in a significant increase in the bronchoconstriction induced by O(3) inhalation and subsequent challenge with allergen. In this model of O(3) exacerbation of asthma, vagal C-fibers initiate reflex bronchoconstriction, vagal myelinated fibers initiate reflex bronchodilation, and mediators released within the airway initiate bronchoconstriction. Copyright © 2012 Elsevier B.V. All rights reserved.

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-14

Members of team Mountaineers pose with officials from the 2014 NASA Centennial Challenges Sample Return Robot Challenge on Saturday, June 14, 2014 at Worcester Polytechnic Institute (WPI) in Worcester, Mass. Team Mountaineer was the only team to complete the level one challenge this year. Team Mountaineer members, from left (in blue shirts) are: Ryan Watson, Marvin Cheng, Scott Harper, Jarred Strader, Lucas Behrens, Yu Gu, Tanmay Mandal, Alexander Hypes, and Nick Ohi Challenge judges and competition staff (in white and green polo shirts) from left are: Sam Ortega, NASA Centennial Challenge program manager; Ken Stafford, challenge technical advisor, WPI; Colleen Shaver, challenge event manager, WPI. During the competition, teams were required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge was to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

Powder bed binder jet 3D printing of Inconel 718: Densification, microstructural evolution and challenges

DOE PAGES

Nandwana, Peeyush; Elliott, Amy M.; Siddel, Derek; ...

2017-01-03

Traditional manufacturing of Inconel 718 components from castings and thermomechanical processing routes involve extensive post processing and machining to attain the desired geometry. Additive manufacturing (AM) technologies including direct energy deposition (DED), selective laser melting (SLM), electron beam melting (EBM) and binder jet 3D printing (BJ3DP) can minimize scrap generation and reduce lead times. While there is extensive literature on the use of melting and solidification based AM technologies, there has been limited research on the use of binder jet 3D printing. In this paper, a brief review on binder jet additive manufacturing of Inconel 718 is presented. In addition,more » existing knowledge on sintering of Inconel 718 has been extended to binder jet 3D printing. We found that supersolidus liquid phase sintering (SLPS) is necessary to achieve full densification of Inconel 718. SLPS is sensitive to the feedstock chemistry that has a strong influence on the liquid volume fraction at the processing temperature. Based on these results, we discuss an empirical framework to determine the role of powder particle size and liquid volume fraction on sintering kinetics. In conclusion, the role of powder packing factor and binder saturation on microstructural evolution is discussed. The current challenges in the use of BJ3DP for fabrication of Inconel 718, as well as, extension to other metal systems, are presented.« less

Protracted downregulation of CX3CR1 on microglia of aged mice after lipopolysaccharide challenge

PubMed Central

Wynne, Angela M; Henry, Christopher J.; Huang, Yan; Cleland, Anthony; Godbout, Jonathan P.

2010-01-01

Fractalkine (CX3CL1) to fractalkine receptor (CX3CR1) interactions in the brain are involved in the modulation of microglial activation. Our recent findings indicate that there is microglial hyperactivity in the aged brain during an inflammatory challenge. The underlying cause of this amplified microglial response in the aged brain is unknown. Therefore, the purpose of this study was to determine the degree to which age-associated impairments of CX3CL1 and CX3CR1 in the brain contribute to exaggerated microglial activation after intraperitoneal (i.p.) injection of lipopolysaccharide (LPS). Here we show that CX3CL1 protein was reduced in the brain of aged (18–22 mo) BALB/c mice compared to adult (3–6 mo) controls. CX3CL1 protein, however, was unaltered by LPS injection. Next, CX3CR1 levels were determined in microglia (CD11b+/CD45low) isolated by Percoll-density gradient separation at 4 and 24 h after LPS injection. Flow cytometric and mRNA analyses of these microglia showed that LPS-injection caused a marked decrease of CX3CR1 and a simultaneous increase of IL-1β at 4 h after LPS injection. While surface expression of CX3CR1 was enhanced on microglia of adult mice by 24 h, it was still significantly downregulated on a subset of microglia from aged mice. This protracted reduction of CX3CR1 corresponded with a delayed recovery from sickness behavior, prolonged IL-1β induction, and decreased TGFβ expression in the aged brain. In the last set of studies BV2 microglia were used to determine effect of TGFβ on CX3CR1. These results showed that TGFβ enhanced CX3CR1 expression and attenuated the LPS-induced increase in IL-1β expression. PMID:20570721

The attenuated NYCBH vaccinia virus deleted for the immune evasion gene, E3L, completely protects mice against heterologous challenge with ectromelia virus.

PubMed

Denzler, Karen L; Schriewer, Jill; Parker, Scott; Werner, Chas; Hartzler, Hollyce; Hembrador, Ed; Huynh, Trung; Holechek, Susan; Buller, R M; Jacobs, Bertram L

2011-12-06

The New York City Board of Health (NYCBH) vaccinia virus (VACV) vaccine strain was deleted for the immune evasion gene, E3L, and tested for its pathogenicity and ability to protect mice from heterologous challenge with ectromelia virus (ECTV). NYCBHΔE3L was found to be highly attenuated for pathogenicity in a newborn mouse model and showed a similar attenuated phenotype as the NYVAC strain of vaccinia virus. Scarification with one or two doses of the attenuated NYCBHΔE3L was able to protect mice equally as well as NYCBH from death, weight loss, and viral spread to visceral organs. A single dose of NYCBHΔE3L resulted in low poxvirus-specific antibodies, and a second dose increased levels of poxvirus-specific antibodies to a level similar to that seen in animals vaccinated with a single dose of NYCBH. However, similar neutralizing antibody titers were observed following one or two doses of NYCBHΔE3L or NYCBH. Thus, NYCBHΔE3L shows potential as a candidate for a safer human smallpox vaccine since it protects mice from challenge with a heterologous poxvirus. Copyright © 2011 Elsevier Ltd. All rights reserved.

Temperature responses to infusion of electrolytes during exercise

NASA Technical Reports Server (NTRS)

Greenleaf, J. E.; Kozlowski, S.; Kaciuba-Uscilko, H.; Nazar, K.; Brzezinska, Z.

1975-01-01

Past studies on the influence of various metal ions on heat regulation in mammals are reviewed, and results of a study on the effect of Na and citrate in isotonic and hypertonic concentrations on temperature elevation during exercise in dogs are presented. Hypertonic administration of Na before or during treadmill running and dosis of citrate during treadmill running significantly raised core temperature over controls and isotonic cases. Thus the higher the plasma Na-osmotic concentration, the greater the inhibition of heat dissipation.

The merits of measuring challenge and hindrance appraisals.

PubMed

Searle, Ben J; Auton, Jaime C

2015-01-01

The challenge-hindrance framework has shown that challenge stressors (work characteristics associated with potential personal gain) tend to have positive outcomes, whereas hindrance stressors (those which obstruct goals) have negative outcomes. However, typical research methods assume that stressors allocated to these categories are appraised consistently by different people and across different situations. We validate new measures of challenge and hindrance appraisals and demonstrate their utility in stress research. We used a cross-sectional survey of American employees (Study 1, n = 333), a diary survey of Australian employees (Study 2, n = 241), and a survey of Australian college students whose performance was evaluated independently (Study 3, n = 350). Even after accounting for the effects of stressors, challenge and hindrance appraisals consistently explained unique variance in affective states, with indications that stressors have indirect effects via appraisals. Such effects were seen within- as well as between-participants (Study 2). Appraisals also had expected associations with specific coping behaviors (Study 1), while challenge appraisal was associated with task performance (Study 3). The scales of challenge and hindrance appraisals were psychometrically sound across multiple contexts. RESULTS highlight the merit of considering appraisal in stress research.

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-14

Sam Ortega, NASA program manager of Centennial Challenges, watches as robots attempt the rerun of the level one challenge during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Saturday, June 14, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-12

Sample Return Robot Challenge staff members confer before the team Survey robots makes it's attempt at the level two challenge during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Thursday, June 12, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

76 FR 41526 - Centennial Challenges 2011 Strong Tether Challenge

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-14

... NATIONAL AERONAUTICS AND SPACE ADMINISTRATION [Notice (11-063)] Centennial Challenges 2011 Strong... scheduled and teams that wish to compete may register. Centennial Challenges is a program of prize... NASA Centennial Challenges Program please visit: http://www.nasa.gov/challenges . General questions and...

Molecular docking performance evaluated on the D3R Grand Challenge 2015 drug-like ligand datasets

NASA Astrophysics Data System (ADS)

Selwa, Edithe; Martiny, Virginie Y.; Iorga, Bogdan I.

2016-09-01

The D3R Grand Challenge 2015 was focused on two protein targets: Heat Shock Protein 90 (HSP90) and Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 (MAP4K4). We used a protocol involving a preliminary analysis of the available data in PDB and PubChem BioAssay, and then a docking/scoring step using more computationally demanding parameters that were required to provide more reliable predictions. We could evidence that different docking software and scoring functions can behave differently on individual ligand datasets, and that the flexibility of specific binding site residues is a crucial element to provide good predictions.

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-11

Team KuuKulgur waits to begin the level one challenge during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Wednesday, June 11, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Wednesday, June 11, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-14

The NASA Centennial Challenges prize, level one, is presented to team Mountaineers for successfully completing level one of the NASA 2014 Sample Return Robot Challenge, from left, Ken Stafford, WPI Challenge technical advisor; Colleen Shaver, WPI Challenge Manager; Ryan Watson, Team Mountaineers; Marvin Cheng, Team Mountaineers; Alexander Hypes, Team Mountaineers; Jarred Strader, Team Mountaineers; Lucas Behrens, Team Mountaineers; Yu Gu, Team Mountaineers; Nick Ohi, Team Mountaineers; Dorothy Rasco, NASA Deputy Associate Administrator for the Space Technology Mission Directorate; Scott Harper, Team Mountaineers; Tanmay Mandal, Team Mountaineers; David Miller, NASA Chief Technologist; Sam Ortega, NASA Program Manager for Centennial Challenges, Saturday, June 14, 2014, at Worcester Polytechnic Institute (WPI) in Worcester, Mass. Team Mountaineers was the only team to complete the level one challenge. During the competition, teams were required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge was to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

78 FR 19742 - Centennial Challenges: 2014 Night Rover Challenge

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-02

... NATIONAL AERONAUTICS AND SPACE ADMINISTRATION [Notice 13-032] Centennial Challenges: 2014 Night... Centennial Challenges 2014 Night Rover Challenge. SUMMARY: This notice is issued in accordance with 51 U.S.C.... Centennial Challenges is a program of prize competitions to stimulate innovation in technologies of interest...

Concept and Design of a 3D Printed Support to Assist Hand Scanning for the Realization of Customized Orthosis.

PubMed

Baronio, Gabriele; Volonghi, Paola; Signoroni, Alberto

2017-01-01

In the rehabilitation field, the use of additive manufacturing techniques to realize customized orthoses is increasingly widespread. Obtaining a 3D model for the 3D printing phase can be done following different methodologies. We consider the creation of personalized upper limb orthoses, also including fingers, starting from the acquisition of the hand geometry through accurate 3D scanning. However, hand scanning procedure presents differences between healthy subjects and patients affected by pathologies that compromise upper limb functionality. In this work, we present the concept and design of a 3D printed support to assist hand scanning of such patients. The device, realized with FDM additive manufacturing techniques in ABS material, allows palmar acquisitions, and its design and test are motivated by the following needs: (1) immobilizing the hand of patients during the palmar scanning to reduce involuntary movements affecting the scanning quality and (2) keeping hands open and in a correct position, especially to contrast the high degree of hypertonicity of spastic subjects. The resulting device can be used indifferently for the right and the left hand; it is provided in four-dimensional sizes and may be also suitable as a palmar support for the acquisition of the dorsal side of the hand.

Concept and Design of a 3D Printed Support to Assist Hand Scanning for the Realization of Customized Orthosis

PubMed Central

Volonghi, Paola

2017-01-01

In the rehabilitation field, the use of additive manufacturing techniques to realize customized orthoses is increasingly widespread. Obtaining a 3D model for the 3D printing phase can be done following different methodologies. We consider the creation of personalized upper limb orthoses, also including fingers, starting from the acquisition of the hand geometry through accurate 3D scanning. However, hand scanning procedure presents differences between healthy subjects and patients affected by pathologies that compromise upper limb functionality. In this work, we present the concept and design of a 3D printed support to assist hand scanning of such patients. The device, realized with FDM additive manufacturing techniques in ABS material, allows palmar acquisitions, and its design and test are motivated by the following needs: (1) immobilizing the hand of patients during the palmar scanning to reduce involuntary movements affecting the scanning quality and (2) keeping hands open and in a correct position, especially to contrast the high degree of hypertonicity of spastic subjects. The resulting device can be used indifferently for the right and the left hand; it is provided in four-dimensional sizes and may be also suitable as a palmar support for the acquisition of the dorsal side of the hand. PMID:29234219

In Vitro Gluten Challenge Test for Celiac Disease Diagnosis.

