Oval pulsed high-dose dexamethasone for myositis

NARCIS (Netherlands)

Hoogendijk, JE; Wokke, JHJ; de Visser, M

To study the short-term effect of oral pulsed high-dose dexamethasone for myositis we treated eight newly diagnosed patients with three 28-day cycles of oral dexamethasone. Primary outcome measures were muscle strength, pain, and serum creatine kinase activity. Sis patients responded. Side effects

Oral pulsed high-dose dexamethasone for myositis

NARCIS (Netherlands)

van der Meulen, M. F.; Hoogendijk, J. E.; Wokke, J. H.; de Visser, M.

2000-01-01

To study the short-term effect of oral pulsed high-dose dexamethasone for myositis we treated eight newly diagnosed patients with three 28-day cycles of oral dexamethasone. Primary outcome measures were muscle strength, pain, and serum creatine kinase activity. Six patients responded. Side effects

Brain-derived neurotrophic factor Val66Met polymorphism and dexamethasone/CRH test results in depressed patients.

Science.gov (United States)

Schüle, Cornelius; Zill, Peter; Baghai, Thomas C; Eser, Daniela; Zwanzger, Peter; Wenig, Nadine; Rupprecht, Rainer; Bondy, Brigitta

2006-09-01

Data suggest that both neurotrophic and hypothalamic-pituitary-adrenocortical (HPA) systems are involved in the pathophysiology of depression. The aim of the present study was to investigate whether the non-conservative brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has an impact on HPA axis activity in depressed patients. At admission, the dexamethasone/CRH (DEX/CRH) test was performed in 187 drug-free in-patients suffering from major depression or depressed state of bipolar disorder (DSM-IV criteria). Moreover, genotyping of BDNF Val66Met polymorphism was carried out using the fluorescence resonance energy transfer method (FRET). Homozygous carriers of the Met/Met genotype showed a significantly higher HPA axis activity during the DEX/CRH test than patients carrying the Val/Val or Val/Met genotype (ACTH, cortisol). Our results further contribute to the hypothesized association between HPA axis dysregulation and reduced neuroplasticity in depression and are consistent with the assumption that BDNF is a stress-responsive intercellular messenger modifying HPA axis activity.

Inter-cellular transport of ran GTPase.

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Deepak Khuperkar

Full Text Available Ran, a member of the Ras-GTPase superfamily, has a well-established role in regulating the transport of macromolecules across the nuclear envelope (NE. Ran has also been implicated in mitosis, cell cycle progression, and NE formation. Over-expression of Ran is associated with various cancers, although the molecular mechanism underlying this phenomenon is unclear. Serendipitously, we found that Ran possesses the ability to move from cell-to-cell when transiently expressed in mammalian cells. Moreover, we show that the inter-cellular transport of Ran is GTP-dependent. Importantly, Ran displays a similar distribution pattern in the recipient cells as that in the donor cell and co-localizes with the Ran binding protein Nup358 (also called RanBP2. Interestingly, leptomycin B, an inhibitor of CRM1-mediated export, or siRNA mediated depletion of CRM1, significantly impaired the inter-cellular transport of Ran, suggesting a function for CRM1 in this process. These novel findings indicate a possible role for Ran beyond nucleo-cytoplasmic transport, with potential implications in inter-cellular communication and cancers.

Identification and characterization of RBM44 as a novel intercellular bridge protein.

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Tokuko Iwamori

2011-02-01

Full Text Available Intercellular bridges are evolutionarily conserved structures that connect differentiating germ cells. We previously reported the identification of TEX14 as the first essential intercellular bridge protein, the demonstration that intercellular bridges are required for male fertility, and the finding that intercellular bridges utilize components of the cytokinesis machinery to form. Herein, we report the identification of RNA binding motif protein 44 (RBM44 as a novel germ cell intercellular bridge protein. RBM44 was identified by proteomic analysis after intercellular bridge enrichment using TEX14 as a marker protein. RBM44 is highly conserved between mouse and human and contains an RNA recognition motif of unknown function. RBM44 mRNA is enriched in testis, and immunofluorescence confirms that RBM44 is an intercellular bridge component. However, RBM44 only partially localizes to TEX14-positive intercellular bridges. RBM44 is expressed most highly in pachytene and secondary spermatocytes, but disappears abruptly in spermatids. We discovered that RBM44 interacts with itself and TEX14 using yeast two-hybrid, mammalian two-hybrid, and immunoprecipitation. To define the in vivo function of RBM44, we generated a targeted deletion of Rbm44 in mice. Rbm44 null male mice produce somewhat increased sperm, and show enhanced fertility of unknown etiology. Thus, although RBM44 localizes to intercellular bridges during meiosis, RBM44 is not required for fertility in contrast to TEX14.

Effects of dexamethasone on brain edema

International Nuclear Information System (INIS)

Takemoto, Motohisa

1982-01-01

Experimental cerebral edema was produced on the right parietal lobe of Wistar male rats with a cold metal probe cooled by liquid nitrogen. Twenty hour later, 3 H-dexamethasone was either intramuscularly or intravenously injected into rats, estimated in the brain tissue by the liquid scintillation counting method. Edematous brain generally contained much higher 3 H-activity than the control. Furthermore, I.V. injection showed higher 3 H-activity than I.M injection in edematous and control brains at all times. For examination of the subcellular distribution of 3 H-dexamethasone in edematous brain, 3 H-activity was most strongly detected in the supernatant fraction (63%), followed by the heavy mitochondrial fraction (25.4%) and the nuclear fraction (8.4%). Although edematous brain tissue constantly demonstrated higher 3 H-activity than the control, its supernatant fraction conversely had less activity. As a next step, distribution of 3 H-dexamethasone in the supernatant fraction was studies. The result was that the high molecular weight fraction in the edematous brain showed higher radioactivity than the control. From these findings, unequivocal distribution of dexamethasone in the supernatant fraction of edematous brain tissue could be correlated with its biochemical action for preventing brain edema. (J.P.N.)

Does dexamethasone have a perineural mechanism of action?

DEFF Research Database (Denmark)

Jæger, P; Grevstad, Jens Ulrik; Koscielniak-Nielsen, Z J

2016-01-01

BACKGROUND: Dexamethasone prolongs block duration. Whether this is achieved via a peripheral or a central mechanism of action is unknown. We hypothesized that perineural dexamethasone added as an adjuvant to ropivacaine prolongs block duration compared with ropivacaine alone, by a locally mediated...... effect when controlled for a systemic action. METHODS: We performed a paired, blinded, randomized trial, including healthy men. All subjects received bilateral blocks of the saphenous nerve with ropivacaine 0.5%, 20 ml mixed with dexamethasone 2 mg in one leg and saline in the other, according...

Analgesic effects of dexamethasone in burn injury

DEFF Research Database (Denmark)

Werner, Mads U; Lassen, Birgit Vibeke; Kehlet, Henrik

2002-01-01

and secondary hyperalgesia. RESULTS: The burn injury induced significant increases in erythema (P burn did not differ between dexamethasone and placebo treatments (P >.6). There were no significant......BACKGROUND AND OBJECTIVES: Glucocorticoids are well-known adjuvant analgesics in certain chronic pain states. There is, however, a paucity of data on their analgesic efficacy in acute pain. Therefore, the aim of the study was to examine the analgesic effects of dexamethasone in a validated burn...... model of acute inflammatory pain in humans. METHODS: Twenty-two volunteers were investigated in a double-blind, randomized, placebo-controlled cross-over study. Intravenous dexamethasone 8 mg or placebo was administered on 2 separate study days. Two hours after drug administration, a first-degree burn...

Effects of dexamethasone on palate mesenchymal cell phospholipase activity

International Nuclear Information System (INIS)

Bulleit, R.F.; Zimmerman, E.F.

1984-01-01

Corticosteroids will induce cleft palate in mice. One suggested mechanism for this effect is through inhibition of phospholipase activity. This hypothesis was tested by measuring the effects of dexamethasone, a synthetic corticosteroid, on phospholipase activity in cultures of palate mesenchymal cells. Palate mesenchymal cells were prelabeled with [3H]arachidonic acid. The cells were subsequently treated with various concentrations of dexamethasone. Concurrently, cultures of M-MSV-transformed 3T3 cells were prepared identically. After treatment, phospholipase activity was stimulated by the addition of serum or epidermal growth factor (EGF), and radioactivity released into the medium was taken as a measure of phospholipase activity. Dexamethasone (1 X 10(-5) or 1 X 10(-4) M) could inhibit serum-stimulated phospholipase activity in transformed 3T3 cells after 1 to 24 hr of treatment. However, no inhibition of activity was measured in palate mesenchymal cells following this period of treatment. Not until 120 hr of treatment with dexamethasone (1 X 10(-4) M) was any significant inhibition of serum-stimulated phospholipase activity observed in palate mesenchymal cells. When EGF was used to stimulate phospholipase activity, dexamethasone (1 X 10(-5) M) caused an increase in phospholipase activity in palate mesenchymal cells. These observations suggested that phospholipase in transformed 3T3 cells was sensitive to inhibition by dexamethasone. However, palate mesenchymal cell phospholipase is only minimally sensitive to dexamethasone, and in certain instances can be enhanced. These results cannot support the hypothesis that corticosteroids mediate their teratogenic effect via inhibition of phospholipase activity

Dexamethasone enhances the anti-emetic effect of metoclopramide ...

African Journals Online (AJOL)

Ninety patients, ASA I or II, aged 21-64years were randomly selected to either the dexamethasone-metoclopramide group, metoclopramide group or dexamethasone group using computer-generated random numbers . Spinal anaesthesia was induced in the sitting position under strict aseptic technique with hyperbaric ...

Dexamethasone for pain after outpatient shoulder surgery

DEFF Research Database (Denmark)

Bjørnholdt, K. T.; Mønsted, P. N.; Søballe, Kjeld

2014-01-01

Background Dexamethasone has analgesic properties when given intravenously before surgery, but the optimal dose has not been determined. We hypothesised that a dose of 40 mg dexamethasone would improve analgesia after outpatient shoulder surgery compared with 8 mg. Methods A randomised, double...... a dose–response relationship, increasing the dexamethasone dose from 8 to 40 mg did not improve analgesia significantly after outpatient shoulder surgery.......) or placebo (D0) before surgery. The primary outcome was pain intensity 8 h after surgery rated on a numeric rating scale of 0 to 10. Secondary outcomes were pain intensity, analgesic consumption and side effects during the first 3 days after surgery. Results Data from 73 patients were available for analysis...

Methoxychlor and Vinclozolin Induce Rapid Changes in Intercellular and Intracellular Signaling in Liver Progenitor Cells.

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Babica, Pavel; Zurabian, Rimma; Kumar, Esha R; Chopra, Rajus; Mianecki, Maxwell J; Park, Joon-Suk; Jaša, Libor; Trosko, James E; Upham, Brad L

2016-09-01

Methoxychlor (MXC) and vinclozolin (VIN) are well-recognized endocrine disrupting chemicals known to alter epigenetic regulations and transgenerational inheritance; however, non-endocrine disruption endpoints are also important. Thus, we determined the effects of MXC and VIN on the dysregulation of gap junctional intercellular communication (GJIC) and activation of mitogen-activated protein kinases (MAPKs) in WB-F344 rat liver epithelial cells. Both chemicals induced a rapid dysregulation of GJIC at non-cytotoxic doses, with 30 min EC50 values for GJIC inhibition being 10 µM for MXC and 126 µM for VIN. MXC inhibited GJIC for at least 24 h, while VIN effects were transient and GJIC recovered after 4 h. VIN induced rapid hyperphosphorylation and internalization of gap junction protein connexin43, and both chemicals also activated MAPK ERK1/2 and p38. Effects on GJIC were not prevented by MEK1/2 inhibitor, but by an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC), resveratrol, and in the case of VIN, also, by a p38 inhibitor. Estrogen (ER) and androgen receptor (AR) modulators (estradiol, ICI 182,780, HPTE, testosterone, flutamide, VIN M2) did not attenuate MXC or VIN effects on GJIC. Our data also indicate that the effects were elicited by the parental compounds of MXC and VIN. Our study provides new evidence that MXC and VIN dysregulate GJIC via mechanisms involving rapid activation of PC-PLC occurring independently of ER- or AR-dependent genomic signaling. Such alterations of rapid intercellular and intracellular signaling events involved in regulations of gene expression, tissue development, function and homeostasis, could also contribute to transgenerational epigenetic effects of endocrine disruptors. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Randomized clinical trial of dexamethasone versus placebo in laparoscopic inguinal hernia repair

DEFF Research Database (Denmark)

Tolver, M A; Strandfelt, P; Bryld, Clara E

2012-01-01

The effect of dexamethasone on recovery and length of convalescence has not been evaluated in patients after laparoscopic groin hernia repair. It was hypothesized that preoperative intravenous dexamethasone would reduce postoperative pain.......The effect of dexamethasone on recovery and length of convalescence has not been evaluated in patients after laparoscopic groin hernia repair. It was hypothesized that preoperative intravenous dexamethasone would reduce postoperative pain....

Dexamethasone Does Not Inhibit Sugammadex Reversal After Rocuronium-Induced Neuromuscular Block.

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Buonanno, Pasquale; Laiola, Anna; Palumbo, Chiara; Spinelli, Gianmario; Servillo, Giuseppe; Di Minno, Raffaele Maria; Cafiero, Tullio; Di Iorio, Carlo

2016-06-01

Sugammadex is a relatively new molecule that reverses neuromuscular block induced by rocuronium. The particular structure of sugammadex traps the cyclopentanoperhydrophenanthrene ring of rocuronium in its hydrophobic cavity. Dexamethasone shares the same steroidal structure with rocuronium. Studies in vitro have demonstrated that dexamethasone interacts with sugammadex, reducing its efficacy. In this study, we investigated the clinical relevance of this interaction and its influence on neuromuscular reversal. In this retrospective case-control study, we analyzed data from 45 patients divided into 3 groups: dexamethasone after induction group (15 patients) treated with 8 mg dexamethasone as an antiemetic drug shortly after induction of anesthesia; dexamethasone before reversal group (15 patients) treated with dexamethasone just before sugammadex injection; and control group (15 patients) treated with 8 mg ondansetron. All groups received 0.6 mg/kg rocuronium at induction, 0.15 mg/kg rocuronium at train-of-four ratio (TOF) 2 for neuromuscular relaxation, and 2 mg/kg sugammadex for reversal at the end of the procedure at TOF2. Neuromuscular relaxation was monitored with a TOF-Watch® system. The control group had a recovery time of 154 ± 54 seconds (mean ± SD), the dexamethasone after induction group 134 ± 55 seconds, and the dexamethasone before reversal group 131 ± 68 seconds. The differences among groups were not statistically significant (P = 0.5141). Our results show that the use of dexamethasone as an antiemetic drug for the prevention of postoperative nausea and vomiting does not interfere with reversal of neuromuscular blockade with sugammadex in patients undergoing elective surgery with general anesthesia in contrast to in vitro studies that support this hypothesis.

Modelling of intercellular synchronization in the Drosophila circadian clock

International Nuclear Information System (INIS)

Jun-Wei, Wang; Ai-Min, Chen; Jia-Jun, Zhang; Zhan-Jiang, Yuan; Tian-Shou, Zhou

2009-01-01

In circadian rhythm generation, intercellular signaling factors are shown to play a crucial role in both sustaining intrinsic cellular rhythmicity and acquiring collective behaviours across a population of circadian neurons. However, the physical mechanism behind their role remains to be fully understood. In this paper, we propose an indirectly coupled multicellular model for the synchronization of Drosophila circadian oscillators combining both intracellular and intercellular dynamics. By simulating different experimental conditions, we find that such an indirect coupling way can synchronize both heterogeneous self-sustained circadian neurons and heterogeneous mutational damped circadian neurons. Moreover, they can also be entrained to ambient light-dark (LD) cycles depending on intercellular signaling. (cross-disciplinary physics and related areas of science and technology)

Paradoxical response to dexamethasone and spontaneous hypocortisolism in Cushing's disease

OpenAIRE

Lila, Anurag R; Sarathi, Vijaya; Bandgar, Tushar R; Shah, Nalini S

2013-01-01

Paradoxical response to dexamethasone and spontaneous development of hypocortisolism are rare features of Cushing's disease. We report a 13-year-old boy with Cushing's disease owing to a pituitary macroadenoma. On initial evaluation, he had partial suppression of serum cortisol by dexamethasone. He developed transient hypocortisolism after first adenomectomy, but the disease recurred after 1 year. Repeat evaluation showed recurrent hypercortisolism and paradoxical response to dexamethasone. H...

The use of dexamethasone in animals: implication for fertility ...

African Journals Online (AJOL)

Exposure to dexamethasone causes numerous changes in various biological systems including the reproductive system and this has huge implication on fertility and pregnancy. Maternal dexamethasone administration promotes foetal lung maturation and thermoregulation in premature foetuses. This indication makes ...

Icam-1 targeted nanogels loaded with dexamethasone alleviate pulmonary inflammation.

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M Carme Coll Ferrer

Full Text Available Lysozyme dextran nanogels (NG have great potential in vitro as a drug delivery platform, combining simple chemistry with rapid uptake and cargo release in target cells with "stealth" properties and low toxicity. In this work, we study for the first time the potential of targeted NG as a drug delivery platform in vivo to alleviate acute pulmonary inflammation in animal model of LPS-induced lung injury. NG are targeted to the endothelium via conjugation with an antibody (Ab directed to Intercellular Adhesion Molecule-1(ICAM-NG, whereas IgG conjugated NG (IgG-NG are used for control formulations. The amount of Ab conjugated to the NG and distribution in the body after intravenous (IV injection have been quantitatively analyzed using a tracer isotope-labeled [125I]IgG. As a proof of concept, Ab-NG are loaded with dexamethasone, an anti-inflammatory therapeutic, and the drug uptake and release kinetics are measured by HPLC. In vivo studies in mice showed that: i ICAM-NG accumulates in mouse lungs (∼120% ID/g vs ∼15% ID/g of IgG-NG; and, ii DEX encapsulated in ICAM-NG, but not in IgG-NG practically blocks LPS-induced overexpression of pro-inflammatory cell adhesion molecules including ICAM-1 in the pulmonary inflammation.

Effects of dexamethasone on liver enzymes and some serum ...

African Journals Online (AJOL)

Concomitant usage of dexamethasone and other medications may alter electrolyte metabolism and increase the formation of potentially hepatotoxic reactive metabolites which can contribute to elevated liver enzymes. The role of dexamethasone in liver functions and electrolyte metabolism during pregnancy in Yankasa ...

Tapered oral dexamethasone for the acute chest syndrome of sickle cell disease

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Quinn, Charles T.; Stuart, Marie J.; Kesler, Karen; Ataga, Kenneth I.; Wang, Winfred C.; Styles, Lori; Smith-Whitley, Kim; Wun, Ted; Raj, Ahsok; Hsu, Lewis L.; Krishnan, Suba; Kuypers, Frans A; Setty, B. N. Yamaja; Rhee, Seungshin; Key, Nigel S.; Buchanan, George R.

2011-01-01

Summary Tapered oral dexamethasone for acute chest syndrome (ACS) in sickle cell anaemia was studied using a novel ACS assessment tool and investigational biomarkers. Twelve participants were randomized (mean age 17.3 years) before early study termination. Dexamethasone decreased duration of hospitalization for ACS by 20.8 h compared to placebo (P=0.024). Rebound pain occurred in both groups (3 dexamethasone vs. 1 placebo). Overall, dexamethasone decreased the leucocyte activation biomarker, sL-selectin; however, participants with rebound pain had higher sL-selectin within 24 h of treatment (dexamethasone or placebo). This ACS assessment tool was feasibly applied, and sL-selectin is a promising biomarker of ACS therapy. PMID:21848879

Dexamethasone minimizes the risk of cranial nerve injury during CEA.

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Regina, Guido; Angiletta, Domenico; Impedovo, Giovanni; De Robertis, Giovanni; Fiorella, Marialuisa; Carratu', Maria Rosaria

2009-01-01

The incidence of cranial and cervical nerve injury during carotid endarterectomy (CEA) ranges from less than 7.6% to more than 50%. Lesions are mainly due to surgical maneuvers such as traction, compression, tissue electrocoagulation, clamping, and extensive dissections. The use of dexamethasone (DEX) and its beneficial effects in spinal cord injuries have already been described. We investigated whether DEX could also be beneficial to minimize the incidence of cranial and cervical nerve injury during CEA. To evaluate whether dexamethasone is able to reduce the incidence of cranial nerve injuries. From March 1999 through April 2006, 1126 patients undergoing CEA because of high-grade carotid stenosis were enrolled and randomized by predetermined randomization tables into two groups. The first group, "A", included 586 patients that all received an intravenous administration of dexamethasone following a therapeutic scheme. The second group, "B", included 540 control subjects that received the standard pre- and postoperative therapy. All patients were submitted to a deep cervical plexus block, eversion carotid endarterectomy, and selective shunting. Three days after the operation, an independent neurologist and otorhinolaryngologist evaluated the presence of cranial nerve deficits. All patients (group A and group B) showing nerve injuries continued the treatment (8 mg of dexamethasone once in the morning) for 7 days and were re-evaluated after 2 weeks, 30 days, and every 3 months for 1 year. Recovery time took from 2 weeks to 12 months, with a mean time of 3.6 months. The chi(2) test was used to compare the two groups and to check for statistical significance. The incidence of cranial nerve dysfunction was higher in group B and the statistical analysis showed a significant effect of dexamethasone in preventing the neurological damage (P = .0081). The incidence of temporary lesions was lower in group A and the chi(2) test yielded a P value of .006. No statistically

Effects of dexamethasone on brain edema. Uptake and distribution of tritiated (/sup 3/H) dexamethasone in cold induced edema

Energy Technology Data Exchange (ETDEWEB)

Takemoto, Motohisa [Okayama Univ. (Japan). School of Medicine

1982-06-01

Experimental cerebral edema was produced on the right parietal lobe of Wistar male rats with a cold metal probe cooled by liquid nitrogen. Twenty hour later, /sup 3/H-dexamethasone was either intramuscularly or intravenously injected into rats, estimated in the brain tissue by the liquid scintillation counting method. Edematous brain generally contained much higher /sup 3/H-activity than the control. Furthermore, I.V. injection showed higher /sup 3/H-activity than I.M injection in edematous and control brains at all times. For examination of the subcellular distribution of /sup 3/H-dexamethasone in edematous brain, /sup 3/H-activity was most strongly detected in the supernatant fraction (63%), followed by the heavy mitochondrial fraction (25.4%) and the nuclear fraction (8.4%). Although edematous brain tissue constantly demonstrated higher /sup 3/H-activity than the control, its supernatant fraction conversely had less activity. As a next step, distribution of /sup 3/H-dexamethasone in the supernatant fraction was studies. The result was that the high molecular weight fraction in the edematous brain showed higher radioactivity than the control. From these findings, unequivocal distribution of dexamethasone in the supernatant fraction of edematous brain tissue could be correlated with its biochemical action for preventing brain edema.

Quantification of gap junctional intercellular communication based on digital image analysis

DEFF Research Database (Denmark)

Hofgaard, Johannes P; Mollerup, Sarah; Holstein-Rathlou, Niels-Henrik

2009-01-01

Intercellular communication via gap junction channels can be quantified by several methods based on diffusion of fluorescent dyes or metabolites. Given the variation in intercellular coupling of cells, even under untreated control conditions, it is of essence to quantify the coupling between...... and in cells receiving dye by intercellular diffusion. The analysis performed is semiautomatic, and comparison with traditional cell counting shows that this method reliably determines the effect of uncoupling by several interventions. This new method of analysis yields a rapid and objective quantification...

The role of dexamethasone in peripheral and neuraxial nerve blocks ...

African Journals Online (AJOL)

pain and prolongs analgesia in the postoperative period when combined with ... management of acute pain and that focused on dexamethasone's ability to prolong ... of dexamethasone to brachial plexus nerve blocks and Akram and Hassani ...

Endocrinologic and psychological effects of short-term dexamethasone in anorexia nervosa.

Science.gov (United States)

Gordon, C M; Emans, S J; DuRant, R H; Mantzoros, C; Grace, E; Harper, G P; Majzoub, J A

2000-09-01

Patients with anorexia nervosa (AN) have hyperactivity of their hypothalamic-pituitary-adrenal (HPA) axis, sometimes accompanied by elevations of cortisol. We examined whether the normal effects of short-term dexamethasone treatment upon HPA axis suppression and appetite stimulation are observed in these patients. Five young women with AN and ten healthy female controls received one week of high-dose oral dexamethasone (2 mg/m2/d) preceded and followed by hormonal evaluation of sensitivity to glucocorticoids and psychological assessments. No differences in hormone levels of the HPA axis were observed between the two groups and control groups at baseline, after dexamethasone suppression, or following ACTH stimulation testing. However, fasting insulin levels were significantly lower in the AN group, both before and after dexamethasone therapy and their serum leptin levels were also significantly lower. The AN group had significantly lower scores on the Anorexia Nervosa Subtest and the Beck Depression Inventory after dexamethasone compared to controls. On daily analog scales, AN patients had higher anxiety scores while on dexamethasone. Normal sensitivity to glucocorticoids was observed in all parameters examined except for mild abnormalities in pancreatic beta-cell function. These data suggest that AN may represent a state of partial glucocorticoid resistance, as in other states of restricted food intake. Furthermore, these pilot data, including the effects of dexamethasone upon psychological outlook in AN, suggest that glucocorticoids are not an effective therapy for these patients.

Dexamethasone and long-term outcome of tuberculous meningitis in Vietnamese adults and adolescents.

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M Estée Török

Full Text Available Dexamethasone has been shown to reduce mortality in patients with tuberculous meningitis but the long-term outcome of the disease is unknown.Vietnamese adults and adolescents with tuberculous meningitis recruited to a randomised, double-blind, placebo-controlled trial of adjunctive dexamethasone were followed-up at five years, to determine the effect of dexamethasone on long-term survival and neurological disability.545 patients were randomised to receive either dexamethasone (274 patients or placebo (271 patients. 50 patients (9.2% were lost to follow-up at five years. In all patients two-year survival, probabilities tended to be higher in the dexamethasone arm (0.63 versus 0.55; p = 0.07 but five-year survival rates were similar (0.54 versus 0.51, p = 0.51 in both groups. In patients with grade 1 TBM, but not with grade 2 or grade 3 TBM, the benefit of dexamethasone treatment tended to persist over time (five-year survival probabilities 0.69 versus 0.55, p = 0.07 but there was no conclusive evidence of treatment effect heterogeneity by TBM grade (p = 0.36. The dexamethasone group had a similar proportion of severely disabled patients among survivors at five years as the placebo group (17/128, 13.2% vs. 17/116, 14.7% and there was no significant association between dexamethasone treatment and disability status at five years (p = 0.32.Adjunctive dexamethasone appears to improve the probability of survival in patients with TBM, until at least two years of follow-up. We could not demonstrate a five-year survival benefit of dexamethasone treatment which may be confined to patients with grade 1 TBM.ClinicalTrials.gov NCT01317654.

Hypertrophic Cardiomyopathy After a Single Dose of Dexamethasone in a Preterm Infant

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Yusuf Kale

2015-08-01

Full Text Available Dexamethasone is widely used in preterm infants with severe pulmonary disease. Hypertrophic cardiomyopathy (HCM is a transient side effect observed after multiple doses of dexamethasone. We report a preterm infant with myocardial hypertrophy after a single dose of dexamethasone (0.5 mg/kg used to treat laryngeal edema secondary to prolonged intubation. A benign course was observed without left ventricular outflow tract obstruction and with recovery within 4 weeks. Myocardial effects of dexamethasone may be independent of dose and duration of treatment. The risk/benefit ratio must be carefully considered before using even a single dose of dexamethasone in preterm infants.

Dexamethasone and Long-Term Outcome of Tuberculous Meningitis in Vietnamese Adults and Adolescents

Science.gov (United States)

Török, M. Estée; Bang, Nguyen Duc; Chau, Tran Thi Hong; Yen, Nguyen Thi Bich; Thwaites, Guy E.; Thi Quy, Hoang; Dung, Nguyen Huy; Hien, Tran Tinh; Chinh, Nguyen Tran; Thi Thanh Hoang, Hoang; Wolbers, Marcel; Farrar, Jeremy J.

2011-01-01

Background Dexamethasone has been shown to reduce mortality in patients with tuberculous meningitis but the long-term outcome of the disease is unknown. Methods Vietnamese adults and adolescents with tuberculous meningitis recruited to a randomised, double-blind, placebo-controlled trial of adjunctive dexamethasone were followed-up at five years, to determine the effect of dexamethasone on long-term survival and neurological disability. Results 545 patients were randomised to receive either dexamethasone (274 patients) or placebo (271 patients). 50 patients (9.2%) were lost to follow-up at five years. In all patients two-year survival, probabilities tended to be higher in the dexamethasone arm (0.63 versus 0.55; p = 0.07) but five-year survival rates were similar (0.54 versus 0.51, p = 0.51) in both groups. In patients with grade 1 TBM, but not with grade 2 or grade 3 TBM, the benefit of dexamethasone treatment tended to persist over time (five-year survival probabilities 0.69 versus 0.55, p = 0.07) but there was no conclusive evidence of treatment effect heterogeneity by TBM grade (p = 0.36). The dexamethasone group had a similar proportion of severely disabled patients among survivors at five years as the placebo group (17/128, 13.2% vs. 17/116, 14.7%) and there was no significant association between dexamethasone treatment and disability status at five years (p = 0.32). Conclusions Adjunctive dexamethasone appears to improve the probability of survival in patients with TBM, until at least two years of follow-up. We could not demonstrate a five-year survival benefit of dexamethasone treatment which may be confined to patients with grade 1 TBM. Trial Registration ClinicalTrials.gov NCT01317654 NCT01317654?term = tuberculous+meningitis&rank = 3 PMID:22174748

Effect of dexamethasone in primary intracerebral hemorrhage in the south west of iran

International Nuclear Information System (INIS)

Sharafadinzadeh, N.; Baghebanian, S.M.; Pipelzadeh, M.; Moravej, A. A.; Ghanavatiz, P.

2008-01-01

Previous study revealed the value of dexamethasone in the treatment of vasogenic edema associated with brain tumor and abscess. However there are poor documented studies about its usefulness in primary intracerebral hemorrhage. In this study we evaluated dexamethasone effects in primary intracerebral hemorrhage. In a double blind randomized placebo-controlled clinical trial we evaluated 200 intracerebral hemorrhage cases between 40 to 80 years old whom were admitted at Golestan Hospital (Ahwaz, IR) between March 2002 and March 2003. They were divided in two groups dexamethasone (N=100) and placebo (N=100). Then mortality, GI bleeding, fever, electrolytes disturbances, hypertension and hyperglycemic status were analyzed in two groups. Ethical considerations were employed and subjects were followed by appropriate statistical methods for 21 days to assess the major outcomes. Mortality was much higher in the dexamethasone group; Dexamethasone group (49.3%) and placebo (23.4%) and also fever was higher seen in the dexamethasone group; dexamethasone group (40.2%) and placebo group (24.7%) but there was not any significant statistical difference between two groups as regards other complications. Dexamethasone is widely used for cerebral edema associated conditions but in this study we saw that it's complications in intracerebral hemorrhage such as increasing fever and mortality are significantly higher. Hence it use for treatment of primary intracerebral hemorrhage should be reconsidered. (author)

β-Hydroxy-β-methylbutyrate (HMB) prevents dexamethasone-induced myotube atrophy.

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Aversa, Zaira; Alamdari, Nima; Castillero, Estibaliz; Muscaritoli, Maurizio; Rossi Fanelli, Filippo; Hasselgren, Per-Olof

2012-07-13

High levels of glucocorticoids result in muscle wasting and weakness. β-hydroxy-β-methylbutyrate (HMB) attenuates the loss of muscle mass in various catabolic conditions but the influence of HMB on glucocorticoid-induced muscle atrophy is not known. We tested the hypothesis that HMB prevents dexamethasone-induced atrophy in cultured myotubes. Treatment of cultured L6 myotubes with dexamethasone resulted in increased protein degradation and expression of atrogin-1 and MuRF1, decreased protein synthesis and reduced myotube size. All of these effects of dexamethasone were attenuated by HMB. Additional experiments provided evidence that the inhibitory effects of HMB on dexamethasone-induced increase in protein degradation and decrease in protein synthesis were regulated by p38/MAPK- and PI3K/Akt-dependent cell signaling, respectively. The present results suggest that glucocorticoid-induced muscle wasting can be prevented by HMB. Copyright © 2012 Elsevier Inc. All rights reserved.

Dexamethasone Treatment Reverses Cognitive Impairment but Increases Brain Oxidative Stress in Rats Submitted to Pneumococcal Meningitis

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Tatiana Barichello

2011-01-01

Full Text Available Pneumococcal meningitis is associated with a significant mortality rate and neurologic sequelae. The animals received either 10 μL of saline or a S. pneumoniae suspension and were randomized into different groups: sham: placebo with dexamethasone 0.7 mg/kg/1 day; placebo with dexamethasone 0.2 mg/kg/7 days; meningitis groups: dexamethasone 0.7 mg/kg/1 day and dexamethasone 0.2 mg/kg/7 days. Ten days after induction we evaluated memory and oxidative stress parameters in hippocampus and cortex. In the step-down inhibitory avoidance task, we observed memory impairment in the meningitis group with dexamethasone 0.2 mg/kg/7 days. The lipid peroxidation was increased in hippocampus in the meningitis groups with dexamethasone and in cortex only in the meningitis group with dexamethasone 0.2 mg/kg/7 days. The protein carbonyl was increased in hippocampus in the meningitis groups with dexamethasone and in cortex in the meningitis groups with and without dexamethasone. There was a decrease in the proteins integrity in hippocampus in all groups receiving treatment with dexamethasone and in cortex in all groups with dexamethasone (0.7 mg/kg/1 day. The mitochondrial superoxide was increased in the hippocampus and cortex in the meningitis group with dexamethasone 0.2 mg/kg/7 days. Our findings demonstrate that dexamethasone reverted cognitive impairment but increased brain oxidative stress in hippocampus and cortex in Wistar rats ten days after pneumococcal meningitis induction.

Dexamethasone, Intravenous Immunoglobulin, and Rituximab Combination Immunotherapy for Pediatric Opsoclonus-Myoclonus Syndrome.

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Pranzatelli, Michael R; Tate, Elizabeth D

2017-08-01

Although pulse-dose dexamethasone is increasingly favored for treating pediatric opsoclonus-myoclonus syndrome (OMS), and multimodal immunotherapy is associated with improved clinical response, there have been no neuroimmunologic studies of dexamethasone-based multimodal disease-modifying therapy. In this observational retrospective study, 19 children with OMS (with or without associated neuroblastoma) underwent multibiomarker evaluation for neuroinflammation. Nine children of varying OMS severity, duration, and treatment status were treated empirically with pulse dexamethasone, intravenous immunoglobulin (IVIg), and rituximab combination immunotherapy (DEXIR-CI). Another 10 children on dexamethasone alone or with IVIg at initial evaluation only provided a comparison group. Motor severity (total score) was scored rater-blinded via videotapes using the validated OMS Evaluation Scale. DEXIR-CI was associated with a 69% reduction in group total score (P = 0.004) and was clinically well tolerated. Patients given the dexamethasone combination exhibited significantly lowered B cell frequencies in cerebrospinal fluid (-94%) and blood (-76%), normalizing the cerebrospinal fluid B cell percentage. The number of patients with positive inflammatory markers dropped 87% (P = 0.002) as did the number of markers. Cerebrospinal fluid oligoclonal bands were positive in four of nine pretreatment patients but zero of six post-treatment patients. In the comparison group, partial response to dexamethasone alone or with IVIg was associated with multiple positive markers for neuroinflammation despite an average of seven months of treatment. Multimechanistic dexamethasone-based combination immunotherapy increases the therapeutic armamentarium for OMS, providing a viable option for less severely affected individuals. Partial response to dexamethasone with or without IVIg is indicative of ongoing neuroinflammation and should be treated promptly and accordingly. Copyright © 2017

Pregabalin and dexamethasone improves post-operative pain treatment after tonsillectomy

DEFF Research Database (Denmark)

Mathiesen, O; Jørgensen, D G; Hilsted, K L

2011-01-01

Post-tonsillectomy pain can be severe. We investigated the analgesic effect from combinations of paracetamol, pregabalin and dexamethasone in adults undergoing tonsillectomy.......Post-tonsillectomy pain can be severe. We investigated the analgesic effect from combinations of paracetamol, pregabalin and dexamethasone in adults undergoing tonsillectomy....

Paradoxical response to dexamethasone and spontaneous hypocortisolism in Cushing's disease

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Lila, Anurag R; Sarathi, Vijaya; Bandgar, Tushar R; Shah, Nalini S

2013-01-01

Paradoxical response to dexamethasone and spontaneous development of hypocortisolism are rare features of Cushing's disease. We report a 13-year-old boy with Cushing's disease owing to a pituitary macroadenoma. On initial evaluation, he had partial suppression of serum cortisol by dexamethasone. He developed transient hypocortisolism after first adenomectomy, but the disease recurred after 1 year. Repeat evaluation showed recurrent hypercortisolism and paradoxical response to dexamethasone. He underwent second surgery and, postoperatively, hypercostisolism persisted even after 2 years of surgery. Repeat evaluations after 8 years of second surgery revealed persistent hypocortisolism despite residual tumour of same size and similar plasma adrenocorticotropic hormone (ACTH) levels. We have also shown that the paradoxical increase in serum cortisol was preceded by a paradoxical increase in ACTH. The paradoxical response persisted despite hypocortisolism. This patient with Cushing's disease had two very rare features: paradoxical response to dexamethasone and spontaneous development of hypocortisolism. PMID:23365169

Proteins mediating intra- and intercellular transport of lipids and lipid-modified proteins

NARCIS (Netherlands)

Neumann, S.

2008-01-01

Proteins mediating intra- and intercellular transport of lipids and lipid-modified proteins In this thesis, I studied the intra- and intercellular transport of lipidic molecules, in particular glycosphingolipids and lipid-modified proteins. The first part focuses on the intracellular transport of

Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma.

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Stewart, A Keith; Rajkumar, S Vincent; Dimopoulos, Meletios A; Masszi, Tamás; Špička, Ivan; Oriol, Albert; Hájek, Roman; Rosiñol, Laura; Siegel, David S; Mihaylov, Georgi G; Goranova-Marinova, Vesselina; Rajnics, Péter; Suvorov, Aleksandr; Niesvizky, Ruben; Jakubowiak, Andrzej J; San-Miguel, Jesus F; Ludwig, Heinz; Wang, Michael; Maisnar, Vladimír; Minarik, Jiri; Bensinger, William I; Mateos, Maria-Victoria; Ben-Yehuda, Dina; Kukreti, Vishal; Zojwalla, Naseem; Tonda, Margaret E; Yang, Xinqun; Xing, Biao; Moreau, Philippe; Palumbo, Antonio

2015-01-08

Lenalidomide plus dexamethasone is a reference treatment for relapsed multiple myeloma. The combination of the proteasome inhibitor carfilzomib with lenalidomide and dexamethasone has shown efficacy in a phase 1 and 2 study in relapsed multiple myeloma. We randomly assigned 792 patients with relapsed multiple myeloma to carfilzomib with lenalidomide and dexamethasone (carfilzomib group) or lenalidomide and dexamethasone alone (control group). The primary end point was progression-free survival. Progression-free survival was significantly improved with carfilzomib (median, 26.3 months, vs. 17.6 months in the control group; hazard ratio for progression or death, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P=0.0001). The median overall survival was not reached in either group at the interim analysis. The Kaplan-Meier 24-month overall survival rates were 73.3% and 65.0% in the carfilzomib and control groups, respectively (hazard ratio for death, 0.79; 95% CI, 0.63 to 0.99; P=0.04). The rates of overall response (partial response or better) were 87.1% and 66.7% in the carfilzomib and control groups, respectively (P<0.001; 31.8% and 9.3% of patients in the respective groups had a complete response or better; 14.1% and 4.3% had a stringent complete response). Adverse events of grade 3 or higher were reported in 83.7% and 80.7% of patients in the carfilzomib and control groups, respectively; 15.3% and 17.7% of patients discontinued treatment owing to adverse events. Patients in the carfilzomib group reported superior health-related quality of life. In patients with relapsed multiple myeloma, the addition of carfilzomib to lenalidomide and dexamethasone resulted in significantly improved progression-free survival at the interim analysis and had a favorable risk-benefit profile. (Funded by Onyx Pharmaceuticals; ClinicalTrials.gov number, NCT01080391.).

Adverse effects of parenteral dexamethasone in the treatment of pemphigus vulgaris

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Mohammad Jamal Uddin

2016-08-01

Full Text Available Background: Pemphigus vulgaris is associated with high morbidity as well as significant mortality rate. Today the risk of death in pemphigus from the side effect of oral prednisolone is greater than risk of death from the disease itself. Objec­tive: To observe the adverse effects of parenteral dexamethasone compared with oral prednisolone in the treatment of pemphigus vulgaris. Methods: An interventional study was carried out in the department of Dermatology and Venereol­ogy, Bangabandu Sheikh Mujib Medical University, Dhaka, Bangladesh. Total number of patients was thirty and among them fifteen patients were treated with parenteral dexamethasone (Group-A and other fifteen were treated with oral prednisolone (Group-B. Results: The study showed statistically significant differences of skin lesion as well as mucosal lesion of pemphigus after 6 weeks of therapy between of two groups (P<0.05. The most common adverse effects were increased body weight(40%, increased appetite(40%, and puffy face(40% in dexamethasone group. In prednisolone group, these side effects were 60% of the subjects. Other side effects in dexamethasone group were hyperglycemia (33.33%, hypertension (26.66%, and sleep disturbance (13.33%. In prednisolone group, other side effects were hyperglycemia(33.33%, hypertension(40%, gastritis (33.33%, nausea, vomiting (13.33% in each , reactivation of tuberculosis, herpes zoster infection, sleep disturbance, and mood change were 6.66% in each group. Conclusion: In the light of the findings of the study, we conclude that each of the treatment of dexamethasone group and prednisolone group is individually effective and safe in the treatment of pemphigus vulgaris but adverse effects are less in parenteral dexamethasone group than oral prednisolone group. So parenteral dexamethasone can be used as an alternative drug in the treatment of pemphigus vulgaris.

Dexamethasone as adjuvant therapy in the treatment of invasive meningococcal diseases.

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Tolaj, Ilir; Dreshaj, Shemsedin; Qehaja, Emine; Tolaj, Jasmina; Doda-Ejupi, Teuta; Mehmeti, Murat

2010-01-01

With this study we want to evaluate the role of dexamethasone adjuvant treatment in different clinical forms of invasive meningococcal diseases. WORK METHODS: This was a randomized, open label trial that was conducted in 147 individuals with meningococcal sepsis. All of the cases have been divided in two groups: (1) Cases with meningococcal disease and CNS infection, and (2) Cases with meningococcal disease and no affection of the CNS. Cases from both groups were treated with dexamethasone, 0.15 mg/kg, every 6 h, for 4 (four) days, as adjuvant therapy. Cases which were not treated with dexamethasone were used as control group. From overall number of cases, in 130 of them, the meningococcal disease was accompanied with meningitis; in other 17 cases only signs of sepsis were present. In both clinical forms, the dexamethasone was used in 92 cases. The higher mortality rate is registered among the cases without meningitis, 17.65%, compared with 6.92% which is registered among cases with meningitis. The overall mortality rate among all cases was 8.2%. The significant difference was recorded only on CSF sugar level between two groups (treated or not with dexamethasone) on the day 1-4 of the hospitalization. Our epidemiological data are in correlation with data from other epidemiological studies. Most of the cases 69.4%, were more than 12 hours sick at home before the hospitalization, 7.5 % of cases were hospitalized within 12 hours from the onset of the diseases, while 23.1% of cases data are missing. This is in correlation with similar data from other studies. Dexamethasone has a limited effect on outcome of the invasive meningococcal disease. Dexamethasone had some effect only during the days of administration in cases with clinical form of sepsis with meningitis, by normalizing the values of CSF sugar earlier.

Herpes simplex virus glycoprotein D relocates nectin-1 from intercellular contacts.

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Bhargava, Arjun K; Rothlauf, Paul W; Krummenacher, Claude

2016-12-01

Herpes simplex virus (HSV) uses the cell adhesion molecule nectin-1 as a receptor to enter neurons and epithelial cells. The viral glycoprotein D (gD) is used as a non-canonical ligand for nectin-1. The gD binding site on nectin-1 overlaps with a functional adhesive site involved in nectin-nectin homophilic trans-interaction. Consequently, when nectin-1 is engaged with a cellular ligand at cell junctions, the gD binding site is occupied. Here we report that HSV gD is able to disrupt intercellular homophilic trans-interaction of nectin-1 and induce a rapid redistribution of nectin-1 from cell junctions. This movement does not require the receptor's interaction with the actin-binding adaptor afadin. Interaction of nectin-1 with afadin is also dispensable for virion surfing along nectin-1-rich filopodia. Cells seeded on gD-coated surfaces also fail to accumulate nectin-1 at cell contact. These data indicate that HSV gD affects nectin-1 locally through direct interaction and more globally through signaling. Copyright © 2016 Elsevier Inc. All rights reserved.

Intercellular protein-protein interactions at synapses.

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Yang, Xiaofei; Hou, Dongmei; Jiang, Wei; Zhang, Chen

2014-06-01

Chemical synapses are asymmetric intercellular junctions through which neurons send nerve impulses to communicate with other neurons or excitable cells. The appropriate formation of synapses, both spatially and temporally, is essential for brain function and depends on the intercellular protein-protein interactions of cell adhesion molecules (CAMs) at synaptic clefts. The CAM proteins link pre- and post-synaptic sites, and play essential roles in promoting synapse formation and maturation, maintaining synapse number and type, accumulating neurotransmitter receptors and ion channels, controlling neuronal differentiation, and even regulating synaptic plasticity directly. Alteration of the interactions of CAMs leads to structural and functional impairments, which results in many neurological disorders, such as autism, Alzheimer's disease and schizophrenia. Therefore, it is crucial to understand the functions of CAMs during development and in the mature neural system, as well as in the pathogenesis of some neurological disorders. Here, we review the function of the major classes of CAMs, and how dysfunction of CAMs relates to several neurological disorders.

Anti-CD163-dexamethasone conjugate inhibits the acute phase response to lipopolysaccharide in rats

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Thomsen, Karen Louise; Møller, Holger Jon; Graversen, Jonas Heilskov

2016-01-01

± 4036 pg/mL, P = 0.03) compared to the low dose dexamethasone. The high dose dexamethasone dose decreased the spleen weight (421 ± 11 mg vs 465 ± 12 mg, P any other group. CONCLUSION: Low-dose anti-CD163-dexamethasone conjugate effectively decreased...

β-Hydroxy-β-methylbutyrate (HMB normalizes dexamethasone-induced autophagy-lysosomal pathway in skeletal muscle.

Directory of Open Access Journals (Sweden)

María D Girón

Full Text Available Dexamethasone-induced muscle atrophy is due to an increase in protein breakdown and a decrease in protein synthesis, associated with an over-stimulation of the autophagy-lysosomal pathway. These effects are mediated by alterations in IGF-1 and PI3K/Akt signaling. In this study, we have investigated the effects of β-Hydroxy-β-methylbutyrate (HMB on the regulation of autophagy and proteosomal systems. Rats were treated during 21 days with dexamethasone as a model of muscle atrophy. Co-administration of HMB attenuated the effects promoted by dexamethasone. HMB ameliorated the loss in body weight, lean mass and the reduction of the muscle fiber cross-sectional area (shrinkage in gastrocnemius muscle. Consequently, HMB produced an improvement in muscle strength in the dexamethasone-treated rats. To elucidate the molecular mechanisms responsible for these effects, rat L6 myotubes were used. In these cells, HMB significantly attenuated lysosomal proteolysis induced by dexamethasone by normalizing the changes observed in autophagosome formation, LC3 II, p62 and Bnip3 expression after dexamethasone treatment. HMB effects were mediated by an increase in FoxO3a phosphorylation and concomitant decrease in FoxO transcriptional activity. The HMB effect was due to the restoration of Akt signaling diminished by dexamethasone treatment. Moreover, HMB was also involved in the regulation of the activity of ubiquitin and expression of MurF1 and Atrogin-1, components of the proteasome system that are activated or up-regulated by dexamethasone. In conclusion, in vivo and in vitro studies suggest that HMB exerts protective effects against dexamethasone-induced muscle atrophy by normalizing the Akt/FoxO axis that controls autophagy and ubiquitin proteolysis.

β-Hydroxy-β-methylbutyrate (HMB) normalizes dexamethasone-induced autophagy-lysosomal pathway in skeletal muscle.

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Girón, María D; Vílchez, Jose D; Shreeram, Sathyavageeswaran; Salto, Rafael; Manzano, Manuel; Cabrera, Elena; Campos, Nefertiti; Edens, Neile K; Rueda, Ricardo; López-Pedrosa, Jose M

2015-01-01

Dexamethasone-induced muscle atrophy is due to an increase in protein breakdown and a decrease in protein synthesis, associated with an over-stimulation of the autophagy-lysosomal pathway. These effects are mediated by alterations in IGF-1 and PI3K/Akt signaling. In this study, we have investigated the effects of β-Hydroxy-β-methylbutyrate (HMB) on the regulation of autophagy and proteosomal systems. Rats were treated during 21 days with dexamethasone as a model of muscle atrophy. Co-administration of HMB attenuated the effects promoted by dexamethasone. HMB ameliorated the loss in body weight, lean mass and the reduction of the muscle fiber cross-sectional area (shrinkage) in gastrocnemius muscle. Consequently, HMB produced an improvement in muscle strength in the dexamethasone-treated rats. To elucidate the molecular mechanisms responsible for these effects, rat L6 myotubes were used. In these cells, HMB significantly attenuated lysosomal proteolysis induced by dexamethasone by normalizing the changes observed in autophagosome formation, LC3 II, p62 and Bnip3 expression after dexamethasone treatment. HMB effects were mediated by an increase in FoxO3a phosphorylation and concomitant decrease in FoxO transcriptional activity. The HMB effect was due to the restoration of Akt signaling diminished by dexamethasone treatment. Moreover, HMB was also involved in the regulation of the activity of ubiquitin and expression of MurF1 and Atrogin-1, components of the proteasome system that are activated or up-regulated by dexamethasone. In conclusion, in vivo and in vitro studies suggest that HMB exerts protective effects against dexamethasone-induced muscle atrophy by normalizing the Akt/FoxO axis that controls autophagy and ubiquitin proteolysis.

The effect of single low-dose dexamethasone on vomiting during awake craniotomy.

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Kamata, Kotoe; Morioka, Nobutada; Maruyama, Takashi; Komayama, Noriaki; Nitta, Masayuki; Muragaki, Yoshihiro; Kawamata, Takakazu; Ozaki, Makoto

2016-12-01

Intraoperative vomiting leads to serious respiratory complications that could influence the surgical decision-making process for awake craniotomy. However, the use of antiemetics is still limited in Japan. The aim of this study was to investigate the effect of prophylactically administered single low-dose dexamethasone on the incidence of vomiting during awake craniotomy. The frequency of hyperglycemia was also examined. We conducted a retrospective case review of awake craniotomy for glioma resection between 2012 and 2015. Of the 124 patients, 91 were included in the analysis. Dexamethasone was not used in 43 patients and the 48 remaining patients received an intravenous bolus of 4.95 mg dexamethasone at anesthetic induction. Because of stable operating conditions, no one required conscious sedation throughout functional mapping and tumor resection. Although dexamethasone pretreatment reduced the incidence of intraoperative vomiting (P = 0.027), the number of patients who complained of nausea was comparable (P = 0.969). No adverse events related to vomiting occurred intraoperatively. Baseline blood glucose concentration did not differ between each group (P = 0.143), but the samples withdrawn before emergence (P = 0.018), during the awake period (P awake craniotomy cases. However, as even a small dose of dexamethasone increases the risk for hyperglycemia, antiemetic prophylaxis with dexamethasone should be administered after careful consideration. Monitoring of perioperative blood glucose concentration is also necessary.

Intravitreal clindamycin and dexamethasone for toxoplasmic retinochoroiditis.

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Kishore, K; Conway, M D; Peyman, G A

2001-01-01

To present a new method for the management of toxoplasmic retinochoroiditis (TRC). The patients were females ranging in age from 10 to 61 years (average 26.5). Four eyes of 4 patients were treated with intravitreal injections of 1.0 mg clindamycin in 0.1 mL and 1.0 mg of dexamethasone in 0.1 mL. The injections were given under general or peribulbar anesthesia. Three patients continued one systemic drug. Follow-up ranged from 11 to 26 months (mean 17.5). A favorable response was noted in each eye within two weeks after the intravitreal injections. All patients required 2 to 4 intravitreal injections in the affected eye for the control of TRC. Visual acuity improved in each eye. The disc and macula were preserved in all eyes. Recurrence was noted in one case, which responded to a repeated intravitreal injection of clindamycin and dexamethasone. Intravitreal injections of clindamycin and dexamethasone are well tolerated and may offer an additional strategy to treat TRC in patients who are unable to afford or tolerate systemic therapy, or whose disease progresses despite systemic therapy.

Preoperative dexamethasone reduces acute but not sustained pain after lumbar disk surgery

DEFF Research Database (Denmark)

Nielsen, Rikke V; Siegel, Hanna; Fomsgaard, Jonna S

2015-01-01

on acute and sustained pain after lumbar disk surgery. In this blinded study, 160 patients undergoing lumbar disk surgery were randomly assigned to 16 mg IV dexamethasone or placebo. All patients received perioperative paracetamol and ibuprofen, and postoperative IV patient-controlled analgesia...... months postoperatively. Acute pain during mobilization (weighted average area under the curve, 2-24 hours) was significantly reduced in the dexamethasone group: 33 (22) mm vs placebo 43 (18) mm, (95% confidence interval [CI] 3-16) P = 0.005. Vomiting 0 to 24 hours postoperatively was reduced....../paralysis of the legs in the dexamethasone and placebo groups, respectively, 3 months postoperatively (P = 0.20). In conclusion, preoperative dexamethasone significantly reduced pain during mobilization and vomiting, after lumbar disk surgery. No significant effects were observed 3 months postoperatively....

On the involvement of host proteins in Cowpea mosaic virus intercellular spread

NARCIS (Netherlands)

Hollander, den P.W.

2014-01-01

Abstract of thesis Paulus den Hollander entitled “On the involvement of host proteins in Cowpea mosaic virus intercellular spread”.

Defence: 18th of November 13.30 h

Abstract

Intercellular spread of Cowpea mosaic virus (CPMV) occurs via movement

Rituximab and Dexamethasone vs Dexamethasone Monotherapy in Newly Diagnosed Patients with Primary Immune Thrombocytopenia

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Gudbrandsdottir, Sif; Birgens, Henrik Sverre; Frederiksen, Henrik

2013-01-01

In this study, we report the results from the largest cohort to date of newly diagnosed adult immune thrombocytopenia patients randomized to treatment with dexamethasone alone or in combination with rituximab. Eligible were patients with platelet counts ≤25×10(9)/L or ≤50×10(9)/L with bleeding sy...

Terbinafine inhibits gap junctional intercellular communication

International Nuclear Information System (INIS)

Lee, Ju Yeun; Yoon, Sei Mee; Choi, Eun Ju; Lee, Jinu

2016-01-01

Terbinafine is an antifungal agent that selectively inhibits fungal sterol synthesis by blocking squalene epoxidase. We evaluated the effect of terbinafine on gap junctional intercellular communication (GJIC). Fluorescence recovery after photobleaching (FRAP) and I-YFP GJIC assays revealed that terbinafine inhibits GJIC in a reversible and dose-dependent manner in FRT-Cx43 and LN215 cells. Treatment with terbinafine did not affect Cx43 phosphorylation status or intracellular Ca 2+ concentration, well-known action mechanisms of various GJIC blockers. While a structurally related chemical, naftifine, attenuated GJIC, epigallocatechin gallate, another potent squalene epoxidase inhibitor with a different structure, did not. These results suggest that terbinafine inhibits GJIC with a so far unknown mechanism of action. - Highlights: • In vitro pharmacological studies were performed on FRT-Cx43 and LN215 cells. • Terbinafine inhibits gap junctional intercellular communication in both cell lines. • The inhibitory effect of terbinafine is reversible and dose-dependent. • Treatment of terbinafine does not alter Cx43 phosphorylation or cytosolic Ca 2+ concentration. • Inhibition of squalene epoxidase is not involved in this new effect of terbinafine.

Impact of prior treatment and depth of response on survival in MM-003, a randomized phase 3 study comparing pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed/refractory multiple myeloma

Science.gov (United States)

San Miguel, Jesus F.; Weisel, Katja C.; Song, Kevin W.; Delforge, Michel; Karlin, Lionel; Goldschmidt, Hartmut; Moreau, Philippe; Banos, Anne; Oriol, Albert; Garderet, Laurent; Cavo, Michele; Ivanova, Valentina; Alegre, Adrian; Martinez-Lopez, Joaquin; Chen, Christine; Renner, Christoph; Bahlis, Nizar Jacques; Yu, Xin; Teasdale, Terri; Sternas, Lars; Jacques, Christian; Zaki, Mohamed H.; Dimopoulos, Meletios A.

2015-01-01

Pomalidomide is a distinct oral IMiD® immunomodulatory agent with direct antimyeloma, stromal-support inhibitory, and immunomodulatory effects. The pivotal, multicenter, open-label, randomized phase 3 trial MM-003 compared pomalidomide + low-dose dexamethasone vs high-dose dexamethasone in 455 patients with refractory or relapsed and refractory multiple myeloma after failure of bortezomib and lenalidomide treatment. Initial results demonstrated significantly longer progression-free survival and overall survival with an acceptable tolerability profile for pomalidomide + low-dose dexamethasone vs high-dose dexamethasone. This secondary analysis describes patient outcomes by treatment history and depth of response. Pomalidomide + low-dose dexamethasone significantly prolonged progression-free survival and favored overall survival vs high-dose dexamethasone for all subgroups analyzed, regardless of prior treatments or refractory status. Both univariate and multivariate analyses showed that no variable relating to either the number (≤ or > 3) or type of prior treatment was a significant predictor of progression-free survival or overall survival. No cross-resistance with prior lenalidomide or thalidomide treatment was observed. Patients achieving a minimal response or better to pomalidomide + low-dose dexamethasone treatment experienced a survival benefit, which was even higher in those achieving at least a partial response (17.2 and 19.9 months, respectively, as compared with 7.5 months for patients with less than minimal response). These data suggest that pomalidomide + low-dose dexamethasone should be considered a standard of care in patients with refractory or relapsed and refractory multiple myeloma regardless of prior treatment. ClinicalTrials.gov: NCT01311687; EudraCT: 2010-019820-30. PMID:26160879

Low-dose dexamethasone during arthroplasty: What do we know about the risks?

NARCIS (Netherlands)

Wegener, Jessica T.; Kraal, Tim; Stevens, Markus F.; Hollmann, Markus W.; Kerkhoffs, Gino M. M. J.; Haverkamp, Daniël

2016-01-01

Dexamethasone is commonly applied during arthroplasty to control post-operative nausea and vomiting (PONV). However, conflicting views of orthopaedic surgeons and anaesthesiologists regarding the use of dexamethasone raise questions about risks of impaired wound healing and surgical site infections

[Inhibition of gap junctional intercellular communication protects astrocytes from hypoxia/reoxygenation injury].

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Tong, Xu-Hui; Gu, Yu-Chen; Jiao, Hao; Yu, Li; Dong, Shu-Ying

2015-01-01

To investigate the effects of inhibiting gap junctional intercellular communication on hypoxia/reoxygenation injury in astrocytes. Primary cultured cerebral cortical astrocytes of neonate rats were divided into normal control group, hypoxia reoxygenation injury group and 18-α-glycyrrhetinic acid and oleamide (gap junctional intercellular channel inhibitors) group. The gap junction intercellular communication was determined by Parachute assay. The viability of astrocyes was detected by MTT assay. The apoptosis of astrocytes were detected with annexin V/PI and Hoechst 33258 staining. Compared with the normal control group, the gap junctional function of astrocytes was increased significantly in ischemia/reperfusion group (Pastrocytes decreased significantly (Pastrocytes in18-α-glycyrrhetinic acid and oleamide group decreased significantly (Pastrocytes increased significantly (Pastrocytes.

Intercellular signalling in Stigmatella aurantiaca.

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Plaga, W; Ulrich, S H

1999-12-01

The myxobacterium Stigmatella aurantiaca is a prokaryotic model used to study intercellular signalling and the genetic determination of morphogenesis. Signalling factors and genes required for the generation of the elaborate multicellular fruiting body are to be identified. Recently, the structure of stigmolone, which is the pheromone necessary for fruiting body formation, was elucidated, and genes involved in development were characterised. Progress has also been made in the genetic accessibility of S. aurantiaca.

Dexamethasone prolongs local analgesia after subcutaneous infiltration of bupivacaine microcapsules in human volunteers

DEFF Research Database (Denmark)

Holte, Kathrine; Werner, Mads U; Lacouture, Peter G

2002-01-01

BACKGROUND: The addition of small amounts of dexamethasone to extended-release formulations of bupivacaine in microcapsules has been found to prolong local analgesia in experimental studies, but no clinical data are available. METHODS: In a double-blinded study, 12 healthy male volunteers were...... randomized to receive simultaneous subcutaneous injections of bupivacaine microcapsules with dexamethasone and bupivacaine microcapsules without dexamethasone in each calf. Local analgesia was assessed with a validated human pain model; main parameters evaluated were thermal, mechanical, and pain detection...... curve [AUC]) were considered best estimate of analgesia. Safety evaluations were performed daily for the first week and at 2 weeks, 6 weeks, and 6 months after injection. RESULTS: The addition of dexamethasone significantly prolonged local analgesia of bupivacaine microcapsules without influence...

Does Dexamethasone Helps in Meningococcal Sepsis?

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Tolaj, Ilir; Ramadani, Hamdi; Mehmeti, Murat; Gashi, Hatixhe; Kasumi, Arbana; Gashi, Visar; Jashari, Haki

2017-06-01

Prompt recognition and aggressive early treatment are the only effective measures against invasive meningococcal disease (IMD). Anti-inflammatory adjunctive treatment remains controversial and difficult to assess in patients with IMD. The purpose of this study was to evaluate the effect of dexamethasone (DXM) as adjunctive treatment in different clinical forms of IMD, and attempt to answer if DXM should be routinely used in the treatment of IMD. In this non-interventional clinical study (NIS), 39 patients with meningococcal septicaemia with or without of meningitis were included, and compared regarding the impact of dexamethasone (DXM), as an adjunctive treatment, on the outcome of IMD. SPSS statistics is used for statistical processing of data. Thirty (76.9%) patients with IMD had sepsis and meningitis, and 9 (23.1%) of them had sepsis alone. Dexamethasone was used in 24 (61.5%) cases, in both clinical groups. The overall mortality rate was 10.3%. Pneumonia was diagnosed in 6 patients (15.4%), arthritis in 3 of them (7.7%), and subdural effusion in one patient (2.6%). The data showed a significant statistical difference on the length of hospitalization, and WBC normalization in groups of patients treated with DXM. The use of DXM as adjunctive therapy in invasive meningococcal disease has a degree of proven benefits and no harmful effects. In fighting this very dangerous and complex infection, even a limited benefit is sufficient to recommend the use of DXM as adjunctive treatment in invasive meningococcal disease.

Comparison the Effect of Granisetron and Dexamethasone on Intravenous Propofol Pain.

Science.gov (United States)

Adinehmehr, Leili; Salimi, Sohrab; Sane, Shahryar; Sina, Venous; Najafizadeh, Rana

2018-01-01

The incidence of propofol injection pain during induction of general anesthesia varies from 28% to 90%. This prospective, randomized, double-blind, placebo-controlled study evaluated the effect of dexamethasone and granisetron for reducing the incidence and severity of propofol injection pain. A total of 227 female subjects received 5 mL of preservative-free saline, 1 mg granisetron (5 ml), or 0.15 mg/kg of dexamethasone (5 ml), intravenously, following exsanguination and occlusion of the veins of the arm. This was followed by a 0.5 mg/kg injection of propofol. Pain scores and intensity of pain recorded immediately following the injection of propofol. Hemodynamic parameters and O 2 sat were recorded 1, 3, 5, and 10 min after propofol injection. The incidence pain following the injection of propofol was significantly decreased with both granisetron and dexamethasone (50.7% and 49.4%). Mean pain score in granisetron group was 3.16 ± 1.23, dexamethasone was 2.73 ± 1.03, and in saline group was 4.82 ± 1.73 ( P = 0.001). Mean pain intensity in granisetron group was 1.16 ± 0.18, dexamethasone was 1.26 ± 0.14, and in saline group was 2.2 ± 0.99 ( P = 0.001). There were no differences in either mean arterial pressure or O 2 Sate at any time point after drugs injection among the groups. There was a significant difference in pulse rate in third minutes between three groups and in the group who received granisetron was lesser ( P = 0.04). Pretreatment with intravenous granisetron (1 mg) and dexamethasone (0.15 mg/kg) before injection of propofol is effective and safe in reducing the incidence and severity of pain due to propofol injection.

Comparison the Effect of Granisetron and Dexamethasone on Intravenous Propofol Pain

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Leili Adinehmehr

2018-01-01

Full Text Available Background: The incidence of propofol injection pain during induction of general anesthesia varies from 28% to 90%. This prospective, randomized, double-blind, placebo-controlled study evaluated the effect of dexamethasone and granisetron for reducing the incidence and severity of propofol injection pain. Materials and Methods: A total of 227 female subjects received 5 mL of preservative-free saline, 1 mg granisetron (5 ml, or 0.15 mg/kg of dexamethasone (5 ml, intravenously, following exsanguination and occlusion of the veins of the arm. This was followed by a 0.5 mg/kg injection of propofol. Pain scores and intensity of pain recorded immediately following the injection of propofol. Hemodynamic parameters and O2sat were recorded 1, 3, 5, and 10 min after propofol injection. Results: The incidence pain following the injection of propofol was significantly decreased with both granisetron and dexamethasone (50.7% and 49.4%. Mean pain score in granisetron group was 3.16 ± 1.23, dexamethasone was 2.73 ± 1.03, and in saline group was 4.82 ± 1.73 (P = 0.001. Mean pain intensity in granisetron group was 1.16 ± 0.18, dexamethasone was 1.26 ± 0.14, and in saline group was 2.2 ± 0.99 (P = 0.001. There were no differences in either mean arterial pressure or O2Sate at any time point after drugs injection among the groups. There was a significant difference in pulse rate in third minutes between three groups and in the group who received granisetron was lesser (P = 0.04. Conclusion: Pretreatment with intravenous granisetron (1 mg and dexamethasone (0.15 mg/kg before injection of propofol is effective and safe in reducing the incidence and severity of pain due to propofol injection.

Comparison the Effect of Granisetron and Dexamethasone on Intravenous Propofol Pain

Science.gov (United States)

Adinehmehr, Leili; Salimi, Sohrab; Sane, Shahryar; Sina, Venous; Najafizadeh, Rana

2018-01-01

Background: The incidence of propofol injection pain during induction of general anesthesia varies from 28% to 90%. This prospective, randomized, double-blind, placebo-controlled study evaluated the effect of dexamethasone and granisetron for reducing the incidence and severity of propofol injection pain. Materials and Methods: A total of 227 female subjects received 5 mL of preservative-free saline, 1 mg granisetron (5 ml), or 0.15 mg/kg of dexamethasone (5 ml), intravenously, following exsanguination and occlusion of the veins of the arm. This was followed by a 0.5 mg/kg injection of propofol. Pain scores and intensity of pain recorded immediately following the injection of propofol. Hemodynamic parameters and O2 sat were recorded 1, 3, 5, and 10 min after propofol injection. Results: The incidence pain following the injection of propofol was significantly decreased with both granisetron and dexamethasone (50.7% and 49.4%). Mean pain score in granisetron group was 3.16 ± 1.23, dexamethasone was 2.73 ± 1.03, and in saline group was 4.82 ± 1.73 (P = 0.001). Mean pain intensity in granisetron group was 1.16 ± 0.18, dexamethasone was 1.26 ± 0.14, and in saline group was 2.2 ± 0.99 (P = 0.001). There were no differences in either mean arterial pressure or O2 Sate at any time point after drugs injection among the groups. There was a significant difference in pulse rate in third minutes between three groups and in the group who received granisetron was lesser (P = 0.04). Conclusion: Pretreatment with intravenous granisetron (1 mg) and dexamethasone (0.15 mg/kg) before injection of propofol is effective and safe in reducing the incidence and severity of pain due to propofol injection. PMID:29862223

Experimental study on effect of dexamethasone to the in-stent restenosis after vascular intervention

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Wang Jianbo; Yang Jianyong; Chen Wei; Zhuang Wenquan; Li Jiaping; Zhang Longjuan

2007-01-01

Objective: To evaluate the effect of dexamethasone to the cultured rat thoracic aortic smooth muscle cells (SMC) in vitro, and explore the role on it's prevention and cure for the in-stent restenosis after vascular intervention. Methods: The rat thoracic aortic SMC were harvested and cultured for six to ten passages. The cultured SMC were synchronized and then restimutated to enter the cell cycle, and treated with incremental concentrations of dexamethasone or without dexamethasone as control. The proliferative assay was performed with MTT method in the different time points after treatment. RT-PCR was performed to assay the level of proliferating cell nuclear antigen (PCNA) mRNA. Results: 1. Dexamethasone progressively inhibited rat aortic SMC proliferation in a concentration-dependent fashion. The A value was statistically significant for different concentrations (F=36.02, P -6 and 10 -5 mol/L (P=0.065) or between 10 -11 mol/L and control group (P 0.567). 2. RT-PCR suggested dexamethasone significantly decreased rat aortic SMC PCNA mRNA transcription in a concentration-dependent fashion. Statistical analysis indicated F=15.407 and P -9 or 10 -11 mol/L groups by post hoc analysis. Conclusions: Dexamethasone inhibits rat aortic SMC proliferation in a concentration- dependent fashion. The data suggest that effective action concentration is 10 -7 mol/L with persistent time up to 96 hours or more. Dexamethasone may play the inhibit role to SMC at lower concentration with prolonging action time. (authors)

The association between soluble intercellular adhesion molecule-1 levels in drained dialysate and peritoneal injury in peritoneal dialysis.

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Igarashi, Yusuke; Morishita, Yoshiyuki; Yoshizawa, Hiromichi; Imai, Reika; Imai, Toshimi; Hirahara, Ichiro; Akimoto, Tetsu; Ookawara, Susumu; Ishibashi, Kenichi; Muto, Shigeaki; Nagata, Daisuke

2017-11-01

Chronic inflammation of the peritoneum causes peritoneal injury in patients on peritoneal dialysis. Intercellular adhesion molecule-1 and its circulating form, soluble intercellular adhesion molecule-1, play pivotal roles in inflammation. However, their role in peritoneal injury is unclear. We measured changes in intercellular adhesion molecule-1 expression in the peritoneum of a peritoneal injury model in rats. The associations between soluble intercellular adhesion molecule-1 levels in drained dialysate and the solute transport rate (D/P-Cr and D/D0-glucose) determined by the peritoneal equilibration test, and matrix metalloproteinase-2 levels in drained dialysate were investigated in 94 peritoneal drained dialysate samples. Intercellular adhesion molecule-1 expression was increased in the peritoneum of rats with peritoneal injury. Soluble intercellular adhesion molecule-1 levels in drained dialysate were significantly positively correlated with D/P-Cr (r = .51, p molecule-1expression is increased in the peritoneum of a peritoneal injury model in the rat, and soluble intercellular adhesion molecule-1 levels in drained dialysate are associated with peritoneal injury in patients on peritoneal dialysis. These results suggest that soluble intercellular adhesion molecule-1 could be a novel biomarker of peritoneal injury in patients on peritoneal dialysis.

Development of schizogenous intercellular spaces in plants

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Kimitsune eIshizaki

2015-07-01

Full Text Available Gas exchange is essential for multicellular organisms. In contrast to the circulatory systems of animals, land plants have tissues with intercellular spaces (ICSs, called aerenchyma, that are critical for efficient gas exchange. Plants form ICSs by two different mechanisms: schizogeny, where localized cell separation creates spaces; and lysogeny, where cells die to create intercellular spaces. In schizogenous ICS formation, specific molecular mechanisms regulate the sites of cell separation and coordinate extensive reorganization of cell walls. Emerging evidence suggests the involvement of extracellular signaling, mediated by peptide ligands and leucine-rich repeat receptor-like kinases, in the regulation of cell wall remodeling during cell separation. Recent work on the liverwort Marchantia polymorpha has demonstrated a critical role for a plasma membrane-associated plant U-box E3 ubiquitin ligase in ICS formation. In this review, I discuss the mechanism of schizogenous ICS formation, focusing on the potential role of extracellular signaling in the regulation of cell separation.

Evaluation of the release behavior of the dexamethasone embedded in polycarbonate polyurethane membranes: an in vitro study

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Kim, Dong Hyun; Kang, Sung Gwon; Lee, Chul Gab; Park, Sang Soo; Lee, Don Haeng; Lee, Gyu Baek; Song, Ho Young

2003-01-01

To evaluate the release behavior of dexamethasone embedded in a polycarbonate polyurethane membrane. Both water-soluble and water-insoluble dexamethasone were tested, and the release behavior of five water-insoluble dexamethasone films of different thickness (78 to 211 μm) was also evaluated. The amount of dexamethasone used was 10% of the total weight of the polyurethan film mass. Each film was placed in a centrifuge tube containing 25 ml of 0.1-M neutral phosphate buffer, and the tubes were placed in a shaking incubator to quantify the amount of drug released into the buffer, absorption spectroscopy (λ max=242 nm) was employed. In the test involving water-soluble dexamethasone, 60%, of the drug was released during the first two hours of the study. Films containing water-insoluble dexamethasone, on the other hand, released 40%, 60% and 75% of the dexamethasone in one, three and seven days, respectively. Both types of film maintained low-dose drug release for 28 days. When release behavior was compared between water-insoluble films of different thickness, thicker film showed less initial burst and more sustained release. Dexamethasone release behavior varies according to drug solubility and membrane thickness, and may thus be conrolled

Targeting Dexamethasone to Macrophages in a Porcine Endotoxemic Model

DEFF Research Database (Denmark)

Granfeldt, Asger; Hvas, Christine Lodberg; Graversen, Jonas Heilskov

2013-01-01

-8 minutes. CONCLUSION: Targeted delivery of dexamethasone to macrophages using a humanized CD163 antibody as carrier exhibits anti-inflammatory effects comparable with 50 times higher concentrations of free dexamethasone and does not inhibit endogenous cortisol production. This antibody-drug complex showing......OBJECTIVES: Macrophages are important cells in immunity and the main producers of pro-inflammatory cytokines. The main objective was to evaluate if specific delivery of glucocorticoid to the macrophage receptor CD163 is superior to systemic glucocorticoid therapy in dampening the cytokine response...

Long-term Effects of Dexamethasone on Reproductive Parameters in Male Mice

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jalogoden Gouyandeh

2015-02-01

Full Text Available Background & aim: The adverse effect of chemical drugs such as dexamethasone as anti-inflammatory -steroidal drugs on different body systems and infertility and reproductive efficiency is of concern. The purpose of this study was to evaluate the long-term effects of dexamethasone on the reproductive system in male rats. Methods: In the present experimental study, fifty matured male mice were divided into five groups including control, placebo and three treatment groups. Control group had no injections, placebo group only received normal saline and treatments groups received dexamethasone (0.1, 0.5 and 1 mg/kg which was injected in peritoneum every other day for a period of twenty days. Their Testosterone was measured by ELISA and testes were dissected for histological examination. The data were analyzed using SPSS 11.5 software. Results: Significant increases were shown in FSH level in all three groups treated with dexamethasone. LH in treatment group of 0.1 mg/kg decreased, but at dose of 1 mg/kg increased significantly.Testosterone levels in a dose of 1 mg/kg significantly increased compared with the control group (p<0.05. However, testis weight, the rate of testicular germ cells, primary spermatocytes, epididymal sperm and fertility significantly increased in all three groups (p<0.05. Conclusion: Dexamethasone had a negative effect on reproduction therefore, the use of this medication at different doses and time periods considers the possible complications beforehand. Keywords: .

Terbinafine inhibits gap junctional intercellular communication

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Lee, Ju Yeun, E-mail: whitewndus@naver.com [College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983 (Korea, Republic of); Yoon, Sei Mee, E-mail: sei_mee@naver.com [College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983 (Korea, Republic of); Department of Integrated OMICS for Biomedical Sciences, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Choi, Eun Ju, E-mail: yureas@naver.com [College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983 (Korea, Republic of); Lee, Jinu, E-mail: jinulee@yonsei.ac.kr [College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983 (Korea, Republic of)

2016-09-15

Terbinafine is an antifungal agent that selectively inhibits fungal sterol synthesis by blocking squalene epoxidase. We evaluated the effect of terbinafine on gap junctional intercellular communication (GJIC). Fluorescence recovery after photobleaching (FRAP) and I-YFP GJIC assays revealed that terbinafine inhibits GJIC in a reversible and dose-dependent manner in FRT-Cx43 and LN215 cells. Treatment with terbinafine did not affect Cx43 phosphorylation status or intracellular Ca{sup 2+} concentration, well-known action mechanisms of various GJIC blockers. While a structurally related chemical, naftifine, attenuated GJIC, epigallocatechin gallate, another potent squalene epoxidase inhibitor with a different structure, did not. These results suggest that terbinafine inhibits GJIC with a so far unknown mechanism of action. - Highlights: • In vitro pharmacological studies were performed on FRT-Cx43 and LN215 cells. • Terbinafine inhibits gap junctional intercellular communication in both cell lines. • The inhibitory effect of terbinafine is reversible and dose-dependent. • Treatment of terbinafine does not alter Cx43 phosphorylation or cytosolic Ca{sup 2+} concentration. • Inhibition of squalene epoxidase is not involved in this new effect of terbinafine.