PubMed

Khalesi, Maryam; Jafari, Seyed Ali; Kiani, Mohammadali; Picarelli, Antonio; Borghini, Raffaele; Sadeghi, Ramin; Eghtedar, Alireza; Ayatollahi, Hosein; Kianifar, Hamid R

2016-02-01

The in vitro gluten challenge test is an important diagnostic modality in celiac disease (CD), especially in patients who begin treatment with a gluten-free diet before adequate diagnostic workup or in cases with atypical CD. Available literature was reviewed regarding the accuracy of the in vitro gluten challenge test for CD diagnosis. MEDLINE, Scopus, and Google Scholar were searched, and studies that used serology and bowel biopsy as the criterion standard for diagnosis were included in our study. Data on authors, publication year, characteristics of the patient and control groups, patients' diet, duration of the gluten challenge test, histology findings, endomysial antibody (EMA) and anti-tissue transglutaminase (tTG) levels, CD markers, and intercellular cell adhesion molecule-1, and human leukocyte antigens before and after the gluten challenge test were extracted. Overall, 15 studies were included in this meta-analysis. Pooled sensitivity %/specificity % was 84/99 for EMA after the challenge, 52/96 for EMA without the challenge, 95.5/98.3 for anti-tTG after the challenge, and 95.1/98.3 for anti-tTG without the challenge test. Sensitivity/specificity for immunological markers were 89/97 for the percentage of CD25⁺-lamina propria lymphocytes, 96/91 for the percentage of CD3⁺-lamina propria lymphocytes, and 96.1/85.7 for the percentage of intercellular cell adhesion molecule-1-lamina propria lymphocytes. The factors that increased the sensitivity of EMA were longer test duration, and the evaluation of patients on a gluten-containing diet or short-term gluten-free diet. The in vitro gluten challenge test can be a useful part of the diagnostic workup of CD, rather than only a model to evaluate its mechanisms.

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-12

Russel Howe of team Survey speaks with Sample Return Robot Challenge staff members after the team's robot failed to leave the starting platform during it's attempt at the level two challenge during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Thursday, June 12, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

Nanoparticle Vaccines Encompassing the Respiratory Syncytial Virus (RSV) G Protein CX3C Chemokine Motif Induce Robust Immunity Protecting from Challenge and Disease

PubMed Central

Jorquera, Patricia A.; Choi, Youngjoo; Oakley, Katie E.; Powell, Thomas J.; Boyd, James G.; Palath, Naveen; Haynes, Lia M.; Anderson, Larry J.; Tripp, Ralph A.

2013-01-01

Nanoparticle vaccines were produced using layer-by-layer fabrication and incorporating respiratory syncytial virus (RSV) G protein polypeptides comprising the CX3C chemokine motif. BALB/c mice immunized with G protein nanoparticle vaccines produced a neutralizing antibody response that inhibited RSV replication in the lungs following RSV challenge. ELISPOT analysis showed that G nanoparticle vaccinated mice had increased levels of RSV G protein-specific IL-4 and IFN-γ secreting cells compared to controls following RSV challenge. Remarkably, RSV challenge of G protein nanoparticle vaccinated mice resulted in increased RSV M2-specific IL-4 and IFN-γ secreting T cells, and increased M2-specific H-2Kd-tetramer positive CD8+ T cells in the lungs compared to controls. Cell type analysis showed vaccination was not associated with increased pulmonary eosinophilia following RSV challenge. These results demonstrate that vaccination of mice with the RSV G protein nanoparticle vaccines induces a potent neutralizing antibody response, increased G protein- and M2- specific T cell responses, and a reduction in RSV disease pathogenesis. PMID:24040360

Metformin, an AMPK activator, stimulates the phosphorylation of aquaporin 2 and urea transporter A1 in inner medullary collecting ducts.

PubMed

Klein, Janet D; Wang, Yanhua; Blount, Mitsi A; Molina, Patrick A; LaRocque, Lauren M; Ruiz, Joseph A; Sands, Jeff M

2016-05-15

Nephrogenic diabetes insipidus (NDI) is characterized by production of very large quantities of dilute urine due to an inability of the kidney to respond to vasopressin. Congenital NDI results from mutations in the type 2 vasopressin receptor (V2R) in ∼90% of families. These patients do not have mutations in aquaporin-2 (AQP2) or urea transporter UT-A1 (UT-A1). We tested adenosine monophosphate kinase (AMPK) since it is known to phosphorylate another vasopressin-sensitive transporter, NKCC2 (Na-K-2Cl cotransporter). We found AMPK expressed in rat inner medulla (IM). AMPK directly phosphorylated AQP2 and UT-A1 in vitro. Metformin, an AMPK activator, increased phosphorylation of both AQP2 and UT-A1 in rat inner medullary collecting ducts (IMCDs). Metformin increased the apical plasma membrane accumulation of AQP2, but not UT-A1, in rat IM. Metformin increased both osmotic water permeability and urea permeability in perfused rat terminal IMCDs. These findings suggest that metformin increases osmotic water permeability by increasing AQP2 accumulation in the apical plasma membrane but increases urea permeability by activating UT-A1 already present in the membrane. Lastly, metformin increased urine osmolality in mice lacking a V2R, a mouse model of congenital NDI. We conclude that AMPK activation by metformin mimics many of the mechanisms by which vasopressin increases urine-concentrating ability. These findings suggest that metformin may be a novel therapeutic option for congenital NDI due to V2R mutations. Copyright © 2016 the American Physiological Society.

Metformin, an AMPK activator, stimulates the phosphorylation of aquaporin 2 and urea transporter A1 in inner medullary collecting ducts

PubMed Central

Wang, Yanhua; Blount, Mitsi A.; Molina, Patrick A.; LaRocque, Lauren M.; Ruiz, Joseph A.

2016-01-01

Nephrogenic diabetes insipidus (NDI) is characterized by production of very large quantities of dilute urine due to an inability of the kidney to respond to vasopressin. Congenital NDI results from mutations in the type 2 vasopressin receptor (V2R) in ∼90% of families. These patients do not have mutations in aquaporin-2 (AQP2) or urea transporter UT-A1 (UT-A1). We tested adenosine monophosphate kinase (AMPK) since it is known to phosphorylate another vasopressin-sensitive transporter, NKCC2 (Na-K-2Cl cotransporter). We found AMPK expressed in rat inner medulla (IM). AMPK directly phosphorylated AQP2 and UT-A1 in vitro. Metformin, an AMPK activator, increased phosphorylation of both AQP2 and UT-A1 in rat inner medullary collecting ducts (IMCDs). Metformin increased the apical plasma membrane accumulation of AQP2, but not UT-A1, in rat IM. Metformin increased both osmotic water permeability and urea permeability in perfused rat terminal IMCDs. These findings suggest that metformin increases osmotic water permeability by increasing AQP2 accumulation in the apical plasma membrane but increases urea permeability by activating UT-A1 already present in the membrane. Lastly, metformin increased urine osmolality in mice lacking a V2R, a mouse model of congenital NDI. We conclude that AMPK activation by metformin mimics many of the mechanisms by which vasopressin increases urine-concentrating ability. These findings suggest that metformin may be a novel therapeutic option for congenital NDI due to V2R mutations. PMID:26962099

Workflows and performances in the ranking prediction of 2016 D3R Grand Challenge 2: lessons learned from a collaborative effort.

PubMed

Gao, Ying-Duo; Hu, Yuan; Crespo, Alejandro; Wang, Deping; Armacost, Kira A; Fells, James I; Fradera, Xavier; Wang, Hongwu; Wang, Huijun; Sherborne, Brad; Verras, Andreas; Peng, Zhengwei

2018-01-01

The 2016 D3R Grand Challenge 2 includes both pose and affinity or ranking predictions. This article is focused exclusively on affinity predictions submitted to the D3R challenge from a collaborative effort of the modeling and informatics group. Our submissions include ranking of 102 ligands covering 4 different chemotypes against the FXR ligand binding domain structure, and the relative binding affinity predictions of the two designated free energy subsets of 15 and 18 compounds. Using all the complex structures prepared in the same way allowed us to cover many types of workflows and compare their performances effectively. We evaluated typical workflows used in our daily structure-based design modeling support, which include docking scores, force field-based scores, QM/MM, MMGBSA, MD-MMGBSA, and MacroModel interaction energy estimations. The best performing methods for the two free energy subsets are discussed. Our results suggest that affinity ranking still remains very challenging; that the knowledge of more structural information does not necessarily yield more accurate predictions; and that visual inspection and human intervention are considerably important for ranking. Knowledge of the mode of action and protein flexibility along with visualization tools that depict polar and hydrophobic maps are very useful for visual inspection. QM/MM-based workflows were found to be powerful in affinity ranking and are encouraged to be applied more often. The standardized input and output enable systematic analysis and support methodology development and improvement for high level blinded predictions.

Workflows and performances in the ranking prediction of 2016 D3R Grand Challenge 2: lessons learned from a collaborative effort

NASA Astrophysics Data System (ADS)

Gao, Ying-Duo; Hu, Yuan; Crespo, Alejandro; Wang, Deping; Armacost, Kira A.; Fells, James I.; Fradera, Xavier; Wang, Hongwu; Wang, Huijun; Sherborne, Brad; Verras, Andreas; Peng, Zhengwei

2018-01-01

The 2016 D3R Grand Challenge 2 includes both pose and affinity or ranking predictions. This article is focused exclusively on affinity predictions submitted to the D3R challenge from a collaborative effort of the modeling and informatics group. Our submissions include ranking of 102 ligands covering 4 different chemotypes against the FXR ligand binding domain structure, and the relative binding affinity predictions of the two designated free energy subsets of 15 and 18 compounds. Using all the complex structures prepared in the same way allowed us to cover many types of workflows and compare their performances effectively. We evaluated typical workflows used in our daily structure-based design modeling support, which include docking scores, force field-based scores, QM/MM, MMGBSA, MD-MMGBSA, and MacroModel interaction energy estimations. The best performing methods for the two free energy subsets are discussed. Our results suggest that affinity ranking still remains very challenging; that the knowledge of more structural information does not necessarily yield more accurate predictions; and that visual inspection and human intervention are considerably important for ranking. Knowledge of the mode of action and protein flexibility along with visualization tools that depict polar and hydrophobic maps are very useful for visual inspection. QM/MM-based workflows were found to be powerful in affinity ranking and are encouraged to be applied more often. The standardized input and output enable systematic analysis and support methodology development and improvement for high level blinded predictions.

Experimental muscle pain challenges the postural stability during quiet stance and unexpected posture perturbation.

PubMed

Hirata, Rogério Pessoto; Ervilha, Ulysses Fernandes; Arendt-Nielsen, Lars; Graven-Nielsen, Thomas

2011-08-01

Musculoskeletal pain impairs postural control and stability. Nine subjects stood as quietly as possible on a moveable force platform before, during, and after experimental pain in the right leg muscles. A moveable force platform was used to measure the center of pressure and provided unexpected perturbations. Lower limb muscle activity, joint angles, and foot pressure distributions were measured. Hypertonic saline was used to induce pain in the vastus lateralis, vastus medialis, or biceps femoris muscle of the right leg. Compared to baseline and control sessions, pain in the knee extensor muscles during quiet standing evoked: 1) larger sway area, greater medial-lateral center of pressure displacement and higher speed (P < .05); 2) increased sway displacement in the anterior-posterior direction (P < .05); and 3) increased electromyography (EMG) activity for left tibialis anterior and left erector spinae muscles (P < .05). Pain provoked longer time to return to an equilibrium posture after forward EMG activity for, and pain in vastus medialis muscle decreased the time for the maximum hip flexion during this perturbation (P < .05). These results show that muscle pain impairs postural stability during quiet standing and after unexpected perturbation, which suggest that people suffering from leg muscle pain are more vulnerable to falls. This article presents the acute responses to leg muscle pain on the postural control. This measure could potentially help clinicians who seek to assess how pain responses may contribute to patient's postural control and stability during quiet standing and after recovering from unexpected perturbations. Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.

Induction of indolamine 2,3-dioxygenase and kynurenine 3-monooxygenase in rat brain following a systemic inflammatory challenge: a role for IFN-gamma?

PubMed

Connor, Thomas J; Starr, Neasa; O'Sullivan, Joan B; Harkin, Andrew

2008-08-15

Inflammation-mediated dysregulation of the kynurenine pathway has been implicated as a contributor to a number of major brain disorders. Consequently, we examined the impact of a systemic inflammatory challenge on kynurenine pathway enzyme expression in rat brain. Indoleamine 2,3-dioxygenase (IDO) expression was induced in cortex and hippocampus following systemic lipopolysaccharide (LPS) administration. Whilst IDO expression was paralleled by increased circulating interferon (IFN)-gamma concentrations, IFN-gamma expression in the brain was only modestly altered following LPS administration. In contrast, induction of IDO was associated with increased central tumour necrosis factor (TNF)-alpha and interleukin (IL)-6 expression. Similarly, in cultured glial cells LPS-induced IDO expression was accompanied by increased TNF-alpha and IL-6 expression, whereas IFN-gamma was not detectable. These findings indicate that IFN-gamma is not required for LPS-induced IDO expression in brain. A robust increase in kynurenine-3-monooxygenase (KMO) expression was observed in rat brain 24h post LPS, without any change in kynurenine aminotransferase II (KAT II) expression. In addition, we report that constitutive expression of KAT II is approximately 8-fold higher than KMO in cortex and 20-fold higher in hippocampus. Similarly, in glial cells constitutive expression of KAT II was approximately 16-fold higher than KMO, and expression of KMO but not KAT II was induced by LPS. These data are the first to demonstrate that a systemic inflammatory challenge stimulates KMO expression in brain; a situation that is likely to favour kynurenine metabolism in a neurotoxic direction. However, our observation that expression of KAT II is much higher than KMO in rat brain is likely to counteract potential neurotoxicity that could arise from KMO induction following an acute inflammation.

Comparison of salt with low-dose furosemide and carperitide for treating acute decompensated heart failure: a single-center retrospective cohort study.

PubMed

Okuhara, Yoshitaka; Hirotani, Shinichi; Ando, Tomotaka; Nishimura, Koichi; Orihara, Yoshiyuki; Komamura, Kazuo; Naito, Yoshiro; Mano, Toshiaki; Masuyama, Tohru

2017-04-01

Hypertonic saline with furosemide has been proposed for a long time as an effective therapeutic option for the treatment of acute decompensated heart failure (ADHF). We previously reported the efficacy of continuous infusion of 1.7 % hypertonic saline plus low-dose furosemide in treatment for ADHF. Although this therapeutic strategy can be a useful option for effective decongestion in treatment for ADHF, there is no study that assesses the effect and safety of saline supplementation compared with standard therapy in Japan. The aim of this study was to investigate the efficacy, safety, and cost-effectiveness of 1.7 % hypertonic saline plus low-dose furosemide infusion compared with carperitide. We compared clinical outcomes, adverse events, and cost for patients receiving carperitide (carperitide group) with those for patients receiving 1.7 % hypertonic saline plus low-dose furosemide (salt group) during the initial hospitalization for ADHF. The cost analysis was performed on the basis of the previous report about cost-effectiveness of acute heart failure. A total of 175 ADHF patients received either carperitide (n = 111) or 1.7 % hypertonic saline plus low-dose furosemide infusion (n = 64) as initial treatment. There were no differences in length of hospital stay (27 ± 19 vs. 25 ± 16 day, p = 0.170) and infusion period (7.2 ± 6.1 vs. 8.4 ± 7.5 day, p = 0.474) between the two groups. The incidence of rehospitalization did not differ at 1 month (7.6 vs. 6.6 %, p = 1.000) and 1 year (36.8 vs. 37.7 %, p = 0.907) between the two groups. The Kaplan-Meier curves revealed no significant difference for 1 year all-cause mortality between the two groups (log-rank, p = 0.724). The single hospitalization cost was 95,314 yen lower and the yearly hospitalization cost 125,628 yen lower in the salt group compared with the carperitide group. Thus, intravenous 1.7 % hypertonic saline plus low-dose furosemide infusion is as effective as

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-12

Sam Ortega, NASA program manager for Centennial Challenges, is seen during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Thursday, June 12, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-11

The Retrievers team robot is seen as it attempts the level one challenge the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Wednesday, June 11, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

Comparison of the effects of 7.2% hypertonic saline and 20% mannitol on whole blood coagulation and platelet function in dogs with suspected intracranial hypertension - a pilot study.

PubMed

Yozova, Ivayla D; Howard, Judith; Henke, Diana; Dirkmann, Daniel; Adamik, Katja N

2017-06-19

Hyperosmolar therapy with either mannitol or hypertonic saline (HTS) is commonly used in the treatment of intracranial hypertension (ICH). In vitro data indicate that both mannitol and HTS affect coagulation and platelet function in dogs. The aim of this study was to compare the effects of 20% mannitol and 7.2% HTS on whole blood coagulation using rotational thromboelastometry (ROTEM®) and platelet function using a platelet function analyzer (PFA®) in dogs with suspected ICH. Thirty client-owned dogs with suspected ICH needing osmotherapy were randomized to receive either 20% mannitol (5 ml/kg IV over 15 min) or 7.2% HTS (4 ml/kg IV over 5 min). ROTEM® (EXTEM® and FIBTEM® assays) and PFA® analyses (collagen/ADP cartridges) were performed before (T 0 ), as well as 5 (T 5 ), 60 (T 60 ) and 120 (T 120 ) minutes after administration of HTS or mannitol. Data at T 5 , T 60 and T 120 were analyzed as a percentage of values at T 0 for comparison between groups, and as absolute values for comparison between time points, respectively. No significant difference was found between the groups for the percentage change of any parameter at any time point except for FIBTEM® clotting time. Within each group, no significant difference was found between time points for any parameter except for FIBTEM® clotting time in the HTS group, and EXTEM® and FIBTEM® maximum clot firmness in the mannitol group. Median ROTEM® values lay within institutional reference intervals in both groups at all time points, whereas median PFA® values were above the reference intervals at T 5 (both groups) and T 60 (HTS group). Using currently recommended doses, mannitol and HTS do not differ in their effects on whole blood coagulation and platelet function in dogs with suspected ICH. Moreover, no relevant impairment of whole blood coagulation was found following treatment with either solution, whereas a short-lived impairment of platelet function was found after both solutions.

Exploring design features for enhancing players' challenge in strategy games.

PubMed

Hsu, Shang Hwa; Wen, Ming-Hui; Wu, Muh-Cherng

2007-06-01

This paper examines how to make a player feel more challenged in a strategic computer game. It is hypothesized that information availability and resource advantage affect play difficulty, which in turn affects the challenge experienced. The difficulty of play can be defined in terms of the mental workload that players experience and the physical effort that players exert. Forty-five male college and graduate students participated in a 3 x 3 (information availability x resource advantage) between-subjects factorial design experiment. This experiment measured player mental workload, physical effort, and challenge. The results indicate that information availability affects player mental workload, and resource advantage affects levels of player physical effort, respectively. Moreover, the relationship between mental workload and challenge was found to be an inverted U-shaped curve; in other words, too much or too little mental workload may decrease player challenge. The relationship between physical effort and challenge exhibited similar characteristics.

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-12

The team Survey robot retrieves a sample during a demonstration of the level two challenge at the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Thursday, June 12, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-14

The University of California Santa Cruz Rover Team prepares their rover for the rerun of the level one challenge during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Saturday, June 14, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-14

Team Cephal's robot is seen on the starting platform during a rerun of the level one challenge at the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Saturday, June 14, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-14

A robot from the Intrepid Systems team is seen during the rerun of the level one challenge during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Saturday, June 14, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-11

A team KuuKulgur robot is seen as it begins the level one challenge during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Wednesday, June 11, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-11

The team Mountaineers robot is seen as it attempts the level one challenge during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Wednesday, June 11, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-11

The Stellar Automation Systems team poses for a picture with their robot after attempting the level one challenge during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Wednesday, June 11, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-12

The team Survey robot is seen as it conducts a demonstration of the level two challenge during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Thursday, June 12, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-11

All four of team KuuKulgur's robots are seen as they attempt the level one challenge during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Wednesday, June 11, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-12

Spectators watch as the team Survey robot conducts a demonstration of the level two challenge during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Thursday, June 12, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-11

Team Middleman's robot, Ro-Bear, is seen as it starts the level one challenge during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Wednesday, June 11, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-14

The team Mountaineers robot is seen after picking up the sample during a rerun of the level one challenge at the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Saturday, June 14, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-14

Two of team KuuKulgur's robots are seen as they attempt a rerun of the level one challenge during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Saturday, June 14, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-14

A robot from the University of Waterloo Robotics Team is seen during the rerun of the level one challenge during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Saturday, June 14, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-12

Members of team Survey follow their robot as it conducts a demonstration of the level two challenge during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Thursday, June 12, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-11

The entrance to Institute Park is seen during the level one challenge as during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Wednesday, June 11, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-14

Sam Ortega, NASA Centennial Challenges Program Manager, speaks at a breakfast opening the TouchTomorrow Festival, held in conjunction with the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Saturday, June 14, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-11

A team KuuKulgur robot approaches the sample as it attempts the level one challenge during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Wednesday, June 11, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-12

The team survey robot is seen on the starting platform before begging it's attempt at the level two challenge during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Thursday, June 12, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-11

The Mountaineers team from West Virginia University, watches as their robot attempts the level one challenge during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Wednesday, June 11, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-12

The team Survey robot is seen as it conducts a demonstration of the level two challenge at the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Thursday, June 12, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-12

Team Survey's robot is seen as it conducts a demonstration of the level two challenge during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Thursday, June 12, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

Online Learning: Addressing Challenges and Seizing Opportunities. Oregon

ERIC Educational Resources Information Center

Alliance for Excellent Education, 2010

2010-01-01

America's K-12 education system faces three significant challenges: (1) increased global demands for skilled workers, (2) significant financial shortfalls, and (3) a looming teacher shortage. Independently, these factors present significant challenges for U.S. schools. In combination, they create a national imperative for swift action to create a…

Online Learning: Addressing Challenges and Seizing Opportunities. Minnesota

ERIC Educational Resources Information Center

Alliance for Excellent Education, 2010

2010-01-01

America's K-12 education system faces three significant challenges: (1) increased global demands for skilled workers, (2) significant financial shortfalls, and (3) a looming teacher shortage. Independently, these factors present significant challenges for U.S. schools. In combination, they create a national imperative for swift action to create a…

Online Learning: Addressing Challenges and Seizing Opportunities. Hawaii

ERIC Educational Resources Information Center

Alliance for Excellent Education, 2010

2010-01-01

America's K-12 education system faces three significant challenges: (1) increased global demands for skilled workers, (2) significant financial shortfalls, and (3) a looming teacher shortage. Independently, these factors present significant challenges for U.S. schools. In combination, they create a national imperative for swift action to create a…

Online Learning: Addressing Challenges and Seizing Opportunities. Idaho

ERIC Educational Resources Information Center

Alliance for Excellent Education, 2010

2010-01-01

America's K-12 education system faces three significant challenges: (1) increased global demands for skilled workers, (2) significant financial shortfalls, and (3) a looming teacher shortage. Independently, these factors present significant challenges for U.S. schools. In combination, they create a national imperative for swift action to create a…

Online Learning: Addressing Challenges and Seizing Opportunities. Wisconsin

ERIC Educational Resources Information Center

Alliance for Excellent Education, 2010

2010-01-01

America's K-12 education system faces three significant challenges: (1) increased global demands for skilled workers, (2) significant financial shortfalls, and (3) a looming teacher shortage. Independently, these factors present significant challenges for U.S. schools. In combination, they create a national imperative for swift action to create a…

5.3 Global challenges in research and strategic planning.

PubMed

Baum, Bruce J; Scott, John; Bickel, Matthias; Gombos, Giorgio; Greenspan, John S; Guo, Wei; Park, No-Hee; Purdell-Lewis, David; Ranney, Richard; Schwarz, Eli; Seymour, Greg; Uoshima, Katsumi

2002-01-01

Health sciences research is experiencing dramatic progress. How can dental schools throughout the world best make these research advances relevant for dental students, as well as providing them with the means to assess and utilize the research advances that will occur in the future? This complex question presents a critical challenge to the dental educational community. Research is clearly integral to the mission of dental education. By providing dental students with active learning strategies, dental educators can inculcate the ability for independent scientific thinking and thereby develop reflective as well as technically competent practitioners. However, there is a shortage of well-trained individuals to fill faculty and research positions in certain parts of the world. Global networks for mutual information exchange are imperative to overcome resource limitations in individual institutions, as is dedicated funding for research in the dental educational setting.