Cavitation of intercellular spaces is critical to establishment of hydraulic properties of compression wood of Chamaecyparis obtusa seedlings.

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Nakaba, Satoshi; Hirai, Asami; Kudo, Kayo; Yamagishi, Yusuke; Yamane, Kenichi; Kuroda, Katsushi; Nugroho, Widyanto Dwi; Kitin, Peter; Funada, Ryo

2016-03-01

When the orientation of the stems of conifers departs from the vertical as a result of environmental influences, conifers form compression wood that results in restoration of verticality. It is well known that intercellular spaces are formed between tracheids in compression wood, but the function of these spaces remains to be clarified. In the present study, we evaluated the impact of these spaces in artificially induced compression wood in Chamaecyparis obtusa seedlings. We monitored the presence or absence of liquid in the intercellular spaces of differentiating xylem by cryo-scanning electron microscopy. In addition, we analysed the relationship between intercellular spaces and the hydraulic properties of the compression wood. Initially, we detected small intercellular spaces with liquid in regions in which the profiles of tracheids were not rounded in transverse surfaces, indicating that the intercellular spaces had originally contained no gases. In the regions where tracheids had formed secondary walls, we found that some intercellular spaces had lost their liquid. Cavitation of intercellular spaces would affect hydraulic conductivity as a consequence of the induction of cavitation in neighbouring tracheids. Our observations suggest that cavitation of intercellular spaces is the critical event that affects not only the functions of intercellular spaces but also the hydraulic properties of compression wood. © The Author 2016. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Dexamethasone Treatment Leads to Enhanced Fear Extinction and Dynamic Fkbp5 Regulation in Amygdala.

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Sawamura, Takehito; Klengel, Torsten; Armario, Antonio; Jovanovic, Tanja; Norrholm, Seth D; Ressler, Kerry J; Andero, Raül

2016-02-01

Posttraumatic stress disorder (PTSD) is both a prevalent and debilitating trauma-related disorder associated with dysregulated fear learning at the core of many of its signs and symptoms. Improvements in the currently available psychological and pharmacological treatments are needed in order to improve PTSD treatment outcomes and to prevent symptom relapse. In the present study, we used a putative animal model of PTSD that included presentation of immobilization stress (IMO) followed by fear conditioning (FC) a week later. We then investigated the acute effects of GR receptor activation on the extinction (EXT) of conditioned freezing, using dexamethasone administered systemically which is known to result in suppression of the HPA axis. In our previous work, IMO followed by tone-shock-mediated FC was associated with impaired fear EXT. In this study, we administered dexamethasone 4 h before EXT training and then examined EXT retention (RET) 24 h later to determine whether dexamethasone suppression rescued EXT deficits. Dexamethasone treatment produced dose-dependent enhancement of both EXT and RET. Dexamethasone was also associated with reduced amygdala Fkbp5 mRNA expression following EXT and after RET. Moreover, DNA methylation of the Fkbp5 gene occurred in a dose-dependent and time course-dependent manner within the amygdala. Additionally, we found dynamic changes in epigenetic regulation, including Dnmt and Tet gene pathways, as a function of both fear EXT and dexamethasone suppression of the HPA axis. Together, these data suggest that dexamethasone may serve to enhance EXT by altering Fkbp5-mediated glucocorticoid sensitivity via epigenetic regulation of Fkbp5 expression.

Melatonin attenuates prenatal dexamethasone-induced blood pressure increase in a rat model.

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Tain, You-Lin; Chen, Chih-Cheng; Sheen, Jiunn-Ming; Yu, Hong-Ren; Tiao, Mao-Meng; Kuo, Ho-Chang; Huang, Li-Tung

2014-04-01

Although antenatal corticosteroid is recommended to accelerate fetal lung maturation, prenatal dexamethasone exposure results in hypertension in the adult offspring. Since melatonin is a potent antioxidant and has been known to regulate blood pressure, we examined the beneficial effects of melatonin therapy in preventing prenatal dexamethasone-induced programmed hypertension. Male offspring of Sprague-Dawley rats were assigned to four groups (n = 12/group): control, dexamethasone (DEX), control + melatonin, and DEX + melatonin. Pregnant rats received intraperitoneal dexamethasone (0.1 mg/kg) from gestational day 16 to 22. In the melatonin-treatment groups, rats received 0.01% melatonin in drinking water during their entire pregnancy and lactation. Blood pressure was measured by an indirect tail-cuff method. Gene expression and protein levels were analyzed by real-time quantitative polymerase chain reaction and Western blotting, respectively. At 16 weeks of age, the DEX group developed hypertension, which was partly reversed by maternal melatonin therapy. Reduced nephron numbers due to prenatal dexamethasone exposure were prevented by melatonin therapy. Renal superoxide and NO levels were similar in all groups. Prenatal dexamethasone exposure led to increased mRNA expression of renin and prorenin receptor and up-regulated histone deacetylase (HDAC)-1 expression in the kidneys of 4-month-old offspring. Maternal melatonin therapy augmented renal Mas protein levels in DEX + melatonin group, and increased renal mRNA expression of HDAC-1, HDAC-2, and HDAC-8 in control and DEX offspring. Melatonin attenuated prenatal DEX-induced hypertension by restoring nephron numbers, altering RAS components, and modulating HDACs. Copyright © 2014 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Multicellular models of intercellular synchronization in circadian neural networks

International Nuclear Information System (INIS)

Henson, Michael A.

2013-01-01

The circadian clock generates 24 h rhythms that drive physiological and behavioral processes in a diverse range of organisms including microbes, plants, insects, and mammals. Recent experimental advances have produced improved understanding of the molecular mechanisms involved in circadian rhythm generation at the single cell level. However, the intercellular mechanisms that allow large populations of coupled pacemaker cells to synchronize and coordinate their rhythms remain poorly understood. The purpose of this article is to review recent progress in dynamic modeling of the circadian clock with a focus on multicellular models required to describe cell population synchronization. Mammalian systems are emphasized to illustrate the highly heterogeneous structure and rich dynamical behavior of multicellular circadian systems. Available multicellular models are characterized with respect to their single cell descriptions, intercellular coupling mechanisms, and network topologies. Examples drawn from our own research are used to demonstrate the advantages associated with integrating detailed single cell models within realistic multicellular networks for prediction of mammalian system dynamics. Mathematical modeling is shown to represent a powerful tool for understanding the intracellular and intercellular mechanisms utilized to robustly synchronize large populations of highly heterogeneous and sparsely coupled single cell oscillators. The article concludes with some possible directions for future research

Does Dexamethasone Helps in Meningococcal Sepsis?

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Tolaj, Ilir; Ramadani, Hamdi; Mehmeti, Murat; Gashi, Hatixhe; Kasumi, Arbana; Gashi, Visar; Jashari, Haki

2017-01-01

Purpose: Prompt recognition and aggressive early treatment are the only effective measures against invasive meningococcal disease (IMD). Anti-inflammatory adjunctive treatment remains controversial and difficult to assess in patients with IMD. The purpose of this study was to evaluate the effect of dexamethasone (DXM) as adjunctive treatment in different clinical forms of IMD, and attempt to answer if DXM should be routinely used in the treatment of IMD. Methods: In this non-interventional clinical study (NIS), 39 patients with meningococcal septicaemia with or without of meningitis were included, and compared regarding the impact of dexamethasone (DXM), as an adjunctive treatment, on the outcome of IMD. SPSS statistics is used for statistical processing of data. Results: Thirty (76.9%) patients with IMD had sepsis and meningitis, and 9 (23.1%) of them had sepsis alone. Dexamethasone was used in 24 (61.5%) cases, in both clinical groups. The overall mortality rate was 10.3%. Pneumonia was diagnosed in 6 patients (15.4%), arthritis in 3 of them (7.7%), and subdural effusion in one patient (2.6%). The data showed a significant statistical difference on the length of hospitalization, and WBC normalization in groups of patients treated with DXM. Conclusion: The use of DXM as adjunctive therapy in invasive meningococcal disease has a degree of proven benefits and no harmful effects. In fighting this very dangerous and complex infection, even a limited benefit is sufficient to recommend the use of DXM as adjunctive treatment in invasive meningococcal disease. PMID:28974828

In vivo relevance of intercellular calcium signaling in Drosophila wing development

OpenAIRE

Brodskiy, Pavel; Brito-Robinson, Teresa; Levis, Megan; Narciso, Cody; Jangula, Jamison; Huizar, Francisco; Wu, Qinfeng; Zartman, Jeremiah

2017-01-01

Recently, organ-scale intercellular Ca2+ transients (ICTs) were reported in the Drosophila wing disc. However, the functional in vivo significance of ICTs remains largely unknown. Here we demonstrate the in vivo relevance of intercellular Ca2+ signaling and its impact on wing development. We report that Ca2+ signaling in vivo decreases as wing discs mature. Ca2+ signaling ex vivo responds to fly extract in a dose-dependent manner. This suggests ICTs occur in vivo due to chemical stimulus that...

Role of dexamethasone in brachial plexus block

International Nuclear Information System (INIS)

Dawood, M.

2015-01-01

To evaluate the effect of dexamethasone added to (lignocaine) on the onset and duration of axillary brachial plexus block. Study Design: Randomized controlled trial. Place and Duration of Study: Combined Military Hospital Rawalpindi, from September 2009 to March 2010. Patients and Methods: A total of 100 patients, who were scheduled for elective hand and forearm surgery under axillary brachial plexus block, were randomly allocated to group A in which patients received 40 ml 1.5% lidocaine with 2 ml of isotonic saline (0.9%) and group B in which patients received 40 ml 1.5% lidocaine with 2 ml of dexamethasone (8 mg). Nerve stimulator with insulated needle for multiple stimulations technique was used to locate the brachial plexus nerves. After the injection onset of action and duration of sensory blockade of brachial plexus were recorded at 5 minutes and 15 minutes interval. Results: Group A showed the onset of action of 21.64 ± 2.30 min and in group B it was 15.42 ± 1.44 min (p< 0.001). Duration of nerve block was 115.08 ± 10.92 min in group A and 265.42 ± 16.56 min in group B (p < 0.001). Conclusion: The addition of dexamethasone to 1.5% lignocaine solution in axillary brachial plexus block prolongs the duration of sensory blockade significantly. (author)

Low-Dose Dexamethasone Therapy from Infancy of Virilizing Congenital Adrenal Hyperplasia

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Stephenson Kerry

2009-12-01

Full Text Available Objective. To assess the growth and control of adrenal androgen secretion in children with virilizing congenital adrenal hyperplasia (CAH treated with dexamethasone. Method. We examined doses used, control of adrenal androgen secretion, and growth and skeletal maturation of 8 children with CAH treated with dexamethasone beginning in infancy. Results. 3 boys and 5 girls with classical CAH (17-hydroxyprogesterone at diagnosis >20,000 ng/dL were treated with dexamethasone beginning at diagnosis ( ; all doses were given in the morning using a dosing syringe to administer a 0.1 mg/mL elixir. The children were treated for years over which time the change in bone age to chronological age ratio (BA/CA was . Most recent height Z' scores were , and body mass index (BMI scores were . Late afternoon levels of 17-hydroxyprogesterone, androstenedione, and testosterone were  ng/dL ( nmol/L,  ng/dL ( nmol/L, and  ng/dL; ( nmol/L, respectively. Conclusions. These observations show that low doses of dexamethasone can be used to effectively treat CAH beginning in infancy.

Removal of dexamethasone from aqueous solution and hospital wastewater by electrocoagulation

International Nuclear Information System (INIS)

Arsand, Daniel R.; Kümmerer, Klaus; Martins, Ayrton F.

2013-01-01

This study is concerned with the removal of the anti-inflammatory dexamethasone from aqueous solution and hospital wastewater by electrocoagulation. The variation of the toxicity during the electrocoagulation was also studied through experiments that were designed and optimized by means of response surface methodology. The coagulation efficiency was evaluated by measuring the dexamethasone concentration by high performance liquid chromatography coupled to a diode array detector. In addition, variation was evaluated through a Vibrio fischeri test. The results showed an increase in the removal of dexamethasone (up to 38.1%) with a rise of the current applied and a decrease of the inter-electrode distance, in aqueous solutions. The application to hospital effluent showed similar results for the removal of dexamethasone. The main effect of the electrocoagulation was that it removed colloids and reduced the organic load of the hospital wastewater. Regarding the current applied, the calculated energy efficiency was 100%. Without pH adjustment of the aqueous solution or hospital wastewater, the residual aluminum concentration always remained lower than 10 mg L −1 , and, with adjustment (to pH 6.5), lower than 0.30 mg L −1 , at the final stage. No toxicity variation was observed during the electrocoagulation process in aqueous solution, either in the presence or absence of dexamethasone. - Highlights: ► Removal of DEX and organic load from aqueous solution and hospital wastewater by EC ► Evaluation of the toxicity during the removal of DEX by EC ► Suggestion of the EC process as a pretreatment for subsequent processes

Removal of dexamethasone from aqueous solution and hospital wastewater by electrocoagulation

Energy Technology Data Exchange (ETDEWEB)

Arsand, Daniel R., E-mail: danielarsand@pelotas.ifsul.edu.br [Chemistry Department, Federal University of Santa Maria, RS (Brazil); Kümmerer, Klaus, E-mail: klaus.kuemmerer@leuphana.de [Institute for Environmental Chemistry, Leuphana University Lüneburg (Germany); Martins, Ayrton F., E-mail: martins@quimica.ufsm.br [Chemistry Department, Federal University of Santa Maria, RS (Brazil)

2013-01-15

This study is concerned with the removal of the anti-inflammatory dexamethasone from aqueous solution and hospital wastewater by electrocoagulation. The variation of the toxicity during the electrocoagulation was also studied through experiments that were designed and optimized by means of response surface methodology. The coagulation efficiency was evaluated by measuring the dexamethasone concentration by high performance liquid chromatography coupled to a diode array detector. In addition, variation was evaluated through a Vibrio fischeri test. The results showed an increase in the removal of dexamethasone (up to 38.1%) with a rise of the current applied and a decrease of the inter-electrode distance, in aqueous solutions. The application to hospital effluent showed similar results for the removal of dexamethasone. The main effect of the electrocoagulation was that it removed colloids and reduced the organic load of the hospital wastewater. Regarding the current applied, the calculated energy efficiency was 100%. Without pH adjustment of the aqueous solution or hospital wastewater, the residual aluminum concentration always remained lower than 10 mg L{sup −1}, and, with adjustment (to pH 6.5), lower than 0.30 mg L{sup −1}, at the final stage. No toxicity variation was observed during the electrocoagulation process in aqueous solution, either in the presence or absence of dexamethasone. - Highlights: ► Removal of DEX and organic load from aqueous solution and hospital wastewater by EC ► Evaluation of the toxicity during the removal of DEX by EC ► Suggestion of the EC process as a pretreatment for subsequent processes.

Dexamethasone and sodium carboxymethyl cellulose prevent postoperative intraperitoneal adhesions in rats

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X.H. Du

2015-04-01

Full Text Available We aimed to evaluate the effects of the barrier agent sodium carboxymethyl cellulose (SCMC with and without dexamethasone for the prevention of postoperative adhesion formation in a rat model of postoperative peritoneal adhesion. A total of 160 three-month old male and female Wistar rats underwent a laparotomy, and adhesions were induced by ileocecal abrasion. Rats were randomly assigned to 4 groups (n=40 each: group A, untreated; group B, treated with SCMC only; group C1, treated with SCMC + 3 mg dexamethasone, and group C2, treated with SCMC + 8 mg dexamethasone. After 12 days, adhesion formation and histopathological changes were compared. In groups A, B, C1, and C2, the mortality rates were 10, 5, 5, and 5%, respectively. In groups C1 and C2, the adhesions were filmy and easy to dissect and were milder compared with those in groups A and B. The total adhesion score in group C1 (3.38±0.49 was significantly lower than that of group B (6.01±0.57; P<0.01 or group A (8.01±0.67; P<0.05. There was no significant difference in adhesion formation between groups C1 and C2. Compared with groups A and B, groups C1 and C2 exhibited milder histopathological changes. SCMC in combination with dexamethasone can prevent adhesion formation and is a better barrier agent than SCMC alone. The safety and feasibility of SCMC in combination with dexamethasone to prevent adhesion formation after abdominal surgery warrants further clinical study.

Rats Born to Mothers Treated with Dexamethasone 15 cH Present Changes in Modulation of Inflammatory Process

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Leoni V. Bonamin

2012-01-01

Full Text Available As little information about the effect of ultra high dilutions of glucocorticoid in reproduction is available in the literature, pregnant female Wistar rats (N=12 were blindly subcutaneously treated during all gestational and lactation period with: dexamethasone 4 mg/kg diluted into dexamethasone 15 cH (mixed; or dexamethasone 4 mg/kg diluted in water; or dexamethasone 15 cH, or vehicle. Parental generation had body weight, food and water consumption monitored. The F1 generation was monitored regarding to newborn development. No birth occurred in both groups treated with dexamethasone 4 mg/kg. After 60 days from birth, 12 male F1 rats were randomly selected from each remaining group and inoculated subcutaneously with 1% carrageenan into the footpad, for evaluation of inflammatory performance. Edema and histopathology of the footpad were evaluated, using specific staining methods, immunohistochemistry and digital histomorphometry. Mothers treated with mixed dexamethasone presented reduced water consumption. F1 rats born to dexamethasone 15 cH treated females presented significant increase in mast cell degranulation, decrease in monocyte percentage, increase in CD18+ PMN cells, and early expression of ED2 protein, in relation to control. The results show that the exposure of parental generation to highly diluted dexamethasone interferes in inflammation modulation in the F1 generation.

Phosphatidylinositol-bisphosphate regulates intercellular coupling in cardiac myocytes

DEFF Research Database (Denmark)

Hofgaard, Johannes P; Banach, Kathrin; Mollerup, Sarah

2008-01-01

that agonist-induced changes in PIP(2) can result in a reduction of the functional coupling of cardiomyocytes and, consequently, in changes in conduction velocity. Intercellular coupling was measured by Lucifer Yellow dye transfer in cultured neonatal rat cardiomyocytes. Conduction velocity was measured...

Aprepitant, granisetron, and dexamethasone versus palonosetron and dexamethasone for prophylaxis of cisplatin-induced nausea and vomiting in patients with upper gastrointestinal cancer: a randomized crossover phase II trial (KDOG 1002).

Science.gov (United States)

Ishido, Kenji; Higuchi, Katsuhiko; Azuma, Mizutomo; Sasaki, Tohru; Tanabe, Satoshi; Katada, Chikatoshi; Yano, Takafumi; Wada, Takuya; Koizumi, Wasaburo

2016-10-01

We conducted a randomized trial to compare the safety and effectiveness of aprepitant, granisetron, and dexamethasone (AGD) with those of palonosetron and dexamethasone (PD) in patients who received highly emetogenic chemotherapy (HEC). Patients with esophageal or gastric cancer who were scheduled to receive HEC including at least 60 mg/m of cisplatin as the first-line treatment were randomly assigned to receive AGD (oral aprepitant 125 mg on day 1 and 80 mg on days 2-3; intravenous granisetron 3 mg on day 1; intravenous dexamethasone 6.6 mg on day 1 and oral dexamethasone 4 mg on days 2-3) or PD (intravenous palonosetron 0.75 mg on day 1; intravenous dexamethasone 13.2 mg on day 1 and oral dexamethasone 8 mg on days 2-3). The primary endpoint was a complete response during the overall study period (0-120 h after the start of chemotherapy) in the first cycle. Eighty-five patients were enrolled, and 84 were eligible. The complete response rate did not differ between the treatment groups, but the proportion of patients with no vomiting was significantly higher in the AGD group than in the PD group (81.4 vs. 58.5%; P=0.031). The results of a quality-of-life survey indicated that the proportion of patients with no or minimal impact on daily life in the vomiting domain was significantly higher in the AGD group (79.1 vs. 53.7%; P=0.020). The primary endpoint of complete response was not achieved, but AGD seems to be more effective than PD for the prevention of HEC-induced vomiting.

Bilateral Intravitreal Dexamethasone Implant for Retinitis Pigmentosa-Related Macular Edema

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Ali Osman Saatci

2013-03-01

Full Text Available Purpose: To report the efficacy of intravitreal dexamethasone implant in a patient with retinitis pigmentosa and bilateral cystoid macular edema unresponsive to topical carbonic anhydrase inhibitors. Case Report: A 36-year-old man with bilateral cystoid macular edema associated with retinitis pigmentosa that was unresponsive to topical carbonic anhydrase inhibitors underwent bilateral 0.7-mg intravitreal dexamethasone implants two weeks apart. Spectral domain optical coherence tomography revealed resolution of macular edema one week following each injection in both eyes and his visual acuity improved. However, macular edema recurred two months later in OS and three months later in OD. Second implant was considered for both eyes. No implant-related complication was experienced during the follow-up of seven months. Conclusion: Inflammatory process seems to play a role in retinitis pigmentosa. Intravitreal dexamethasone implant may offer retina specialists a therapeutic option especially in cases unresponsive to other treatment regimens in eyes with retinitis pigmentosa-related macular edema.

Dexamethasone-(C21-phosphoramide)-[anti-EGFR]: molecular design, synthetic organic chemistry reactions, and antineoplastic cytotoxic potency against pulmonary adenocarcinoma (A549).

Science.gov (United States)

Coyne, Cody P; Narayanan, Lakshmi

2016-01-01

Corticosteroids are effective in the management of a variety of disease states, such as several forms of neoplasia (leukemia and lymphoma), autoimmune conditions, and severe inflammatory responses. Molecular strategies that selectively "target" delivery of corticosteroids minimize or prevents large amounts of the pharmaceutical moiety from passively diffusing into normal healthy cell populations residing within tissues and organ systems. The covalent immunopharmaceutical, dexamethasone-(C21-phosphoramide)-[anti-EGFR] was synthesized by reacting dexamethasone-21-monophosphate with a carbodiimide reagent to form a dexamethasone phosphate carbodiimide ester that was subsequently reacted with imidazole to create an amine-reactive dexamethasone-(C21-phosphorylimidazolide) intermediate. Monoclonal anti-EGFR immunoglobulin was combined with the amine-reactive dexamethasone-(C21-phosphorylimidazolide) intermediate, resulting in the synthesis of the covalent immunopharmaceutical, dexamethasone-(C21-phosphoramide)-[anti-EGFR]. Following spectrophotometric analysis and validation of retained epidermal growth factor receptor type 1 (EGFR)-binding avidity by cell-ELISA, the selective anti-neoplasic cytotoxic potency of dexamethasone-(C21-phosphoramide)-[anti-EGFR] was established by MTT-based vitality stain methodology using adherent monolayer populations of human pulmonary adenocarcinoma (A549) known to overexpress the tropic membrane receptors EGFR and insulin-like growth factor receptor type 1. The dexamethasone:IgG molar-incorporation-index for dexamethasone-(C21-phosphoramide)-[anti-EGFR] was 6.95:1 following exhaustive serial microfiltration. Cytotoxicity analysis: covalent bonding of dexamethasone to monoclonal anti-EGFR immunoglobulin did not significantly modify the ex vivo antineoplastic cytotoxicity of dexamethasone against pulmonary adenocarcinoma at and between the standardized dexamethasone equivalent concentrations of 10(-9) M and 10(-5) M. Rapid increases in

The role of adjunctive dexamethasone in the treatment of bacterial meningitis: an updated systematic meta-analysis

Directory of Open Access Journals (Sweden)

Shao M

2016-07-01

Full Text Available Mei Shao,1 Peng Xu,2 Jun Liu,3 Wenyun Liu,1 Xiujie Wu1 1Department of Neurosurgery, Linyi People’s Hospital, 2Department of Neurosurgery, Linyi Yishui Central Hospital, Linyi, 3Department of Neurosurgery, Binzhou Medical College, Yantai, Shandong, People’s Republic of China Background: Bacterial meningitis is a serious infection in children and adults worldwide, with considerable morbidity, mortality, and severe neurological sequelae. Dexamethasone is often used before antibiotics in cases of this disease, and improves outcomes.Objective: Although several studies have identified the role of adjunctive dexamethasone therapy in the treatment of bacterial meningitis, the results are still inconclusive. The aim of this study was to systematically evaluate the therapeutic and adverse effect of adjunctive dexa­methasone in patients with bacterial meningitis.Materials and methods: Relevant randomized, double-blind, placebo-controlled trials of dexamethasone in bacterial meningitis published between 2000 and 2016 were retrieved from the common electronic databases. The odds ratio (OR and risk ratio (RR with their 95% confidence interval (CI were employed to calculate the effect.Results: A total of ten articles including 2,459 bacterial meningitis patients (1,245 in the dexamethasone group and 1,214 in the placebo group were included in this meta-analysis. Our result found that dexamethasone was not associated with a significant reduction in follow-up mortality (292 of 1,245 on dexamethasone versus 314 of 1,214 on placebo; OR =0.91, 95% CI =0.80–1.03, P=0.14 and severe neurological sequelae (22.4% versus 24.1%, OR =0.84, 95% CI =0.54–1.29, P=0.42. However, dexamethasone seemed to reduce hearing loss among survivors (21.2% versus 26.1%; OR =0.76, 95% CI =0.59–0.98, P=0.03. No significant difference was found between these two groups in adverse events.Conclusion: Our results suggested that adjunctive dexamethasone might not be beneficial in the

Altered calcium handling and increased contraction force in human embryonic stem cell derived cardiomyocytes following short term dexamethasone exposure

Energy Technology Data Exchange (ETDEWEB)

Kosmidis, Georgios; Bellin, Milena; Ribeiro, Marcelo C.; Meer, Berend van; Ward-van Oostwaard, Dorien [Department of Anatomy and Embryology, Leiden University Medical Center, Leiden (Netherlands); Passier, Robert [Department of Anatomy and Embryology, Leiden University Medical Center, Leiden (Netherlands); MIRA, University of Twente (Netherlands); Tertoolen, Leon G.J.; Mummery, Christine L. [Department of Anatomy and Embryology, Leiden University Medical Center, Leiden (Netherlands); Casini, Simona, E-mail: s.casini@amc.uva.nl [Department of Anatomy and Embryology, Leiden University Medical Center, Leiden (Netherlands)

2015-11-27

One limitation in using human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) for disease modeling and cardiac safety pharmacology is their immature functional phenotype compared with adult cardiomyocytes. Here, we report that treatment of human embryonic stem cell derived cardiomyocytes (hESC-CMs) with dexamethasone, a synthetic glucocorticoid, activated glucocorticoid signaling which in turn improved their calcium handling properties and contractility. L-type calcium current and action potential properties were not affected by dexamethasone but significantly faster calcium decay, increased forces of contraction and sarcomeric lengths, were observed in hESC-CMs after dexamethasone exposure. Activating the glucocorticoid pathway can thus contribute to mediating hPSC-CMs maturation. - Highlights: • Dexamethasone accelerates Ca{sup 2+} transient decay in hESC-CMs. • Dexamethasone enhances SERCA and NCX function in hESC-CMs. • Dexamethasone increases force of contraction and sarcomere length in hESC-CMs. • Dexamethasone does not alter I{sub Ca,L} and action potential characteristics in hESC-CMs.

Altered calcium handling and increased contraction force in human embryonic stem cell derived cardiomyocytes following short term dexamethasone exposure

International Nuclear Information System (INIS)

Kosmidis, Georgios; Bellin, Milena; Ribeiro, Marcelo C.; Meer, Berend van; Ward-van Oostwaard, Dorien; Passier, Robert; Tertoolen, Leon G.J.; Mummery, Christine L.; Casini, Simona

2015-01-01

One limitation in using human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) for disease modeling and cardiac safety pharmacology is their immature functional phenotype compared with adult cardiomyocytes. Here, we report that treatment of human embryonic stem cell derived cardiomyocytes (hESC-CMs) with dexamethasone, a synthetic glucocorticoid, activated glucocorticoid signaling which in turn improved their calcium handling properties and contractility. L-type calcium current and action potential properties were not affected by dexamethasone but significantly faster calcium decay, increased forces of contraction and sarcomeric lengths, were observed in hESC-CMs after dexamethasone exposure. Activating the glucocorticoid pathway can thus contribute to mediating hPSC-CMs maturation. - Highlights: • Dexamethasone accelerates Ca"2"+ transient decay in hESC-CMs. • Dexamethasone enhances SERCA and NCX function in hESC-CMs. • Dexamethasone increases force of contraction and sarcomere length in hESC-CMs. • Dexamethasone does not alter I_C_a_,_L and action potential characteristics in hESC-CMs.

The experimental study of the effect of dexamethasone, lidocaine and contrast medium on the activity of collagenase

International Nuclear Information System (INIS)

Wu Zhiqun; Liu Weimin; Li Zhonghua; Yang Peng

2007-01-01

Objective: To study the effects of hormone, anesthetic and contrast medium on the activities of collagenase lysis. Methods: Nuclear tissues were divided into equal amount for different groups and same units of collagenase were used for the lysis. The only difference in the control group from experimental groups was that there were no dexamethasone, lidocaine or omnipaque but existing in experimental groups. Twenty four hours later, the concentrations of the hydroxyproline were determined in different groups and the data were analyzed by statistical software with computer. Results: 1. The concentrations of hydroxyproline in the dexamethasone group, lidocaine group and omnipaque group were significantly lower than that of control group, especially that of lidocaine group, P value was <0.05 or 0.01. 2. The concentrations of hydroxyproline in the dexamethasone + lidocaine group, dexamethasone + omnipaque group, lidocaine+omnipaque group and dexamethasone + lidocaine + omnipaque group were significantly lower than that of control group; and simultaneously lower in dexamethasone group, lidocaine group, omnipaque group respectively; P value was also <0.05 or 0.01. Conclusion: Dexamethasone, lidocaine and omnipaque can individually inhibit the activity of collagenase at different degrees, so they shouldn't be used together with collagenase in treating the lumber disc herniation. (authors)

Extracellular ultrathin fibers sensitive to intracellular reactive oxygen species: Formation of intercellular membrane bridges

Energy Technology Data Exchange (ETDEWEB)

Jung, Se-Hui; Park, Jin-Young; Joo, Jung-Hoon; Kim, Young-Myeong; Ha, Kwon-Soo, E-mail: ksha@kangwon.ac.kr

2011-07-15

Membrane bridges are key cellular structures involved in intercellular communication; however, dynamics for their formation are not well understood. We demonstrated the formation and regulation of novel extracellular ultrathin fibers in NIH3T3 cells using confocal and atomic force microscopy. At adjacent regions of neighboring cells, phorbol 12-myristate 13-acetate (PMA) and glucose oxidase induced ultrathin fiber formation, which was prevented by Trolox, a reactive oxygen species (ROS) scavenger. The height of ROS-sensitive ultrathin fibers ranged from 2 to 4 nm. PMA-induced formation of ultrathin fibers was inhibited by cytochalasin D, but not by Taxol or colchicine, indicating that ultrathin fibers mainly comprise microfilaments. PMA-induced ultrathin fibers underwent dynamic structural changes, resulting in formation of intercellular membrane bridges. Thus, these fibers are formed by a mechanism(s) involving ROS and involved in formation of intercellular membrane bridges. Furthermore, ultrastructural imaging of ultrathin fibers may contribute to understanding the diverse mechanisms of cell-to-cell communication and the intercellular transfer of biomolecules, including proteins and cell organelles.

Effects of thyroxine and dexamethasone on rat submandibular glands

International Nuclear Information System (INIS)

Sagulin, G.B.; Roomans, G.M.

1989-01-01

Glucocorticoids and thyroxine are known to have a marked effect on the flow rate and protein composition of rat parotid saliva in hormonally intact animals. In the present study, the effects of a one-week treatment of male rats with dexamethasone and thyroxine were studied by electron microscopy and x-ray micro-analysis, and by measurement of the flow rate and determination of the chemical composition of pilocarpine-induced submandibular saliva. Thyroxine had the most extensive effects on the submandibular gland. The acinar cells were enlarged and filled with mucus; the cellular calcium concentration was significantly increased. The flow rate of the submandibular saliva was significantly reduced compared with that in saline-injected control animals. Thyroxine caused an increase in the concentrations of protein, total calcium, and potassium in the saliva. Dexamethasone had no significant effects on gland ultrastructure or on the elemental composition of the acinar cells; flow rate was not affected, but the concentrations of protein, calcium, and potassium were significantly increased. The effects of dexamethasone and thyroxine on the flow rate and protein composition of pilocarpine-induced rat submandibular saliva differ from those reported earlier for rat parotid saliva after simultaneous stimulation with pilocarpine and isoproterenol

Protection against dexamethasone-induced muscle atrophy is related to modulation by testosterone of FOXO1 and PGC-1{alpha}

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Qin, Weiping, E-mail: weiping.qin@mssm.edu [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peters VA Medical Center, Bronx, NY (United States); Department of Medicine, Mount Sinai School of Medicine, NY (United States); Pan, Jiangping; Wu, Yong [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peters VA Medical Center, Bronx, NY (United States); Bauman, William A. [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peters VA Medical Center, Bronx, NY (United States); Department of Medicine, Mount Sinai School of Medicine, NY (United States); Department of Rehabilitation Medicine, Mount Sinai School of Medicine, NY (United States); Cardozo, Christopher, E-mail: Chris.Cardozo@mssm.edu [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peters VA Medical Center, Bronx, NY (United States); Department of Medicine, Mount Sinai School of Medicine, NY (United States); Department of Rehabilitation Medicine, Mount Sinai School of Medicine, NY (United States)

2010-12-17

Research highlights: {yields} In rat gastrocnemius muscle, dexamethasone reduced PGC-1{alpha} cellular and nuclear levels without altering mRNA levels for this factor. {yields} Dexamethasone reduced phosphorylating of p38 MAPK, which stabilizes PGC-1{alpha} and promotes its nuclear entry. {yields} Co-administration of testosterone with dexamethasone increased cellular and nuclear levels of PGC-1{alpha} protein without changing its mRNA levels. {yields} Co-administration of testosterone restored p38 MAPK levels to those of controls. -- Abstract: Glucocorticoid-induced muscle atrophy results from muscle protein catabolism and reduced protein synthesis, associated with increased expression of two muscle-specific ubiquitin ligases (MAFbx and MuRF1), and of two inhibitors of protein synthesis, REDD1 and 4EBP1. MAFbx, MuRF1, REDD1 and 4EBP1 are up-regulated by the transcription factors FOXO1 and FOXO3A. The transcriptional co-activator PGC-1{alpha} has been shown to attenuate many forms of muscle atrophy and to repress FOXO3A-mediated transcription of atrophy-specific genes. Dexamethasone-induced muscle atrophy can be prevented by testosterone, which blocks up-regulation by dexamethasone of FOXO1. Here, an animal model of dexamethasone-induced muscle atrophy was used to further characterize effects of testosterone to abrogate adverse actions of dexamethasone on FOXO1 levels and nuclear localization, and to determine how these agents affect PGC-1{alpha}, and its upstream activators, p38 MAPK and AMPK. In rat gastrocnemius muscle, testosterone blunted the dexamethasone-mediated increase in levels of FOXO1 mRNA, and FOXO1 total and nuclear protein. Dexamethasone reduced total and nuclear PGC-1{alpha} protein levels in the gastrocnemius; co-administration of testosterone with dexamethasone increased total and nuclear PGC-1{alpha} levels above those present in untreated controls. Testosterone blocked dexamethasone-induced decreases in activity of p38 MAPK in the gastrocnemius

Low dose gamma irradiation enhances defined signaling components of intercellular reactive oxygen-mediated apoptosis induction

International Nuclear Information System (INIS)

Bauer, G

2011-01-01

Transformed cells are selectively removed by intercellular ROS-mediated induction of apoptosis. Signaling is based on the HOCl and the NO/peroxynitrite pathway (major pathways) and the nitryl chloride and the metal-catalyzed Haber-Weiss pathway (minor pathways). During tumor progression, resistance against intercellular induction of apoptosis is acquired through expression of membrane-associated catalase. Low dose radiation of nontransformed cells has been shown to enhance intercellular induction of apoptosis. The present study was performed to define the signaling components which are modulated by low dose gamma irradiation. Low dose radiation induced the release of peroxidase from nontransformed, transformed and tumor cells. Extracellular superoxide anion generation was strongly enhanced in the case of transformed cells and tumor cells, but not in nontransformed cells. Enhancement of peroxidase release and superoxide anion generation either increased intercellular induction of apoptosis of transformed cells, or caused a partial protection under specific signaling conditions. In tumor cells, low dose radiation enhanced the production of major signaling components, but this had no effect on apoptosis induction, due to the strong resistance mechanism of tumor cells. Our data specify the nature of low dose radiation-induced effects on specific signaling components of intercellular induction of apoptosis at defined stages of multistep carcinogenesis.

Comparison of the effects of intravitreal bevacizumab and dexamethasone in experimental posterior penetrating eye injury

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Ayse Oner

2018-04-01

Full Text Available AIM: To compare the effects of intravitreal anti-vascular endothelial growth factor (VEGF and dexamethasone in an experimental rabbit model of posterior penetrating ocular injury. METHODS: Thirty white New Zealand rabbits were included in the study. A posterior penetrating ocular injury was performed at the superotemporal quadrant. They were randomly divided into three groups. The rabbits in group 1 received intravitreal dexamethasone, in group 2 they received intravitreal bevacizumab and those in group 3 received intravitreal physiological saline solution in both eyes. All eyes were examined ophthalmologically on the 1st, 3rd, 7th, 14th and 28th days following the injury and the clinical findings were scored. On the day 28, the eyes were enucleated, evaluated and scored macroscopically, histopathologically and scanning electron microscopically. RESULTS: The median clinical score on the 14th and 28th days and the median macroscopic score of the dexamethasone group was significantly better than that of control (P=0.004, 0.018. Dexamethasone group was also better than that of bevacizumab group but the differences did not reach statistical significance. Retinal detachment rate was 8.3%, 16.6% and 12.5% in the dexamethasone group, bevacizumab group and control group, respectively (P=0.476. More extensive fibrocelluler proliferations were observed in controls compared with dexamethasone and bevacizumab groups. But these differences did not reach the statistical significance (P=0.538. In scanning electron microscopy all groups showed fibreous stalk and dense collagen fibrils in vitreous. CONCLUSION: This study shows that intravitreal injection of both dexamethasone and bevacizumab may reduce the intraocular fibrous proliferation after an experimental posterior penetrating ocular injury in rabbits.

Effects of dexamethasone and pheniramine hydrogen maleate on stress response in patients undergoing elective laparoscopic cholecystectomy.

Science.gov (United States)

Karaman, Kerem; Bostanci, Erdal Birol; Aksoy, Erol; Ulas, Murat; Yigit, Tuba; Erdemli, Mehmet Ozcan; Ercin, Ugur; Bilgihan, Ayse; Saydam, Gul; Akoglu, Musa

2013-02-01

Laparoscopic cholecystectomy (LC) still leads to significant postoperative nausea and vomiting (PONV) and pain. Our aim was to evaluate the efficacy of dexamethasone or pheniramine hydrogen maleate, either alone or combined, in reducing the stress response and symptoms after LC. Patients were randomly assigned to 1 of 4 groups, each consisting of 20 patients: control, dexamethasone (8 mg/2 mL), pheniramine hydrogen maleate (45.5 mg/2 mL), and the combined group. The drugs were given before anesthesia induction. C-reactive protein levels (CRP) and visual analog scale (VAS) scores were significantly less in the dexamethasone (P = .003) and combined groups (P pheniramine hydrogen maleate (P = .005) significantly reduced PONV. Dexamethasone significantly reduced postoperative pain and the systemic acute-phase response, whereas these effects were only partially attained with pheniramine hydrogen maleate. Both dexamethasone and pheniramine hydrogen maleate significantly reduced PONV. An additive effect seemed to occur if these drugs were used in combination. Copyright © 2013 Elsevier Inc. All rights reserved.

Dexamethasone-(C21-phosphoramide-[anti-EGFR]: molecular design, synthetic organic chemistry reactions, and antineoplastic cytotoxic potency against pulmonary adenocarcinoma (A549

Directory of Open Access Journals (Sweden)

Coyne CP

2016-08-01

Full Text Available Cody P Coyne,1 Lakshmi Narayanan2 1Department of Basic Sciences, 2Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, MS, USA Purpose: Corticosteroids are effective in the management of a variety of disease states, such as several forms of neoplasia (leukemia and lymphoma, autoimmune conditions, and severe inflammatory responses. Molecular strategies that selectively “target” delivery of corticosteroids minimize or prevents large amounts of the pharmaceutical moiety from passively diffusing into normal healthy cell populations residing within tissues and organ systems. Materials and methods: The covalent immunopharmaceutical, dexamethasone-(C21-phosphoramide-[anti-EGFR] was synthesized by reacting dexamethasone-21-monophosphate with a carbodiimide reagent to form a dexamethasone phosphate carbodiimide ester that was subsequently reacted with imidazole to create an amine-reactive dexamethasone-(C21-phosphorylimidazolide intermediate. Monoclonal anti-EGFR immunoglobulin was combined with the amine-reactive dexamethasone-(C21-phosphorylimidazolide intermediate, resulting in the synthesis of the covalent immunopharmaceutical, dexamethasone-(C21-phosphoramide-[anti-EGFR]. Following spectrophotometric analysis and validation of retained epidermal growth factor receptor type 1 (EGFR-binding avidity by cell-ELISA, the selective anti-neoplasic cytotoxic potency of dexamethasone-(C21-phosphoramide-[anti-EGFR] was established by MTT-based vitality stain methodology using adherent monolayer populations of human pulmonary adenocarcinoma (A549 known to overexpress the tropic membrane receptors EGFR and insulin-like growth factor receptor type 1. Results: The dexamethasone:IgG molar-incorporation-index for dexamethasone-(C21-phosphoramide-[anti-EGFR] was 6.95:1 following exhaustive serial microfiltration. Cytotoxicity analysis: covalent bonding of dexamethasone to monoclonal anti-EGFR immunoglobulin

Synthesis of dexamethasone-4-14C

International Nuclear Information System (INIS)

Rao, P.N.; Cessac, J.W.; Hill, K.A.

1982-01-01

The bismethylenedioxy (BMD) derivative of dexamethasone 2 was silylated with trimethylchlorosilane and imidazole in dimethylformamide to give the 11β-trimethylsilyloxy BMD derivative 3. The Δ 1 -double bond in 3 was hydrogenated over 5% palladium on carbon to give the Δ 4 -3-oxo steroid 4. Oxidation of 4 with potassium permanganate-sodium metaperiodate gave the seco-acid 5 which on subsequent treatment with acetic anhydride; sodium acetate and triethylamine gave the enol-lactone 6. The enol-lactone 6 was reacted with 14 C-methylmagnesium iodide to give an adduct 7a which on heating at reflux with lithium 2,6-di-t-butylphenoxide in dioxane gave the Δ 4 -3-oxo derivative 8. Compound 8 was heated at reflux with m-iodylbenzoic acid and diphenyl diselenide in toluene to give the Δsup(1,4)-3-oxo steroid 9. The protecting BMD and silyl groups were removed in a single step by reaction with aqueous trifluoroacetic acid containing 2N hydrochloric acid at room temperature to give dexamethasone-4- 14 C 10. (author)

Gap Junctional Intercellular Communication and Breast Cancer Metastasis to Bone

National Research Council Canada - National Science Library

Donahue, Henry

2001-01-01

.... We found that: 1) expressing the metastasis suppressing gene BRMS1 in diverse cancer cell lines, including breast and melanoma, restores homotypic gap junctional intercellular communication (GJIC); 2...

Compatibility and stability of aloxi (palonosetron hydrochloride) admixed with dexamethasone sodium phosphate.

Science.gov (United States)

Trissel, Lawrence A; Zhang, Yanping

2004-01-01

The purpose of this study was to evaluate the physical and chemical stability of palonosetron hydrochloride 0.25 mg admixed with dexamethasone (as sodium phophate) 10 mg or 20 mg in 5% dextrose injection or 0.9% sodium chloride injection in polyvinylchloride minibags, and also admixed with dexamethasone (as sodium phosphate) 3.3 mg in 5% dextrose injection or 0.9% sodium chloride injection in polypropylene syringes, at 4 deg C stored in the dark for 14 days, and at 23 deg C exposed to normal laboratory fluorescent light over 48 hours. Test samples of palonosetron hydrochloride 5 micrograms/mL with dexamethasone (as sodium phosphate) 0.2 mg/mL and also 0.4 mg/mL were prepared in polyvinylchloride minibags of each infusion solution. Additionally, palonosetron hydrochloride 25 micrograms/mL with dexamethasone (as sodium phosphate) 0.33 mg/mL in each infusion solution were prepared as 10 mL of test solution in 20-mL polypropylene syringes. Evaluations for physical and chemical stability were performed on samples taken initially and after 1, 3, 7 and 14 days of storage at 4 deg C and after 1, 4, 24 and 48 hours at 23 deg C. Physical stability was assessed using visual observation in normal room light and using a high-intensity monodirectional light beam. In addition, turbidity and particle content were measured electronically. Chemical stability of the drug was evaluated by using a stability-indicating high-performance liquid chromatographic analytical technique. All samples were physically compatible throughout the study. The solutions remained clear and showed little or no change in particulate burden and haze level. Additionally, little or no loss of palonosetron hydrochloride and dexamethasone occurred in any of the samples at either temperature throughout the entire study period. Admixtures of palonosetron hydrochloride with dexamethasone sodium phosphate in 5% dextrose injection or in 0.9% sodium chloride injection packaged in polyvinylchloride minibags or in

Variable effects of dexamethasone on protein synthesis in clonal rat osteosarcoma cells

International Nuclear Information System (INIS)

Hodge, B.O.; Kream, B.E.

1988-01-01

We examined the effects of dexamethasone on protein synthesis in clonal rat osteoblastic osteosarcoma (ROS) cell lines by measuring the incorporation of [ 3 H]proline into collagenase-digestible and noncollagen protein in the cell layer and medium of the cultures. In ROS 17/2 and subclone C12 of ROS 17/2.8, dexamethasone decreased collagen synthesis with no change in DNA content of the cultures. In ROS 17/2.8 and its subclone G2, dexamethasone stimulated collagen and noncollagen protein synthesis, with a concomitant decrease in the DNA content of the cells. These data indicate that ROS cell lines are phenotypically heterogeneous and suggest that in normal bone there may be distinct subpopulations of osteoblasts with varying phenotypic traits with respect to the regulation of protein synthesis

Effects of dexamethasone coadministered with oseltamivir on the pharmacokinetics of oseltamivir in healthy volunteers

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Jang K

2017-03-01

Full Text Available Kyungho Jang,1,2,* Min-Kyoung Kim,3,4,* Jaeseong Oh,1 SeungHwan Lee,1 Joo-Youn Cho,1 Kyung-Sang Yu,1 Tai Kiu Choi,3 Sang-Hyuk Lee,3,4 Kyoung Soo Lim4 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, 2Center for Clinical Pharmacology and Biomedical Research Institute, Chonbuk National University Medical School, Jeonju, 3Department of Psychiatry, 4Department of Clinical Pharmacology and Therapeutics, CHA University School of Medicine and CHA Bundang Medical Center, Seongnam, Republic of Korea *These authors contributed equally to this work Purpose: Oseltamivir is widely used in the treatment and prophylaxis of influenza A and B viral infections. It is ingested as an oral prodrug that is rapidly metabolized by carboxylesterase 1 (CES1 to its active form, oseltamivir carboxylate. Dexamethasone is also used in the treatment of acute respiratory distress syndrome, a severe complication of influenza; however, its influence on the pharmacokinetics (PK of oseltamivir is controversial. The aim of this study was to investigate the effects of coadministering oseltamivir and dexamethasone on the PK of oseltamivir in healthy volunteers. Methods: An open-label, two-period, one-sequence, multiple-dose study was conducted in 19 healthy male volunteers. Oseltamivir (75 mg was orally administered on Day 1 and Day 8, and dexamethasone (1.5 mg was administered once daily from Day 3 to Day 8. Serial blood and urine samples were collected for PK analysis of oseltamivir and oseltamivir carboxylate on Day 1 and Day 8. Oseltamivir and oseltamivir carboxylate concentrations in plasma and urine were determined using liquid chromatography–tandem mass spectrometry. Results: Area under the plasma concentration–time curve (AUC of oseltamivir and oseltamivir carboxylate decreased after dexamethasone treatment for 6 days. The geometric mean ratio (90% confidence interval of the metabolic ratio

Effect of sound on gap-junction-based intercellular signaling: Calcium waves under acoustic irradiation.

Science.gov (United States)

Deymier, P A; Swinteck, N; Runge, K; Deymier-Black, A; Hoying, J B

2015-01-01

We present a previously unrecognized effect of sound waves on gap-junction-based intercellular signaling such as in biological tissues composed of endothelial cells. We suggest that sound irradiation may, through temporal and spatial modulation of cell-to-cell conductance, create intercellular calcium waves with unidirectional signal propagation associated with nonconventional topologies. Nonreciprocity in calcium wave propagation induced by sound wave irradiation is demonstrated in the case of a linear and a nonlinear reaction-diffusion model. This demonstration should be applicable to other types of gap-junction-based intercellular signals, and it is thought that it should be of help in interpreting a broad range of biological phenomena associated with the beneficial therapeutic effects of sound irradiation and possibly the harmful effects of sound waves on health.

A multicenter, randomized, controlled trial of dexamethasone for bronchiolitis.

Science.gov (United States)

Corneli, Howard M; Zorc, Joseph J; Mahajan, Prashant; Majahan, Prashant; Shaw, Kathy N; Holubkov, Richard; Reeves, Scott D; Ruddy, Richard M; Malik, Baqir; Nelson, Kyle A; Bregstein, Joan S; Brown, Kathleen M; Denenberg, Matthew N; Lillis, Kathleen A; Cimpello, Lynn Babcock; Tsung, James W; Borgialli, Dominic A; Baskin, Marc N; Teshome, Getachew; Goldstein, Mitchell A; Monroe, David; Dean, J Michael; Kuppermann, Nathan

2007-07-26

Bronchiolitis, the most common infection of the lower respiratory tract in infants, is a leading cause of hospitalization in childhood. Corticosteroids are commonly used to treat bronchiolitis, but evidence of their effectiveness is limited. We conducted a double-blind, randomized trial comparing a single dose of oral dexamethasone (1 mg per kilogram of body weight) with placebo in 600 children (age range, 2 to 12 months) with a first episode of wheezing diagnosed in the emergency department as moderate-to-severe bronchiolitis (defined by a Respiratory Distress Assessment Instrument score > or =6). We enrolled patients at 20 emergency departments during the months of November through April over a 3-year period. The primary outcome was hospital admission after 4 hours of emergency department observation. The secondary outcome was the Respiratory Assessment Change Score (RACS). We also evaluated later outcomes: length of hospital stay, later medical visits or admissions, and adverse events. Baseline characteristics were similar in the two groups. The admission rate was 39.7% for children assigned to dexamethasone, as compared with 41.0% for those assigned to placebo (absolute difference, -1.3%; 95% confidence interval [CI], -9.2 to 6.5). Both groups had respiratory improvement during observation; the mean 4-hour RACS was -5.3 for dexamethasone, as compared with -4.8 for placebo (absolute difference, -0.5; 95% CI, -1.3 to 0.3). Multivariate adjustment did not significantly alter the results, nor were differences detected in later outcomes. In infants with acute moderate-to-severe bronchiolitis who were treated in the emergency department, a single dose of 1 mg of oral dexamethasone per kilogram did not significantly alter the rate of hospital admission, the respiratory status after 4 hours of observation, or later outcomes. (ClinicalTrials.gov number, NCT00119002 [ClinicalTrials.gov].). Copyright 2007 Massachusetts Medical Society.

Silibinin, dexamethasone, and doxycycline as potential therapeutic agents for treating vesicant-inflicted ocular injuries

International Nuclear Information System (INIS)

Tewari-Singh, Neera; Jain, Anil K.; Inturi, Swetha; Ammar, David A.; Agarwal, Chapla; Tyagi, Puneet; Kompella, Uday B.; Enzenauer, Robert W.; Petrash, J. Mark; Agarwal, Rajesh

2012-01-01

There are no effective and approved therapies against devastating ocular injuries caused by vesicating chemical agents sulfur mustard (SM) and nitrogen mustard (NM). Herein, studies were carried out in rabbit corneal cultures to establish relevant ocular injury biomarkers with NM for screening potential efficacious agents in laboratory settings. NM (100 nmol) exposure of the corneas for 2 h (cultured for 24 h), showed increases in epithelial thickness, ulceration, apoptotic cell death, epithelial detachment microbullae formation, and the levels of VEGF, cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9). Employing these biomarkers, efficacy studies were performed with agent treatments 2 h and every 4 h thereafter, for 24 h following NM exposure. Three agents were evaluated, including prescription drugs dexamethasone (0.1%; anti-inflammatory steroid) and doxycycline (100 nmol; antibiotic and MMP inhibitor) that have been studied earlier for treating vesicant-induced eye injuries. We also examined silibinin (100 μg), a non-toxic natural flavanone found to be effective in treating SM analog-induced skin injuries in our earlier studies. Treatments of doxycycline + dexamethasone, and silibinin were more effective than doxycycline or dexamethasone alone in reversing NM-induced epithelial thickening, microbullae formation, apoptotic cell death, and MMP-9 elevation. However, dexamethasone and silibinin alone were more effective in reversing NM-induced VEGF levels. Doxycycline, dexamethasone and silibinin were all effective in reversing NM-induced COX-2 levels. Apart from therapeutic efficacy of doxycycline and dexamethasone, these results show strong multifunctional efficacy of silibinin in reversing NM-induced ocular injuries, which could help develop effective and safe therapeutics against ocular injuries by vesicants. -- Highlights: ► Established injury biomarkers in rabbit corneal culture with nitrogen mustard (NM) ► This NM model is a cost effective

Silibinin, dexamethasone, and doxycycline as potential therapeutic agents for treating vesicant-inflicted ocular injuries

Energy Technology Data Exchange (ETDEWEB)

Tewari-Singh, Neera, E-mail: Neera.Tewari-Singh@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Jain, Anil K., E-mail: Anil.Jain@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Inturi, Swetha, E-mail: Swetha.Inturi@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Ammar, David A., E-mail: David.Ammar@ucdenver.edu [Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO 80045 (United States); Agarwal, Chapla, E-mail: Chapla.Agarwal@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Tyagi, Puneet, E-mail: Puneet.Tyagi@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Kompella, Uday B., E-mail: Uday.Kompella@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Enzenauer, Robert W., E-mail: Robert.Enzenauer@ucdenver.edu [Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO 80045 (United States); Petrash, J. Mark, E-mail: Mark.Petrash@ucdenver.edu [Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO 80045 (United States); Agarwal, Rajesh, E-mail: Rajesh.Agarwal@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States)

2012-10-01

There are no effective and approved therapies against devastating ocular injuries caused by vesicating chemical agents sulfur mustard (SM) and nitrogen mustard (NM). Herein, studies were carried out in rabbit corneal cultures to establish relevant ocular injury biomarkers with NM for screening potential efficacious agents in laboratory settings. NM (100 nmol) exposure of the corneas for 2 h (cultured for 24 h), showed increases in epithelial thickness, ulceration, apoptotic cell death, epithelial detachment microbullae formation, and the levels of VEGF, cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9). Employing these biomarkers, efficacy studies were performed with agent treatments 2 h and every 4 h thereafter, for 24 h following NM exposure. Three agents were evaluated, including prescription drugs dexamethasone (0.1%; anti-inflammatory steroid) and doxycycline (100 nmol; antibiotic and MMP inhibitor) that have been studied earlier for treating vesicant-induced eye injuries. We also examined silibinin (100 μg), a non-toxic natural flavanone found to be effective in treating SM analog-induced skin injuries in our earlier studies. Treatments of doxycycline + dexamethasone, and silibinin were more effective than doxycycline or dexamethasone alone in reversing NM-induced epithelial thickening, microbullae formation, apoptotic cell death, and MMP-9 elevation. However, dexamethasone and silibinin alone were more effective in reversing NM-induced VEGF levels. Doxycycline, dexamethasone and silibinin were all effective in reversing NM-induced COX-2 levels. Apart from therapeutic efficacy of doxycycline and dexamethasone, these results show strong multifunctional efficacy of silibinin in reversing NM-induced ocular injuries, which could help develop effective and safe therapeutics against ocular injuries by vesicants. -- Highlights: ► Established injury biomarkers in rabbit corneal culture with nitrogen mustard (NM) ► This NM model is a cost effective

Intercellular signaling pathways active during intervertebral disc growth, differentiation, and aging.

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Dahia, Chitra Lekha; Mahoney, Eric J; Durrani, Atiq A; Wylie, Christopher

2009-03-01

Intervertebral discs at different postnatal ages were assessed for active intercellular signaling pathways. To generate a spatial and temporal map of the signaling pathways active in the postnatal intervertebral disc (IVD). The postnatal IVD is a complex structure, consisting of 3 histologically distinct components, the nucleus pulposus, fibrous anulus fibrosus, and endplate. These differentiate and grow during the first 9 weeks of age in the mouse. Identification of the major signaling pathways active during and after the growth and differentiation period will allow functional analysis using mouse genetics and identify targets for therapy for individual components of the disc. Antibodies specific for individual cell signaling pathways were used on cryostat sections of IVD at different postnatal ages to identify which components of the IVD were responding to major classes of intercellular signal, including sonic hedgehog, Wnt, TGFbeta, FGF, and BMPs. We present a spatial/temporal map of these signaling pathways during growth, differentiation, and aging of the disc. During growth and differentiation of the disc, its different components respond at different times to different intercellular signaling ligands. Most of these are dramatically downregulated at the end of disc growth.

Prophylactic antiemetic effects of midazolam, dexamethasone, and its combination after middle ear surgery

International Nuclear Information System (INIS)

Makhdoom, Naeem K; Farid, Magdy F

2009-01-01

To evaluate and compare the efficacy of the combination of midazolam and dexamethasone, with midazolam and dexamethasone alone, for the prevention of postoperative nausea and vomiting (PONV) in female patients undergoing middle ear surgery. A prospective, randomized, double-blind, placebo-controlled study in 80 female patients (mean age 32.6 years), undergoing middle ear surgery with general anesthesia at Ohud Hospital, Madina, Kingdom of Saudi Arabia from May 2007 to May 2008. Patients were classified into 4 groups. They received intravenous normal saline (S group), midazolam 0.075 mg/kg (M group), or dexamethasone 10 mg (D group), or a combination of midazolam and dexamethasone (MD group), before the induction of anesthesia. Postoperatively for 24 hours observation and assessment of nausea, vomiting, rescue anti-emetics, and side effects of the study drugs such as headache and drowsiness were carried out. There was a significant difference between the 4 groups. The MD group was the least to develop PONV compared to other groups (p<0.01). Regarding nausea, there was a non-significant difference between the 4 groups, although the MD group developed the least symptoms among the 4 groups, there were no significant differences in pain intensity and side effects such as, headache, dizziness, and drowsiness between the 4 groups. The combination of midazolam 0.075 mg/kg and dexamethasone 10 mg intravenously is better than either drug alone in reducing the incidence of PONV in female patients after middle ear surgery. (author)

Dexamethasone PONV prophylaxis alters the hypothalamic-pituitary-adrenal axis after transsphenoidal pituitary surgery.

Science.gov (United States)

Burkhardt, Till; Rotermund, Roman; Schmidt, Nils-Ole; Kiefmann, Rainer; Flitsch, Jörg

2014-07-01

Postoperative nausea and vomiting (PONV) is common after general anesthesia and are reported by approximately 20% to 25% of all patients and up to 39% of patients undergoing neurosurgical procedures. The most common standard prophylaxis is a single application of 4 mg of dexamethasone before initiating anesthesia. Dexamethasone is known to suppress adreno-corticotroph hormone and cortisol levels. The objective was to find out whether this prophylaxis has an effect on the postoperative levels of cortisol in patients undergoing transsphenoidal pituitary surgery, and therefore simulates pituitary deficiency. A retrospective analysis of the files of 136 consecutive patients who were operated during a course of 6 months were included. Nineteen patients with a known history of PONV received a standard dose of 4 mg of dexamethasone perioperatively. Blood tests were drawn at the first postoperative day and were compared with blood tests of patients who had no history of PONV and therefore received no prophylaxis. Patients who were treated with a dexamethasone PONV prophylaxis showed no significant changes in cortisol levels; preoperative median of 93 μg/L (range, 39 to 427) and a postoperative median of 87 μg/L (range, 10 to 733; P=0.798) opposed to patients who did not receive such treatment; preoperative cortisol 114 μg/L (range, 10 to 387) and postoperative levels of 273 μg/L (range, 10 to 1352; Ptranssphenoidal surgery, the probability that dexamethasone PONV prophylaxis suppresses postoperative cortisol levels should be considered.

Simultaneous RP-HPLC determination of sparfloxacin and dexamethasone in pharmaceutical formulations

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Syed Naeem Razzaq

2013-06-01

Full Text Available The present study describes the development and subsequent validation of simple and accurate stability indicating RP-HPLC method for the determination of sparfloxacin and dexamethasone in pharmaceutical formulations in the presence of their stress-induced degradation products. Both the drugs and their stress-induced degradation products were separated within 10 minutes using C8 column and mixture of methanol and 0.02 M phosphate buffer pH 3.0 (60:40 v/v, respectively as mobile phase at 270 nm using diode array detector. Regression analysis showed linearity in the range of 15-105 µg/mL for sparfloxacin and 5-35 µg/mL for dexamethasone. All the analytes were adequately resolved with acceptable tailing. Peak purity of the two drugs was also greater than 0.9999, showing no co-elution peaks. The developed method was applied for simultaneous determination of sparfloxacin and dexamethasone in pharmaceutical formulations for stability studies.

Biodegradable hyaluronic acid hydrogels to control release of dexamethasone through aqueous Diels–Alder chemistry for adipose tissue engineering

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Fan, Ming; Ma, Ye; Zhang, Ziwei; Mao, Jiahui [School of Materials Science and Engineering, Nanjing University of Science and Technology, Nanjing (China); Tan, Huaping, E-mail: hptan@njust.edu.cn [School of Materials Science and Engineering, Nanjing University of Science and Technology, Nanjing (China); Hu, Xiaohong [School of Material Engineering, Jinling Institute of Technology, Nanjing (China)

2015-11-01

A robust synthetic strategy of biopolymer-based hydrogels has been developed where hyaluronic acid derivatives reacted through aqueous Diels–Alder chemistry without the involvement of chemical catalysts, allowing for control and sustain release of dexamethasone. To conjugate the hydrogel, furan and maleimide functionalized hyaluronic acid were synthesized, respectively, as well as furan functionalized dexamethasone, for the covalent immobilization. Chemical structure, gelation time, morphologies, swelling kinetics, weight loss, compressive modulus and dexamethasone release of the hydrogel system in PBS at 37 °C were studied. The results demonstrated that the aqueous Diels–Alder chemistry provides an extremely selective reaction and proceeds with high efficiency for hydrogel conjugation and covalent immobilization of dexamethasone. Cell culture results showed that the dexamethasone immobilized hydrogel was noncytotoxic and preserved proliferation of entrapped human adipose-derived stem cells. This synthetic approach uniquely allows for the direct fabrication of biologically functionalized gel scaffolds with ideal structures for adipose tissue engineering, which provides a competitive alternative to conventional conjugation techniques such as copper mediated click chemistry. - Highlights: • A biodegradable hyaluronic acid hydrogel was crosslinked via aqueous Diels–Alder chemistry. • Dexamethasone was covalently immobilized into the hyaluronic acid hydrogel via aqueous Diels–Alder chemistry. • Dexamethasone could be released from the Diels–Alder hyaluronic acid hydrogel in a controlled fashion.

Biodegradable hyaluronic acid hydrogels to control release of dexamethasone through aqueous Diels–Alder chemistry for adipose tissue engineering

International Nuclear Information System (INIS)

Fan, Ming; Ma, Ye; Zhang, Ziwei; Mao, Jiahui; Tan, Huaping; Hu, Xiaohong

2015-01-01

A robust synthetic strategy of biopolymer-based hydrogels has been developed where hyaluronic acid derivatives reacted through aqueous Diels–Alder chemistry without the involvement of chemical catalysts, allowing for control and sustain release of dexamethasone. To conjugate the hydrogel, furan and maleimide functionalized hyaluronic acid were synthesized, respectively, as well as furan functionalized dexamethasone, for the covalent immobilization. Chemical structure, gelation time, morphologies, swelling kinetics, weight loss, compressive modulus and dexamethasone release of the hydrogel system in PBS at 37 °C were studied. The results demonstrated that the aqueous Diels–Alder chemistry provides an extremely selective reaction and proceeds with high efficiency for hydrogel conjugation and covalent immobilization of dexamethasone. Cell culture results showed that the dexamethasone immobilized hydrogel was noncytotoxic and preserved proliferation of entrapped human adipose-derived stem cells. This synthetic approach uniquely allows for the direct fabrication of biologically functionalized gel scaffolds with ideal structures for adipose tissue engineering, which provides a competitive alternative to conventional conjugation techniques such as copper mediated click chemistry. - Highlights: • A biodegradable hyaluronic acid hydrogel was crosslinked via aqueous Diels–Alder chemistry. • Dexamethasone was covalently immobilized into the hyaluronic acid hydrogel via aqueous Diels–Alder chemistry. • Dexamethasone could be released from the Diels–Alder hyaluronic acid hydrogel in a controlled fashion

Pinoresinol diglucoside exhibits protective effect on dexamethasone ...

African Journals Online (AJOL)

Purpose: To investigate the effect of pinoresinol diglucoside (PDG) on dexamethasone-induced osteoporosis in rats. Methods: Sixty Wistar rats were randomly and equally divided into normal, control, alendronate and PDG (10, 20 or 40 mg/kg) groups. Bone tissue parameters, including length, transverse diameter, weight, ...

21 CFR 520.540a - Dexamethasone powder.

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2010-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.540a Dexamethasone powder. (a... such as acute arthritic lameness, and for various stress conditions where corticosteroids are required...

Is there a relationship between hypoxia, contact resistance, and intercellular communication

International Nuclear Information System (INIS)

Dertinger, H.; Guichard, M.; Malaise, E.P.

1983-01-01

This investigation addresses the shape of radiation survival curves of cells cultures as multicell spheroids. It is shown that spheroids of cells capable of intercellular communication by gap-junctions display survival curves lacking a radioresistant fraction of hypoxic cells. Compared to the corresponding monolayers, these spheriod survival curves exhibit a uniform increase in radioresistance due to the ''contact effect''. In contrast, biphasic survival curves indicative of hypoxic cells are obtained with non-communicating spheroids, however, without indication of a contact effect. Evidence is presented that this relationship between intercellular communication, hypoxia, and contact effect may possibly also hold for survival curves of solid tumors. (orig.)

Effect of intratympanic dexamethasone, memantine and piracetam on cellular apoptosis due to cisplatin ototoxicity.

Science.gov (United States)

Topdag, M; Iseri, M; Gelenli, E; Yardimoglu, M; Yazir, Y; Ulubil, S A; Topdag, D O; Ustundag, E

2012-11-01

This study aimed to contribute to the literature on the prevention and treatment of ototoxicity due to various drugs and chemicals. This study compared the histological effects of intratympanic dexamethasone, memantine and piracetam on cellular apoptosis due to cisplatin ototoxicity, in 36 rats. Dexamethasone and memantine had significant effects on the stria vascularis, organ of Corti and spiral ganglion (p piracetam decreased the apoptosis rate, this effect was not statistically significant (p > 0.05). Dexamethasone and memantine were found superior to piracetam in reducing apoptosis due to cisplatin ototoxicity. Further studies of this subject are needed, incorporating electron microscopy and auditory brainstem response testing.

Competitive inhibition of [3H]dexamethasone binding to mammary glucocorticoid receptor by leupeptin

International Nuclear Information System (INIS)

Hsieh, L.C.C.; Su, C.; Markland, F.S. Jr.

1987-01-01

The inhibitory effect of leupeptin on [ 3 H]dexamethasone binding to the glucocorticoid receptor from lactating goat mammary cytosol has been studied. Leupeptin (10 mM) caused a significant (about 35%) inhibition of [ 3 H]dexamethasone binding to glucocorticoid receptor. Binding inhibition is further increased following filtration of unlabeled cytosolic receptor through a Bio-Gel A 0.5-m column. Binding inhibition was partially reversed by monothioglycerol at 10 mM concentration. A double reciprocal plot revealed that leupeptin appears to be a competitive inhibitor of [ 3 H]dexamethasone binding to the glucocorticoid receptor. Low salt sucrose density gradient centrifugation revealed that the leupeptin-treated sample formed a slightly larger (approximately 9 S) receptor complex (leupeptin-free complex sediments at 8 S)

Comparative study of preoperative use of oral gabapentin, intravenous dexamethasone and their combination in gynaecological procedure

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Neha Agrawal

2015-01-01

Full Text Available Background: We studied the effects of oral gabapentin and intravenous (I.V. dexamethasone given together or separately 1 h before the start of surgery on intraoperative hemodynamics Postoperative analgesia and postoperative nausea vomiting (PONV in patients undergoing gynaecological procedure. Materials and Methods: Patients were randomly divided into three groups: Group 1 (gabapentin, n = 46 received 400 mg gabapentin, Group 2 (dexamethasone, n = 46 received 8 mg dexamethasone and Group 3 (gabapentin plus dexamethasone, n = 46 received both 400 mg gabapentin and 8 mg dexamethasone I.V. 1 h before the start of surgery. Standard induction and maintenance of anesthesia were accomplished. Visual analog scale for pain was recorded for 12 h. Side effects were noted. Results: Hemodynamics at various time interval (0, 5, 10, 15, 20, 25 and 30 min of laryngeal mask airway insertion and PONV were found significantly lower in Group 3 than in Group 1 and Group 2 (P 3 was significantly longer in Group 3 (510.00 ± 61.64 min than in Group 1 (352.83 ± 80.61 min and in Group 2 (294.78 ± 60.76 min, (P < 0.05. Conclusion: The present study concludes that the combination of oral Gabapentin and I.V. dexamethasone has significantly less hemodynamic changes, better postoperative analgesia and less incidence of PONV than individual administration of each drug.

Acute Activation of Metabolic Syndrome Components in Pediatric Acute Lymphoblastic Leukemia Patients Treated with Dexamethasone

NARCIS (Netherlands)

Warris, Lidewij T.; van den Akker, Erica L. T.; Bierings, Marc B.; van den Bos, Cor; Zwaan, Christian M.; Sassen, Sebastiaan D. T.; Tissing, Wim J. E.; Veening, Margreet A.; Pieters, Rob; van den Heuvel-Eibrink, Marry M.

2016-01-01

Although dexamethasone is highly effective in the treatment of pediatric acute lymphoblastic leukemia (ALL), it can cause serious metabolic side effects. Because studies regarding the effects of dexamethasone are limited by their small scale, we prospectively studied the direct effects of treating

Low-functional programming of the CREB/BDNF/TrkB pathway mediates cognitive impairment in male offspring after prenatal dexamethasone exposure.

Science.gov (United States)

Dong, Wanting; Xu, Dan; Hu, Zewen; He, Xia; Guo, Zijing; Jiao, Zhexiao; Yu, Ying; Wang, Hui

2018-02-01

Adverse intrauterine environments can increase susceptibility to neuropsychiatric diseases that are related to cognitive impairment. In this study, we observed the cognitive impairment of male offspring rats after prenatal dexamethasone exposure (PDE) and explored the associated intrauterine programming mechanism. Pregnant Wistar rats were subcutaneously injected with 0.2mg/kgd dexamethasone from gestational day 9 (GD9) to GD20. A cohort of the pregnant rat group was sacrificed on GD20, and the male fetal rats were collected. Another group of pregnant rats delivered their offspring naturally, and the male adult offspring rats were subjected to behavioural tests postnatally at 26 weeks and then sacrificed. The adult PDE male offspring rats exhibited cognitive impairment, decreased cell proliferation and increased cell apoptosis in the hippocampus, along with damaged synaptic plasticity and disrupted protein synthesis. Meanwhile, activation of GR and downregulation of the cAMP responsive element binding protein (CREB)/brain-derived neurotrophic factor (BDNF)/tropomyosin receptor tyrosine B (TrkB) signalling pathway were found in the adult PDE offspring rats. Further examinations indicated consistent alterations to the fetal hippocampus by PDE. We concluded that PDE can cause cognitive impairment in adult male offspring rats. The mechanism may be associated with low-functional programming of the hippocampal CREB/BDNF/TrkB signalling pathway. Copyright © 2017 Elsevier B.V. All rights reserved.

Granisetron plus dexamethasone for prevention of postoperative nausea and vomiting in patients undergoing laparoscopic surgery: A meta-analysis.

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Zhu, Min; Zhou, Chengmao; Huang, Bing; Ruan, Lin; Liang, Rui

2017-06-01

Objective This study was designed to compare the effectiveness of granisetron plus dexamethasone for preventing postoperative nausea and vomiting (PONV) in patients undergoing laparoscopic surgery. Methods We searched the literature in the Cochrane Library, PubMed, EMBASE, and CNKI. Results In total, 11 randomized controlled trials were enrolled in this analysis. The meta-analysis showed that granisetron in combination with dexamethasone was significantly more effective than granisetron alone in preventing PONV in patients undergoing laparoscopy surgery. No significant differences in adverse reactions (dizziness and headache) were found in association with dexamethasone. Conclusion Granisetron in combination with dexamethasone was significantly more effective than granisetron alone in preventing PONV in patients undergoing laparoscopic surgery, with no difference in adverse reactions between the two groups. Granisetron alone or granisetron plus dexamethasone can be used to prevent PONV in patients undergoing laparoscopic surgery.

Cortisol secretion after adrenocorticotrophin (ACTH and Dexamethasone tests in healthy female and male dogs

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Castillo Victor

2009-08-01

Full Text Available Abstract Background For the conclusive diagnosis of Cushing's Syndrome, a stimulating ACTH test or a low suppressive Dexamethasone test is used. Reports in other species than the dog indicate that plasma cortisol concentration after ACTH administration is affected by gender. We investigated the effect of gender on the cortisol response to ACTH and Dexamethasone tests in dogs. Methods Seven healthy adult Cocker Spaniels (4 females and 3 males were assigned to a two by two factorial design: 4 dogs (2 females and 2 males received IV Dexamethasone 0.01 mg/kg, while the other 3 dogs received an IV saline solution (control group. Two weeks later the treatments were reversed. After one month, ACTH was given IV (250 μg/animal to 4 dogs (2 female and 2 males while the rest was treated with saline solution (control group. Cortisol concentrations were determined by a direct solid-phase radioimmunoassay and cholesterol and triglycerides by commercial kits. Results and Discussion No effect of treatment was observed in metabolite concentrations, but females presented higher cholesterol concentrations. ACTH-treated dogs showed an increase in cortisol levels in the first hour after sampling until 3 hours post injection. Cortisol concentrations in Dexamethasone-treated dogs decreased one hour post injection and remained low for 3 hours, thereafter cortisol concentrations increased. The increase in cortisol levels from one to two hours post ACTH injection was significantly higher in females than males. In Dexamethasone-treated males cortisol levels decreased one hour post injection up to 3 hours; in females the decrease was more pronounced and prolonged, up to 5 hours post injection. Conclusion We have demonstrated that cortisol response to ACTH and Dexamethasone treatment in dogs differs according to sex.

High performance liquid chromatography determination of dexamethasone in plasma to evaluate its systemic absorption following intra-space pterygomandibular injection of twin-mix (mixture of 2 % lignocaine with 1:200,000 epinephrine and 4 mg dexamethasone): randomized control trial.

Science.gov (United States)

Bhargava, Darpan; Deshpande, Ashwini; Thomas, Shaji; Sharma, Yogesh; Khare, Piush; Sahu, Sanjeev Kumar; Dubey, Suyash; Pandey, Ankit; Sreekumar, K

2016-09-01

To determine systemic absorption of dexamethasone by detection of plasma concentration using high performance liquid chromatography following its administration along with local anesthetic agent as a mixture via pterygomandibular space. A prospective randomized double-blind clinical study was undertaken to analyze the plasma concentration of dexamethasone after intra-space pterygomandibular injection along with local anesthesia. The study was performed as per split mouth model where the mandibular quadrant allocation was done on a random basis considering each of the 30 patients is included in the two study interventions (SS and CS). For the study site (SS) procedures, dexamethasone was administered as a mixture (2 % lignocaine with 1:200,000 epinephrine and 4 mg dexamethasone) intra-space. In the control site (CS) procedures, a regular standard inferior alveolar nerve block was administered, and dexamethasone was given as intramuscular injection. The plasma dexamethasone determination was done in venous blood 30- and 60-min post injection using high performance liquid chromatography (HPLC). The clinical parameters like pain; swelling; and mouth opening on the first, third, and seventh post-operative day were analyzed and compared. No significant difference was found in the clinical parameters assessed; comparative evaluation showed less swelling in the SS interventions. The plasma concentration of dexamethasone for the CS interventions was 226 ± 47 ng/ml at 30-min and 316 ± 81.6 ng/ml at 60-min post injection, and for SS, it was 221 ± 81.6 ng/ml at 30-min and 340 ± 105 ng/ml at 60-min post injection. On inter-site (CS and SS) comparison, no statistically significant difference was ascertained in dexamethasone plasma concentration at 30-min post injection (P = 0.77) and at 60-min post injection. (P = 0.32). Intra-space (pterygomandibular space) administration of dexamethasone can achieve statistically similar plasma concentration

Simultaneous Determination of Ciprofloxacin Hydrochloride and Dexamethasone Sodium Phosphate in Eye Drops by HPLC

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Prakash Katakam

2012-01-01

Full Text Available A liquid chromatographic method was developed and validated for the simultaneous determination of ciprofloxacin hydrochloride and dexamethasone sodium phosphate in bulk and pharmaceutical formulations. Optimum separation was achieved in less than 5 min using a C18 column (250 mmx4.6 mm i.d, 5μ particle size by isocratic elution. The mobile phase consisting of a mixture of mixed phosphate buffer (pH 4 and acetonitrile (65:35, v/v was used. Column effluents were monitored at 254 nm at a flow rate of 1ml/min. Retention times of ciprofloxacin hydrochloride and dexamethasone sodium phosphate were 2.0 and 3.16 min respectively. The linearity of ciprofloxacin hydrochloride and dexamethasone sodium phosphate was in the range of 3-18 μg/ml and 1-6 μg/ml respectively. Developed method was economical in terms of the time taken and amount of solvent consumed for each analysis. The method was validated and successfully applied to the simultaneous determination of ciprofloxacin hydrochloride and dexamethasone sodium phosphate in bulk and pharmaceutical formulations.

β–Hydroxy β–Methylbutyrate Improves Dexamethasone-Induced Muscle Atrophy by Modulating the Muscle Degradation Pathway in SD Rat

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Choi, Yeon Ja; Park, Min Hi; Jang, Eun Ji; Park, Chan Hum; Yoon, Changshin; Kim, Nam Deuk; Kim, Mi Kyung; Chung, Hae Young

2014-01-01

Skeletal muscle atrophy results from various conditions including high levels of glucocorticoids, and β–hydroxy β–methylbutyrate (HMB; a metabolite of leucine) is a potent therapeutical supplement used to treat various muscle disorders. Recent studies have demonstrated that HMB inhibits dexamethasone-induced atrophy in cultured myotubes, but its effect on dexamethasone-induced muscle atrophy has not been determined in vivo. In the present study, we investigated the effect of HMB on dexamethasone-induced muscle atrophy in rats. Treatment with dexamethasone weakened grip strengths and increased muscle damage as determined by increased serum creatine kinase levels and by histological analysis. Dexamethasone treatment also reduced both soleus and gastrocnemius muscle masses. However, HMB supplementation significantly prevented reductions in grip strengths, reduced muscle damage, and prevented muscle mass and protein concentration decrease in soleus muscle. Biochemical analysis demonstrated that dexamethasone markedly increased levels of MuRF1 protein, which causes the ubiquitination and degradation of MyHC. Indeed, dexamethasone treatment decreased MyHC protein expression and increased the ubiquitinated-MyHC to MyHC ratio. However, HMB supplementation caused the down-regulations of MuRF1 protein and of ubiquitinated-MyHC. Furthermore, additional experiments provided evidence that HMB supplementation inhibited the nuclear translocation of FOXO1 induced by dexamethasone, and showed increased MyoD expression in the nuclear fractions of soleus muscles. These findings suggest that HMB supplementation attenuates dexamethasone-induced muscle wasting by regulating FOXO1 transcription factor and subsequent MuRF1 expression. Accordingly, our results suggest that HMB supplementation could be used to prevent steroid myopathy. PMID:25032690

Comparison of granisetron alone and granisetron plus dexamethasone in the prophylaxis of cytotoxic-induced emesis.

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Carmichael, J.; Bessell, E. M.; Harris, A. L.; Hutcheon, A. W.; Dawes, P. J.; Daniels, S.; Bessel, E. M.

1994-01-01

Two hundred and seventy-eight adult chemonaive patients, receiving moderately emetogenic chemotherapy were randomly allocated to receive either intravenous (i.v.) granisetron 3 mg plus i.v. dexamethasone 8 mg or i.v. granisetron 3 mg plus i.v. placebo dexamethasone prior to chemotherapy. Eight-two per cent of all patients recruited were female, and 91% of all patients consumed less than 10 units of alcohol per week, suggesting a study population with an increased risk of nausea and vomiting. In the first 24 h 85% of patients who received granisetron plus dexamethasone were complete responders compared with 75.9% of the patients receiving granisetron alone (P = 0.053). There were statistically significant improvements in complete response over 7 days (P = 0.029) and in the numbers of patients receiving rescue antiemetic (P = 0.0004). Toxicity was minimal with no significant differences between treatment groups. These results confirm the antiemetic activity of granisetron and show that it has an additive effect in combination with dexamethasone. PMID:7981069

Dexamethasone-induced radioresistance occurring independent of human papilloma virus gene expression in cervical carcinoma cells

International Nuclear Information System (INIS)

Rutz, H.P.; Mariotta, M.; Mirimanoff, R.O.; Knebel Doeberitz, M. von

1998-01-01

The aim of this study was to investigate the role of HPV 18 E6 and E7 gene products with respect to radiosensitivity of two cervical carcinoma cell lines. The two cervical carcinoma lines C4-1 and SW 756 were used in which treatment with dexamethasone allows to modulate expression levels of HPV 18 E6 and E7 genes: Upregulation in C4-1, down-regulation in SW 756. Effects of treatment with dexamethasone on plating efficiency and radiosensitivity were assessed using a clonogenic assay. Treatment with dexamethasone increased plating efficiency of the C4-1 cells, but did not affect plating efficiency of SW 756 cells. Treatment with dexamethasone induced enhanced radioresistance in both cell lines. Thus, in C4-1 cells the observed changes in radioresistance correlate to the enhancement in expression of HPV 18 genes E6/E7, whereas in SW 756, a reduced expression correlates negatively with the enhanced radioresistance. (orig./MG) [de

Effect of dexamethasone in low volume supraclavicular brachial plexus block: A double-blinded randomized clinical study

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Arun Kumar Alarasan

2016-01-01

Full Text Available Background and Aims: With the use of ultrasound, a minimal effective volume of 20 ml has been described for supraclavicular brachial plexus block. However achieving a long duration of analgesia with this minimal volume remains a challenge. We aimed to determine the effect of dexamethasone on onset and duration of analgesia in low volume supraclavicular brachial plexus block. Material and Methods: Sixty patients were randomly divided into two groups of 30 each. Group C received saline (2 ml + 20 ml of 0.5% bupivacaine and Group D received dexamethasone (8 mg + 20 ml of 0.5% bupivacaine in supraclavicular brachial plexus block. Hemodynamic variables and visual analog scale (VAS score were noted at regular intervals until 450 min. The onset and duration of sensory and motor block were measured. The incidence of "Halo" around brachial plexus was observed. Student′s t-test and Chi-square test were used for statistical analysis. Results: The onset of sensory and motor block was significantly earlier in dexamethasone group (10.36 ± 1.99 and 12 ± 1.64 minutes compared to control group (12.9 ± 2.23 and 18.03 ± 2.41 minutes. The duration of sensory and motor block was significantly prolonged in dexamethasone group (366 ± 28.11 and 337.33 ± 28.75 minutes compared to control group (242.66 ± 26.38 and 213 ± 26.80 minutes. The VAS score was significantly lower in dexamethasone group after 210 min. "Halo" was present around the brachial plexus in all patients in both the groups. Conclusion: Dexamethasone addition significantly increases the duration of analgesia in patients receiving low volume supraclavicular brachial plexus block. No significant side-effects were seen in patients receiving dexamethasone as an adjunct.

Dexamethasone-induced radioresistance occurring independent of human papilloma virus gene expression in cervical carcinoma cells

Energy Technology Data Exchange (ETDEWEB)

Rutz, H.P.; Mariotta, M.; Mirimanoff, R.O. [Lab. de Radiobiologie, Service de Radio-Oncologie, CHUV, Lausanne (Switzerland); Knebel Doeberitz, M. von [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Inst. fuer Virusforschung

1998-02-01

The aim of this study was to investigate the role of HPV 18 E6 and E7 gene products with respect to radiosensitivity of two cervical carcinoma cell lines. The two cervical carcinoma lines C4-1 and SW 756 were used in which treatment with dexamethasone allows to modulate expression levels of HPV 18 E6 and E7 genes: Upregulation in C4-1, down-regulation in SW 756. Effects of treatment with dexamethasone on plating efficiency and radiosensitivity were assessed using a clonogenic assay. Treatment with dexamethasone increased plating efficiency of the C4-1 cells, but did not affect plating efficiency of SW 756 cells. Treatment with dexamethasone induced enhanced radioresistance in both cell lines. Thus, in C4-1 cells the observed changes in radioresistance correlate to the enhancement in expression of HPV 18 genes E6/E7, whereas in SW 756, a reduced expression correlates negatively with the enhanced radioresistance. (orig./MG) [Deutsch] Das Ziel dieser Studie lag darin, die Rolle der HPV-18-Gene E6 und E7 in bezug auf die Strahlenempfindlichkeit von menschlichen Zervixkarzinomzellen zu untersuchen. Wir verwendeten zwei menschliche Zervixkarzinomzellinien, C4-1 und SW 756, in welchen die Expression der viralen Gene HPV 18 E6 und E7 mit Dexamethason moduliert werden kann: In C4-1 bewirkt die Behandlung mit Dexamethason eine Erhoehung der Expression dieser Gene, in SW 756 eine Verminderung. Die Wirkung auf die Wachstumsfaehigkeit der Zellen und auf die Wachstumshemmung durch die Bestrahlung wurde unter Verwendung eines klonogenen Assays bestimmt. Dexamethason bewirkte eine erhoehte Wachstumsfaehigkeit der C4-1 Zellen, ohne die Wachstumsfaehigkeit der SW-756-Zellen zu beeinflussen, wie schon frueher beschrieben. Die Resistenz beider Zellinien gegenueber Bestrahlung wurde erhoeht. Somit besteht in den C4-1-Zellen eine Korrelation der Expression der viralen Gene mit der Zunahme der Strahlenresistenz, wogegen in den SW-756-Zellen die Abnahme der Expression im Gegensatz zu

Magnetic hyaluronic acid nanospheres via aqueous Diels-Alder chemistry to deliver dexamethasone for adipose tissue engineering.

Science.gov (United States)

Jia, Yang; Fan, Ming; Chen, Huinan; Miao, Yuting; Xing, Lian; Jiang, Bohong; Cheng, Qifan; Liu, Dongwei; Bao, Weikang; Qian, Bin; Wang, Jionglu; Xing, Xiaodong; Tan, Huaping; Ling, Zhonghua; Chen, Yong

2015-11-15

Biopolymer-based nanospheres have great potential in the field of drug delivery and tissue regenerative medicine. In this work, we present a flexible way to conjugate a magnetic hyaluronic acid (HA) nanosphere system that are capable of vectoring delivery of adipogenic factor, e.g. dexamethasone, for adipose tissue engineering. Conjugation of nanospheres was established by aqueous Diels-Alder chemistry between furan and maleimide of HA derivatives. Simultaneously, a furan functionalized dexamethasone peptide, GQPGK, was synthesized and covalently immobilized into the nanospheres. The magnetic HA nanospheres were fabricated by encapsulating super-paramagnetic iron oxide nanoparticles, which exhibited quick magnetic sensitivity. The aqueous Diels-Alder chemistry made nanospheres high binding efficiency of dexamethasone, and the vectoring delivery of dexamethasone could be easily controlled by a external magnetic field. The potential application of the magnetic HA nanospheres on vectoring delivery of adipogenic factor was confirmed by co-culture of human adipose-derived stem cells (ASCs). In vitro cytotoxicity tests demonstrated that incorporation of dexamethasone into magnetic HA nanospheres showed high efficiency to promote ASCs viabilities, in particular under a magnetic field, which suggested a promising future for adipose regeneration applications. Copyright © 2015 Elsevier Inc. All rights reserved.

Cyclodextrin-Based Nanohydrogels Containing Polyamidoamine Units: A New Dexamethasone Delivery System for Inflammatory Diseases

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Monica Argenziano

2017-06-01

Full Text Available Glucocorticoids are widely prescribed in treatment of rheumatoid arthritis, asthma, systemic lupus erythematosus, lymphoid neoplasia, skin and eye inflammations. However, well-documented adverse effects offset their therapeutic advantages. In this work, novel nano-hydrogels for the sustained delivery of dexamethasone were designed to increase both bioavailability and duration of the administered drug and reducing the therapeutic dose. Hydrogels are soft materials consisting of water-swollen cross-linked polymers to which the insertion of cyclodextrin (CD moieties adds hydrophobic drug-complexing sites. Polyamidoamines (PAAs are biocompatible and biodegradable polymers apt to create CD moieties in hydrogels. In this work, β or γ-CD/PAA nanogels have been developed. In vitro studies showed that a pretreatment for 24–48 h with dexamethasone-loaded, β-CD/PAA nanogel (nanodexa inhibits adhesion of Jurkat cells to human umbilical vein endothelial cells (HUVEC in conditions mimicking inflammation. This inhibitory effect was faster and higher than that displayed by free dexamethasone. Moreover, nanodexa inhibited COX-2 expression induced by PMA+A23187 in Jurkat cells after 24–48 h incubation in the 10−8–10−5 M concentration range, while dexamethasone was effective only at 10−5 M after 48 h treatment. Hence, the novel nanogel-dexamethasone formulation combines faster action with lower doses, suggesting the potential for being more manageable than the free drug, reducing its adverse side effects.

Sustained release ophthalmic dexamethasone: In vitro in vivo correlations derived from the PK-Eye.

Science.gov (United States)

Awwad, Sahar; Day, Richard M; Khaw, Peng T; Brocchini, Steve; Fadda, Hala M

2017-04-30

Corticosteroids have long been used to treat intraocular inflammation by intravitreal injection. We describe dexamethasone loaded poly-DL-lactide-co-glycolide (PLGA) microparticles that were fabricated by thermally induced phase separation (TIPS). The dexamethasone loaded microparticles were evaluated using a two-compartment, in vitro aqueous outflow model of the eye (PK-Eye) that estimates drug clearance time from the back of the eye via aqueous outflow by the anterior route. A dexamethasone dose of 0.20±0.02mg in a 50μL volume of TIPS microparticles resulted in a clearance t 1/2 of 9.6±0.3days using simulated vitreous in the PK-Eye. Since corticosteroids can also clear through the retina, it is necessary to account for clearance through the back of the eye. Retinal permeability data, published human ocular pharmacokinetics (PK) and the PK-Eye clearance times were then used to establish in vitro in vivo correlations (IVIVCs) for intraocular clearance times of corticosteroid formulations. A t 1/2 of 48h was estimated for the dexamethasone-TIPS microparticles, which is almost 9 times longer than that reported for dexamethasone suspension in humans. The prediction of human clearance times of permeable molecules from the vitreous compartment can be determined by accounting for drug retinal permeation and determining the experimental clearance via the anterior aqueous outflow pathway using the PK-Eye. Copyright © 2017. Published by Elsevier B.V.

Silencing Dkk1 expression rescues dexamethasone-induced suppression of primary human osteoblast differentiation.

LENUS (Irish Health Repository)

Butler, Joseph S

2010-09-01

The Wnt\\/β-catenin pathway is a major signaling cascade in bone biology, playing a key role in bone development and remodeling. The objectives of this study were firstly, to determine the effects of dexamethasone exposure on Wnt\\/β-catenin signaling at an intracellular and transcriptional level, and secondly, to assess the phenotypic effects of silencing the Wnt antagonist, Dickkopf-1 (Dkk1) in the setting of dexamethasone exposure.

Anti-CD163-dexamethasone protects against apoptosis after ischemia/reperfusion injuries in the rat liver

DEFF Research Database (Denmark)

Møller, Lin Nanna Okholm; Knudsen, Anders Riegels; Andersen, Kasper Jarlhelt

2015-01-01

, high dose dexamethasone, low dose dexamethasone or placebo intravenously 18 h before laparotomy with subsequent 60 min of liver ischemia. After reperfusion for 24 h the animals had their liver removed. Bloods were drawn 30 min and 24 h post ischemia induction. Liver cell apoptosis and necrosis were...

Intercellular Uptake of Technetium-99m Pertechnetate by Different Types of Cell Lines

International Nuclear Information System (INIS)

Safri Zainal Abidin; Raizulnasuha Abdul Rashid; Muhammad Afiq Khairil Anuar; Wan Nordiana A Abd Rahman

2015-01-01

The purpose of this study is to determine the technetium-99m pertechnetate ( 99m TcO 4 ) intercellular uptake by different types of cell lines. HeLa, human fetal osteoblast (hFOB), glial and glioma cell lines grown in 6-wells culture plates were incubated with 99m TcO 4 of activity of 200, 400, 600, 800 and 1000 μCi for 30 minutes at 37 degree Celsius and 5 % CO 2 humidified atmosphere. After incubation, the cells were washed 3 times with phosphate buffer saline to remove the extracellular traces of 99m TcO 4 . Measurement of the intercellular 99m TcO 4 into the cells was calculated. The intercellular uptake of 99m TcO 4 was found to be inversely correlate to the radioactivity. HHeLa cell shows the highest uptake followed by hFOB, glial and glioma cell lines. Comparison of uptake between normal and cancer cells present indistinguishable results. The findings of this study suggest that the intercellular uptake of 99m TcO 4 is highly dependent on the type of cells despite no significant different of uptake was found between normal and cancer cell lines. The level of radioactivity is also an important determinant factor that influence the uptake of 99m TcO 4 into the cell. The study will be the first precedent toward understanding the cellular characteristics and pharmacokinetic of non-invasive imaging tracer for future molecular imaging and therapy. (author)

Long-term outcomes and cost effectiveness of high-dose dexamethasone for cardiac surgery : A randomised trial

NARCIS (Netherlands)

Dieleman, J. M.; de Wit, G. A.; Nierich, A. P.; Rosseel, P. M.; van der Maaten, J. M.; Hofland, J.; Diephuis, J. C.; de Lange, F.; Boer, C.; Neslo, R. E.; Moons, K. G.; van Herwerden, L. A.; Tijssen, J. G.; Kalkman, C. J.; van Dijk, D.

Prophylactic intra-operative administration of dexamethasone may improve short-term clinical outcomes in cardiac surgical patients. The purpose of this study was to evaluate long-term clinical outcomes and cost effectiveness of dexamethasone versus placebo. Patients included in the multicentre,

Long-term outcomes and cost effectiveness of high-dose dexamethasone for cardiac surgery: a randomised trial

NARCIS (Netherlands)

Dieleman, J. M.; de Wit, G. A.; Nierich, A. P.; Rosseel, P. M.; van der Maaten, J. M.; Hofland, J.; Diephuis, J. C.; de Lange, F.; Boer, C.; Neslo, R. E.; Moons, K. G.; van Herwerden, L. A.; Tijssen, J. G.; Kalkman, C. J.; van Dijk, D.

2017-01-01

Prophylactic intra-operative administration of dexamethasone may improve short-term clinical outcomes in cardiac surgical patients. The purpose of this study was to evaluate long-term clinical outcomes and cost effectiveness of dexamethasone versus placebo. Patients included in the multicentre,

Low-Dose Dexamethasone Therapy from Infancy of Virilizing Congenital Adrenal Hyperplasia

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Scott A. Rivkees

2009-01-01

Full Text Available Objective. To assess the growth and control of adrenal androgen secretion in children with virilizing congenital adrenal hyperplasia (CAH treated with dexamethasone. Method. We examined doses used, control of adrenal androgen secretion, and growth and skeletal maturation of 8 children with CAH treated with dexamethasone beginning in infancy. Results. 3 boys and 5 girls with classical CAH (17-hydroxyprogesterone at diagnosis >20,000 ng/dL were treated with dexamethasone beginning at diagnosis (<10 days of age. Patients were also treated with fludrocortisone and sodium chloride. The average initial medication dose was 0.1 mg (0.28±0.015 mg/m2; all doses were given in the morning using a dosing syringe to administer a 0.1 mg/mL elixir. The children were treated for 6.5±2.0 years over which time the change in bone age to chronological age ratio (ΔBA/ΔCA was 0.9±0.06. Most recent height Z' scores were +0.5±0.2, and body mass index (BMI scores were 18±0.2. Late afternoon levels of 17-hydroxyprogesterone, androstenedione, and testosterone were 780±238 ng/dL (23.4±7 nmol/L, 42±10 ng/dL (1.4±0.3 nmol/L, and 11.5±3 ng/dL; (0.4±0.1 nmol/L, respectively. Conclusions. These observations show that low doses of dexamethasone can be used to effectively treat CAH beginning in infancy.

Atomoxetine Prevents Dexamethasone-Induced Skeletal Muscle Atrophy in Mice

Science.gov (United States)

Jesinkey, Sean R.; Korrapati, Midhun C.; Rasbach, Kyle A.; Beeson, Craig C.

2014-01-01

Skeletal muscle atrophy remains a clinical problem in numerous pathologic conditions. β2-Adrenergic receptor agonists, such as formoterol, can induce mitochondrial biogenesis (MB) to prevent such atrophy. Additionally, atomoxetine, an FDA-approved norepinephrine reuptake inhibitor, was positive in a cellular assay for MB. We used a mouse model of dexamethasone-induced skeletal muscle atrophy to investigate the potential role of atomoxetine and formoterol to prevent muscle mass loss. Mice were administered dexamethasone once daily in the presence or absence of formoterol (0.3 mg/kg), atomoxetine (0.1 mg/kg), or sterile saline. Animals were euthanized at 8, 16, and 24 hours or 8 days later. Gastrocnemius muscle weights, changes in mRNA and protein expression of peroxisome proliferator–activated receptor-γ coactivator-1 α (PGC-1α) isoforms, ATP synthase β, cytochrome c oxidase subunit I, NADH dehydrogenase (ubiquinone) 1 β subcomplex, 8, ND1, insulin-like growth factor 1 (IGF-1), myostatin, muscle Ring-finger protein-1 (muscle atrophy), phosphorylated forkhead box protein O 3a (p-FoxO3a), Akt, mammalian target of rapamycin (mTOR), and ribosomal protein S6 (rp-S6; muscle hypertrophy) in naive and muscle-atrophied mice were measured. Atomoxetine increased p-mTOR 24 hours after treatment in naïve mice, but did not change any other biomarkers. Formoterol robustly activated the PGC-1α-4-IGF1–Akt-mTOR-rp-S6 pathway and increased p-FoxO3a as early as 8 hours and repressed myostatin at 16 hours. In contrast to what was observed with acute treatment, chronic treatment (7 days) with atomoxetine increased p-Akt and p-FoxO3a, and sustained PGC-1α expression and skeletal muscle mass in dexamethasone-treated mice, in a manner comparable to formoterol. In conclusion, chronic treatment with a low dose of atomoxetine prevented dexamethasone-induced skeletal muscle wasting and supports a potential role in preventing muscle atrophy. PMID:25292181

Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem-cell transplantation: MRC Myeloma IX randomized trial results

Science.gov (United States)

Morgan, Gareth J.; Davies, Faith E.; Gregory, Walter M.; Bell, Sue E.; Szubert, Alexander J.; Navarro Coy, Nuria; Cook, Gordon; Feyler, Sylvia; Johnson, Peter R.E.; Rudin, Claudius; Drayson, Mark T.; Owen, Roger G.; Ross, Fiona M.; Russell, Nigel H.; Jackson, Graham H.; Child, J. Anthony

2012-01-01

Background Thalidomide is active in multiple myeloma and is associated with minimal myelosuppression, making it a good candidate for induction therapy prior to high-dose therapy with autologous stem-cell transplantation. Design and Methods Oral cyclophosphamide, thalidomide, and dexamethasone was compared with infusional cyclophosphamide, vincristine, doxorubicin, and dexamethasone in patients with newly diagnosed multiple myeloma. Results The post-induction overall response rate (≥ partial response) for the intent-to-treat population was significantly higher with cyclophosphamide-thalidomide-dexamethasone (n=555) versus cyclophosphamide-vincristine-doxorubicin-dexamethasone (n=556); 82.5% versus 71.2%; odds ratio 1.91; 95% confidence interval 1.44–2.55; P<0.0001. The complete response rates were 13.0% with cyclophosphamide-thalidomide-dexamethasone and 8.1% with cyclophos-phamide-vincristine-doxorubicin-dexamethasone (P=0.0083), with this differential response being maintained in patients who received autologous stem-cell transplantation (post-transplant complete response 50.0% versus 37.2%, respectively; P=0.00052). Cyclophosphamide-thalidomide-dexamethasone was non-inferior to cyclophosphamide-vincristine-doxorubicin-dexamethasone for progression-free and overall survival, and there was a trend toward a late survival benefit with cyclophosphamide-thalidomide-dexamethasone in responders. A trend toward an overall survival advantage for cyclophosphamide-thalidomide-dexamethasone over cyclophosphamide-vincristine-doxorubicin-dexamethasone was also observed in a subgroup of patients with favorable interphase fluorescence in situ hybridization. Compared with cyclophosphamide-vincristine-doxorubicin-dexamethasone, cyclophosphamide-thalidomide-dexamethasone was associated with more constipation and somnolence, but a lower incidence of cytopenias. Conclusions The cyclophosphamide-thalidomide-dexamethasone regimen showed improved response rates and was not inferior

Intercellular Adhesion Molecule-1 Levels in Experimental Brain Injury and the Effects of Alpha-tocopherol

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Nilgun Senol

2014-06-01

Full Text Available Aim: The mechanisms, responsible for the secondary injuries occuring after acute injury of the brain are; release of nitrous oxide which is an inflammatory mediator, abnormal formation of free oxygen radicals and excessive stimulation of excitatory aminoacids. In this study, it is aimed to investigate changes in intercellular adhesion molecule levels in the brain, that occur subsequent to blunt head trauma, and after administration of an antioxidant agent, vitamin E. Material and Method: In this study, rats were divided into 4 groups. In group A; rats had only skin incision, group B; rats were traumatized after the skin incision, group C; isotonic (30mg/kg was given intraperitoneally after 30 minutes of the trauma, group D; alpha-tocopherol (30mg/kg was given intraperitoneally, after 30 minutes of the trauma. All the rats in these groups were sacrified after 24 hours. Biparietal and bifrontal lobs were taken about 3x5x1mm tickness and intercellular adhesion molecule-1 levels were studied by enzyme-linked immunosorbent assay kit. Results: As the result of the statistical analysis, it is detected that although there is an increase in intercellular adhesion molecule levels in brain parenchyma after trauma, it is statistically unsignificant. However, as the traumatized group and the group given alpha-tocopherol after trauma was compared, a statistically significant decrease in intercellular adhesion molecule-1 levels in the alpha-tocopherol given group was seen. Discussion: Alpha-tocopherol, an antioxidant agent, causes decrease in intercellular adhesion molecule levels, by decreasing inflammation.

The effects of dexamethasone on the Na,K-ATPase activity and pump function of corneal endothelial cells.

Science.gov (United States)

Hatou, Shin; Yamada, Masakazu; Mochizuki, Hiroshi; Shiraishi, Atsushi; Joko, Takeshi; Nishida, Teruo

2009-05-01

The Na(+)- and K(+)-dependent ATPase (Na,K-ATPase) expressed in the basolateral membrane of corneal endothelial cells plays an important role in the pump function of the corneal endothelium. We investigated the possible role of dexamethasone in the regulation of Na,K-ATPase activity and pump function in corneal endothelial cells. Confluent monolayers of mouse corneal endothelial cells were exposed to dexamethasone. ATPase activity of the cells was evaluated by spectrophotometric measurement of phosphate released from ATP with the use of ammonium molybdate, with Na,K-ATPase activity being defined as the portion of total ATPase activity sensitive to ouabain. Pump function of the cells was measured with the use of an Ussing chamber, with the pump function attributable to Na,K-ATPase activity being defined as the portion of the total short-circuit current sensitive to ouabain. Western blot analysis was examined to measure the expression of the Na,K-ATPase alpha(1)-subunit. Dexamethasone (1 or 10 microM) increased the Na,K-ATPase activity and pump function of the cultured cells. These effects of dexamethasone were blocked by cycloheximide, a protein synthesis inhibitor. Western blot analysis also indicated that dexamethasone increased the expression of the Na,K-ATPase alpha(1)-subunit, whereas it decreased the expression of the phospho-Na,K-ATPase alpha(1)-subunit. Our results suggest that dexamethasone stimulates Na,K-ATPase activity in mouse corneal endothelial cells. The effect of dexamethasone activation in these cells is mediated by Na,K-ATPase synthesis and increase in an enzymatic activity by dephosphorylation of Na,K-ATPase alpha(1)-subunits.

Effects of Maternal Dexamethasone Exposure During Lactation on ...

African Journals Online (AJOL)

olayemitoyin

examined the effects of lactational dexamethasone exposure on metabolic imbalance and oxidative stress marker in the liver ... control. Basal Fasting Blood Sugar (FBS) was also significantly (p<0.001) higher in the Dex ... Exposure to stress and glucocorticoids hormone ..... Energy expenditure and energy intake during.

A Retrospective Study Evaluating the Effect of Low Doses of Perineural Dexamethasone on Ropivacaine Brachial Plexus Peripheral Nerve Block Analgesic Duration.

Science.gov (United States)

Schnepper, Gregory D; Kightlinger, Benjamin I; Jiang, Yunyun; Wolf, Bethany J; Bolin, Eric D; Wilson, Sylvia H

2017-09-23

Examination of the effectiveness of perineural dexamethasone administered in very low and low doses on ropivacaine brachial plexus block duration. Retrospective evaluation of brachial plexus block duration in a large cohort of patients receiving peripheral nerve blocks with and without perineural dexamethasone in a prospectively collected quality assurance database. A single academic medical center. A total of 1,942 brachial plexus blocks placed over a 16-month period were reviewed. Demographics, nerve block location, and perineural dexamethasone utilization and dose were examined in relation to block duration. Perineural dexamethasone was examined as none (0 mg), very low dose (2 mg or less), and low dose (greater than 2 mg to 4 mg). Continuous catheter techniques, local anesthetics other than ropivacaine, and block locations with fewer than 15 subjects were excluded. Associations between block duration and predictors of interest were examined using multivariable regression models. A subgroup analysis of the impact of receiving dexamethasone on block duration within each block type was also conducted using a univariate linear regression approach. A total of 1,027 subjects were evaluated. More than 90% of brachial plexus blocks contained perineural dexamethasone (≤4 mg), with a median dose of 2 mg. Increased block duration was associated with receiving any dose of perineural dexamethasone (P block duration did not differ with very low- or low-dose perineural dexamethasone after controlling for other factors (P = 0.420). Perineural dexamethasone prolonged block duration compared with ropivacaine alone; however, duration was not greater with low-dose compared with very low-dose perineural dexamethasone. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Effects of Antenatal Betamethasone and Dexamethasone in Preterm Neonates

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Chen-Yu Chen

2005-09-01

Conclusion: In our study, no significant differences between antenatal betamethasone and dexamethasone were found in complications of preterm neonates. Incomplete courses of antenatal corticosteroids were associated with an increased incidence of RDS compared with complete courses.

Levels Of Serum Intercellular And Vascular Adhesion Molecules In ...

African Journals Online (AJOL)

The study evaluated the possible significant role of soluble intercellular and vascular adhesion molecule-1 (sICAM-1 and sVCAM-1), sE-selectin and interluekin-1β in development nephropathy in patients with insulin dependent diabetes mellitus (IDDM). This study included 60 patients with type 1 diabetes mellitus (IDDM) ...

Intracameral dexamethasone reduces inflammation on the first postoperative day after cataract surgery in eyes with and without glaucoma.

Science.gov (United States)

Chang, Diane T W; Herceg, Michael C; Bilonick, Richard A; Camejo, Larissa; Schuman, Joel S; Noecker, Robert J

2009-01-01

To evaluate whether dexamethasone injected intracamerally at the conclusion of surgery can safely and effectively reduce postoperative inflammation and improve surgical outcomes in eyes with and without glaucoma. Retrospective chart review of 176 consecutive eyes from 146 patients receiving uncomplicated phacoemulsification (PE) (n = 118 total, 82 with glaucoma), glaucoma drainage device (GDD) (n = 35), combined PE/GDD (n = 11) and combined PE/endoscopic cyclophotocoagulation (n = 12). Ninety-one eyes from 76 patients were injected with 0.4 mg dexamethasone intracamerally at the conclusion of surgery. All eyes received standard postoperative prednisolone and ketorolac eyedrops. Outcomes were measured for four to eight weeks by subjective complaints, visual acuity (VA), slit-lamp biomicroscopy, intraocular pressure (IOP) and postoperative complications. Dexamethasone significantly reduced the odds of having an increased anterior chamber (AC) cell score after PE (p = 0.0013). Mean AC cell score +/- SD in nonglaucomatous eyes was 1.3 +/- 0.8 in control and 0.8 +/- 0.7 with dexamethasone; scores in glaucomatous eyes were 1.3 +/- 0.7 in control and 0.9 +/- 0.8 with dexamethasone. Treated nonglaucomatous eyes had significantly fewer subjective complaints after PE (22.2% vs 64.7% in control; p = 0.0083). Dexamethasone had no significant effects on VA, corneal changes, IOP one day and one month after surgery, or long-term complications. Intracameral dexamethasone given at the end of cataract surgery significantly reduces postoperative AC cells in eyes with and without glaucoma, and improves subjective reports of recovery in nonglaucomatous eyes. There were no statistically significant risks of IOP elevation or other complications in glaucomatous eyes.

The effects of dexamethasone on post-asphyxial cerebral oxygenation in the preterm fetal sheep

Science.gov (United States)

Lear, Christopher A; Koome, Miriam E; Davidson, Joanne O; Drury, Paul P; Quaedackers, Josine S; Galinsky, Robert; Gunn, Alistair J; Bennet, Laura

2014-01-01

Exposure to clinical doses of the glucocorticoid dexamethasone increases brain activity and causes seizures in normoxic preterm fetal sheep without causing brain injury. In contrast, the same treatment after asphyxia increased brain injury. We hypothesised that increased injury was in part mediated by a mismatch between oxygen demand and oxygen supply. In preterm fetal sheep at 0.7 gestation we measured cerebral oxygenation using near-infrared spectroscopy, electroencephalographic (EEG) activity, and carotid blood flow (CaBF) from 24 h before until 72 h after asphyxia induced by 25 min of umbilical cord occlusion. Ewes received dexamethasone intramuscularly (12 mg 3 ml–1) or saline 15 min after the end of asphyxia. Fetuses were studied for 3 days after occlusion. During the first 6 h of recovery after asphyxia, dexamethasone treatment was associated with a significantly greater fall in CaBF (P < 0.05), increased carotid vascular resistance (P < 0.001) and a greater fall in cerebral oxygenation as measured by the difference between oxygenated and deoxygenated haemoglobin (delta haemoglobin; P < 0.05). EEG activity was similarly suppressed in both groups. From 6 to 10 h onward, dexamethasone treatment was associated with a return of CaBF to saline control levels, increased EEG power (P < 0.005), greater epileptiform transient activity (P < 0.001), increased oxidised cytochrome oxidase (P < 0.05) and an attenuated increase in [delta haemoglobin] (P < 0.05). In conclusion, dexamethasone treatment after asphyxia is associated with greater hypoperfusion in the critical latent phase, leading to impaired intracerebral oxygenation that may exacerbate neural injury after asphyxia. PMID:25384775

Dexamethasone facilitates fear extinction and safety discrimination in PTSD: A placebo-controlled, double-blind study.

Science.gov (United States)

Michopoulos, Vasiliki; Norrholm, Seth D; Stevens, Jennifer S; Glover, Ebony M; Rothbaum, Barbara O; Gillespie, Charles F; Schwartz, Ann C; Ressler, Kerry J; Jovanovic, Tanja

2017-09-01

Psychophysiological hallmarks of posttraumatic stress disorder (PTSD) include exaggerated fear responses, impaired inhibition and extinction of conditioned fear, and decreased discrimination between safety and fear cues. This increased fear load associated with PTSD can be a barrier to effective therapy thus indicating the need for new treatments to reduce fear expression in people with PTSD. One potential biological target for reducing fear expression in PTSD is the hypothalamic-pituitary-adrenal (HPA) axis, which is dysregulated in PTSD. Recent translational rodent studies and cross-sectional clinical studies have shown that dexamethasone administration and the resulting suppression of cortisol in individuals with PTSD leads to a decrease in the fear responses characteristic of PTSD. These data, taken together, suggest that dexamethasone may serve as a novel pharmacologic intervention for heightened fear responses in PTSD. We conducted a double-blind, placebo-controlled trial to test our hypothesis that dexamethasone administration and the concomitant suppression of HPA axis hyperactivity would attenuate fear expression and enhance fear extinction in individuals with PTSD. Study participants (n=62) were recruited from Grady Memorial Hospital in Atlanta, GA. Participants were randomized to receive dexamethasone or placebo prior to fear conditioning and extinction, in a counterbalanced design (treatments separated by a week). Both PTSD- (n=37) and PTSD+ (n=25) participants showed significant startle increases in the presence of the danger signal during placebo and dexamethasone treatments (all pextinction blocks during both conditions (p's≤0.001), with PTSD+ participants showing deficits in fear extinction and safety discrimination in the placebo condition. Notably, extinction and discrimination deficits in PTSD+ subjects were markedly reversed with dexamethasone (pextinction and discrimination in individuals with PTSD. Copyright © 2017 Elsevier Ltd. All rights

Effect of retinol and cigarette-smoke and condensate on dye-coupled intercellular communication between hamster tracheal epithelial cells

NARCIS (Netherlands)

Rutten, A.A.J.J.L.; Jongen, W.M.F.; Haan, L.H.J.de; Hendriksen, E.G.J.; Koeman, J.H.

1988-01-01

The dye-coupled intercellular communication across gap junctions in primary hamster tracheal epithelial cells has been studied in serum-free, hormone-supplemented medium. In the absence of vitamin A, non-cytotoxic concentrations of cigarette-smoke condensate (CSC) inhibited intercellular

Longstanding refractory pseudophakic cystoid macular edema resolved using intravitreal 0.7 mg dexamethasone implants

Directory of Open Access Journals (Sweden)

Brynskov T

2013-06-01

Full Text Available Troels Brynskov,1,2 Caroline Schmidt Laugesen,1 Jakob Halborg,1 Henrik Kemp,1 Torben Lykke Sørensen1,21Department of Ophthalmology, Copenhagen University Hospital Roskilde, Roskilde, Denmark; 2Faculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkBackground: Refractory pseudophakic cystoid macular edema (PCME following cataract surgery has long posed a challenge to clinicians, but intravitreal injections with a sustained delivery 0.7 mg dexamethasone implant has emerged as a promising therapy for this condition.Objective: To present a case of longstanding and refractory PCME with complete remission through 189 days of follow-up after two successive injections with intravitreal dexamethasone implants.Case report: A 59-year-old male had experienced metamorphopsia for approximately 4 years and had been diagnosed with PCME 15 months earlier. Since the time of the diagnosis, the condition had been refractory to both subtenon triamcinolone acetonide and a total of five injections with intravitreal ranibizumab. After the last injection with ranibizumab, central subfield mean thickness was 640 µm, and the best corrected visual acuity was 78 Early Treatment Diabetic Retinopathy Study letters. Following an intravitreal injection with a dexamethasone implant, the macular edema resolved at the next follow-up. The macular edema returned 187 days after the first injection and was treated with another intravitreal dexamethasone implant. Again, the macular edema subsided completely, and best corrected visual acuity improved to 84 Early Treatment Diabetic Retinopathy Study letters, a condition which was maintained through an additional 189 days of follow-up.Conclusion: Chronic PCME is traditionally a difficult condition to treat, but we are encouraged by the optimal response experienced with intravitreal sustained release dexamethasone implants in our patient whose longstanding PCME had been refractory to previous treatments with both

The effect of a chitosan-gelatin matrix and dexamethasone on the behavior of rabbit mesenchymal stem cells

International Nuclear Information System (INIS)

Medrado, G C B; Machado, C B; Valerio, P; Sanches, M D; Goes, A M

2006-01-01

Cartilage tissue has poor capability of self-repair, especially in the case of severe cartilage damage due to trauma or age-related degeneration. Cell-based tissue engineering using scaffolds has provided an option for the repair of defects in adult cartilage tissue. Mesenchymal stem cells (MSC) and chondrocytes are the two major cell sources for cartilage tissue engineering. The present study combined culture conditions of MSC in a chitosan-gelatin matrix in chondrogenic media to evaluate their effects on MSC viability and chondrogenesis for cartilage tissue engineering. MSC were harvested from rabbit bone marrows and cultured in chondrogenic media supplemented, or not, with dexamethasone in a chitosan-gelatin film (C-GF). The association of C-GF and dexamethasone promoted significant increase in cell adhesivity, viability and proliferation when compared to MCS cultured in media without dexamethasone or C-GF. In addition, dexamethasone promoted increase in the collagen concentration of MSC cultures. A reduction of alkaline phosphatase activity after three weeks of culture in chondrogenic media was verified. No influence of the C-GF or of dexamethasone was observed in this matter. Therefore, it is reasonable to suggest that biomaterial-based chitosan-gelatin and chondrogenic media supplemented with dexamethasone may stimulate the proliferation and differentiation of MSC according to the complex environmental conditions. The information presented here should be useful for the development of biomaterials to regulate the chondrogenesis of MSC suitable for cartilage tissue engineering

The effect of a chitosan-gelatin matrix and dexamethasone on the behavior of rabbit mesenchymal stem cells

Energy Technology Data Exchange (ETDEWEB)

Medrado, G C B [Medicine School, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG (Brazil); Machado, C B [Biochemistry and Immunology Department, Biological Sciences Institute, UFMG - Federal University of Minas Gerais, mailbox 486, zip code 31270-901, Belo Horizonte, MG (Brazil); Valerio, P [Biochemistry and Immunology Department, Biological Sciences Institute, UFMG - Federal University of Minas Gerais, mailbox 486, zip code 31270-901, Belo Horizonte, MG (Brazil); Sanches, M D [Medicine School, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG (Brazil); Goes, A M [Biochemistry and Immunology Department, Biological Sciences Institute, UFMG - Federal University of Minas Gerais, mailbox 486, zip code 31270-901, Belo Horizonte, MG (Brazil)

2006-09-15

Cartilage tissue has poor capability of self-repair, especially in the case of severe cartilage damage due to trauma or age-related degeneration. Cell-based tissue engineering using scaffolds has provided an option for the repair of defects in adult cartilage tissue. Mesenchymal stem cells (MSC) and chondrocytes are the two major cell sources for cartilage tissue engineering. The present study combined culture conditions of MSC in a chitosan-gelatin matrix in chondrogenic media to evaluate their effects on MSC viability and chondrogenesis for cartilage tissue engineering. MSC were harvested from rabbit bone marrows and cultured in chondrogenic media supplemented, or not, with dexamethasone in a chitosan-gelatin film (C-GF). The association of C-GF and dexamethasone promoted significant increase in cell adhesivity, viability and proliferation when compared to MCS cultured in media without dexamethasone or C-GF. In addition, dexamethasone promoted increase in the collagen concentration of MSC cultures. A reduction of alkaline phosphatase activity after three weeks of culture in chondrogenic media was verified. No influence of the C-GF or of dexamethasone was observed in this matter. Therefore, it is reasonable to suggest that biomaterial-based chitosan-gelatin and chondrogenic media supplemented with dexamethasone may stimulate the proliferation and differentiation of MSC according to the complex environmental conditions. The information presented here should be useful for the development of biomaterials to regulate the chondrogenesis of MSC suitable for cartilage tissue engineering.

Does Dexamethasone Helps in Meningococcal Sepsis?

OpenAIRE

Tolaj, Ilir; Ramadani, Hamdi; Mehmeti, Murat; Gashi, Hatixhe; Kasumi, Arbana; Gashi, Visar; Jashari, Haki

2017-01-01

Purpose: Prompt recognition and aggressive early treatment are the only effective measures against invasive meningococcal disease (IMD). Anti-inflammatory adjunctive treatment remains controversial and difficult to assess in patients with IMD. The purpose of this study was to evaluate the effect of dexamethasone (DXM) as adjunctive treatment in different clinical forms of IMD, and attempt to answer if DXM should be routinely used in the treatment of IMD. Methods: In this non-interventional cl...

Differential effects of rapamycin and dexamethasone in mouse models of established allergic asthma.

Directory of Open Access Journals (Sweden)

Elizabeth M Mushaben

Full Text Available The mammalian target of rapamycin (mTOR plays an important role in cell growth/differentiation, integrating environmental cues, and regulating immune responses. Our lab previously demonstrated that inhibition of mTOR with rapamycin prevented house dust mite (HDM-induced allergic asthma in mice. Here, we utilized two treatment protocols to investigate whether rapamycin, compared to the steroid, dexamethasone, could inhibit allergic responses during the later stages of the disease process, namely allergen re-exposure and/or during progression of chronic allergic disease. In protocol 1, BALB/c mice were sensitized to HDM (three i.p. injections and administered two intranasal HDM exposures. After 6 weeks of rest/recovery, mice were re-exposed to HDM while being treated with rapamycin or dexamethasone. In protocol 2, mice were exposed to HDM for 3 or 6 weeks and treated with rapamycin or dexamethasone during weeks 4-6. Characteristic features of allergic asthma, including IgE, goblet cells, airway hyperreactivity (AHR, inflammatory cells, cytokines/chemokines, and T cell responses were assessed. In protocol 1, both rapamycin and dexamethasone suppressed goblet cells and total CD4(+ T cells including activated, effector, and regulatory T cells in the lung tissue, with no effect on AHR or total inflammatory cell numbers in the bronchoalveolar lavage fluid. Rapamycin also suppressed IgE, although IL-4 and eotaxin 1 levels were augmented. In protocol 2, both drugs suppressed total CD4(+ T cells, including activated, effector, and regulatory T cells and IgE levels. IL-4, eotaxin, and inflammatory cell numbers were increased after rapamycin and no effect on AHR was observed. Dexamethasone suppressed inflammatory cell numbers, especially eosinophils, but had limited effects on AHR. We conclude that while mTOR signaling is critical during the early phases of allergic asthma, its role is much more limited once disease is established.

Pregabalin and dexamethasone for postoperative pain control: a randomized controlled study in hip arthroplasty

DEFF Research Database (Denmark)

Mathiesen, O.; Jacobsen, L.S.; Holm, H.E.

2008-01-01

Background. Optimal pain treatment with minimal side-effects is essential for early mobility and recovery in patients undergoing total hip arthroplasty. We investigated the analgesic effect of pregabalin and dexamethasone in this surgical procedure. Methods. One hundred and twenty patients were...... randomly allocated to either Group A (placebo), Group B (pregabalin 300 mg), or Group C (pregabalin 300 mg+dexamethasone 8 mg). The medication and acetaminophen 1 g were given before operation. Spinal anaesthesia was performed. Postoperative pain treatment was with acetaminophen 1 g three times daily...... with the other groups. Conclusions. Pregabalin resulted in a 50% reduction in 24 h postoperative morphine requirements. This was not associated with a reduced incidence of nausea or vomiting. Pregabalin resulted in increased levels of sedation. Combining pregabalin and dexamethasone provided no additional...

Expression of ICAM-1 in blood-spinal cord barrier disruption and CNS radiation injury

International Nuclear Information System (INIS)

Nordal, R.A.; Li, Y.-Q.; Wong, C.S.

2003-01-01

Full text: Intercellular adhesion molecule-1 (ICAM-1) expression is increased following a number of CNS insults in association with blood-brain barrier (BBB) disruption. While disruption of ICAM-1 expression reduces injury in diverse pathologies ranging from trauma to ischemia, its role in CNS radiation injury is not understood. Adult rats received 0 to 22 Gy to a 1.6 cm length of the cervical spinal cord. Expression of ICAM-1 was studied using immunohistochemistry (IHC). Blood-spinal cord barrier (BSCB) disruption was detected by IHC for endogenous albumin and the BBB protein endothelial barrier antigen (EBA). To assess the role of ICAM-1 in the mechanisms of BSCB disruption, animals received IV injections of an ICAM-1-specific blocking antibody (IA-29) or vehicle control, and BSCB disruption was examined by albumin IHC. ICAM-1, albumin, and EBA staining areas were quantified by digital image analysis. ICAM-1 expression localized predominantly to endothelium in non-irradiated spinal cord sections. Some expression was also identified in astrocytes. ICAM-1 expression was increased in white matter, but not in grey matter following radiation. After 22 Gy, ICAM-1 protein increased at 24 hours, and increased again from baseline at 17-20 weeks. Induction was seen in both the total immunostained area, and in the number of ICAM-1 positive glia. A dose response was observed in ICAM-1 expression 20 weeks after 16-20 Gy. BSCB disruption also increased with doses 16-20 Gy at 20 weeks. Blocking ICAM-1 with IA-29 significantly decreased BSCB leakage of albumin at 24 hours (p=0.03). Regions with both increased ICAM-1 expression and BSCB disruption were identified in white matter. Thus the dose response and spatial distribution of increased ICAM-1 expression parallels that for BSCB disruption. These results are consistent with a role for increased ICAM-1 expression in radiation-induced BSCB disruption. The effect of blocking ICAM-1 with a neutralizing antibody suggests its

The effect of intraoperative administration of dexamethasone for PONV prophylaxis on perioperative blood glucose level in obese and normal weight children.

Science.gov (United States)

Gnatzy, Richard; Hempel, Gunther; Kaisers, Udo X; Höhne, Claudia

2015-11-01

The incidence of postoperative nausea and vomiting (PONV) can be reduced by dexamethasone. Single-dose administration may cause elevated blood glucose levels in obese adults. No data are available for children. The aim was to evaluate perioperative blood glucose changes related to body weight in children who received dexamethasone. This prospective observational study included 62 children. All patients received total intravenous anesthesia and a single dose of dexamethasone (0.15 mg/kg, maximum 8 mg). Blood glucose levels were measured up to 6 h. Standard deviation scores (SDS) were calculated using age- and gender-specific body mass index (BMI) percentiles, pBlood glucose levels increased from 5.52±0.52 to 6.74±0.84 mmol/L 6 h after dexamethasone without correlation to the BMI-SDS. This study showed an increase of perioperative blood glucose (normoglycemic ranges) after single dose of dexamethasone, but no BMI-dependent effect was observed in children. Therefore, low-dose dexamethasone may be used in obese children for PONV prophylaxis.

Dexamethasone Intravitreal Implant for Diabetic Macular Edema During Pregnancy

DEFF Research Database (Denmark)

Concillado, Michael; Lund-Andersen, Henrik; Mathiesen, Elisabeth R

2016-01-01

PURPOSE: To describe the management of diabetic macular edema during pregnancy with the use of a dexamethasone slow-release intravitreal implant. DESIGN: Retrospective, observational, consecutive case series. METHODS: The study included 5 pregnant women who presented with diabetic macular edema...... injection. RESULTS: Diabetic macular edema involving the foveal center was observed between gestational weeks 9 and 23 in 10 eyes of 5 patients. Dexamethasone intravitreal implant injection was given 10 times in 9 eyes with a mean preinjection center field retinal thickness of 535 μm (range, 239-727 μm...... center field thickness and in 6 of 8 eyes by an increase in BCVA of 5 or more approxETDRS letters. A mild transient rise in intraocular pressure occurred in 3 out of 8 eyes. CONCLUSION: Diabetic macular edema involving the foveal center that presented during pregnancy responded promptly to intravitreal...

Biodegradable hyaluronic acid hydrogels to control release of dexamethasone through aqueous Diels-Alder chemistry for adipose tissue engineering.

Science.gov (United States)

Fan, Ming; Ma, Ye; Zhang, Ziwei; Mao, Jiahui; Tan, Huaping; Hu, Xiaohong

2015-11-01

A robust synthetic strategy of biopolymer-based hydrogels has been developed where hyaluronic acid derivatives reacted through aqueous Diels-Alder chemistry without the involvement of chemical catalysts, allowing for control and sustain release of dexamethasone. To conjugate the hydrogel, furan and maleimide functionalized hyaluronic acid were synthesized, respectively, as well as furan functionalized dexamethasone, for the covalent immobilization. Chemical structure, gelation time, morphologies, swelling kinetics, weight loss, compressive modulus and dexamethasone release of the hydrogel system in PBS at 37°C were studied. The results demonstrated that the aqueous Diels-Alder chemistry provides an extremely selective reaction and proceeds with high efficiency for hydrogel conjugation and covalent immobilization of dexamethasone. Cell culture results showed that the dexamethasone immobilized hydrogel was noncytotoxic and preserved proliferation of entrapped human adipose-derived stem cells. This synthetic approach uniquely allows for the direct fabrication of biologically functionalized gel scaffolds with ideal structures for adipose tissue engineering, which provides a competitive alternative to conventional conjugation techniques such as copper mediated click chemistry. Copyright © 2015. Published by Elsevier B.V.

1,4-Naphthoquinones: From Oxidative Damage to Cellular and Inter-Cellular Signaling

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Lars-Oliver Klotz

2014-09-01

Full Text Available Naphthoquinones may cause oxidative stress in exposed cells and, therefore, affect redox signaling. Here, contributions of redox cycling and alkylating properties of quinones (both natural and synthetic, such as plumbagin, juglone, lawsone, menadione, methoxy-naphthoquinones, and others to cellular and inter-cellular signaling processes are discussed: (i naphthoquinone-induced Nrf2-dependent modulation of gene expression and its potentially beneficial outcome; (ii the modulation of receptor tyrosine kinases, such as the epidermal growth factor receptor by naphthoquinones, resulting in altered gap junctional intercellular communication. Generation of reactive oxygen species and modulation of redox signaling are properties of naphthoquinones that render them interesting leads for the development of novel compounds of potential use in various therapeutic settings.

77 FR 32010 - New Animal Drugs; Altrenogest; Dexamethasone; Florfenicol

Science.gov (United States)

2012-05-31

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 510, 516, 520, 522, and 558 [Docket No. FDA-2012-N-0002] New Animal Drugs; Altrenogest; Dexamethasone; Florfenicol AGENCY: Food and Drug Administration, HHS. [[Page 32011

Downregulation of sphingosine 1-phosphate (S1P) receptor 1 by dexamethasone inhibits S1P-induced mesangial cell migration.

Science.gov (United States)

Koch, Alexander; Jäger, Manuel; Völzke, Anja; Grammatikos, Georgios; Zu Heringdorf, Dagmar Meyer; Huwiler, Andrea; Pfeilschifter, Josef

2015-06-01

Sphingosine 1-phosphate (S1P) is generated by sphingosine kinase (SK)-1 and -2 and acts mainly as an extracellular ligand at five specific receptors, denoted S1P1-5. After activation, S1P receptors regulate important processes in the progression of renal diseases, such as mesangial cell migration and survival. Previously, we showed that dexamethasone enhances SK-1 activity and S1P formation, which protected mesangial cells from stress-induced apoptosis. Here we demonstrate that dexamethasone treatment lowered S1P1 mRNA and protein expression levels in rat mesangial cells. This effect was abolished in the presence of the glucocorticoid receptor antagonist RU-486. In addition, in vivo studies showed that dexamethasone downregulated S1P1 expression in glomeruli isolated from mice treated with dexamethasone (10 mg/kg body weight). Functionally, we identified S1P1 as a key player mediating S1P-induced mesangial cell migration. We show that dexamethasone treatment significantly lowered S1P-induced migration of mesangial cells, which was again reversed in the presence of RU-486. In summary, we suggest that dexamethasone inhibits S1P-induced mesangial cell migration via downregulation of S1P1. Overall, these results demonstrate that dexamethasone has functional important effects on sphingolipid metabolism and action in renal mesangial cells.

Effect of Dexamethasone on Characteristics of Supraclavicular Nerve Block with Bupivacaine and Ropivacaine: A Prospective, Double-blind, Randomized Control Trial.

Science.gov (United States)

Bindal, Deeksha; Narang, Neeraj; Mahindra, Rekha; Gupta, Himanshu; Kubre, Jyotsna; Saxena, Anudeep

2018-01-01

Dexamethasone as an adjuvant to bupivacaine and ropivacaine for supraclavicular brachial plexus (SCBP) block prolongs motor and sensory blockade. However, comparison of effect of dexamethasone (8 mg) when added to these two local anesthetics has not been well studied. This study was conducted to compare analgesic efficacy of dexamethasone as adjuvant to bupivacaine and ropivacaine in SCBP block. Nerve stimulator-guided SCBP block was given to 120 patients, randomly assigned to one of four groups: ( n = 30 in each group) Group B, BD, R, and RD received 30 ml (0.5%) bupivacaine + 2 ml saline, 30 ml (0.5%) bupivacaine + dexamethasone 8 mg, 30 ml (0.5%) ropivacaine + 2 ml saline, and 30 ml (0.5%) ropivacaine + dexamethasone 8 mg, respectively. Time for request of the first rescue analgesic, 24-h analgesic consumption, and different block characteristics were assessed. Student's t -test, Chi-square test, ANOVA were used for statistical analysis. Dexamethasone significantly prolonged time for request of the first rescue analgesic of both ropivacaine (1211.83 ± 32.86 vs. 283.17 ± 7.71 min){ p R, RD block. The addition of dexamethasone to bupivacaine and ropivacaine in SCBP block prolonged time for first rescue analgesia and reduced the requirement of rescue analgesics with faster onset and prolonged duration of sensory and motor block, with the effect being stronger with ropivacaine.

The intercellular synchronization of Ca2+ oscillations evaluates Cx36-dependent coupling.

Directory of Open Access Journals (Sweden)

Sabine Bavamian

Full Text Available Connexin36 (Cx36 plays an important role in insulin secretion by controlling the intercellular synchronization of Ca(2+ transients induced during stimulation. The lack of drugs acting on Cx36 channels is a major limitation in further unraveling the molecular mechanism underlying this effect. To screen for such drugs, we have developed an assay allowing for a semi-automatic, fluorimetric quantification of Ca(2+ transients in large populations of MIN6 cells. Here, we show that (1 compared to control cells, MIN6 cells with reduced Cx36 expression or function showed decreased synchrony of glucose-induced Ca(2+ oscillations; (2 glibenclamide, a sulphonylurea which promotes Cx36 junctions and coupling, increased the number of synchronous MIN6 cells, whereas quinine, an antimalarial drug which inhibits Cx36-dependent coupling, decreased this proportion; (3 several drugs were identified that altered the intercellular Ca(2+ synchronization, cell coupling and distribution of Cx36; (4 some of them also affected insulin content. The data indicate that the intercellular synchronization of Ca(2+ oscillations provides a reliable and non-invasive measurement of Cx36-dependent coupling, which is useful to identify novel drugs affecting the function of β-cells, neurons, and neuron-related cells that express Cx36.

Dexamethasone selectively suppresses microglial trophic responses to hippocampal deafferentation

DEFF Research Database (Denmark)

Woods, A G; Poulsen, F R; Gall, C M

1999-01-01

hippocampus. Daily dexamethasone injections almost completely blocked increases in insulin-like growth factor-1 messenger RNA content, but did not perturb increases in ciliary neurotrophic factor or basic fibroblast growth factor messenger RNA content, in the deafferented dentate gyrus molecular layer...

Intracameral dexamethasone reduces inflammation on the first postoperative day after cataract surgery in eyes with and without glaucoma

Directory of Open Access Journals (Sweden)

Diane TW Chang

2009-05-01

Full Text Available Diane TW Chang, Michael C Herceg, Richard A Bilonick, Larissa Camejo, Joel S Schuman, Robert J NoeckerDepartment of Ophthalmology, University of Pittsburgh Medical Center, Eye Center, Pittsburgh, PA, USAPurpose: To evaluate whether dexamethasone injected intracamerally at the conclusion of surgery can safely and effectively reduce postoperative inflammation and improve surgical outcomes in eyes with and without glaucoma.Methods: Retrospective chart review of 176 consecutive eyes from 146 patients receiving uncomplicated phacoemulsification (PE (n = 118 total, 82 with glaucoma, glaucoma drainage device (GDD (n = 35, combined PE/GDD (n = 11 and combined PE/endoscopic cyclophotocoagulation (n = 12. Ninety-one eyes from 76 patients were injected with 0.4 mg dexamethasone intracamerally at the conclusion of surgery. All eyes received standard postoperative prednisolone and ketorolac eyedrops. Outcomes were measured for four to eight weeks by subjective complaints, visual acuity (VA, slit-lamp biomicroscopy, intraocular pressure (IOP and postoperative complications.Results: Dexamethasone significantly reduced the odds of having an increased anterior chamber (AC cell score after PE (p = 0.0013. Mean AC cell score ± SD in nonglaucomatous eyes was 1.3 ± 0.8 in control and 0.8 ± 0.7 with dexamethasone; scores in glaucomatous eyes were 1.3 ± 0.7 in control and 0.9 ± 0.8 with dexamethasone. Treated nonglaucomatous eyes had significantly fewer subjective complaints after PE (22.2% vs 64.7% in control; p = 0.0083. Dexamethasone had no significant effects on VA, corneal changes, IOP one day and one month after surgery, or long-term complications.Conclusions: Intracameral dexamethasone given at the end of cataract surgery significantly reduces postoperative AC cells in eyes with and without glaucoma, and improves subjective reports of recovery in nonglaucomatous eyes. There were no statistically significant risks of IOP elevation or other complications in

A New Technique for Quantitative Determination of Dexamethasone in Pharmaceutical and Biological Samples Using Kinetic Spectrophotometric Method

Directory of Open Access Journals (Sweden)

Ali Mohammad Akhoundi-Khalafi

2015-01-01

Full Text Available Dexamethasone is a type of steroidal medications that is prescribed in many cases. In this study, a new reaction system using kinetic spectrophotometric method for quantitative determination of dexamethasone is proposed. The method is based on the catalytic effect of dexamethasone on the oxidation of Orange G by bromate in acidic media. The change in absorbance as a criterion of the oxidation reaction progress was followed spectrophotometrically. To obtain the maximum sensitivity, the effective reaction variables were optimized. Under optimized experimental conditions, calibration graph was linear over the range 0.2–54.0 mg L−1. The calculated detection limit (3sb/m was 0.14 mg L−1 for six replicate determinations of blank signal. The interfering effect of various species was also investigated. The present method was successfully applied for the determination of dexamethasone in pharmaceutical and biological samples satisfactorily.

Comparative Study of Intrathecal Dexamethasone with Epinephrine as Adjuvants to Lidocaine in Cesarean Section

Directory of Open Access Journals (Sweden)

Fereshteh Naziri

2013-09-01

Full Text Available Background: Different additives have been used with local anesthetics to provide prolonged duration of sensory block in spinal anesthesia. The aim of present study was to evaluate the onset and duration of sensory block of intrathecal dexamethasone and epinephrine as adjuvants to lidocaine in patients who were candidate for cesarean section. Materials and Methods: This double-blind clinical trial research was conducted on 90 pregnant women candidate for cesarean section under spinal anesthesia. Patients were randomly allocated to receive intrathecally either 75 mg hyperbaric lidocaine plus 100 μg epinephrine or 75 mg hyperbaric lidocaine plus 4 mg dexamethasone or 75 mg hyperbaric lidocaine. The onset and duration of sensory block as well as postoperative analgesia were assessed. Results: The time to reach the peak sensory block in lidocaine group was shorter than that of other two groups (p<0.001. Duration of sensory block in the control group, dexamethasone group, and epinephrine group were 64.16±7.99 min, 74.79±12.78 min, and 99.30±10.93 min, respectively (p<0.001. Conclusion: The present research shows that intrathecal dexamethasone and intrathecal epinephrine as adjuvant to lidocaine increases sensory block duration in the women candidate for cesarean section.

Disruption of myoblast alignment by highly motile rhabdomyosarcoma cell in tissue structure.

Science.gov (United States)

Li, Menglu; Nagamori, Eiji; Kino-Oka, Masahiro

2017-02-01

Rhabdomyosarcoma (RMS) is a highly malignant tumor type of skeletal muscle origin, hallmarked by local invasion. Interaction between invasive tumor cells and normal cells plays a major role in tumor invasion and metastasis. Culturing tumor cells in a three-dimensional (3D) model can translate tumor malignancy relevant cell-cell interaction. To mimic tumor heterogeneity in vitro, a co-culture system consisting of a malignant embryonal rhabdomyosarcoma (ERMS) cell line RD and a normal human skeletal muscle myoblast (HSMM) cell line was established by cell sheet technology. Various ratios of RDs to HSMMs were employed to understand the quantitative effect on intercellular interactions. Disruption of sheet structure was observed in heterogeneous cell sheets having a low ratio of RDs to HSMMs, whereas homogeneous HSMM or RD sheets maintained intact structure. Deeper exploration of dynamic tumor cell behavior inside HSMM sheets revealed that HSMM cell alignment was disrupted by highly motile RDs. This study demonstrated that RMS cells are capable of compromising their surrounding environment through induced decay of HSMMs alignment in a cell-based 3D system. This suggests that muscle disruption might be a major consequence of RMS cell invasion into muscles, which could be a promising target to preventing tumor invasion. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Bortezomib or high-dose dexamethasone for relapsed multiple myeloma

NARCIS (Netherlands)

P.G. Richardson (Paul Gerard); P. Sonneveld (Pieter); M.W. Schuster (Michael); D. Irwin (David); E.A. Stadtmauer (Edward); T. Facon (Thierry); J-L. Harousseau (Jean-Luc); D. Ben-Yehuda (Dina); S. Lonial (Sagar); H. Goldschmidt (Hartmut); D. Reece (Donna); J.F. San Miguel (Jesús Fernando); J. Bladé (Joan); M. Boccadoro (Mario); J. Cavenagh (Jamie); W. Dalton (William); A.L. Boral (Anthony); D.-L. Esseltine (Dixie-Lee); J.B. Porter (Jane); D. Schenkein (David); K.C. Anderson (Kenneth)

2005-01-01

textabstractBACKGROUND: This study compared bortezomib with high-dose dexamethasone in patients with relapsed multiple myeloma who had received one to three previous therapies. METHODS: We randomly assigned 669 patients with relapsed myeloma to receive either an intravenous bolus of bortezomib (1.3

Longstanding refractory pseudophakic cystoid macular edema resolved using intravitreal 0.7 mg dexamethasone implants

DEFF Research Database (Denmark)

Brynskov, Troels; Laugesen, Caroline Schmidt; Halborg, Jakob

2013-01-01

Refractory pseudophakic cystoid macular edema (PCME) following cataract surgery has long posed a challenge to clinicians, but intravitreal injections with a sustained delivery 0.7 mg dexamethasone implant has emerged as a promising therapy for this condition.......Refractory pseudophakic cystoid macular edema (PCME) following cataract surgery has long posed a challenge to clinicians, but intravitreal injections with a sustained delivery 0.7 mg dexamethasone implant has emerged as a promising therapy for this condition....

Optimal cellular mobility for synchronization arising from the gradual recovery of intercellular interactions

International Nuclear Information System (INIS)

Uriu, Koichiro; Ares, Saúl; Oates, Andrew C; Morelli, Luis G

2012-01-01

Cell movement and intercellular signaling occur simultaneously during the development of tissues, but little is known about how movement affects signaling. Previous theoretical studies have shown that faster moving cells favor synchronization across a population of locally coupled genetic oscillators. An important assumption in these studies is that cells can immediately interact with their new neighbors after arriving at a new location. However, intercellular interactions in cellular systems may need some time to become fully established. How movement affects synchronization in this situation has not been examined. Here, we develop a coupled phase oscillator model in which we consider cell movement and the gradual recovery of intercellular coupling experienced by a cell after movement, characterized by a moving rate and a coupling recovery rate, respectively. We find (1) an optimal moving rate for synchronization and (2) a critical moving rate above which achieving synchronization is not possible. These results indicate that the extent to which movement enhances synchrony is limited by a gradual recovery of coupling. These findings suggest that the ratio of time scales of movement and signaling recovery is critical for information transfer between moving cells. (paper)

Dexamethasone hepatic induction in rats subsequently treated with high dose buprenorphine does not lead to respiratory depression

International Nuclear Information System (INIS)

Hreiche, Raymond; Megarbane, Bruno; Pirnay, Stephane; Borron, Stephen W.; Monier, Claire; Risede, Patricia; Milan, Nathalie; Descatoire, Veronique; Pessayre, Dominique; Baud, Frederic J.

2006-01-01

In humans, asphyxic deaths and severe poisonings have been attributed to high-dosage buprenorphine, a maintenance therapy for heroin addiction. However, in rats, intravenous buprenorphine at doses up to 90 mg kg -1 was not associated with significant effects on arterial blood gases. In contrast, norbuprenorphine, the buprenorphine major cytochrome P450 (CYP) 3A-derived metabolite, is a potent respiratory depressant. Thus, our aim was to study the consequences of CYP3A induction on buprenorphine-associated effects on resting ventilation in rats. We investigated the effects on ventilation of 30 mg kg -1 buprenorphine alone or following cytochrome P450 (CYP) 3A induction with dexamethasone, using whole body plethysmography (N = 24) and arterial blood gases (N = 12). Randomized animals in 4 groups received sequential intraperitoneal dosing with: (dexamethasone [days 1-3] + buprenorphine [day 4]), (dexamethasone solvent [days 1-3] + buprenorphine [day 4]), (dexamethasone [days 1-3] + buprenorphine solvent [day 4]), or (dexamethasone solvent [days 1-3] + buprenorphine solvent [day 4]). Buprenorphine alone caused a significant rapid and sustained increase in the inspiratory time (P -1 buprenorphine on rat ventilation. Our results suggest a limited role of drug-mediated CYP3A induction in the occurrence of buprenorphine-attributed respiratory depression in addicts

Antenatal dexamethasone before asphyxia promotes cystic neural injury in preterm fetal sheep by inducing hyperglycemia.

Science.gov (United States)

Lear, Christopher A; Davidson, Joanne O; Mackay, Georgia R; Drury, Paul P; Galinsky, Robert; Quaedackers, Josine S; Gunn, Alistair J; Bennet, Laura

2018-04-01

Antenatal glucocorticoid therapy significantly improves the short-term systemic outcomes of prematurely born infants, but there is limited information available on their impact on neurodevelopmental outcomes in at-risk preterm babies exposed to perinatal asphyxia. Preterm fetal sheep (0.7 of gestation) were exposed to a maternal injection of 12 mg dexamethasone or saline followed 4 h later by asphyxia induced by 25 min of complete umbilical cord occlusion. In a subsequent study, fetuses received titrated glucose infusions followed 4 h later by asphyxia to examine the hypothesis that hyperglycemia mediated the effects of dexamethasone. Post-mortems were performed 7 days after asphyxia for cerebral histology. Maternal dexamethasone before asphyxia was associated with severe, cystic brain injury compared to diffuse injury after saline injection, with increased numbers of seizures, worse recovery of brain activity, and increased arterial glucose levels before, during, and after asphyxia. Glucose infusions before asphyxia replicated these adverse outcomes, with a strong correlation between greater increases in glucose before asphyxia and greater neural injury. These findings strongly suggest that dexamethasone exposure and hyperglycemia can transform diffuse injury into cystic brain injury after asphyxia in preterm fetal sheep.

Expression of a defence-related intercellular barley peroxidase in transgenic tobacco

DEFF Research Database (Denmark)

Kristensen, B.K.; Brandt, J.; Bojsen, K.

1997-01-01

genetically, phenotypically and biochemically. The T-DNA was steadily inherited through three generations. The barley peroxidase is expressed and sorted to the intercellular space in the transgenic tobacco plants. The peroxidase can be extracted from the intercellular space in two molecular forms from both...... barley and transgenic tobacco. The tobacco expressed forms are indistinguishable from the barley expressed forms as determined by analytical isoelectric focusing (pI 8.5) and Western-blotting. Staining for N-glycosylation showed that one form only was glycosylated. The N-terminus of purified Prx8 from...... transgenic tobacco was blocked by pyroglutamate, after the removal of which, N-terminal sequencing verified the transit signal-peptide cleavage site deduced from the cDNA sequence. Phenotype comparisons show that the constitutive expression of Prx8 lead to growth retardation. However, an infection assay...

Pre-treatment with dexamethasone attenuates experimental ventilator-induced lung injury.

Science.gov (United States)

Reis, Fernando Fonseca Dos; Reboredo, Maycon de Moura; Lucinda, Leda Marília Fonseca; Bianchi, Aydra Mendes Almeida; Rabelo, Maria Aparecida Esteves; Fonseca, Lídia Maria Carneiro da; Oliveira, Júlio César Abreu de; Pinheiro, Bruno Valle

2016-01-01

To evaluate the effects that administering dexamethasone before the induction of ventilator-induced lung injury (VILI) has on the temporal evolution of that injury. Wistar rats were allocated to one of three groups: pre-VILI administration of dexamethasone (dexamethasone group); pre-VILI administration of saline (control group); or ventilation only (sham group). The VILI was induced by ventilation at a high tidal volume. Animals in the dexamethasone and control groups were euthanized at 0, 4, 24, and 168 h after VILI induction. We analyzed arterial blood gases, lung edema, cell counts (total and differential) in the BAL fluid, and lung histology. At 0, 4, and 24 h after VILI induction, acute lung injury (ALI) scores were higher in the control group than in the sham group (p grupos: administração de dexametasona pré-LPIVM (grupo dexametasona); administração de salina pré-LPIVM (grupo controle); e somente ventilação (grupo sham). A LPIVM foi realizada por ventilação com volume corrente alto. Os animais dos grupos dexametasona e controle foram sacrificados em 0, 4, 24 e 168 h após LPIVM. Analisamos gasometria arterial, edema pulmonar, contagens de células (totais e diferenciais) no lavado broncoalveolar e histologia de tecido pulmonar. Em 0, 4 e 24 h após LPIVM, os escores de lesão pulmonar aguda (LPA) foram maiores no grupo controle que no grupo sham (p grupo dexametasona não foi significativamente diferente daquele observado no grupo sham e foi menor que o observado no grupo controle (p grupos controle e dexametasona, com pico em 4 h após LPIVM (p grupo dexametasona que no grupo controle em 4 e 24 h após LPIVM (p grupo controle. A administração de dexametasona antes de LPIVM atenua os efeitos da lesão em ratos Wistar. Os mecanismos moleculares dessa lesão e o possível papel clínico dos corticosteroides na LPIVM ainda precisam ser elucidados.

Coronary Heart Disease Alters Intercellular Communication by Modifying Microparticle-Mediated MicroRNA Transport

Science.gov (United States)

Finn, Nnenna A.; Eapen, Danny; Manocha, Pankaj; Kassem, Hatem Al; Lassegue, Bernard; Ghasemzadeh, Nima; Quyyumi, Arshed; Searles, Charles D.

2013-01-01

Coronary heart disease (CHD) is characterized by abnormal intercellular communication and circulating microRNAs (miRNAs) are likely involved in this process. Here, we show that CHD was associated with changes in the transport of circulating miRNA, particularly decreased miRNA enrichment in microparticles (MPs). Additionally, MPs from CHD patients were less efficient at transferring miRNA to cultured HUVECs, which correlated with their diminished capacity to bind developmental endothelial locus-1 (Del-1). In summary, CHD was associated with distinct changes in circulating miRNA transport and these changes may contribute to the abnormal intercellular communication that underlies CHD initiation and progression. PMID:24042051

Aqueous Humor Penetration and Biological Activity of Moxifloxacin 0.5% Ophthalmic Solution Alone or with Dexamethasone 0.1.

Science.gov (United States)

Gomes, Rachel L R; Viana, Rodrigo Galvão; Melo, Luiz Alberto S; Cruz, Alessandro Carvalho; Suenaga, Eunice Mayumi; Kenyon, Kenneth R; Campos, Mauro

2017-03-01

To compare aqueous humor concentrations of topically applied moxifloxacin 0.5% ophthalmic solution alone or in combination with dexamethasone 0.1% and to correlate these concentrations with the minimum inhibitory concentrations (MICs) for common endophthalmitis-causing organisms. Sixty-eight patients undergoing routine phacoemulsification with intraocular lens implantation received either moxifloxacin 0.5% alone or moxifloxacin 0.5% combined with dexamethasone. For both groups, 1 drop of the test solution was instilled 4 times daily 1 day preoperatively and 1 drop 1 h preoperatively. An aqueous humor sample obtained immediately before paracentesis was submitted to high-performance liquid chromatography-tandem mass spectrometry to determine the moxifloxacin concentration. The mean concentrations of moxifloxacin were 986.6 ng/mL in the moxifloxacin with dexamethasone group and 741.3 ng/mL in the moxifloxacin group (P = 0.13). Moxifloxacin concentrations of all samples exceeded the MICs for Staphylococcus epidermidis, S. aureus, and Streptococcus pneumoniae. All samples in the moxifloxacin with dexamethasone group and 94% in the moxifloxacin group achieved the MIC for Enterococcus species. For quinolone-resistant S. aureus, the MIC was achieved in 29% in the moxifloxacin with dexamethasone group and 9% in the moxifloxacin group (P = 0.06). Aqueous humor moxifloxacin concentrations were higher when topically administrated in combination with dexamethasone compared to the moxifloxacin alone. However, this difference was not statistically significant. Nevertheless, the MICs of the most common pathogens associated with endophthalmitis were exceeded in both study groups.

Impairment of wound healing after operative treatment of mandibular fractures, and the influence of dexamethasone.

Science.gov (United States)

Snäll, Johanna; Kormi, Eeva; Lindqvist, Christian; Suominen, Anna Liisa; Mesimäki, Karri; Törnwall, Jyrki; Thorén, Hanna

2013-12-01

Our aim was to clarify the incidence of impaired wound healing after open reduction and ostheosynthesis of mandibular fractures, and to find out whether the use of dexamethasone during the operation increased the risk. Patients were drawn from a larger group of healthy adult dentate patients who had participated in a single-blind, randomised study, the aim of which was to clarify the benefits of operative dexamethasone after treatment of facial fractures. The present analysis comprised 41 patients who had had open reduction and fixation of mandibular fractures with titanium miniplates and monocortical screws through one or 2 intraoral approaches. The outcome variable was impaired healing of the wound. The primary predictive variable was the perioperative use of dexamethasone; other potential predictive variables were age, sex, smoking habit, type of fracture, delay in treatment, and duration of operation. Wound healing was impaired in 13/41 patients (32%) (13/53 of all fractures). The incidence among patients who were given dexamethasone and those who were not did not differ significantly. Only age over 25 was significantly associated with delayed healing (p=0.02). The use of dexamethasone 30 mg perioperatively did not significantly increase the risk of impaired wound healing in healthy patients with clinically uninfected mandibular fractures fixed with titanium miniplates through an intraoral approach. Older age is a significant predictor of impaired healing, which emphasises the importance of thorough anti-infective care in these patients during and after the operation. Copyright © 2013 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Identification of cysteine-644 as the covalent site of attachment of dexamethasone 21-mesylate to murine glucocorticoid receptors in WEHI-7 cells

International Nuclear Information System (INIS)

Smith, L.I.; Bodwell, J.E.; Mendel, D.B.; Ciardelli, T.; North, W.G.; Munck, A.