Osmotic regulation of myo-inositol uptake in primary astrocyte cultures.

PubMed

Isaacks, R E; Bender, A S; Kim, C Y; Prieto, N M; Norenberg, M D

1994-03-01

Uptake of myo-inositol by astrocytes in hypertonic medium (440 mosm/kg H2O) was increased near 3-fold after incubation for 24 hours, which continued for 72 hours, as compared with the uptake by cells cultured in isotonic medium (38 nmoles/mg protein). myo-Inositol uptake by astrocytes cultured in hypotonic medium (180 mosm/kg H2O) for periods up to 72 hours was reduced by 74% to 8 to 10 nmoles/mg protein. Astrocytes incubated in either hypotonic or hypertonic medium for 24 hours and then placed in isotonic medium reversed the initial down- or up-regulation of uptake. Activation of chronic RVD and RVI correlates with regulation of myo-inositol uptake. A 30 to 40 mosm/kg H2O deviation from physiological osmolality can influence myo-inositol homeostasis. The intracellular content of myo-inositol in astrocytes in isotonic medium was 25.6 +/- 1.3 micrograms/mg protein (28 mM). This level of myo-inositol is sufficient for this compound to function as an osmoregulator in primary astrocytes and it is likely to contribute to the maintenance of brain volume.

Nurse managers' challenges in project management.

PubMed

Suhonen, Marjo; Paasivaara, Leena

2011-11-01

To analyse the challenges that nurse managers meet in project management. Project management done by nurse managers has a significant role in the success of projects conducted in work units. The data were collected by open interviews (n = 14). The participants were nurse managers, nurses and public health nurses. Data analysis was carried out using qualitative content analysis. The three main challenges nurse managers faced in project management in health-care work units were: (1) apathetic organization and management, (2) paralysed work community and (3) cooperation between individuals being discouraged. Nurse managers' challenges in project management can be viewed from the perspective of the following paradoxes: (1) keeping up projects-ensuring patient care, (2) enthusiastic management-effective management of daily work and (3) supporting the work of a multiprofessional team-leadership of individual employees. It is important for nurse managers to learn to relate these paradoxes to one another in a positive way. Further research is needed, focusing on nurse managers' ability to promote workplace spirituality, nurse managers' emotional intelligence and their enthusiasm in small projects. © 2011 Blackwell Publishing Ltd.

Occupational Resources: Career Information. CHOICE (Challenging Options in Career Education). [Grade 3].

ERIC Educational Resources Information Center

Mid-Hudson Migrant Education Center, New Paltz, NY.

Designed to teach migrant students about the world of work and how academic subjects relate to jobs and careers, this illustrated CHOICE (Challenging Options in Career Education) Occupational Resources text provides career and job information and basic job market entry skills information for junior and senior high school students written at a…

Corneal Sensitivity Following Lacrimal Gland Excision in the Rat

PubMed Central

Meng, Ian D.; Barton, Stephen T.; Mecum, Neal E.; Kurose, Masayuki

2015-01-01

Purpose. Dry eye disease (DED) produces ocular pain and irritation, yet a detailed characterization of ocular sensitivity in a preclinical model of DED is lacking. The aim of the present study was to assess nociceptive behaviors in an aqueous tear deficiency model of DED in the rat. Methods. Spontaneous blinking, corneal mechanical thresholds, and eye wipe behaviors elicited by hypertonic saline (5.0 M) were examined over a period of 8 weeks following the unilateral excision of either the exorbital lacrimal gland or of the exorbital and infraorbital lacrimal glands, and in sham surgery controls. The effect of topical proparacaine on spontaneous blinking and of systemic morphine (0.5–3.0 mg/kg, subcutaneous [SC]) on spontaneous blinking and eye wipe responses were also examined. Results. Lacrimal gland excision resulted in mechanical hypersensitivity and an increase in spontaneous blinking in the ipsilateral eye over an 8-week period that was more pronounced after infra- and exorbital gland excision. The time spent eye wiping was also enhanced in response to hypertonic saline (5.0 M) at both 1- and 8-week time-points, but only in infra- and exorbital gland excised animals. Morphine attenuated spontaneous blinking, and the response to hypertonic saline in dry eye animals and topical proparacaine application reduced spontaneous blinking down to control levels. Conclusions. These results indicate that aqueous tear deficiency produces hypersensitivity in the rat cornea. In addition, the increase in spontaneous blinks and their reduction by morphine and topical anesthesia indicate the presence of persistent irritation elicited by the activation of corneal nociceptors. PMID:26024120

Chemical renal denervation in the rat.

PubMed

Consigny, Paul M; Davalian, Dariush; Donn, Rosy; Hu, Jie; Rieser, Matthew; Stolarik, Deanne

2014-02-01

The recent success of renal denervation in lowering blood pressure in drug-resistant hypertensive patients has stimulated interest in developing novel approaches to renal denervation including local drug/chemical delivery. The purpose of this study was to develop a rat model in which depletion of renal norepinephrine (NE) could be used to determine the efficacy of renal denervation after the delivery of a chemical to the periadventitial space of the renal artery. Renal denervation was performed on a single renal artery of 90 rats (n = 6 rats/group). The first study determined the time course of renal denervation after surgical stripping of a renal artery plus the topical application of phenol in alcohol. The second study determined the efficacy of periadventitial delivery of hypertonic saline, guanethidine, and salicylic acid. The final study determined the dose-response relationship for paclitaxel. In all studies, renal NE content was determined by liquid chromatography-mass spectrometry. Renal NE was depleted 3 and 7 days after surgical denervation. Renal NE was also depleted by periadventitial delivery of all agents tested (hypertonic saline, salicylic acid, guanethidine, and paclitaxel). A dose response was observed after the application of 150 μL of 10(-5) M through 10(-2) M paclitaxel. We developed a rat model in which depletion of renal NE was used to determine the efficacy of renal denervation after perivascular renal artery drug/chemical delivery. We validated this model by demonstrating the efficacy of the neurotoxic agents hypertonic saline, salicylic acid, and guanethidine and increasing doses of paclitaxel.

Effect of drink carbohydrate content on postexercise gastric emptying, rehydration, and the calculation of net fluid balance.

PubMed

Clayton, David J; Evans, Gethin H; James, Lewis J

2014-02-01

The purpose of this study was to examine the gastric emptying and rehydration effects of hypotonic and hypertonic glucose-electrolyte drinks after exercise-induced dehydration. Eight healthy males lost ~1.8% body mass by intermittent cycling and rehydrated (150% of body mass loss) with a hypotonic 2% (2% trial) or a hypertonic 10% (10% trial) glucose-electrolyte drink over 60 min. Blood and urine samples were taken at preexercise, postexercise, and 60, 120, 180, and 240 min postexercise. Gastric and test drink volume were determined 15, 30, 45, 60, 90, and 120 min postexercise. At the end of the gastric sampling period 0.3% (2% trial) and 42.1% (10% trial; p < .001) of the drinks remained in the stomach. Plasma volume was lower (p < .01) and serum osmolality was greater (p < .001) at 60 and 120 min during the 10% trial. At 240 min, 52% (2% trial) and 64% (10% trial; p < .001) of the drinks were retained. Net fluid balance was greater from 120 min during the 10% trial (p < .001). When net fluid balance was corrected for the volume of fluid in the stomach, it was greater at 60 and 120 min during the 2% trial (p < .001). These results suggest that the reduced urine output following ingestion of a hypertonic rehydration drink might be mediated by a slower rate of gastric emptying, but the slow gastric emptying of such solutions makes rehydration efficiency difficult to determine in the hours immediately after drinking, compromising the calculation of net fluid balance.

Impact of dehydration on the forebrain preoptic recess walls in the mudskipper, Periophthalmus modestus: a possible locus for the center of thirst.

PubMed

Hamasaki, Sawako; Mukuda, Takao; Kaidoh, Toshiyuki; Yoshida, Masayuki; Uematsu, Kazumasa

2016-10-01

The forebrain lamina terminalis has not yet been examined for the role of osmosensing in teleosts, although the thirst center is well known to be present in this vascular permeable forebrain region in mammals. Here, we examined vascular permeability and neuronal responsiveness to dehydration in the lamina terminalis of the mudskipper, a euryhaline goby. Evans blue and N-hydroxysulfosuccinimide-biotin both bind to blood proteins, and are impermeable to the blood-brain barrier. Intraperitoneal injection of these probes stained the walls of the preoptic recess (PR) of the third ventricle, indicating increased vascular permeability in this region. When mudskippers kept in isotonic brackish water (ca. 11 psu) were challenged to seawater (ca. 34 psu) for 3 h, body water content showed a 1 % decrease, compared with mudskippers without hypertonic challenge. Simultaneously, the number of immunohistochemically identified cFos-expressing neurons in the anterior parvocellular preoptic nucleus (PPa) of the PR walls increased in a site-specific manner by approximately 1.6-fold compared with controls. Thus, these findings indicate that PPa neurons are activated, following dehydration in mudskippers. Taken together, the vascularly permeable PR walls may be involved in osmosensing, as in the mammalian thirst center.

The Growth of Neurosurgery in East Africa: Challenges.

PubMed

Santos, Maria M; Qureshi, Mubashir M; Budohoski, Karol P; Mangat, Halinder S; Ngerageza, Japhet G; Schöller, Karsten; Shabani, Hamisi K; Zubkov, Micaella R; Härtl, Roger

2018-05-01

As the second of 3 articles in this series, the aim of this article is to provide readers with an understanding of the development of neurosurgery in East Africa (foundations), the challenges that arise in providing neurosurgical care in developing countries (challenges), and an overview of traditional and novel approaches to overcoming these challenges and improving health care in the region (innovations). Recognizing the challenges that need to be addressed is the first step to implementing efficient and qualified surgery delivery systems in low- and middle-income countries. We reviewed the major challenges facing health care in East Africa and grouped them into 5 categories: 1) burden of surgical disease and workforce crisis; 2) global health view of surgery as "the neglected stepchild"; 3) need for recognizing the surgical system as an interdependent network and importance of organizational and equipment deficits; 4) lack of education in the community, failure of primary care systems, and net result of overwhelming tertiary care systems; 5) personal and professional burnout as well as brain drain of promising human resources from low- and middle-income countries in East Africa and similar regions across the world. Each major challenge was detailed and analyzed by authors who have worked or are currently working in the region, providing a personal perspective. Copyright © 2018. Published by Elsevier Inc.

The Eighth Industrial Fluids Properties Simulation Challenge

PubMed Central

Schultz, Nathan E.; Ahmad, Riaz; Brennan, John K.; Frankel, Kevin A.; Moore, Jonathan D.; Moore, Joshua D.; Mountain, Raymond D.; Ross, Richard B.; Thommes, Matthias; Shen, Vincent K.; Siderius, Daniel W.; Smith, Kenneth D.

2016-01-01

The goal of the eighth industrial fluid properties simulation challenge was to test the ability of molecular simulation methods to predict the adsorption of organic adsorbates in activated carbon materials. In particular, the eighth challenge focused on the adsorption of perfluorohexane in the activated carbon BAM-109. Entrants were challenged to predict the adsorption in the carbon at 273 K and relative pressures of 0.1, 0.3, and 0.6. The predictions were judged by comparison to a benchmark set of experimentally determined values. Overall good agreement and consistency were found between the predictions of most entrants. PMID:27840542

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-14

Ahti Heinla, left, and Sulo Kallas, right, from Estonia, prepare team KuuKulgur's robot for the rerun of the level one challenge during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Saturday, June 14, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-12

A sample can be seen on the competition field as the team Survey robot conducts a demonstration of the level two challenge during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Thursday, June 12, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-12

Jascha Little of team Survey is seen as he follows the teams robot as it conducts a demonstration of the level two challenge during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Thursday, June 12, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-11

The University of California Santa Cruz Rover Team poses for a picture with their robot after attempting the level one challenge during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Wednesday, June 11, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. is one of eighteen teams competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-14

The University of California Santa Cruz Rover Team's robot is seen prior to starting it's second attempt at the level one challenge during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Saturday, June 14, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-11

The Oregon State University Mars Rover Team poses for a picture with their robot following their attempt at the level one challenge during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Wednesday, June 11, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. is one of eighteen teams competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-11

The University of Waterloo Robotics Team, from Canada, prepares to place their robot on the start platform during the level one challenge at the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Wednesday, June 11, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-12

Sam Ortega, NASA program manager for Centennial Challenges, is interviewed by a member of the media before the start of level two competition at the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Thursday, June 12, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-11

Jerry Waechter of team Middleman from Dunedin, Florida, speaks about his team's robot, Ro-Bear, as it makes it attempt at the level one challenge during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Wednesday, June 11, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

Challenges in and lessons learned during the implementation of the 1-3-7 malaria surveillance and response strategy in China: a qualitative study.

PubMed

Lu, Guangyu; Liu, Yaobao; Beiersmann, Claudia; Feng, Yu; Cao, Jun; Müller, Olaf

2016-10-05

China has made great progress in malaria control over the last century and now aims to eliminate malaria by 2020. In 2012, the country launched its 1-3-7 surveillance and response strategy for malaria elimination. The strategy involves to case reporting within 1 day, case investigation within 3 days, and focus investigation and public health actions within 7 days. The aim of this study was to evaluate the challenges in and lessons learned during the implementation of the 1-3-7 strategy in China so far. This qualitative study was conducted in two provinces in China: Gansu province (northwestern China) and Jiangsu province (southeastern China) in 2014. Key informant interviews (n = 6) and in-depth interviews (n = 36) about the implementation aspects of the 1-3-7 strategy were conducted with malaria experts, health staff, laboratory practitioners, and village doctors at the provincial, city, county, township, and village levels. Broad themes related to the challenges in and lessons learned during the implementation of the 1-3-7 strategy were identified according to: case reporting within 1 day, case investigation within 3 days, focus investigation within 7 days, and the overall strategy. The major challenges outlined were related to respecting the timeline of surveillance procedures, the absence of or difficulties in following guidelines on conducting focus investigations, diagnostics, and the increasing number of returning migrant workers from malaria-endemic countries. Important lessons learned revolve around the importance of continuous capacity building, supervision and motivation, quality control, information technology support, applied research, governmental commitment, and intersectoral collaboration. Surveillance is a key intervention in malaria elimination programs. The Chinese 1-3-7 strategy has already proven to be successful but still needs to be improved. In particular, dealing appropriately with imported malaria cases through the screening of

78 FR 49296 - Centennial Challenges 2014 Sample Return Robot Challenge

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-13

... Return Robot Challenge AGENCY: National Aeronautics and Space Administration (NASA). ACTION: Notice of Centennial Challenges 2014 Sample Return Robot Challenge. SUMMARY: This notice is issued in accordance with 51 U.S.C. 20144(c). The 2014 Sample Return Robot Challenge is scheduled and teams that wish to...

Diplomatic Solutions to Additive Challenges

DTIC Science & Technology

Additive manufacturing (AM) technology, colloquially known as 3D printing , will bring significant benefits to society, but also poses great risks...regimes, are not sufficient to address the challenges presented by 3D printing technology. The DOS should evaluate and promote unconventional strategies...from printed weapons proliferation. Working with other nations to resolve the appropriate balance between development and security, and to promote norms

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-11

Kenneth Stafford, Assistant Director of Robotics Engineering and Director of the Robotics Resource Center at the Worcester Polytechnic Institute (WPI), verifies the location of the target sample during the level one challenge during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Wednesday, June 11, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-14

Members of the Mountaineers team from West Virginia University celebrate after their robot returned to the starting platform after picking up the sample during a rerun of the level one challenge during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Saturday, June 14, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

Restructuring Principal Preparation in Illinois: Perspectives on Implementation Successes, Challenges, and Future Outlook. Executive Summary. IERC 2015-3

ERIC Educational Resources Information Center

Klostermann, Brenda K.; Pareja, Amber Stitziel; Hart, Holly; White, Bradford R.; Huynh, Michelle Hanh

2015-01-01

The goals of the current mixed methods study--the Illinois Principal Preparation Implementation Review Project (I-PREP)--are to describe how the new policy is being implemented, learning which aspects of the implementation have been challenging and why they present challenges, and how programs are addressing challenges and realizing improvements…

42 CFR 426. 325 - What may be challenged.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 3 2012-10-01 2012-10-01 false What may be challenged. 426. 325 Section 426. 325 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... DETERMINATIONS General Provisions for the Review of LCDs and NCDs § 426. 325 What may be challenged. (a) Only...

42 CFR 426. 325 - What may be challenged.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 3 2013-10-01 2013-10-01 false What may be challenged. 426. 325 Section 426. 325 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... DETERMINATIONS General Provisions for the Review of LCDs and NCDs § 426. 325 What may be challenged. (a) Only...

42 CFR 426. 325 - What may be challenged.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false What may be challenged. 426. 325 Section 426. 325 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... General Provisions for the Review of LCDs and NCDs § 426. 325 What may be challenged. (a) Only LCDs or...

42 CFR 426. 325 - What may be challenged.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 3 2011-10-01 2011-10-01 false What may be challenged. 426. 325 Section 426. 325 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... General Provisions for the Review of LCDs and NCDs § 426. 325 What may be challenged. (a) Only LCDs or...

75 FR 47316 - Centennial Challenges 2010 Strong Tether Challenge

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-05

... NATIONAL AERONAUTICS AND SPACE ADMINISTRATION Centennial Challenges 2010 Strong Tether Challenge... teams that wish to compete may register. Centennial Challenges is a program of prize competitions to..., please visit: http://www.spaceward.org/elevator2010-ts . For general information on the NASA Centennial...

Global 3ν oscillation analysis: Status of unknown parameters and future systematic challenges for ORCA and PINGU

NASA Astrophysics Data System (ADS)

Capozzi, Francesco; Lisi, Eligio; Marrone, Antonio

2016-04-01

Within the standard 3ν oscillation framework, we illustrate the status of currently unknown oscillation parameters: the θ23 octant, the mass hierarchy (normal or inverted), and the possible CP-violating phase δ, as derived by a (preliminary) global analysis of oscillation data available in 2015. We then discuss some challenges that will be faced by future, high-statistics analyses of spectral data, starting with one-dimensional energy spectra in reactor experiments, and concluding with two-dimensional energy-angle spectra in large-volume atmospheric experiments. It is shown that systematic uncertainties in the spectral shapes can noticeably affect the prospective sensitivities to unknown oscillation parameters, in particular to the mass hierarchy.

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-12

Russel Howe of team Survey, center, works on a laptop to prepare the team's robot for a demonstration run after the team's robot failed to leave the starting platform during it's attempt at the level two challenge at the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Thursday, June 12, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

Ocean Science Video Challenge Aims to Improve Science Communication

NASA Astrophysics Data System (ADS)

Showstack, Randy

2013-10-01

Given today's enormous management and protection challenges related to the world's oceans, a new competition calls on ocean scientists to effectively communicate their research in videos that last up to 3 minutes. The Ocean 180 Video Challenge, named for the number of seconds in 3 minutes, aims to improve ocean science communication while providing high school and middle school teachers and students with new and interesting educational materials about current science topics.

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-11

during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Wednesday, June 11, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-12

during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Thursday, June 12, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-14

The NASA Centennial Challenges prize, level one, is presented to team Mountaineers for successfully completing level one of the NASA 2014 Sample Return Robot Challenge, from left, Ryan Watson, Team Mountaineers; Lucas Behrens, Team Mountaineers; Jarred Strader, Team Mountaineers; Yu Gu, Team Mountaineers; Scott Harper, Team Mountaineers; Dorothy Rasco, NASA Deputy Associate Administrator for the Space Technology Mission Directorate; Laurie Leshin, Worcester Polytechnic Institute (WPI) President; David Miller, NASA Chief Technologist; Alexander Hypes, Team Mountaineers; Nick Ohi,Team Mountaineers; Marvin Cheng, Team Mountaineers; Sam Ortega, NASA Program Manager for Centennial Challenges; and Tanmay Mandal, Team Mountaineers;, Saturday, June 14, 2014, at Worcester Polytechnic Institute (WPI) in Worcester, Mass. Team Mountaineers was the only team to complete the level one challenge. During the competition, teams were required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge was to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

Role of permissive hypotension, hypertonic resuscitation and the global increased permeability syndrome in patients with severe hemorrhage: adjuncts to damage control resuscitation to prevent intra-abdominal hypertension.

PubMed

Duchesne, Juan C; Kaplan, Lewis J; Balogh, Zsolt J; Malbrain, Manu L N G

2015-01-01

Secondary intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are closely related to fluid resuscitation. IAH causes major deterioration of the cardiac function by affecting preload, contractility and afterload. The aim of this review is to discuss the different interactions between IAH, ACS and resuscitation, and to explore a new hypothesis with regard to damage control resuscitation, permissive hypotension and global increased permeability syndrome. Review of the relevant literature via PubMed search. The recognition of the association between the development of ACS and resuscitation urged the need for new approach in traumatic shock management. Over a decade after wide spread application of damage control surgery damage control resuscitation was developed. DCR differs from previous resuscitation approaches by attempting an earlier and more aggressive correction of coagulopathy, as well as metabolic derangements like acidosis and hypothermia, often referred to as the 'deadly triad' or the 'bloody vicious cycle'. Permissive hypotension involves keeping the blood pressure low enough to avoid exacerbating uncontrolled haemorrhage while maintaining perfusion to vital end organs. The potential detrimental mechanisms of early, aggressive crystalloid resuscitation have been described. Limitation of fluid intake by using colloids, hypertonic saline (HTS) or hyperoncotic albumin solutions have been associated with favourable effects. HTS allows not only for rapid restoration of circulating intravascular volume with less administered fluid, but also attenuates post-injury oedema at the microcirculatory level and may improve microvascular perfusion. Capillary leak represents the maladaptive, often excessive, and undesirable loss of fluid and electrolytes with or without protein into the interstitium that generates oedema. The global increased permeability syndrome (GIPS) has been articulated in patients with persistent systemic inflammation failing

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-11

Team KuuKulgur watches as their robots attempt the level one competition during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Wednesday, June 11, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

Relationship challenges and relationship maintenance activities following disclosure of transsexualism.

PubMed

Alegría, C Aramburu

2010-12-01

• Transsexual persons are increasing their visibility in society, and health care providers and others (such as social workers) will be called upon to help with issues that transsexual persons face. Challenges that face transsexual persons often include issues involving relationships. Psychiatric and mental health nurses and other caregivers can increase their therapeutic skills in working with couples that include transsexual persons by becoming aware of these challenges and subsequent activities that can help with them. • This research study looks at couple relationships in which one partner reveals male-to-female transsexual identity. These are relationships that were established as man-woman and now will transition into relationships that include a male-to-female person and a female partner. • Common challenges for these couples include issues related to: (1) sexual identity and relationship uncertainty; (2) male-to-female transition decision making; and (3) presenting in public. • Relationship maintenance activities that helped the couples in the study maintain and strengthen their relationships through these challenges include: (1) communication; (2) self-talk (for example, putting the situation in perspective); (3) social networks; (4) positive interactions; (5) impression management (for example, managing displays of affection in public); and (6) social activism. This qualitative study describes the relational dynamics that help sustain relationships of couples that include male-to-female transsexual persons (MTF) and their natal female partners (NF) following disclosure of transsexualism. Relationship challenges and relationship maintenance activities are identified. Each partner in 17 MTF-NF couples participated in individual surveys and interviews. The data were coded for themes related to relationship challenges and activities. MTF-NF couples experience challenges within the contexts of their relationships and of society. These challenges

Thermal and Power Challenges in High Performance Computing Systems

NASA Astrophysics Data System (ADS)

Natarajan, Venkat; Deshpande, Anand; Solanki, Sudarshan; Chandrasekhar, Arun

2009-05-01

This paper provides an overview of the thermal and power challenges in emerging high performance computing platforms. The advent of new sophisticated applications in highly diverse areas such as health, education, finance, entertainment, etc. is driving the platform and device requirements for future systems. The key ingredients of future platforms are vertically integrated (3D) die-stacked devices which provide the required performance characteristics with the associated form factor advantages. Two of the major challenges to the design of through silicon via (TSV) based 3D stacked technologies are (i) effective thermal management and (ii) efficient power delivery mechanisms. Some of the key challenges that are articulated in this paper include hot-spot superposition and intensification in a 3D stack, design/optimization of thermal through silicon vias (TTSVs), non-uniform power loading of multi-die stacks, efficient on-chip power delivery, minimization of electrical hotspots etc.

The Challenges of Leadership.

PubMed

Myrtle, Robert C

Perhaps in no other period in recent times have the challenges leaders face been so profound. In these times of uncertainty and turbulence, we look to leaders who create a sense of purpose, who generate feelings of trust and optimism, and who tap the passion, talent, and efforts of those so essential to the success of the organization and of the people it serves. Our research suggests that becoming the leader whom people look to and admire requires an active commitment to responding to 5 essential leadership challenges. These are (1) creating a sense of purpose, (2) devising means for aligning the actions of the followers with that sense of purpose, (3) establishing a context that enables others to behave in a way that is consistent with the vision and values of the organization, (4) ensuring that the work that is done provides meaning to those engaging in the work activities, and (5) adding to the sum of everyone's knowledge through learning through reflective actions. In this article, we describe these challenges and offer suggestions that you can take to become a more effective and respected leader.