1988-01-01

Dexamethasone 21-mesylate is a highly specific synthetic glucocorticoid derivative that binds covalently to glucocorticoid receptors via sulfhydryl groups. The authors have identified the amino acid that reacts with the dexamethasone 21-mesylate by using enzymatic digestion and microsequencing for radiolabel. Nonactivated glucocorticoid receptors obtained from labeling intact WEHI-7 mouse thymoma cells with [ 3 H]dexamethasone 21-mesylate were immunopurified and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Trypsin digestion followed by reversed-phase high-performance liquid chromatography (reversed-phase HPLC) produced a single [ 3 H]dexamethasone 21-mesylate labeled peptide. Automated Edman degradation of this peptide revealed that the [ 3 H]dexamethasone 21-mesylate was located at position 5 from the amino terminus. Dual-isotope labeling studies with [ 3 H]dexamethasone 21-mesylate and [ 35 S]methionine demonstrated that this peptide contained methionine. Staphylococcus aureus V8 protease digestion of [ 3 H]dexamethasone 21-mesylate labeled steroid-binding subunits generated a different radiolabeled peptide containing label at position 7 from the amino terminus. On the basis of the published amino acid sequence of the murine glucocorticoid receptor, their data clearly identify cysteine-644 as the single residue in the steroid-binding domain that covalently binds dexamethasone 21-mesylate. They have confirmed this finding by demonstrating that a synthetic peptide representing the amino acid sequence 640-650 of the murine glucocorticoid receptor behaves in an identical manner on reversed-phase HPLC as the trypsin-generated peptide from intact cells

Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma

DEFF Research Database (Denmark)

San-Miguel, Jesús F; Hungria, Vânia T M; Yoon, Sung-Soo

2014-01-01

with bortezomib (1·3 mg/m(2) on days 1, 4, 8, 11, intravenously) and dexamethasone (20 mg on days 1, 2, 4, 5, 8, 9, 11, 12, orally). Patients, physicians, and the investigators who did the data analysis were masked to treatment allocation; crossover was not permitted. The primary endpoint was progression...

Efect of intercellular extracts from banana inoculated leaves with Mycosphaerella fijiensis Morelet, on chloroplast electronic transport of Grande naine (AAA cv.

Directory of Open Access Journals (Sweden)

Michel Leiva-Mora

2003-01-01

Full Text Available Some foliar pathogens colonize intercellular spaces of damage tissues during infection process, mediated by toxins production and diffusion to kill adjacent healthy cells. Due to the absence of reliable bioassays, the physiologic effects of several phytotoxins are still ignored on cellular membranous systems of the affected cells. In the present work it was extracted the intercellular content from not inoculated and inoculated banana leaves with different Mycosphaerella fijiensis strains. Their effects on chloroplasts of Grande naine cv were evaluated by the absorbance evolution (595 nm of Hill reactive (DCPIP, mixture with 810 ì l of chloroplasts suspension and 99 ì l of the intercellular contents. The electronic exchange on chloroplasts suspension was inhibited by intercellular contents of inoculated leaves. The intercellular contents from leaves inoculated with I1 (high virulence strain had a major inhibiter effect respect to leaves inoculates with G1 strain (low virulence, showing a correspondence between the inhibiter effect of intercellular contents and the affection levels of affected tissues. The procedures used in this work will let to make studies concerned with Mycosphaerella fijiensis-Musa spp interactions and the future breeding programs. Key words: banana breeding, black Sigatoka, host pathogen interaction, physiological bioassays

Antenatal Dexamethasone Exposure in Preterm Infants Is Associated with Allergic Diseases and the Mental Development Index in Children

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Wan-Ning Tseng

2016-12-01

Full Text Available Background: Antenatal steroid administration may benefit fetal lung maturity in preterm infants. Although some studies have shown that this treatment may increase asthma in childhood, the correlation between antenatal dexamethasone exposure and allergic diseases remains unclear. The purpose of this study is to investigate the association between antenatal dexamethasone and T cell expression in childhood allergic diseases. Methods: We recruited a cohort of preterm infants born at Kaohsiung Chang Gung Memorial Hospital between 2007 and 2010 with a gestational age of less than 35 weeks and body weight at birth of less than 1500 g. The status of antenatal exposure to steroids and allergic diseases were surveyed using a modified ISAAC questionnaire for subjects aged 2–5 years old. We analyzed Th1/Th2/Th17 expression of mRNA, cytokines (using the Magpix® my-system, and mental development index (MDI. Results: Among the 40 patients that were followed, the data showed that the antenatal dexamethasone exposure group (N = 24 had a significantly higher incidence of allergic diseases (75.0% vs. 18.8%, p < 0.0001 when compared to the non-dexamethasone exposure group (N = 16, especially with regard to asthma (41.7% vs. 0.0%, p = 0.003 and allergic rhinitis (58.3% vs. 18.8%, p = 0.013, but not atopic dermatitis. No statistical difference was observed in the mRNA expression levels of total white blood cell count between the dexamethasone exposure and non-exposure groups (p > 0.05. However, the asthma group had higher IL-5 levels (p = 0.009, and the MDI was shown to be significantly higher in the dexamethasone exposure group (90.38 ± 3.31 vs. 79.94 ± 3.58, p = 0.043 while no significant difference was found between the PDI of the two groups. Conclusions: Exposure to antenatal dexamethasone in preterm infants will increase their susceptibility to allergic diseases, particularly asthma and allergic rhinitis. Preterm infants’ exposure to antenatal

Tunneling nanotubes spread fibrillar α-synuclein by intercellular trafficking of lysosomes.

Science.gov (United States)

Abounit, Saïda; Bousset, Luc; Loria, Frida; Zhu, Seng; de Chaumont, Fabrice; Pieri, Laura; Olivo-Marin, Jean-Christophe; Melki, Ronald; Zurzolo, Chiara

2016-10-04

Synucleinopathies such as Parkinson's disease are characterized by the pathological deposition of misfolded α-synuclein aggregates into inclusions throughout the central and peripheral nervous system. Mounting evidence suggests that intercellular propagation of α-synuclein aggregates may contribute to the neuropathology; however, the mechanism by which spread occurs is not fully understood. By using quantitative fluorescence microscopy with co-cultured neurons, here we show that α-synuclein fibrils efficiently transfer from donor to acceptor cells through tunneling nanotubes (TNTs) inside lysosomal vesicles. Following transfer through TNTs, α-synuclein fibrils are able to seed soluble α-synuclein aggregation in the cytosol of acceptor cells. We propose that donor cells overloaded with α-synuclein aggregates in lysosomes dispose of this material by hijacking TNT-mediated intercellular trafficking. Our findings thus reveal a possible novel role of TNTs and lysosomes in the progression of synucleinopathies. © 2016 The Authors.

Xenobiotic Modulation of Human Mammary Epithelial Cell Gap Junctional Intercellular Communication and Growth

National Research Council Canada - National Science Library

Ruch, Randall

1999-01-01

.... These agents also inhibit gap junctional intercellular communication (GJIC). This inhibition may contribute to the enhancement of breast epithelial growth and breast cancer formation by xenobiotics...

Initial high anti-emetic efficacy of granisetron with dexamethasone is not maintained over repeated cycles.

Science.gov (United States)

de Wit, R.; van den Berg, H.; Burghouts, J.; Nortier, J.; Slee, P.; Rodenburg, C.; Keizer, J.; Fonteyn, M.; Verweij, J.; Wils, J.

1998-01-01

We have reported previously that the anti-emetic efficacy of single agent 5HT3 antagonists is not maintained when analysed with the measurement of cumulative probabilities. Presently, the most effective anti-emetic regimen is a combination of a 5HT3 antagonist plus dexamethasone. We, therefore, assessed the sustainment of efficacy of such a combination in 125 patients, scheduled to receive cisplatin > or = 70 mg m(-2) either alone or in combination with other cytotoxic drugs. Anti-emetic therapy was initiated with 10 mg of dexamethasone and 3 mg of granisetron intravenously, before cisplatin. On days 1-6, patients received 8 mg of dexamethasone and 1 mg of granisetron twice daily by oral administration. Protection was assessed during all cycles and calculated based on cumulative probability analyses using the method of Kaplan-Meier and a model for transitional probabilities. Irrespective of the type of analysis used, the anti-emetic efficacy of granisetron/dexamethasone decreased over cycles. The initial complete acute emesis protection rate of 66% decreased to 30% according to the method of Kaplan-Meier and to 39% using the model for transitional probabilities. For delayed emesis, the initial complete protection rate of 52% decreased to 21% (Kaplan-Meier) and to 43% (transitional probabilities). In addition, we observed that protection failure in the delayed emesis period adversely influenced the acute emesis protection in the next cycle. We conclude that the anti-emetic efficacy of a 5HT3 antagonist plus dexamethasone is not maintained over multiple cycles of highly emetogenic chemotherapy, and that the acute emesis protection is adversely influenced by protection failure in the delayed emesis phase. PMID:9652766

Granistron and dexamethasone provide more improved prevention of postoperative emesis than granisetron alone in children.

Science.gov (United States)

Fujii, Y; Tanaka, H; Toyooka, H

1996-12-01

Dexamethasone decreases chemotherapy-induced emesis when added to antiemetic regimens. This study was designed to compare the effectiveness of granisetron and dexamethasone with granisetron alone in the prevention of post-operative vomiting after strabismus repair, tonsillectomy with or without adenoidectomy in children. In a randomized, double-blind study, 60 healthy children, 4-10 yr of age, received either granisetron 40 micrograms.kg-1 and saline (Group S) or granisetron 40 micrograms.kg-1 and dexamethasone 4 mg (Group D) iv immediately after the induction of anaesthesia. All subjects received anaesthetics consisting of sevoflurane and nitrous oxide in oxygen Postoperative pain was treated with acetaminophen pr or pentazocine iv. Postoperatively, during the first 24 hr after anaesthesia, the frequencies of retching and vomiting, and the incidence of adverse events were recorded by nursing staff. There were no differences between the treatment groups with regard to demographics, surgical procedure, anaesthetic administered or analgesics used for postoperative pain. The frequency of the symptoms was 27% and 7% in Groups S and D, respectively (P < 0.05). The incidence of adverse events was comparable in the two groups. The prophylactic administration of granisetron and dexamethasone was more effective than granisetron alone in the prevention of postoperative vomiting in paediatric subjects undergoing strabismus repair, tonsillectomy and adenoidectomy.

Cytochrome P450-mediated metabolism of tumour promoters modifies the inhibition of intercellular communication: a modified assay for tumour promotion

DEFF Research Database (Denmark)

Vang, Ole; Wallin, H.; Doehmer, J.

1993-01-01

The role of metabolism of tumour promoters on the inhibition of intercellular communication was investigated in a modified V79 metabolic cooperation system. V79 cells, which stably express different rat cytochrome P450 enzymes (CYP1A1, CYP1A2 or CYP2B1), were used in the metabolic cooperation assay...... B1 and 4-nitrobiphenyl, did not inhibit metabolic cooperation in either V79 cells expressing or cells not expressing cytochrome P450. We conclude that cytochrome P450-associated metabolism plays an important role in the inhibition of gap junctional intercellular communication of some tumour...... promoters. The modified metabolic cooperation assay presented here is valuable for detecting some inhibitory chemicals which have been 'false negative' in previous assays for gap junctional intercellular communication. The assay also discloses that cytochrome P450 metabolism alters intercellular...

The effect of preoperative dexamethasone on pain 1 year after lumbar disc surgery

DEFF Research Database (Denmark)

Nielsen, Rikke Vibeke; Fomsgaard, Jonna; Mathiesen, Ole

2016-01-01

discectomy. METHODS: This is a prospective 1-year follow-up on a single-centre, randomized, and blinded trial exploring the analgesic effect of 16 mg IV dexamethasone or placebo after lumbar discectomy. One year follow-up was a written questionnaire including back and leg pain (VAS 0-100 mm), Short Form 36...... survey (SF-36), EuroQol 5D (EQ-5D), OSWESTRY Low Back Pain Questionnaire, duration of sick leave, working capability, contentment with surgical result. RESULTS: Response rate was 71% (55 patients) in the dexamethasone group, 58% (44 patients) in the placebo group. Leg pain (VAS) was significantly lower...... in the placebo group compared to the dexamethasone group: 17 (95% CI 10-26) vs 26 (95% CI 19-33) mm, respectively (mean difference 9 mm (95% CI -1 to 0), (P = 0.03). No difference regarding back pain. The placebo group reported significantly more improvement of leg pain and were significantly more satisfied...

Evaluation of hyperglycaemic response to intra-operative dexamethasone administration in patients undergoing elective intracranial surgery: A randomised, prospective study.

Science.gov (United States)

Sethi, Rakesh; Naqash, Imtiaz A; Bajwa, Sukhminder Jit Singh; Dutta, Vikas; Ramzan, Altaf Umar; Zahoor, Syed Amir

2016-01-01

The glucocorticoid dexamethasone in a bolus dose of 8-10 mg followed by quarterly dose of 4 mg is commonly used during intracranial surgery so as to reduce oedema and vascular permeability. However, the detrimental hyperglycaemic effects of dexamethasone may override its potentially beneficial effects. The present prospective, randomised study aimed at comparing the degree and magnitude of hyperglycaemia induced by prophylactic administration of dexamethasone in patients undergoing elective craniotomy. Sixty American Society of Anaesthesiologist (ASA) grade-I and II patients were randomly assigned to three groups of 20 patients each. Group-I received dexamethasone during surgery for the first time. Group-II received dexamethasone in addition to receiving it pre-operatively, whereas Group-III (control group) patients were administered normal saline as placebo. Baseline blood glucose (BG) was measured in all the three groups before induction of anaesthesia and thereafter after every hour for 4 h and then two-hourly. Besides intra- and intergroup comparison of BG, peak BG concentration was also recorded for each patient. Statistical analysis was carried out with analysis of variance (ANOVA) and Student's t-test and value of P < 0.05 was considered statistically significant. Baseline BG reading were higher and statistically significant in Group-II as compared with Group-I and Group-III (P < 0.05). However, peak BG levels were significantly higher in Group-I than in Group-II and III (P < 0.05). Similarly, the magnitude of change in peak BG was significantly higher in Group-I as compared to Group-II and III (P < 0.05). Peri-operative administration of dexamethasone during neurosurgical procedures can cause significant increase in BG concentration especially in patients who receive dexamethasone intra-operatively only.

ATM splicing variants as biomarkers for low dose dexamethasone treatment of A-T.

Science.gov (United States)

Menotta, Michele; Biagiotti, Sara; Spapperi, Chiara; Orazi, Sara; Rossi, Luigia; Chessa, Luciana; Leuzzi, Vincenzo; D'Agnano, Daniela; Soresina, Annarosa; Micheli, Roberto; Magnani, Mauro

2017-07-05

Ataxia Telangiectasia (AT) is a rare incurable genetic disease, caused by biallelic mutations in the Ataxia Telangiectasia-Mutated (ATM) gene. Treatment with glucocorticoid analogues has been shown to improve the neurological symptoms that characterize this syndrome. Nevertheless, the molecular mechanism underlying the glucocorticoid action in AT patients is not yet understood. Recently, we have demonstrated that Dexamethasone treatment may partly restore ATM activity in AT lymphoblastoid cells by a new ATM transcript, namely ATMdexa1. In the present study, the new ATMdexa1 transcript was also identified in vivo, specifically in the PMBCs of AT patients treated with intra-erythrocyte Dexamethasone (EryDex). In these patients it was also possible to isolate new "ATMdexa1 variants" originating from canonical and non-canonical splicing, each containing the coding sequence for the ATM kinase domain. The expression of the ATMdexa1 transcript family was directly related to treatment and higher expression levels of the transcript in patients' blood correlated with a positive response to Dexamethasone therapy. Neither untreated AT patients nor untreated healthy volunteers possessed detectable levels of the transcripts. ATMdexa1 transcript expression was found to be elevated 8 days after the drug infusion, while it decreased 21 days after treatment. For the first time, the expression of ATM splicing variants, similar to those previously observed in vitro, has been found in the PBMCs of patients treated with EryDex. These findings show a correlation between the expression of ATMdexa1 transcripts and the clinical response to low dose dexamethasone administration.

Efficacy of two regimens of dexamethasone for management of preterm labour: pilot study

International Nuclear Information System (INIS)

Rasool, A.; Farooq, U.

2017-01-01

Background: Dexamethasone is widely used for prevention of respiratory distress syndrome (RDS), necrotising enterocolitis (NEC) and intra-ventricular haemorrhage (IVH) in preterm babies; decreasing the neonatal mortality rate. There is no consensus on the dose of corticosteroid administered to the mother expected to have a preterm baby. This study is conducted to compare the effectiveness of two popular regimens of dexamethasone administration in decreasing incidence of RDS, necrotizing enterocolitis, IVH and neonatal mortality rate. Methods: Randomized control trial was conducted at Ayub Teaching Hospital, Abbottabad from 1st to 31st August, 2014. Sample size was set at 50. Block randomization was employed in the trial to allocate the patients into corresponding groups 'A' and 'B'. Group A was administered 6mg dexamethasone in 4 doses 12 hours apart and group B was administered 2 doses 12 hours apart. Results: Forty-eight patients participated in the study with 24 patients in each group. Mean age and period gestation of participants were 28.4 years±4.3 SD and 34 weeks±1.9 SD respectively. Four patients in group A gave birth to neonate with RDS compared to two cases in group B. Group B had higher incidence of necrotizing enterocolitis and neonatal mortalities. However, none of these differences observed were statistically significant. No case of IVH was reported in either of the groups. Conclusion: Both the popular regimens of dexamethasone administration are equally effective in decreasing the incidence of neonatal diseases. (author)

The efficacy of dexamethasone reducing postoperative pain and emesis after total knee arthroplasty: A systematic review and meta-analysis.

Science.gov (United States)

Fan, Zhengrui; Ma, Jianxiong; Kuang, Mingjie; Zhang, Lukai; Han, Biao; Yang, Baocheng; Wang, Ying; Ma, Xinlong

2018-04-01

Total knee arthroplasty (TKA) is gradually emerging as the treatment of choice for end-stage osteoarthritis. In the past, Perioperative dexamethasone treatment is still a controversial subject in total knee arthroplasty. Therefore, we write this systematic review and meta-analysis to evaluate the efficacy of dexamethasone on pain and recovery after Total knee Arthroplasty. Embase, Pubmed, and Cochrane Library were comprehensively searched. Randomized controlled trials, cohort studies were included in our meta-analysis. Eight studies that compared dexamethasone groups with placebo groups were included in our meta-analysis. The research was reported according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. Randomized controlled trials were included in our meta-analysis. Our study demonstrated that the dexamethasone group was more effective than the placebo group in term of VAS score at 24 h(P meta-analysis demonstrated that dexamethasone decreased postoperative pain, the incidence of POVN, and total opioid consumption effectively which played a critical role in rapid recovery to TKA. However, we still need large sample size, high quality studies to explore the relationship between complications and dose response to give the final conclusion. Copyright © 2018. Published by Elsevier Ltd.

The effect of single low-dose dexamethasone on blood glucose concentrations in the perioperative period: a randomized, placebo-controlled investigation in gynecologic surgical patients.

Science.gov (United States)

Murphy, Glenn S; Szokol, Joseph W; Avram, Michael J; Greenberg, Steven B; Shear, Torin; Vender, Jeffery S; Gray, Jayla; Landry, Elizabeth

2014-06-01

The effect of single low-dose dexamethasone therapy on perioperative blood glucose concentrations has not been well characterized. In this investigation, we examined the effect of 2 commonly used doses of dexamethasone (4 and 8 mg at induction of anesthesia) on blood glucose concentrations during the first 24 hours after administration. Two hundred women patients were randomized to 1 of 6 groups: Early-control (saline); Early-4 mg (4 mg dexamethasone); Early-8 mg (8 mg dexamethasone); Late-control (saline); Late-4 mg (4 mg dexamethasone); and Late-8 mg (8 mg dexamethasone). Blood glucose concentrations were measured at baseline and 1, 2, 3, and 4 hours after administration in the early groups and at baseline and 8 and 24 hours after administration in the late groups. The incidence of hyperglycemic events (the number of patients with at least 1 blood glucose concentration >180 mg/dL) was determined. Blood glucose concentrations increased significantly over time in all control and dexamethasone groups (from median baselines of 94 to 102 mg/dL to maximum medians ranging from 141 to 161.5 mg/dL, all P < 0.001). Blood glucose concentrations did not differ significantly between the groups receiving dexamethasone (either 4 or 8 mg) and those receiving saline at any measurement time. The incidence of hyperglycemic events did not differ in any of the early (21%-28%, P = 0.807) or late (13%-24%, P = 0.552) groups. Because blood glucose concentrations during the first 24 hours after administration of single low-dose dexamethasone did not differ from those observed after saline administrations, these results suggest clinicians need not avoid using dexamethasone for nausea and vomiting prophylaxis out of concerns related to hyperglycemia.

A randomized, double-masked, parallel-group, comparative study to evaluate the clinical efficacy and safety of 1% azithromycin–0.1% dexamethasone combination compared to 1% azithromycin alone, dexamethasone 0.1% alone, and vehicle in the treatment of subjects with blepharitis

Directory of Open Access Journals (Sweden)

Hosseini K

2016-08-01

Full Text Available Kamran Hosseini,1 Richard L Lindstrom,2,3 Gary Foulks,4 Kelly K Nichols5 1InSite Vision, Alameda, CA, 2Minnesota Eye Consultants, 3Department of Ophthalmology and Visual Neurosciences, University of Minnesota Medical School, Minneapolis, MN, 4Department of Ophthalmology and Vision Science, School of Medicine, University of Louisville, Louisville, KY, 5School of Optometry, University of Alabama at Birmingham, Birmingham, AL, USA Purpose: To evaluate the clinical efficacy and safety of a 1% azithromycin–0.1% dexamethasone combination in DuraSite (“combination” compared to 0.1% dexamethasone in DuraSite, 1% azithromycin in DuraSite, and vehicle in the treatment of subjects with blepharitis.Materials and methods: This was a Phase III, double-masked, vehicle-controlled, four-arm study in which 907 subjects with blepharitis were randomized to combination (n=305, 0.1% dexamethasone (n=298, 1% azithromycin (n=155, or vehicle (n=149. Ten study visits were scheduled: screening visit, days 1 and 4 (dosing phase and 15, and months 1–6 (follow-up phase. On day 1, subjects applied one drop of the study drug to the eyelid of the inflamed eye(s twice daily, and continued with twice-daily dosing for 14 days. After completing 14 days of dosing, subjects were followed for 6 months for efficacy and safety.Results: A total of 57 subjects (6.3% had complete clinical resolution at day 15: 25 (8.2%, 17 (5.7%, 8 (5.2%, and 7 (4.7% subjects in the combination-, 0.1% dexamethasone-, 1% azithromycin-, and vehicle-treatment groups, respectively. The combination was superior to 1% azithromycin and vehicle alone, but not to 0.1% dexamethasone alone. Mean composite (total clinical sign and symptom scores improved in all four treatment groups during the posttreatment evaluation phase for the intent-to-treat population, but outcomes were superior when a drop containing 0.1% dexamethasone was utilized. Clinical response was noted as early as day 4, and persisted as long

Effect of Submucosal Injection of Dexamethasone on Post-operative Sequelae of Third Molar Surgery

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S P Deo

2011-06-01

Full Text Available Introduction: This study was carried out to evaluate the effects of a single pre-operative sub-mucosal injection of dexamethasone after third molar surgery to see the effects on post-operative discomfort. Methods: This study was a prospective, double-blind, randomized, clinical trial. The subjects were forty patients who underwent surgical removal of the mandibular impacted third molar under local anesthesia and after being randomly assigned to receive either an 8 mg dexamethasone as submucosal injection or a normal saline injection into the lower buccal vestibule adjacent to the third molar. The maximum interincisal distance and facial contours were measured at the baseline and post-surgically on Day 2 and 7. Post-operative pain was evaluated subjectively using a visual analog scale and objectively by counting the number of analgesic tablets used. All subjects were operated upon by the same investigator to minimize the difference from inter-operator variability. Results: There was a signicant difference in the measurements of the degree of swelling and trismus between the two groups on the 2nd post-operative day. In contrast, there was no statistically signicant difference between the groups on the 7th post-operative day. The test group also used fewer analgesics post-operatively. Conclusions: Submucosal injection of dexamethasone after third molar surgery is effective in reducing postoperative swelling and trismus. It also delays the onset of post-operative pain. Keywords: dexamethasone, submucosal injection, third molar, third molar surgery, third molar extraction

Proteins Play Important Role in Intercellular Adhesion Affecting on Fruit Textural Quality

DEFF Research Database (Denmark)

Bahadur Adhikari, Khem; Shomer, Ilan

2012-01-01

Fruit textural quality is becoming a major quality parameter for export, postharvest preservation, handling and processing. The main determinant of textural quality is intercellular adhesion (ICA) as attributed by the cell wall (CW) and its components. The importance of CW protein in ICA strength......Fruit textural quality is becoming a major quality parameter for export, postharvest preservation, handling and processing. The main determinant of textural quality is intercellular adhesion (ICA) as attributed by the cell wall (CW) and its components. The importance of CW protein in ICA...... strengthening was exempli ed in Medjoul date (Phoenix dactylifera L.) fruit, as a model. Fruit mesocarp sensitively responded to culture environment which was assayed in vitro at pH 3.5( pKa) in presence of organic acid molecules. The max penetration force, as a measure of ICA strength, of p...

The use of dexamethasone in women with preterm premature ...

African Journals Online (AJOL)

The use of dexamethasone in women with preterm premature rupture of membranes - A multicentre, double-blind, placebocontrolled, randomised trial. R.C. Pattinson, J.D. Makin, M. Funk, S.D. Delport, A.P. Macdonald, K. Norman, G. Kirsten, C. Stewart, D. Woods, G. Moller, E. Coetzee, P. Smith, J. Anthony, M. Schoon, ...

Linezolid and dexamethasone experience in a serious case of listeria rhombencephalitis.

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Yılmaz, Pakize Ö; Mutlu, Nevzat M; Sertçelik, Ahmet; Baştuğ, Aliye; Doğu, Cihangir; Kışlak, Sümeyye

2016-01-01

Listeria rhombencephalitis is a rare cause of brain stem encephalitis. We report a case with a history of immunosupressive therapy due to Takayasu's arteritis that was treated with corticosteroids and linezolid for Listeria rhombencephalitis. A 63-year-old woman was admitted to the hospital with fever, headache, nausea, and vomiting. The patient's body temperature was 38°C, and she had a stiff neck. Listeria monocytogenes was isolated from the cerebrospinal fluid (CSF), and penicillin G and gentamicin treatment was initiated. Linezolid and dexamethasone were added. Due to hematuria and thrombocytopenia, the linezolid was discontinued. In immunocompromised patients with CNS infections, Listeria rhombencephalitis should be suspected. Linezolid can be used in combination with dexamethasone. Copyright © 2016 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

Terbinafine inhibits gap junctional intercellular communication.

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Lee, Ju Yeun; Yoon, Sei Mee; Choi, Eun Ju; Lee, Jinu

2016-09-15

Terbinafine is an antifungal agent that selectively inhibits fungal sterol synthesis by blocking squalene epoxidase. We evaluated the effect of terbinafine on gap junctional intercellular communication (GJIC). Fluorescence recovery after photobleaching (FRAP) and I-YFP GJIC assays revealed that terbinafine inhibits GJIC in a reversible and dose-dependent manner in FRT-Cx43 and LN215 cells. Treatment with terbinafine did not affect Cx43 phosphorylation status or intracellular Ca(2+) concentration, well-known action mechanisms of various GJIC blockers. While a structurally related chemical, naftifine, attenuated GJIC, epigallocatechin gallate, another potent squalene epoxidase inhibitor with a different structure, did not. These results suggest that terbinafine inhibits GJIC with a so far unknown mechanism of action. Copyright © 2016 Elsevier Inc. All rights reserved.

Use of the Dexamethasone-Corticotrophin Releasing Hormone Test to Assess Hypothalamic-Pituitary-Adrenal Axis Function in Rheumatoid Arthritis

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Eman A. Hasan

2009-01-01

Full Text Available Objectives. Hypothalamic-Pituitary-Adrenal axis function may be abnormal in rheumatoid arthritis (RA. A pilot study in 7 patients suggested impaired glucocorticoid feedback in some patients after the dexamethasone-corticotrophin releasing hormone (CRH test. This study aimed to investigate the dexamethasone-corticotrophin releasing factor test in a larger group of patients and relate the results to characteristics of the disease. Methods. Outpatients with active RA (≥3 swollen and tender joints and C-reactive protein > 10 mg/L took dexamethasone (1.5 mg at 23:00 hour in the evening. Next day, baseline saliva and plasma samples were collected, CRH was infused at 11:00 hour, and 4 serial blood and saliva samples were collected. Plasma samples were stored at −80∘C and a radioimmunoassay performed for saliva and plasma cortisol. Results. All 20 participants showed normal dexamethasone suppression and mounted no response to the CRH challenge. In samples with measurable cortisol, there was a strong correlation between saliva and plasma values (r = 0.876, n = 26, P<.01. Conclusion. No abnormalities were found in the Dexamethasone-CRH test in RA patients in contrast to a previous pilot study. Salivary cortisol measurement may offer an alternative noninvasive technique to plasma cortisol in RA patients in future studies.

Stomatal responses to flooding of the intercellular air spaces suggest a vapor-phase signal between the mesophyll and the guard cells.

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Sibbernsen, Erik; Mott, Keith A

2010-07-01

Flooding the intercellular air spaces of leaves with water was shown to cause rapid closure of stomata in Tradescantia pallida, Lactuca serriola, Helianthus annuus, and Oenothera caespitosa. The response occurred when water was injected into the intercellular spaces, vacuum infiltrated into the intercellular spaces, or forced into the intercellular spaces by pressurizing the xylem. Injecting 50 mm KCl or silicone oil into the intercellular spaces also caused stomata to close, but the response was slower than with distilled water. Epidermis-mesophyll grafts for T. pallida were created by placing the epidermis of one leaf onto the exposed mesophyll of another leaf. Stomata in these grafts opened under light but closed rapidly when water was allowed to wick between epidermis and the mesophyll. When epidermis-mesophyll grafts were constructed with a thin hydrophobic filter between the mesophyll and epidermis stomata responded normally to light and CO(2). These data, when taken together, suggest that the effect of water on stomata is caused partly by dilution of K(+) in the guard cell and partly by the existence of a vapor-phase signal that originates in the mesophyll and causes stomata to open in the light.

Emergency department treatment of viral gastritis using intravenous ondansetron or dexamethasone in children.

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Stork, Christine M; Brown, Kathleen M; Reilly, Tracey H; Secreti, LaLaina; Brown, Lawrence H

2006-10-01

To compare the efficacy of intravenous ondansetron or dexamethasone compared with intravenous fluid therapy alone in children presenting to the emergency department with refractory vomiting from viral gastritis who had failed attempts at oral hydration. This double-blind, randomized, controlled trial was performed in a tertiary care pediatric emergency department. Children aged 6 months to 12 years presenting with more than three episodes of vomiting in the past 24 hours, mild/moderate dehydration, and failed oral hydration were included. Patients with other medical causes were excluded. Subjects were randomized to dexamethasone 1 mg/kg (15 mg maximum), ondansetron 0.15 mg/kg, or placebo (normal saline [NS], 10 mL). All subjects also received intravenous NS at 10-20 mL/kg/hr. Oral fluid tolerance was evaluated at two and four hours. Those not tolerating oral fluids at four hours were admitted. Discharged patients were evaluated at 24 and 72 hours for vomiting and repeat health care visits. The primary study outcome was hospitalization rates between the groups. Data were analyzed using chi-square test, Kruskal-Wallis test, Mantel-Haenszel test, and analysis of variance, with p hydration than NS-treated patients (29 [67.4%]; relative risk, 1.28; 95% confidence interval = 1.02 to 1.68). There were no differences in number of mean episodes of vomiting or repeat visits to health care at 24 and 72 hours in the ondansetron, dexamethasone, or NS groups. In children with dehydration secondary to vomiting from acute viral gastritis, ondansetron with intravenous rehydration improves tolerance of oral fluids after two hours and reduces the hospital admission rate when compared with intravenous rehydration with or without dexamethasone.

Clinical applications of the sustained-release dexamethasone implant for treatment of macular edema

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Rocío Herrero-Vanrell, Jose Augusto Cardillo

2011-02-01

Full Text Available Rocío Herrero-Vanrell1, Jose Augusto Cardillo2, Baruch D Kuppermann31Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Complutense University, Madrid, Spain; 2Hospital de Olhos de Araraquara, Araraquara, São Paulo, Brazil; 3Gavin Herbert Eye Institute, University of California, Irvine, CA, USAAbstract: Macular edema is one of the leading causes of vision loss among patients with retinal vein occlusion, diabetic retinopathy, and posterior chamber inflammatory disease. However, the treatment of macular edema is considerably limited by the difficulty in delivering effective doses of therapeutic agents into the vitreous cavity. In recent years, the development of a sustained-release dexamethasone intravitreal implant (Ozurdex® has enabled more controlled drug release at a stable rate over a long period of time, with a potentially lower rate of adverse events. Clinical studies indicate that this dexamethasone implant is a promising new treatment option for patients with persistent macular edema resulting from retinal vein occlusion, diabetic retinopathy, and uveitis or Irvine-Gass syndrome.Keywords: diabetic retinopathy, macular edema, Ozurdex®, posterior-segment inflammatory disease, retinal vein occlusion, sustained-release dexamethasone implant

Switching to Aflibercept in Diabetic Macular Edema Not Responding to Ranibizumab and/or Intravitreal Dexamethasone Implant

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Antoine Herbaut

2017-01-01

Full Text Available Purpose. To assess short-term functional and anatomical outcomes of refractory diabetic macular edema (DME following a switch from ranibizumab or dexamethasone to aflibercept. Methods. We included retrospectively eyes with persistent DME after at least 3 ranibizumab and/or one dexamethasone implant intravitreal injections (IVI. The primary endpoint was the mean change in visual acuity (VA at month 6 (M6 after switching. Results. Twenty-five eyes were included. Before switching to aflibercept, 23 eyes received a median of 9.5 ranibizumab, and among them, 6 eyes received one dexamethasone implant after ranibizumab and 2 eyes received only one dexamethasone implant. Baseline VA, before any IVI, was 52.9 ± 16.5 letters, and preswitch VA was 57.1 ± 19.6 letters. The mean VA gain was +8 letters (p=0.01 between preswitch and M6. The mean central retinal thickness was 470.8 ± 129.9 μm before the switch and 303.3 ± 59.1 μm at M6 (p=0.001. Conclusion. Switching to aflibercept in refractory DME results in significant functional and anatomical improvement. The study was approved by the France Macula Federation ethical committee (FMF 2017-138.

Health-Related Quality-of-Life Results From the Open-Label, Randomized, Phase III ASPIRE Trial Evaluating Carfilzomib, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone in Patients With Relapsed Multiple Myeloma.

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Stewart, A Keith; Dimopoulos, Meletios A; Masszi, Tamás; Špička, Ivan; Oriol, Albert; Hájek, Roman; Rosiñol, Laura; Siegel, David S; Niesvizky, Ruben; Jakubowiak, Andrzej J; San-Miguel, Jesus F; Ludwig, Heinz; Buchanan, Jacqui; Cocks, Kim; Yang, Xinqun; Xing, Biao; Zojwalla, Naseem; Tonda, Margaret; Moreau, Philippe; Palumbo, Antonio

2016-11-10

Purpose To determine the effects of carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide and dexamethasone (Rd) on health-related quality of life (HR-QoL) in the Carfilzomib, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone for the Treatment of Patients With Relapsed Multiple Myeloma (ASPIRE) trial. Methods Patients with relapsed multiple myeloma were randomly assigned to receive KRd or Rd. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and myeloma-specific module were administered at baseline; day 1 of cycles 3, 6, 12, and 18; and after treatment. The Global Health Status/Quality of Life (GHS/QoL) scale and seven subscales (fatigue, nausea and vomiting, pain, physical functioning, role functioning, disease symptoms, and adverse effects of treatment) were compared between groups using a mixed model for repeated measures. The percentages of responders with ≥ 5- or 15-point GHS/QoL improvement at each cycle were compared between groups. Results Baseline questionnaire compliance was excellent (94.1% of randomly assigned patients). KRd patients had higher GHS/QoL scores versus Rd patients over 18 treatment cycles (two-sided P < .001). The minimal important difference was met at cycle 12 (5.6 points) and approached at cycle 18 (4.8 points). There was no difference between groups for the other prespecified subscales from ASPIRE. A higher proportion of KRd patients met the GHS/QoL responder definition (≥ 5-point improvement) with statistical differences at cycle 12 (KRd v Rd patients, 25.5% v 17.4%, respectively) and 18 (KRd v Rd patients, 24.2% v 12.9%, respectively). Conclusion KRd improves GHS/QoL without negatively affecting patient-reported symptoms when compared with Rd. These data further support the benefit of KRd in patients with relapsed multiple myeloma.

Effects of trophic exposure to diclofenac and dexamethasone on hematological parameters and immune response in freshwater fish.

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Ribas, João Luiz Coelho; Zampronio, Aleksander R; Silva de Assis, Helena C

2016-04-01

The aim of the present study was to evaluate the effects of diclofenac and dexamethasone on hematological parameters and immune response in the fish species Hoplias malabaricus after trophic exposure. Fish were fed twice every week with Astyanax sp., which were given an intraperitoneal inoculation with diclofenac (0 μg/kg, 0.2 μg/kg, 2.0 μg/kg, or 20.0 μg/kg) or dexamethasone (0.03 μg/kg, 0.3 μg/kg, or 3.0 μg/kg). After 12 doses, the hematological parameters and lipopolysaccharide-induced nitric oxide production by head kidney monocytic lineage were evaluated. Exposed fish also received 1 mg/kg of carrageenan intraperitoneal, and cell migration to the peritoneal cavity was evaluated after 4 h. Diclofenac and dexamethasone altered the red blood cell count, as well as hematocrit and hemoglobin levels. The total blood leukocyte count decreased in all groups. A significantly reduced carrageenan-induced leukocyte migration to the peritoneal cavity, particularly of polymorphonuclear cells, was observed at all tested doses, suggesting a possible immunosuppressive effect. The basal nitric oxide synthesis of head kidney cell cultures was reduced at the highest dose of diclofenac and was increased at the highest dose of dexamethasone. The lipopolysaccharide-stimulated nitric oxide production was reduced in all treatments, thus corroborating the immunosuppressive effect. Although some fish responses were variable for different drugs, the results suggested that trophic exposure to diclofenac and dexamethasone can lead to hematological changes and immunotoxic effects, causing negative impacts in aquatic organisms. © 2015 SETAC.

Ibrutinib alone or with dexamethasone for relapsed or relapsed and refractory multiple myeloma: phase 2 trial results.

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Richardson, Paul G; Bensinger, William I; Huff, Carol Ann; Costello, Caitlin L; Lendvai, Nikoletta; Berdeja, Jesus G; Anderson, Larry D; Siegel, David S; Lebovic, Daniel; Jagannath, Sundar; Laubach, Jacob P; Stockerl-Goldstein, Keith E; Kwei, Long; Clow, Fong; Elias, Laurence; Salman, Zeena; Graef, Thorsten; Bilotti, Elizabeth; Vij, Ravi

2018-03-01

Novel therapies with unique new targets are needed for patients who are relapsed/refractory to current treatments for multiple myeloma. Ibrutinib is a first-in-class, once-daily, oral covalent inhibitor of Bruton tyrosine kinase, which is overexpressed in the myeloma stem cell population. This study examined various doses of ibrutinib ± low-dose dexamethasone in patients who received ≥2 prior lines of therapy, including an immunomodulatory agent. Daily ibrutinib ± weekly dexamethasone 40 mg was assessed in 4 cohorts using a Simon 2-stage design. The primary objective was clinical benefit rate (CBR; ≥minimal response); secondary objectives included safety. Patients (n = 92) received a median of 4 prior regimens. Ibrutinib + dexamethasone produced the highest CBR (28%) in Cohort 4 (840 mg + dexamethasone; n = 43), with median duration of 9·2 months (range, 3·0-14·7). Progression-free survival was 4·6 months (range, 0·4-17·3). Grade 3-4 haematological adverse events included anaemia (16%), thrombocytopenia (11%), and neutropenia (2%); grade 3-4 non-haematological adverse events included pneumonia (7%), syncope (3%) and urinary tract infection (3%). Ibrutinib + dexamethasone produced notable responses in this heavily pre-treated population. The encouraging efficacy, coupled with the favourable safety and tolerability profile of ibrutinib, supports its further evaluation as part of combination treatment. © 2018 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

A transwell assay that excludes exosomes for assessment of tunneling nanotube-mediated intercellular communication.

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Thayanithy, Venugopal; O'Hare, Patrick; Wong, Phillip; Zhao, Xianda; Steer, Clifford J; Subramanian, Subbaya; Lou, Emil

2017-11-13

Tunneling nanotubes (TNTs) are naturally-occurring filamentous actin-based membranous extensions that form across a wide spectrum of mammalian cell types to facilitate long-range intercellular communication. Valid assays are needed to accurately assess the downstream effects of TNT-mediated transfer of cellular signals in vitro. We recently reported a modified transwell assay system designed to test the effects of intercellular transfer of a therapeutic oncolytic virus, and viral-activated drugs, between cells via TNTs. The objective of the current study was to demonstrate validation of this in vitro approach as a new method for effectively excluding diffusible forms of long- and close-range intercellular transfer of intracytoplasmic cargo, including exosomes/microvesicles and gap junctions in order to isolate TNT-selective cell communication. We designed several steps to effectively reduce or eliminate diffusion and long-range transfer via these extracellular vesicles, and used Nanoparticle Tracking Analysis to quantify exosomes following implementation of these steps. The experimental approach outlined here effectively reduced exosome trafficking by >95%; further use of heparin to block exosome uptake by putative recipient cells further impeded transfer of these extracellular vesicles. This validated assay incorporates several steps that can be taken to quantifiably control for extracellular vesicles in order to perform studies focused on TNT-selective communication.

Dexamethasone as Adjuvant to Bupivacaine Prolongs the Duration of Thermal Antinociception and Prevents Bupivacaine-Induced Rebound Hyperalgesia via Regional Mechanism in a Mouse Sciatic Nerve Block Model

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An, Ke; Elkassabany, Nabil M.; Liu, Jiabin

2015-01-01

Background Dexamethasone has been studied as an effective adjuvant to prolong the analgesia duration of local anesthetics in peripheral nerve block. However, the route of action for dexamethasone and its potential neurotoxicity are still unclear. Methods A mouse sciatic nerve block model was used. The sciatic nerve was injected with 60ul of combinations of various medications, including dexamethasone and/or bupivacaine. Neurobehavioral changes were observed for 2 days prior to injection, and then continuously for up to 7 days after injection. In addition, the sciatic nerves were harvested at either 2 days or 7 days after injection. Toluidine blue dyeing and immunohistochemistry test were performed to study the short-term and long-term histopathological changes of the sciatic nerves. There were six study groups: normal saline control, bupivacaine (10mg/kg) only, dexamethasone (0.5mg/kg) only, bupivacaine (10mg/kg) combined with low-dose (0.14mg/kg) dexamethasone, bupivacaine (10mg/kg) combined with high-dose (0.5mg/kg) dexamethasone, and bupivacaine (10mg/kg) combined with intramuscular dexamethasone (0.5mg/kg). Results High-dose perineural dexamethasone, but not systemic dexamethasone, combined with bupivacaine prolonged the duration of both sensory and motor block of mouse sciatic nerve. There was no significant difference on the onset time of the sciatic nerve block. There was “rebound hyperalgesia” to thermal stimulus after the resolution of plain bupivacaine sciatic nerve block. Interestingly, both low and high dose perineural dexamethasone prevented bupivacaine-induced hyperalgesia. There was an early phase of axon degeneration and Schwann cell response as represented by S-100 expression as well as the percentage of demyelinated axon and nucleus in the plain bupivacaine group compared with the bupivacaine plus dexamethasone groups on post-injection day 2, which resolved on post-injection day 7. Furthermore, we demonstrated that perineural dexamethasone

Pre- and postoperative dexamethasone does not reduce bleaching-induced tooth sensitivity: A randomized, triple-masked clinical trial.

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Rezende, Márcia; Bonafé, Elize; Vochikovski, Laína; Farago, Paulo Vitor; Loguercio, Alessandro Dourado; Reis, Alessandra; Kossatz, Stella

2016-01-01

Tooth sensitivity (TS) is the most common side effect of dental bleaching therapies. Dexamethasone has been used with tooth bleaching to reduce TS. The efficacy of dexamethasone for this purpose has not been well studied. The authors conducted a triple-masked, randomized, clinical trial with a parallel design involving 63 healthy participants who received either a placebo or dexamethasone. The placebo or dexamethasone (8 milligrams) was administered 1 hour before the in-office bleaching (35% hydrogen peroxide) and extra doses of 4 mg were administered every 6 hours for a total of 48 hours. TS was recorded on 2 scales: visual analog scale (0-10) and numeric rating scale (0-4) in different periods. The color evaluations were performed before and 1 month after dental bleaching with visual shade guides VITA Classical (VITA Zahnfabrik) and VITA Bleachedguide 3D-MASTER (VITA Zahnfabrik), and for a shade guide evaluation, the authors used a digital spectrophotometer, VITA Easyshade (VITA Zahnfabrik). The absolute risk of TS was evaluated by a Fisher exact test. Data of TS intensity using the NRS scale for the 2 groups were compared with Mann-Whitney and Friedman tests, whereas data from the visual analog scale were evaluated by 2-way repeated measures analysis of variance. The color changes between groups were compared using a t test (α = .05). In both groups, the authors detected a high risk of TS, which was approximately 90%. No significant difference was observed in terms of TS intensity. A whitening of approximately 3 shade guide units of the VITA Classical was detected in both groups, which were statistically similar. The use of dexamethasone before bleaching did not reduce the risk and intensity of bleaching-induced TS. The use of the steroidal anti-inflammatory agent dexamethasone was not capable of preventing TS arising from in-office dental bleaching. Copyright © 2016 American Dental Association. Published by Elsevier Inc. All rights reserved.

Randomized clinical trial of preoperative dexamethasone on postoperative nausea and vomiting after laparoscopy for suspected appendicitis

DEFF Research Database (Denmark)

Kleif, J.; Kirkegaard, A.; Vilandt, J.

2017-01-01

Background: Few studies have investigated the effects of preoperative dexamethasone in acute surgical patients. This study examined the effects of 8 mg dexamethasone administered intravenously 30 min before surgery for suspected acute appendicitis. Methods: A multicentre, parallel-group, double......-blind, placebo-controlled study was conducted at two university hospitals in Denmark. Adults undergoing laparoscopic surgery for suspected appendicitis were eligible for inclusion. Participants, healthcare staff and investigators were blinded until all data analysis had been done. The primary outcome...

Intravenous Dexamethasone Pulse Therapy For Extensive Alopecia Areata

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Thappa Devinder Mohan

1999-01-01

Full Text Available Patient with extensive alopecia areata (>30% scalp involvement were given 32mg of dexamethasone in 200 ml of 5% dextrose intravenously on three consecutive days (total 96mg every four weeks. Response was quantified as 1 to 25%, 25% to 50%, 50 to 75% and 75 to 100% of terminal hair growth by mapping and serial photographs. They were examined monthly for side effects of steroids. Six patients (5 male and 1 female with a mean age of 32 years were recruited. They had alopecia areata for a period ranging from 3 months to 2.5 years. All the six cases did not show further worsening of alopecia after 3 pulses. However, two of them showed less than 25% hair growth after 4 pulses and did not turn up for follow up. In 2 cases, 25 to 50% growth was observed an 50 to 75% growth was seen in 2 patients (one of them with ophiasic pattern after 6 pulses. The results were cosmetically acceptable for three of them. No adverse effect to steroids was encountered and the patients are still under follow up. The preliminary results show that dexamethasone pulse therapy is safe and effective for extensive alopecia areata.

Transformed hairy roots of Discaria trinervis: a valuable tool for studying actinorhizal symbiosis in the context of intercellular infection.

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Imanishi, Leandro; Vayssières, Alice; Franche, Claudine; Bogusz, Didier; Wall, Luis; Svistoonoff, Sergio

2011-11-01

Among infection mechanisms leading to root nodule symbiosis, the intercellular infection pathway is probably the most ancestral but also one of the least characterized. Intercellular infection has been described in Discaria trinervis, an actinorhizal plant belonging to the Rosales order. To decipher the molecular mechanisms underlying intercellular infection with Frankia bacteria, we set up an efficient genetic transformation protocol for D. trinervis based on Agrobacterium rhizogenes. We showed that composite plants with transgenic roots expressing green fluorescent protein can be specifically and efficiently nodulated by Frankia strain BCU110501. Nitrogen fixation rates and feedback inhibition of nodule formation by nitrogen were similar in control and composite plants. In order to challenge the transformation system, the MtEnod11 promoter, a gene from Medicago truncatula widely used as a marker for early infection-related symbiotic events in model legumes, was introduced in D. trinervis. MtEnod11::GUS expression was related to infection zones in root cortex and in the parenchyma of the developing nodule. The ability to study intercellular infection with molecular tools opens new avenues for understanding the evolution of the infection process in nitrogen-fixing root nodule symbioses.

Efficacy of dexamethasone suppression test during the diagnosis of primary pigmented nodular adrenocortical disease in Chinese adrenocorticotropic hormone-independent Cushing syndrome.

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Chen, Shi; Li, Ran; Lu, Lin; Duan, Lian; Zhang, Xuebin; Tong, Anli; Pan, Hui; Zhu, Huijuan; Lu, Zhaolin

2018-01-01

To evaluate the cut-off value of the ratio of 24 h urinary free cortisol (24 h UFC) levels post-dexamethasone to prior-dexamethasone in dexamethasone suppression test (DST) during the diagnosis of primary pigmented nodular adrenocortical disease in Chinese adrenocorticotropic hormone-independent Cushing syndrome. Retrospective study. The patients diagnosed with primary pigmented nodular adrenocortical disease (PPNAD, n = 25), bilateral macronodular adrenal hyperplasia (BMAH, n = 27), and adrenocortical adenoma (ADA, n = 84) were admitted to the Peking Union Medical College Hospital from 2001 to 2016. Serum cortisol, adrenocorticotropic hormone (ACTH), and 24 h UFC were measured before and after low-dose dexamethasone suppression test (LDDST) and high-dose dexamethasone suppression test (HDDST). After LDDST and HDDST, 24 h UFC elevated in patients with PPNAD (paired t-test, P = 0.007 and P = 0.001), while it remained unchanged in the BMAH group (paired t-test, P = 0.471 and P = 0.414) and decreased in the ADA group (paired t-test, P = 0.002 and P = 0.004). The 24 h UFC level after LDDST was higher in PPNAD and BMAH as compared to ADA (P < 0.017), while no significant difference was observed between PPNAD and BMAH. After HDDST, 24 h UFC was higher in patients with PPNAD as compared to that of ADA and BMAH (P < 0.017). The cut-off value of 24 h UFC (Post-L-Dex)/(Pre-L-Dex) was 1.16 with 64.0% sensitivity and 77.9% specificity, and the cut-off value of 24 h UFC (Post-H-Dex)/(Pre-H-Dex) was 1.08 with 84.0% sensitivity and 75.6% specificity. The ratio of post-dexamethasone to prior-dexamethasone had a unique advantage in distinguishing PPNAD from BMAH and ADA.

Application of Photoshop-based image analysis and TUNEL for the distribution and quantification of dexamethasone-induced apoptotic cells in rat thymus.

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Hussar, Piret; Tokin, Ivan; Hussar, Ulo; Filimonova, Galina; Suuroja, Toivo

2006-01-01

The aim of the present study was to determine the target site cells in the rat thymus after exposure to the synthetic glucocorticoid, dexamethasone, at therapeutic doses. The findings of histology and histochemistry (Feulgen, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling--TUNEL) with quantification by computerized histomorphometry are described. A quantified investigation of apoptotic and mitotic thymic lymphocytes in 36 young adult Wistar rats was performed at 1-7 days after a 3-day injection of dexamethasone (a total dose of 1.2 mg/rat intraperitoneally). At the first day after dexamethasone administration the moderate involution and atrophy of thymus histology were observed with simultaneous fall in cortical cellularity and mitotic activity of thymocytes. More rapid fall appeared in the inner cortex. The number of apoptotic (TUNEL-positive) cells was significantly increased. On the days 5 and 7 the expression of apoptosis and the cell proliferation were at almost normal level. The findings suggest that dexamethasone-induced apoptosis of cortical thymic lymphocytes, mainly correlated with synchronous inhibition of mitosis and cell number fall in thymus. The main target sites of dexamethasone injury were cells in the inner cortex of lobuli thymi.

Influence of Dexamethasone on Some Reproductive Hormones and Uterine Progesterone Receptor Localization in Pregnant Yankasa Sheep in Semiarid Zones of Nigeria

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Dauda Yahi

2017-01-01

Full Text Available Dexamethasone is widely used in both veterinary and human medical practices. However, it seems to cause some deleterious effects on pregnancy probably by causing changes in the reproductive hormone levels and their corresponding receptor concentrations. This study investigated the effects of dexamethasone on these parameters. Twenty healthy adult Yankasa sheep comprising 18 ewes and 2 rams were used for this study. Pregnancies were achieved by natural mating after estrus synchronization. Dexamethasone was administered at 0.25 mg/kg body weight on days 1, 3, and 5 during first trimester; days 51, 53, and 55 during second trimester; and days 101, 103, and 105 during the third trimester. Blood samples were collected biweekly for hormonal assay. Uterine biopsies were harvested through caesarean section for immunohistochemical analysis. Results showed that dexamethasone significantly (p0.05 effect on estrogen, while progesterone receptors (PR were upregulated. The abortion could probably be due to decreased progesterone concentrations as a consequence of the adverse effects on placenta. The PR upregulation may be a compensatory mechanism to increase progesterone sensitivity. It was concluded that dexamethasone should not be used in advanced pregnancy in Yankasa sheep.

Pregabalin and dexamethasone in combination with paracetamol for postoperative pain control after abdominal hysterectomy. A randomized clinical trial

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Rasmussen, M L; Dierking, G; Lech, K

2008-01-01

BACKGROUND: Multimodal analgesia may be important for optimal postoperative pain treatment and facilitation of early mobilization and recovery. We investigated the analgesic effect of pregabalin and dexamethasone in combination with paracetamol after abdominal hysterectomy. METHODS: One hundred...... and sixteen patients were randomly assigned to either group A (paracetamol+placebo x 2), group B (paracetamol+pregabalin+placebo) or group C (paracetamol+pregabalin+dexamethasone). According to randomization and preoperatively, patients received paracetamol 1000 mg, pregabalin 300 mg, dexamethasone 8 mg...... or placebo. General anaesthesia was performed. Postoperative pain treatment was paracetamol 1000 mg x 4 and patient-controlled intravenous morphine, 2.5 mg bolus. Nausea was treated with ondansetron. Morphine consumption, pain score (visual analogue scale) at rest and during mobilization, nausea, sedation...

Comparison of Effectiveness of Betamethasone gel Applied to the Tracheal Tube and IV Dexamethasone on Postoperative Sore Throat: A Randomized Controlled Trial.

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Tabari, Masumeh; Soltani, Ghasem; Zirak, Nahid; Alipour, Moammad; Khazaeni, Kamran

2013-09-01

Postoperative sore throat is a common complaint in patients with endotracheal intubation and has potentially dangerous complications. This randomized controlled trial study investigated the incidence of postoperative sore throat after general anesthesia when betamethasone gel is applied to a tracheal tube compared with when IV dexamethasone is prescribed. Two hundred and twenty five American Society of Anesthesiologist (ASA)-class I and II patients undergoing elective abdominal surgery with tracheal intubation were randomly divided into three groups: betamethasone gel, intravenous (IV) dexamethasone, and control groups. In the post-anesthesia care unit, a blinded anesthesiologist interviewed all patients regarding postoperative sore throat at 1,6, and 24 hours after surgery. The incidence of sore throat was significantly lower in the betamethasone gel group compared with the IV dexamethasone and control groups, 1, 6, and 24 hours after surgery. In the first day after surgery 10.7% of the betamethasone group had sore throat whereas 26.7% of the IV dexamethasone group and 30.7% of the control group had sore throat. Bucking before extubation was observed in 14(18.4%), 8(10.4%), and 9(12.2%) patients, in the IV dexamethasone, betamethasone gel, and control group, respectively. We concluded that wide spread application of betamethasone gel over tracheal tubes effectively mitigates postoperative sore throat, compared with IV dexamethasone application.

Comparison of Effectiveness of Betamethasone gel Applied to the Tracheal Tube and IV Dexamethasone on Postoperative sore Throat: A Randomized Controlled Trial

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Masoomeh Tabari

2013-10-01

Full Text Available Introduction: Postoperative sore throat is a common complaint in patients with endotracheal intubation and has potentially dangerous complications. This randomized controlled trial study investigated the incidence of postoperative sore throat after general anesthesia when betamethasone gel is applied to a tracheal tube compared with when IV dexamethasone is prescribed.   Materials and Methods: Two hundred and twenty five American Society of Anesthesiologist (ASA-class I and II patients undergoing elective abdominal surgery with tracheal intubation were randomly divided into three groups: betamethasone gel, intravenous (IV dexamethasone, and control groups. In the post-anesthesia care unit, a blinded anesthesiologist interviewed all patients regarding postoperative sore throat at 1,6, and 24 hours after surgery.   Results: The incidence of sore throat was significantly lower in the betamethasone gel group compared with the IV dexamethasone and control groups, 1, 6, and 24 hours after surgery. In the first day after surgery 10.7% of the betamethasone group had sore throat whereas 26.7% of the IV dexamethasone group and 30.7% of the control group had sore throat. Bucking before extubation was observed in 14(18.4%, 8(10.4%, and 9(12.2% patients, in the IV dexamethasone, betamethasone gel, and control group, respectively.   Conclusion:  We concluded that wide spread application of betamethasone gel over tracheal tubes effectively mitigates postoperative sore throat, compared with IV dexamethasone application.

Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma.

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Dimopoulos, Meletios A; Oriol, Albert; Nahi, Hareth; San-Miguel, Jesus; Bahlis, Nizar J; Usmani, Saad Z; Rabin, Neil; Orlowski, Robert Z; Komarnicki, Mieczyslaw; Suzuki, Kenshi; Plesner, Torben; Yoon, Sung-Soo; Ben Yehuda, Dina; Richardson, Paul G; Goldschmidt, Hartmut; Reece, Donna; Lisby, Steen; Khokhar, Nushmia Z; O'Rourke, Lisa; Chiu, Christopher; Qin, Xiang; Guckert, Mary; Ahmadi, Tahamtan; Moreau, Philippe

2016-10-06

Daratumumab showed promising efficacy alone and with lenalidomide and dexamethasone in a phase 1-2 study involving patients with relapsed or refractory multiple myeloma. In this phase 3 trial, we randomly assigned 569 patients with multiple myeloma who had received one or more previous lines of therapy to receive lenalidomide and dexamethasone either alone (control group) or in combination with daratumumab (daratumumab group). The primary end point was progression-free survival. At a median follow-up of 13.5 months in a protocol-specified interim analysis, 169 events of disease progression or death were observed (in 53 of 286 patients [18.5%] in the daratumumab group vs. 116 of 283 [41.0%] in the control group; hazard ratio, 0.37; 95% confidence interval [CI], 0.27 to 0.52; P<0.001 by stratified log-rank test). The Kaplan-Meier rate of progression-free survival at 12 months was 83.2% (95% CI, 78.3 to 87.2) in the daratumumab group, as compared with 60.1% (95% CI, 54.0 to 65.7) in the control group. A significantly higher rate of overall response was observed in the daratumumab group than in the control group (92.9% vs. 76.4%, P<0.001), as was a higher rate of complete response or better (43.1% vs. 19.2%, P<0.001). In the daratumumab group, 22.4% of the patients had results below the threshold for minimal residual disease (1 tumor cell per 10 5 white cells), as compared with 4.6% of those in the control group (P<0.001); results below the threshold for minimal residual disease were associated with improved outcomes. The most common adverse events of grade 3 or 4 during treatment were neutropenia (in 51.9% of the patients in the daratumumab group vs. 37.0% of those in the control group), thrombocytopenia (in 12.7% vs. 13.5%), and anemia (in 12.4% vs. 19.6%). Daratumumab-associated infusion-related reactions occurred in 47.7% of the patients and were mostly of grade 1 or 2. The addition of daratumumab to lenalidomide and dexamethasone significantly lengthened

Dexamethasone treatment induces susceptibility of outbred Webster mice to experimental infection with Besnoitia darlingi isolated from opossums (Didelphis virginiana).

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Elsheikha, Hany M; Rosenthal, Benjamin M; Mansfield, Linda S

2005-04-01

The Sarcocystidae comprise a diverse, monophyletic apicomplexan parasite family, most of whose members form intracellular cysts in their intermediate hosts. The extent of pathology associated with such cyst formation can range widely. We currently lack experimental animal models for many of these infections. Here we explored dexamethasone treatment as a means to render outbred mice susceptible to Besnoitia darlingi infection and demonstrated that this approach allows viable parasites to be subsequently isolated from these mice and maintained in tissue culture. Besnoitia bradyzoites recovered from crushed cysts derived from naturally infected opossums (Didelphis virginiana) replicated and reproduced the development of besnoitiosis in mice treated with dexamethasone (0.5 mg/ml drinking water) daily for 12 days post infection (DPI). Isolates recovered from the peritoneal exudates of these mice were viable and were maintained in long-term tissue cultures. In contrast, control mice given saline without dexamethasone and challenged with similar bradyzoites remained clinically normal for up to 70 DPI. An additional group of mice challenged with the same inoculum of bradyzoites and given dexamethasone at the same concentration and treated with sulfadiazine (1 mg/ml drinking water) daily for 12 DPI also remained normal for up to 70 DPI. Severe disease developed more rapidly in dexamethasone-treated mice inoculated with culture-derived B. darlingi tachyzoites than in those inoculated with cyst-derived bradyzoites. B. darlingi tachyzoite-infected, untreated control mice developed signs of illness at 18 DPI. In contrast, mice treated with sulfadiazine showed no clinical signs up to 50 DPI. Although dexamethasone treatment was required to establish B. darlingi infection in outbred mice inoculated with opossum-derived B. darlingi bradyzoites, no such treatment was required for mice inoculated with culture-derived B. darlingi tachyzoites. Finally, sulfadiazine was highly

Effects of melatonin on prenatal dexamethasone-induced epigenetic alterations in hippocampal morphology and reelin and glutamic acid decarboxylase 67 levels.

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Lui, Chun-Chung; Hsu, Mei-Hsin; Kuo, Ho-Chang; Chen, Chih-Cheng; Sheen, Jiunn-Ming; Yu, Hong-Ren; Tiao, Mao-Meng; Tain, You-Lin; Chang, Kow-Aung; Huang, Li-Tung

2015-01-01

Prenatal glucocorticoid exposure causes brain damage in adult offspring; however, the underlying mechanisms remain unclear. Melatonin has been shown to have beneficial effects in compromised pregnancies. Pregnant Sprague-Dawley rats were administered vehicle (VEH) or dexamethasone between gestation days 14 and 21. The programming effects of prenatal dexamethasone exposure on the brain were assessed at postnatal days (PND) 7, 42, and ∼120. Melatonin was administered from PND21 to the rats exposed to dexamethasone, and the outcome was assessed at ∼PND120. In total, there were four groups: VEH, vehicle plus melatonin (VEHM), prenatal dexamethasone-exposure (DEX), and prenatal dexamethasone exposure plus melatonin (DEXM). Spatial memory, gross hippocampal morphology, and hippocampal biochemistry were examined. Spatial memory assessed by the Morris water maze showed no significant differences among the four groups. Brain magnetic resonance imaging showed that all rats with prenatal dexamethasone exposure (DEX + DEXM) exhibited increased T2-weighted signals in the hippocampus. There were no significant differences in the levels of mRNA expression of hippocampal reln, which encodes reelin, and GAD1, which encodes glutamic acid decarboxylase 67, at PND7. At both PND42 and ∼PND120, reln and GAD1 mRNA expression levels were decreased. At ∼PND120, melatonin restored the reduced levels of hippocampal reln and GAD1 mRNA expression in the DEXM group. In addition, melatonin restored the reln mRNA expression levels by (1) reducing DNA methyltransferase 1 (DNMT1) mRNA expression and (2) reducing the binding of DNMT1 and the methyl-CpG binding protein 2 (MeCP2) to the reln promoter. The present study showed that prenatal dexamethasone exposure induced gross alterations in hippocampal morphology and reduced the levels of hippocampal mRNA expression of reln and GAD1. Spatial memory was unimpaired. Thus, melatonin had a beneficial effect in restoring hippocampal reln m

Short-term effects of intravitreal dexamethasone implant (OZURDEX® on choroidal thickness in patients with naive branch retinal vein occlusion

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Hasan Basri Arifoglu

Full Text Available ABSTRACT Purpose: The objective of this study was to evaluate subfoveal choroidal thickness (SFCT using enhanced depth imaging optical coherence tomography (EDI-OCT in patients with naïve branch retinal vein occlusion (BRVO before and after intravitreal dexamethasone implant (Ozurdex® injection. Methods: Thirty-nine patients with unilateral BRVO and 35 healthy subjects were included in this prospective study. Choroidal thickness was evaluated by EDI-OCT at baseline and 1 month after dexamethasone implant. Results: The mean SFCT measured in 39 patients with BRVO was 299.41 ± 55.86 µm, significantly greater than that in contralateral eyes (283.76 ± 57.44 µm; p=0.009 and control eyes (276.14 ± 39.06 µm; p=0.044. The mean SFCT after the treatment was 279.64 ± 50.96 µm, significantly thinner than that before intravitreal dexamethasone therapy (p=0.004. Conclusions: SFCT in treatment-naive BRVO eyes was significantly greater than that in contralateral eyes and healthy eyes and decreased significantly after intravitreal dexamethasone implantation.

Examination of dexamethasone sodium sulfate and hyperbaric oxygenation in experimentally produced cerebral edema. With special reference to their combination

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Kanaya, H; Onodera, H; Watanabe, M; Kamata, K [Iwate Medical Coll., Morioka (Japan). School of Medicine

1975-06-01

Dexamethasone sodium sulfate and hyperbaric oxygenation were used for experimentally produced cerebral edema for the examination of the water content of the brain and cerebrovascular permeability using /sup 203/Hg as the tracer. Although dexamethasone starts lowering vascular permeability of the edematous brain at one hour after the intravenous injection, a lapse of 24 hours is required until the water content returns to normal. Although hyperbaric oxygenation dose not reduce cerebrovascular permeability, it brings back the water content of the brain to normal immediately after pressurization. Since the combination of dexamethasone and hyperbaric oxygenation maintains the water content of the brain almost normal throughout the entire process, it is ideal for the treatment of cerebral edema.

Intraperitoneal Dexamethasone As A New Method for Relieving Postoperative Shoulder Pain after Gynecologic Laparoscopy

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Zahra Asgari

2012-01-01

Full Text Available Background: In this study, we tried to show the efficacy of Intraperitoneal dexamethasoneon relieving shoulder pain after gynecologic laparoscopy.Materials and Methods: In this double-blind randomized clinical trial, 63 patients who werecandidates for gynecologic laparoscopy were included. At the end of the procedure patientsrandomly received 16 mg dexamethasone (n=31 or placebo (n=32 intraperitoneally. Visualanalogue scale (VAS was used for clinical evaluation of pain severity during 24 hours afterlaparoscopy . A physician, who was not aware whether patients were treated with drug or placebo,evaluated the patients.Results: The severity of pain in the dexamethasone group within 0, 2, 4, 8, 12, 24 hoursafter procedure was significantly less than in the placebo group (p<0.001. The averageconsumption of opioids as analgesic/ sedative in the placebo group was more than thedexamethasone group (p=0.025.Conclusion: Findings of this study show that the prescription of 16 mg of dexamethasone(single dose in the peritoneal cavity may significantly reduce the severity of painafter Laparoscopy in comparison with placebo and may decrease the need for narcoticsas pain relief (Registration Number: IRCT201105306640N1.

Co-administration of dexamethasone increases severity and accelerates onset day of neutropenia in bladder cancer patients on methotrexate, vinblastine, adriamycin and cisplatin chemotherapy: a retrospective cohort study.

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Itai, Shingo; Suga, Yukio; Hara, Yusuke; Izumi, Kouji; Maeda, Yuji; Kitagawa, Yasuhide; Ishizaki, Junko; Shimada, Tsutomu; Mizokami, Atsushi; Sai, Yoshimichi

2017-01-01

Bladder cancer patients receiving methotrexate, vinblastine, adriamycin and cisplatin (MVAC) chemotherapy are co-administered with dexamethasone as an anti-emetic. We examined whether or not dexamethasone affects the severity and onset day of MVAC-induced severe neutropenia. This was a retrospective study of bladder cancer patients treated with MVAC chemotherapy with or without dexamethasone as an antiemetic at Kanazawa University Hospital during January 2005 - December 2009. Patients were categorized into three groups; no dexamethasone use (Dex (-)), dexamethasone on day 2 (Dex 1 day), and dexamethasone on days 2, 3 and 4 (Dex multiday). We evaluated the incidence of grade 3/4 neutropenia and the day of onset of first severe neutropenic episode during the first course of MVAC chemotherapy. Logistic regression was used to investigate whether co-administration of dexamethasone was a risk factor for severe neutropenia. Episodes of grade 3/4 neutropenia occurred in 3 out of 6 (50.0%), 11 out of 12 (91.7%) and 6 out of 6 (100%) patients in the Dex (-), Dex 1 day, and Dex multiday groups, respectively. The appearance day of first severe neutropenia in the Dex multiday group (13.2 ± 1.0) was significantly accelerated compared to the Dex (-) group (17.7 ± 2.1). Univariate logistic regression analysis revealed that dexamethasone is a risk factor for severe neutropenia (OR 17.0; 95%CI: 1.3-223.1). Co-administration of dexamethasone for anti-emesis brings forward the first appearance of neutropenia, and increases the severity of neutropenia, in bladder cancer patients receiving MVAC chemotherapy.

Injection dexamethasone in preventing postoperative nausea and vomiting: a comparison with placebo in the patients undergoing laparoscopic cholecystectomy

International Nuclear Information System (INIS)

Kashmiri, Z.U.A.; Sheikh, Z.; Haider, S.

2006-01-01

To determine the efficacy of intravenous dexamethasone for preventing postoperative nausea and vomiting (PONV) in patients undergoing laparoscopic cholecystectomy (lap-chole) and comparing it with normal saline (placebo). After the approval of the hospital's ethical committee, the study was conducted on 60 patients who were randomly divided into two groups, each group containing 30 patients. All belonged to A.S.A-I and A.S.A-II. Randomization was done by envelope draw method. Injections dexamethasone (8 mg in 2mls) and normal saline ( 2 mls ) were given intravenously to respective groups just before induction of anesthesia. Fisher's exact test was applied to compare proportion of PONV between two groups for the recovery room data, while Chi-square test was applied to compare the proportion of PONV between two groups during first 12 hours and second 12 hours. The p-value was calculated at the level of significance chosen as 0.05. In the recovery room where the patient stayed for one hour 10% of patients in the dexamethasone group in comparison with 33% of the patients in the placebo group experienced PONV (p=0.028). In the ward, during first 12 hours observation period, 27% of the patients in the dexamethasone group in comparison with 43% of the patients in the placebo group experienced PONV (p=0.176). During the second 12 hours observation period, 30% of the patients in the dexamethasone in comparison with 80% of the patients in the placebo group experienced PONV (p<0.001). (author)

Comparison of 1 mg and 2 mg overnight dexamethasone suppression tests for the screening of Cushing's syndrome in obese patients.

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Sahin, Mustafa; Kebapcilar, Levent; Taslipinar, Abdullah; Azal, Omer; Ozgurtas, Taner; Corakci, Ahmet; Akgul, Emin Ozgur; Taslipinar, Mine Yavuz; Yazici, Mahmut; Kutlu, Mustafa

2009-01-01

Obesity is currently a major public health problem and one of the potential underlying causes of obesity in a minority of patients is Cushing's syndrome (CS). Traditionally, the gold standard screening test for CS is 1 mg dexamethasone overnight suppression test. However, it is known that obese subjects have high false positive results with this test. We have therefore compared the 1 mg and 2 mg overnight dexamethasone suppression tests in obese subjects. Patients whose serum cortisol after ODST was >50 nM underwent and a low-dose dexamethasone suppression test (LDDST); 24-hour urine cortisol was collected for basal urinary free cortisol (UFC). For positive results after overnight 1-mg dexamethasone suppression test we also performed the overnight 2-mg dexamethasone suppression test. We prospectively evaluated 100 patients (22 men and 78 women, ranging in age from 17 to 73 years with a body mass index (BMI) >30 kg/m2 who had been referred to our hospital-affiliated endocrine clinic because of simple obesity. Suppression of serum cortisol to suppression. Thyroid function tests, lipid profiles, homocysteine, antithyroglobulin, anti-thyroid peroxidase antibody levels, vitamin B12, folate levels, insulin resistance [by homeostasis model assessment (HOMA)] and 1.0 mg postdexamethasone (postdex) suppression cortisol levels were measured. We found an 8% false-positive rate in 1 mg overnight test and 2% in 2 mg overnight test (p=0.001). There was no correlation between the cortisol levels after ODST and other parameters. Our results indicate that the 2 mg overnight dexamethasone suppression test (ODST) is more convenient and accurate than 1-mg ODST as a screening test for excluding CS in subjects with simple obesity.

Clarithromycin (Biaxin)-lenalidomide-low-dose dexamethasone (BiRd) versus lenalidomide-low-dose dexamethasone (Rd) for newly diagnosed myeloma.

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Gay, Francesca; Rajkumar, S Vincent; Coleman, Morton; Kumar, Shaji; Mark, Tomer; Dispenzieri, Angela; Pearse, Roger; Gertz, Morie A; Leonard, John; Lacy, Martha Q; Chen-Kiang, Selina; Roy, Vivek; Jayabalan, David S; Lust, John A; Witzig, Thomas E; Fonseca, Rafael; Kyle, Robert A; Greipp, Philip R; Stewart, A Keith; Niesvizky, Ruben

2010-09-01

The objective of this case-matched study was to compare the efficacy and toxicity of the addition of clarithromycin (Biaxin) to lenalidomide/low-dose dexamethasone (BiRd) vs. lenalidomide/low-dose dexamethasone (Rd) for newly diagnosed myeloma. Data from 72 patients treated at the New York Presbyterian Hospital-Cornell Medical Center were retrospectively compared with an equal number of matched pair mates selected among patients seen at the Mayo Clinic who received Rd. Case matching was blinded and was performed according to age, gender, and transplant status. On intention-to-treat analysis, complete response (45.8% vs. 13.9%, P < 0.001) and very-good-partial-response or better (73.6% vs. 33.3%, P < 0.001) were significantly higher with BiRd. Time-to-progression (median 48.3 vs. 27.5 months, P = 0.071), and progression-free survival (median 48.3 vs. 27.5 months, P = 0.044) were higher with BiRd. There was a trend toward better OS with BiRd (3-year OS: 89.7% vs. 73.0%, P = 0.170). Main grade 3-4 toxicities of BiRd were hematological, in particular thrombocytopenia (23.6% vs. 8.3%, P = 0.012). Infections (16.7% vs. 9.7%, P = 0.218) and dermatological toxicity (12.5% vs. 4.2%, P = 0.129) were higher with Rd. Results of this case-matched analysis suggest that there is significant additive value when clarithromycin is added to Rd. Randomized phase III trials are needed to confirm these results. © 2010 Wiley-Liss, Inc.

A single-arm Phase II validation study of preventing oxaliplatin-induced hypersensitivity reactions by dexamethasone: the AVOID trial

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Yoshida Y

2015-11-01

Full Text Available Yoichiro Yoshida,1 Keiji Hirata,2 Hiroshi Matsuoka,3 Shigeyoshi Iwamoto,4 Masahito Kotaka,5 Hideto Fujita,6 Naoya Aisu,1 Seiichiro Hoshino,1 Takeo Kosaka,6 Kotaro Maeda,3 Fumiaki Kiyomi,7 Yuichi Yamashita1 1Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, Fukuoka, Japan; 2Department of Surgery, Fukuoka Sanno Hospital, Fukuoka, Japan; 3Department of Surgery, Fujita Health University School of Medicine, Toyoake, Japan; 4Department of Surgery, Kansai Medical University Hirakata Hospital, Osaka, Japan; 5Gastrointestinal Cancer Center, Sano Hospital, Kobe, Japan; 6Department of Surgical Oncology, Kanazawa Medical University, Uchinada, Japan; 7Academia, Industry and Government Collaborative Research Institute of Translational Medicine for Life Innovation, Fukuoka University, Fukuoka, Japan Background: Patients with colorectal cancer treated with oxaliplatin are at risk of hypersensitivity reactions, with the incidence estimated to be 12%–20%. Coinfusion of dexamethasone and oxaliplatin could potentially reduce the incidence of these reactions, but oxaliplatin is reported to be incompatible with alkaline compounds in solution. However, in a previous retrospective study we found that the pH of a solution of dexamethasone and oxaliplatin was less than 7.4, and that hypersensitivity to oxaliplatin could have been prevented by coinfusion of dexamethasone. We aimed to evaluate the effectiveness of coinfusion of dexamethasone and oxaliplatin to prevent oxaliplatin-induced hypersensitivity reactions.Patients and methods: The AVOID trial was a prospective, multicenter, open-label, single-arm Phase II trial conducted from January to September 2013. The study included 73 patients who received capecitabine plus oxaliplatin (XELOX or XELOX plus bevacizumab therapy for colorectal cancer. In all patients, oxaliplatin was administered in combination with dexamethasone. The primary outcome measure was the presence of

The effect of dexamethasone on respirator-dependent very-low-birth-weight infants is best predicted by chest X-ray

International Nuclear Information System (INIS)

Schrod, L.; Neuhaus, T.; Horwitz, A.E.; Speer, C.P.