RadioAstron Observations of the Quasar 3C273: A Challenge to the Brightness Temperature Limit

NASA Astrophysics Data System (ADS)

Kovalev, Y. Y.; Kardashev, N. S.; Kellermann, K. I.; Lobanov, A. P.; Johnson, M. D.; Gurvits, L. I.; Voitsik, P. A.; Zensus, J. A.; Anderson, J. M.; Bach, U.; Jauncey, D. L.; Ghigo, F.; Ghosh, T.; Kraus, A.; Kovalev, Yu. A.; Lisakov, M. M.; Petrov, L. Yu.; Romney, J. D.; Salter, C. J.; Sokolovsky, K. V.

2016-03-01

Inverse Compton cooling limits the brightness temperature of the radiating plasma to a maximum of 1011.5 K. Relativistic boosting can increase its observed value, but apparent brightness temperatures much in excess of 1013 K are inaccessible using ground-based very long baseline interferometry (VLBI) at any wavelength. We present observations of the quasar 3C 273, made with the space VLBI mission RadioAstron on baselines up to 171,000 km, which directly reveal the presence of angular structure as small as 26 μas (2.7 light months) and brightness temperature in excess of 1013 K. These measurements challenge our understanding of the non-thermal continuum emission in the vicinity of supermassive black holes and require a much higher Doppler factor than what is determined from jet apparent kinematics.

Use of Lactobacillus johnsonii in broilers challenged with Salmonella sofia.

PubMed

Olnood, Chen G; Beski, Sleman S M; Choct, Mingan; Iji, Paul A

2015-09-01

The effects of Lactobacillus johnsonii (L. johnsonii) on gut microflora, bird performance and intestinal development were assessed using 288 one-day-old Cobb broilers challenged with Salmonella sofia ( S . sofia ). The experiment was a 3 × 2 factorial design which consisted of three treatments, a negative control (NC) with no additives, a positive control (PC) containing antimicrobials (zinc-bacitracin, 50 mg/kg) and a probiotic group (Pro), and with the two factors being unchallenged or challenged with S . sofia . A probiotic preparation of L . johnsonii (10 9 cfu/chick) was administered to chicks individually by oral gavage on days 1, 3, 7 and 12. Chicks were individually challenged with S. sofia (10 7 cfu/chick) by oral gavage on d 2, 8 and 13. Results showed that the challenge itself markedly reduced ( P < 0.05) bird performance and feed intake. And, transient clinical symptoms of the infection with S . sofia were observed from the second time they were challenged with S . sofia in the negative challenge groups. The novel probiotic candidate L . johnsonii reduced the number of S . sofia and Clostridium perfringens in the gut environment, and improved the birds' colonization resistance to S . sofia .

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-10

A team KuuKulgur Robot from Estonia is seen on the practice field during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Tuesday, June 10, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Team KuuKulgur is one of eighteen teams competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-14

Worcester Polytechnic Institute (WPI) President Laurie Leshin, speaks at a breakfast opening the TouchTomorrow Festival, held in conjunction with the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Saturday, June 14, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-11

The team AERO robot drives off the starting platform during the level one competition at the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Wednesday, June 11, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-14

David Miller, NASA Chief Technologist, speaks at a breakfast opening the TouchTomorrow Festival, held in conjunction with the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Saturday, June 14, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-11

The Oregon State University Mars Rover Team's robot is seen during level one competition at the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Wednesday, June 11, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-10

Jerry Waechter of team Middleman from Dunedin, Florida, works on their robot named Ro-Bear during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Tuesday, June 10, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Team Middleman is one of eighteen teams competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-11

Members of the Oregon State University Mars Rover Team prepare their robot to attempt the level one competition at the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Wednesday, June 11, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

Online Learning: Addressing Challenges and Seizing Opportunities. New Mexico

ERIC Educational Resources Information Center

Alliance for Excellent Education, 2010

2010-01-01

America's K-12 education system faces three significant challenges: (1) increased global demands for skilled workers, (2) significant financial shortfalls, and (3) a looming teacher shortage. Independently, these factors present significant challenges for U.S. schools. In combination, they create a national imperative for swift action to create a…

Online Learning: Addressing Challenges and Seizing Opportunities. New Hampshire

ERIC Educational Resources Information Center

Alliance for Excellent Education, 2010

2010-01-01

America's K-12 education system faces three significant challenges: (1) increased global demands for skilled workers, (2) significant financial shortfalls, and (3) a looming teacher shortage. Independently, these factors present significant challenges for U.S. schools. In combination, they create a national imperative for swift action to create a…

Localization of antigen-specific lymphocytes following lymph node challenge.

PubMed Central

Liu, H; Splitter, G A

1986-01-01

The effect of subcutaneous injections of Brucella abortus strain 19 antigen on the specific localization of autologous lymphocytes in the regional nodes of calves was analysed by fluorescent labelling and flow cytometry. Both in vitro and in vivo FITC labelling of lymphocytes indicated the preferential migration of lymphocytes from a previously challenged lymph node to a recently challenged lymph node. However, lymphocytes from a lymph node challenged with B. abortus failed to localize preferentially in a lymph node challenged with a control antigen, Listeria monocytogenes. Lymph node cells, enriched for T lymphocytes and isolated from primary stimulated or secondary challenged B. abortus lymph nodes, could proliferate when cultured with autologous antigen-pulsed macrophages. The kinetics of [3H]thymidine incorporation in lymphocytes from secondarily challenged lymph nodes occurred earlier and to a greater extent when compared with lymphocytes from primary challenged lymph nodes. Our data show that the accumulation of B. abortus-specific lymphocytes in secondarily challenged lymph nodes is increased by the presence of the specific antigen. Images Figure 4 PMID:2426183

Endoscopic management of intrabiliary-ruptured hepatic hydatid cyst.

PubMed

Singh, Virendra; Reddy, Deevaguntla Chandrasekhar; Verma, Ganga Ram; Singh, Gurpreet

2006-06-01

Intrabiliary rupture of hepatic hydatid cyst causes serious morbidity and mortality. These patients are usually managed surgically. We evaluated the feasibility and outcome of an alternative method of treatment of these patients. Seven patients with ruptured hepatic hydatid into the biliary tract underwent endoscopic treatment consisting of endoscopic sphincterotomy, cyst material extraction and hypertonic saline lavage via nasocystic catheter. Median age of patients was 40 years (range 17-50 years) with a male:female ratio of 2:5. Abdominal pain, jaundice and fever were seen in all patients. Six out of seven patients were positive for hydatid serology. All patients were successfully treated by endoscopic sphincterotomy, clearance of cyst material and hypertonic saline lavage. On a follow-up of 6 months to 4 years (median, 3.5 years), ultrasonography, computed tomography of the abdomen and magnetic resonance imaging of the abdomen showed a complete cure. There were no complications related to procedure. This study demonstrates endoscopic treatment as one of the therapeutic options of ruptured hepatic hydatid cyst into the biliary tract.

Incentive or Habit Learning in Amphibians?

PubMed Central

Muzio, Rubén N.; Pistone Creydt, Virginia; Iurman, Mariana; Rinaldi, Mauro A.; Sirani, Bruno; Papini, Mauricio R.

2011-01-01

Toads (Rhinella arenarum) received training with a novel incentive procedure involving access to solutions of different NaCl concentrations. In Experiment 1, instrumental behavior and weight variation data confirmed that such solutions yield incentive values ranging from appetitive (deionized water, DW, leading to weight gain), to neutral (300 mM slightly hypertonic solution, leading to no net weight gain or loss), and aversive (800 mM highly hypertonic solution leading to weight loss). In Experiment 2, a downshift from DW to a 300 mM solution or an upshift from a 300 mM solution to DW led to a gradual adjustment in instrumental behavior. In Experiment 3, extinction was similar after acquisition with access to only DW or with a random mixture of DW and 300 mM. In Experiment 4, a downshift from DW to 225, 212, or 200 mM solutions led again to gradual adjustments. These findings add to a growing body of comparative evidence suggesting that amphibians adjust to incentive shifts on the basis of habit formation and reorganization. PMID:22087217

Constructing kidney-like tissues from cells based on programs for organ development: toward a method of in vitro tissue engineering of the kidney.

PubMed

Rosines, Eran; Johkura, Kohei; Zhang, Xing; Schmidt, Heidi J; Decambre, Marvalyn; Bush, Kevin T; Nigam, Sanjay K

2010-08-01

The plausibility of constructing vascularized three-dimensional (3D) kidney tissue from cells was investigated. The kidney develops from mutual inductive interactions between cells of the ureteric bud (UB), derived from the Wolffian duct (WD), and the metanephric mesenchyme (MM). We found that isolated MMs were capable of inducing branching morphogenesis of the WD (an epithelial tube) in recombination cultures; suggesting that the isolated MM retains inductive capacity for WD-derived epithelial tubule cells other than those from the UB. Hanging drop aggregates of embryonic and adult renal epithelial cells from UB and mouse inner medullary collecting duct cell (IMCD) lines, which are ultimately of WD origin, were capable of inducing MM epithelialization and tubulogenesis with apparent connections (UB cells) and collecting duct-like tubules with lumens (IMCD). This supports the view that the collecting system can be constructed from certain epithelial cells (those ultimately of WD origin) when stimulated by MM. Although the functions of the MM could not be replaced by cultured mesenchymal cells, primary MM cells and one MM-derived cell line (BSN) produced factors that stimulate UB branching morphogenesis, whereas another, rat inducible metanephric mesenchyme (RIMM-18), supported WD budding as a feeder layer. This indicates that some MM functions can be recapitulated by cells. Although engineering of a kidney-like tissue from cultured cells alone remains to be achieved, these results suggest the feasibility of such an approach following the normal developmental progression of the UB and MM. Consistent with this notion, implants of kidney-like tissues constructed in vitro from recombinations of the UB and MM survived for over 5 weeks and achieved an apparently host-derived glomerular vasculature. Lastly, we addressed the issue of optimal macro- and micro-patterning of kidney-like tissue, which might be necessary for function of an organ assembled using a tissue

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-11

Team AERO, from the Worcester Polytechnic Institute (WPI) transports their robot to the competition field for the level one of the competition during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Wednesday, June 11, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-11

Robots that will be competing in the Level one competition are seen as they sit in impound prior to the start of competition at the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Wednesday, June 11, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-14

Dorothy Rasco, NASA Deputy Associate Administrator for the Space Technology Mission Directorate, speaks at the TouchTomorrow Festival, held in conjunction with the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Saturday, June 14, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-10

The University of Waterloo Robotics Team, from Ontario, Canada, prepares their robot for the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Tuesday, June 10, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. The team from the University of Waterloo is one of eighteen teams competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-11

Jim Rothrock, left, and Carrie Johnson, right, of the Wunderkammer Laboratory team pose for a picture with their robot after attempting the level one competition during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Wednesday, June 11, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Eighteen teams are competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-10

The Oregon State University Mars Rover Team follows their robot on the practice field during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Tuesday, June 10, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. The Oregon State University Mars Rover Team is one of eighteen teams competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-10

The Oregon State University Mars Rover Team, from Corvallis, Oregon, follows their robot on the practice field during the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Tuesday, June 10, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. The Oregon State University Mars Rover Team is one of eighteen teams competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

Association between continuous peripheral i.v. infusion of 3% sodium chloride injection and phlebitis in adults.