2001-01-01

Background. Chronic lung disease (CLD) in premature infants shows a variable clinical course with different radiological manifestations. Objective. To evaluate the correlation between parameters of transmembrane permeability [albumin/secretory component (SC)] and oxidative stress [malondialdehyde (MDA)/SC] in tracheal aspirate fluid (TAF) and radiological findings with the effect of a 5-day course of dexamethasone (0.5 mg/kg per day). Materials and methods. Fifty ventilator-dependent premature infants with birth weights 2 x mean airway pressure > 40 % at day 5, compared to pretreatment values. About 80 % of the responders showed homogeneous lung opacification on chest X-ray, reflecting leaky lung syndrome. In contrast, seven of eight infants with predominantly emphysema on radiology were non-responders; 80 % of infants with a mixed radiological picture characterized by predominance of consolidations alternating with regions of emphysema were also non-responders. Ratios of albumin/SC and MDA/SC in TAF decreased significantly within 3 days after the onset of dexamethasone. However, MDA/SC was persistently higher in non-responders compared to responders. Opaque lungs were largely improved by dexamethasone, in contrast to streaky or patchy consolidations and emphysema. In a logistic regression model, radiographic classification was the most important factor influencing the response to dexamethasone with a positive predictive value of 86 %, followed by albumin/SC ratio. Conclusions. The optimum timing of dexamethasone treatment may be determined by the stage of developing CLD and radiological findings rather than by the age of the premature infant. (orig.)

Benzo[a]pyrene induces intercellular adhesion molecule-1 through a caveolae and aryl hydrocarbon receptor mediated pathway

International Nuclear Information System (INIS)

Oesterling, Elizabeth; Toborek, Michal; Hennig, Bernhard

2008-01-01

Toxicologic and epidemiologic studies have linked benzo[a]pyrene (B[a]P) exposure with cardiovascular diseases such as atherosclerosis. The mechanisms of action leading to these diseases have not been fully understood. One key step in the development of atherosclerosis is vascular endothelial dysfunction, which is characterized by increased adhesiveness. To determine if B[a]P could lead to increased endothelial adhesiveness, the effects of B[a]P on human endothelial cell intercellular adhesion molecule-1 (ICAM-1) expression was investigated. B[a]P was able to increase ICAM-1 protein only after pretreatment with the aryl hydrocarbon receptor (AhR) agonist β-naphthoflavone (β-NF). Knockdown of AhR by siRNA or treatment with AhR antagonist α-naphthoflavone (α-NF) eliminated the induction of ICAM-1 from B[a]P, confirming the necessity of AhR in this process. Likewise, B[a]P only increased monocyte adhesion to the vascular endothelium when cells were pretreated with β-NF. Experiments were done to define a signaling mechanism. B[a]P increased phosphorylation of MEK and p38-MAPK, and inhibitors to these proteins blunted the ICAM-1 induction. B[a]P was also able to increase AP-1 DNA binding and phosphorylation of cJun. Phosphorylation of cJun was disrupted by MEK and p38-MAPK inhibitors linking the signaling cascade. Finally, the importance of membrane microdomains, caveolae, was demonstrated by knockdown of the structural protein caveolin-1. Disruption of caveolae eliminated the B[a]P-induced ICAM-1 expression. These data suggest a possible pro-inflammatory mechanism of action of B[a]P involving caveolae, leading to increased vascular endothelial adhesiveness, and this inflammation may be a critical step in the development of B[a]P-induced atherosclerosis

Stomatal Responses to Flooding of the Intercellular Air Spaces Suggest a Vapor-Phase Signal Between the Mesophyll and the Guard Cells1[OA

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Sibbernsen, Erik; Mott, Keith A.

2010-01-01

Flooding the intercellular air spaces of leaves with water was shown to cause rapid closure of stomata in Tradescantia pallida, Lactuca serriola, Helianthus annuus, and Oenothera caespitosa. The response occurred when water was injected into the intercellular spaces, vacuum infiltrated into the intercellular spaces, or forced into the intercellular spaces by pressurizing the xylem. Injecting 50 mm KCl or silicone oil into the intercellular spaces also caused stomata to close, but the response was slower than with distilled water. Epidermis-mesophyll grafts for T. pallida were created by placing the epidermis of one leaf onto the exposed mesophyll of another leaf. Stomata in these grafts opened under light but closed rapidly when water was allowed to wick between epidermis and the mesophyll. When epidermis-mesophyll grafts were constructed with a thin hydrophobic filter between the mesophyll and epidermis stomata responded normally to light and CO2. These data, when taken together, suggest that the effect of water on stomata is caused partly by dilution of K+ in the guard cell and partly by the existence of a vapor-phase signal that originates in the mesophyll and causes stomata to open in the light. PMID:20472750

The influence of dexamethasone and ketolgan on postoperative nausea and vomiting and estimation of risk factors in women undergoing gynecologic laparoscopic surgeries.

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Rimaitis, Kestutis; Svitojūte, Asta; Macas, Andrius

2010-01-01

The aim of this study was to determine the effect of dexamethasone and ketolgan on postoperative nausea and vomiting and to evaluate risk factors for postoperative nausea and vomiting. A prospective, double-blind, randomized clinical study was carried out. One hundred fifty-three ASA I-II women undergoing laparoscopic gynecologic operations were randomized into three groups: dexamethasone group (n=51), ketolgan group (n=51), and control group (n=51). Patients in the dexamethasone group were given 4 mg of dexamethasone intravenously before the induction of general anesthesia, the ketolgan group received 30-mg ketolgan intravenously, and control group did not receive any medication. The incidence and severity of postoperative nausea and vomiting were registered 24 hours after the surgery. The incidence of postoperative nausea and vomiting in the dexamethasone group was 13.8%; in the ketolgan group, 37.3%, and in the control group, 58.9% (P=0.026). Patients with a history of migraine suffered from postoperative nausea and vomiting in 70.3% of cases and migraine-free patients in 25.8% of cases (P=0.015). Opioids for postoperative analgesia increased the incidence of postoperative nausea and vomiting as compared with nonsteroidal anti-inflammatory drugs (P=0.00002). Preoperative medication with dexamethasone significantly reduces the incidence of postoperative nausea and vomiting. Avoidance of opioids for postoperative analgesia reduces the incidence of postoperative nausea and vomiting. Migraine and motion sickness are independent risk factors for postoperative nausea and vomiting.

Influence of Dexamethasone on Some Reproductive Hormones and Uterine Progesterone Receptor Localization in Pregnant Yankasa Sheep in Semiarid Zones of Nigeria.

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Yahi, Dauda; Ojo, Nicholas Adetayo; Mshelia, Gideon Dauda

2017-01-01

Dexamethasone is widely used in both veterinary and human medical practices. However, it seems to cause some deleterious effects on pregnancy probably by causing changes in the reproductive hormone levels and their corresponding receptor concentrations. This study investigated the effects of dexamethasone on these parameters. Twenty healthy adult Yankasa sheep comprising 18 ewes and 2 rams were used for this study. Pregnancies were achieved by natural mating after estrus synchronization. Dexamethasone was administered at 0.25 mg/kg body weight on days 1, 3, and 5 during first trimester; days 51, 53, and 55 during second trimester; and days 101, 103, and 105 during the third trimester. Blood samples were collected biweekly for hormonal assay. Uterine biopsies were harvested through caesarean section for immunohistochemical analysis. Results showed that dexamethasone significantly ( p progesterone concentrations and caused abortion in Yankasa sheep but had no significant ( p > 0.05) effect on estrogen, while progesterone receptors (PR) were upregulated. The abortion could probably be due to decreased progesterone concentrations as a consequence of the adverse effects on placenta. The PR upregulation may be a compensatory mechanism to increase progesterone sensitivity. It was concluded that dexamethasone should not be used in advanced pregnancy in Yankasa sheep.

Effect of dexamethasone added to lidocaine in supraclavicular brachial plexus block: A prospective, randomised, double-blind study

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Prashant A Biradar

2013-01-01

Full Text Available Background: Different additives have been used to prolong brachial plexus block. We performed a prospective, randomised, double-blind study to evaluate the effect of dexamethasone added to lidocaine on the onset and duration of supraclavicular brachial plexus block as this is the most common type of brachial block performed in our institute. Methods: Sixty American Society of Anaesthesiologist′s physical status I and II patients undergoing elective hand, forearm and elbow surgery under brachial plexus block were randomly allocated to receive either 1.5% lidocaine (7 mg/kg with adrenaline (1:200,000 and 2 ml of normal saline (group C, n=30 or 1.5% lidocaine (7 mg/kg with adrenaline (1:200,000 and 2 ml of dexamethasone (8 mg (group D, n=30. The block was performed using a nerve stimulator. Onset and duration of sensory and motor blockade were assessed. The sensory and motor blockade of radial, median, ulnar and musculocutaneous nerves were evaluated and recorded at 5, 10, 20, 120 min, and at every 30 min thereafter. Results: Two patients were excluded from the study because of block failure. The onset of sensory and motor blockade (13.4±2.8 vs. 16.0±2.3 min and 16.0±2.7 vs. 18.7±2.8 min, respectively were significantly more rapid in the dexamethasone group than in the control group ( P=0.001. The duration of sensory and motor blockade (326±58.6 vs. 159±20.1 and 290.6±52.7 vs. 135.5±20.3 min, respectively were significantly longer in the dexamethasone group than in the control group ( P=0.001. Conclusion: Addition of dexamethasone to 1.5% lidocaine with adrenaline in supraclavicular brachial plexus block speeds the onset and prolongs the duration of sensory and motor blockade.

Granisetron plus dexamethasone for prevention of postoperative nausea and vomiting in patients undergoing laparoscopic surgery: A meta-analysis

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Zhu, Min; Zhou, Chengmao; Huang, Bing; Ruan, Lin; Liang, Rui

2017-01-01

Objective This study was designed to compare the effectiveness of granisetron plus dexamethasone for preventing postoperative nausea and vomiting (PONV) in patients undergoing laparoscopic surgery. Methods We searched the literature in the Cochrane Library, PubMed, EMBASE, and CNKI. Results In total, 11 randomized controlled trials were enrolled in this analysis. The meta-analysis showed that granisetron in combination with dexamethasone was significantly more effective than granisetron alone...

Maternal Melatonin Therapy Rescues Prenatal Dexamethasone and Postnatal High-Fat Diet Induced Programmed Hypertension in Male Rat Offspring

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Tain, You-Lin; Sheen, Jiunn-Ming; Yu, Hong-Ren; Chen, Chih-Cheng; Tiao, Mao-Meng; Hsu, Chien-Ning; Lin, Yu-Ju; Kuo, Kuang-Che; Huang, Li-Tung

2015-01-01

Prenatal dexamethasone (DEX) exposure and high-fat (HF) intake are linked to hypertension. We examined whether maternal melatonin therapy prevents programmed hypertension synergistically induced by prenatal DEX plus postnatal HF in adult offspring. We also examined whether DEX and melatonin causes renal programming using next-generation RNA sequencing (NGS) technology. Pregnant Sprague-Dawley rats received intraperitoneal dexamethasone (0.1 mg/kg) or vehicle from gestational day 16 to 22. In ...

The inhibitory effect of dexamethasone on platelet-derived growth factor-induced vascular smooth muscle cell migration through up-regulating PGC-1α expression

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Xu, Wei; Guo, Ting; Zhang, Yan; Jiang, Xiaohong; Zhang, Yongxian; Zen, Ke; Yu, Bo; Zhang, Chen-Yu

2011-01-01

Dexamethasone has been shown to inhibit vascular smooth muscle cell (VSMC) migration, which is required for preventing restenosis. However, the mechanism underlying effect of dexamethasone remains unknown. We have previously demonstrated that peroxisome proliferator-activated receptor gamma (PPARγ) coactivator-1 alpha (PGC-1α) can inhibit VSMC migration and proliferation. Here, we investigated the role of PGC-1α in dexamethasone-reduced VSMC migration and explored the possible mechanism. We first examined PGC-1α expression in cultured rat aortic VSMCs. The results revealed that incubation of VSMCs with dexamethasone could significantly elevate PGC-1α mRNA expression. In contrast, platelet-derived growth factor (PDGF) decreased PGC-1α expression while stimulating VSMC migration. Mechanistic study showed that suppression of PGC-1α by small interfering RNA strongly abrogated the inhibitory effect of dexamethasone on VSMC migration, whereas overexpression of PGC-1α had the opposite effect. Furthermore, an analysis of MAPK signal pathways showed that dexamethasone inhibited ERK and p38 MAPK phosphorylation in VSMCs. Overexpression of PGC-1α decreased both basal and PDGF-induced p38 MAPK phosphorylation, but it had no effect on ERK phosphorylation. Finally, inhibition of PPARγ activation by a PPARγ antagonist GW9662 abolished the suppressive effects of PGC-1α on p38 MAPK phosphorylation and VSMC migration. These effects of PGC-1α were enhanced by a PPARγ agonist troglitazone. Collectively, our data indicated for the first time that one of the anti-migrated mechanisms of dexamethasone is due to the induction of PGC-1α expression. PGC-1α suppresses PDGF-induced VSMC migration through PPARγ coactivation and, consequently, p38 MAPK inhibition.

Creation of lung-targeted dexamethasone immunoliposome and its therapeutic effect on bleomycin-induced lung injury in rats.

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Xue-Yuan Chen

Full Text Available OBJECTIVE: Acute lung injury (ALI, is a major cause of morbidity and mortality, which is routinely treated with the administration of systemic glucocorticoids. The current study investigated the distribution and therapeutic effect of a dexamethasone(DXM-loaded immunoliposome (NLP functionalized with pulmonary surfactant protein A (SP-A antibody (SPA-DXM-NLP in an animal model. METHODS: DXM-NLP was prepared using film dispersion combined with extrusion techniques. SP-A antibody was used as the lung targeting agent. Tissue distribution of SPA-DXM-NLP was investigated in liver, spleen, kidney and lung tissue. The efficacy of SPA-DXM-NLP against lung injury was assessed in a rat model of bleomycin-induced acute lung injury. RESULTS: The SPA-DXM-NLP complex was successfully synthesized and the particles were stable at 4°C. Pulmonary dexamethasone levels were 40 times higher with SPA-DXM-NLP than conventional dexamethasone injection. Administration of SPA-DXM-NLP significantly attenuated lung injury and inflammation, decreased incidence of infection, and increased survival in animal models. CONCLUSIONS: The administration of SPA-DXM-NLP to animal models resulted in increased levels of DXM in the lungs, indicating active targeting. The efficacy against ALI of the immunoliposomes was shown to be superior to conventional dexamethasone administration. These results demonstrate the potential of actively targeted glucocorticoid therapy in the treatment of lung disease in clinical practice.

Disrupted epithelial/macrophage crosstalk via Spinster homologue 2-mediated S1P signaling may drive defective macrophage phagocytic function in COPD.

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Tran, Hai B; Jersmann, Hubertus; Truong, Tung Thanh; Hamon, Rhys; Roscioli, Eugene; Ween, Miranda; Pitman, Melissa R; Pitson, Stuart M; Hodge, Greg; Reynolds, Paul N; Hodge, Sandra

2017-01-01

We have previously established a link between impaired phagocytic capacity and deregulated S1P signaling in alveolar macrophages from COPD subjects. We hypothesize that this defect may include a disruption of epithelial-macrophage crosstalk via Spns2-mediated intercellular S1P signaling. Primary alveolar macrophages and bronchial epithelial cells from COPD subjects and controls, cell lines, and a mouse model of chronic cigarette smoke exposure were studied. Cells were exposed to 10% cigarette smoke extract, or vehicle control. Spns2 expression and subcellular localization was studied by immunofluorescence, confocal microscopy and RT-PCR. Phagocytosis was assessed by flow-cytometry. Levels of intra- and extracellular S1P were measured by S1P [3H]-labeling. Spns2 expression was significantly increased (pS1P in the airway and that there is a possible disruption of epithelial/macrophage cross talk via Spns2-mediated S1P signaling in COPD and in response to cigarette smoke exposure.

Predicting the neurobehavioral side effects of dexamethasone in pediatric acute lymphoblastic leukemia

NARCIS (Netherlands)

Warris, Lidewij T.; van den Akker, Erica L. T.; Aarsen, Femke K.; Bierings, Marc B.; van den Bos, Cor; Tissing, Wim J. E.; Sassen, Sebastiaan D. T.; Veening, Margreet A.; Zwaan, Christian M.; Pieters, Rob; van den Heuvel-Eibrink, Marry M.

2016-01-01

Although dexamethasone is an effective treatment for acute lymphoblastic leukemia (ALL), it can induce a variety of serious neurobehavioral side effects. We hypothesized that these side effects are influenced by glucocorticoid sensitivity at the tissue level. We therefore prospectively studied

Dexamethasone-suppressed cortisol awakening response predicts treatment outcome in posttraumatic stress disorder

NARCIS (Netherlands)

Nijdam, M. J.; van Amsterdam, J. G. C.; Gersons, B. P. R.; Olff, M.

2015-01-01

Posttraumatic stress disorder (PTSD) has been associated with several alterations in the neuroendocrine system, including enhanced cortisol suppression in response to the dexamethasone suppression test. The aim of this study was to examine whether specific biomarkers of PTSD predict treatment

EFFECTS OF DEXAMETHASONE AND PHENIRAMINE MALEATE ON HEMODYNAMIC AND RESPIRATORY PARAMETERS AFTER CEMENTATION IN CEMENTED PARTIAL HIP PROSTHESIS.

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Yektaş, Abdulkadir; Gümüş, Funda; Totoz, Tolga; Gül, Nurten; Erkalp, Kerem; Alagöl, Ayşin

2015-02-01

To prevent hemodynamic and respiratory changes that are likely to occur during cementation in partial hip prosthesis by prophylactic use of pheniramine maleate and dexamethasone. The study included 40 patients aged between 60 and 85 years with an American Society ofAnesthesiologists (ASA) grade of II-III who underwent partial hip prosthesis. Just after spinal anesthesia, 4 mL normal saline was pushed in patients in Group S, whereas 45.5 mg pheniramine maleate and 8 mg dexamethasone mixture was pushed intravenously in a total volume of 4 mL in patients in Group PD. Amounts of atropine and adrenaline administered after cementation were significantly higher in Group S than in Group PD (P pheniramine maleate and dexamethasone in partial hip prosthesis led to an increase in SpO2 value and a decrease in the utilization of adrenaline and atropine after cementation.

Cell walls as a stage for intercellular communication regulating shoot meristem development

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Toshiaki eTameshige

2015-05-01

Full Text Available Aboveground organs of plants are ultimately derived/generated from the shoot apical meristem (SAM, which is the proliferative tissue located at the apex of the stem. The SAM contains a population of stem cells that provide new cells for organ/tissue formation. The SAM is composed of distinct cell layers and zones with different properties. Primordia of lateral organs develop at the periphery of the SAM. The shoot apex is a dynamic and complex tissue, and as such intercellular communications among cells, layers and zones play significant roles in the coordination of cell proliferation, growth and differentiation to achieve elaborate morphogenesis. Recent findings have highlighted the importance of a number of singling molecules acting in the cell wall space for the intercellular communication, including classic phytohormones and secretory peptides. Moreover, accumulating evidences reveal that cell wall properties and their modifying enzymes modulate hormone actions. In this review, we overview how behaviors of singling molecules and changes of cell wall properties are integrated for the shoot meristem regulation.

Dexamethasone attenuates VEGF expression and inflammation but not barrier dysfunction in a murine model of ventilator-induced lung injury.

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Maria A Hegeman

Full Text Available BACKGROUND: Ventilator-induced lung injury (VILI is characterized by vascular leakage and inflammatory responses eventually leading to pulmonary dysfunction. Vascular endothelial growth factor (VEGF has been proposed to be involved in the pathogenesis of VILI. This study examines the inhibitory effect of dexamethasone on VEGF expression, inflammation and alveolar-capillary barrier dysfunction in an established murine model of VILI. METHODS: Healthy male C57Bl/6 mice were anesthetized, tracheotomized and mechanically ventilated for 5 hours with an inspiratory pressure of 10 cmH2O ("lower" tidal volumes of ∼7.5 ml/kg; LVT or 18 cmH2O ("higher" tidal volumes of ∼15 ml/kg; HVT. Dexamethasone was intravenously administered at the initiation of HVT-ventilation. Non-ventilated mice served as controls. Study endpoints included VEGF and inflammatory mediator expression in lung tissue, neutrophil and protein levels in bronchoalveolar lavage fluid, PaO2 to FiO2 ratios and lung wet to dry ratios. RESULTS: Particularly HVT-ventilation led to alveolar-capillary barrier dysfunction as reflected by reduced PaO2 to FiO2 ratios, elevated alveolar protein levels and increased lung wet to dry ratios. Moreover, VILI was associated with enhanced VEGF production, inflammatory mediator expression and neutrophil infiltration. Dexamethasone treatment inhibited VEGF and pro-inflammatory response in lungs of HVT-ventilated mice, without improving alveolar-capillary permeability, gas exchange and pulmonary edema formation. CONCLUSIONS: Dexamethasone treatment completely abolishes ventilator-induced VEGF expression and inflammation. However, dexamethasone does not protect against alveolar-capillary barrier dysfunction in an established murine model of VILI.

Compatibility and Stability of Rolapitant Injectable Emulsion Admixed with Dexamethasone Sodium Phosphate.

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Wu, George; Yeung, Stanley; Chen, Frank

2017-01-01

Neurokinin-1 receptor antagonist, 5-hydroxytryptamine-3 receptor antagonist, and dexamethasone combination therapy is the standard of care for the prevention of chemotherapy-induced nausea and vomiting. Herein, we describe the physical and chemical stability of an injectable emulsion of the Neurokinin-1 receptor antagonist rolapitant 185 mg in 92.5 mL (free base, 166.5 mg in 92.5 mL) admixed with either 2.5 mL of dexamethasone sodium phosphate (10 mg) or 5 mL of dexamethasone sodium phosphate (20 mg). Admixtures were prepared and stored in two types of container closures (glass and Crystal Zenith plastic bottles) and four types of intravenous administration tubing sets (or intravenous tubing sets). The assessment of the physical and chemical stability was conducted on admixtures packaged in bottled samples stored at room temperature (20°C to 25°C under fluorescent light) and evaluated at 0, 1, and 6 hours. For admixtures in intravenous tubing sets, the assessment of physicochemical stability was performed after 0 and 7 hours of storage at 20°C to 25°C, and then after 20 hours (total 27 hours) under refrigeration (2°C to 8°C) and protected from light. Physical stability was assessed by visually examining the bottle contents under normal room light and measuring turbidity and particulate matter. Chemical stability was assessed by measuring the pH of the admixture and determining drug concentrations through high-performance liquid chromatographic analysis. Results showed that all samples were physically compatible throughout the duration of the study. The admixtures stayed within narrow and acceptable ranges in pH, turbidity, and particulate matter. Admixtures of rolapitant and dexamethasone were chemically stable when stored in glass and Crystal Zenith bottles for at least 6 hours at room temperature, as well as in the four selected intravenous tubing sets for 7 hours at 20°C to 25°C and then for 20 (total 27 hours) hours at 2°C to 8°C. No loss of potency

Urtica dioica extract attenuates depressive like behavior and associative memory dysfunction in dexamethasone induced diabetic mice.

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Patel, Sita Sharan; Udayabanu, Malairaman

2014-03-01

Evidences suggest that glucocorticoids results in depression and is a risk factor for type 2 diabetes. Further diabetes induces oxidative stress and hippocampal dysfunction resulting in cognitive decline. Traditionally Urtica dioica has been used for diabetes mellitus and cognitive dysfunction. The present study investigated the effect of the hydroalcoholic extract of Urtica dioica leaves (50 and 100 mg/kg, p.o.) in dexamethasone (1 mg/kg, i.m.) induced diabetes and its associated complications such as depressive like behavior and cognitive dysfunction. We observed that mice administered with chronic dexamethasone resulted in hypercortisolemia, oxidative stress, depressive like behavior, cognitive impairment, hyperglycemia with reduced body weight, increased water intake and decreased hippocampal glucose transporter-4 (GLUT4) mRNA expression. Urtica dioica significantly reduced hyperglycemia, plasma corticosterone, oxidative stress and depressive like behavior as well as improved associative memory and hippocampal GLUT4 mRNA expression comparable to rosiglitazone (5 mg/kg, p.o.). Further, Urtica dioica insignificantly improved spatial memory and serum insulin. In conclusion, Urtica dioica reversed dexamethasone induced hyperglycemia and its associated complications such as depressive like behavior and cognitive dysfunction.

Fatal Gastrointestinal Hemorrhage in a Young Boy with Newly Diagnosed Metastatic Medulloblastoma on High Dose Dexamethasone

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Victor Wong

2014-01-01

Full Text Available A 10-year-old boy with newly diagnosed metastatic medulloblastoma was placed on high dose dexamethasone and ranitidine prior to surgery. The child underwent subtotal resection and was discharged 5 days postoperatively with an uneventful hospital course on a tapering dose of dexamethasone and ranitidine. Over the next 2 days the patient complained of mild abdominal distension with flatulence, without pain, vomiting, or dysmotility. On follow-up in clinic 5 days after discharge, he had normal vital signs when he suddenly became pale and had loss of consciousness. Emergent computerized tomography of the head showed no acute hemorrhage and complete blood count revealed hemoglobin of 4.2 gm/dL. In spite of maximum resuscitation with copious blood products the patient died. Autopsy revealed evidence of duodenal perforation with intraluminal hemorrhage. This case demonstrates a rare fatal complication of high dose dexamethasone therapy even with concurrent gastrointestinal prophylactic therapy. We provide a review of the limited literature on steroid use in pediatric neurooncology with regard to gastrointestinal bleeding.

The influence of betamethasone and dexamethasone on motor development in young rats

NARCIS (Netherlands)

Gramsbergen, A; Mulder, EJH

Synthetic corticosteroids such as dexamethasone and betamethasone are widely used in clinical practice of the perinatal period to enhance lung maturation. However, indications emerged both on the basis of investigations in humans and in experimental animals that such treatment leads to abnormal

A novel brain trauma model in the mouse : effects of dexamethasone treatment

NARCIS (Netherlands)

Hortobágyi, Tibor; Hortobagyi, S; Gorlach, C; Harkany, T; Benbyo, Z; Gorogh, T; Nagel, W; Wahl, M

2000-01-01

We describe a novel methodological approach for inducing cold lesion in the mouse as a model of human cortical contusion trauma. To validate its reproducibility and reliability, dexamethasone (Dxm) was repeatedly applied to demonstrate possible antioedematous drug effects. Following tho induction of

Serum deprivation induces glucose response and intercellular coupling in human pancreatic adenocarcinoma PANC-1 cells.

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Hiram-Bab, Sahar; Shapira, Yuval; Gershengorn, Marvin C; Oron, Yoram

2012-03-01

This study aimed to investigate whether the previously described differentiating islet-like aggregates of human pancreatic adenocarcinoma cells (PANC-1) develop glucose response and exhibit intercellular communication. Fura 2-loaded PANC-1 cells in serum-free medium were assayed for changes in cytosolic free calcium ([Ca]i) induced by depolarization, tolbutamide inhibition of K(ATP) channels, or glucose. Dye transfer, assayed by confocal microscopy or by FACS, was used to detect intercellular communication. Changes in messenger RNA (mRNA) expression of genes of interest were assessed by quantitative real-time polymerase chain reaction. Proliferation was assayed by the MTT method. Serum-deprived PANC-1 cell aggregates developed [Ca]i response to KCl, tolbutamide, or glucose. These responses were accompanied by 5-fold increase in glucokinase mRNA level and, to a lesser extent, of mRNAs for K(ATP) and L-type calcium channels, as well as increase in mRNA levels of glucagon and somatostatin. Trypsin, a proteinase-activated receptor 2 agonist previously shown to enhance aggregation, modestly improved [Ca]i response to glucose. Glucose-induced coordinated [Ca]i oscillations and dye transfer demonstrated the emergence of intercellular communication. These findings suggest that PANC-1 cells, a pancreatic adenocarcinoma cell line, can be induced to express a differentiated phenotype in which cells exhibit response to glucose and form a functional syncytium similar to those observed in pancreatic islets.

Permissive effect of dexamethasone on the increase of proenkephalin mRNA induced by depolarization of chromaffin cells

International Nuclear Information System (INIS)

Naranjo, J.R.; Mocchetti, I.; Schwartz, J.P.; Costa, E.

1986-01-01

In cultured bovine chromaffin cells, changes in the dynamic state of enkephalin stores elicited experimentally were studied by measuring cellular proenkephalin mRNA, as well as enkephalin precursors and authentic enkephalin content of cells and culture media. In parallel, tyrosine hydroxylase mRNA and catecholamine cell content were also determined. Low concentrations (0.5-100 pM) of dexamethasone increased the cell contents of proenkephalin mRNA and enkephalin-containing peptides. High concentrations of the hormone(1 μM) were required to increase the cell contents of tyrosine hydroxylase mRNA and catecholamines. Depolarization of the cells with 10 μM veratridine resulted in a depletion of enkephalin and catecholamine stores after 24 hr. The enkephalin, but not the catecholamine, content was restored by 48 hr. An increase in proenkephalin mRNA content might account for the recovery; this increase was curtailed by tetrodotoxin and enhanced by 10 pM dexamethasone. Tyrosine hydroxylase mRNA content was not significantly modified by depolarization, even in the presence of 1 μM dexamethasone. Aldosterone, progesterone, testosterone, or estradiol (1 μM) failed to change proenkephalin mRNA. Hence, dexamethasone appears to exert a specific permissive action on the stimulation of the proenkephalin gene elicited by depolarization. Though the catecholamines and enkephalins are localized in the same chromaffin granules and are coreleased by depolarization, the genes coding for the processes that are rate limiting in the production of these neuromodulators can be differentially regulated

DOES THE ADDITION OF DEXAMETHASON TO LOCAL ANESTHETIC PROLONG THE ANALGESIA OF INTERSCALEN PLEXUS BRACHIALIS BLOCK IN PATIENTS WITH SHOULDER SURGERY?

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Nancheva Jasminka

2016-07-01

Full Text Available Abstract: Introduction: Peripherial nerve blocks is a suitable alternative to general anesthesia especially for one-day case surgery. Interscalene approach of plexus brachialis block as much as supraclavicular and infraclavicular provide reliable, safe, effective, low cost and most complete anesthesia with satisfactory postoperative analgesia for upper limb surgery. Postoperative analgesia of plexus brachialis blocks can be prolonged by using different drugs as adjuvants with local anesthetics. Dexamethasone has been shown to prolong the duration of postoperative analgesia when given as an adjunct for peripheral nerve blocks. The investigation was randomized, prospective, double blinded and controlled study. Objective: The study was designed to compare the effects of dexamethasone administered as an adjunct to bupivacaine in interscalene brachial plexus block on the onset, duration and postoperative analgesia in patients under the shoulder surgery. Methods: A prospective, double-blind study was undertaken in patients scheduled for shoulder surgeries under the interscalene brachial plexus block. We enrolled 60 patients, ASA I-II both sexes, aged 19-65 years, weighing 54-89 kg, divided to two groups G1 and G2. The brachial plexus block was performed by interscalene approach and mixture of 2% lidocaine (12ml and 0.5% bupivacaine (22 ml either alone or combined with dexamethasone (4 mg. The block was performed by using double technique neurostimulator/ultrasound technique. Results: In our investigation we found a significant increase in onset and duration of motor and sensory block in Group G2 (with dexamethasone as compared to Group G1 patients (p < 0.01. Conclusion: Addition of dexamethasone to local anesthetic drugs in interscalene plexus brachialis block, significantly prolongs the duration of analgesia and motor block in patients undergoing shoulder arthroscopy. Moreover, it is a remarkably safe and costeffective method of providing

Investigation of intercellular salicylic acid accumulation during compatible and incompatible Arabidopsis-pseudomonas syringae interactions using a fast neutron-generated mutant allele of EDS5 identified by genetic mapping and whole-genome sequencing.

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Jessie L Carviel

Full Text Available A whole-genome sequencing technique developed to identify fast neutron-induced deletion mutations revealed that iap1-1 is a new allele of EDS5 (eds5-5. RPS2-AvrRpt2-initiated effector-triggered immunity (ETI was compromised in iap1-1/eds5-5 with respect to in planta bacterial levels and the hypersensitive response, while intra- and intercellular free salicylic acid (SA accumulation was greatly reduced, suggesting that SA contributes as both an intracellular signaling molecule and an antimicrobial agent in the intercellular space during ETI. During the compatible interaction between wild-type Col-0 and virulent Pseudomonas syringae pv. tomato (Pst, little intercellular free SA accumulated, which led to the hypothesis that Pst suppresses intercellular SA accumulation. When Col-0 was inoculated with a coronatine-deficient strain of Pst, high levels of intercellular SA accumulation were observed, suggesting that Pst suppresses intercellular SA accumulation using its phytotoxin coronatine. This work suggests that accumulation of SA in the intercellular space is an important component of basal/PAMP-triggered immunity as well as ETI to pathogens that colonize the intercellular space.

Biodegradable polyurethane nanocomposites containing dexamethasone for ocular route

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Rodrigues da Silva, Gisele [Federal University of Sao Joao Del Rei, School of Pharmacy, Divinopolis, Minas Gerais (Brazil); Silva-Cunha, Armando da [Federal University of Minas Gerais, School of Pharmacy, Belo Horizonte, Minas Gerais (Brazil); Behar-Cohen, Francine [INSERM, Physiopathology of ocular diseases: Therapeutic innovations, Institut des Cordeliers, Paris (France); Laboratoire d' Innovations Therapeutiques, Fondation Rothschild, Paris (France); Universite Rene Descartes, Hotel Dieu University Hospital, Paris (France); Ayres, Eliane [Federal University of Minas Gerais, Department of Metallurgical and Materials Engineering, Belo Horizonte, Minas Gerais (Brazil); Orefice, Rodrigo L., E-mail: rorefice@demet.ufmg.br [Federal University of Minas Gerais, Department of Metallurgical and Materials Engineering, Belo Horizonte, Minas Gerais (Brazil)

2011-03-12

The treatment of posterior segment ocular diseases, such as uveitis, by using eye drops and oral drugs is usually not effective due to the body's natural barriers to drug penetration. In this study, ocular implants to treat uveitis were synthesized by incorporating dexamethasone acetate, an important type of corticoid used in the treatment of some uveitis, into a biodegradable polyurethane containi clay nanoparticles. Biodegradable polyurethane nanocomposites having poly(caprolactone) oligomers as soft segments were obtained by delaminating clay particles within a polyurethane aqueous dispersion. The drug was incorporated into the polymer by dispersing it in the waterborne polyurethane followed by a drying step. Nanoparticles derived from clay were demonstrated to be able to tailor the mechanical properties of polyurethanes to achieve values that can match the properties of ocular soft tissues. Infrared spectra (FTIR) showed that the presence of clay particles was able to change the microphase separation process typical of polyurethanes. X-ray diffraction and small angle x-ray scattering (SAXS) results were explored to show that the incorporation of both dexamethasone acetate and nanocomponents derived from clay led to a less defined two-phase polyurethane. The presence of clay nanoparticles increased the rate of drug release measured in vitro. Human retinal pigment epithelial cells (ARPE-19) were cultured in contact with polyurethanes and polyurethane nanocomposites, and the viability of them (evaluated by using MTT assay after 7 days) showed that no toxic components were released from polyurethanes containing no drugs during the test.

Biodegradable polyurethane nanocomposites containing dexamethasone for ocular route

International Nuclear Information System (INIS)

Rodrigues da Silva, Gisele; Silva-Cunha, Armando da; Behar-Cohen, Francine; Ayres, Eliane; Orefice, Rodrigo L.

2011-01-01

The treatment of posterior segment ocular diseases, such as uveitis, by using eye drops and oral drugs is usually not effective due to the body's natural barriers to drug penetration. In this study, ocular implants to treat uveitis were synthesized by incorporating dexamethasone acetate, an important type of corticoid used in the treatment of some uveitis, into a biodegradable polyurethane containi clay nanoparticles. Biodegradable polyurethane nanocomposites having poly(caprolactone) oligomers as soft segments were obtained by delaminating clay particles within a polyurethane aqueous dispersion. The drug was incorporated into the polymer by dispersing it in the waterborne polyurethane followed by a drying step. Nanoparticles derived from clay were demonstrated to be able to tailor the mechanical properties of polyurethanes to achieve values that can match the properties of ocular soft tissues. Infrared spectra (FTIR) showed that the presence of clay particles was able to change the microphase separation process typical of polyurethanes. X-ray diffraction and small angle x-ray scattering (SAXS) results were explored to show that the incorporation of both dexamethasone acetate and nanocomponents derived from clay led to a less defined two-phase polyurethane. The presence of clay nanoparticles increased the rate of drug release measured in vitro. Human retinal pigment epithelial cells (ARPE-19) were cultured in contact with polyurethanes and polyurethane nanocomposites, and the viability of them (evaluated by using MTT assay after 7 days) showed that no toxic components were released from polyurethanes containing no drugs during the test.

Effect of adding dexamethasone to bupivacaine on transversus abdominis plane block for abdominal hysterectomy: A prospective randomized controlled trial

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Amany S Ammar

2012-01-01

Full Text Available Purpose: Different adjuvants have been used to improve the quality and increase the duration of local anesthetics during various nerve block techniques. The current study was aimed to evaluate the effect of adding dexamethasone to bupivacaine on the quality and duration of transversus abdominis plane (TAP block. Methods: Sixty adult patients undergoing elective open abdominal hysterectomy were randomly allocated to receive TAP block using 20 mL of bupivacaine hydrochloride 0.25% + 2 mL saline 0.9% (control group, n=30 or 20 mL of bupivacaine hydrochloride 0.25% + 2 mL dexamethasone "8 mg" (dexamethasone group, n=30. The primary outcome was postoperative pain, as evaluated by visual analog scale (VAS for pain scoring at 1, 2, 4, 12, 24 and 48 h postoperatively, whereas the secondary outcomes were time to first analgesia (TFA, morphine consumption and the occurrence of nausea, vomiting or somnolence. Results: The pain VAS score was significantly lower at the postoperative 2 h (4.9 vs. 28.1, P=0.01, 4 h (12.2 vs. 31.1, P=0.01 and 12 h (15.7 vs. 25.4, P=0.02. Furthermore, TFA was significantly longer in the dexamethasone group (459.8 vs. 325.4 min, P=0.002, with lesser morphine requirements in the postoperative 48 h (4.9 vs. 21.2 mg, P=0.003 and lower incidence of nausea and vomiting (6 vs. 14, P=0.03. No complications attributed to the block were recorded. Conclusion: Addition of dexamethasone to bupivacaine in TAP block prolonged the duration of the block and decreased the incidence of nausea and vomiting.

Detection of cancerous kidney tissue areas by means of infrared spectroscopy of intercellular fluid

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Urboniene, V.; Jankevicius, F.; Zelvys, A.; Steiner, G.; Sablinskas, V.

2014-03-01

In this work the infrared absorption spectra of intercellular fluid of normal and tumor kidney tissue were recorded and analyzed. The samples were prepared by stamping freshly resected tissue onto a CaF2 substrate. FT-IR spectra obtained from intracellular fluid of tumor tissue exhibit stronger absorption bands in the spectral region from 1000-1200 cm-1 and around 1750 cm-1 than those obtained from normal tissue. It is likely the spectra of extracellular matrix of kidney tumor tissue with large increases in the intensities of these bands represent a higher concentration of fatty acids and glycerol. Amide I and amide II bands are stronger in spectra of normal tissue indicating a higher level of proteins. The results demonstrate that FT-IR spectroscopy of intercellular fluids is a novel approach for a quick diagnosis during surgical resection, which can improve the therapy of kidney tumors.

Effect of Dexamethasone and Pheniramine Maleate in Patients Undergoing Elective Laparoscopic Cholecystectomy.

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Shrestha, B B; Karmacharya, M; Gharti, B B; Timilsina, B; Ghimire, P

2014-01-01

Laparoscopic cholecystectomy (LC) is elective surgical procedure for uncomplicated gallstone disease and gallbladder polyp. The objective of this study was to assess the efficacy of Dexamethasone and Pheniramine hydrogen maleate on reducing stress response and pain after surgery in patients undergoing laparoscopic cholecystectomy. After obtaining approval from the institutional ethics committee and written informed consent, 120 patients undergoing elective laparoscopic cholecystectomy were enrolled in the study from Sep 2103 to Aug 2014 at Department of Surgery, Manipal College of Medical Sciences, Pokhara, Nepal. Patients were randomized to receive either 8mg/2ml of Dexamethasone + 45.5/2ml Pheniramine hydrogen maleate (treatment group, n= 60) or 5 ml of normal saline (control group, n=60) 90 minutes before skin incision. There was a reduction of total bilirubin, C-reactive protein (CRP) value and Visual Analogue Score (VAS) in treatment group as compared to control group (p Pheniramine hydrogen maleate prior to surgical skin incision helps to reduce both postoperative pain and acute physiological stress.

Thalidomide, clarithromycin, lenalidomide and dexamethasone therapy in newly diagnosed, symptomatic multiple myeloma.

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Mark, Tomer M; Bowman, Isaac A; Rossi, Adriana C; Shah, Manan; Rodriguez, Melissa; Quinn, Ryann; Pearse, Roger N; Zafar, Faiza; Pekle, Karen; Jayabalan, David; Ely, Scott; Coleman, Morton; Chen-Kiang, Selina; Niesvizky, Ruben

2014-12-01

We studied T-BiRD (thalidomide [Thalomid(®)], clarithromycin [Biaxin(®)], lenalidomide [Revlimid(®)] and dexamethasone) in symptomatic, newly diagnosed multiple myeloma. In 28-day cycles, patients received dexamethasone 40 mg/day on days 1, 8, 15, 22, clarithromycin 500 mg twice daily on days 1-28; lenalidomide 25 mg/day on days 1-21; and thalidomide 100 mg/day (50 mg/day on days 1-7 of cycle 1 only) on days 1-28. Twenty-six patients received a median of 6 cycles (range 0-41). Overall response rate (ORR) was 80% for the group and 100% in 11 patients who underwent autologous stem cell transplantation as part of first-line therapy. The 4-year overall survival rate was 74.9%, and the median progression-free survival was 35.6 months. Eight patients discontinued due to regimen toxicity. Grade 3 non hematologic toxicity affected 12 patients (46.2%). T-BiRD is a highly active regimen with potential toxicity limitations. ClinicalTrials.gov identifier: NCT00538733.

Effect of postoperative dexamethasone on pain, emesis and haemorrhage in tonsillectomy by dissection method

International Nuclear Information System (INIS)

Khan, K.A.; Faiz, S.B.

2013-01-01

Objectives: To compare the effect of postoperative intravenous dose of dexamethasone on morbidity in patients undergoing tonsillectomy. Design: Randomized control trial. Place and Duration of Study: This study was conducted in ENT Department Shaikh Khalifa Bin Zayed Al Nahyan Hospital (CMH) Muzaffarabad from 10th Jan 2010 to 15th Feb 2011. Patients and Methods: After getting informed consent, a total of 60 patients who fulfilled the inclusion criteria were selected and tonsillectomy by dissection method was carried out. They were divided into two groups of 30 each using a random numbers table. Group A received 0.25 mg/kg body weight (maximum 20 mg) of Dexamethasone postoperatively intravenously for 03 days while group B (control group) did not receive any steroid. Results: In group A, 80% patients had mild pain, 16.7% had moderate pain and 3.3% had a severe pain while in group B, 30% patients had mild pain, 6.7% had moderate pain and 63.3% had severe pain (p< 0.05). In group A, 76.7% patients had mild emesis while in group B, 86.7% had moderate emesis (p< 0.05). There was an insignificant difference in secondary hemorrhage. Conclusion: Dexamethasone given postoperatively significantly reduces the morbidity that is pain, episodes of emesis thus early recovery to a normal lifestyle with no effect on secondary hemorrhage in patients undergoing Tonsillectomy by dissection method. (author)

Chemopreventive agents attenuate rapid inhibition of gap junctional intercellular communication induced by environmental toxicants

Czech Academy of Sciences Publication Activity Database

Babica, Pavel; Čtveráčková, Lucie; Lenčešová, Zuzana; Trosko, J. E.; Upham, B. L.

2016-01-01

Roč. 68, č. 5 (2016), s. 827-837 ISSN 0163-5581 R&D Projects: GA MŠk LH12034 Institutional support: RVO:67985939 Keywords : gap junctional intercellular communication * chemopreventive agents * environmental toxicants Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 2.447, year: 2016

Prenatal Dexamethasone and Postnatal High-Fat Diet Decrease Interferon Gamma Production through an Age-Dependent Histone Modification in Male Sprague-Dawley Rats

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Yu, Hong-Ren; Tain, You-Lin; Sheen, Jiunn-Ming; Tiao, Mao-Meng; Chen, Chih-Cheng; Kuo, Ho-Chang; Hung, Pi-Lien; Hsieh, Kai-Sheng; Huang, Li-Tung

2016-01-01

Overexposure to prenatal glucocorticoid (GC) disturbs hypothalamic-pituitary-adrenocortical axis-associated neuroendocrine metabolism and susceptibility to metabolic syndrome. A high-fat (HF) diet is a major environmental factor that can cause metabolic syndrome. We aimed to investigate whether prenatal GC plus a postnatal HF diet could alter immune programming in rat offspring. Pregnant Sprague-Dawley rats were given intraperitoneal injections of dexamethasone or saline at 14–21 days of gestation. Male offspring were then divided into four groups: vehicle, prenatal dexamethasone exposure, postnatal HF diet (VHF), and prenatal dexamethasone exposure plus a postnatal HF diet (DHF). The rats were sacrificed and adaptive immune function was evaluated. Compared to the vehicle, the DHF group had lower interferon gamma (IFN-γ) production by splenocytes at postnatal day 120. Decreases in H3K9 acetylation and H3K36me3 levels at the IFN-γ promoter correlated with decreased IFN-γ production. The impaired IFN-γ production and aberrant site-specific histone modification at the IFN-γ promoter by prenatal dexamethasone treatment plus a postnatal HF diet resulted in resilience at postnatal day 180. Prenatal dexamethasone and a postnatal HF diet decreased IFN-γ production through a site-specific and an age-dependent histone modification. These findings suggest a mechanism by which prenatal exposure to GC and a postnatal environment exert effects on fetal immunity programming. PMID:27669212

Prenatal Dexamethasone and Postnatal High-Fat Diet Decrease Interferon Gamma Production through an Age-Dependent Histone Modification in Male Sprague-Dawley Rats

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Hong-Ren Yu

2016-09-01

Full Text Available Overexposure to prenatal glucocorticoid (GC disturbs hypothalamic-pituitary-adrenocortical axis-associated neuroendocrine metabolism and susceptibility to metabolic syndrome. A high-fat (HF diet is a major environmental factor that can cause metabolic syndrome. We aimed to investigate whether prenatal GC plus a postnatal HF diet could alter immune programming in rat offspring. Pregnant Sprague-Dawley rats were given intraperitoneal injections of dexamethasone or saline at 14–21 days of gestation. Male offspring were then divided into four groups: vehicle, prenatal dexamethasone exposure, postnatal HF diet (VHF, and prenatal dexamethasone exposure plus a postnatal HF diet (DHF. The rats were sacrificed and adaptive immune function was evaluated. Compared to the vehicle, the DHF group had lower interferon gamma (IFN-γ production by splenocytes at postnatal day 120. Decreases in H3K9 acetylation and H3K36me3 levels at the IFN-γ promoter correlated with decreased IFN-γ production. The impaired IFN-γ production and aberrant site-specific histone modification at the IFN-γ promoter by prenatal dexamethasone treatment plus a postnatal HF diet resulted in resilience at postnatal day 180. Prenatal dexamethasone and a postnatal HF diet decreased IFN-γ production through a site-specific and an age-dependent histone modification. These findings suggest a mechanism by which prenatal exposure to GC and a postnatal environment exert effects on fetal immunity programming.

[Comparison the effects of prilocaine and the addition of dexketoprofen and dexamethasone to prilocaine for intravenous regional anesthesia].

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Borazan, Hale; Sahin, Osman; Uluer, Mehmet Selçuk; Keçecioğlu, Ahmet; Sarıtaş, Tuba Berra; Otelcioğlu, Seref

2014-01-01

The aim of this study was to compare the anesthetic and analgesic effects of prilocaine alone, prilocaine added dexketoprofen and dexamethasone during intravenous regional anesthesia (IVRA). Forty five patients undergoing forearm or hand surgery were randomly assigned to one of three groups to receive (Group P) 3 mg/kg 0.5% prilocaine; (Group PDK) 3 mg/kg 0.5% prilocaine plus 50 mg dexketoprofen; (Group PDM) 3 mg/kg 0.5% prilocaine plus 8 mg dexamethasone in total 40 ml volume for IVRA. The onset and duration of sensory and motor blocks, hemodynamic datas, duration of analgesia and tourniquet, time to first analgesic requirement, visual analog scale (VAS), total analgesic consumption in 24 hours and patient satisfaction score were assessed and recorded. Time to onset of sensory block was found to be longer in Group P (pdexketoprofen and dexamethasone to prilocaine during IVRA improves the quality of both anesthesia and analgesia moreover dexketoprofen provides beter postoperative analgesia during the first 24 hour after surgery.

Stability-Indicating HPLC Method for Simultaneous Determination of Chloramphenicol, Dexamethasone Sodium Phosphate and Tetrahydrozoline Hydrochloride in Ophthalmic Solution.

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AlAani, Hashem; Alnukkary, Yasmin

2016-03-01

A simple stability-indicating RP-HPLC assay method was developed and validated for quantitative determination of Chloramphenicol, Dexamethasone Sodium Phosphate and Tetrahydrozoline Hydrochloride in ophthalmic solution in the presence of 2-amino-1-(4-nitrophenyl)propane-1,3-diol, a degradation product of Chloramphenicol, and Dexamethasone, a degradation product of Dexamethasone Sodium Phosphate. Effective chromatographic separation was achieved using C18 column (250 mm, 4.6 mm i.d., 5 μm) with isocratic mobile phase consisting of acetonitrile - phosphate buffer (pH 4.0; 0.05 M) (30:70, v/v) at a flow rate of 1 mL/minute. The column temperature was maintained at 40°C and the detection wavelength was 230 nm. The proposed HPLC procedure was statistically validated according to the ICH guideline, and was proved to be stability-indicating by resolution of the APIs from their forced degradation products. The developed method is suitable for the routine analysis as well as stability studies.

Direct round window membrane application of dexamethasone in the protection of the guinea pigs'cochlea against irradiation damage

International Nuclear Information System (INIS)

Li Ying; Guo GuangWei; Su Jiping

2009-01-01

Objective: To investigate the protective effect of dexamethasone applied to round window membrane (RWM) against radiation-induced inner ear damage in guinea pigs, in order to provide the evidence for preventing and treating radiation-induced inner ear damage. Methods: 130 guinea pigs were randomly divided into four groups. (1) Dexamethasone group( n = 45): The guinea pigs were injected with dexamethasone through an intact RWM on right ear for one time after being treated with 70 Gy 60 Co γ irradiation. (2) Irradiation group(n = 45) : The guinea pigs were treated with 70 Gy 60 Co γ irradiation. (3) Saline group (n = 30): Applying of normal saline through an intact RWM on right ear for one time after being treated with 70 Gy 60 Co γ irradiation. (4) Control group(n =45) : Auditory brainstem response (ABR) was tested before the 3 rd day, the second week and the second month after irradiation (treatment) in the first three groups. The animals were sacrificed right after the ABR test and the middle ear mucosa was observed simultaneously. The hair cells were observed by surface preparation of the basilar membrane and scanning electron microscope ( SEM). Results: The normal ABR threshold is (8.2 ± 2.8) dB. The ABR thresholds increased in those of the three groups treated with irradiation and were rising with time. At the 3rd day, the second week and the second month, ABR thresholds of the dexamethasone group were (24.0 ± 14.1), (27.1 ± 9.9) and (38.0 ± 15.1) dB, respectively, while the irradiation group were (24.5 ± 13.5), (39.5 ± 15.4) and (57.2 ± 18.4) dB. The saline group were (27.0 ± 14.6) and (42.8 ± 13.5) dB, respectively. ABR thresholds of the dexamethasone group at the second week and the second month both decreased compared with those of the irradiation group and saline group ( P < 0.05) . In the control group, the outer hair cell lost by 8.0 ± 2.7 and inner hair cell by 3.7 ± 1.2. The lost quantities of the inner hair cells and outer hair cells

Prophylactic Use of Oral Acetaminophen or IV Dexamethasone and Combination of them on Prevention Emergence Agitation in Pediatric after Adenotonsillectomy

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Parvin Sajedi

2014-01-01

Full Text Available Background: The present study was aimed to evaluate the efficacy of acetaminophen plus dexamethasone on post-operative emergence agitation in pediatric adenotonsillectomy. Methods: A total of 128 patients were randomized and assigned among four groups as: Intravenous (IV dexamethasone, oral acetaminophen, IV dexamethasone plus oral acetaminophen, placebo. Group 1 received 0.2 mg/kg dexamethasone plus 0.25 mg/kg strawberry syrup 2 h before surgery. Group 2 received 20 mg/kg oral acetaminophen (0.25 ml/kg with 0.05 ml/kg IV normal saline. Group 3 received 20 mg/kg acetaminophen and 0.2 mg/kg dexamethasone intravenously. Group 4 received 0.25 ml/kg strawberry syrup and 0.05 ml/kg normal saline. Agitation was measured according to Richmond agitation sedation score in the post anesthetic care unit (PACU after admission, 10, 20 and 30 min after extubation. Pain score was measured with FACE scale. Nurse satisfaction was measured with verbal analog scale. If agitation scale was 3 ≥ or pain scale was 4 ≥ meperidine was prescribed. If symptoms did not control wit in 15 min midazolam was prescribed. Patients were discharged from PACU according Modified Alderet Score. Data were analyzed with ANOVA, Chi-square, and Kruskal-Wallis among four groups. P < 0.05 was considered statistically significant. Results: A total of 140 patients were recruited in the study, which 12 of them were excluded. Thus, 128 patients were randomized and assigned among four groups. The four treatment groups were generally matched at baseline data. Median of pain score in 0, 10, 20 and 30 min after extubation were different between each study group with the control group (<0.001, 0.003 respectively. Also median of agitation score in 0, 10, 20 and 30 min after extubation were different between each study group with the control group (<0.001. Incidence of pain and incidence of agitation after extubation were not statistically identical among groups (P < 0.001 and P = 0

Intravitreal dexamethasone implants for the treatment of refractory scleritis combined with uveitis in adult-onset Still's disease: a case report.

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Ahn, Seong Joon; Hwang, Sun Jin; Lee, Byung Ro

2016-11-08

Adult-onset Still's disease is a systemic inflammatory disease which presents with uveitis and scleritis in the eye. Intravitreal dexamethasone implants are used for the treatment of refractory uveitis. A 19-year-old woman diagnosed to have adult-onset Still's disease for fevers, joint pain, and a salmon-colored bumpy rash presented with scleritis and uveitis in the left eye. Topical and systemic steroids with oral methotrexate failed to control the inflammation. We performed intravitreal injections of dexamethasone implants for side effects of steroid and refractory ocular inflammation. The therapy resulted in improvements in the patient's uveitis with reductions in scleral vessel engorgement and redness. There was no recurrence of uveitis or scleritis during 4 months following treatment. Intravitreal injections of dexamethasone implants may result in clinical improvements of refractory scleritis combined with uveitis.

Vorinostat in combination with lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma

International Nuclear Information System (INIS)

Siegel, D S; Richardson, P; Dimopoulos, M; Moreau, P; Mitsiades, C; Weber, D; Houp, J; Gause, C; Vuocolo, S; Eid, J; Graef, T; Anderson, K C

2014-01-01

The addition of vorinostat to lenalidomide/dexamethasone represents a novel combination therapy in multiple myeloma (MM), informed by laboratory studies suggesting synergy. This was a phase I, multicenter, open-label, non-randomized, dose-escalating study in patients with relapsed or relapsed and refractory MM. Clinical evaluation, electrocardiogram, laboratory studies and adverse events were obtained and assessed. The maximum-tolerated dose was not reached owing to a non-occurrence of two dose-limiting toxicities per six patients tested at any of the dosing levels. Patients tolerated the highest dose tested (Level 5) and this was considered the maximum administered dose: at 400 mg vorinostat on days 1–7 and 15–21, 25 mg lenalidomide on days 1–21 and 40 mg dexamethasone on days 1, 8, 15 and 22, per 28-day cycle. Drug-related adverse events were reported in 90% of patients serious adverse experiences were reported in 45% of the patients and 22% of all patients had adverse experiences considered, possibly related to study drug by the investigators. A confirmed partial response or better was reported for 14/30 patients (47%) evaluable for efficacy, including 31% of patients previously treated with lenalidomide. Vorinostat in combination with lenalidomide and dexamethasone proved tolerable with appropriate supportive care, with encouraging activity observed

A preliminary study of local administration of dexamethasone after tooth extraction: Better preservation of residual alveolar ridge?

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Poštić Srđan D.

2014-01-01

Full Text Available Background/Aim. It is important that the height of the edentulous alveolar ridge after tooth extraction remains at a reasonable acceptable level for as long as possible. The aim of this study was to report preliminary results of the clinical effect of local oral submucous administration of dexamethasone after tooth extractions in order to prepare alveolar supporting tissues for acceptance of removable dentures. Methods. In a total of 15 patients (11 partially and 4 completely edentulous the quantity of 0.25 mL to 0.5 mL of dexamethasone was injected bucally and orally in the region of the tooth socket after complicated extractions. Results. Healing of extraction wounds was uneventful in all the patients, without pain or local inflammation. Conclusion. Dexamethasone can be locally applied to oral tissues to prevent post-extraction inflammation and extensive resorption of the residual alveolar ridge. The obtained results are promising for patients undergoing classic prosthodontic rehabilitation soon after tooth extraction, demonstrating that there are no adverse effects after local oral corticosteroids administration. [Projekat Ministarstva nauke Republike Srbije, br. 175021

Atrial natriuretic peptide: a possible mediator involved in dexamethasone's inhibition of cell proliferation in multiple myeloma.

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Ding, Jiang-Hua; Chang, Yu-Sui

2012-08-01

Atrial natriuretic peptide (ANP) has been recognized for several decades for its role of regulating blood pressure. Recently, cumulating evidences show that ANP plays an anticancer role in various solid tumors via blocking the kinase cascade of Ras-MEK1/2-ERK1/2 with the result of inhibition of DNA synthesis. ANP, as well as its receptors (NPR-A and NPR-C) has been identified present in the embryonic stem cell and a wide range of cancer cells. Various lymphoid organs, such as lymph nodes, have been detected the presence of ANP. Multiple myeloma (MM), though the therapies have evolved significantly, is still an incurable disease as B lymphocyte cell neoplasm. Dexamethasone is the cornerstone in treatment of MM via inactivation of Ras-MEK1/2-ERK1/2 cascade reaction. Coincidently, dexamethasone can increase the expression of ANP markedly. Nevertheless, the role of ANP in MM is unclear. Based on these results above, we raise the hypothesis that ANP is involved in mediating dexamethasone's inhibition of proliferation in MM cells, which suggests that ANP may be a potential agent to treat MM. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Intercellular Communication in Malignant Pleural Mesothelioma: Properties of Tunneling Nanotubes

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Justin William Ady

2014-10-01

Full Text Available Malignant pleural mesothelioma is a particularly aggressive and locally invasive malignancy with a poor prognosis despite advances in understanding of cancer cell biology and development of new therapies. At the cellular level, cultured mesothelioma cells present a mesenchymal appearance and a strong capacity for local cellular invasion. One important but underexplored area of mesothelioma cell biology is intercellular communication. Our group has previously characterized in multiple histological subtypes of mesothelioma a unique cellular protrusion known as tunneling nanotubes (TnTs. TnTs are long, actin filament-based, narrow cytoplasmic extensions that are non-adherent when cultured in vitro and are capable of shuttling cellular cargo between connected cells. Our prior work confirmed the presence of nanotube structures in tumors resected from patients with human mesothelioma. In our current study, we quantified the number of TnTs/cell among various mesothelioma subtypes and normal mesothelial cells using confocal microscopic techniques. We also examined TnT length among adherent cells and cells in suspension. We further examined potential approaches to the in vivo study of TnTs in animal models of cancer. We have developed novel approaches to study TnTs in aggressive solid tumor malignancies and define fundamental characteristics of TnTs in malignant mesothelioma. There is mounting evidence that TnTs play an important role in intercellular communication in mesothelioma and thus merit further investigation of their role in vivo.

Regulation Involved in Colonization of Intercellular Spaces of Host Plants in Ralstonia solanacearum

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Yasufumi Hikichi

2017-06-01

Full Text Available A soil-borne bacterium Ralstonia solanacearum invading plant roots first colonizes the intercellular spaces of the root, and eventually enters xylem vessels, where it replicates at high levels leading to wilting symptoms. After invasion into intercellular spaces, R. solanacearum strain OE1-1 attaches to host cells and expression of the hrp genes encoding components of the type III secretion system (T3SS. OE1-1 then constructs T3SS and secrets effectors into host cells, inducing expression of the host gene encoding phosphatidic acid phosphatase. This leads to suppressing plant innate immunity. Then, OE1-1 grows on host cells, inducing quorum sensing (QS. The QS contributes to regulation of OE1-1 colonization of intercellular spaces including mushroom-type biofilm formation on host cells, leading to its virulence. R. solanacearum strains AW1 and K60 produce methyl 3-hydroxypalmitate (3-OH PAME as a QS signal. The methyltransferase PhcB synthesizes 3-OH PAME. When 3-OH PAME reaches a threshold level, it increases the ability of the histidine kinase PhcS to phosphorylate the response regulator PhcR. This results in elevated levels of functional PhcA, the global virulence regulator. On the other hand, strains OE1-1 and GMI1000 produce methyl 3-hydroxymyristate (3-OH MAME as a QS signal. Among R. solanacearum strains, the deduced PhcB and PhcS amino acid sequences are related to the production of QS signals. R. solanacearum produces aryl-furanone secondary metabolites, ralfuranones, which are extracellularly secreted and required for its virulence, dependent on the QS. Interestingly, ralfuranones affect the QS feedback loop. Taken together, integrated signaling via ralfuranones influences the QS, contributing to pathogen virulence.

The status of intercellular junctions in established lens epithelial cell lines.

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Dave, Alpana; Craig, Jamie E; Sharma, Shiwani

2012-01-01

Cataract is the major cause of vision-related disability worldwide. Mutations in the crystallin genes are the most common known cause of inherited congenital cataract. Mutations in the genes associated with intercellular contacts, such as Nance-Horan Syndrome (NHS) and Ephrin type A receptor-2 (EPHA2), are other recognized causes of congenital cataract. The EPHA2 gene has been also associated with age-related cataract, suggesting that intercellular junctions are important in not only lens development, but also in maintaining lens transparency. The purpose of this study was to analyze the expression and localization of the key cell junction and cytoskeletal proteins, and of NHS and EPHA2, in established lens epithelial cell lines to determine their suitability as model epithelial systems for the functional investigation of genes involved in intercellular contacts and implicated in cataract. The expression and subcellular localization of occludin and zona occludens protein-1 (ZO-1), which are associated with tight junctions; E-cadherin, which is associated with adherence junctions; and the cytoskeletal actin were analyzed in monolayers of a human lens epithelial cell line (SRA 01/04) and a mouse lens epithelial cell line (αTN4). In addition, the expression and subcellular localization of the NHS and EPHA2 proteins were analyzed in these cell lines. Protein or mRNA expression was respectively determined by western blotting or reverse transcription-polymerase chain reaction (RT-PCR), and localization was determined by immunofluorescence labeling. Human SRA 01/04 and mouse αTN4 lens epithelial cells expressed either the proteins of interest or their encoding mRNA. Occludin, ZO-1, and NHS proteins localized to the cellular periphery, whereas E-cadherin, actin, and EPHA2 localized in the cytoplasm in these cell lines. The human SRA 01/04 and mouse αTN4 lens epithelial cells express the key junctional proteins. The localization patterns of these proteins suggest that

Laminin-332 alters connexin profile, dye coupling and intercellular Ca2+ waves in ciliated tracheal epithelial cells

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Olsen Colin E

2006-08-01

Full Text Available Abstract Background Tracheal epithelial cells are anchored to a dynamic basement membrane that contains a variety of extracellular matrix proteins including collagens and laminins. During development, wound repair and disease of the airway epithelium, significant changes in extracellular matrix proteins may directly affect cell migration, differentiation and events mediated by intercellular communication. We hypothesized that alterations in cell matrix, specifically type I collagen and laminin α3β3γ2 (LM-332 proteins within the matrix, directly affect intercellular communication in ciliated rabbit tracheal epithelial cells (RTEC. Methods Functional coupling of RTEC was monitored by microinjection of the negatively charged fluorescent dyes, Lucifer Yellow and Alexa 350, into ciliated RTEC grown on either a LM-332/collagen or collagen matrix. Coupling of physiologically significant molecules was evaluated by the mechanism and extent of propagated intercellular Ca2+ waves. Expression of connexin (Cx mRNA and proteins were assayed by reverse transcriptase – polymerase chain reaction and immunocytochemistry, respectively. Results When compared to RTEC grown on collagen alone, RTEC grown on LM-332/collagen displayed a significant increase in dye transfer. Although mechanical stimulation of RTEC grown on either LM-332/collagen or collagen alone resulted in intercellular Ca2+ waves, the mechanism of transfer was dependent on matrix: RTEC grown on LM-332/collagen propagated Ca2+waves via extracellular purinergic signaling whereas RTEC grown on collagen used gap junctions. Comparison of RTEC grown on collagen or LM-332/collagen matrices revealed a reorganization of Cx26, Cx43 and Cx46 proteins. Conclusion Alterations in airway basement membrane proteins such as LM-332 can induce connexin reorganizations and result in altered cellular communication mechanisms that could contribute to airway tissue function.

Intrinsically disordered proteins aggregate at fungal cell-to-cell channels and regulate intercellular connectivity.

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Lai, Julian; Koh, Chuan Hock; Tjota, Monika; Pieuchot, Laurent; Raman, Vignesh; Chandrababu, Karthik Balakrishna; Yang, Daiwen; Wong, Limsoon; Jedd, Gregory

2012-09-25

Like animals and plants, multicellular fungi possess cell-to-cell channels (septal pores) that allow intercellular communication and transport. Here, using a combination of MS of Woronin body-associated proteins and a bioinformatics approach that identifies related proteins based on composition and character, we identify 17 septal pore-associated (SPA) proteins that localize to the septal pore in rings and pore-centered foci. SPA proteins are not homologous at the primary sequence level but share overall physical properties with intrinsically disordered proteins. Some SPA proteins form aggregates at the septal pore, and in vitro assembly assays suggest aggregation through a nonamyloidal mechanism involving mainly α-helical and disordered structures. SPA loss-of-function phenotypes include excessive septation, septal pore degeneration, and uncontrolled Woronin body activation. Together, our data identify the septal pore as a complex subcellular compartment and focal point for the assembly of unstructured proteins controlling diverse aspects of intercellular connectivity.

INHIBITION OF GAP JUNCTIONAL INTERCELLULAR COMMUNICATION BY PERFLUORINATED COMPOUNDS IN RAT LIVER AND DOLPHIN KIDNEY EPITHELIAL CELL LINES IN VITRO AND SPRAGUE-DAWLEY RATS IN VIVO

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Abstract Gap Junctional Intercellular Communication (GJIC) is the major pathway of intercellular signal transduction, and is, thus, important for normal cell growth and function. Recent studies have revealed a global distribution of some perfluorinated organic compounds e...

Cost-effectiveness of carfilzomib plus dexamethasone compared with bortezomib plus dexamethasone for patients with relapsed or refractory multiple myeloma in the United States.

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Jakubowiak, Andrzej J; Houisse, Ivan; Májer, István; Benedict, Ágnes; Campioni, Marco; Panjabi, Sumeet; Ailawadhi, Sikander

2017-12-01

We assessed the economic value of carfilzomib 56 mg/m 2 and dexamethasone (Kd56) vs. bortezomib and dexamethasone (Vd) for relapsed/refractory multiple myeloma (R/RMM) using ENDEAVOR trial results. Cost-effectiveness of Kd56 vs. Vd was assessed using a partitioned survival model by estimating progression-free survival, overall survival, and direct costs over a lifetime horizon. Surveillance Epidemiology and End Results (SEER) survival data were extrapolated after matching registry and ENDEAVOR patients. Utilities were sourced from the literature and mapped from patient-reported quality of life in ENDEAVOR to estimate quality-adjusted life-years (QALYs) from life-years (LYs). The model predicted an average gain of 1.66 LYs and 1.50 QALYs with Kd56 vs. Vd, and lifetime additional costs of $182,699, resulting in an incremental cost-effectiveness ratio (ICER) of $121,828/QALY gained. The ICER was $114,793/QALY in patients with 1 prior treatment; $99,263/QALY in those not transplanted, and discount in bortezomib price. Kd56 is cost-effective for patients with R/RMM at a willingness-to-pay threshold of $150,000/QALY. Trial data in the model may limit generalizability; however, SEER registry data mitigates this challenge. Kd56 provides additional value in key subgroups, and remains cost-effective after steep comparator discounts.

Lipopolysaccharide-induced inhibition of transcription of tlr4 in vitro is reversed by dexamethasone and correlates with presence of conserved NFκB binding sites

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Bonin, Camila P., E-mail: mila_bonin@yahoo.com.br [Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-900 (Brazil); Baccarin, Raquel Y.A., E-mail: baccarin@usp.br [Department of Clinics, School of Veterinary Medicine, University of São Paulo, São Paulo 05508-900 (Brazil); Nostell, Katarina, E-mail: katarina.nostell@slu.se [Department of Clinical Sciences, Swedish University of Agricultural Sciences, Box 7054, 750 07 Uppsala (Sweden); Nahum, Laila A., E-mail: laila@nahum.com.br [Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte 30190-002 (Brazil); Faculdade Infórium de Tecnologia, Belo Horizonte 30130-180 (Brazil); Fossum, Caroline, E-mail: caroline.fossum@bvf.slu.se [Department of Biomedicine and Veterinary Public Health, Section for Immunology, Swedish University of Agricultural Sciences, BMC, Box 588, SE 751 23 Uppsala (Sweden); Camargo, Maristela M. de, E-mail: mmcamar@usp.br [Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-900 (Brazil)

2013-03-08

Highlights: ► Chimpanzees, horses and humans have regions of similarity on TLR4 and MD2 promoters. ► Rodents have few regions of similarity on TLR4 promoter when compared to primates. ► Conserved NFkB binding sites were found in the promoters of TLR4 and MD2. ► LPS-induced inhibition of TLR4 transcription is reversed by dexamethasone. ► LPS-induced transcription of MD2 is inhibited by dexamethasone. -- Abstract: Engagement of Toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS) is a master trigger of the deleterious effects of septic shock. Horses and humans are considered the most sensitive species to septic shock, but the mechanisms explaining these phenomena remain elusive. Analysis of tlr4 promoters revealed high similarity among LPS-sensitive species (human, chimpanzee, and horse) and low similarity with LPS-resistant species (mouse and rat). Four conserved nuclear factor kappa B (NFκB) binding sites were found in the tlr4 promoter and two in the md2 promoter sequences that are likely to be targets for dexamethasone regulation. In vitro treatment of equine peripheral blood mononuclear cells (eqPBMC) with LPS decreased transcripts of tlr4 and increased transcription of md2 (myeloid differentiation factor 2) and cd14 (cluster of differentiation 14). Treatment with dexamethasone rescued transcription of tlr4 after LPS inhibition. LPS-induced transcription of md2 was inhibited in the presence of dexamethasone. Dexamethasone alone did not affect transcription of tlr4 and md2.

Effects of Dexamethasone and Insulin Alone or in Combination on Energy and Protein Metabolism Indicators and Milk Production in Dairy Cows in Early Lactation - A Randomized Controlled Trial.

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Sami, Mehrdad; Mohri, Mehrdad; Seifi, Hesam A

2015-01-01

This study investigated the effects of dexamethasone and insulin, when administered at 3rd or 10th day of lactation on energy and protein metabolism in dairy cows. Two hundred Holstein cows were enrolled in a randomized controlled clinical trial. The cows were randomly assigned to receive 1 of 4 treatments at 3 or 10 days in milk: control group, 10-mL i.m. injection of sterile water, group insulin, s.c. injection of 100 units of insulin, group dexamethasone, i.m. injection of 20 mg of dexamethasone, group insulin plus dexamethasone, i.m. injection of 20 mg of dexamethasone and 100 units of insulin. The cows randomly assigned to receive the treatments on 3 or 10 days of lactation. Serum samples obtained at the time of enrollment, time of treatment and at 2, 4, 7 and 14 days after intervention. The sera were analyzed for β-hydroxybutyrate (BHBA), nonesterified fatty acids (NEFA), glucose, cholesterol, albumin, urea, and aspartate amino transferase (AST). Data were analyzed using a repeated measures mixed model that accounted for the effects of parity, body condition score, dystocia, retained placenta, metritis and the random effect of cow. There was no significant interaction of group of treatment and time of intervention (day 3 or 10 post-partum) on serum components. Cows that received insulin or dexamethasone alone or in combination, had lower BHBA 2 days after treatment compared with control cows, whereas concentrations of NEFA, were unaffected suggesting that glucocorticoids lipolytic effects do not appear to be important in healthy cows. AST activities significantly reduced in cows that received dexamethasone with or without insulin at 2 and 4 days after treatment. Albumin and urea concentrations 2 days after treatment were higher for cows that received dexamethasone only or dexamethasone plus insulin compared with control and Ins received cows. There were no treatment effects on test-day milk production, milk fat and protein percentages. The results suggested

Effects of awakening and the use of topical dexamethasone and levofloxacin on the cytokine levels in tears following corneal transplantation.

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Fodor, Mariann; Petrovski, Goran; Pásztor, Dorottya; Gogolák, Péter; Rajnavölgyi, Éva; Berta, András

2014-01-01

To study the short-term effect of eye opening and use of topical dexamethasone phosphate 0.1% and levofloxacin 0.5% on the cytokine levels in human tears. Prospective experimental design was used for tear collection from eyes of 10 healthy controls and 20 patients four days after penetrating keratoplasty (PKP) at awakening and after instilling dexamethasone or levofloxacin. The concentrations of different cytokines were measured by cytometric bead array. At eye opening, IL-6 levels were higher in the PKP group as compared to the controls. Thirty minutes later, the released levels of IL-10, IL-13, IL-17, IFNγ, and CCL5 increased in controls, while CXCL8 decreased in both control and PKP groups. The release of the cytokines remained stable after 30 mins except for IFNγ, which showed a decrease in the controls following levofloxacin instillation. No short-term effects of the topically used dexamethasone and levofloxacin could be detected on the cytokine levels in controls and after PKP. Evidence of changes in the levels and time course of tear cytokines after awakening or eye opening could be established and the short-term confounding effects of dexamethasone and levofloxacin on the levels of released cytokines in human tears could be excluded.

Postoperative nausea and vomiting prophylaxis: A comparative study of ondansetron, granisetron and granisetron and dexamethasone combination after modified radical mastectomy

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Pushplata Gupta

2014-01-01

Full Text Available Background: Post-operative nausea and vomiting (PONV is commonly seen after modified radical mastectomy (MRM. In this randomized double-blind prospective study we compared the efficacy of ondansetron, granisetron and granisetron and dexamethasone combination for prevention of PONV following MRM in female patients. Materials and Methods: A total of 75 patients (20-60 years of age undergoing elective MRM were randomly allocated to one of the three groups of 25 patients each. Group O received ondansetron 4 mg, Group G received granisetron 40 mcg/kg and group granisetron and dexamethasone (G + D received granisetron 40 mcg/kg + dexamethasone 8 mg prior to induction. All episodes of PONV within 24 h after induction of anesthesia were recorded. Statistical Analysis: Statistical analysis was done using Kruskal-Wallis test (nonparametric ANOVA. Results: The incidence of complete response (no PONV, no rescue medication was 96% with G+D, as compared with 86% with granisetron and 4% with ondansetron during 0-3h after surgery which was clinically significant (P < 0.05. Similarly clinically significant response was seen during 3-6, 6-9, 9-12 and 12-24 h of surgery. Conclusion: Granisetron and dexamethasone combination is more effective for prevention of PONV in comparison to individual ondansetron and granisetron in MRM.

Pre-emptive 8 mg dexamethasone and 120 mg etoricoxib for pain prevention after periodontal surgery: A randomised controlled clinical trial

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Kranti Konuganti

2015-01-01

Full Text Available Several anti-inflammatory drugs have been used to reduce pain and discomfort after periodontal surgeries. This study evaluates the efficacy of using etoricoxib and dexamethasone for pain prevention after open-flap debridement surgery. In this study, 60 patients who were undergoing open flap debridment surgery were randomly assigned to receive a single dose preoperative medication 1 hour prior to surgery. The patients were divided into three groups. In Group 1, 20 patients were given placebo drug orally. In Group 2, 20 patients were given 8 mg Dexamethasone orally and in Group 3, 20 patients were given 120 mg Etoricoxib orally. Patients were instructed to complete a pain diary hourly for the first 8 hours after each surgery and three times a day on the following 3 days. The four point verbal rating scale (VRS 4 and Numerical rate scale were used to assess discomfort. Post-operative Assessment of Pain and Discomfort showed that persistent discomfort and pain were found to be more in the placebo group compared to dexamethasone and etoricoxib group. The adoption of a preemptive medication protocol using either etoricoxib or dexamethasone may be considered effective for pain and discomfort prevention after open-flap debridement surgeries.

Dexamethasone stimulates expression of C-type Natriuretic Peptide in chondrocytes

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Beier Frank

2006-11-01

Full Text Available Abstract Background Growth of endochondral bones is regulated through the activity of cartilaginous growth plates. Disruption of the physiological patterns of chondrocyte proliferation and differentiation – such as in endocrine disorders or in many different genetic diseases (e.g. chondrodysplasias – generally results in dwarfism and skeletal defects. For example, glucocorticoid administration in children inhibits endochondral bone growth, but the molecular targets of these hormones in chondrocytes remain largely unknown. In contrast, recent studies have shown that C-type Natriuretic Peptide (CNP is an important anabolic regulator of cartilage growth, and loss-of-function mutations in the human CNP receptor gene cause dwarfism. We asked whether glucocorticoids could exert their activities by interfering with the expression of CNP or its downstream signaling components. Methods Primary mouse chondrocytes in monolayer where incubated with the synthetic glucocorticoid Dexamethasone (DEX for 12 to 72 hours. Cell numbers were determined by counting, and real-time PCR was performed to examine regulation of genes in the CNP signaling pathway by DEX. Results We show that DEX does influence expression of key genes in the CNP pathway. Most importantly, DEX significantly increases RNA expression of the gene encoding CNP itself (Nppc. In addition, DEX stimulates expression of Prkg2 (encoding cGMP-dependent protein kinase II and Npr3 (natriuretic peptide decoy receptor genes. Conversely, DEX was found to down-regulate the expression of the gene encoding its receptor, Nr3c1 (glucocorticoid receptor, as well as the Npr2 gene (encoding the CNP receptor. Conclusion Our data suggest that the growth-suppressive activities of DEX are not due to blockade of CNP signaling. This study reveals a novel, unanticipated relationship between glucocorticoid and CNP signaling and provides the first evidence that CNP expression in chondrocytes is regulated by endocrine

Protective effect of lemongrass oil against dexamethasone induced hyperlipidemia in rats: possible role of decreased lecithin cholesterol acetyl transferase activity.

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Kumar, V R Santhosh; Inamdar, Md Naseeruddin; Nayeemunnisa; Viswanatha, G L

2011-08-01

To evaluate the anti-hyperlipidemic activity of lemongrass oil against in dexamethasone induced hyperlipidemia in rats. Administration of dexamethasone was given at 10 mg/kg, sc. to the adult rats for 8 d induces hyperlipidemia characterized by marked increase in serum cholesterol and triglyceride levels along with increase in atherogenic index. Lemongrass oil (100 and 200 mg/kg, po.) treatment has showed significant inhibition against dexamethasone hyperlipidemia by maintaining the serum levels of cholesterol, triglycerides and atherogenic index near to the normal levels and the antihyperlipidemic effect of the lemongross oil was comparable with atorvastatin 10 mg/kg, po. The possible mechanism may be associated with decrease in lecithin cholesterol acetyl transferase (LCAT) activity. These results suggested that Lemon gross oil possess significant anti-hyperlipidemic activity. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Intercellular K⁺ accumulation depolarizes Type I vestibular hair cells and their associated afferent nerve calyx.

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Contini, D; Zampini, V; Tavazzani, E; Magistretti, J; Russo, G; Prigioni, I; Masetto, S

2012-12-27

Mammalian vestibular organs contain two types of sensory receptors, named Type I and Type II hair cells. While Type II hair cells are contacted by several small afferent nerve terminals, the basolateral surface of Type I hair cells is almost entirely enveloped by a single large afferent nerve terminal, called calyx. Moreover Type I, but not Type II hair cells, express a low-voltage-activated outward K(+) current, I(K,L), which is responsible for their much lower input resistance (Rm) at rest as compared to Type II hair cells. The functional meaning of I(K,L) and associated calyx is still enigmatic. By combining the patch-clamp whole-cell technique with the mouse whole crista preparation, we have recorded the current- and voltage responses of in situ hair cells. Outward K(+) current activation resulted in K(+) accumulation around Type I hair cells, since it induced a rightward shift of the K(+) reversal potential the magnitude of which depended on the amplitude and duration of K(+) current flow. Since this phenomenon was never observed for Type II hair cells, we ascribed it to the presence of a residual calyx limiting K(+) efflux from the synaptic cleft. Intercellular K(+) accumulation added a slow (τ>100ms) depolarizing component to the cell voltage response. In a few cases we were able to record from the calyx and found evidence for intercellular K(+) accumulation as well. The resulting depolarization could trigger a discharge of action potentials in the afferent nerve fiber. Present results support a model where pre- and postsynaptic depolarization produced by intercellular K(+) accumulation cooperates with neurotransmitter exocytosis in sustaining afferent transmission arising from Type I hair cells. While vesicular transmission together with the low Rm of Type I hair cells appears best suited for signaling fast head movements, depolarization produced by intercellular K(+) accumulation could enhance signal transmission during slow head movements. Copyright �

Ondansetron, granisetron, and dexamethasone compared for the prevention of postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy : A randomized placebo-controlled study.

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Erhan, Yamac; Erhan, Elvan; Aydede, Hasan; Yumus, Okan; Yentur, Alp

2008-06-01

Laparoscopic cholecystectomies are associated with an appreciably high rate of postoperative nausea and vomiting (PONV). This study was designed to compare the effectiveness of ondansetron, granisetron, and dexamethasone for the prevention of PONV in patients after laparoscopic cholecystectomy. A total of 80 American Society of Anesthesiologists (ASA) physical class I-II patients scheduled for laparoscopic cholecystectomy were included in this randomized, double blind, placebo-controlled study. All patients received a similar standardized anesthesia and operative treatment. Patients were randomly divided into four groups (n = 20 each). Group 1, consisting of control patients, received 0.9% NaCl; group 2 patients received ondansetron 4 mg i.v.; group 3 patients received granisetron 3 mg i.v.; and group 4 patients received dexamethasone 8 mg i.v., all before the induction of anesthesia. Both nausea and vomiting were assessed during the first 24 h after the procedure. The total incidence of PONV was 75% with placebo, 35% with ondansetron, 30% with granisetron, and 25% with dexamethasone. The incidence of PONV was significantly less frequent in groups receiving antiemetics (p granisetron, and ondansetron were not significant. Prophylactic dexamethasone 8 mg i.v. significantly reduced the incidence of PONV in patients undergoing laparoscopic cholecystectomy. Dexamethasone 8 mg was as effective as ondansetron 4 mg and granisetron 3 mg, and it was more effective than placebo.

Grain dust induces IL-8 production from bronchial epithelial cells: the effect of dexamethasone on IL-8 production.

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Park, H S; Suh, J H; Kim, H Y; Kwon, O J; Choi, D C

1999-04-01

Recent publications have suggested an active participation of neutrophils to induce bronchoconstriction after inhalation of grain dust (GD). To further understand the role of neutrophils in the pathogenesis of GD-induced asthma, this investigation was designed to determine whether human bronchial epithelial cells could produce IL-8 production and to observe the effect of dexamethasone on IL-8 production. We cultured Beas-2B, a bronchial epithelial cell line. To observe GD-induced responses, four concentrations (1 to 200 microg/mL) of GD were incubated for 24 hours and compared with those without incubation of GD. To evaluate the effect of pro-inflammatory cytokines on IL-8 production, epithelial cells were incubated with peripheral blood mononuclear cell (PBMC) culture supernatant, which was derived from the culture of PBMC from a GD-induced asthmatic subject under the exposure to 10 microg/mL of GD, and compared with those cultured without addition of PBMC supernatant. The level of released IL-8 in the supernatant was measured by enzyme-linked immunosorbent assay. To evaluate the effect of dexamethasone on IL-8 production, four concentrations (5 to 5000 ng/mL) of dexamethasone were pre-incubated for 24 hours and the same experiments were repeated. There was significant production of IL-8 from bronchial epithelial cells with additions of GD in a dose-dependent manner (P < .05), which was significantly augmented with additions of PBMC supernatant (P < .05) at each concentration. Compared with the untreated sample, pretreatment of dexamethasone could induced a remarkable inhibitions (15% to 55%) of IL-8 production from bronchial epithelial cells in a dose-dependent manner. These results suggest that IL-8 production from bronchial epithelial cells may contribute to neutrophil recruitment occurring in GD-induced airway inflammation. The downregulation of IL-8 production by dexamethasone from bronchial epithelial cells may contribute to the efficacy of this compound in

Dexamethasone Modifies Cystatin C-Based Diagnosis of Acute Kidney Injury During Cisplatin-Based Chemotherapy

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Timothy J. Pianta

2017-03-01

Full Text Available Background/Aims: Plasma cystatin C (pCysC may be superior to serum creatinine (sCr as a surrogate of GFR. However, the performance of pCysC for diagnosing acute kidney injury (AKI after cisplatin-based chemotherapy is potentially affected by accompanying corticosteroid anti-emetic therapy and hydration. Methods: In a prospective observational study pCysC, sCr, urinary kidney injury molecule-1 (KIM-1, and urinary clusterin were measured over 2 weeks in 27 patients given first-cycle chemotherapy. The same variables were measured over 2 weeks in Sprague–Dawley rats given a single intraperitoneal injection of dexamethasone, cisplatin, or both, and in controls. Results: In patients, pCysC increases were greater than sCr 41% vs. 16%, mean paired difference 25% (95% CI: 16–34%], relative increases were ≥ 50% in 9 patients (35% for pCysC compared with 2 (8% for sCr (p = 0.04 and increases in sCr were accompanied by increased KIM-1 and clusterin excretion, but increases in pCysC alone were not. In rats, dexamethasone administration produced dose-dependent increases in pCysC (and augmented cisplatin-induced increases in pCysC, but did not augment histological injury, increases in sCr, or KIM-1 and clusterin excretion. Conclusions: In the presence of dexamethasone, elevation of pCysC does not reliably diagnose AKI after cisplatin-based chemotherapy.

Differential response to dexamethasone on the TXB2 release in guinea-pig alveolar macrophages induced by zymosan and cytokines

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M. E. Salgueiro

1997-01-01

Full Text Available Glucocorticosteroids reduce the production of inflammatory mediators but this effect may depend on the stimulus. We have compared the time course of the effect of dexamethasone on the thromboxane B2 (TXB2 release induced by cytokine stimulation and zymosan in guinea-pig alveolar macrophages. Interleukin-1β (IL-1β, tumour necrosis factor-α (TNF-α and opsonized zymosan (OZ, all stimulate TXB2 release. High concentrations of dexamethasone (1–10 μM inhibit the TXB2 production induced by both cytokines and OZ, but the time course of this response is different. Four hours of incubation with dexamethasone reduce the basal TXB2 release and that induced by IL-1β and TNF-α, but do not modify the TXB2 release induced by OZ. However, this stimulus was reduced after 24 h incubation. Our results suggest that the antiinflammatory activity of glucocorticosteroids shows some dependence on stimulus and, therefore, may have more than one mechanism involved.

Compression induced intercellular shaping for some geometric cellular lattices

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Adonai Gimenez Calbo

2001-03-01

Full Text Available The wall perimeter fraction, which contact neighboring cells, was named compression ratio (alpha. A zero compression ratio indicates maximum intercellular (air volume (vG, v/v and neglectable contact among cells, while alpha=1 indicates complete adherence between neighboring cells and no vG in the lattice. The maximum intercellular air volume (beta, v/v, when alpha=0, was 0.593 for triangular, 0.2146 for square and 0,0931 for hexagonal lattices. The equation alpha=1- (vG/beta½ was derived to relate alpha, beta and vG in the studied lattices. The relation (P S=p/alpha between cell turgor (P S and the tissue aggregating pressure (p, defined as the compression to keep in place a layer of cells, was demonstrated using the compression ratio concept. Intercellular deformations of Ipomea batatas L. roots obtained with pressure chamber were used to test alpha, vG, p and P S as a function of compression. Volumetric and transversal elastic extensibilities and the lamella media tearing forces were obtained and alpha constancy was considered as a criteria of cellular shape stability.A fração do perímetro da parede celular em contato com células vizinha foi denominada razão de compressão (alfa. Razão de compressão zero indica volume intercelular (vG, v/v máximo e contato neglível entre as células, enquanto alfa=1 ocorre quando há completa aderência com as células vizinhas (vG=0. O volume (gasoso intercelular máximo (beta, v/v, quando alfa=0, foi 0,593, 0,2146 e 0,0931 para látices triangulares, quadradas e hexagonais. A equação derivada para relacionar alfa, beta and vG nas látices estudadas foi alfa=1- (vG/beta½. A razão de compressão foi em seguida empregada para estabelecer a relação P S=p/alfa entre a pressão de turgescência (P S e a pressão de agregação (p, definida com a compressão para manter uma camada de células no seu lugar. As deformações intercelulares de batata-doce obtidas com procedimentos de c

Markedly diminished epidermal keratinocyte expression of intercellular adhesion molecule-1 (ICAM-1) in Sezary syndrome

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Nickoloff, B.J.; Griffiths, E.M.; Baadsgaard, O.; Voorhees, J.J.; Hanson, C.A.; Cooper, K.D. (Univ. of Michigan Medical Center, Ann Arbor (USA))

1989-04-21

In mucosis fungoides the malignant T cells express lymphocyte function-associated antigen-1, which allows them to bind to epidermal keratinocytes expressing the gamma interferon-inducible intercellular adhesion molecule-1. In this report, a patient with leukemic-stage mucosis fungoides (Sezary syndrome) had widespread erythematous dermal infiltrates containing malignant T cells, but without any epidermotropism. The authors discovered that the T cells expressed normal amounts of functional lymphocyte function-associated antigen-1, but the keratinocytes did not express significant levels of intercellular adhesion molecule-1, which was probably due to the inability of the malignant T cells to produce gamma interferon. These results support the concept that the inability of malignant T cells to enter the epidermis may contribute to emergence of more clinically aggressive T-cell clones that are no longer confined to the skin, but infiltrate the blood, lymph nodes, and viscera, as is seen in Sezary syndrome.

Revisiting the Dexamethasone Suppression Test in unipolar major depression: an exploratory study

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Rihmer Zoltan

2008-11-01

Full Text Available Abstract Background Important methodological questions still exist concerning the Dexamethasone Suppression Test (DST, including the possibility of a better way of interpreting it. The aim of the present study was to explore the feasibility of an alternative way of interpreting DST results. Methods A total of 50 patients with major depression aged 41.0 ± 11.4 years old participated in the study. Past and present suicide attempts were recorded. Psychometric assessment included the Hamilton Depression Rating Scale (HDRS, the Hamilton Anxiety Scale (HAS, the Newcastle Depression Diagnostic Scale (NDDS, the Diagnostic Melancholia Scale (DMS and the General Assessment of Functioning (GAF scale. The 1 mg DST protocol was used. Analysis methods included the chi square test and analysis of covariance (ANCOVA with Fisher least significant difference (LSD as post hoc tests. Results In all, 34 patients (68% were suppressors, 16 (32% were non-suppressors and 14 patients had cortisol values above 5 μg/dl at baseline. Baseline cortisol level did not influence the classical DST interpretation. A total of 18 patients (36% showed an increase of their cortisol levels after dexamethasone administration and 32 patients (64% showed a decrease. Reducers had less melancholic features, similar levels of depression, better sleep and less suicidal thoughts in comparison to increasers. No relationship of DST to suicidality was found. Discussion The present study explored the pattern of cortisol response to dexamethasone suppression and suggested an alternative way of coding and interpreting the DST on the basis of whether the cortisol levels remain stable or increase vs decrease after the administration of cortisol. The results put forward a complex way of understanding the relationship of the DST results with clinical symptoms.

Dexamethasone palmitate ameliorates macrophages-rich graft-versus-host disease by inhibiting macrophage functions.

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Nishiwaki, Satoshi; Nakayama, Takayuki; Murata, Makoto; Nishida, Tetsuya; Terakura, Seitaro; Saito, Shigeki; Kato, Tomonori; Mizuno, Hiroki; Imahashi, Nobuhiko; Seto, Aika; Ozawa, Yukiyasu; Miyamura, Koichi; Ito, Masafumi; Takeshita, Kyosuke; Kato, Hidefumi; Toyokuni, Shinya; Nagao, Keisuke; Ueda, Ryuzo; Naoe, Tomoki

2014-01-01

Macrophage infiltration of skin GVHD lesions correlates directly with disease severity, but the mechanisms underlying this relationship remain unclear and GVHD with many macrophages is a therapeutic challenge. Here, we characterize the macrophages involved in GVHD and report that dexamethasone palmitate (DP), a liposteroid, can ameliorate such GVHD by inhibiting macrophage functions. We found that host-derived macrophages could exacerbate GVHD in a mouse model through expression of higher levels of pro-inflammatory TNF-α and IFN-γ, and lower levels of anti-inflammatory IL-10 than resident macrophages in mice without GVHD. DP significantly decreased the viability and migration capacity of primary mouse macrophages compared to conventional dexamethasone in vitro. DP treatment on day 7 and day 14 decreased macrophage number, and attenuated GVHD score and subsequent mortality in a murine model. This is the first study to provide evidence that therapy for GVHD should be changed on the basis of infiltrating cell type.

Influence of Dexamethasone on Some Reproductive Hormones and Uterine Progesterone Receptor Localization in Pregnant Yankasa Sheep in Semiarid Zones of Nigeria

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Yahi, Dauda; Ojo, Nicholas Adetayo; Mshelia, Gideon Dauda

2017-01-01

Dexamethasone is widely used in both veterinary and human medical practices. However, it seems to cause some deleterious effects on pregnancy probably by causing changes in the reproductive hormone levels and their corresponding receptor concentrations. This study investigated the effects of dexamethasone on these parameters. Twenty healthy adult Yankasa sheep comprising 18 ewes and 2 rams were used for this study. Pregnancies were achieved by natural mating after estrus synchronization. Dexa...

Exploring the role of lipids in intercellular conduits: breakthroughs in the pipeline

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Elise eDelage

2013-12-01

Full Text Available It has been known for more than a century that most of the plant cells are connected to their neighbors through membranous pores perforating the cell wall, namely plasmodesmata (PDs. The recent discovery of tunneling nanotubes (TNTs, thin membrane bridges established between distant mammalian cells, suggests that intercellular communication mediated through cytoplasmic continuity could be a conserved feature of eukaryotic organisms. Although TNTs differ from PDs in their formation and architecture, both are characterized by a continuity of the plasma membrane between two cells, delimiting a nanotubular channel supported by actin-based cytoskeleton. Due to this unusual membrane organization, lipids are likely to play critical roles in the formation and stability of intercellular conduits like TNTs and PDs, but also in regulating the transfer through these structures. While it is crucial for a better understanding of those fascinating communication highways, the study of TNT lipid composition and dynamics turned out to be extremely challenging. The present review aims to give an overview of the recent findings in this context. We will also discuss some of the promising imaging approaches, which might be the key for future breakthroughs in the field and could also benefit the research on PDs.

Effects of antenatal corticosteroids on maternal serum indicators of infection in women at risk for preterm delivery: A randomized trial comparing betamethasone and dexamethasone

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Azar Danesh

2012-01-01

Full Text Available Objective: To compare the effect of betamethasone and dexamethasone on maternal white blood cell (WBC and differential count, erythrocyte sedimentation rate (ESR, Apgar score, maternal and fetal plasma glucose and length of admission to delivery, gestational age at delivery in women at risk of preterm labor (PTL. Study Design: Two hundred and forty pregnant women at risk for PTL with intact membranes or preterm premature rupture of the membranes (PPROM were randomly allocated to receive either two intramuscular injections of 12 mg betamethasone at 24-h intervals or 4 injections of 6 mg dexamethasone at 12-h intervals. Blood tests for WBC and differential count, ESR and fasting plasma glucose were drawn before betamethasone or dexamethasone injection and after injection every 24 h for two days. Pregnancy outcome was assessed as Apgar score, fetal plasma glucose and length of gestation. Result : In the preterm delivery group with intact membranes, no significant differences were found between the two groups in the maternal serum indicators of infection. The mean gestational age at delivery, 1- and 5-min Apgar score were higher in the dexamethasone group than in the betamethasone group. In the PPROM group, a significant rise in WBC count was occurred (12.4 cells/mm 3 vs. 10.5 cells/mm 3 , P < 0.001, none of the other maternal serum indicators of infection and outcome variables showed significant differences between the dexamethasone and betamethasone groups. Conclusions : Dexamethasone compared to betamethasone significantly increased WBC count in women with PPROM, but in women at risk of PTL with intact membranes none of the maternal serum indicators of infection showed significant differences.

The Effect of Ketamine and Dexamethasone in Combination with Lidocaine on the Onset and Duration of Axillary Block in Hand and Forearm Soft Tissue Surgery.

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Zaman, Behrooz; Hojjati Ashrafi, Siavash; Seyed Siamdoust, Seyedalireza; Hassani, Valiollah; Mohamad Taheri, Siavash; Noorizad, Samad

2017-10-01

Using peripheral nerve block compared to general anesthesia has gained more popularity due to reduced postoperative pain, less need for post-surgery analgesic drugs, reduced incidence of nausea, shortness of PACU time, and increased patient satisfaction. The aim of this study was to compare the effect of ketamine and dexamethasone as additives to lidocaine on duration and onset of axillary block action. In this clinical trial, all patients who referred to Hazrat-e-Fatemeh hospital for forearm and hand soft tissue surgery with informed consent were randomly divided into three groups in order to examine the onset and duration of axillary block: lidocaine + ketamine, lidocaine + dexamethasone in axillary block, and lidocaine alone (control). Then, the onset and duration of sensory and motor blocks were measured and recorded every three minutes and after the surgery. Quantitative and qualitative variables were analyzed using ANOVA or Kruskal-Wallis test and Chi-square or Fisher exact test in SPSS v.22. Duration of sensory and motor block axillary was significantly higher in lidocaine + dexamethasone group than in lidocaine + ketamine group (P block axillary between the three groups (P > 0.05). According to the results of our study, we can conclude that adding dexamethasone or ketamine to lidocaine could improve duration of sensory and motor axillary block in patients undergoing forearm and hand soft tissue surgery. However, dexamethasone had the highest effect on duration of block axillary. We proved that dexamethasone or ketamine added to lidocaine had no effect on the onset of block axillary.

On the influence of dexamethason-21-iso-nicotinate on histamine blood level in horses with reference to the facultative occurrence of laminitis

International Nuclear Information System (INIS)

Rautschka, R.

1987-10-01

In some cases laminitis may result as a consequence of corticoid therapy in horses. It was the aim of this investigation to prove, if there is a connection between therapeutic doses of a corticoid (dexamethasone-21-iso-nicotinate) and the liberation of histamine into the equine plasma. 40 veterinarians reported 23 cases of laminitis after treating the horses with various corticoids. To determine histamine levels in equine plasma, a method used in human medicine (Faraj, 1984) was adapted accordingly. The principle of this method consists of enzymatic coupling of a tritium-labelled methyl group to the histamine contained in plasma. From the investigation the conclusion could be drawn, that it was not possible to induce liberation of histamine into equine plasma by therapeutic doses of dexamethasone-21-iso-nicotinate. Finally, plasma levels of three horses, suffering from chronical obstructive pulmonary disease (COPD) treated therapeutically with dexamethasone-21-iso-nicotinate, were determined. Conclusively a connection between the i.m. application of dexamethasone-21-iso-nicotinate and an inducement of histamine liberation into equine plasma could not be proven. 226 refs., 11 figs., 12 tabs. (G.Q.)

Antenatal dexamethasone after asphyxia increases neural injury in preterm fetal sheep.

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Miriam E Koome

Full Text Available BACKGROUND AND PURPOSE: Maternal glucocorticoid treatment for threatened premature delivery dramatically improves neonatal survival and short-term morbidity; however, its effects on neurodevelopmental outcome are variable. We investigated the effect of maternal glucocorticoid exposure after acute asphyxia on injury in the preterm brain. METHODS: Chronically instrumented singleton fetal sheep at 0.7 of gestation received asphyxia induced by complete umbilical cord occlusion for 25 minutes. 15 minutes after release of occlusion, ewes received a 3 ml i.m. injection of either dexamethasone (12 mg, n = 10 or saline (n = 10. Sheep were killed after 7 days recovery; survival of neurons in the hippocampus and basal ganglia, and oligodendrocytes in periventricular white matter were assessed using an unbiased stereological approach. RESULTS: Maternal dexamethasone after asphyxia was associated with more severe loss of neurons in the hippocampus (CA3 regions, 290 ± 76 vs 484 ± 98 neurons/mm(2, mean ± SEM, P<0.05 and basal ganglia (putamen, 538 ± 112 vs 814 ± 34 neurons/mm(2, P<0.05 compared to asphyxia-saline, and with greater loss of both total (913 ± 77 vs 1201 ± 75/mm(2, P<0.05 and immature/mature myelinating oligodendrocytes in periventricular white matter (66 ± 8 vs 114 ± 12/mm(2, P<0.05, vs sham controls 165 ± 10/mm(2, P<0.001. This was associated with transient hyperglycemia (peak 3.5 ± 0.2 vs. 1.4 ± 0.2 mmol/L at 6 h, P<0.05 and reduced suppression of EEG power in the first 24 h after occlusion (maximum -1.5 ± 1.2 dB vs. -5.0 ± 1.4 dB in saline controls, P<0.01, but later onset and fewer overt seizures. CONCLUSIONS: In preterm fetal sheep, exposure to maternal dexamethasone during recovery from asphyxia exacerbated brain damage.

In vivo effects of dexamethasone and indomethacin on neutrophil-induced alterations of nasal epithelial mucosubstances

Energy Technology Data Exchange (ETDEWEB)

Hotchkiss, J A; Portereiko, J V; Harkema, J R

1988-12-01

Previous studies have shown that neutrophils migrating through rat nasal mucosal epithelium, in response to intranasal instillation of endotoxin, induce a transient decrease in stored epithelial mucosubstances. Prostaglandins and leukotrienes can either increase or decrease mucous secretion of airway epithelia in vitro. In this study, rats were treated with indomethacin a specific inhibitor of prostaglandin synthesis, or with dexamethasone, a general inhibitor of arachidonic acid metabolism, and challenged with intranasally instilled endotoxin. Dexamethasone alone or in combination with indomethacin, but not indomethacin alone, significantly altered the neutrophil response to intranasally instilled endotoxin and may have inhibited the neutrophil-induced decrease in stored mucosubstances. These data suggest that leukotrienes and possibly prostaglandins play a significant role in the coordinated response of the nasal mucosal epitholium to an acute inflammatory stimulus. (author)

In vivo effects of dexamethasone and indomethacin on neutrophil-induced alterations of nasal epithelial mucosubstances

International Nuclear Information System (INIS)

Hotchkiss, J.A.; Portereiko, J.V.; Harkema, J.R.

1988-01-01

Previous studies have shown that neutrophils migrating through rat nasal mucosal epithelium, in response to intranasal instillation of endotoxin, induce a transient decrease in stored epithelial mucosubstances. Prostaglandins and leukotrienes can either increase or decrease mucous secretion of airway epithelia in vitro. In this study, rats were treated with indomethacin a specific inhibitor of prostaglandin synthesis, or with dexamethasone, a general inhibitor of arachidonic acid metabolism, and challenged with intranasally instilled endotoxin. Dexamethasone alone or in combination with indomethacin, but not indomethacin alone, significantly altered the neutrophil response to intranasally instilled endotoxin and may have inhibited the neutrophil-induced decrease in stored mucosubstances. These data suggest that leukotrienes and possibly prostaglandins play a significant role in the coordinated response of the nasal mucosal epitholium to an acute inflammatory stimulus. (author)

Electrotonic potentials in Aloe vera L.: Effects of intercellular and external electrodes arrangement.

Science.gov (United States)

Volkov, Alexander G; Nyasani, Eunice K; Tuckett, Clayton; Scott, Jessenia M; Jackson, Mariah M Z; Greeman, Esther A; Greenidge, Ariane S; Cohen, Devin O; Volkova, Maia I; Shtessel, Yuri B

2017-02-01

Electrostimulation of plants can induce plant movements, activation of ion channels, ion transport, gene expression, enzymatic systems activation, electrical signaling, plant-cell damage, enhanced wound healing, and influence plant growth. Here we found that electrical networks in plant tissues have electrical differentiators. The amplitude of electrical responses decreases along a leaf and increases by decreasing the distance between polarizing Pt-electrodes. Intercellular Ag/AgCl electrodes inserted in a leaf and extracellular Ag/AgCl electrodes attached to the leaf surface were used to detect the electrotonic potential propagation along a leaf of Aloe vera. There is a difference in duration and amplitude of electrical potentials measured by electrodes inserted in a leaf and those attached to a leaf's surface. If the external reference electrode is located in the soil near the root, it changes the amplitude and duration of electrotonic potentials due to existence of additional resistance, capacitance, ion channels and ion pumps in the root. The information gained from this study can be used to elucidate extracellular and intercellular communication in the form of electrical signals within plants. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of Dexamethasone and Insulin Alone or in Combination on Energy and Protein Metabolism Indicators and Milk Production in Dairy Cows in Early Lactation - A Randomized Controlled Trial.

Directory of Open Access Journals (Sweden)

Mehrdad Sami

Full Text Available This study investigated the effects of dexamethasone and insulin, when administered at 3rd or 10th day of lactation on energy and protein metabolism in dairy cows.Two hundred Holstein cows were enrolled in a randomized controlled clinical trial. The cows were randomly assigned to receive 1 of 4 treatments at 3 or 10 days in milk: control group, 10-mL i.m. injection of sterile water, group insulin, s.c. injection of 100 units of insulin, group dexamethasone, i.m. injection of 20 mg of dexamethasone, group insulin plus dexamethasone, i.m. injection of 20 mg of dexamethasone and 100 units of insulin. The cows randomly assigned to receive the treatments on 3 or 10 days of lactation. Serum samples obtained at the time of enrollment, time of treatment and at 2, 4, 7 and 14 days after intervention. The sera were analyzed for β-hydroxybutyrate (BHBA, nonesterified fatty acids (NEFA, glucose, cholesterol, albumin, urea, and aspartate amino transferase (AST. Data were analyzed using a repeated measures mixed model that accounted for the effects of parity, body condition score, dystocia, retained placenta, metritis and the random effect of cow.There was no significant interaction of group of treatment and time of intervention (day 3 or 10 post-partum on serum components. Cows that received insulin or dexamethasone alone or in combination, had lower BHBA 2 days after treatment compared with control cows, whereas concentrations of NEFA, were unaffected suggesting that glucocorticoids lipolytic effects do not appear to be important in healthy cows. AST activities significantly reduced in cows that received dexamethasone with or without insulin at 2 and 4 days after treatment. Albumin and urea concentrations 2 days after treatment were higher for cows that received dexamethasone only or dexamethasone plus insulin compared with control and Ins received cows. There were no treatment effects on test-day milk production, milk fat and protein percentages

Intercellular Ca2+ Waves: Mechanisms and Function

Science.gov (United States)

Sanderson, Michael J.

2012-01-01

Intercellular calcium (Ca2+) waves (ICWs) represent the propagation of increases in intracellular Ca2+ through a syncytium of cells and appear to be a fundamental mechanism for coordinating multicellular responses. ICWs occur in a wide diversity of cells and have been extensively studied in vitro. More recent studies focus on ICWs in vivo. ICWs are triggered by a variety of stimuli and involve the release of Ca2+ from internal stores. The propagation of ICWs predominately involves cell communication with internal messengers moving via gap junctions or extracellular messengers mediating paracrine signaling. ICWs appear to be important in both normal physiology as well as pathophysiological processes in a variety of organs and tissues including brain, liver, retina, cochlea, and vascular tissue. We review here the mechanisms of initiation and propagation of ICWs, the key intra- and extracellular messengers (inositol 1,4,5-trisphosphate and ATP) mediating ICWs, and the proposed physiological functions of ICWs. PMID:22811430

Mobile Transcripts and Intercellular Communication in Plants.

Science.gov (United States)

Saplaoura, E; Kragler, F

2016-01-01

Phloem serves as a highway for mobile signals in plants. Apart from sugars and hormones, proteins and RNAs are transported via the phloem and contribute to the intercellular communication coordinating growth and development. Different classes of RNAs have been found mobile and in the phloem exudate such as viral RNAs, small interfering RNAs (siRNAs), microRNAs, transfer RNAs, and messenger RNAs (mRNAs). Their transport is considered to be mediated via ribonucleoprotein complexes formed between phloem RNA-binding proteins and mobile RNA molecules. Recent advances in the analysis of the mobile transcriptome indicate that thousands of transcripts move along the plant axis. Although potential RNA mobility motifs were identified, research is still in progress on the factors triggering siRNA and mRNA mobility. In this review, we discuss the approaches used to identify putative mobile mRNAs, the transport mechanism, and the significance of mRNA trafficking. © 2016 Elsevier Inc. All rights reserved.

Disruption of tumor neovasculature by microbubble enhanced ultrasound: a potential new physical therapy of anti-angiogenesis.

Science.gov (United States)

Liu, Zheng; Gao, Shunji; Zhao, Yang; Li, Peijing; Liu, Jia; Li, Peng; Tan, Kaibin; Xie, Feng

2012-02-01

Tumor angiogenesis is of vital importance to the growth and metastasis of solid tumors. The angiogenesis is featured with a defective, leaky and fragile vascular construction. Microbubble enhanced ultrasound (MEUS) cavitation is capable of mechanical disruption of small blood vessels depending on effective acoustic pressure amplitude. We hypothesized that acoustic cavitation combining high-pressure amplitude pulsed ultrasound (US) and circulating microbubble could potentially disrupt tumor vasculature. A high-pressure amplitude, pulsed ultrasound device was developed to induce inertial cavitation of circulating microbubbles. The tumor vasculature of rat Walker 256 was insonated percutaneously with two acoustic pressures, 2.6 MPa and 4.8 MPa, both with intravenous injection of a lipid microbubble. The controls were treated by the ultrasound only or sham ultrasound exposure. Contrast enhanced ultrasound (CEUS) and histology were performed to assess tumor circulation and pathological changes. The CEUS results showed that the circulation of Walker 256 tumors could be completely blocked off for 24 hours in 4.8 MPa treated tumors. The CEUS gray scale value (GSV) indicated that there was significant GSV drop-off in both of the two experimental groups but none in the controls. Histology showed that the tumor microvasculature was disrupted into diffuse hematomas accompanied by thrombosis, intercellular edema and multiple cysts formation. The 24 hours of tumor circulation blockage resulted in massive necrosis of the tumor. MEUS provides a new, simple physical method for anti-angiogenic therapy and may have great potential for clinical applications. Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Effects of dexamethasone and insulin on the synthesis of triacylglycerols and phosphatidylcholine and the secretion of very-low-density lipoproteins and lysophosphatidylcholine by monolayer cultures of rat hepatocytes.

OpenAIRE

Mangiapane, E H; Brindley, D N

1986-01-01

Rat hepatocytes in monolayer culture were preincubated for 19 h with 1 microM-dexamethasone, and the incubation was continued for a further 23 h with [14C]oleate, [3H]glycerol and 1 microM-dexamethasone. Dexamethasone increased the secretion of triacylglycerol into the medium in particles that had the properties of very-low-density lipoproteins. The increased secretion was matched by a decrease in the triacylglycerol and phosphatidylcholine that remained in the hepatocytes. Preincubating the ...

Tunneling Nanotubes and Gap Junctions–Their Role in Long-Range Intercellular Communication during Development, Health, and Disease Conditions

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Jennifer Ariazi

2017-10-01

Full Text Available Cell-to-cell communication is essential for the organization, coordination, and development of cellular networks and multi-cellular systems. Intercellular communication is mediated by soluble factors (including growth factors, neurotransmitters, and cytokines/chemokines, gap junctions, exosomes and recently described tunneling nanotubes (TNTs. It is unknown whether a combination of these communication mechanisms such as TNTs and gap junctions may be important, but further research is required. TNTs are long cytoplasmic bridges that enable long-range, directed communication between connected cells. The proposed functions of TNTs are diverse and not well understood but have been shown to include the cell-to-cell transfer of vesicles, organelles, electrical stimuli and small molecules. However, the exact role of TNTs and gap junctions for intercellular communication and their impact on disease is still uncertain and thus, the subject of much debate. The combined data from numerous laboratories indicate that some TNT mediate a long-range gap junctional communication to coordinate metabolism and signaling, in relation to infectious, genetic, metabolic, cancer, and age-related diseases. This review aims to describe the current knowledge, challenges and future perspectives to characterize and explore this new intercellular communication system and to design TNT-based therapeutic strategies.

Peptic ulcer disease and other complications in patients receiving dexamethasone palliation for brain metastasis

International Nuclear Information System (INIS)

Penzner, R.D.; Lipsett, J.A.

1982-01-01

A retrospective analysis was done of 106 patients who received radiation therapy for brain metastasis. Dexamethasone therapy was instituted in 97 patients. Peptic ulcer disease developed in 5 of 89 patients (5.6 percent) who received a dosage of at least 12 mg a day, but did not occur in patients who received a lower dose or in those who did not receive steroids. The interval between institution of dexamethasone therapy and the development of peptic ulcer disease ranged from three to nine weeks. Two patients had perforated ulcers, one of whom required surgical resection. Peptic ulcer disease contributed to the general deterioration and death of three of the five patients. Overall, in 14 of the 89 patients (15.7 percent) a complication of steroid therapy developed in the form of peptic ulcer disease, steroid myopathy or diabetes mellitus (or a combination of these)

Subdural infusion of dexamethasone inhibits leukomyelitis after acute spinal cord injury in a rat model

Czech Academy of Sciences Publication Activity Database

Kwiecien, J. M.; Jarocz, B.; Urdzíková, Lucia; Rola, R.; Dabrowski, W.

2015-01-01

Roč. 53, č. 1 (2015), s. 41-51 ISSN 1641-4640 Institutional support: RVO:68378041 Keywords : spinal cord injury * leukomyelitis * macrophage s * subdural infusion * dexamethasone Subject RIV: FH - Neurology Impact factor: 1.233, year: 2015

INTRAVITREAL DEXAMETHASONE IMPLANT AS ADJUVANT TREATMENT FOR BEVACIZUMAB- AND RANIBIZUMAB-RESISTANT NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Prospective Pilot Study.

Science.gov (United States)

Barikian, Anita; Salti, Haytham; Safar, Ammar; Mahfoud, Ziyad R; Bashshur, Ziad F

2017-07-01

To study the benefit of intravitreal dexamethasone implant in the management of neovascular age-related macular degeneration resistant to bevacizumab and ranibizumab. Patients with persistent macular fluid on optical coherence tomography despite monthly treatment with at least three consecutive bevacizumab injections followed by at least three ranibizumab injections were prospectively enrolled. A single dexamethasone implant was administered followed by intravitreal ranibizumab 1 week later. Ranibizumab was continued afterward on an as-needed basis. Main outcomes were improvement in central retinal thickness and best-corrected visual acuity. Nineteen patients (19 eyes) were enrolled. There was no significant change in best-corrected visual acuity over 6 months. Greatest reduction in mean central retinal thickness, from 295.2 μm to 236.2 μm, occurred 1 month after dexamethasone implant (P macular intraretinal fluid in eyes with neovascular age-related macular degeneration resistant to bevacizumab and ranibizumab. However, this treatment had a limited duration.

Adult Coats’ Disease Successfully Managed with the Dexamethasone Intravitreal Implant (Ozurdex® Combined with Retinal Photocoagulation

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Sebastián Martínez-Castillo

2012-03-01

Full Text Available Purpose: To report a case of Coats’ disease managed with the dexamethasone intravitreal implant Ozurdex® (Allergan, Inc., Irvine, Calif., USA combined with retinal photocoagulation. Methods: A 46-year-old female with 20/200 visual acuity was diagnosed with Coats’ disease with secondary retinal vasoproliferative tumor. An initial approach was performed with an intravitreal injection of the sustained-release dexamethasone implant Ozurdex. After reattachment of the retina, the telangiectatic vessels were treated with laser photocoagulation. Results: The patient’s visual acuity improved to 20/25 after the intravitreal Ozurdex. No further recurrences of exudation were evident through the 12-month follow-up. Conclusions: Ozurdex may be an effective initial therapeutic approach for Coats’ disease with immediate anatomical response and visual improvement.

The effect of water saturation deficit on the volume of intercellular space in laeves

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J. Czerski

2015-01-01

Full Text Available The volume of intercellular spaces in leaves at various stages of water saturation was determined by method of Czerski (1964, 1968. The investigation were performed with the following plant species: Vicia faba L., Nicotiana tabacum L. var. rustica, Solarium tuberosum L. var. Flisak, Helichrysum bracteatum Wild., Bmssica napus L. var. oleifera, Beta vulgaris L. var. saccharifera.

Is the Use of Dexamethasone Effective in Controlling Pain Associated with Symptomatic Irreversible Pulpitis? A Systematic Review.

Science.gov (United States)

Nogueira, Brenna M L; Silva, Ludmylla G; Mesquita, Carla R M; Menezes, Sílvio A F; Menezes, Tatiany O A; Faria, Antônio G M; Porpino, Mariana T M

2018-05-01

Endodontic pain is a symptom of pulpal and/or periapical inflammation. One strategy for pain reduction is using medications, such as dexamethasone. A definitive protocol for preventing and controlling pain caused by irreversible pulpitis during endodontic treatment has not yet been established. This is a systematic review to answer the following question: is the use of dexamethasone effective in controlling pain associated with symptomatic irreversible pulpitis? This study was registered in the PROSPERO database (CRD42017058704), and Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement recommendations were followed. MEDLINE, Scopus, ScienceDirect, Web of Science, Latin American Caribbean Health Sciences Literature, Cochrane Library, and Google Scholar databases were used in our research. No restrictions were applied to dates or language of publication. All records identified electronically were organized and evaluated by 2 independent authors, and, in case of doubt, a third author made the decision. The Cochrane Collaboration tool was used. The data were analyzed with RevMan 5 software (The Cochrane Collaboration, Copenhagen, Denmark), and data from eligible studies were dichotomous (with and without pain). A total of 4825 studies were identified. After screening, 523 studies were selected, and, after careful evaluation, only 5 articles remained. All meta-analyses revealed a global effect (P < .05, P < .05, and P < .05), which means that 4 mg dexamethasone helps relieve pain, sometimes for up to 8, 12, and 24 hours. The pain felt by patients diagnosed with symptomatic irreversible pulpitis may be alleviated by administering 4 mg dexamethasone either by mouth or through intraligamentary and mainly supraperiosteal injections into the root canal for up to 24 hours. Copyright © 2018 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

The efficacy of adding dexamethasone, midazolam, or epinephrine to 0.5% bupivacaine in supraclavicular brachial plexus block.

Science.gov (United States)

El-Baradey, Ghada F; Elshmaa, Nagat S

2014-11-01

The aim was to assess the effectiveness of adding either dexamethasone or midazolam in comparison with epinephrine addition to 0.5% bupivacaine in supraclavicular brachial plexus block. This is a prospective randomized controlled observer-blinded study. This study was carried out in Tanta University Hospital on 60 patients of both sexes; American Society of Anesthesiologists physical Status I and II, age range from 18 to 45 years undergo elective surgery to upper limb. All patients were anesthetized with ultrasound guided supraclavicular brachial plexus block and randomly divided into three groups (each group 20 patients) Group E (epinephrine): 30 mL bupivacaine 0.5%with 1:200,000 epinephrine (5 μg/mL). Group D (dexamethasone): 30 mL bupivacaine 0.5% and dexamethasone 8 mg. Group M (midazolam): 30 ml bupivacaine 0.5% and midazolam 50 μg/kg. The primary outcome measures were onset and duration of sensory and motor block and time to first analgesic request. The windows version of SPSS 11.0.1 (SPSS Inc., Chicago, IL, USA) was used for statistical analysis. Data were presented in form of mean ± standard deviation multiple analysis of variance (ANOVA) was used to compare the three groups and Scheffe test was used after ANOVA. Power of significance P < 0.05 was considered to be statistically significant. Onset of sensory and motor block was significantly rapid (P < 0.05) in Groups D and M in comparison with Group E. Time of administration of rescue analgesic, duration of sensory and motor block showed significant increase (P < 0.05) in Group D in comparison with Group M which showed significant increase (P < 0.05) in comparison with Group E. In comparison with epinephrine and midazolam addition of dexamethasone to bupivacaine had rapid onset of block and longer time to first analgesic request with fewer side-effects.

[Value of desmopressin stimulation test and high dose dexamethasone suppression testin the etiologic diagnosis of ACTH dependent Cushing's syndrome].

Science.gov (United States)

Zhang, Weiwei; Yu, Yerong; Tan, Huiwen; Wang, Chun; Li, Jianwei; An, Zhenmei; Liu, Yuping

2016-03-22

To investigate the value of desmopressin (DDAVP) stimulation test and high dose dexamethasone suppression test (HDDST) in establishing the cause of ACTH dependent Cushing's syndrome. The clinical data of patients with ACTH dependent Cushing's syndrome at West China Hospital from January 1, 2010 to September 30, 2015 was analyzed. The sensitivity and specificity of DDAVP stimulation test, HDDST, and the diagnostic accordance rate when the two tests were combined, were evaluated based on the diagnostic gold standard. A total of 85 patients with Cushing's disease and 10 patients with ectopic ACTH syndrome were included. The sensitivity and specificity of DDAVP stimulation test were 87% and 5/5, respectively, whereas those of HDDST were 79% and 8/10, respectively. The standard high dose dexamethasone suppression test showed a higher sensitivity than overnight 8 mg dexamethasone suppression test. When the two tests had consistent results, the diagnostic accordance rate was 100%. DDAVP stimulation test and HDDST are both efficient modalities for the diagnosis of Cushing's Disease and ectopic ACTH syndrome. The accuracy of diagnosis can be further improved by combining the two tests.

The effects of dexamethasone (DXM) and vitamin A on the growth and metamorphosis of gamma irradiated, thyroxine induced Bufo melanostictus tadpoles

International Nuclear Information System (INIS)

Ahmad, M.; Haider, N.; Siddiqui, R.Q.R.

1980-01-01

This study deals with the effects of vitamin A and dexamethasone (DXM) on the metamorphosis of irradiated tadpoles. Results indicate that hypervitaminosis A depresses the metamorphosing action of thyroxine for several days. On the contrary, dexamethasone accelerates the action of exogenous thyroxine on tadpoles. Thus present data suggest that DXM supresses STH synthesis and promotes TSH secretion. Moreover, muscle appears to be its target tissue and DXM seems to promote the proteolytic digestion of the larval tail. (author)

Effects of Dexamethasone and Insulin Alone or in Combination on Energy and Protein Metabolism Indicators and Milk Production in Dairy Cows in Early Lactation – A Randomized Controlled Trial

Science.gov (United States)

Sami, Mehrdad; Mohri, Mehrdad; Seifi, Hesam A.

2015-01-01

Objectives This study investigated the effects of dexamethasone and insulin, when administered at 3rd or 10th day of lactation on energy and protein metabolism in dairy cows. Materials and Methods Two hundred Holstein cows were enrolled in a randomized controlled clinical trial. The cows were randomly assigned to receive 1 of 4 treatments at 3 or 10 days in milk: control group, 10-mL i.m. injection of sterile water, group insulin, s.c. injection of 100 units of insulin, group dexamethasone, i.m. injection of 20 mg of dexamethasone, group insulin plus dexamethasone, i.m. injection of 20 mg of dexamethasone and 100 units of insulin. The cows randomly assigned to receive the treatments on 3 or 10 days of lactation. Serum samples obtained at the time of enrollment, time of treatment and at 2, 4, 7 and 14 days after intervention. The sera were analyzed for β-hydroxybutyrate (BHBA), nonesterified fatty acids (NEFA), glucose, cholesterol, albumin, urea, and aspartate amino transferase (AST). Data were analyzed using a repeated measures mixed model that accounted for the effects of parity, body condition score, dystocia, retained placenta, metritis and the random effect of cow. Results There was no significant interaction of group of treatment and time of intervention (day 3 or 10 post-partum) on serum components. Cows that received insulin or dexamethasone alone or in combination, had lower BHBA 2 days after treatment compared with control cows, whereas concentrations of NEFA, were unaffected suggesting that glucocorticoids lipolytic effects do not appear to be important in healthy cows. AST activities significantly reduced in cows that received dexamethasone with or without insulin at 2 and 4 days after treatment. Albumin and urea concentrations 2 days after treatment were higher for cows that received dexamethasone only or dexamethasone plus insulin compared with control and Ins received cows. There were no treatment effects on test-day milk production, milk fat and

Multilayer poly(3,4-ethylenedioxythiophene)-dexamethasone and poly(3,4-ethylenedioxythiophene)-polystyrene sulfonate-carbon nanotubes coatings on glassy carbon microelectrode arrays for controlled drug release.

Science.gov (United States)

Castagnola, Elisa; Carli, Stefano; Vomero, Maria; Scarpellini, Alice; Prato, Mirko; Goshi, Noah; Fadiga, Luciano; Kassegne, Sam; Ricci, Davide

2017-07-13

The authors present an electrochemically controlled, drug releasing neural interface composed of a glassy carbon (GC) microelectrode array combined with a multilayer poly(3,4-ethylenedioxythiophene) (PEDOT) coating. The system integrates the high stability of the GC electrode substrate, ideal for electrical stimulation and electrochemical detection of neurotransmitters, with the on-demand drug-releasing capabilities of PEDOT-dexamethasone compound, through a mechanically stable interlayer of PEDOT-polystyrene sulfonate (PSS)-carbon nanotubes (CNT). The authors demonstrate that such interlayer improves both the mechanical and electrochemical properties of the neural interface, when compared with a single PEDOT-dexamethasone coating. Moreover, the multilayer coating is able to withstand 10 × 10 6 biphasic pulses and delamination test with negligible change to the impedance spectra. Cross-section scanning electron microscopy images support that the PEDOT-PSS-CNT interlayer significantly improves the adhesion between the GC substrate and PEDOT-dexamethasone coating, showing no discontinuities between the three well-interconnected layers. Furthermore, the multilayer coating has superior electrochemical properties, in terms of impedance and charge transfer capabilities as compared to a single layer of either PEDOT coating or the GC substrate alone. The authors verified the drug releasing capabilities of the PEDOT-dexamethasone layer when integrated into the multilayer interface through repeated stimulation protocols in vitro, and found a pharmacologically relevant release of dexamethasone.

Investigating Disruption

DEFF Research Database (Denmark)

Lundgaard, Stine Schmieg; Rosenstand, Claus Andreas Foss

This book shares knowledge collected from 2015 and onward within the Consortium for Digital Disruption anchored at Aalborg University (www.dd.aau.dk). Evidenced by this publication, the field of disruptive innovation research has gone through several stages of operationalizing the theory. In recent...... years, researchers are increasingly looking back towards the origins of the theory in attempts to cure it from its most obvious flaws. This is especially true for the use of the theory in making predictions about future disruptions. In order to continue to develop a valuable theory of disruption, we...... find it useful to first review what the theory of disruptive innovation initially was, how it has developed, and where we are now. A cross section of disruptive innovation literature has been reviewed in order to form a general foundation from which we might better understand the changing world...

Synthesis of a Cytokinin Linked by a Spacer to Dexamethasone and Biotin: Conjugates to Detect Cytokinin-Binding Proteins

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You Wang

2016-04-01

Full Text Available Yeast cells expressing cDNA libraries have provided two new approaches to facilitate further identification of cytokinin-binding proteins and receptors. These are the yeast three hybrid (Y3H system and fluorescence activated cell sorting (FACS. The Y3H system requires a synthetic hybrid ligand comprising an “anchor” moiety (e.g., dexamethasone linked to a cytokinin via a spacer. In the yeast nucleus, this ligand by binding connects two fusion proteins leading to a reporter gene activation and detection and characterisation of cytokinin binding proteins. Herein is reported the first synthesis of dexamethasone-cytokinin ligands with a spacer linkage. This was attached to the purine ring of 6-benzylaminopurine (BAP at positions 2, 8 or 9. To achieve this, dexamethasone was modified by periodate oxidation yielding a carboxylic group used for conjugation to the spacer by amide formation. Biotinyl derivatives of cytokinins for FACS included those synthesised by reaction of an activated ester of biotin with 8-(10-amino-decylamino derivatives of BAP and BAP 9-riboside. Properties of the conjugates and some biological situations where they could be applicable are discussed briefly.

Relationship of glucocorticoid receptor expression in peripheral blood mononuclear cells and the cochlea of guinea pigs and effects of dexamethasone administration.

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Ling Lu

Full Text Available BACKGROUND: Glucocorticoids (GCs are widely used to treat sudden sensorineural hearing loss (SSNHL and significantly improve hearing. However, GC insensitivity has been observed in some patients of SSNHL. OBJECTIVE: To study the correlation between GR expression in peripheral blood mononuclear cells (PBMCs and in the cochlea of guinea pigs at mRNA and protein levels. METHODS: One group of guinea pigs received dexamethasone (10 mg/kg/day intraperitoneally for 7 consecutive days (dexamethasone group, and another group of guinea pigs received normal saline (control group. Real time PCR and Western blotting were used to detect the expression of GR mRNA and GR protein in PBMCs and the cochleae. RESULTS: The GR mRNA and GR protein were detected in both PBMCs and the cochlear tissue of guinea pigs. GR mRNA and GR protein levels in PBMCs were positively correlated with those in the cochlea. The expression of GR mRNA and GR protein was significantly increased in the dexamethasone group compared to the control group. CONCLUSIONS: Levels of GR mRNA and GR protein in the PBMCs were positively correlated with those in the cochlea of guinea pigs. Systemic dexamethasone treatment can significantly up-regulate GR expression in PBMCs and in the cochlea. Measurement of the GR level in PBMCs could be used as an indicator of GR level in the cochlea.

Effect of venous dexamethasone, oral caffeine and acetaminophen on relative frequency and intensity of postdural puncture headache after spinal anesthesia.

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Masoudifar, Mehrdad; Aghadavoudi, Omid; Adib, Sajjad

2016-01-01

Postdural puncture headache (PDPH) is a relatively common complication after regional anesthesia, especially in younger people, bothersome to patients and needs prophylaxis to prevent this complication. This study was conducted aiming to determine the preventive effect of dexamethasone plus caffeine and acetaminophen on relative frequency and intensity of PDPH after spinal anesthesia. In a clinical trial study, 90 candidates for the lower extremities orthopedic elective operation were divided into two groups of 45 individuals each. Intervention group received the compound of 500 mg acetaminophen +65 mg oral caffeine +8 mg venous dexamethasone an hour before spinal blocking, and the control group received placebo tablets + a dexamethasone equivalent volume of venous normal saline. The level of postoperative headache at the time of entrance to recovery and discharge, 6, 12, 24, 48, and 72 h postoperatively were measured based on Visual Analog Scale criterion in the two groups and then compared with each other. During the study, 24 patients in the control group and 17 patients in the intervention group were afflicted with headache; however, with no significant difference (P = 0.14). Total frequency of headache incidence was 35 times in the control group and 27 times in the intervention group (P = 0.32). Though the taking of acetaminophen + caffeine + dexamethasone is associated with a decrease in headache intensity and duration and decrease in PDPH incidence, compared with placebo, however, no essentially and statistically significant effect was produced.

Stability-indicating liquid Chromatographic assaymethod for Opthalmic solutions containing combination of Dexamethasone and Chloramphenicol

International Nuclear Information System (INIS)

Rao, R.M.; Al-Ashban, R.M.; Shah, A.H.

2004-01-01

A selective high-performance chromatographic procedure for the stability monitoring of ophthalmic solutions containing a combination of dexamethasone and chloramphenicolis demonstrated. The separation of the active components and the degradation product of chloramphenicol (1-amino-1-(4-nitrophenyl)-propane-1, 3diol) was achieved on a u-Bondapack C-18 column ( 5 um, 300 mm x 3.9 mm) maintained at ambient temperature (15-20C) by utilizing a mobile phase consisting acidified water (5% actified water with glacial acetic acid ) : acetonitrile : triethyl amine 700 : 300 : 2and pH was adjusted to 5.0 by using 10 M Na OH. The flow rate was 1.5 ml min-1; and elutes were followed with UV-detection at 254 nm. Complete resolution of dexamethasone, chloramphenicol and its hydrolytic product could be attained. The sensitivity, accuracy and specificity were tested. The method was successfully applied in post-marketing stability of the commercial batches of ophthalmic solutions. (author)

Evaluation of gabapentin and dexamethasone alone or in combination for pain control after adenotonsillectomy in children

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Sabry Mohammad Amin

2014-01-01

Full Text Available Background: Different methods and many drugs have been used to control the post-operative pain. In this study, we evaluate the role of gabapentin premedication and/or dexamethasone in management of post-operative pain following adenotonsillectomy in children. Materials and Methods: In a double-blind randomized study, 120 children were subjected for adenotonsillectomy classified into three equal groups. Group G: Gabapentin 10 mg/kg was given orally 2 h before induction of anesthesia (Gabapentin syrup 250 mg/5 ml. Group D: Children in this group received placebo pre-operatively and received dexamethasone 0.15 mg/kg intravenously after induction of anesthesia, but before surgery. Group C: Children in this group received combination of oral gabapentin 10 mg/kg 2 h before induction of anesthesia and intra-operative 0.15 mg/kg dexamethasone intravenously. All children underwent general anesthesia. Pain score was assisted post-operatively 2 h, 4 h, 6 h, 8 h, 12 h and 18 h after recovery using face, legs, activity, cry, consolability scale. Results: Pain score in Group C and Group G was significantly less at 4 h, 6 h and 8 h post-operatively than in Group D (P 0.05. The time to first analgesia was longer in the Group C than in Group G and Group D and the time to first analgesia was significantly longer in Group G than in Group D (P < 0.05. The total amount of pethidine was less in Group C and Group G than in Group D (P < 0.05. The incidence of post-operative nausea and vomiting was statically insignificant among all groups and no reported post-operative bleeding. Conclusion: Gabapentin 10 mg/kg premedication combined with intra-operative dexamethasone 0.15 mg/kg prolongs the post-operative analgesia following adenotonsillectomy in children and decreases the amount of pethidine used post-operatively with no reported adverse effects or increase in the incidence of post-operative bleeding.

Effect of dexamethasone on skeletal muscle Na+,K+ pump subunit specific expression and K+ homeostasis during exercise in humans

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Nordsborg, Nikolai; Ovesen, Jakob; Thomassen, Martin

2008-01-01

The effect of dexamethasone on Na(+),K(+) pump subunit expression and muscle exchange of K(+) during exercise in humans was investigated. Nine healthy male subjects completed a randomized double blind placebo controlled protocol, with ingestion of dexamethasone (Dex: 2 x 2 mg per day) or placebo...... (Pla) for 5 days. Na(+),K(+) pump catalytic alpha1 and alpha2 subunit expression was approximately 17% higher (P ...). The results indicate that an increased Na(+),K(+) pump expression per se is of importance for thigh K(+) reuptake at the onset of low and moderate intensity exercise, but less important during high intensity exercise....

Effects of Neonatal Dexamethasone Treatment on the Cardiovascular Stress Response of Children at School Age

NARCIS (Netherlands)

Karemaker, Rosa; Karemaker, John M.; Kavelaars, Annemieke; Tersteeg-Kamperman, Marijke; Baerts, Wim; Veen, Sylvia; Samsom, Jannie F.; van Bel, Frank; Heijnen, Cobi J.

2008-01-01

OBJECTIVE. The goal was to investigate cardiovascular responses to a psychosocial stressor in school-aged, formerly premature boys and girls who had been treated neonatally with dexamethasone or hydrocortisone because of chronic lung disease. METHODS. We compared corticosteroid-treated, formerly

Anterior migration of dexamethasone implant in a pseudophakic patient with intact posterior capsule

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Nilufer Kocak

2014-01-01

Full Text Available Intravitreal application of Ozurdex ® (Allergan, Inc., Irvine, CA, USA which is a biodegradable, sustained-release dexamethasone implant has been reported to be effective in the treatment of macular edema. Migration of such implant into the anterior chamber has been recently described in cases without perfect zonular or the posterior capsular integrity. Herein, we report the first case with anterior migration of Ozurdex ® implant that mislocated just behind the intraocular lens (IOL in an intact capsular bag. It is thought that such implant migrated anteriorly towards into the posterior chamber through weak zonules as the present case had a medical history of uneventful phacoemulsification surgery with the implantation of posterior chamber IOL. However, the migrated implant was well tolerated since there was no sign of the corneal complication, rise in intraocular pressure, and anterior chamber reaction. Close follow-up was scheduled to find out any signs of anterior segment pathology. Meanwhile dexamethasone implant completely degraded at the 4 th month of postoperative follow-up.

Robust synchronization analysis in nonlinear stochastic cellular networks with time-varying delays, intracellular perturbations and intercellular noise.

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Chen, Po-Wei; Chen, Bor-Sen

2011-08-01

Naturally, a cellular network consisted of a large amount of interacting cells is complex. These cells have to be synchronized in order to emerge their phenomena for some biological purposes. However, the inherently stochastic intra and intercellular interactions are noisy and delayed from biochemical processes. In this study, a robust synchronization scheme is proposed for a nonlinear stochastic time-delay coupled cellular network (TdCCN) in spite of the time-varying process delay and intracellular parameter perturbations. Furthermore, a nonlinear stochastic noise filtering ability is also investigated for this synchronized TdCCN against stochastic intercellular and environmental disturbances. Since it is very difficult to solve a robust synchronization problem with the Hamilton-Jacobi inequality (HJI) matrix, a linear matrix inequality (LMI) is employed to solve this problem via the help of a global linearization method. Through this robust synchronization analysis, we can gain a more systemic insight into not only the robust synchronizability but also the noise filtering ability of TdCCN under time-varying process delays, intracellular perturbations and intercellular disturbances. The measures of robustness and noise filtering ability of a synchronized TdCCN have potential application to the designs of neuron transmitters, on-time mass production of biochemical molecules, and synthetic biology. Finally, a benchmark of robust synchronization design in Escherichia coli repressilators is given to confirm the effectiveness of the proposed methods. Copyright © 2011 Elsevier Inc. All rights reserved.

A randomized clinical trial to compare the efficacy of submucosal aprotinin injection and intravenous dexamethasone in reducing pain and swelling after third molar surgery: a prospective study.

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Arakeri, Gururaj; Rai, Kirthi Kumar; Shivakumar, H R; Jayade, Bhushan

2013-03-01

The purpose of this study was to compare two different groups of drugs, aprotinin and dexamethasone for its efficacy in reducing post operative swelling and pain after third molar surgery. Fifty consecutive patients requiring surgical removal of single mandibular third molar (class II position B) under local anesthesia were randomly divided into two groups, each group consisting of 25 patients. One group was administered 8 mg dexamethasone through intravenous route pre-operatively. The other group received 1 ml of Aprotinin through submucosal route in operating area after the onset of local anesthesia. Swelling was assessed by measuring facial contours at baseline and at 1st, 3rd and 7th post-operative days. Pain was measured on the 1st, 3rd and 7th post-operative days using visual analog scale. Based on statistical analysis (paired t test and Wilcoxon's signed ranking test), the results showed statistically significant difference in post operative swelling and pain on 3rd postoperative day in dexamethasone group as compared to aprotinin group. The results of present study showed a similar reduction in the severity of pain and swelling at the aprotinin and dexamethasone sites on 1st and 7th postoperative day. It was also noticed that the aprotinin promoted a greater reduction of swelling and pain on 3rd postoperative day. It appeared that, benefits of aprotinin against the risks of dexamethasone and its efficacy in controlling pain and swelling after third molar surgery makes aprotinin to be a valuable alternative to dexamethasone.

Dexamethasone intravitreal implant downregulates PDGFR-α and upregulates caveolin-1 in experimental branch retinal vein occlusion

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Cehofski, Lasse Jørgensen; Kruse, Anders; Magnusdottir, Sigriður Olga

2018-01-01

while the left control eye was given an identical injection without an implant. Fifteen days after BRVO and DEX implant intervention the retinas were excised and analyzed with tandem mass tag based mass spectrometry. A total of 26 significantly changed proteins were identified. Dexamethasone...... following an intervention with a dexamethasone (DEX) implant this study combined an experimental model of BRVO with proteomic techniques. In six Danish Landrace pigs experimental BRVO was induced in both eyes using argon laser. After inducing BRVO a DEX implant was injected in the right eye of each animal......-α and caveolin-1 were confirmed with immunohistochemistry. DEX implant intervention may inhibit PDGF signaling by decreasing the retinal level of PDGFR-α while an increased content of caveolin-1 may help maintain the integrity of the blood-retinal barrier....

A Randomized Cross‐over Study of High‐dose Metoclopramide plus Dexamethasone versus Granisetron plus Dexamethasone in Patients Receiving Chemotherapy with High‐dose Cisplatin

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Eguchi, Kenji; Shinkai, Tetsu; Tamura, Tomohide; Ohe, Yuichiro; Nisio, Masato; Kunikane, Hiroshi; Arioka, Hitoshi; Karato, Atsuya; Nakashima, Hajime; Sasaki, Yasutsuna; Tajima, Kinuko; Tada, Noriko; Saijo, Nagahiro

1994-01-01

We carried out a randomized, single‐blind, cross‐over trial to compare the antiemetic effect, for both acute and delayed emesis, of granisetron plus dexamethasone (GRN+Dx) with that of high‐dose metoclopramide plus dexamethasone (HDMP + Dx). Fifty‐four patients with primary or metastatic lung cancer, given single‐dose cisplatin (> 80 mg/m2) chemotherapy more than twice, were enrolled in this study. They were treated with both HDMP+Dx and GRN+Dx in two consecutive chemotherapy courses. On day 1, patients experienced a mean of 2.5 (SD=4.3) and 0,1 (SD = 0.4) episodes of vomiting in the HDMP+Dx and the GRN + Dx groups, respectively (P=0.0008). Complete response rate on day 1 was 45 and 90% in the HDMP+Dx and the GRN+Dx groups, respectively (P= 0.0001). Patients treated with GRN+Dx had a tendency to suffer more episodes of vomiting than the HDMP+Dx group on days 2–5, but it was not statistically significant. Twenty‐four patients (57%) preferred the GRN+Dx treatment and 14 patients (33%), HDMP + Dx. In the HDMP + Dx group, nine patients (21%) had an extrapyramidal reaction, and 5 patients (12%) had constipation that lasted for at least two days. In contrast, no patients had extrapyramidal reactions, and IS patients (43%) had constipation in the GRN+Dx group (P < 0.01). GRN+Dx was more effective than HDMP+Dx only in preventing the acute emesis induced by cisplatin. An effective treatment for delayed emesis is still needed. PMID:7829401

CHANGES OF INTERCELLULAR COOPERATION IN PERIPHERAL BLOOD IN TREATED PATIENTS WITH CARDIOLOGIC DISEASES

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L. N. Korichkina

2009-01-01

Full Text Available Aim. To study changes of intercellular cooperation in peripheral blood induced by treatment in patients with arterial hypertension (HT, ischemic heart disease (IHD and chronic heart failure (CHF.Material and methods. 610 patients were involved into the study, including 250 patients with HT of stages I-III (50 untreated patients, 150 patients with IHD and 210 patients with CHF of stages I-III. All patients were treated except 50 hypertensive ones. 80 healthy patients (40 men, 40 women were included into control group. Blood smears of patients were evaluated (Romanovsky's stain. A number of leukocyte, autorosettes and autorosettes with erythrocyte lysis was calculated. The cellular association consisting of a neutrophil, monocyte or eosinocyte with 3 or more erythrocytes skintight to their surface defined as autorosettes. Erythrocytes number and hemoglobin level determined in peripheral blood.Results. Single autorosettes in peripheral blood were observed in patients of control group and in untreated patients with HT. Treated patients with HT, IHD and CHF had increased number of autorossets and autorosettes with erythrocytes lysis. This phenomenon resulted in reduction of erythrocytes number and hemoglobin level in peripheral blood.Conclusion. Treated patients with cardiologic diseases had changes in intercellular cooperation. It should be considered at intensive and long term therapy.

Neurotoxicity induced by dexamethasone in the human neuroblastoma SH-SY5Y cell line can be prevented by folic acid.

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Budni, J; Romero, A; Molz, S; Martín-de-Saavedra, M D; Egea, J; Del Barrio, L; Tasca, C I; Rodrigues, A L S; López, M G

2011-09-08

Folic acid (folate) is a vitamin of the B-complex group that is essential for cell replication. Folate is a major determinant of one-carbon metabolism, in which S-adenosylmethionine donates methyl groups that are crucial for neurological function. Many roles for folic acid have been reported, including neuroprotective and antidepressant properties. On the other hand, increased concentrations of corticoids have proven neurotoxic effects and hypersecretion of glucocorticoids has been linked to different mood disorders. The purpose of this study was to investigate the potential protective effect of folic acid on dexamethasone-induced cellular death in SH-SY5Y neuroblastoma cell line and the possible intracellular signaling pathway involved in such effect. Exposure to 1 mM dexamethasone for 48 h caused a significant reduction of cell viability measured as 3-[4,5 dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) reduction. Exposure of SH-SY5Y cells for 72 h to increasing concentrations of folate (1-300 μM) was not cytotoxic. However, pretreatment with folate (10-300 μM) reduced dexamethasone-induced toxicity in a significant manner. To explore the putative intracellular signaling pathways implicated in the protective effect of folate we used different protein kinase inhibitors. The protective effect of folic acid on dexamethasone-induced neurotoxicity was reversed by the phosphatidylinositol-3 kinase/Akt (PI3K/Akt, LY294002), Ca²⁺/Calmodulin-dependent protein kinase II (CaMKII, KN-93), and protein kinase A (PKA, H-89) inhibitors, but not the mitogen-activated protein/extracellular signal-regulated kinase (MEK1/2, PD98059) and protein kinase C (PKC, chelerythrine) inhibitors. In conclusion, the results of this study show that folic acid can protect against dexamethasone-induced neurotoxicity and its protective mechanism is related to a signaling pathway that involves PI3K/Akt, CaMKII, and PKA. Copyright © 2011. Published by Elsevier Ltd.

Induction of regulatory dendritic cells by dexamethasone and 1alpha,25-Dihydroxyvitamin D(3)

DEFF Research Database (Denmark)

Pedersen, Anders Elm; Gad, Monika; Walter, Mark R

2004-01-01

D(3) the active form of Vitamin D(3) (D(3)) in combination with dexamethasone (Dex) has a synergistic effect on LPS-induced maturation of DC. Monocyte-derived DCs cultured with D(3) and Dex during LPS-induced maturation have a low stimulatory effect on allogeneic T cells comparable...

Digital Disruption

DEFF Research Database (Denmark)

Rosenstand, Claus Andreas Foss

det digitale domæne ud over det niveau, der kendetegner den nuværende debat, så præsenteres der ny viden om digital disruption. Som noget nyt udlægges Clayton Christens teori om disruptiv innovation med et særligt fokus på små organisationers mulighed for eksponentiel vækst. Specielt udfoldes...... forholdet mellem disruption og den stadig accelererende digitale udvikling i konturerne til ny teoridannelse om digital disruption. Bogens undertitel ”faretruende og fascinerende forandringer” peger på, at der er behov for en nuanceret debat om digital disruption i modsætning til den tone, der er slået an i...... videre kalder et ”disruption-råd”. Faktisk er rådet skrevet ind i 2016 regeringsgrundlaget for VLK-regeringen. Disruption af organisationer er ikke et nyt fænomen; men hastigheden, hvormed det sker, er stadig accelererende. Årsagen er den globale mega-trend: Digitalisering. Og derfor er specielt digital...

Dexamethasone Protects Against Tourniquet-Induced Acute Ischemia-Reperfusion Injury in Mouse Hindlimb

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Ryan M. Corrick

2018-03-01

Full Text Available Extremity injuries with hemorrhage have been a significant cause of death in civilian medicine and on the battlefield. The use of a tourniquet as an intervention is necessary for treatment to an injured limb; however, the tourniquet and subsequent release results in serious acute ischemia-reperfusion (IR injury in the skeletal muscle and neuromuscular junction (NMJ. Much evidence demonstrates that inflammation is an important factor to cause acute IR injury. To find effective therapeutic interventions for tourniquet-induced acute IR injuries, our current study investigated effect of dexamethasone, an anti-inflammatory drug, on tourniquet-induced acute IR injury in mouse hindlimb. In C57/BL6 mice, a tourniquet was placed on unilateral hindlimb (left hindlimb at the hip joint for 3 h, and then released for 24 h to induce IR. Three hours of tourniquet and 24 h of release (24-h IR caused gastrocnemius muscle injuries including rupture of the muscle sarcolemma and necrosis (42.8 ± 2.3% for infarct size of the gastrocnemius muscle. In the NMJ, motor nerve terminals disappeared, and endplate potentials were undetectable in 24-h IR mice. There was no gastrocnemius muscle contraction in 24-h IR mice. Western blot data showed that inflammatory cytokines (TNFα and IL-1β were increased in the gastrocnemius muscle after 24-h IR. Treatment with dexamethasone at the beginning of reperfusion (1 mg/kg, i.p. significantly inhibited expression of TNFα and IL-1β, reduced rupture of the muscle sarcolemma and infarct size (24.8 ± 2.0%, and improved direct muscle stimulation-induced gastrocnemius muscle contraction in 24-h IR mice. However, this anti-inflammatory drug did not improve NMJ morphology and function, and sciatic nerve-stimulated skeletal muscle contraction in 24-h IR mice. The data suggest that one-time treatment with dexamethasone at the beginning of reperfusion only reduced structural and functional impairments of the skeletal muscle but not the

Extended low-dose dexamethasone suppression test for diagnosis of atypical Cushing's syndrome in dogs.

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Fowler, K M; Frank, L A; Morandi, F; Whittemore, J C

2017-07-01

The purpose of this study was to evaluate extension of the low-dose dexamethasone suppression (LDDS) test from 8 h to 12 h to detect possible hypercortisolemia associated with atypical hyperadrenocorticism (AHAC). Twelve client-owned dogs were enrolled in the study: 6 healthy dogs (group 1) and 6 dogs with suspected AHAC (group 2). Baseline EDTA plasma samples were collected for endogenous ACTH determination using an immunoradiometric assay. Serum samples were collected before and at 4, 8, 10, and 12 h post-administration of 0.01 mg/kg dexamethasone IV for cortisol concentration determination via chemiluminescent assay. Mean endogenous ACTH concentration did not differ between groups (group 1: 22.4 pg/mL, group 2: 20.0 pg/mL; P > 0.2). Mean baseline cortisol concentration also did not differ significantly between groups (group 1: 3.03 μg/dL, group 2: 4.95 μg/dL; P > 0.2) nor was there any difference in mean cortisol concentration between the groups at any other time point (P > 0.2). The cortisol concentration from 1 dog in group 2 suppressed to 0.7 μg/dL at 8 h but increased to 1.5 μg/dL at 10 h and 3.7 μg/dL at 12 h post-dexamethasone. Based on results of this study, use of an extended LDDS test could not differentiate between healthy dogs and dogs with AHAC. Diagnosis of AHAC should continue to be based on prior established criteria until new testing has been identified. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative evaluation of megadose methylprednisolone with dexamethasone for treatment of primary typical optic neuritis

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Menon Vimala

2007-01-01

Full Text Available Aim: To compare the efficacy of intravenous methylprednisolone and intravenous dexamethasone on visual recovery and evaluate their side-effects for the treatment of optic neuritis. Materials and Methods: Prospective, randomized case-controlled study including 21 patients of acute optic neuritis presenting within eight days of onset and with visual acuity less then 20/60 in the affected eye who were randomly divided into two groups. Group I received intravenous dexamethasone 200 mg once daily for three days and Group II received intravenous methylprednisolone 250 mg/six-hourly for three days followed by oral prednisolone for 11 days. Parameters tested were pupillary reactions, visual acuity, fundus findings, color vision, contrast sensitivity, Goldmann visual fields and biochemical investigations for all patients at presentation and follow-up. Results: Both groups were age and sex-matched. LOGMAR visual acuity at presentation was 1.10 ± 0.52 in Group I and 1.52 ± 0.43 in Group II. On day 90 of steroid therapy, visual acuity improved to 0.28 ± 0.33 in Group I and 0.36 ± 0.41 in Group II ( P =0.59. At three months there was no statistically significant difference in the color vision, contrast sensitivity, stereoacuity, Goldman fields and the amplitude and latency of visually evoked response between the two groups. The concentration of vitamin C, glucose, sodium, potassium, urea and creatinine were within the reported normal limits. Conclusion: Intravenous dexamethasone is an effective treatment for optic neuritis. However, larger studies are required to establish it as a safe, inexpensive and effective modality for the treatment of optic neuritis.

Does Growth Impairment Underlie the Adverse Effects of Dexamethasone on Development of Noradrenergic Systems?

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Slotkin, Theodore A; Ko, Ashley; Seidler, Frederic J

2018-06-20

Glucocorticoids are given in preterm labor to prevent respiratory distress but these agents evoke neurobehavioral deficits in association with reduced brain region volumes. To determine whether the neurodevelopmental effects are distinct from growth impairment, we gave developing rats dexamethasone at doses below or within the therapeutic range (0.05, 0.2 or 0.8 mg/kg) at different stages: gestational days (GD) 17-19, postnatal days (PN) 1-3 or PN7-9. In adolescence and adulthood, we assessed the impact on noradrenergic systems in multiple brain regions, comparing the effects to those on somatic growth or on brain region growth. Somatic growth was reduced with exposure in all three stages, with greater sensitivity for the postnatal regimens; brain region growth was impaired to a lesser extent. Norepinephrine content and concentration were reduced depending on the treatment regimen, with a rank order of deficits of PN7-9 > PN1-3 > GD17-19. However, brain growth impairment did not parallel reduced norepinephrine content in magnitude, dose threshold, sex or regional selectivity, or temporal pattern, and even when corrected for reduced brain region weights (norepinephrine per g tissue), the dexamethasone-exposed animals showed subnormal values. Regression analysis showed that somatic growth impairment accounted for an insubstantial amount of the reduction in norepinephrine content, and brain growth impairment accounted for only 12%, whereas specific effects on norepinephrine accounted for most of the effect. The adverse effects of dexamethasone on noradrenergic system development are not simply related to impaired somatic or brain region growth, but rather include specific targeting of neurodifferentiation. Copyright © 2018. Published by Elsevier B.V.