PubMed

Meng, Lina; Nguyen, Cherwyn M; Patel, Samit; Mlynash, Michael; Caulfield, Anna Finley

2018-03-01

One institution's experience with use of peripheral i.v. (PIV) catheters for prolonged infusions of 3% sodium chloride injection at rates up to 100 mL/hr is described. A prospective, observational, 13-month quality assurance project was conducted at an academic medical center to evaluate frequencies of patient and catheter phlebitis among adult inpatients who received both an infusion of 3% sodium chloride injection for a period of ≥4 hours through a dedicated PIV catheter and infusions of routine-care solutions (RCSs) through separate PIV catheters during the same hospital stay. Sixty patients received PIV infusions through a total of 291 catheters during the study period. The majority of patients (78%) received infusions of 3% sodium chloride injection for intracranial hypertension, with 30% receiving such infusions in the intensive care unit. Phlebitis occurred in 28 patients (47%) during infusions of 3% sodium chloride and 26 patients (43%) during RCS infusions ( p = 0.19). Catheter phlebitis occurred in 73 catheters (25%), with no significant difference in the frequencies of catheter phlebitis with infusion of 3% sodium chloride versus RCSs (30% [32 of 106 catheters]) versus 22% [41 of 185 catheters]), p = 0.16). Patient and catheter phlebitis rates were not significantly different with infusions of 3% sodium chloride injection versus RCSs, suggesting that an osmolarity cutoff value of 900 mOsm/L for peripheral infusions of hypertonic saline solutions may not be warranted. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Sustainable Materials Management (SMM) Electronics Challenge Data

EPA Pesticide Factsheets

On September 22, 2012, EPA launched the SMM Electronics Challenge. The Challenge encourages electronics manufacturers, brand owners and retailers to strive to send 100 percent of the used electronics they collect from the public, businesses and within their own organizations to third-party certified electronics refurbishers and recyclers. The Challenge??s goals are to: 1). Ensure responsible recycling through the use of third-party certified recyclers, 2). Increase transparency and accountability through public posting of electronics collection and recycling data, and 3). Encourage outstanding performance through awards and recognition. By striving to send 100 percent of used electronics collected to certified recyclers and refurbishers, Challenge participants are ensuring that the used electronics they collect will be responsibly managed by recyclers that maximize reuse and recycling, minimize exposure to human health and the environment, ensure the safe management of materials by downstream handlers, and require destruction of all data on used electronics. Electronics Challenge participants are publicly recognized on EPA's website as a registrant, new participant, or active participant. Awards are offered in two categories - tier and champion. Tier awards are given in recognition of achieving all the requirements under a gold, silver or bronze tier. Champion awards are given in two categories - product and non-product. For champion awards, a product is an it

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

Consigny, Paul M., E-mail: paul.consigny@av.abbott.com; Davalian, Dariush, E-mail: dariush.davalian@av.abbott.com; Donn, Rosy, E-mail: rosy.donn@av.abbott.com

Introduction: The recent success of renal denervation in lowering blood pressure in drug-resistant hypertensive patients has stimulated interest in developing novel approaches to renal denervation including local drug/chemical delivery. The purpose of this study was to develop a rat model in which depletion of renal norepinephrine (NE) could be used to determine the efficacy of renal denervation after the delivery of a chemical to the periadventitial space of the renal artery. Methods: Renal denervation was performed on a single renal artery of 90 rats (n = 6 rats/group). The first study determined the time course of renal denervation after surgical stripping ofmore » a renal artery plus the topical application of phenol in alcohol. The second study determined the efficacy of periadventitial delivery of hypertonic saline, guanethidine, and salicylic acid. The final study determined the dose–response relationship for paclitaxel. In all studies, renal NE content was determined by liquid chromatography–mass spectrometry. Results: Renal NE was depleted 3 and 7 days after surgical denervation. Renal NE was also depleted by periadventitial delivery of all agents tested (hypertonic saline, salicylic acid, guanethidine, and paclitaxel). A dose response was observed after the application of 150 μL of 10{sup −5} M through 10{sup −2} M paclitaxel. Conclusion: We developed a rat model in which depletion of renal NE was used to determine the efficacy of renal denervation after perivascular renal artery drug/chemical delivery. We validated this model by demonstrating the efficacy of the neurotoxic agents hypertonic saline, salicylic acid, and guanethidine and increasing doses of paclitaxel.« less

Experimental muscle pain increases variability of neural drive to muscle and decreases motor unit coherence in tremor frequency band.

PubMed

Yavuz, Utku Ş; Negro, Francesco; Falla, Deborah; Farina, Dario

2015-08-01

It has been observed that muscle pain influences force variability and low-frequency (<3 Hz) oscillations in the neural drive to muscle. In this study, we aimed to investigate the effect of experimental muscle pain on the neural control of muscle force at higher frequency bands, associated with afferent feedback (alpha band, 5-13 Hz) and with descending cortical input (beta band, 15-30 Hz). Single-motor unit activity was recorded, in two separate experimental sessions, from the abductor digiti minimi (ADM) and tibialis anterior (TA) muscles with intramuscular wire electrodes, during isometric abductions of the fifth finger at 10% of maximal force [maximum voluntary contraction (MVC)] and ankle dorsiflexions at 25% MVC. The contractions were repeated under three conditions: no pain (baseline) and after intramuscular injection of isotonic (0.9%, control) and hypertonic (5.8%, painful) saline. The results showed an increase of the relative power of both the force signal and the neural drive at the tremor frequency band (alpha, 5-13 Hz) between the baseline and hypertonic (painful) conditions for both muscles (P < 0.05) but no effect on the beta band. Additionally, the strength of motor unit coherence was lower (P < 0.05) in the hypertonic condition in the alpha band for both muscles and in the beta band for the ADM. These results indicate that experimental muscle pain increases the amplitude of the tremor oscillations because of an increased variability of the neural control (common synaptic input) in the tremor band. Moreover, the concomitant decrease in coherence suggests an increase in independent input in the tremor band due to pain. Copyright © 2015 the American Physiological Society.

Bacillus sp. LT3 improves the survival of gnotobiotic brine shrimp (Artemia franciscana) larvae challenged with Vibrio campbellii by enhancing the innate immune response and by decreasing the activity of shrimp-associated vibrios.

PubMed

Niu, Yufeng; Defoirdt, Tom; Baruah, Kartik; Van de Wiele, Tom; Dong, Shuanglin; Bossier, Peter

2014-10-10

Bacteria belonging to the genus Bacillus are amongst the most intensively studied group of bacteria for use as probiotics in aquaculture. However, the exact mechanism of action of these bacteria is often not well described, and the microbiota that are naturally present in cultures of test organisms often compromise the interpretation of the results. The present study aimed to evaluate the putative probiotic effect of Bacillus sp. LT3 in a model system with gnotobiotic brine shrimp Artemia franciscana larvae. The strain significantly increased the survival of brine shrimp larvae challenged with Vibrio campbellii when administered 6h before the challenge. Under these conditions, LT3 was able to colonize the brine shrimp gastrointestinal tract and to decrease the in vivo pathogen activity as indicated by the bioluminescence of the V. campbellii associated with brine shrimp larvae. In order to investigate the effect of the Bacillus strain on the innate immune system of the brine shrimp larvae, prophenoloxidase and transglutaminase mRNA levels were monitored, while heat shock protein 70 mRNA levels were measured as an indicator of physiological stress. Interestingly, 12h after challenge, the prophenoloxidase mRNA level in the larvae pre-treated with LT3 and challenged with V. campbellii was approximately 8-fold higher than in the other treatments. Further, a decreased mRNA level of transglutaminase gene and heat shock protein 70 gene suggested that pretreatment with LT3 results in less stress and tissue damage in the brine shrimp larvae upon V. campbellii challenge. These results indicated that Bacillus sp. LT3 could improve the survival of brine shrimp larvae when challenged with pathogenic V. campbellii, both by decreasing the in vivo activity of the pathogen and by priming the innate immune response through activating the prophenoloxidase system. Copyright © 2014 Elsevier B.V. All rights reserved.

The Challenging Experience Questionnaire: Characterization of challenging experiences with psilocybin mushrooms.

PubMed

Barrett, Frederick S; Bradstreet, Matthew P; Leoutsakos, Jeannie-Marie S; Johnson, Matthew W; Griffiths, Roland R

2016-12-01

Acute adverse psychological reactions to classic hallucinogens ("bad trips" or "challenging experiences"), while usually benign with proper screening, preparation, and support in controlled settings, remain a safety concern in uncontrolled settings (such as illicit use contexts). Anecdotal and case reports suggest potential adverse acute symptoms including affective (panic, depressed mood), cognitive (confusion, feelings of losing sanity), and somatic (nausea, heart palpitation) symptoms. Responses to items from several hallucinogen-sensitive questionnaires (Hallucinogen Rating Scale, the States of Consciousness Questionnaire, and the Five-Dimensional Altered States of Consciousness questionnaire) in an Internet survey of challenging experiences with the classic hallucinogen psilocybin were used to construct and validate a Challenging Experience Questionnaire. The stand-alone Challenging Experience Questionnaire was then validated in a separate sample. Seven Challenging Experience Questionnaire factors (grief, fear, death, insanity, isolation, physical distress, and paranoia) provide a phenomenological profile of challenging aspects of experiences with psilocybin. Factor scores were associated with difficulty, meaningfulness, spiritual significance, and change in well-being attributed to the challenging experiences. The factor structure did not differ based on gender or prior struggle with anxiety or depression. The Challenging Experience Questionnaire provides a basis for future investigation of predictors and outcomes of challenging experiences with classic hallucinogens. © The Author(s) 2016.

CDOCKER and lambda λ -dynamics for prospective prediction in D3R Grand Challenge 2

NASA Astrophysics Data System (ADS)

Ding, Xinqiang; Hayes, Ryan L.; Vilseck, Jonah Z.; Charles, Murchtricia K.; Brooks, Charles L.

2018-01-01

The opportunity to prospectively predict ligand bound poses and free energies of binding to the Farnesoid X Receptor in the D3R Grand Challenge 2 provided a useful exercise to evaluate CHARMM based docking (CDOCKER) and λ-dynamics methodologies for use in "real-world" applications in computer aided drug design. In addition to measuring their current performance, several recent methodological developments have been analyzed retrospectively to highlight best procedural practices in future applications. For pose prediction with CDOCKER, when the protein structure used for rigid receptor docking was close to the crystallographic holo structure, reliable poses were obtained. Benzimidazoles, with a known holo receptor structure, were successfully docked with an average RMSD of 0.97 Å. Other non-benzimidazole ligands displayed less accuracy largely because the receptor structures we chose for docking were too different from the experimental holo structures. However, retrospective analysis has shown that when these ligands were re-docked into their holo structures, the average RMSD dropped to 1.18 Å for all ligands. When sulfonamides and spiros were docked with the apo structure, which agrees more with their holo structure than the structures we chose, five out of six ligands were correctly docked. These docking results emphasize the need for flexible receptor docking approaches. For λ-dynamics techniques, including multisite λ-dynamics (MSλD), reasonable agreement with experiment was observed for the 33 ligands investigated; root mean square errors of 2.08 and 1.67 kcal/mol were obtained for free energy sets 1 and 2, respectively. Retrospectively, soft-core potentials, adaptive landscape flattening, and biasing potential replica exchange (BP-REX) algorithms were critical to model large substituent perturbations with sufficient precision and within restrictive timeframes, such as was required with participation in Grand Challenge 2. These developments, their

2014 NASA Centennial Challenges Sample Return Robot Challenge

NASA Image and Video Library

2014-06-10

A pair of Worcester Polytechnic Institute (WPI) students walk past a pair of team KuuKulgur's robots on the campus quad, during a final tuneup before the start of competition at the 2014 NASA Centennial Challenges Sample Return Robot Challenge, Tuesday, June 10, 2014, at the Worcester Polytechnic Institute (WPI) in Worcester, Mass. Team KuuKulgur is one of eighteen teams competing for a $1.5 million NASA prize purse. Teams will be required to demonstrate autonomous robots that can locate and collect samples from a wide and varied terrain, operating without human control. The objective of this NASA-WPI Centennial Challenge is to encourage innovations in autonomous navigation and robotics technologies. Innovations stemming from the challenge may improve NASA's capability to explore a variety of destinations in space, as well as enhance the nation's robotic technology for use in industries and applications on Earth. Photo Credit: (NASA/Joel Kowsky)

Estimating challenge load due to disease outbreaks and other challenges using reproduction records of sows.

PubMed

Mathur, P K; Herrero-Medrano, J M; Alexandri, P; Knol, E F; ten Napel, J; Rashidi, H; Mulder, H A

2014-12-01

A method was developed and tested to estimate challenge load due to disease outbreaks and other challenges in sows using reproduction records. The method was based on reproduction records from a farm with known disease outbreaks. It was assumed that the reduction in weekly reproductive output within a farm is proportional to the magnitude of the challenge. As the challenge increases beyond certain threshold, it is manifested as an outbreak. The reproduction records were divided into 3 datasets. The first dataset called the Training dataset consisted of 57,135 reproduction records from 10,901 sows from 1 farm in Canada with several outbreaks of porcine reproductive and respiratory syndrome (PRRS). The known disease status of sows was regressed on the traits number born alive, number of losses as a combination of still birth and mummified piglets, and number of weaned piglets. The regression coefficients from this analysis were then used as weighting factors for derivation of an index measure called challenge load indicator. These weighting factors were derived with i) a two-step approach using residuals or year-week solutions estimated from a previous step, and ii) a single-step approach using the trait values directly. Two types of models were used for each approach: a logistic regression model and a general additive model. The estimates of challenge load indicator were then compared based on their ability to detect PRRS outbreaks in a Test dataset consisting of records from 65,826 sows from 15 farms in the Netherlands. These farms differed from the Canadian farm with respect to PRRS virus strains, severity and frequency of outbreaks. The single-step approach using a general additive model was best and detected 14 out of the 15 outbreaks. This approach was then further validated using the third dataset consisting of reproduction records of 831,855 sows in 431 farms located in different countries in Europe and America. A total of 41 out of 48 outbreaks detected

Current Challenges for HTCMC Aero-Propulsion Components

NASA Technical Reports Server (NTRS)

DiCarlo, James A.; Bansal, Narottam P.