Postural Control in Lowlanders With COPD Traveling to 3100 m: Data From a Randomized Trial Evaluating the Effect of Preventive Dexamethasone Treatment

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Lara Muralt

2018-06-01

Full Text Available Objective: To evaluate the effects of acute exposure to high altitude and preventive dexamethasone treatment on postural control in patients with chronic obstructive pulmonary disease (COPD.Methods: In this randomized, double-blind parallel-group trial, 104 lowlanders with COPD GOLD 1-2 age 20–75 years, living near Bishkek (760 m, were randomized to receive either dexamethasone (2 × 4 mg/day p.o. or placebo on the day before ascent and during a 2-day sojourn at Tuja-Ashu high altitude clinic (3100 m, Kyrgyzstan. Postural control was assessed with a Wii Balance BoardTM at 760 m and 1 day after arrival at 3100 m. Patients were instructed to stand immobile on both legs with eyes open during five tests of 30 s each, while the center of pressure path length (PL was measured.Results: With ascent from 760 to 3100 m the PL increased in the placebo group from median (quartiles 29.2 (25.8; 38.2 to 31.5 (27.3; 39.3 cm (P < 0.05; in the dexamethasone group the corresponding increase from 28.8 (22.8; 34.5 to 29.9 (25.2; 37.0 cm was not significant (P = 0.10. The mean difference (95% CI between dexamethasone and placebo groups in altitude-induced changes (treatment effect was -0.3 (-3.2 to 2.5 cm, (P = 0.41. Multivariable regression analysis confirmed a significant increase in PL with higher altitude (coefficient 1.6, 95% CI 0.2 to 3.1, P = 0.031 but no effect of dexamethasone was shown (coefficient -0.2, 95% CI -0.4 to 3.6, P = 0.925, even when controlled for several potential confounders. PL changes were related more to antero-posterior than lateral sway. Twenty-two of 104 patients had an altitude-related increase in the antero-posterior sway velocity of >25%, what has been associated with an increased risk of falls in previous studies.Conclusion: Lowlanders with COPD travelling from 760 to 3100 m revealed postural instability 24 h after arriving at high altitude, and this was not prevented by dexamethasone.Trial Registration

Methylmercury inhibits gap junctional intercellular communication in primary cultures of rat proximal tubular cells

Energy Technology Data Exchange (ETDEWEB)

Yoshida, Minoru; Sumi, Yawara [Department of Chemistry, St. Marianna University School of Medicine, Kawasagi (Japan); Kujiraoka, Toru [Department of Physiology, St. Marianna University School of Medicine, Kawasagi (Japan); Hara, Masayuki [Department of Anatomy, St. Marianna University School of Medicine, Kawasagi (Japan); Nakazawa, Hirokazu [Department of Chemistry, Faculty of Sciences, Meisei University (Japan)

1998-03-01

Methylmercury (MeHg) causes renal injury in addition to central and peripheral neuropathy. To clarify the mechanism of nephrotoxicity by MeHg, we investigated the effect of this compound on intercellular communication through gap junction channels in primary cultures of rat renal proximal tubular cells. Twenty minutes after exposure to 30 {mu}M MeHg, gap junctional intercellular communication (GJIC), which was assessed by dye coupling, was markedly inhibited before appearance of cytotoxicity. When the medium containing MeHg was exchanged with MeHg-free medium, dye coupling recovered abruptly. However, the dye-coupling was abolished again 30 min after replacement with control medium, and the cells were damaged. Intracellular calcium concentration, [Ca{sup 2+}]{sub i}, which modulates the function of gap junctions, significantly increased following exposure of the cells to 30 {mu}M MeHg and returned to control level following replacement with MeHg-free medium. These results suggest that the inhibiting effect of MeHg on GJIC is related to the change in [Ca{sup 2+}]{sub i}, and may be involved in the pathogenesis of renal dysfunction. (orig.) With 5 figs., 23 refs.

Inhibition of intercellular communication by airborne particulate matter

Energy Technology Data Exchange (ETDEWEB)

Heussen, G.A.H. (Landbouwhogeschool Wageningen (Netherlands). Dept. of Toxicology)

1991-04-01

To investigate the inhibition of gap junction mediated intercellular communication (IC) by extracts of airborne particulate matter (APM), V79 cells were incubated with extracts of APM and subsequently microinjected with the fluorescent dye Lucifer Yellow, after which the number of fluorescent (= communicating) cells was determined. To compare inhibitory effects on IC with mutagenicity, APM was also tested in the Salmonella microsome assay. Six different extracts were tested, two outdoor extracts representing a heavily polluted and a relatively clean sample, and four indoor extracts, taken either in livingrooms with or without wood combustion in an open fire place, or in a room with or without cigarette smoking. Non-cytotoxic doses of outdoor and indoor APM inhibited IC in V79 cells in dose- and time-dependent manner. Mutagenicity data and IC data were correlated. These results suggest that APM has tumor promoter activity in addition to mutagenic activity. (orig.).

Dexamethasone up-regulates skeletal muscle maximal Na+,K+ pump activity by muscle group specific mechanisms in humans

DEFF Research Database (Denmark)

Nordsborg, Nikolai; Goodmann, Craig; McKenna, Michael J.

2005-01-01

Dexamethasone, a widely clinically used glucocorticoid, increases human skeletal muscle Na+,K+ pump content, but the effects on maximal Na+,K+ pump activity and subunit specific mRNA are unknown. Ten healthy male subjects ingested dexamethasone for 5 days and the effects on Na+,K+ pump content......, maximal activity and subunit specific mRNA level (a1, a2, ß1, ß2, ß3) in deltoid and vastus lateralis muscle were investigated. Before treatment, maximal Na+,K+ pump activity, as well as a1, a2, ß1 and ß2 mRNA levels were higher (P ... increased Na+,K+ pump maximal activity in vastus lateralis and deltoid by 14 ± 7% (P Na+,K+ pump content by 18 ± 9% (P

Dexamethasone nanowafer as an effective therapy for dry eye disease.

Science.gov (United States)

Coursey, Terry G; Henriksson, Johanna Tukler; Marcano, Daniela C; Shin, Crystal S; Isenhart, Lucas C; Ahmed, Faheem; De Paiva, Cintia S; Pflugfelder, Stephen C; Acharya, Ghanashyam

2015-09-10

Dry eye disease is a major public health problem that affects millions of people worldwide. It is presently treated with artificial tear and anti-inflammatory eye drops that are generally administered several times a day and may have limited therapeutic efficacy. To improve convenience and efficacy, a dexamethasone (Dex) loaded nanowafer (Dex-NW) has been developed that can release the drug on the ocular surface for a longer duration of time than drops, during which it slowly dissolves. The Dex-NW was fabricated using carboxymethyl cellulose polymer and contains arrays of 500 nm square drug reservoirs filled with Dex. The in vivo efficacy of the Dex-NW was evaluated using an experimental mouse dry eye model. These studies demonstrated that once a day Dex-NW treatment on alternate days during a five-day treatment period was able to restore a healthy ocular surface and corneal barrier function with comparable efficacy to twice a day topically applied dexamethasone eye drop treatment. The Dex-NW was also very effective in down regulating expression of inflammatory cytokines (TNF-α, and IFN-γ), chemokines (CXCL-10 and CCL-5), and MMP-3, that are stimulated by dry eye. Despite less frequent dosing, the Dex-NW has comparable therapeutic efficacy to topically applied Dex eye drops in experimental mouse dry eye model, and these results provide a strong rationale for translation to human clinical trials for dry eye. Copyright © 2015 Elsevier B.V. All rights reserved.

Treatment of refractory uveitic macular edema: results of a first and second implant of long-acting intravitreal dexamethasone

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Zola M

2017-11-01

Full Text Available Marta Zola, Cristina Briamonte, Umberto Lorenzi, Federica Machetta, Federico M Grignolo, Antonio M Fea Ophthalmic Eye Hospital, Department of Surgical Sciences, University of Turin, Italy Purpose: The purpose of this study was to report the functional and anatomical outcomes of a prospective study resulting from repeated dexamethasone intravitreal implants in patients with uveitic refractory macular edema.Methods: Twelve eyes of 9 patients with intermediate and posterior noninfectious inflammatory uveitis complicated with refractory macular edema were regularly reviewed after a dexamethasone intravitreal implant. Patients were examined at baseline, 30, 90, 135, and 180 days with best-corrected visual acuity (BCVA, complete slit-lamp examination, intraocular pressure (IOP, optical coherence tomography, and fluorescein angiography. After 6 months of follow-up, eyes were reassessed to receive a second implant. Results: BCVA significantly improved when comparing the baseline values after the first and second implant (16.2 and 25.8 letters, respectively, 9.6 letters improvements, p<0.05. BCVA was better after the second implant compared to the first one throughout the follow-up, but without statistical significance. Mean central macular thickness (CMT was 446.3±129.9 µm at baseline and was significantly reduced until day 135 (p<0.05. CMT reductions after the second injection showed a similar pattern, though differences were not statistically significant. Cataract progression was observed in 4 of 8 phakic eyes (50% after the first implant, and in 2 of 3 phakic eyes following the second implant, with 1 eye requiring cataract surgery. One eye developed an IOP >30 mmHg 30 days after the second implant, treated topically.Conclusion: Repeated dexamethasone intravitreal implants in uveitic patients with refractory macular edema can be used effectively in a clinical setting with an acceptable safety profile. Keywords: uveitis, macular edema

Typhi–Induced Septic Shock and Acute Respiratory Distress Syndrome in a Previously Healthy Teenage Patient Treated With High-Dose Dexamethasone

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Melissa Brosset Ugas MD

2016-05-01

Full Text Available Typhoid fever is commonly characterized by fever and abdominal pain. Rare complications include intestinal hemorrhage, bowel perforation, delirium, obtundation, and septic shock. Herein we describe the case of a previously healthy 16-year-old male without history of travel, diagnosed with typhoid fever complicated by septic shock and acute respiratory distress syndrome treated with high-dose dexamethasone. This case details severe complications of typhoid fever that are uncommonly seen in developed countries, and the successful response to high-dose dexamethasone as adjunct therapy. High-dose dexamethasone treatment has reportedly decreased Salmonella Typhi mortality, but controlled studies specifically performed in children are lacking, and most reports of its use are over 30 years old and all have originated in developing countries. Providers should include Salmonella Typhi in the differential diagnosis of the pediatric patient with fever, severe abdominal pain, and enteritis, and be aware of its potentially severe complications and the limited data on safety and efficacy of adjunctive therapies that can be considered in addition to antibiotics.

Activation of L-type calcium channels is required for gap junction-mediated intercellular calcium signaling in osteoblastic cells

DEFF Research Database (Denmark)

Jørgensen, Niklas Rye; Teilmann, Stefan Cuoni; Henriksen, Zanne

2003-01-01

The propagation of mechanically induced intercellular calcium waves (ICW) among osteoblastic cells occurs both by activation of P2Y (purinergic) receptors by extracellular nucleotides, resulting in "fast" ICW, and by gap junctional communication in cells that express connexin43 (Cx43), resulting...... in "slow" ICW. Human osteoblastic cells transmit intercellular calcium signals by both of these mechanisms. In the current studies we have examined the mechanism of slow gap junction-dependent ICW in osteoblastic cells. In ROS rat osteoblastic cells, gap junction-dependent ICW were inhibited by removal...... of extracellular calcium, plasma membrane depolarization by high extracellular potassium, and the L-type voltage-operated calcium channel inhibitor, nifedipine. In contrast, all these treatments enhanced the spread of P2 receptor-mediated ICW in UMR rat osteoblastic cells. Using UMR cells transfected to express Cx...

Development and Evaluation of a Novel Microemulsion of Dexamethasone and Tobramycin for Topical Ocular Administration.

Science.gov (United States)

Bachu, Rinda Devi; Stepanski, Marina; Alzhrani, Rami M; Jung, Rose; Boddu, Sai H S

2018-05-01

The purpose of this study was to develop and evaluate a novel dexamethasone- and tobramycin-loaded microemulsion for its potential for treating anterior segment eye infections. The microemulsion was evaluated for pH, particle size, zeta potential, light transmittance, morphology, and in vitro drug release. Sterility of the microemulsion was evaluated by direct as well as plate inoculation methods. Anti-inflammatory activity of dexamethasone, bactericidal activity of tobramycin, and cytotoxicity of the microemulsion were assessed and compared to that of the marketed eye drop suspension (Tobradex ® ). Histological evaluation was performed in bovine corneas to assess the safety of microemulsion in comparison to Tobradex suspension. In addition, the stability of the microemulsion was studied at 4°C, 25°C, and 40°C. The pH of the microemulsion was close to the pH of tear fluid. The microemulsion displayed an average globule size under 20 nm, with light transmittance around 95%-100%. The aseptically prepared microemulsion remained sterile for up to 14 days. The cytotoxicity of the microemulsion in bovine corneal endothelial cells was comparable to that of the Tobradex suspension. The anti-inflammatory activity of dexamethasone and the antibacterial activity of tobramycin from the microemulsion were significantly higher than those of the Tobradex suspension (P microemulsion was found to be stable at 4°C and 25°C for 3 months. In conclusion, the developed microemulsion could be explored as a suitable alternative to the marketed suspension for treating anterior segment eye infections.

Disruption?

DEFF Research Database (Denmark)

2016-01-01

This is a short video on the theme disruption and entrepreneurship. It takes the form of an interview with John Murray......This is a short video on the theme disruption and entrepreneurship. It takes the form of an interview with John Murray...

Dexamethasone-responsive hypertension in young women with suppressed renin and aldosterone

International Nuclear Information System (INIS)

Hoefnagels, W.H.L.; Hofman, J.A.; Smals, A.G.H.; Drayer, J.I.M.; Kloppenborg, P.W.C.; Benraad, T.J.

1978-01-01

Pronounced hypoaldosteronism was found in three young women with hypertension and symptoms of mineralocorticoid overproduction - i.e., hyporeninaemia, hypokalaemia, and a fall in blood-pressure after diuretic therapy. Plasma 11-deoxycorticosterone and 18-hydroxy-11-deoxycorticosterone concentrations were normal. Treatment with dexamethasone induced a return to normal of blood-pressure and plasma-potassium and an increase in plasma-renin activity and urinary aldosterone excretion. The data suggest that hypertension in these patients is maintained by overproduction of an unknown adrenocorticotropin-dependent mineralocortocoid. (author)

Additive manufacturing of scaffolds with dexamethasone controlled release for enhanced bone regeneration.

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Costa, Pedro F; Puga, Ana M; Díaz-Gomez, Luis; Concheiro, Angel; Busch, Dirk H; Alvarez-Lorenzo, Carmen

2015-12-30

The adoption of additive manufacturing in tissue engineering and regenerative medicine (TERM) strategies greatly relies on the development of novel 3D printable materials with advanced properties. In this work we have developed a material for bone TERM applications with tunable bioerosion rate and dexamethasone release profile which can be further employed in fused deposition modelling (the most common and accessible 3D printing technology in the market). The developed material consisted of a blend of poly-ϵ-caprolactone (PCL) and poloxamine (Tetronic®) and was processed into a ready-to-use filament form by means of a simplified melt-based methodology, therefore eliminating the utilization of solvents. 3D scaffolds composed of various blend formulations were additively manufactured and analyzed revealing blend ratio-specific degradation rates and dexamethasone release profiles. Furthermore, in vitro culture studies revealed a similar blend ratio-specific trend concerning the osteoinductive activity of the fabricated scaffolds when these were seeded and cultured with human mesenchymal stem cells. The developed material enables to specifically address different regenerative requirements found in various tissue defects. The versatility of such strategy is further increased by the ability of additive manufacturing to accurately fabricate implants matching any given defect geometry. Copyright © 2015 Elsevier B.V. All rights reserved.

The effect of granisetron dexamethasone combination on postoperative nausea and vomiting in gynecological operations

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Ziya Kaya

2010-06-01

Full Text Available Objectives: Postoperative nausea and vomiting (PONV is one of the most frequent adverse effects of anesthesia. PONV postpones hospital stays and also delays recover and getting better, of the patients. The objective of the current study is to compare efficacy of prophylactic granisetron(40 μ/kg + dexamethasone (4 mg combination against PONV in different anesthesia models.Materials and Methods: 72 patients with an age range of 18-72 years and ASA 1 or 2 were enrolled in the present study. The patients were assigned as group 1 propofol-remifentanil (P-R, group 2 propofol- nitrous oxide (P-N2O, group 3 sevoflurane- nitrous oxide (S-N2O and group 4 sevoflurane-remifentanyl-air (S-R+H. Inductions of the patients in all groups were made with intravenous 2-3 mg/kg propofol, 1μ/kg remifentanil and 0.2 mg/kg cis-atracurium. 4 mg of dexamethasone by bolus and 40 μ/kg of granisetron by infusion were administered to the patients in all groups after induction. During the last 10 minutes of the operation, 1mg/kg tramadol was administered.Postoperative nausea and vomiting, VAS scores, and additional antiemetic needs were recorded during postoperative 48 hours.Results: Postoperative 48 hours follow up revealed that PONV was seen 27%, 16%, 38%, 48% frequencies in (P+R, (P+ N2O, (S+ N2O, (S+R+H groups, respectively.While antiemetic requirement was not observed in (P+ N2O and (S+ N2O groups, the patients in (P+R and (S+R+H groups needed additional antiemetic drugs with a frequency of 5.5% and 11% respectively.Conclusion: Granisetron, dexamethasone combination in different anesthetic models did not reveal significant difference in terms of postoperative nausea, vomiting, and additional antiemetic usage.

Effects of dexamethasone and insulin on the synthesis of triacylglycerols and phosphatidylcholine and the secretion of very-low-density lipoproteins and lysophosphatidylcholine by monolayer cultures of rat hepatocytes.

Science.gov (United States)

Mangiapane, E H; Brindley, D N

1986-01-01

Rat hepatocytes in monolayer culture were preincubated for 19 h with 1 microM-dexamethasone, and the incubation was continued for a further 23 h with [14C]oleate, [3H]glycerol and 1 microM-dexamethasone. Dexamethasone increased the secretion of triacylglycerol into the medium in particles that had the properties of very-low-density lipoproteins. The increased secretion was matched by a decrease in the triacylglycerol and phosphatidylcholine that remained in the hepatocytes. Preincubating the hepatocytes for the total 42 h period with 36 nM-insulin decreased the amount of triacylglycerol in the medium and in the cells after the final incubation for 23 h with radioactive substrates. However, insulin had no significant effect on the triacylglycerol content of the cell and medium when it was present only in the final 23 h incubation. Insulin antagonized the effects of dexamethasone in stimulating the secretion of triacylglycerol from the hepatocytes, especially when it was present throughout the total 42 h period. The labelling of lysophosphatidylcholine in the medium when hepatocytes were incubated with [14C]oleate and [3H]glycerol was greater than that of phosphatidylcholine. The appearance of this lipid in the medium, unlike that of triacylglycerol and phosphatidylcholine, was not stimulated by dexamethasone, or inhibited by colchicine. However, the presence of lysophosphatidylcholine in the medium was decreased when the hepatocytes were incubated with both dexamethasone and insulin. These findings are discussed in relation to the control of the synthesis of glycerolipids and the secretion of very-low-density lipoproteins and lysophosphatidylcholine by the liver, particularly in relation to the interactions of glucocorticoids and insulin. PMID:3513755

The Effect of Dexamethasone on Symptoms of Posttraumatic Stress Disorder and Depression After Cardiac Surgery and Intensive Care Admission: Longitudinal Follow-Up of a Randomized Controlled Trial.

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Kok, Lotte; Hillegers, Manon H; Veldhuijzen, Dieuwke S; Cornelisse, Sandra; Nierich, Arno P; van der Maaten, Joost M; Rosseel, Peter M; Hofland, Jan; Sep, Milou S; Dieleman, Jan M; Vinkers, Christiaan H; Peelen, Linda M; Joëls, Marian; van Dijk, Diederik

2016-03-01

Cardiac surgery and postoperative admission to the ICU may lead to posttraumatic stress disorder and depression. Perioperatively administered corticosteroids potentially alter the risk of development of these psychiatric conditions, by affecting the hypothalamic-pituitary-adrenal axis. However, findings of previous studies are inconsistent. We aimed to assess the effect of a single dose of dexamethasone compared with placebo on symptoms of posttraumatic stress disorder and depression and health-related quality of life after cardiac surgery and ICU admission. Follow-up study of a randomized clinical trial. Five Dutch heart centers. Cardiac surgery patients (n = 1,244) who participated in the Dexamethasone for Cardiac Surgery trial. A single intraoperative IV dose of dexamethasone or placebo was administered in a randomized, double-blind way. Symptoms of posttraumatic stress disorder, depression, and health-related quality of life were assessed with validated questionnaires 1.5 years after randomization. Data were available for 1,125 patients (90.4%); of which 561 patients received dexamethasone and 564 patients received placebo. Overall, the prevalence of psychopathology was not influenced by dexamethasone. Posttraumatic stress disorder and depression were present in, respectively, 52 patients (9.3%) and 69 patients (12.3%) who received dexamethasone and in 66 patients (11.7%) and 78 patients (13.8%) who received placebo (posttraumatic stress disorder: odds ratio, 0.82; 95% CI, 0.55-1.20; p = 0.30; depression: odds ratio, 0.92; 95% CI, 0.64-1.31; p = 0.63). Subgroup analysis revealed a lower prevalence of posttraumatic stress disorder (odds ratio, 0.23; 95% CI, 0.07-0.72; p stress disorder and depression. However, in female patients, beneficial effects on the occurrence of posttraumatic stress disorder and depression may be present.

The effect of dexamethasone and triiodothyronine on terminal differentiation of primary bovine chondrocytes and chondrogenically differentiated mesenchymal stem cells.

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Randau, Thomas M; Schildberg, Frank A; Alini, Mauro; Wimmer, Matthias D; Haddouti, El-Mustapha; Gravius, Sascha; Ito, Keita; Stoddart, Martin J

2013-01-01

The newly evolved field of regenerative medicine is offering solutions in the treatment of bone or cartilage loss and deficiency. Mesenchymal stem cells, as well as articular chondrocytes, are potential cells for the generation of bone or cartilage. The natural mechanism of bone formation is that of endochondral ossification, regulated, among other factors, through the hormones dexamethasone and triiodothyronine. We investigated the effects of these hormones on articular chondrocytes and chondrogenically differentiated mesenchymal stem cells, hypothesizing that these hormones would induce terminal differentiation, with chondrocytes and differentiated stem cells being similar in their response. Using a 3D-alginate cell culture model, bovine chondrocytes and chondrogenically differentiated stem cells were cultured in presence of triiodothyronine or dexamethasone, and cell proliferation and extracellular matrix production were investigated. Collagen mRNA expression was measured by real-time PCR. Col X mRNA and alkaline phosphatase were monitored as markers of terminal differentiation, a prerequisite of endochondral ossification. The alginate culture system worked well, both for the culture of chondrocytes and for the chondrogenic differentiation of mesenchymal stem cells. Dexamethasone led to an increase in glycosaminoglycan production. Triiodothyronine increased the total collagen production only in chondrocytes, where it also induced signs of terminal differentiation, increasing both collagen X mRNA and alkaline phosphatase activity. Dexamethasone induced terminal differentiation in the differentiated stem cells. The immature articular chondrocytes used in this study seem to be able to undergo terminal differentiation, pointing to their possible role in the onset of degenerative osteoarthritis, as well as their potential for a cell source in bone tissue engineering. When chondrocyte-like cells, after their differentiation, can indeed be moved on towards terminal

Stability of i.v. admixture containing metoclopramide, diphenhydramine hydrochloride, and dexamethasone sodium phosphate in 0.9% sodium chloride injection.

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Kintzel, Polly E; Zhao, Ting; Wen, Bo; Sun, Duxin

2014-12-01

The chemical stability of a sterile admixture containing metoclopramide 1.6 mg/mL, diphenhydramine hydrochloride 2 mg/mL, and dexamethasone sodium phosphate 0.16 mg/mL in 0.9% sodium chloride injection was evaluated. Triplicate samples were prepared and stored at room temperature without light protection for a total of 48 hours. Aliquots from each sample were tested for chemical stability immediately after preparation and at 1, 4, 8, 24, and 48 hours using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Metoclopramide, diphenhydramine hydrochloride, and dexamethasone sodium phosphate were selectively monitored using multiple-reaction monitoring. Samples were diluted differently for quantitation using three individual LC-MS/MS methods. To determine the drug concentration of the three compounds in the samples, three calibration curves were constructed by plotting the peak area or the peak area ratio versus the concentration of the calibration standards of each tested compound. Apixaban was used as an internal standard. Linearity of the calibration curve was evaluated by the correlation coefficient r(2). Constituents of the admixture of metoclopramide 1.6 mg/mL, diphenhydramine hydrochloride 2 mg/mL, and dexamethasone sodium phosphate 0.16 mg/mL in 0.9% sodium chloride injection retained more than 90% of their initial concentrations over 48 hours of storage at room temperature without protection from light. The observed variability in concentrations of these three compounds was within the limits of assay variability. An i.v. admixture containing metoclopramide 1.6 mg/mL, diphenhydramine hydrochloride 2 mg/mL, and dexamethasone sodium phosphate 0.16 mg/mL in 0.9% sodium chloride injection was chemically stable for 48 hours when stored at room temperature without light protection. Copyright © 2014 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Mechanisms of dexamethasone-mediated inhibition of Toll-like receptor signaling induced by Neisseria meningitidis and Streptococcus pneumoniae

DEFF Research Database (Denmark)

Mogensen, Trine; Berg, Randi S; Paludan, Søren R

2008-01-01

Excessive inflammation contributes to the pathogenesis of bacterial meningitis, which remains a serious disease despite treatment with antibiotics. Therefore, anti-inflammatory drugs have important therapeutic potential, and clinical trials have revealed that early treatment with dexamethasone...

Intercellular communication and cell proliferation in precision-cut rat liver slices : effect of medium composition and DDT

NARCIS (Netherlands)

Graaf, I.A.M.; Tajima, O.; Groten, J.P.; Wolterbeek, A.P.M.

2000-01-01

Gap junctional intercellular communication (GJIC) and cell proliferation were studied in control and 1,1'-bis(p-chlorophenyl)-2,2,2,-trichloroethane (DDT) treated precision-cut liver slices of rat by evaluating connexin 32 (Cx32) expression and 5-bromo-2'-deoxyuridine (BrdU) incorporation. In

Effective cross-over to granisetron after failure to ondansetron, a randomized double blind study in patients failing ondansetron plus dexamethasone during the first 24 hours following highly emetogenic chemotherapy

Science.gov (United States)

de Wit, R; de Boer, A C; vd Linden, G H M; Stoter, G; Sparreboom, A; Verweij, J

2001-01-01

In view of the similarity in chemical structure of the available 5HT3-receptor antagonists it is assumed, whilst these agents all act at the same receptor, that failure to one agent would predict subsequent failure to all 5HT3-receptor antagonists. We conducted a randomized double blind trial of granisetron 3 mg plus dexamethasone 10 mg versus continued treatment with ondansetron 8 mg plus dexamethasone 10 mg in patients with protection failure on ondansetron 8 mg plus dexamethasone 10 mg during the first 24 hours following highly emetogenic chemotherapy. Of 40 eligible patients, 21 received ondansetron + dexamethasone and 19 received granisetron + dexamethasone. We found a significant benefit from crossing-over to granisetron after failure on ondansetron. Of the 19 patients who crossed over to granisetron, 9 patients obtained complete protection, whereas this was observed in 1 of the 21 patients continuing ondansetron, P = 0.005. These results indicate that there is no complete cross-resistance between 5HT3-receptor antagonists, and that patients who have acute protection failure on one 5HT3-receptor antagonist should be offered cross-over to another 5HT3-receptor antagonist. © 2001 Cancer Research Campaign  http://www.bjcancer.com PMID:11710819

Functional aspects of dexamethasone upregulated nicotinic acetylcholine receptors in C2C12 myotubes

NARCIS (Netherlands)

Maestrone, E; Lagostena, L; Henning, RH; DenHertog, A; Nobile, M

Three days of treatment with the glucocorticoid dexamethasone (1 nM-mu M) induced a concentration-dependent up-regulation of muscle nicotinic acetylcholine receptor (nAChR) in C2C12 mouse myotubes (EC(50)=10+/-7.3 nM), as assessed by [H-3]alpha-BuTx binding. The maximum increase in binding amounted

Disruption of fibronectin matrix affects type IV collagen, fibrillin and laminin deposition into extracellular matrix of human trabecular meshwork (HTM) cells.

Science.gov (United States)

Filla, Mark S; Dimeo, Kaylee D; Tong, Tiegang; Peters, Donna M

2017-12-01

Fibronectin fibrils are a major component of the extracellular matrix (ECM) of the trabecular meshwork (TM). They are a key mediator of the formation of the ECM which controls aqueous humor outflow and contributes to the pathogenesis of glaucoma. The purpose of this work was to determine if a fibronectin-binding peptide called FUD, derived from the Streptococcus pyogenes Functional Upstream Domain of the F1 adhesin protein, could be used to control fibronectin fibrillogenesis and hence ECM formation under conditions where its expression was induced by treatment with the glucocorticoid dexamethasone. FUD was very effective at preventing fibronectin fibrillogenesis in the presence or absence of steroid treatment as well as the removal of existing fibronectin fibrils. Disruption of fibronectin fibrillogenesis by FUD also disrupted the incorporation of type IV collagen, laminin and fibrillin into the ECM. The effect of FUD on these other protein matrices, however, was found to be dependent upon the maturity of the ECM when FUD was added. FUD effectively disrupted the incorporation of these other proteins into matrices when added to newly confluent cells that were forming a nascent ECM. In contrast, FUD had no effect on these other protein matrices if the cell cultures already possessed a pre-formed, mature ECM. Our studies indicate that FUD can be used to control fibronectin fibrillogenesis and that these fibrils play a role in regulating the assembly of other ECM protein into matrices involving type IV collagen, laminin, and fibrillin within the TM. This suggests that under in vivo conditions, FUD would selectively disrupt fibronectin fibrils and de novo assembly of other proteins into the ECM. Finally, our studies suggest that targeting fibronectin fibril assembly may be a viable treatment for POAG as well as other glaucomas involving excessive or abnormal matrix deposition of the ECM. Copyright © 2017 Elsevier Ltd. All rights reserved.

Characterization of buffy coat-derived granulocytes for clinical use: a comparison with granulocyte colony-stimulating factor/dexamethasone-pretreated donor-derived products.

Science.gov (United States)

van de Geer, A; Gazendam, R P; Tool, A T J; van Hamme, J L; de Korte, D; van den Berg, T K; Zeerleder, S S; Kuijpers, T W

2017-02-01

Buffy coat-derived granulocytes have been described as an alternative to the apheresis product from donors pretreated with dexamethasone and granulocyte colony-stimulating factor (G-CSF). The latter is - dependent on the local and national settings - obtained following a demanding and time-consuming procedure, which is undesirable in critically ill septic patients. In contrast, buffy coat-derived products have a large volume and are often heavily contaminated with red cells and platelets. We developed a new pooled buffy coat-derived product with high purity and small volume, and performed a comprehensive functional characterization of these granulocytes. We pooled ten buffy coats following the production of platelet concentrates. Saline 0·9% was added to decrease the viscosity and the product was split into plasma, red cells and a 'super' buffy coat. Functional data of the granulocytes were compared to those obtained with granulocytes from healthy controls and G-CSF/dexamethasone-pretreated donors. Buffy coat-derived granulocytes showed adhesion, chemotaxis, reactive oxygen species production, degranulation, NETosis and in vitro killing of Staphylococcus aureus, Escherichia coli and Aspergillus species comparable to control and G-CSF/dexamethasone-derived granulocytes. Candida killing was superior compared to G-CSF/dexamethasone-derived granulocytes. Immunophenotyping was normal; especially no signs of activation in the buffy coat-derived granulocytes were seen. Viability was reduced. Buffy coats are readily available in the regular blood production process and would take away the concerns around the apheresis product. The product described appears a promising alternative for transfusion purposes. © 2017 International Society of Blood Transfusion.

Comparison of clinical effects of prilocaine, dexamethasone added to prilocaine and levobupivacaine on brachial plexus block

International Nuclear Information System (INIS)

Saritas, A.; Sabuncu, C.

2014-01-01

Objective: To determine whether the addition of 8mg dexamethasone to axillary brachial plexus block would prolong the duration of sensory and motor block in patients undergoing hand and forearm surgery. Methods: The prospective, randomised, double-blinded study was conducted at the Eskisehir Osmangazi University Medical School, Turkey, from October 2008 to December 2009. It comprised 45 American Society of Anaesthesiologists grade I and II patients under elective surgery of the hand and forearm. The patients were randomly divided into 3 groups: 5 mg/kg of 2% prilocaine was applied to Group 1; 5 mg/kg of 2% prilocaine +8mg of dexamethasone (2ml) was applied to Group 2; and 1.5 mg/kg 0.5% levobupivacaine was applied to Group 3. Sensory and motor block onset time as well as the duration of motor and sensory block of those were monitored and recorded. SPSS 15 was used for statistical analysis. Results: Of the 45 patients, 27 (60%) were men and 18 (40%) were women. There was no significant difference among the groups in terms of demographic data. Based on the duration of motor and sensory block, similar periods of time in Group 1 and Group 2 were noted, whereas this period was statistically different and significantly longer in Group 3 (p<0.001). There were no complications encountered. Conclusion: The addition of dexamethasone to prilocaine prolonged the duration of sensory and motor block. It could be used as an effective adjuvant agent. Levobupivacain could be a more appropriate local anaesthetic in post-operative analgesia and prolonged surgical procedures. (author)

Experimental Bothrops atrox envenomation: Efficacy of antivenom therapy and the combination of Bothrops antivenom with dexamethasone.

Directory of Open Access Journals (Sweden)

Gabriella Neves Leal Santos Barreto

2017-03-01

Full Text Available Bothrops atrox snakes are the leading cause of snake bites in Northern Brazil. The venom of this snake is not included in the antigen pool used to obtain the Bothrops antivenom. There are discrepancies in reports on the effectiveness of this antivenom to treat victims bitten by B. atrox snakes. However, these studies were performed using a pre-incubation of the venom with the antivenom and, thus, did not simulate a true case of envenomation treatment. In addition, the local lesions induced by Bothrops venoms are not well resolved by antivenom therapy. Here, we investigated the efficacy of the Bothrops antivenom in treating the signs and symptoms caused by B. atrox venom in mice and evaluated whether the combination of dexamethasone and antivenom therapy enhanced the healing of local lesions induced by this envenomation. In animals that were administered the antivenom 10 minutes after the envenomation, we observed an important reduction of edema, dermonecrosis, and myonecrosis. When the antivenom was given 45 minutes after the envenomation, the edema and myonecrosis were reduced, and the fibrinogen levels and platelet counts were restored. The groups treated with the combination of antivenom and dexamethasone had an enhanced decrease in edema and a faster recovery of the damaged skeletal muscle. Our results show that Bothrops antivenom effectively treats the envenomation caused by Bothrops atrox and that the use of dexamethasone as an adjunct to the antivenom therapy could be useful to improve the treatment of local symptoms observed in envenomation caused by Bothrops snakes.

Treatment of acute relapses in multiple sclerosis at home with oral dexamethasone : a pilot study

NARCIS (Netherlands)

De Keyser, J; Zwanikken, C; Zorgdrager, A; Oenema, D

The objective of this study was to investigate the feasibility of treating relapses of multiple sclerosis (MS) at home with oral dexamethasone. Twenty-five out of 28 consecutive patients with MS who presented with a relapse of less than 2 weeks' duration were treated on an open basis with oral

Lysophosphatidic Acid Disrupts Junctional Integrity and Epithelial Cohesion in Ovarian Cancer Cells

Directory of Open Access Journals (Sweden)

Yueying Liu

2012-01-01

Full Text Available Ovarian cancer metastasizes via exfoliation of free-floating cells and multicellular aggregates from the primary tumor to the peritoneal cavity. A key event in EOC metastasis is disruption of cell-cell contacts via modulation of intercellular junctional components including cadherins. Ascites is rich in lysophosphatidic acid (LPA, a bioactive lipid that may promote early events in ovarian cancer dissemination. The objective of this paper was to assess the effect of LPA on E-cadherin junctional integrity. We report a loss of junctional E-cadherin in OVCAR3, OVCA429, and OVCA433 cells exposed to LPA. LPA-induced loss of E-cadherin was concentration and time dependent. LPA increased MMP-9 expression and promoted MMP-9-catalyzed E-cadherin ectodomain shedding. Blocking LPA receptor signaling inhibited MMP-9 expression and restored junctional E-cadherin staining. LPA-treated cells demonstrated a significant decrease in epithelial cohesion. Together these data support a model wherein LPA induces MMP-9 expression and MMP-9-catalyzed E-cadherin ectodomain shedding, resulting in loss of E-cadherin junctional integrity and epithelial cohesion, facilitating metastatic dissemination of ovarian cancer cells.

Dexamethasone abrogates the antimicrobial and antibiofilm activities of different drugs against clinical isolates of Staphylococcus aureus and Pseudomonas aeruginosa

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Aquila Rodrigues

2017-01-01

Full Text Available Staphylococcus aureus and Pseudomonas aeruginosa are part of the human microbiota and are also important bacterial pathogens, for which therapeutic options are lacking nowadays. The combined administration of corticosteroids and antimicrobials is commonly used in the treatment of infectious diseases to control inflammatory processes and to minimize potential toxicity of antimicrobials, avoiding sequelae. Although different pharmaceutical dosage forms of antimicrobials combined to corticosteroids are available, studies on the interference of corticosteroids on the pharmacological activity of antimicrobials are scarce and controversial. Here, we provide evidence of the interference of dexamethasone on the pharmacological activity of clinically important antimicrobial drugs against biofilms and planktonic cells of S. aureus and P. aeruginosa. Broth microdilution assays of minimal inhibitory concentration (MIC, minimum bactericidal concentration (MBC, and minimum biofilm eradication concentration (MBEC of gentamicin, chloramphenicol, oxacillin, ceftriaxone and meropenem were conducted with and without the addition of dexamethasone. The effect of all drugs was abrogated by dexamethasone in their MIC, MBC, and MBEC, except gentamicin and meropenem, for which the MBC was not affected in some strains. The present study opens doors for more investigations on in vitro and in vivo effects and safety of the combination of antimicrobials and glucocorticoids.

Increasing the endogenous NO level causes catalase inactivation and reactivation of intercellular apoptosis signaling specifically in tumor cells.

Science.gov (United States)

Bauer, Georg

2015-12-01

Tumor cells generate extracellular superoxide anions and are protected against intercellular apoptosis-inducing HOCl- and NO/peroxynitrite signaling through the expression of membrane-associated catalase. This enzyme decomposes H2O2 and thus prevents HOCl synthesis. It efficiently interferes with NO/peroxynitrite signaling through oxidation of NO and decomposition of peroxynitrite. The regulatory potential of catalase at the crosspoint of ROS and RNS chemical biology, as well as its high local concentration on the outside of the cell membrane of tumor cells, establish tight control of intercellular signaling and thus prevent tumor cell apoptosis. Therefore, inhibition of catalase or its inactivation by singlet oxygen reactivate intercellular apoptosis-inducing signaling. Nitric oxide and peroxynitrite are connected with catalase in multiple and meaningful ways, as (i) NO can be oxidated by compound I of catalase, (ii) NO can reversibly inhibit catalase, (iii) peroxynitrite can be decomposed by catalase and (iv) the interaction between peroxynitrite and H2O2 leads to the generation of singlet oxygen that inactivates catalase. Therefore, modulation of the concentration of free NO through addition of arginine, inhibition of arginase, induction of NOS expression or inhibition of NO dioxygenase triggers an autoamplificatory biochemical cascade that is based on initial formation of singlet oxygen, amplification of superoxide anion/H2O2 and NO generation through singlet oxygen dependent stimulation of the FAS receptor and caspase-8. Finally, singlet oxygen is generated at sufficiently high concentration to inactivate protective catalase and to reactivate intercellular apoptosis-inducing ROS signaling. This regulatory network allows to establish several pathways for synergistic interactions, like the combination of modulators of NO metabolism with enhancers of superoxide anion generation, modulators of NO metabolism that act at different targets and between modulators of

Increasing the endogenous NO level causes catalase inactivation and reactivation of intercellular apoptosis signaling specifically in tumor cells

Science.gov (United States)

Bauer, Georg

2015-01-01

Tumor cells generate extracellular superoxide anions and are protected against intercellular apoptosis-inducing HOCl- and NO/peroxynitrite signaling through the expression of membrane-associated catalase. This enzyme decomposes H2O2 and thus prevents HOCl synthesis. It efficiently interferes with NO/peroxynitrite signaling through oxidation of NO and decomposition of peroxynitrite. The regulatory potential of catalase at the crosspoint of ROS and RNS chemical biology, as well as its high local concentration on the outside of the cell membrane of tumor cells, establish tight control of intercellular signaling and thus prevent tumor cell apoptosis. Therefore, inhibition of catalase or its inactivation by singlet oxygen reactivate intercellular apoptosis-inducing signaling. Nitric oxide and peroxynitrite are connected with catalase in multiple and meaningful ways, as (i) NO can be oxidated by compound I of catalase, (ii) NO can reversibly inhibit catalase, (iii) peroxynitrite can be decomposed by catalase and (iv) the interaction between peroxynitrite and H2O2 leads to the generation of singlet oxygen that inactivates catalase. Therefore, modulation of the concentration of free NO through addition of arginine, inhibition of arginase, induction of NOS expression or inhibition of NO dioxygenase triggers an autoamplificatory biochemical cascade that is based on initial formation of singlet oxygen, amplification of superoxide anion/H2O2 and NO generation through singlet oxygen dependent stimulation of the FAS receptor and caspase-8. Finally, singlet oxygen is generated at sufficiently high concentration to inactivate protective catalase and to reactivate intercellular apoptosis-inducing ROS signaling. This regulatory network allows to establish several pathways for synergistic interactions, like the combination of modulators of NO metabolism with enhancers of superoxide anion generation, modulators of NO metabolism that act at different targets and between modulators of

Disruptions in JET

International Nuclear Information System (INIS)

Wesson, J.A.; Gill, R.D.; Hugon, M.

1989-01-01

In JET, both high density and low-q operation are limited by disruptions. The density limit disruptions are caused initially by impurity radiation. This causes a contraction of the plasma temperature profile and leads to an MHD unstable configuration. There is evidence of magnetic island formation resulting in minor disruptions. After several minor disruptions, a major disruption with a rapid energy quench occurs. This event takes place in two stages. In the first stage there is a loss of energy from the central region. In the second stage there is a more rapid drop to a very low temperature, apparently due to a dramatic increase in impurity radiation. The final current decay takes place in the resulting cold plasma. During the growth of the MHD instability the initially rotating mode is brought to rest. This mode locking is believed to be due to an electromagnetic interaction with the vacuum vessel and external magnetic field asymmetries. The low-q disruptions are remarkable for the precision with which they occur at q ψ = 2. These disruptions do not have extended precursors or minor disruptions. The instability grows and locks rapidly. The energy quench and current decay are generally similar to those of the density limit. (author). 43 refs, 35 figs, 3 tabs

[Comparison of antiemesis effects of granisetron, aprepitant and dexamethasone to palonosetron, aprepitant and dexamethasone in treatment of high-emetic risk chemotherapy-induced nausea and vomiting - a retrospective study for efficacy and safety in a single institute].

Science.gov (United States)

Osawa, Hiroshi; Goto, Hiroaki; Myojo, Tomohiro

2013-05-01

Nausea and vomiting are among the most problematic symptoms experienced by patients with cancer who are receiving chemotherapy. 5-hydroxytryptamine 3(5-HT3)-receptor antagonists, NK1 receptor antagonists(aprepitant)and dexamethasone are now the standard therapies for preventing chemotherapy-induced nausea and vomiting(CINV)that follow highly emetogenic chemotherapy, such as cisplatin and anthracycline. However, since it is not cleared which 5-HT3-recepter antagonist is a proper treatment for combined use with aprepitant and dexamethasone, we conducted a questionnaire survey, which used the numerical rating scale(NRS), for comparing palonosetron with granisetron in the same patient. Palonosetron showed a significant improvement of nausea for both acute(within 24 hours)and delayed phase(24-120 hours later), regardless of the type of chemotherapy(cisplatin or anthracycline-based regimen). Furthermore, palonosetron had a tolerable safety profile. Our study suggests that palonosetron-based antiemetic treatment will be a preferred choice for preventing CINV following highly emetogenic chemotherapy.

Effect of premedication with ibuprofen and dexamethasone on success rate of inferior alveolar nerve block for teeth with asymptomatic irreversible pulpitis: a randomized clinical trial.

Science.gov (United States)

Shahi, Shahriar; Mokhtari, Hadi; Rahimi, Saeed; Yavari, Hamid Reza; Narimani, Shima; Abdolrahimi, Majid; Nezafati, Saeed

2013-02-01

The aim of this study was to compare 2 kinds of anti-inflammatory medicines (ie, dexamethasone and ibuprofen) with a placebo according to their effects on the success rates of an inferior alveolar nerve block (IANB) for the endodontic treatment of mandibular molars with irreversible pulpitis. A total of 165 patients were divided into 3 groups of 55 patients each and were given a capsule of the same color and size (ie, a placebo of lactose powder, 400 mg ibuprofen, or 0.5 mg dexamethasone). One hour after the oral administration of the capsules, all the patients received a standard IANB. In patients with a successful IANB, the teeth were examined with a cold pulp test. Patients were asked to assess their pain using the visual analog scale. Then, endodontic access cavity preparation was initiated. In case of pain during the treatment, the patients were asked to rate the pain on the visual analog scale. Success was defined as no or mild pain during treatment. The chi-square test and analysis of variance were used to compare qualitative and quantitative data among the groups. No significant differences were found regarding the sex of the patients in the 3 groups (P > .05). The dexamethasone group showed significantly higher success rates compared with the placebo group (P = .001). There were no significant differences between the ibuprofen and placebo groups (P = .055) or the dexamethasone and ibuprofen groups (P = .34). Premedication with dexamethasone increased the success rate of an IANB in mandibular molars with asymptomatic irreversible pulpitis. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Preliminary study of 24 h bone scintigraphy after dexamethason intervention for differentiating the benign from malignant bone lesions

International Nuclear Information System (INIS)

Fan Yang; Li Yaming; Han Chunqi; Li Deshun; Ma Aiping; Liang Chenrong; Sun Zhenqiu; Liu Hao; Sun Xiaorong; Yin Yafu

2001-01-01

Objective: To explore the clinical value of 24 h bone scintigraphy after dexamethason intervention for differentiating the benign and malignant bone lesions. Methods: Twenty patients with malignant bone lesion (242 foci) and 21 patients with benign bone lesion (102 foci) were randomly divided into non-intervention group and intervention group for the comparative study. The patients in the non-intervention group underwent bone scintigraphy 3 and 24 h after the tracer administration, while the patients in the intervention group were given dexamethason 6.75 mg orally after 3 h bone imaging, then underwent 24 h bone in aging. Different regions of interest were drawn in 3 and 24 h imaging, then the radionuclide uptake ratios (RUR) of 24 h to 3 h was calculated. Results: There were no significant differences in RUR of benign lesions between the non-intervention group and intervention group (q =0.94, P > 0.05). There were significant differences in RUR between the malignant lesions in the non-intervention group and that in the intervention group (q 20.10, P < 0.01); there were significant differences in RUR between the benign and the malignant lesions in the non-intervention group (q = 1.81, P < 0.05); and there were also significant differences in RUR between the benign and the malignant lesions in the intervention group (q = 16.39, P < 0.01). The sensitivity, specificity and accuracy of differentiating the benign and malignant bone lesions by RUR with non-intervention and intervention were 75.5%, 86.2%, 65.8% and 81.5%, 87.5%, 83.1%, respectively. Conclusions: Comparing with the routine bone imaging, 24 h bone scintigraphy after dexamethason intervention elevated the diagnosis efficiency for differentiation of the benign and malignant bone lesions. 24 h bone scintigraphy associated with dexamethason intervention is convenient and acceptable in differentiation of benign and malignant bone lesions, and it is proved to be of great value for clinical application

Bcl2-independent chromatin cleavage is a very early event during induction of apoptosis in mouse thymocytes after treatment with either dexamethasone or ionizing radiation.

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Hahn, Peter J; Lai, Zhi-Wei; Nevaldine, Barbara; Schiff, Ninel; Fiore, Nancy C; Silverstone, Allen E

2003-11-01

We have quantified the emergence of early chromatin breaks during the signal transduction phase of apoptosis in mouse thymocytes after treatment with either ionizing radiation or dexamethasone. Dexamethasone at 1 microM can induce significant levels of DNA breaks (equivalent to the amount induced directly by 7.5 Gy ionizing radiation) within 0.5 h of treatment. The execution phase of apoptosis was not observed until 4-6 h after the same treatment. The presence of the Bcl2 transgene under the control of the p56lck promoter almost completely inhibited apoptosis up to 24 h after treatment, but it had virtually no effect on the early chromatin cleavage occurring in the first 6 h. Ionizing radiation induced chromatin cleavage both directly by damaging DNA and indirectly with kinetics similar to the induction of chromatin cleavage by dexamethasone. The presence of the Bcl2 transgene had no effect on the direct or indirect radiation-induced cleavage in the first 6 h, but after the first 6 h, the Bcl2 gene inhibited further radiation-induced chromatin cleavage. These results suggest that endonucleases are activated within minutes of treatment with either dexamethasone or ionizing radiation as part of the very early signal transduction phase of apoptosis, and prior to the irreversible commitment to cell death.

Comparison of Effect of Oral Premedication with Ibuprofen or Dexamethasone on Anesthetic Efficacy of Inferior Alveolar Nerve Block in Patients with Irreversible Pulpitis: A Prospective, Randomized, Controlled, Double-blind Study.

Science.gov (United States)

Bidar, Maryam; Mortazavi, Soheil; Forghani, Maryam; Akhlaghi, Saeed

2017-01-01

The purpose of this prospective, randomized, double-blind, placebo-controlled study was to determine the effect of preoperative oral administration of ibuprofen or dexamethasone on the success rate of inferior alveolar nerve block (IANB) in patients with symptomatic irreversible pulpitis. Seventy-eight patients with irreversible pulpitis were randomly divided into 3 groups (26 per group) and given one of the following at 1 hr prior to performing local anesthesia: a placebo; 400 mg ibuprofen; or 4 mg dexamethasone. Each patient recorded their pain level on a visual analog scale before taking the medication or placebo, at 15 min after completion of IANB, and during treatment if pain occurred. The success of the anesthesia was defined as no or mild pain at any stage during the endodontic procedure. The success rate of the IANB was 38.5, 73.1, and 80.8% with the placebo, ibuprofen, and dexamethasone, respectively. Both ibuprofen and dexamethasone were significantly more effective than the placebo. No significant difference was observed, however, between the two experimental medications in terms of effectiveness. The results of the present study suggest that premedication with ibuprofen or dexamethasone increases the success rate of an IANB in patients with symptomatic irreversible pulpitis in the mandibular molars.

Digital disruption ?syndromes.

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Sullivan, Clair; Staib, Andrew

2017-05-18

The digital transformation of hospitals in Australia is occurring rapidly in order to facilitate innovation and improve efficiency. Rapid transformation can cause temporary disruption of hospital workflows and staff as processes are adapted to the new digital workflows. The aim of this paper is to outline various types of digital disruption and some strategies for effective management. A large tertiary university hospital recently underwent a rapid, successful roll-out of an integrated electronic medical record (EMR). We observed this transformation and propose several digital disruption "syndromes" to assist with understanding and management during digital transformation: digital deceleration, digital transparency, digital hypervigilance, data discordance, digital churn and post-digital 'depression'. These 'syndromes' are defined and discussed in detail. Successful management of this temporary digital disruption is important to ensure a successful transition to a digital platform. What is known about this topic? Digital disruption is defined as the changes facilitated by digital technologies that occur at a pace and magnitude that disrupt established ways of value creation, social interactions, doing business and more generally our thinking. Increasing numbers of Australian hospitals are implementing digital solutions to replace traditional paper-based systems for patient care in order to create opportunities for improved care and efficiencies. Such large scale change has the potential to create transient disruption to workflows and staff. Managing this temporary disruption effectively is an important factor in the successful implementation of an EMR. What does this paper add? A large tertiary university hospital recently underwent a successful rapid roll-out of an integrated electronic medical record (EMR) to become Australia's largest digital hospital over a 3-week period. We observed and assisted with the management of several cultural, behavioural and

Use of cultured cells with defects of citrulline metabolism in diagnosis and in the study of intercellular communication

Energy Technology Data Exchange (ETDEWEB)

Davidson, J S

1985-01-01

Citrullinemia and argininosuccinic aciduria are two disorders resulting from defects in two consecutive enzymes of the urea cycle, argininosuccinate synthetase and argininosuccinate lyase. Fibroblast cell lines were derived from patients with these disorders and the diagnoses, which had been made on the basis of amino acid levels in plasma and urine, were confirmed by demonstrating that the cell lines were unable to incorporate /sup 14/C-citrulline into protein. DNA from the argininosuccinate synthetase-deficient (ASS-) cells was analysed by restriction enzyme digestion and hybridisation to a cDNA probe which had been cloned from human argininosuccinate synthetase mRNA. No defect in the patient's DNA could be demonstrated, indicating that no major deletions in the argininosuccinate synthetase genes were present in this patient. Co-cultures of the ASS- and argininosuccinate lyase-deficient (ASL-) fibroblasts were able to incorporate /sup 14/C-citrulline into protein. Co-cultures of ASS- and ASL-cells were used as an assay system for measuring intercellular junctional communication. This allowed quantitation of the effects of pH and extra-cellular divalent cations on junctional communication. Tumor promoters such as phorbol esters and organochlorine pesticides have been reported to inhibit intercellular junctional communication in other systems, and this inhibitory activity may be related to the mechanism of tumor promotion. Retinoic acid and other retinoids also inhibited junctional communication, and the inhibitory effects of retinoic acid and TPA were additive. It is concluded that co-cultures of ASS- and ASL-cells constitute a useful system for providing quantitative measurements of intercellular junctional communication under a wide range of experimental conditions.

Development and characterization of nanoparticulate formulation of a water soluble prodrug of dexamethasone by HIP complexation.

Science.gov (United States)

Gaudana, Ripal; Parenky, Ashwin; Vaishya, Ravi; Samanta, Swapan K; Mitra, Ashim K

2011-01-01

The objective of this study was to develop and characterize a nanoparticulate-based sustained release formulation of a water soluble dipeptide prodrug of dexamethasone, valine-valine-dexamethasone (VVD). Being hydrophilic in nature, it readily leaches out in the external aqueous medium and hence partitions poorly into the polymeric matrix resulting in minimal entrapment in nanoparticles. Hence, hydrophobic ion pairing (HIP) complexation of the prodrug was employed with dextran sulphate as a complexing polymer. A novel, solid in oil in water emulsion method was employed to encapsulate the prodrug in HIP complex form in poly(lactic-co-glycolic acid) matrix. Nanoparticles were characterized with respect to size, zeta potential, crystallinity of entrapped drug and surface morphology. A significant enhancement in the entrapment of the prodrug in nanoparticles was achieved. Finally, a simple yet novel method was developed which can also be applicable to encapsulate other charged hydrophilic molecules, such as peptides and proteins.

Na,K-pump modulates intercellular communication in vascular wall

DEFF Research Database (Denmark)

Matchkov, Vladimir

were used as a model for electrical coupling of SMCs by measuring membrane capacitance (Cm). SMCs were uncoupled (evaluated by inhibition of vasomotion and desynchronization of calcium transients in vascular wall, or by reduction to half of Cm measured in paired A7r5 cells) when the Na......  Ouabain, a specific inhibitor of the Na,K-pump, has previously been shown to interfere with intercellular communication. Here we test the hypothesis that the communication between vascular smooth muscle cells (SMCs) is regulated through an interaction between the Na,K-pump and the Na......,Ca-exchanger leading to an increase in the intracellular calcium concentration in discrete areas near the plasma membrane. The intracellular calcium concentration in individual SMCs was imaged in cultured rat aortic SMCs (A7r5) and simultaneously with isometric force in rat mesenteric small arteries. Paired A7r5 cells...

Na,K-pump modulates intercellular communication in vascular wall

DEFF Research Database (Denmark)

Matchkov, Vladimir; Nilsson, Holger; Aalkjær, Christian

  Ouabain, a specific inhibitor of the Na,K-pump, has previously been shown to interfere with intercellular communication. Here we test the hypothesis that the communication between vascular smooth muscle cells (SMCs) is regulated through an interaction between the Na,K-pump and the Na...... were used as a model for electrical coupling of SMCs by measuring membrane capacitance (Cm). SMCs were uncoupled (evaluated by inhibition of vasomotion and desynchronization of calcium transients in vascular wall, or by reduction to half of Cm measured in paired A7r5 cells) when the Na,K-pump...... was inhibited either by a low concentration of ouabain or by ATP depletion. Uncoupling with ouabain was associated with a localized increase of intracellular calcium in discrete sites near the plasma membrane. Reduction of Na,K-pump activity by removal of extracellular potassium also uncoupled cells, but only...

The effect of dexamethasone and promethazine in combination with buparvaquone in the management of East Coast fever

Directory of Open Access Journals (Sweden)

M. Gwamaka

2004-11-01

Full Text Available The effects of dexamethasone and promethazine on the amelioration of pulmonary oedema in East Coast fever were investigated. The clinical effects of these drugs were further investigated when used in conjunction with the antitheilerial drug, buparvaquone. In the first experiment, 15 crossbred (Friesian x Zebu steers were divided into four groups. With the exception of the animals in group IV, that served as a control group all the others were infected with Theileria parva sporozoites. On the second day of the febrile reaction, the steers in groups I and II were treated with dexamethasone (0.1 mg/kg and promethazine (1 mg/kg, respectively. Group III steers served as the infected untreated controls. On the fifth day of the febrile reaction the animals in groups I, II and III were infused intravenously with tattoo ink suspension and 1 h later sacrificed for post-mortem examination and tissue sampling. The clinical picture indicated that both drugs significantly mitigated dyspnoea and the post mortem examination revealed a significant reduction in morphological changes. Tattoo ink particle count reflected a significant (P < 0.01 reduction in vascular leakage in the treated animals, with promethazine being significantly (P < 0.05 more effective than dexamethasone in this respect. In the second experiment, 18 steers were infected with T. parva sporozoites, and then were randomly allotted into three groups each of which contained six animals. After the onset of ECF clinical signs, the animals in the first two groups were treated with buparvaquone in combination with either dexamethasone (group I or promethazine (group II, and the third group was treated with buparvaquone alone. The results indicated that all the animals in groups I, II and III recovered well and no significant differences were observed in clinical disposition between the groups. Two months later, serum samples were collected from the refractory animals and demonstrated the presence of

Antiemetic effects of granisetron versus dexamethasone in clonidine premedicated children undergoing strabismus surgery

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Indu Sen

2007-01-01

Full Text Available In a prospective, double blind, randomized trial, 120 children, aged 3-8 years,ASAI-II, undergoing strabismus repair were randomly divided into three groups (n = 40 each. Oral clonidine premedication (4gg.kg-1 was administered to all the patients two hours prior to surgery. Soon after induction of anaesthesia, Group G patients were administered intravenous granisetron (40gg.kg-1 , Group D intravenous dexamethasone (150gg.kg-1 and group S received 4ml normal saline. Postoperatively, children were continuously monitored and assessed half-hourly till discharge and then after 24 hours for vomiting and pain. The overall incidence of postoperative emesis was lower (15.4% in the Group G compared with the Group D (21.6% in the first 24 hours (P>0.05. The Group S had a highest incidence of postoperative vomiting ((37% P value < 0.0324 compared to group G. The frequency of early vomiting was highest in the S group. Both G and D groups showed better control of delayed emetic episodes. We observed that in children who were premedicated with clonidine, both IV granisetron or dexamethasone were efficacious in reducing the incidence and severity of POV in day-care strabismus surgery.

Simvastatin Ameliorates Matrix Stiffness-Mediated Endothelial Monolayer Disruption.

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Marsha C Lampi

Full Text Available Arterial stiffening accompanies both aging and atherosclerosis, and age-related stiffening of the arterial intima increases RhoA activity and cell contractility contributing to increased endothelium permeability. Notably, statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase inhibitors whose pleiotropic effects include disrupting small GTPase activity; therefore, we hypothesized the statin simvastatin could be used to attenuate RhoA activity and inhibit the deleterious effects of increased age-related matrix stiffness on endothelial barrier function. Using polyacrylamide gels with stiffnesses of 2.5, 5, and 10 kPa to mimic the physiological stiffness of young and aged arteries, endothelial cells were grown to confluence and treated with simvastatin. Our data indicate that RhoA and phosphorylated myosin light chain activity increase with matrix stiffness but are attenuated when treated with the statin. Increases in cell contractility, cell-cell junction size, and indirect measurements of intercellular tension that increase with matrix stiffness, and are correlated with matrix stiffness-dependent increases in monolayer permeability, also decrease with statin treatment. Furthermore, we report that simvastatin increases activated Rac1 levels that contribute to endothelial barrier enhancing cytoskeletal reorganization. Simvastatin, which is prescribed clinically due to its ability to lower cholesterol, alters the endothelial cell response to increased matrix stiffness to restore endothelial monolayer barrier function, and therefore, presents a possible therapeutic intervention to prevent atherogenesis initiated by age-related arterial stiffening.

Intercellular deposits of basement membrane material in active human pituitary adenomas detected by immunostaining for laminin and electron microscopy

DEFF Research Database (Denmark)

Holck, S; Wewer, U M; Albrechtsen, R

1986-01-01

and one patient with Cushing's syndrome). Concurrently, at the ultrastructural level, bunches of basement membrane-like material intermingled between the adenoma cells were demonstrated in seven of these ten active adenomas. Furthermore, secretory granules were entrapped occasionally in this intercellular...

Drosophila wing imaginal discs respond to mechanical injury via slow InsP3R-mediated intercellular calcium waves

Science.gov (United States)

Restrepo, Simon; Basler, Konrad

2016-08-01

Calcium signalling is a highly versatile cellular communication system that modulates basic functions such as cell contractility, essential steps of animal development such as fertilization and higher-order processes such as memory. We probed the function of calcium signalling in Drosophila wing imaginal discs through a combination of ex vivo and in vivo imaging and genetic analysis. Here we discover that wing discs display slow, long-range intercellular calcium waves (ICWs) when mechanically stressed in vivo or cultured ex vivo. These slow imaginal disc intercellular calcium waves (SIDICs) are mediated by the inositol-3-phosphate receptor, the endoplasmic reticulum (ER) calcium pump SERCA and the key gap junction component Inx2. The knockdown of genes required for SIDIC formation and propagation negatively affects wing disc recovery after mechanical injury. Our results reveal a role for ICWs in wing disc homoeostasis and highlight the utility of the wing disc as a model for calcium signalling studies.

The effect of dexamethasone on the radiation survival response and misonidazole-induced hypoxic-cell cytotoxicity in Chinese hamster cells V-79-753B in vitro

International Nuclear Information System (INIS)

Millar, B.C.; Jinks, S.

1981-01-01

Overnight exposure of Chinese hamster cells, V-79-753B, to microgram quantities of the synthetic corticosteroid, dexamethasone, resulted in a decrease in sensitivity towards radiation, both in air and in hypoxia. The effect was dose-modifying and the oxygen enhancement ratio did not change appreciably. Similarly, when dexamethasone-treated hypoxic cells were irradiated in the presence of misonidazole, a hypoxic cell radiosensitizer, there was a decrease in radiation sensitivity compared with untreated hypoxic cells irradiated with misonidazole. (author)

Pharmacokinetics and tolerance study of intravitreal injection of dexamethasone-loaded nanoparticles in rabbits

OpenAIRE

Sun, Hongfan

2009-01-01

Linhua Zhang1, Yue Li2, Chao Zhang1, Yusheng Wang2, Cunxian Song11Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, China; 2Department of Ophthalmology, Institute of Ophthalmology of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi’an, ChinaAbstract: The aim of the study was to investigate the tolerance and pharmacokinetics of dexamethasone (DEX)-loaded poly(lactic acid–co-glycolic acid) ...

Disruption of a Quorum Sensing mechanism triggers tumorigenesis: a simple discrete model corroborated by experiments in mammary cancer stem cells

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Kirnasovsky Oleg U

2010-04-01

Full Text Available Abstract Background The balance between self-renewal and differentiation of stem cells is expected to be tightly controlled in order to maintain tissue homeostasis throughout life, also in the face of environmental hazards. Theory, predicting that homeostasis is maintained by a negative feedback on stem cell proliferation, implies a Quorum Sensing mechanism in higher vertebrates. Results Application of this theory to a cellular automata model of stem cell development in disrupted environments shows a sharply dichotomous growth dynamics: maturation within 50-400 cell cycles, or immortalization. This dichotomy is mainly driven by intercellular communication, low intensity of which causes perpetual proliferation. Another driving force is the cells' kinetic parameters. Reduced tissue life span of differentiated cells results in uncontrolled proliferation. Model's analysis, showing that under the Quorum Sensing control, stem cell fraction within a steady state population is fixed, is corroborated by experiments in breast carcinoma cells. Experimental results show that the plating densities of CD44+ cells and of CD44+/24lo/ESA+ cells do not affect stem cell fraction near confluence. Conclusions This study suggests that stem cell immortalization may be triggered by reduced intercellular communication, rather than exclusively result from somatic evolution, and implies that stem cell proliferation can be attenuated by signal manipulation, or enhanced by cytotoxics targeted to differentiated cells. In vivo verification and identification of the Quorum Sensing mediating molecules will pave the way to a higher level control of stem cell proliferation in cancer and in tissue engineering. Reviewers This article was reviewed by Glenn Webb and Marek Kimmel.

Quantitative measurements of intercellular adhesion between a macrophage and cancer cells using a cup-attached AFM chip.

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Kim, Hyonchol; Yamagishi, Ayana; Imaizumi, Miku; Onomura, Yui; Nagasaki, Akira; Miyagi, Yohei; Okada, Tomoko; Nakamura, Chikashi

2017-07-01

Intercellular adhesion between a macrophage and cancer cells was quantitatively measured using atomic force microscopy (AFM). Cup-shaped metal hemispheres were fabricated using polystyrene particles as a template, and a cup was attached to the apex of the AFM cantilever. The cup-attached AFM chip (cup-chip) approached a murine macrophage cell (J774.2), the cell was captured on the inner concave of the cup, and picked up by withdrawing the cup-chip from the substrate. The cell-attached chip was advanced towards a murine breast cancer cell (FP10SC2), and intercellular adhesion between the two cells was quantitatively measured. To compare cell adhesion strength, the work required to separate two adhered cells (separation work) was used as a parameter. Separation work was almost 2-fold larger between a J774.2 cell and FP10SC2 cell than between J774.2 cell and three additional different cancer cells (4T1E, MAT-LyLu, and U-2OS), two FP10SC2 cells, or two J774.2 cells. FP10SC2 was established from 4T1E as a highly metastatic cell line, indicates separation work increased as the malignancy of cancer cells became higher. One possible explanation of the strong adhesion of macrophages to cancer cells observed in this study is that the measurement condition mimicked the microenvironment of tumor-associated macrophages (TAMs) in vivo, and J774.2 cells strongly expressed CD204, which is a marker of TAMs. The results of the present study, which were obtained by measuring cell adhesion strength quantitatively, indicate that the fabricated cup-chip is a useful tool for measuring intercellular adhesion easily and quantitatively. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of caudal dexamethasone with ropivacaine for post-operative analgesia in paediatric herniotomies: A randomised controlled study

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Santosh Choudhary

2016-01-01

Full Text Available Background and Aims: Caudal analgesia is one of the most popular regional blocks in paediatric patients undergoing infra-umbilical surgeries but with the drawback of short duration of action after single shot local anaesthetic injection. We evaluated whether caudal dexamethasone 0.1 mg/kg as an adjuvant to the ropivacaine improved analgesic efficacy after paediatric herniotomies. Methods: Totally 128 patients of 1–5 years age group, American Society of Anaesthesiologists physical status I and II undergoing elective inguinal herniotomy were randomly allocated to two groups in double-blind manner. Group A received 1 ml/kg of 0.2% ropivacaine caudally and Group B received 1 ml/kg of 0.2% ropivacaine, in which 0.1 mg/kg dexamethasone was added for caudal analgesia. Post operative pain by faces, legs, activity, cry and consolability tool score, rescue analgesic requirement and adverse effects were noted for 24 h. Results: Results were statistically analysed using Student's t-test. Pain scores measured at 1, 2, 4, and 6 h post-operative, were lower in Group B as compared to Group A. Mean duration of analgesia in Group A was 248.4 ± 54.1 min and in Group B was 478.046 ± 104.57 min with P = 0.001. Rescue analgesic requirement was more in Group A as compared to Group B. Adverse effects after surgery were comparable between the two groups. Conclusion: Caudal dexamethasone added to ropivacaine is a good alternative to prolong post-operative analgesia with less pain score compared to caudal ropivacaine alone.

Piper sarmentosum is comparable to glycyrrhizic acid in reducing visceral fat deposition in adrenalectomised rats given dexamethasone.

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Fairus, A; Ima Nirwana, S; Elvy Suhana, M R; Tan, M H; Santhana, R; Farihah, H S

2013-01-01

Visceral obesity may be due to the dysregulation of cortisol production or metabolism that lead to metabolic disease. In adipose tissue, the enzyme 11beta-hydroxysteroid dehydrogenase type 1 regulates cortisol metabolism (11beta-HSD1). A previous study showed an increase in the visceral fat deposition in adrenalectomised rats given intramuscular dexamethasone. Glycyrrhizic acid (GCA) has been shown to reduce fat deposition because it is a known potent inhibitor of the 11beta-HSD1 enzyme. Piper sarmentosum (PS) is an edible medicinal plant commonly used in Asia as traditional medicine for treating diabetes, hypertension and joint pains. In this study, we determined the effects of PS extract on the disposition and morphology of perirenal adipocytes of adrenalectomised rats given intramuscular dexamethasone. A total of 21 male Spraque Dawley rats were adrenalectomised and given intramuscular dexamethasone, 120 μg/kg/day. These rats were further divided into three groups: adrenalectomised control (ADR+Dexa; n=7), GCA-treated (ADR+Dexa+GCA; dose=240 mg/kg/day; n=7) and PS-treated (ADR+Dexa+PS; dose=125 mg/kg/day; n=7) groups. The various treatments were given via gastric gavage following 2 weeks of adrenalectomy. Treatment with PS extract for 8 weeks showed decreased deposition of perirenal adipocytes which was similar to the GCA-treated group. However, PS-treated rats had thinner adipocyte membrane compared with that of the GCA-treated group. In conclusion, PS extract decreased perirenal fat deposition and reduced the diameter of the adipocyte membrane. However, the mechanisms of action needed further study.

Disruptions in Tokamaks

International Nuclear Information System (INIS)

Bondeson, A.

1987-01-01

This paper discusses major and minor disruptions in Tokamaks. A number of models and numerical simulations of disruptions based on resistive MHD are reviewed. A discussion is given of how disruptive current profiles are correlated with the experimentally known operational limits in density and current. It is argued that the q a =2 limit is connected with stabilization of the m=2/n=1 tearing mode for a approx.< 2.7 by resistive walls and mode rotation. Experimental and theoretical observations indicate that major disruptions usually occur in at least two phases, first a 'predisruption', or loss of confinement in the region 1 < q < 2, leaving the q approx.= 1 region almost unaffected, followed by a final disruption of the central part, interpreted here as a toroidal n = 1 external kink mode. (author)

Proposed mechanism of action for twin mix anaesthesia when used as intra-space pterygomandibular injection for inferior alveolar nerve block with emphasis on effects of perineural injection of dexamethasone

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Darpan Bhargava

2018-01-01

Full Text Available There has been recent research on the use of dexamethasone as an adjunct to local anaesthetics to enhance the block characteristics and improve post-operative pain outcomes. Numerous studies have shown that perineural dexamethasone improves post-operative analgesia, along with other clinical benefits. Intra-space pterygomandibular twin mix anaesthesia is a novel technique for inferior alveolar nerve block used for mandibular anaesthesia. Twin mix anaesthesia has its advantages in shortening the latency and prolonging the duration of the soft tissue anaesthesia, along with improving the quality of life in the post-operative period after mandibular oral surgical procedures. The concern regarding the use of perineural dexamethasone has been discussed.

Retrospective analysis of an oral combination of dexamethasone, uracil plus tegafur and cyclophosphamide for hormone-refractory prostate cancer.

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Hatano, Koji; Nonomura, Norio; Nishimura, Kazuo; Kawashima, Atsunari; Mukai, Masatoshi; Nagahara, Akira; Nakai, Yasutomo; Nakayama, Masashi; Takayama, Hitoshi; Tsujimura, Akira; Okuyama, Akihiko

2011-02-01

To evaluate the clinical utility of an oral combination of dexamethasone, uracil plus tegafur and cyclophosphamide as a treatment for patients with hormone-refractory prostate cancer. Fifty-seven patients with hormone-refractory prostate cancer were treated with an oral administration of dexamethasone (1.0 mg/day), uracil plus tegafur (400 mg/day) and cyclophosphamide (100 mg/day). The median patient age was 71 years. Sixteen patients had symptomatic bone metastasis, 31 had asymptomatic bone metastasis and 8 showed lymph node metastasis. Eight patients presented with only biochemical progression as evaluated by serum prostate-specific antigen levels. Thirty-six (63%) of 57 patients demonstrated a ≥50% decline in serum prostate-specific antigen levels. The median time to prostate-specific antigen progression was 7.2 months. In patients with a prostate-specific antigen decline of ≥50%, the median time to progression was 13.3 months. With respect to pre-treatment markers, the duration of response to initial hormonal treatment was associated with the time to prostate-specific antigen progression. In 11 of 16 (69%) patients who complained of bone pain, the pain improved and became stable in 5 of those patients (31%). Most adverse events were mild and only three (5%) patients showed neutropenia of Grade 3 or higher. The combination of dexamethasone, uracil plus tegafur and cyclophosphamide is an effective and well tolerated regimen for hormone-refractory prostate cancer. To evaluate the survival benefits, further randomized studies are required.

Phloroglucinol functions as an intracellular and intercellular chemical messenger influencing gene expression in Pseudomonas protegens.

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Clifford, Jennifer C; Buchanan, Alex; Vining, Oliver; Kidarsa, Teresa A; Chang, Jeff H; McPhail, Kerry L; Loper, Joyce E

2016-10-01

Bacteria can be both highly communicative and highly competitive in natural habitats and antibiotics are thought to play a role in both of these processes. The soil bacterium Pseudomonas protegens Pf-5 produces a spectrum of antibiotics, two of which, pyoluteorin and 2,4-diacetylphloroglucinol (DAPG), function in intracellular and intercellular communication, both as autoinducers of their own production. Here, we demonstrate that phloroglucinol, an intermediate in DAPG biosynthesis, can serve as an intercellular signal influencing the expression of pyoluteorin biosynthesis genes, the production of pyoluteorin, and inhibition of Pythium ultimum, a phytopathogenic oomycete sensitive to pyoluteorin. Through analysis of RNAseq data sets, we show that phloroglucinol had broad effects on the transcriptome of Pf-5, significantly altering the transcription of more than two hundred genes. The effects of nanomolar versus micromolar concentrations of phloroglucinol differed both quantitatively and qualitatively, influencing the expression of distinct sets of genes or having opposite effects on transcript abundance of certain genes. Therefore, our results support the concept of hormesis, a phenomenon associated with signalling molecules that elicit distinct responses at different concentrations. Phloroglucinol is the first example of an intermediate of antibiotic biosynthesis that functions as a chemical messenger influencing gene expression in P. protegens. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

Crystal structure of the Haemophilus influenzae Hap adhesin reveals an intercellular oligomerization mechanism for bacterial aggregation

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Meng, Guoyu; Spahich, Nicole; Kenjale, Roma; Waksman, Gabriel; St Geme, Joseph W

2011-01-01

Bacterial biofilms are complex microbial communities that are common in nature and are being recognized increasingly as an important determinant of bacterial virulence. However, the structural determinants of bacterial aggregation and eventual biofilm formation have been poorly defined. In Gram-negative bacteria, a major subgroup of extracellular proteins called self-associating autotransporters (SAATs) can mediate cell–cell adhesion and facilitate biofilm formation. In this study, we used the Haemophilus influenzae Hap autotransporter as a prototype SAAT to understand how bacteria associate with each other. The crystal structure of the H. influenzae HapS passenger domain (harbouring the SAAT domain) was determined to 2.2 Å by X-ray crystallography, revealing an unprecedented intercellular oligomerization mechanism for cell–cell interaction. The C-terminal SAAT domain folds into a triangular-prism-like structure that can mediate Hap–Hap dimerization and higher degrees of multimerization through its F1–F2 edge and F2 face. The intercellular multimerization can give rise to massive buried surfaces that are required for overcoming the repulsive force between cells, leading to bacterial cell–cell interaction and formation of complex microcolonies. PMID:21841773

Australasian randomised trial to evaluate the role of maternal intramuscular dexamethasone versus betamethasone prior to preterm birth to increase survival free of childhood neurosensory disability (A*STEROID): study protocol

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2013-01-01

Background Both dexamethasone and betamethasone, given to women at risk of preterm birth, substantially improve short-term neonatal health, increase the chance of the baby being discharged home alive, and reduce childhood neurosensory disability, remaining safe into adulthood. However, it is unclear which corticosteroid is of greater benefit to mother and child. This study aims to determine whether giving dexamethasone to women at risk of preterm birth at less than 34 weeks’ gestation increases the chance of their children surviving free of neurosensory disability at two years’ corrected age, compared with betamethasone. Methods/Design Design randomised, multicentre, placebo controlled trial. Inclusion criteria women at risk of preterm birth at less than 34 weeks’ gestation with a singleton or twin pregnancy and no contraindications to the use of antenatal corticosteroids and who give informed consent. Trial entry & randomisation at telephone randomisation eligible women will be randomly allocated to either the dexamethasone group or the betamethasone group, allocated a study number and corresponding treatment pack. Study groups women in the dexamethasone group will be administered two syringes of 12 mg dexamethasone (dexamethasone sodium phosphate) and women in the betamethasone group will be administered two syringes of 11.4 mg betamethasone (Celestone Chronodose). Both study groups consist of intramuscular treatments 24 hours apart. Primary study outcome death or any neurosensory disability measured in children at two years’ corrected age. Sample size a sample size of 1449 children is required to detect either a decrease in death or any neurosensory disability from 27.0% to 20.1% with dexamethasone compared with betamethasone, or an increase from 27.0% to 34.5% (two-sided alpha 0.05, 80% power, 5% loss to follow up, design effect 1.2). Discussion This study will provide high-level evidence of direct relevance for clinical practice. If one drug clearly

The In Vivo Granulopoietic Response to Dexamethasone Injection Is Abolished in Perforin-Deficient Mutant Mice and Corrected by Lymphocyte Transfer from Nonsensitized Wild-Type Donors

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Pedro Xavier-Elsas

2015-01-01

Full Text Available Exogenously administered glucocorticoids enhance eosinophil and neutrophil granulocyte production from murine bone-marrow. A hematological response dependent on endogenous glucocorticoids underlies bone-marrow eosinophilia induced by trauma or allergic sensitization/challenge. We detected a defect in granulopoiesis in nonsensitized, perforin-deficient mice. In steady-state conditions, perforin- (Pfp- deficient mice showed significantly decreased bone-marrow and blood eosinophil and neutrophil counts, and colony formation in response to GM-CSF, relative to wild-type controls of comparable age and/or weight. By contrast, peripheral blood or spleen total cell and lymphocyte numbers were not affected by perforin deficiency. Dexamethasone enhanced colony formation by GM-CSF-stimulated progenitors from wild-type controls, but not Pfp mice. Dexamethasone injection increased bone-marrow eosinophil and neutrophil counts in wild-type controls, but not Pfp mice. Because perforin is expressed in effector lymphocytes, we examined whether this defect would be corrected by transferring wild-type lymphocytes into perforin-deficient recipients. Short-term reconstitution of the response to dexamethasone was separately achieved for eosinophils and neutrophils by transfer of distinct populations of splenic lymphocytes from nonsensitized wild-type donors. Transfer of the same amount of splenic lymphocytes from perforin-deficient donors was ineffective. This demonstrates that the perforin-dependent, granulopoietic response to dexamethasone can be restored by transfer of innate lymphocyte subpopulations.