2007-01-01

In comparison to the best metallic materials, HTCMC aero-propulsion engine components offer the opportunity of reduced weight and higher temperature operation, with corresponding improvements in engine cooling requirements, emissions, thrust, and specific fuel consumption. Although much progress has been made in the development of advanced HTCMC constituent materials and processes, major challenges still remain for their implementation into these components. The objectives of this presentation are to briefly review (1) potential HTCMC aero-propulsion components and their generic material performance requirements, (2) recent progress at NASA and elsewhere concerning advanced constituents and processes for meeting these requirements, (3) key HTCMC component implementation challenges that are currently being encountered, and (4) on-going activities within the new NASA Fundamental Aeronautics Program that are addressing these challenges.

Repeated adolescent 3,4-methylenedioxymethamphetamine (MDMA) exposure in rats attenuates the effects of a subsequent challenge with MDMA or a 5-hydroxytryptamine(1A) receptor agonist.

PubMed

Piper, Brian J; Vu, Huyen L; Safain, Mina G; Oliver, Andrew J; Meyer, Jerrold S

2006-05-01

Adolescent users of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) may escalate their dose because of the development of tolerance. We examined the influence of intermittent adolescent MDMA exposure on the behavioral, physiological, and neurochemical responses to a subsequent MDMA "binge" or to a 5-hydroxytryptamine(1A) (5-HT(1A)) receptor challenge. Male Sprague-Dawley rats were given MDMA (10 mg/kg b.i.d.) or saline every 5th day on postnatal days (PDs) 35 to 60. One week later on PD 67, animals were challenged with either multiple doses of MDMA (four 5 or 10 mg/kg doses) or a single dose of the 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.1 or 0.5 mg/kg). Adolescent MDMA exposure partially attenuated the hyperthermic effects of the PD 67 MDMA challenge, completely blocked the locomotor hypoactivity otherwise observed on the day after the challenge, and also prevented MDMA-induced serotonin neurotoxicity assessed on PD 74 by measuring regional [(3)H]citalopram binding to the serotonin transporter (SERT). Adolescent MDMA-treated animals also showed a partial attenuation of the serotonin syndrome but not the hypothermic response to the high dose of 8-OH-DPAT. However, there was no effect of MDMA administration on regional [(3)H]N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide trihydrochloride (WAY-100635) binding to 5-HT(1A) receptors in the brain or spinal cord. These results suggest that chronic, intermittent MDMA exposure during adolescence induces neuroadaptive changes that can protect against the adverse consequences of a subsequent dose escalation. On the other hand, the same exposure pattern appears to produce a partial 5-HT(1A) receptor desensitization, which may negatively influence the therapeutic responses of chronic MDMA users treated with serotonergic agents for various affective or anxiety disorders.

Zika vaccines and therapeutics: landscape analysis and challenges ahead.

PubMed

Wilder-Smith, Annelies; Vannice, Kirsten; Durbin, Anna; Hombach, Joachim; Thomas, Stephen J; Thevarjan, Irani; Simmons, Cameron P

2018-06-06

Various Zika virus (ZIKV) vaccine candidates are currently in development. Nevertheless, unique challenges in clinical development and regulatory pathways may hinder the licensure of high-quality, safe, and effective ZIKV vaccines. Implementing phase 3 efficacy trials will be difficult given the challenges of the spatio-temporal heterogeneity of ZIKV transmission, the unpredictability of ZIKV epidemics, the broad spectrum of clinical manifestations making a single definite endpoint difficult, a lack of sensitive and specific diagnostic assays, and the need for inclusion of vulnerable target populations. In addition to a vaccine, drugs for primary prophylaxis, post-exposure prophylaxis, or treatment should also be developed to prevent or mitigate the severity of congenital Zika syndrome. Establishing the feasibility of immune correlates and/or surrogates are a priority. Given the challenges in conducting phase 3 trials at a time of waning incidence, human challenge trials should be considered to evaluate efficacy. Continued financial support and engagement of industry partners will be essential to the successful development, licensure, and accessibility of Zika vaccines or therapeutics.

Challenges facing early career academic cardiologists.

PubMed

Tong, Carl W; Ahmad, Tariq; Brittain, Evan L; Bunch, T Jared; Damp, Julie B; Dardas, Todd; Hijar, Amalea; Hill, Joseph A; Hilliard, Anthony A; Houser, Steven R; Jahangir, Eiman; Kates, Andrew M; Kim, Darlene; Lindman, Brian R; Ryan, John J; Rzeszut, Anne K; Sivaram, Chittur A; Valente, Anne Marie; Freeman, Andrew M

2014-06-03

Early career academic cardiologists currently face unprecedented challenges that threaten a highly valued career path. A team consisting of early career professionals and senior leadership members of American College of Cardiology completed this white paper to inform the cardiovascular medicine profession regarding the plight of early career cardiologists and to suggest possible solutions. This paper includes: 1) definition of categories of early career academic cardiologists; 2) general challenges to all categories and specific challenges to each category; 3) obstacles as identified by a survey of current early career members of the American College of Cardiology; 4) major reasons for the failure of physician-scientists to receive funding from National Institute of Health/National Heart Lung and Blood Institute career development grants; 5) potential solutions; and 6) a call to action with specific recommendations. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Osmosis in Cortical Collecting Tubules

PubMed Central

Schafer, James A.; Troutman, Susan L.; Andreoli, Thomas E.

1974-01-01

The present experiments were designed to evaluate the effects of varying the osmolality of luminal solutions on the antidiuretic hormone (ADH)-independent water and solute permeability properties of isolated rabbit cortical collecting tubules. In the absence of ADH, the osmotic water permeability coefficient (cm s–1) Pfl→b, computed from volume flows from hypotonic lumen to isotonic bath, was 20 ± 4 x 10–4 (SEM); the value of Pfb→l in the absence of ADH, computed from volume flows from isotonic bath to hypertonic lumen, was 88 ± 15 x 10–4 cm s–1. We also measured apparent urea permeability coefficients (cm s–1) from 14C-urea fluxes from lumen to bath (P DDurea l→b) and from bath to lumen (P DDurea b→l). For hypotonic luminal solutions and isotonic bathing solutions, P DDurea l→b was 0.045 ± 0.004 x 10–4 and was unaffected by ADH. The ADH-independent values of P DDurea l→b and P urea b→l were, respectively, 0.216 ± 0.022 x 10–4 cm s–1 and 0.033 ± 0.002 x 10–4 cm s–1 for isotonic bathing solutions and luminal solutions made hypertonic with urea, i.e., there was an absolute increase in urea permeability and asymmetry of urea fluxes. Significantly, P DDurea l→b did not rise when luminal hypertonicity was produced by sucrose; and, bathing fluid hypertonicity did not alter tubular permeability to water or to urea. We interpret these data to indicate that luminal hypertonicity increased the leakiness of tight junctions to water and urea but not sucrose. Since the value of Pfb→l in the absence of ADH, when tight junctions were open to urea, was approximately half of the value of Pfl→b in the presence of ADH, when tight junctions were closed to urea, we conclude that tight junctions are negligible paracellular shunts for lumen to bath osmosis with ADH. These findings, together with those in the preceding paper, are discussed in terms of a solubility-diffusion model for water permeation in which ADH increases water solubility in

Challenging Oneself Intermittently to Improve Health

PubMed Central

Mattson, Mark P.

2014-01-01

Humans and their predecessors evolved in environments where they were challenged intermittently with: 1) food scarcity; 2) the need for aerobic fitness to catch/kill prey and avoid or repel attackers; and 3) exposure to biological toxins present in foodstuffs. Accordingly, cells and organ systems acquired and retained molecular signaling and metabolic pathways through which the environmental challenges enhanced the functionality and resilience of the cells and organisms. Within the past 60 years there has been a precipitous diminution of such challenges in modern societies because of the development of technologies that provide a continuous supply of energy-dense processed foods and that largely eliminate the need for physical exertion. As a consequence of the modern ‘couch potato’ lifestyle, signaling pathways that mediate beneficial effects of environmental challenges on health and disease resistance are disengaged, thereby rendering people vulnerable to obesity, diabetes, cardiovascular disease, cancers and neurodegenerative disorders. Reversal of the epidemic of diseases caused by unchallenging lifestyles will require a society-wide effort to re-introduce intermittent fasting, exercise and consumption of plants containing hormetic phytochemicals into daily and weekly routines. PMID:25552960

A hyperosmolar-colloidal additive to the CPB-priming solution reduces fluid load and fluid extravasation during tepid CPB.

PubMed

Kvalheim, V; Farstad, M; Haugen, O; Brekke, H; Mongstad, A; Nygreen, E; Husby, P

2008-01-01

Cardiopulmonary bypass(CPB) is associated with fluid overload. We hypothesized that fluid gain during CPB could be reduced by substituting parts of a crystalloid prime with 7.2% hypertonic saline and 6% poly (O-2-hydroxyethyl) starch solution (HyperHaes). 14 animals were randomized to a control group (Group C) or to Group H. CPB-prime in Group C was Ringer's solution. In group H, 4 ml/kg of Ringer's solution was replaced by the hypertonic saline/hydroxyethyl starch solution. After 60 min stabilization, CPB was initiated and continued for 120 min. All animals were allowed drifting of normal temperature (39.0 degrees C) to about 35.0 degrees C. Fluid was added to the CPB circuit as needed to maintain a 300-ml level in the venous reservoir. Blood chemistry, hemodynamic parameters, fluid balance, plasma volume, fluid extravasation rate (FER), tissue water content and acid-base parameters were measured/calculated. Total fluid need during 120 min CPB was reduced by 60% when hypertonic saline/hydroxyethyl starch solution was added to the CPB prime (p < 0.01). The reduction was related to a lowered FER. The effect was most pronounced during the first 30 min on CPB, with 0.6 (0.43) (Group H) compared with 1.5 (0.40) ml/kg/min (Group C) (p < 0.01). Hemodynamics and laboratory parameters were similar in both groups. Serum concentrations of sodium and chloride increased to maximum levels of 148 (1.5) and 112 (1.6) mmol/l in Group H. To conclude: addition of 7.2% hypertonic saline and 6% poly (O-2-hydroxyethyl) starch solution to crystalloid CPB prime reduces fluid needs and FER during tepid CPB.

Drinking-Induced Plasma Vasopressin and Norepinephrine Changes in Dehydrated Humans

NASA Technical Reports Server (NTRS)

Geelen, Ghislaine; Greenleaf, John E.; Keil, Lanny C.

1996-01-01

After 24-h water deprivation, five men (23-41 yr; 78 +/- 3.6 kg) consumed, within 4.0-6.2 min, 12 mL/kg of one of six fluid formulations (16.5 C) once a week over a period of 6 weeks: water, hypotonic saline (0.045% Na(+)), isotopic saline (0.36%, Na(+)), hypertonic glucose 9 7%, glucose), and two commercial mildly hypertonic 9.7% carbohydrate drinks. Blood samples were drawn 5 min before and: 3, 9, 15, 30, and 70 min after completion of drinking. Ingestion induced no significant change in plasma Na(+), K(+), osmotic, or protein concentrations, blood pressure; or heart rate. Plasma volume (PV) was increases (P <0.05) between 30-70 min with isotonic saline and the two commercial drinks. Ingestion induced a decrease in plasma AVP (PAVP) at 3 min, which was maximal (P < 0.05) at 15 min with all drinks. Thus, the act of drinking, independent of the composition or osmolality of the fluid absorbed, leads to a prompt inhibition of PAVP secretion in man. With the exception of rehydration with isotonic saline, this prompt response was followed by a long lasting inhibition of PAVP. There was no change in PRA, plasma aldosterone, atrial natriuretic peptide, or epinephrine, but an increase in plasma norepinephrine occurred immediately after ingestion, which suggests, like that for PAVP depression, a drinking-stimulate neural mechanism.