Zika Virus Infection in Dexamethasone-immunosuppressed Mice Demonstrating Disseminated Infection with Multi-organ Involvement Including Orchitis Effectively Treated by Recombinant Type I Interferons.

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Chan, Jasper Fuk-Woo; Zhang, Anna Jinxia; Chan, Chris Chung-Sing; Yip, Cyril Chik-Yan; Mak, Winger Wing-Nga; Zhu, Houshun; Poon, Vincent Kwok-Man; Tee, Kah-Meng; Zhu, Zheng; Cai, Jian-Piao; Tsang, Jessica Oi-Ling; Chik, Kenn Ka-Heng; Yin, Feifei; Chan, Kwok-Hung; Kok, Kin-Hang; Jin, Dong-Yan; Au-Yeung, Rex Kwok-Him; Yuen, Kwok-Yung

2016-12-01

Disseminated or fatal Zika virus (ZIKV) infections were reported in immunosuppressed patients. Existing interferon-signaling/receptor-deficient mouse models may not be suitable for evaluating treatment effects of recombinant interferons. We developed a novel mouse model for ZIKV infection by immunosuppressing BALB/c mice with dexamethasone. Dexamethasone-immunosuppressed male mice (6-8weeks) developed disseminated infection as evidenced by the detection of ZIKV-NS1 protein expression and high viral loads in multiple organs. They had ≥10% weight loss and high clinical scores soon after dexamethasone withdrawal (10dpi), which warranted euthanasia at 12dpi. Viral loads in blood and most tissues at 5dpi were significantly higher than those at 12dpi (Pvirus dissemination, inflammation of various tissues, especially orchitis, may be potential complications of ZIKV infection with significant implications on disease transmission and male fertility. Interferon treatment should be considered in patients at high risks for ZIKV-associated complications when the potential benefits outweigh the side effects of treatment. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Effects of antenatal dexamethasone administration on fetal and uteroplacental Doppler waveforms in women at risk for spontaneous preterm birth

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Elwani Elsnosy

2017-03-01

Conclusion: Maternal dexamethasone administration to pregnant women at risk of preterm labor improves the blood flow of the maternal uterine artery, fetal MCA, descending aorta and umbilical artery 24 h after its administration.

The use of cultured cells with defects of citrulline metabolism in diagnosis and in the study of intercellular communication

International Nuclear Information System (INIS)

Davidson, J.S.

1985-02-01

Citrullinemia and argininosuccinic aciduria are two disorders resulting from defects in two consecutive enzymes of the urea cycle, argininosuccinate synthetase and argininosuccinate lyase. Fibroblast cell lines were derived from patients with these disorders and the diagnoses, which had been made on the basis of amino acid levels in plasma and urine, were confirmed by demonstrating that the cell lines were unable to incorporate 14 C-citrulline into protein. DNA from the argininosuccinate synthetase-deficient (ASS-) cells was analysed by restriction enzyme digestion and hybridisation to a cDNA probe which had been cloned from human argininosuccinate synthetase mRNA. No defect in the patient's DNA could be demonstrated, indicating that no major deletions in the argininosuccinate synthetase genes were present in this patient. Co-cultures of the ASS- and argininosuccinate lyase-deficient (ASL-) fibroblasts were able to incorporate 14 C-citrulline into protein. Co-cultures of ASS- and ASL-cells were used as an assay system for measuring intercellular junctional communication. This allowed quantitation of the effects of pH and extra-cellular divalent cations on junctional communication. Tumor promoters such as phorbol esters and organochlorine pesticides have been reported to inhibit intercellular junctional communication in other systems, and this inhibitory activity may be related to the mechanism of tumor promotion. Retinoic acid and other retinoids also inhibited junctional communication, and the inhibitory effects of retinoic acid and TPA were additive. It is concluded that co-cultures of ASS- and ASL-cells constitute a useful system for providing quantitative measurements of intercellular junctional communication under a wide range of experimental conditions

Dexamethasone concentration gradients along scala tympani after application to the round window membrane.

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Plontke, Stefan K; Biegner, Thorsten; Kammerer, Bernd; Delabar, Ursular; Salt, Alec N

2008-04-01

Local application of dexamethasone-21-dihydrogen-phosphate (Dex-P) to the round window (RW) membrane of guinea pigs produces a substantial basal-apical concentration gradient in scala tympani (ST) perilymph. In recent years, intratympanically applied glucocorticoids are increasingly being used for the treatment of inner ear disease. Although measurements of intracochlear concentrations after RW application exist, there is limited information on the distribution of these drugs in the inner ear fluids. It has been predicted from computer simulations that substantial concentration gradients will occur after RW application, with lower concentrations expected in apical turns. Concentration gradients of other substances along the cochlea have recently been confirmed using a sequential apical sampling method to obtain perilymph. Dexamethasone-21-dihydrogen-phosphate (10 mg/ml) was administered to the RW membrane of guinea pigs (n = 9) in vivo for 2 to 3 hours. Perilymph was then collected using a protocol in which 10 samples, each of approximately 1 mul, were taken sequentially from the cochlear apex into capillary tubes. Dexamethasone-21-dihydrogen-phosphate concentration of the samples was analyzed by high-performance liquid chromatography. Interpretation of sample data using a finite element model allowed the longitudinal gradients of Dex-P in ST to be quantified. The Dex-P content of the first sample in each experiment (dominated by perilymph from apical regions) was substantially lower than that of the third and fourth sample (dominated by basal turn perilymph). These findings qualitatively demonstrated the existence of a concentration gradient along ST. After detailed analysis of the measured sample concentrations using an established finite element computer model, the mean basal-apical concentration gradient was estimated to be 17,000. Both absolute concentrations of Dex-P in ST and the basal-apical gradients were found to vary substantially. The existence of

Upper and lower respiratory tract microbiota in horses: bacterial communities associated with health and mild asthma (inflammatory airway disease) and effects of dexamethasone.

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Bond, Stephanie L; Timsit, Edouard; Workentine, Matthew; Alexander, Trevor; Léguillette, Renaud

2017-08-23

The microbial composition of the equine respiratory tract, and differences due to mild equine asthma (also called Inflammatory Airway Disease (IAD)) have not been reported. The primary treatment for control of IAD in horses are corticosteroids. The objectives were to characterize the upper and lower respiratory tract microbiota associated with respiratory health and IAD, and to investigate the effects of dexamethasone on these bacterial communities using high throughput sequencing. The respiratory microbiota of horses was dominated by four major phyla, Proteobacteria (43.85%), Actinobacteria (21.63%), Firmicutes (16.82%), and Bacteroidetes (13.24%). Fifty genera had a relative abundance > 0.1%, with Sphingomonas and Pantoea being the most abundant. The upper and lower respiratory tract microbiota differed in healthy horses, with a decrease in richness in the lower airways, and 2 OTUs that differed in abundance. There was a separation between bacterial communities in the lower respiratory tract of healthy and IAD horses; 6 OTUs in the tracheal community had different abundance with disease status, with Streptococcus being increased in IAD horses. Treatment with dexamethasone had an effect on the lower respiratory tract microbiota of both heathy and IAD horses, with 8 OTUs increasing in abundance (including Streptococcus) and 1 OTU decreasing. The lower respiratory tract microbiota differed between healthy and IAD horses. Further research on the role of Streptococcus in IAD is warranted. Dexamethasone treatment affected the lower respiratory tract microbiota, which suggests that control of bacterial overgrowth in IAD horses treated with dexamethasone could be part of the treatment strategy.

Gap junction mediated intercellular metabolite transfer in the cochlea is compromised in connexin30 null mice.

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Qing Chang

Full Text Available Connexin26 (Cx26 and connexin30 (Cx30 are two major protein subunits that co-assemble to form gap junctions (GJs in the cochlea. Mutations in either one of them are the major cause of non-syndromic prelingual deafness in humans. Because the mechanisms of cochlear pathogenesis caused by Cx mutations are unclear, we investigated effects of Cx30 null mutation on GJ-mediated ionic and metabolic coupling in the cochlea of mice. A novel flattened cochlear preparation was used to directly assess intercellular coupling in the sensory epithelium of the cochlea. Double-electrode patch clamp recordings revealed that the absence of Cx30 did not significantly change GJ conductance among the cochlear supporting cells. The preserved electrical coupling is consistent with immunolabeling data showing extensive Cx26 GJs in the cochlea of the mutant mice. In contrast, dye diffusion assays showed that the rate and extent of intercellular transfer of multiple fluorescent dyes (including a non-metabolizable D-glucose analogue, 2-NBDG among cochlear supporting cells were severely reduced in Cx30 null mice. Since the sensory epithelium in the cochlea is an avascular organ, GJ-facilitated intercellular transfer of nutrient and signaling molecules may play essential roles in cellular homeostasis. To test this possibility, NBDG was used as a tracer to study the contribution of GJs in transporting glucose into the cochlear sensory epithelium when delivered systemically. NBDG uptake in cochlear supporting cells was significantly reduced in Cx30 null mice. The decrease was also observed with GJ blockers or glucose competition, supporting the specificity of our tests. These data indicate that GJs facilitate efficient uptake of glucose in the supporting cells. This study provides the first direct experimental evidence showing that the transfer of metabolically-important molecules in cochlear supporting cells is dependent on the normal function of GJs, thereby suggesting a

Inhibition of hepatocyte gap junctional intercellular communication by tumor promoters

International Nuclear Information System (INIS)

Ruch, R.J.

1988-01-01

The mechanisms by which tumor promoters enhance neoplasia are poorly understood. One effect common to most tumor promoters is their ability to inhibit the cell-to-cell exchange of small molecules and ions through gap junctions, i.e., gap junctional intercellular communication (IC). IC maybe necessary for normal growth control and the loss of IC may predispose cells to enhanced growth. In the present studies, the effects of liver tumor promoters and other agents on IC between rodent hepatocytes in primary culture has been studied. IC was detected between hepatocytes: (1) autoradiographically following the passage and incorporation of [5- 3 H]uridine nucleotides from pre-labeled donor hepatocytes to non-labeled, adjacent recipient hepatocytes and (2) by fluorescence microscopy after microinjection of fluorescent Lucifer Yellow CH dye into hepatocytes and visualizing dye spread into adjacent hepatocytes

Simultaneous Determination of Dexamethasone, Ondansetron, Granisetron, Tropisetron, and Azasetron in Infusion Samples by HPLC with DAD Detection

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Fu-chao Chen

2017-01-01

Full Text Available A simple and rapid high-performance liquid chromatography with diode array detector (HPLC-DAD method has been developed and validated for simultaneous quantification of five antiemetic agents in infusion samples: dexamethasone, ondansetron, granisetron, tropisetron, and azasetron. The chromatographic separation was achieved on a Phenomenex C18 column (4.6 mm × 150 mm, 5 μm using acetonitrile-50 mM KH2PO4 buffer-triethylamine (25 : 74 : 1; v/v; pH 4.0. Flow rate was 1.0 mL/min with a column temperature of 30°C. Validation of the method was made in terms of specificity, linearity, accuracy, and intra- and interday precision, as well as quantification and detection limits. The developed method can be used in the laboratory to routinely quantify dexamethasone, ondansetron, granisetron, tropisetron, and azasetron simultaneously and to evaluate the physicochemical stability of referred drugs in mixtures for endovenous use.

In vitro early changes in intercellular junctions by treatment with a chemical carcinogen.

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Tachikawa, T; Kohno, Y; Matsui, Y; Yoshiki, S

1986-06-01

To examine early intercellular junction changes caused by treatment with 9,10-dimethyl-1,2-benzanthracene (DMBA), rat lingual epithelium was cultivated in isolation and observed by electrophysiological, freeze-fracture and whole-mount electron microscopy. Electrophysiological measurements showed a transient decrease in membrane potential of -10.2 mV 6 h after the treatment. It returned to almost the same level as that of the control group 1 day later. Six hours after treatment, input resistance decreased rapidly to 5.3 M omega but increased to 18.0 M omega 12 h after treatment. Transient reduction of input resistance and membrane potential occurred prior to the decrease in the coupling ratio 6 h after treatment with DMBA. In freeze-fracture replicas, the number of gap junctions decreased by approximately 45% of the control value 6 h after treatment with DMBA. At 12 h and thereafter, the number and area of gap junctions subsequently decreased by 60-80% of the control value. Alterations in the number and area of desmosomes were similar to those of the gap junctions. The formation of epithelial cytoskeletons, partially devoid of the 2-4 and 5-8 nm filaments was also observed. A decrease in the density of filament networks beneath the plasma membranes was especially apparent. Treatment with a carcinogen brought about morphological cellular changes as early as 6 h after treatment, and such early changes might trigger metabolic cellular abnormalities. Affected cells appear to move away from normal cells in a process of repeated destruction and revision of intercellular junctions, and cytoskeletons.

Wound Disruption Following Colorectal Operations.

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Moghadamyeghaneh, Zhobin; Hanna, Mark H; Carmichael, Joseph C; Mills, Steven; Pigazzi, Alessio; Nguyen, Ninh T; Stamos, Michael J

2015-12-01

Postoperative wound disruption is associated with high morbidity and mortality. We sought to identify the risk factors and outcomes of wound disruption following colorectal resection. The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was used to examine the clinical data of patients who underwent colorectal resection from 2005 to 2013. Multivariate regression analysis was performed to identify risk factors of wound disruption. We sampled a total of 164,297 patients who underwent colorectal resection. Of these, 2073 (1.3 %) had wound disruption. Patients with wound disruption had significantly higher mortality (5.1 vs. 1.9 %, AOR: 1.46, P = 0.01). The highest risk of wound disruption was seen in patients with wound infection (4.8 vs. 0.9 %, AOR: 4.11, P disruption such as chronic steroid use (AOR: 1.71, P disruption compared to open surgery (AOR: 0.61, P disruption occurs in 1.3 % of colorectal resections, and it correlates with mortality of patients. Wound infection is the strongest predictor of wound disruption. Chronic steroid use, obesity, severe COPD, prolonged operation, non-elective admission, and serum albumin level are strongly associated with wound disruption. Utilization of the laparoscopic approach may decrease the risk of wound disruption when possible.

The combined dexamethasone/TSST paradigm--a new method for psychoneuroendocrinology.

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Julie Andrews

Full Text Available The two main physiological systems involved in the regulation of the stress response are the hypothalamus-pituitary-adrenal (HPA axis and the sympathetic nervous system (SNS. However, the interaction of these systems on the stress response remains poorly understood. To better understand the cross-regulatory effects of the different systems involved in stress regulation, we developed a new stress paradigm that keeps the activity of the HPA constant when exposing subjects to psychosocial stress. Thirty healthy male participants were recruited and randomly assigned to either a dexamethasone (DEX; n = 15 or placebo (PLC; n = 15 group. All subjects were instructed to take the Dexamethasone (2 mg or Placebo pill the night before coming to the laboratory to undergo the Trier Social Stress Task (TSST. Salivary cortisol, salivary alpha amylase (sAA, heart rate, blood pressure and subjective stress were assessed throughout the protocol. As expected, the DEX group presented with suppressed cortisol levels. In comparison, their heart rate was elevated by approximately ten base points compared to the PLC group, with increases throughout the protocol and during the TSST. Neither sAA, nor systolic or diastolic blood pressures showed significant group differences. Subjective stress levels significantly increased from baseline, and were found to be higher before and after the TSST after DEX compared to placebo. These results demonstrate a significant interaction between the HPA and the SNS during acute stress. The SNS activity was found to be elevated in the presence of a suppressed HPA axis, with some further effects on subjective levels of stress. The method to suppress the HPA prior to inducing stress was found to completely reliable, without any adverse side effects. Therefore, we propose this paradigm as a new method to investigate the interaction of the two major stress systems in the regulation of the stress response.

The clinical outcomes of surgical management of anterior chamber migration of a dexamethasone implant (Ozurdex®).

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Kang, Hyunseung; Lee, Min Woo; Byeon, Suk Ho; Koh, Hyoung Jun; Lee, Sung Chul; Kim, Min

2017-09-01

Our purpose was to describe the clinical course, and individualized management approaches, of patients with migration of a dexamethasone implant into the anterior chamber. This was a retrospective review of four patients with seven episodes of anterior chamber migration of a dexamethasone implant. After 924 intravitreal dexamethasone injections, anterior migration of the implant occurred in four eyes of four patients (0.43%). All four eyes were pseudophakic: one eye had a posterior chamber intraocular lens in the capsular bag but in a post-laser posterior capsulotomy state, two eyes had a sulcus intraocular lens (IOL), and one eye had an iris-fixated retropupillary IOL. All eyes had a prior vitrectomy and no lens capsule. The time interval from injection to detection of the implant migration ranged from 2 to 6 weeks. Of the four eyes with corneal edema, only one eye required a corneal transplantation, although it was unclear whether the implant migration was the direct cause of the corneal decompensation because the patient had a history of bullous keratopathy resulting from an extended history of uveitis. All patients underwent surgical intervention: two patients with a repositioning procedure, and the other two patients with removal due to repeated episodes, although surgical removal was not always necessary to reverse the corneal complications. In our study, not all patients required surgical removal of the implants. Repositioning the implant back into the vitreous cavity may be considered as an option in cases involving the first episode with no significant corneal endothelial decompensation. Considering potential anterior segment complications and the loss of drug effectiveness together, an individualized approach is recommended to obtain the best treatment outcomes and to minimize the risk of corneal complications.

Effect of high-dose dexamethasone on the outcome of acute encephalitis due to Japanese encephalitis virus.

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Hoke, C H; Vaughn, D W; Nisalak, A; Intralawan, P; Poolsuppasit, S; Jongsawas, V; Titsyakorn, U; Johnson, R T

1992-04-01

Death due to Japanese encephalitis usually occurs in the first 5 days of hospitalization as a result of deepening coma with respiratory arrest. Death may result from edema-induced increases in intracranial pressure that might be reduced by the administration of steroids. Sixty-five patients presenting in Thailand to four hospitals with a diagnosis of acute Japanese encephalitis were randomized in a double-masked fashion and stratified by initial mental status into a placebo group (saline) or a treatment group (dexamethasone 0.6 mg/kg intravenously as a loading dose followed by 0.2 mg/kg every 6 h for 5 days). Fifty-five of the 65 had confirmed Japanese encephalitis as demonstrated by detection of virus or by Japanese encephalitis virus-specific IgM antibody. Important outcome measures included mortality (24%, treatment group; 27%, control group), days to alert mental status (3.9 vs. 6.2), and neurologic status 3 months after discharge (45% abnormal in each group). No statistically significant benefit of high-dose dexamethasone could be detected.

A water-soluble, mucoadhesive quaternary ammonium chitosan-methyl-β-cyclodextrin conjugate forming inclusion complexes with dexamethasone.

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Piras, Anna Maria; Zambito, Ylenia; Burgalassi, Susi; Monti, Daniela; Tampucci, Silvia; Terreni, Eleonora; Fabiano, Angela; Balzano, Federica; Uccello-Barretta, Gloria; Chetoni, Patrizia

2018-03-30

The ocular bioavailability of lipophilic drugs, such as dexamethasone, depends on both drug water solubility and mucoadhesion/permeation. Cyclodextrins and chitosan are frequently employed to either improve drug solubility or prolong drug contact onto mucosae, respectively. Although the covalent conjugation of cyclodextrin and chitosan brings to mucoadhesive drug complexes, their water solubility is restricted to acidic pHs. This paper describes a straightforward grafting of methyl-β-cyclodextrin (MCD) on quaternary ammonium chitosan (QA-Ch60), mediated by hexamethylene diisocyanate. The resulting product is a water-soluble chitosan derivative, having a 10-atom long spacer between the quaternized chitosan and the cyclodextrin. The derivative is capable of complexing the model drug dexamethasone and stable complexes were also observed for the lyophilized products. Furthermore, the conjugate preserves the mucoadhesive properties typical of quaternized chitosan and its safety as solubilizing excipient for ophthalmic applications was preliminary assessed by in vitro cytotoxicity evaluations. Taken as a whole, the observed features appear promising for future processing of the developed product into 3D solid forms, such as controlled drug delivery systems, films or drug eluting medical devices.

Evaluation of dimethyl sulfoxide and dexamethasone on pulmonary contusion in experimental blunt thoracic trauma.

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Boybeyi, Ozlem; Bakar, Bulent; Aslan, Mustafa Kemal; Atasoy, Pinar; Kisa, Ucler; Soyer, Tutku

2014-12-01

A thoracic trauma model was designed to evaluate the effect of dimethyl sulfoxide (DMSO) and dexamethasone (DX) on histopathologic and oxidative changes in lung parenchyma seen after pulmonary contusion. Twenty-four Wistar albino rats were included in the study. They were allocated into control (CG, n=6), sham (SG, n=6), DX (DXG, n=6), and DMSO (DMG, n=6) groups. Only a lung biopsy was performed in CG. In the experimental groups, blunt thoracic trauma was induced by dropping a cylindrical metal weight (0.5 kg) through a stainless steel tube onto the right hemithorax from a height of 0.4 m (E=1.96 J). In the SG, 1 mL of physiologic saline was injected intraperitoneally, in the DXG 10 mg/kg of DX was injected intraperitoneally, and in the DMG 1.2 g/mL of DMSO was injected intraperitoneally 15 minutes after trauma. After 6 hours, lung biopsy was performed for histopathologic and oxidative injury markers. Histopathologically, congestion, hemorrhage, neutrophil infiltration, endothelial-nitric oxide synthase (E-NoS), and total pathologic score were significantly higher in SG, DXG, and DMG when compared with CG (p<0.05). Neutrophil infiltration, total pathologic score, and E-NoS were significantly decreased in DMG when compared with SG and DXG (p<0.05). Biochemically, superoxide dismutase (SOD) level was significantly higher in SG, DXG, and DMG than in CG. SOD level was significantly lower in DXG and DMG than in SG (p<0.05). DMSO prevents further injury by decreasing neutrophil infiltration and endothelial injury in lung contusions. DX may have a role in the progression of inflammation but not in preventing the pathologic disruption of pulmonary parenchyma. Georg Thieme Verlag KG Stuttgart · New York.

Loss of Dishevelleds disrupts planar polarity in ependymal motile cilia and results in hydrocephalus

Science.gov (United States)

Ohata, Shinya; Nakatani, Jin; Herranz-Pérez, Vicente; Cheng, JrGang; Belinson, Haim; Inubushi, Toshiro; Snider, William D.; García-Verdugo, Jose Manuel; Wynshaw-Boris, Anthony; Álvarez-Buylla, Arturo

2014-01-01

SUMMARY Defects in ependymal (E) cells, which line the ventricle and generate cerebrospinal fluid flow through ciliary beating, can cause hydrocephalus. Dishevelled genes (Dvls) are essential for Wnt signaling and Dvl2 has been shown to localize to the rootlet of motile cilia. Using the hGFAP-Cre;Dvl1−/−;2flox/flox;3+/− mouse, we show that compound genetic ablation of Dvls causes hydrocephalus. In hGFAP-Cre;Dvl1−/−;2flox/flox;3+/− mutants, E cells differentiated normally, but the intracellular and intercellular rotational alignments of ependymal motile cilia were disrupted. As a consequence, the fluid flow generated by the hGFAP-Cre;Dvl1−/−;2flox/flox;3+/− E cells was significantly slower than that observed in control mice. Dvls were also required for the proper positioning of motile cilia on the apical surface. Tamoxifen-induced conditional removal of Dvls in adult mice also resulted in defects in intracellular rotational alignment and positioning of ependymal motile cilia. These results suggest that Dvls are continuously required for E cell planar polarity and may prevent hydrocephalus. PMID:25043421

Endocrine Disrupting Chemicals (EDCs)

Science.gov (United States)

... Center Pacientes y Cuidadores Hormones and Health The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) Steroid and Hormone ... Hormones and Health › Endocrine Disrupting Chemicals (EDCs) The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) EDCs Myth vs. ...

Efficacy of intravitreal dexamethasone implant for prostaglandin-induced refractory pseudophakic cystoid macular edema: case report and review of the literature

Directory of Open Access Journals (Sweden)

Sacchi M

2014-07-01

Full Text Available Matteo Sacchi, Edoardo Villani, Francesca Gilardoni, Paolo Nucci University Eye Clinic, San Giuseppe Hospital, University of Milan, Milan, Italy Background: Macular edema is a known complication even after uneventful cataract surgery. The chronic use of prostaglandin analogs is a risk factor for the development of pseudophakic cystoid macular edema (CME. Nonsteroidal anti-inflammatory drugs (NSAIDs are considered first-line therapy but refractory postsurgical CME represents a therapeutic challenge, as there is not an evidence-based treatment.Objective: To report the use of a single implant of intravitreal dexamethasone for tafluprost-associated pseudophakic CME refractory to NSAIDs and to sub-Tenon’s corticosteroid injections.Case report: A 64-year-old female with ocular hypertension treated with tafluprost experienced decreased vision (visual acuity 20/60 and metamorphopsia 2 months after uneventful cataract extraction. Spectral domain optical coherence tomography (SD-OCT revealed CME. After 1 month of topical and oral NSAIDs, CME was still evident on SD-OCT (visual acuity 20/50. Two sub-Tenon’s betamethasone injections were performed at a 2-week interval. As CME was still present, 2 months after the diagnosis of CME (visual acuity 20/40, the patient underwent a single dexamethasone intravitreal implant. One month later, macular appearance was normal, and visual acuity increased to 20/30. This result was maintained throughout the 6 months of follow-up.Conclusion: In this report, a single implant of intravitreal dexamethasone successfully treated pseudophakic CME associated with the use of prostaglandin analogs unresponsive to NSAIDs and sub-Tenon’s betamethasone. The results of this report need to be corroborated by powered, prospective, randomized trials. The need for repeated treatments as well as the retreatment interval in patients requiring more than a single injection are issues still needing further investigations. Keywords

Radial distribution of dilated intercellular spaces of the esophageal squamous epithelium in patients with reflux disease exhibiting discrete endoscopic lesions

NARCIS (Netherlands)

Vieth, M; Fiocca, R; Haringsma, J; Delarive, J; Wiesel, PH; Tam, W; Tytgat, GNJ; Dent, J; Edebo, A; Lundell, L; Stolte, M

2004-01-01

Introduction: Dilatation of intercellular spaces of the esophageal squamous epithelium has been suggested as a marker of early acid reflux-induced damage. This change is a potentially useful addition to histomorphological changes that represent so called minimal endoscopic lesions. We have assessed

Dexamethasone protects RAW264.7 macrophages from growth arrest and apoptosis induced by H2O2 through alteration of gene expression patterns and inhibition of nuclear factor-kappa B (NF-κB) activity

International Nuclear Information System (INIS)

Fong, C.-C.; Zhang Yaou; Zhang Qi; Tzang, C.-H.; Fong, W.-F.; Wu, R.S.S.; Yang Mengsu

2007-01-01

In this study, the effect of dexamethasone, a synthetic glucocorticoid, on H 2 O 2 stimulated murine RAW264.7 macrophages was investigated. It was found that dexamethasone protected the cells from apoptosis induced by H 2 O 2 . A cDNA microarray, which consists of 1000 genes selected from a mouse clone set provided from NIA, was used to study the gene expression profiles involved in the protective effect. Our data show that dexamethasone exerts the anti-apoptosis function by changing the expression patterns of many genes involved inhibiting the up-regulation of apoptosis promoting genes and the down-regulation of cell cycle stimulating genes as well as keeping the up-regulation of cell survival related genes. Our study also revealed that dexamethasone protects RAW264.7 macrophages from H 2 O 2 induced apoptosis through blocking nuclear factor-kappa B (NF-κB) activity

Pre-operative use of dexamethasone does not reduce incidence or intensity of bleaching-induced tooth sensitivity. A triple-blind, parallel-design, randomized clinical trial.

Science.gov (United States)

da Costa Poubel, Luiz Augusto; de Gouvea, Cresus Vinicius Deppes; Calazans, Fernanda Signorelli; Dip, Etyene Castro; Alves, Wesley Veltri; Marins, Stella Soares; Barcelos, Roberta; Barceleiro, Marcos Oliveira

2018-04-25

This study evaluated the effect of the administration of pre-operative dexamethasone on tooth sensitivity stemming from in-office bleaching. A triple-blind, parallel-design, randomized clinical trial was conducted on 70 volunteers who received dexamethasone or placebo capsules. The drugs were administered in a protocol of three daily 8-mg doses of the drug, starting 48 h before the in-office bleaching treatment. Two bleaching sessions with 37.5% hydrogen peroxide gel were performed with a 1-week interval. Tooth sensitivity (TS) was recorded on visual analog scales (VAS) and numeric rating scales (NRS) in different periods up to 48 h after bleaching. The color evaluations were also performed. The absolute risk of TS and its intensity were evaluated by using Fisher's exact test. Comparisons of the TS intensity (NRS and VAS data) were performed by using the Mann-Whitney U test and a two-way repeated measures ANOVA and Tukey's test, respectively. In both groups, a high risk of TS (Dexa 80% x Placebo 94%) was detected. No significant difference was observed in terms of TS intensity. A whitening of approximately 3 shade guide units of the VITA Classical was detected in both groups, which were statistically similar. It was concluded that the administration pre-operatively of dexamethasone, in the proposed protocol, does not reduce the incidence or intensity of bleaching-induced tooth sensitivity. The use of dexamethasone drug before in-office bleaching treatment does not reduce incidence or intensity of tooth sensitivity. NCT02956070.

Evolution of altruism in spatial prisoner's dilemma: Intra- and inter-cellular interactions

Science.gov (United States)

Yokoi, Hiroki; Uehara, Takashi; Sakata, Tomoyuki; Naito, Hiromi; Morita, Satoru; Tainaka, Kei-ichi

2014-12-01

Iterated prisoner's dilemma game is carried out on lattice with “colony” structure. Each cell is regarded as a colony which contains plural players with an identical strategy. Both intra- and inter-cellular interactions are assumed. In the former a player plays with all other players in the same colony, while in the latter he plays with one player each from adjacent colonies. Spatial patterns among four typical strategies exhibit various dynamics and winners. Both theory and simulation reveal that All Cooperation (AC) wins, when the members of colony or the intensity of noise increases. This result explains the evolution of altruism in animal societies, even though errors easily occur in animal communications.

Disruptions in the TFTR tokamak

International Nuclear Information System (INIS)

Janos, A.; Fredrickson, E.D.; McGuire, K.; Batha, S.H.; Bell, M.G.; Bitter, M.; Budny, R.; Bush, C.E.; Efthimion, P.C.; Hawryluk, R.J.; Hill, K.W.; Hosea, J.; Jobes, F.C.; Johnson, D.W.; Levinton, F.; Mansfield, D.; Meade, D.; Medley, S.S.; Monticello, D.; Mueller, D.; Nagayama, Y.; Owens, D.K.; Park, H.; Park, W.; Post, D.E.; Schivell, J.; Strachan, J.D.; Taylor, G.; Ulrickson, M.; Goeler, S. von; Wilfrid, E.; Wong, K.L.; Yamada, M.; Young, K.M.; Zarnstorff, M.C.; Zweben, S.J.; Drake, J.F.; Kleva, R.G.; Fleischmann, H.H.

1993-03-01

For a successful reactor, it will be useful to predict the occurrence of disruptions and to understand disruption effects including how a plasma disrupts onto the wall and how reproducibly it does so. Studies of disruptions on TFTR at both high-β pol and high-density have shown that, in both types, a fast growing m/n=1/1 mode plays an important role. In highdensity disruptions, a newly observed fast m/n = 1/1 mode occurs early in the thermal decay phase. For the first time in TFTR q-profile measurements just prior to disruptions have been made. Experimental studies of heat deposition patterns on the first wall of TFTR due to disruptions have provided information on MHD phenomena prior to or during the disruption, how the energy is released to the wall, and the reproducibility of the heat loads from disruptions. This information is important in the design of future devices such as ITER. Several new processes of runaway electron generation are theoretically suggested and their application to TFTR and ITER is considered, together with a preliminary assessment of x-ray data from runaways generated during disruptions

Regulation of hormone release by cultured cells from a thyrotropin-growth hormone-secreting pituitary tumor. Direct inhibiting effects of 3,5,3'-triiodothyronine and dexamethasone on thyrotropin secretion.

Science.gov (United States)

Lamberts, S W; Oosterom, R; Verleun, T; Krenning, E P; Assies, H

1984-08-01

The regulation of TSH and GH secretion was investigated in cultured tumor cells prepared from a mixed TSH/GH secreting pituitary tumor. The tumor tissue had been removed transsphenoidally from a patient with hyperthyroidism and inappropriately high serum TSH levels and acromegaly. TSH and GH secretion by cultured cells were stimulated in a parallel way by TRH (300 nM) and LHRH (50 nM), but were unaffected by bromocriptine (10 nM). Exposure of the tumor cells to dexamethasone (0.1 microM) or T3 (50 nM) had differential effects on hormone secretion. GH secretion was greatly stimulated by dexamethasone, but unaffected by T3. TSH secretion was inhibited both by T3 and by dexamethasone. So, T3 and glucocorticoids inhibit TSH release by the human pituitary tumor cells studied at least partly by means of a direct effect.

Multimodal analgesia with gabapentin, ketamine and dexamethasone in combination with paracetamol and ketorolac after hip arthroplasty: a preliminary study

DEFF Research Database (Denmark)

Rasmussen, Michael; Mathiesen, Ole; Dierking, Gerd

2010-01-01

It has been hypothesized that combinations of analgesics with different mechanisms of action may reduce or even prevent postoperative pain. We, therefore, investigated the analgesic effect of gabapentin, dexamethasone and low-dose ketamine in combination with paracetamol and ketorolac as compared...

BINARY DISRUPTION BY MASSIVE BLACK HOLES: HYPERVELOCITY STARS, S STARS, AND TIDAL DISRUPTION EVENTS

Energy Technology Data Exchange (ETDEWEB)

Bromley, Benjamin C. [Department of Physics and Astronomy, University of Utah, 115 S 1400 E, Rm 201, Salt Lake City, UT 84112 (United States); Kenyon, Scott J.; Geller, Margaret J.; Brown, Warren R., E-mail: bromley@physics.utah.edu, E-mail: skenyon@cfa.harvard.edu, E-mail: mgeller@cfa.harvard.edu, E-mail: wbrown@cfa.harvard.edu [Smithsonian Astrophysical Observatory, 60 Garden Street, Cambridge, MA 02138 (United States)

2012-04-20

We examine whether disrupted binary stars can fuel black hole growth. In this mechanism, tidal disruption produces a single hypervelocity star (HVS) ejected at high velocity and a former companion star bound to the black hole. After a cluster of bound stars forms, orbital diffusion allows the black hole to accrete stars by tidal disruption at a rate comparable to the capture rate. In the Milky Way, HVSs and the S star cluster imply similar rates of 10{sup -5} to 10{sup -3} yr{sup -1} for binary disruption. These rates are consistent with estimates for the tidal disruption rate in nearby galaxies and imply significant black hole growth from disrupted binaries on 10 Gyr timescales.

Statistical analysis of JET disruptions

International Nuclear Information System (INIS)

Tanga, A.; Johnson, M.F.

1991-07-01

In the operation of JET and of any tokamak many discharges are terminated by a major disruption. The disruptive termination of a discharge is usually an unwanted event which may cause damage to the structure of the vessel. In a reactor disruptions are potentially a very serious problem, hence the importance of studying them and devising methods to avoid disruptions. Statistical information has been collected about the disruptions which have occurred at JET over a long span of operations. The analysis is focused on the operational aspects of the disruptions rather than on the underlining physics. (Author)

Stability of Diphenhydramine Hydrochloride, Lorazepam, and Dexamethasone Sodium Phosphate in 0.9% Sodium Chloride Stored in Polypropylene Syringes.

Science.gov (United States)

Anderson, Collin R; Halford, Zachery; MacKay, Mark

2015-01-01

Chemotherapy induced nausea and vomiting is problematic for many patients undergoing chemotherapy. Multiple-drug treatments have been developed to mitigate chemotherapy induced nausea and vomiting. A patient-controlled infusion of diphenhydramine hydrochloride, lorazepam, and dexamethasone sodium phosphate has been studied in patients who are refractory to first-line therapy. Unfortunately, the physical and chemical compatibility of this three-drug combination is not available in the published literature. Chemical compatibility was evaluated using high-performance liquid chromatography with ultraviolet detection. Visual observation was employed to detect change in color, clarity, or gas evolution. Turbidity and pH measurements were performed in conjunction with visual observation at hours 0, 24, and 48. Results showed that diphenhydramine hydrochloride 4 mg/mL, lorazepam 0.16 mg/mL, and dexamethasone sodium phosphate 0.27 mg/mL in 0.9% sodium chloride stored in polypropylene syringes were compatible, and components retained greater than 95% of their original concentration over 48 hours when stored at room temperature.

Disruptions in DIII-D

International Nuclear Information System (INIS)

Reiman, A.; Taylor, P.; Kellman, A.; LaHaye, R.

1996-01-01

We report on the results of a statistical analysis of the DIII-D disruption data base, and on an examination of a selected subset of the shots to determine the likely causes of disruptions. The statistical analysis focuses on the dependence of the disruption rate on key dimensionless parameters. We find that the disruption frequency is high at modest values of the parameters, and that it can be relatively low at operational limits. For example, the disruption frequency in an ITER relevant regime (β N /l i ∼ 2, 3 G > 0.6, where n G is the Greenwald limit) is approximately 23%. For this range of q, the disruption frequency rises only modestly to about 35% at the β limit, consistent with previous observations of a soft β limit for this q regime. For the range 6 95 G G < .9) in all q regimes we have studied. The location of the minimum moves to higher density with increasing q

Disruption model

International Nuclear Information System (INIS)

Murray, J.G.; Bronner, G.

1982-07-01

Calculations of disruption time and energy dissipation have been obtained by simulating the plasma as an electrical conducting loop that varies in resistivity, current density, major radius. The calculations provide results which are in good agreement with experimental observations. It is believed that this approach allows engineering designs for disruptions to be completed in large tokamaks such as INTOR or FED

A Phase III clinical study to evaluate the efficacy of combined azithromycin and dexamethasone in the treatment of blepharoconjunctivitis

Directory of Open Access Journals (Sweden)

Hosseini K

2013-11-01

Full Text Available Kamran Hosseini,1,2 Judith Hutcheson,1 Richard L Lindstrom3–5 1Clinical Affairs, 2Regulatory Affairs, InSite Vision Incorporated, Alameda, CA, USA; 3Minnesota Eye Consultants, Bloomington, MN, USA; 4University of Minnesota Department of Ophthalmology, Minneapolis, MN, USA; 5University of California, Irvine Gavin Herbert Eye Institute, Irvine, CA, USA Purpose: The purpose of this study was to evaluate the clinical and antimicrobial efficacy and safety of ISV-502 (1.0% azithromycin and 0.1% dexamethasone compared to 1.0% azithromycin or 0.1% dexamethasone in the treatment of subjects with blepharoconjunctivitis. Patients and methods: Patients with verified blepharoconjunctivitis were randomized to receive ISV-502 (Group 1; n=140, 1.0% azithromycin alone (Group 2; n=141, or 0.1% dexamethasone alone (Group 3; n=136. Bacterial cultures were obtained from the conjunctiva and eyelid. Treatment was instilled in both eyes twice daily at 12-hour intervals for 14 days. The primary endpoint was complete resolution of clinical signs and symptoms at Day 15. The secondary endpoint was complete bacterial eradication at Day 15 among subjects with positive bacterial cultures at baseline. Results: Significantly more Group 1 subjects met the primary endpoint (27.1% than those in Group 2 (15.6%; P=0.028, but not compared to Group 3 (23.5%; P=0.581. Significantly more Group 1 patients (60% had complete bacterial eradication at Day 15 compared with Group 3 (40.2%; P=0.007, but there was no difference compared with Group 2 (66.3%; P=0.306. Adverse events were reported in about 25% of the subjects, with an equal distribution among treatment arms; the most common adverse event was irritation at the instillation site. Visual acuity and intraocular pressure differences were not statistically significant, but did show age and sex differences between groups. Conclusion: ISV-502 is effective in the treatment of blepharoconjunctivitis as evaluated by clinical cure and

Comparison of the Effect of Ondansetrone - Dexamethasone, Dexamethasone – Metoclopeamide and Ondansetron - Normal Saline in Decreasing Post Operative Nausa and Vomitting (PONV after Middle Ear Surgery

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Haddadi Soudabeh

2009-09-01

Full Text Available Background: The incidence of post-operative nausea and vomitting (PONV is increased after middle ear surgery and it may complicate and interact with reconstruction after surgery, so prevention and treatment of these complications are necessary.The aim of this study was to evaluate the efficacy of anti-emetic combinations in decreasing the PONV after middle ear surgery.Materials and methods: This double blind clinical trial was carried out during 2007-2008 on 111 patients of 15-45 years old with ASA I-II who were candidates for elective middle ear surgery under general anesthesia. The patients were divided into three groups. Patients in the ON group received Ondansetrone 0.1mg/kg + Nacl 0.9% 2cc, OD group received Ondansetrone 0.1mg/kg + Dexamethasone 0.15mg/kg and MD group received Dexamethasone 0.15mg/kg+ Metoclopramide 0.15mg/kg intravenously just before the end of surgery. The patients were evaluated for nausea, vomiting, need of anti-emetic drugs and drug dosage in recovery, 1-6, 6-12 and 12-24 hours after operation and then all data were statistically analyzed by SPSS software, Chi-square, ANOVA and t- Test. P<0.05 was significant.Results: There were no significant differences among three groups in age and sex. The incidence of PONV among 3 groups was not significantly different during 24 hours after operation. (P=0.271 but the incidence of PONV in the first six hours was different among 3 groups (P=0.007 (ON: 8.1%, OD: 0%, MD: 21.6%. Also Metoclopramide consumption was significant between three groups. Conclusion: This study showed that the need to anti-emetic drugs in first 6 hours was the least in OD group, but the difference in the incidence of PONV was not significant otherwise.

Internal disruption in tokamaks

International Nuclear Information System (INIS)

Kuvshinov, B.N.; Savrukhin, P.V.

1990-01-01

A review of results of experimental and theoretical investigations of internal disruption in tokamaks is given. Specific features of various types of saw-tooth oscillations are described and their classification is performed. Theoretical models of the process of development of internal disruption instability are discussed. Effect of internal disruption on parameters of plasma, confined in tokamak, is considered. Scalings of period and amplitude of saw-tooth oscillations, as well as version radius are presented. Different methods for stabilizing instability of internal disruption are described

Internal disruptions in tokamaks

International Nuclear Information System (INIS)

Kuvshinov, B.N.; Savrukhin, P.V.

1990-01-01

Experimental and theoretical studies of the phenomenon of internal disruptions in tokamaks are reviewed. A classification scheme is introduced and the features of different types of sawtooth oscillations are described. A theoretical model for the development of the internal disruption instability is discussed. The effect of internal disruptions on the parameters of plasma confined in tokamaks is discussed. Scaling laws for the period and amplitude of sawtooth oscillations, as well as for the inversion radius, are presented. Different methods of stabilizing the internal disruption instability are described

Maternal Dexamethasone Exposure Alters Synaptic Inputs to Gonadotropin-Releasing Hormone Neurons in the Early Postnatal Rat

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Wei Ling Lim

2016-08-01

Full Text Available Maternal dexamethasone (DEX; a glucocorticoid receptor agonist exposure delays pubertal onset and alters reproductive behaviour in the adult offspring. However, little is known whether maternal DEX exposure affects the offspring’s reproductive function by disrupting the gonadotropin-releasing hormone (GnRH neuronal function in the brain. Therefore, this study determined the exposure of maternal DEX on the GnRH neuronal spine development and synaptic cluster inputs to GnRH neurons using transgenic rats expressing enhanced green fluorescent protein (EGFP under the control of GnRH promoter. Pregnant females were administered with DEX (0.1mg/kg or vehicle (VEH, water daily during gestation day 13-20. Confocal imaging was used to examine the spine density of EGFP-GnRH neurons by three-dimensional rendering and synaptic cluster inputs to EGFP-GnRH neurons by synapsin I immunohistochemistry on postnatal day 0 (P0 males. The spine morphology and number on GnRH neurons did not change between the P0 males following maternal DEX and VEH treatment. The number of synaptic clusters within the organum vasculosum of the lamina terminalis (OVLT was decreased by maternal DEX exposure in P0 males. Furthermore, the number and levels of synaptic cluster inputs in close apposition with GnRH neurons was decreased following maternal DEX exposure in the OVLT region of P0 males. In addition, the post synaptic marker molecule, post-synaptic density 95 was observed in GnRH neurons following both DEX and VEH treatment. These results suggest that maternal DEX exposure alters neural afferent inputs to GnRH neurons during early postnatal stage, which could lead to reproductive dysfunction during adulthood.

Effects of alpha-tocopherol on superoxide production and plasma intercellular adhesion molecule-1 and antibodies to oxidized LDL in chronic smokers

NARCIS (Netherlands)

Tits, van L.J.; Waart, de F.; Hak-Lemmers, H.L.M.; Heijst, P.; Graaf, de J.; Demacker, P.N.; Stalenhoef, A.F.

2001-01-01

Antioxidants have been postulated to exert beneficial effects in atherosclerosis. Atherosclerosis is associated with raised plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1) and autoantibodies against oxidized low-density lipoprotein (oxLDL). It is not known whether antioxidants

A Comparative Study on the Efficacy of Submucosal Injection of Dexamethasone Versus Methylprednisolone in Reducing Postoperative Sequelae After Third Molar Surgery.

Science.gov (United States)

Lim, Daniel; Ngeow, Wei Cheong

2017-11-01

To compare the efficacy of preoperative submucosal injection of 4 mg of dexamethasone versus 40 mg of methylprednisolone in reducing postoperative sequelae after surgical removal of impacted mandibular third molars. This prospective, randomized, double-blind study included 65 patients who required surgical removal of impacted mandibular third molars with Class II or position B impaction (Pell and Gregory classification). Patients were randomly assigned to 1 of 3 groups: dexamethasone, methylprednisolone, or placebo (control). Surgery was performed with patients under local anesthesia. Baseline measurements were obtained preoperatively, and subsequent assessments were made on postoperative day 1, 2, 5, and 7 to measure postoperative facial swelling by use of 2 linear measurements: interincisal mouth opening width and visual analog scale score for pain. The amount of analgesics consumed was recorded. Wound healing also was assessed on postoperative day 7. Descriptive and multivariate statistics were computed, and significance was set at P Kruskal-Wallis test), whereas the methylprednisolone group had significantly less pain (P Kruskal-Wallis test) and consumed a lower amount of analgesics (P test) during the early postoperative days. The study findings suggest that a single preoperative dose of dexamethasone versus methylprednisolone was equally effective in reducing postoperative swelling and trismus. Pain control by these corticosteroids, however, was variable. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Repeat Intravitreal Dexamethasone Implant for Refractory Cystoid Macular Edema in Syphilitic Uveitis

Directory of Open Access Journals (Sweden)

Cassandra C. Lautredou

2018-01-01

Full Text Available Purpose. To report the successful utilization of adjunctive repeat intravitreal corticosteroid therapy for the treatment of cystoid macular edema in syphilis-related uveitis. Methods/Patients. An HIV-positive patient with treated ocular syphilis who developed refractory cystoid macular edema (CME was treated with repeat intravitreal corticosteroid therapy including dexamethasone intravitreal implants. Results. Treatment led to the resolution of CME and improvement in visual acuity. Conclusions. Intravitreal corticosteroid therapy may be a viable adjunctive treatment for refractory CME in patients with treated syphilitic uveitis. Corticosteroid-induced exacerbation of infection is unlikely in patients with an adequate serologic treatment response.

Granisetron versus Granisetron-Dexamethasone for Prevention of Postoperative Nausea and Vomiting in Pediatric Strabismus Surgery: A Randomized Double-Blind Trial

Directory of Open Access Journals (Sweden)

Renu Sinha

2016-01-01

Full Text Available Aim. Efficacy of granisetron and combination of granisetron and dexamethasone was evaluated for prevention of postoperative nausea and vomiting (PONV in children undergoing elective strabismus surgery. Methods. A total of 136 children (1–15 years were included. Children received either granisetron (40 mcg/kg [group G] or combination of granisetron (40 mcg/kg and dexamethasone (150 mcg/kg [group GD]. Intraoperative fentanyl requirement and incidence and severity of oculocardiac reflex were assessed. PONV severity was assessed for first 24 hours and if score was >2, it was treated with metoclopramide. Postoperative analgesia was administered with intravenous fentanyl and ibuprofen. Results. The demographic profile, muscles operated, and fentanyl requirement were comparable. Complete response to PONV in first 24 hours was observed in 75% (51/68 of children in group G and 76.9% (50/65 of children in group GD, which was comparable statistically (p=0.96, Fisher exact test; OR 1.11, 95% CI 0.50, 2.46. Incidence of PONV between 0 and 24 hours was comparable. One child in group G required rescue antiemetic in first 24 hours and none of the children had severe PONV in group GD. There was no significant difference in incidence or severity of oculocardiac reflex. Conclusion. Dexamethasone did not increase efficacy of granisetron for prevention of PONV in elective pediatric strabismus surgery. Registration number of clinical trial was CTRI/2009/091/001000.

Effects of dexamethasone-21-isonicotinate on peripheral insulin action in dairy cows 5 days after surgical correction of abomasal displacement.

Science.gov (United States)

Kusenda, M; Kaske, M; Piechotta, M; Locher, L; Starke, A; Huber, K; Rehage, J

2013-01-01

Dexamethasone frequently is used for treatment of ketosis in dairy cows, but its effects are not fully understood. Dexamethasone treatment affects whole body insulin sensitivity. Twelve German Holstein cows, 2-4 weeks postpartum, 5 days after omentopexy to correct left abomasal displacement. Randomized, blinded, case-control study. Treatment with dexamethasone-21-isonicotinate (DG; 40 μg/kg IM; n = 6) or saline (control group [CG], 15 mL IM, n = 6) on day 0 (d0). Blood samples were obtained before (d0) and after treatment (d1 and d2), and analyzed for glucose, insulin, and nonesterified fatty acid (NEFA) concentrations. Hepatic triglycerides (TAG) were measured in liver samples taken on d0 and d2. Five consecutive hyperinsulinemic-euglycemic clamps (HEC-I-V; insulin dosages: 0.1, 0.5, 2, 5, 10 mU/kg/min, respectively) were performed on d1 and steady state glucose infusion rate (SSGIR), insulin concentration (SSIC), insulin sensitivity index (ISI = SSGIR/SSIC), and plasma NEFA concentration (SSNEFA) were assessed. Compared with CG-cows, DG-cows on d1 had higher plasma glucose (P = .004) and insulin (P insulin-stimulated decrease in SSNEFA (HEC-II, P = .006; HEC-III, P = .01; HEC-IV, P = .003; HEC-V, P = .011). Decrease in hepatic TAG content in DG-cows was higher compared with CG-cows (P insulin sensitivity and affects glucose and lipid metabolism in early lactating dairy cows. Copyright © 2012 by the American College of Veterinary Internal Medicine.

Adverse event management in patients with relapsed and refractory multiple myeloma taking pomalidomide plus low-dose dexamethasone: A pooled analysis.

Science.gov (United States)

Moreau, Philippe; Dimopoulos, Meletios A; Richardson, Paul G; Siegel, David S; Cavo, Michele; Corradini, Paolo; Weisel, Katja; Delforge, Michel; O'Gorman, Peter; Song, Kevin; Chen, Christine; Bahlis, Nizar; Oriol, Albert; Hansson, Markus; Kaiser, Martin; Anttila, Pekka; Raymakers, Reinier; Joao, Cristina; Cook, Gordon; Sternas, Lars; Biyukov, Tsvetan; Slaughter, Ana; Hong, Kevin; Herring, Jennifer; Yu, Xin; Zaki, Mohamed; San-Miguel, Jesus

2017-09-01

Heavily pretreated patients with relapsed and refractory multiple myeloma are susceptible to treatment-related adverse events (AEs). Managing AEs are important to ensure patients continue therapy long enough to receive the best clinical benefit. Data from the MM-002, MM-003, and MM-010 trials were pooled to further characterize the safety profile of pomalidomide plus low-dose dexamethasone and AE management. This analysis included 1088 patients who received ≥ 2 prior therapies, including lenalidomide and bortezomib, and progressed ≤ 60 days of last therapy. Patients received 28-day cycles of pomalidomide 4 mg/day on days 1-21 and low-dose dexamethasone 40 mg (20 mg if aged > 75 years) weekly until disease progression or unacceptable toxicity. Thromboprophylaxis was required. The most common grade 3/4 AEs were neutropenia (56.2%), anemia (32.3%), and thrombocytopenia (25.8%), which occurred within the first few cycles of treatment. Grade 3/4 infections occurred in 33.7% patients, of whom 13.9% had pneumonia, and 40.3% had neutropenia. Pomalidomide dose reductions or interruptions were reported in 24.2% and 66.0% of patients, respectively. AEs were managed by dose modifications and/or supportive care. Pomalidomide plus low-dose dexamethasone showed an acceptable safety profile, and AEs were well managed according to study protocols and established guidelines. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Aprepitant plus granisetron and dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients with gastric cancer treated with S-1 plus cisplatin.

Science.gov (United States)

Oyama, Katsunobu; Fushida, Sachio; Kaji, Masahide; Takeda, Toshiya; Kinami, Shinichi; Hirono, Yasuo; Yoshimoto, Katsuhiro; Yabushita, Kazuhisa; Hirosawa, Hisashi; Takai, Yuki; Nakano, Tatsuo; Kimura, Hironobu; Yasui, Toshiaki; Tsuneda, Atsushi; Tsukada, Tomoya; Kinoshita, Jun; Fujimura, Takashi; Ohta, Tetsuo

2013-11-01

We aimed to evaluate the efficacy of a new combination antiemetic therapy comprising aprepitant, granisetron, and dexamethasone in gastric cancer patients undergoing chemotherapy with cisplatin and S-1. Gastric cancer patients scheduled to receive their first course of chemotherapy with cisplatin (60 mg/m(2)) and S-1 (80 mg/m(2)) were treated with a new combination antiemetic therapy aprepitant, granisetron, and dexamethasone on day 1; aprepitant and dexamethasone on days 2 and 3; and dexamethasone on day 4. The patients reported vomiting, nausea, use of rescue therapy, and change in the amount of diet intake, and completed the Functional Living Index-Emesis (FLIE) questionnaire. The primary endpoint was complete response (CR; no emesis and use of no rescue antiemetics) during the overall study phase (0-120 h after cisplatin administration). The secondary endpoints included complete protection (CP; CR plus no significant nausea); change in the amount of diet intake; and the impact of chemotherapy-induced nausea and vomiting (CINV) on daily life during the overall, acute (0-24 h), and delayed (24-120 h) phases. Fifty-three patients were included. CR was achieved in 88.7, 98.1, and 88.7% of patients in the overall, acute, and delayed phases, respectively. The corresponding rates of CP were 67.9, 96.2, and 67.9%. Approximately half of the patients had some degree of anorexia. FLIE results indicated that 79.5% of patients reported "minimal or no impact of CINV on daily life". Addition of aprepitant to standard antiemetic therapy was effective in gastric cancer patients undergoing treatment with cisplatin and S-1.

Symposium on disruptive instabilities at Garching

International Nuclear Information System (INIS)

Lackner, K.

1979-01-01

The phenomenon of disruptive instabilities was investigated with a special care at the IPP at Garching. After lectures and panel sessions it appears suitable, to subdivide the disruptive phenomena into four classes: 1. The internal disruption (the socalled saw-tooth oscillators). 2. the socalled reconnection disruptions. 3. The large disruptions. 4. The small disruptions. The four appearance forms of the phenomena are briefly explained. (GG) [de

Structured Self-Rated Response to Iontophoresis with Verapamil and Dexamethasone in Peyronie’s Disease

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Abas Kokab

2014-01-01

Full Text Available Introduction. New therapies evolve for the treatment of Peyronie's disease (PD including the application of dexamethasone and verapamil using Electro Motive Drug Administration (EMDA. Patients and Methods. Patients with PD were routinely offered Potaba, Vitamin E, tamoxifen or colchicine for 6 to 18 months and for those with no improvement, 18 applications of dexamethasone and verapamil using EMDA occurred over a 6 week period. All 30 patients receiving EMDA therapy completed a questionnaire before and after treatment. The data was collected from December 2004 to November 2009 and analysed to evaluate the effectiveness of the treatment. Results. Median age of patients was 59 (range 39–71. Curvature was the most common presenting complaint (73.3% followed by pain (23.3%, erectile dysfunction (13.3%, and lump (13.3%. 24/30 (80% reported an improvement in symptoms after EMDA. 16 of the responders (66.7% had a stable plaque for at least 6 months. The patients who complained of shortening of the penis (P=0.003 or lowered sexual desire (P=0.024 expressed subsequently significant response to treatment. There was statistically significant (P=0.019 improvement of penile deviation reported by responding men. Conclusion. A significant proportion of patients who received EMDA reported decreased curvature following iontophoresis. No serious adverse reactions developed.

Survey of disruption causes at JET

International Nuclear Information System (INIS)

De Vries, P.C.; Johnson, M.F.; Alper, B.; Hender, T.C.; Riccardo, V.; Buratti, P.; Koslowski, H.R.

2011-01-01

A survey has been carried out into the causes of all 2309 disruptions over the last decade of JET operations. The aim of this survey was to obtain a complete picture of all possible disruption causes, in order to devise better strategies to prevent or mitigate their impact. The analysis allows the effort to avoid or prevent JET disruptions to be more efficient and effective. As expected, a highly complex pattern of chain of events that led to disruptions emerged. It was found that the majority of disruptions had a technical root cause, for example due to control errors, or operator mistakes. These bring a random, non-physics, factor into the occurrence of disruptions and the disruption rate or disruptivity of a scenario may depend more on technical performance than on physics stability issues. The main root cause of JET disruptions was nevertheless due to neo-classical tearing modes that locked, closely followed in second place by disruptions due to human error. The development of more robust operational scenarios has reduced the JET disruption rate over the last decade from about 15% to below 4%. A fraction of all disruptions was caused by very fast, precursorless unpredictable events. The occurrence of these disruptions may set a lower limit of 0.4% to the disruption rate of JET. If one considers on top of that human error and all unforeseen failures of heating or control systems this lower limit may rise to 1.0% or 1.6%, respectively.

ATP- and gap junction-dependent intercellular calcium signaling in osteoblastic cells

DEFF Research Database (Denmark)

Jorgensen, N R; Geist, S T; Civitelli, R

1997-01-01

mechanically induced calcium waves in two rat osteosarcoma cell lines that differ in the gap junction proteins they express, in their ability to pass microinjected dye from cell to cell, and in their expression of P2Y2 (P2U) purinergic receptors. ROS 17/2.8 cells, which express the gap junction protein......Many cells coordinate their activities by transmitting rises in intracellular calcium from cell to cell. In nonexcitable cells, there are currently two models for intercellular calcium wave propagation, both of which involve release of inositol trisphosphate (IP3)- sensitive intracellular calcium...... stores. In one model, IP3 traverses gap junctions and initiates the release of intracellular calcium stores in neighboring cells. Alternatively, calcium waves may be mediated not by gap junctional communication, but rather by autocrine activity of secreted ATP on P2 purinergic receptors. We studied...

Effect of Intravenous Dexamethasone on Preparing the Cervix and Labor Induction

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Fatemeh Laloha

2015-10-01

Full Text Available The use of corticosteroids is one of the methods put forward for the strengthening and speeding up the process of labor. After identification of glucocorticoid receptors in human amnion, the role of corticosteroids in starting the process of labor has been studied in numerous studies. The purpose of this study was to determine the effect of intravenous Dexamethasone on preparing the cervix and on labor induction. A randomized, clinical, and double – blind trial was conducted on 172 women divided into a control and an experimental group. The inclusion criteria were that they had to be primparous, in or before the 40th week of pregnancy, and with Bishop scores (B.S.s of 4 or lower. The exclusion criteria were diabetes, preeclampsia, macrosomia, twin pregnancy, rupture of the membrane (ROM, breech, and women suffering from background diseases. The B.S.s of the women was measured in charge of the study, and each woman was intravenously injected with eight milligrams of Dexamethasone or eight milligrams of distilled water. Four hours after the injections, the B.S.s of the participants was measured, and they were put under the conditions of labor induction using oxytocin. Information was collected in checklists A and B. The patients were compared with respect to B.S., the time the induction started, the average interval between the start of induction and the beginning of the active phase of childbirth, and the average length of time between the start of the active phase and the second stage of childbirth. The first and five minutes Apgar scores of the two groups of women were compared. The frequencies, the means,  and the standard deviations were calculated using the SPSS – 16 software, and analysis of the results was performed with the Student’s t- test and the chi-square test with PPPP

Intercellular distribution of mutations induced in oopcytes of Drosophila melanogaster by chemical and physical mutagens

International Nuclear Information System (INIS)

Traut, H.

1979-01-01

When females of Drosophila melanogaster are treated with chemical or physical mutagens, not only in one but also in both of the two homologous X chromosomes of a given oocyte, a recessive sex-linked lethal mutation may be induced. A method is described that discriminates between such single and double mutations. A theory is developed to show how a comparison betweeen the expected and the observer frequency of double mutations yields an indication of the intercellular distribution (random or nonrandom) of recessive lethal mutations induced by mutagenic agents in oocytes and, consequently, of the distribution (homogenous or nonhomogeneous) of those agents. Three agents were tested: FUdR (12.5, 50.0 and 81.0 μg/ml), mitomycin C (130.0 μg/ml) and x rays (2000 R, 150 kV). After FUdR feeding, no increase in the mutation frequency usually observed in D. melanogaster without mutagenic treatment was obtained (u = 0.13%, namely three single mutations among 2332 chromosomes tested). After mitomycin C feeding 104 single and three double mutations were obtained. All of the 50 mutations observed after x irradiation were single mutations. The results obtained in the mitomycin C and radiation experiments favor the assumption of a random intercellular distribution of recessive lethal mutations induced by these two agents in oocytes of D. melanogaster. Reasons are discussed why for other types of mutagenic agents nonrandom distributions may be observed with our technique

Statistical analysis of disruptions in JET

International Nuclear Information System (INIS)

De Vries, P.C.; Johnson, M.F.; Segui, I.

2009-01-01

The disruption rate (the percentage of discharges that disrupt) in JET was found to drop steadily over the years. Recent campaigns (2005-2007) show a yearly averaged disruption rate of only 6% while from 1991 to 1995 this was often higher than 20%. Besides the disruption rate, the so-called disruptivity, or the likelihood of a disruption depending on the plasma parameters, has been determined. The disruptivity of plasmas was found to be significantly higher close to the three main operational boundaries for tokamaks; the low-q, high density and β-limit. The frequency at which JET operated close to the density-limit increased six fold over the last decade; however, only a small reduction in disruptivity was found. Similarly the disruptivity close to the low-q and β-limit was found to be unchanged. The most significant reduction in disruptivity was found far from the operational boundaries, leading to the conclusion that the improved disruption rate is due to a better technical capability of operating JET, instead of safer operations close to the physics limits. The statistics showed that a simple protection system was able to mitigate the forces of a large fraction of disruptions, although it has proved to be at present more difficult to ameliorate the heat flux.

A phase IIb trial of vorinostat in combination with lenalidomide and dexamethasone in patients with multiple myeloma refractory to previous lenalidomide-containing regimens.

Science.gov (United States)

Sanchez, Larysa; Vesole, David H; Richter, Joshua R; Biran, Noa; Bilotti, Elizabeth; McBride, Laura; Anand, Palka; Ivanovski, Kristin; Siegel, David S

2017-02-01

Clinical trials of vorinostat, a Class I/II histone deacetylase inhibitor, in combination with proteasome inhibitors and immunomodulatory agents have shown activity in relapsed/refractory multiple myeloma. This phase IIb, open-label, single-institution study evaluated the efficacy of vorinostat in combination with lenalidomide and dexamethasone in lenalidomide-refractory patients. Patients were considered lenalidomide-refractory if they had no clinical response (vorinostat 400 mg days 1-7 and 15-21, lenalidomide 25 mg days 1-21, and dexamethasone 40 mg days 1, 8, 15 and 22 in 28-day cycles. Twenty-five patients were enrolled, median age was 65 years and patients had received a median of 5 prior regimens. The overall response rate was 24% (6 partial responses) and clinical benefit rate (≥stable disease) was 80%. Median time to a partial response was 1·9 months and median duration of response was 3·3 months. Median progression-free survival was 5·3 months. Most common grade 3/4 adverse events were neutropenia (48%), thrombocytopenia (32%), anaemia (20%) and gastrointestinal toxicities (16%). In this heavily pre-treated population, vorinostat in combination with lenalidomide and dexamethasone was active in lenalidomide-refractory patients. © 2016 John Wiley & Sons Ltd.

Improvements in disruption prediction at ASDEX Upgrade

Energy Technology Data Exchange (ETDEWEB)

Aledda, R., E-mail: raffaele.aledda@diee.unica.it; Cannas, B., E-mail: cannas@diee.unica.it; Fanni, A., E-mail: fanni@diee.unica.it; Pau, A., E-mail: alessandro.pau@diee.unica.it; Sias, G., E-mail: giuliana.sias@diee.unica.it

2015-10-15

Highlights: • A disruption prediction system for AUG, based on a logistic model, is designed. • The length of the disruptive phase is set for each disruption in the training set. • The model is tested on dataset different from that used during the training phase. • The generalization capability and the aging of the model have been tested. • The predictor performance is compared with the locked mode detector. - Abstract: In large-scale tokamaks disruptions have the potential to create serious damage to the facility. Hence disruptions must be avoided, but, when a disruption is unavoidable, minimizing its severity is mandatory. A reliable detection of a disruptive event is required to trigger proper mitigation actions. To this purpose machine learning methods have been widely studied to design disruption prediction systems at ASDEX Upgrade. The training phase of the proposed approaches is based on the availability of disrupted and non-disrupted discharges. In literature disruptive configurations were assumed appearing into the last 45 ms of each disruption. Even if the achieved results in terms of correct predictions were good, it has to be highlighted that the choice of such a fixed temporal window might have limited the prediction performance. In fact, it generates confusing information in cases of disruptions with disruptive phase different from 45 ms. The assessment of a specific disruptive phase for each disruptive discharge represents a relevant issue in understanding the disruptive events. In this paper, the Mahalanobis distance is applied to define a specific disruptive phase for each disruption, and a logistic regressor has been trained as disruption predictor. The results show that enhancements on the achieved performance on disruption prediction are possible by defining a specific disruptive phase for each disruption.

Improvements in disruption prediction at ASDEX Upgrade

International Nuclear Information System (INIS)

Aledda, R.; Cannas, B.; Fanni, A.; Pau, A.; Sias, G.

2015-01-01

Highlights: • A disruption prediction system for AUG, based on a logistic model, is designed. • The length of the disruptive phase is set for each disruption in the training set. • The model is tested on dataset different from that used during the training phase. • The generalization capability and the aging of the model have been tested. • The predictor performance is compared with the locked mode detector. - Abstract: In large-scale tokamaks disruptions have the potential to create serious damage to the facility. Hence disruptions must be avoided, but, when a disruption is unavoidable, minimizing its severity is mandatory. A reliable detection of a disruptive event is required to trigger proper mitigation actions. To this purpose machine learning methods have been widely studied to design disruption prediction systems at ASDEX Upgrade. The training phase of the proposed approaches is based on the availability of disrupted and non-disrupted discharges. In literature disruptive configurations were assumed appearing into the last 45 ms of each disruption. Even if the achieved results in terms of correct predictions were good, it has to be highlighted that the choice of such a fixed temporal window might have limited the prediction performance. In fact, it generates confusing information in cases of disruptions with disruptive phase different from 45 ms. The assessment of a specific disruptive phase for each disruptive discharge represents a relevant issue in understanding the disruptive events. In this paper, the Mahalanobis distance is applied to define a specific disruptive phase for each disruption, and a logistic regressor has been trained as disruption predictor. The results show that enhancements on the achieved performance on disruption prediction are possible by defining a specific disruptive phase for each disruption.

Cisplatin-Induced Conditioned Taste Aversion: Attenuation by Dexamethasone but not Zacopride or GR38032F

Science.gov (United States)

1992-01-01

SR2-1 Cisplatin-induced conditioned taste aversion: ateuto by dexamethasone but not zacopride or GR38032F Nm I- Paul C Mele, John R. McDonough, David...to 5-H1’, receptor blockade. 5-HT., receptor antagonists; Zacopridc: GR38032F; Desamethasone: Cisplatin: Taste aversion (conditioned) I. Introductlon...intake) was used as the area known as the chemoreceptor trigger zone (Borri- index of the CTA. son, 1974). Moreover. the findings that rats, ferrets

The effect of dexamethasone on thyrocytes from patients with Graves' disease

International Nuclear Information System (INIS)

Zhao Yaping; Wang Jialin

2002-01-01

To investigate the effect of dexamethasone (DEX) on thyrocytes of patients with Graves' Disease (GD), thyrocytes from GD were cultured in the presence of 10 -6 -10 -2 mol/L DEX. the growth of thyrocyte was measured by MTT method. Apoptosis, Fas expression were detected by Tunnel method and S-P method respectively. The result showed that 1) DEX in 10 -6 -10 -2 mol/L could kill the thyrocytes directly in time dependently. 2) Apoptosis and fas expression of thyrocyte cultured with DEX were significantly increased. 3) The rate of apoptosis was positively correlated with Fas expressions level. This results suggest that DEX can regulate the functions of thyroid by killing thyrocytes directly and inducing thyroid apoptosis

Detection of the intercellular adhesion gene cluster (ica in clinical Staphylococcus aureus isolates

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Namvar, Amirmorteza Ebrahimzadeh

2013-04-01

Full Text Available [english] is a major hospital and community pathogen having the aptitude to cause a wide variety of infections in men. The ability of microorganisms to produce biofilm facilitates them to withstand the host immune response and is recognized as one factor contributing to chronic or persistent infections. It was demonstrated that the -encoded genes lead to the biosynthesis of polysaccharide intercellular adhesion (PIA molecules, and may be involved in the accumulation phase of biofilm formation. Different studies have shown the decisive role of the gene as virulence factors in staphylococcal infections. This study was carried out to demonstrate the relationship between gene and production of slime layer in strains. Sixty strains were isolated from patients. The isolates were identified morphologically and biochemically following standard laboratory methods. After identification, the staphylococcal isolates were maintained in trypticase soy broth (TSB, to which 15% glycerol was added, and stored at –20°C. Slime formation and biofilm assay was monitored. A PCR assay was developed to identify the presence of (intercellular adhesion gene gene in all isolates. Thirty-nine slime producing colonies with CRA plates (65% formed black colors, the remaining 21 isolates were pink (35%. In the quantitative biofilm assay 35 (58% produced biofilm while 25 (42% isolates did not exhibit this property. All isolates were positive for detection of gene by PCR method. The interaction of and in the investigated isolates may be important in slime layer formation and biofilm phenomena.We propose PCR detection of the gene locus as a rapid and effective method to be used for discrimination between potentially virulent and nonvirulent isolates, with implications for therapeutic and preventive measures pertainin to the management of colonized indwelling catheters.

Intercellular contact: its influence on the Dsub(q) of mammalian cell survival curves

International Nuclear Information System (INIS)

Durand, R.E.; Sutherland, R.M.

1975-01-01

Cell survival in tissues exposed to a given dose of ionizing radiation is usually greater than that of similar cells grown individually in vitro, despite the fact that the radiosensitivities (D 0 ) are virtually identical under the two conditions. An analogous increase in cell survival is observed when Chinese hamster V79-171 cells are grown in suspension culture and irradiated as multicell spheroids. Unfortunately, the information gained from the survival curves so obtained is limited by the inhomogeneity of the cell population with respect to both degree of contact and cell cycle position. The latter can be studied using synchronized small spheroids. The ratio of Dsub(q) of spheroid cells to Dsub(q) of single cells increased as the cells progressed through the cell cycle, from a minimum of 1.3 for G 1 phase cells to a maximum of 2.2 for late S-phase cells. The enhanced survival, or 'contact effect', developed slowly as the spheroids grew, after an initial latent period of about one generation cycle of the cells. A second effect of intercellular contact on mammalian cell survival has also been observed. When cells are assayed under conditions in which intercellular contact is maintained, the net cellular survival is increased further. This effect is different from the usual repair of potentially lethal damage, in that it occurs much more slowly and results in modification of the survival-curve shoulder. Not all cell types tested have shown enhanced survival when grown as spheroids. Several MNNG-induced mutants of the Chinese hamster V79-171 line have been isolated and sublines which do and do not show the contact effect are now available. These may permit study of the mechanism(s) of contact effects. (author)

Disruption prediction at JET

International Nuclear Information System (INIS)

Milani, F.

1998-12-01

The sudden loss of the plasma magnetic confinement, known as disruption, is one of the major issue in a nuclear fusion machine as JET (Joint European Torus). Disruptions pose very serious problems to the safety of the machine. The energy stored in the plasma is released to the machine structure in few milliseconds resulting in forces that at JET reach several Mega Newtons. The problem is even more severe in the nuclear fusion power station where the forces are in the order of one hundred Mega Newtons. The events that occur during a disruption are still not well understood even if some mechanisms that can lead to a disruption have been identified and can be used to predict them. Unfortunately it is always a combination of these events that generates a disruption and therefore it is not possible to use simple algorithms to predict it. This thesis analyses the possibility of using neural network algorithms to predict plasma disruptions in real time. This involves the determination of plasma parameters every few milliseconds. A plasma boundary reconstruction algorithm, XLOC, has been developed in collaboration with Dr. D. O'Brien and Dr. J. Ellis capable of determining the plasma wall/distance every 2 milliseconds. The XLOC output has been used to develop a multilayer perceptron network to determine plasma parameters as l i and q ψ with which a machine operational space has been experimentally defined. If the limits of this operational space are breached the disruption probability increases considerably. Another approach for prediction disruptions is to use neural network classification methods to define the JET operational space. Two methods have been studied. The first method uses a multilayer perceptron network with softmax activation function for the output layer. This method can be used for classifying the input patterns in various classes. In this case the plasma input patterns have been divided between disrupting and safe patterns, giving the possibility of

BiRd (clarithromycin, lenalidomide, dexamethasone): an update on long-term lenalidomide therapy in previously untreated patients with multiple myeloma.

Science.gov (United States)

Rossi, Adriana; Mark, Tomer; Jayabalan, David; Christos, Paul; Zafar, Faiza; Pekle, Karen; Pearse, Roger; Chen-Kiang, Selina; Coleman, Morton; Niesvizky, Ruben

2013-03-14

The combination of clarithromycin, lenalidomide, and dexamethasone (BiRd) was evaluated as therapy for treatment-naive symptomatic multiple myeloma (MM), with overall response at 2 years of 90%. We reviewed the long-term follow-up of initial BiRd therapy. Seventy-two patients were given dexamethasone 40 mg weekly, clarithromycin 500 mg twice daily, and lenalidomide 25 mg daily on days 1 to 21 of a 28-day cycle. After a median follow-up of 6.6 years, overall response rates were 93%, with a very good partial response or better of 68%. Median progression-free survival was 49 months. Evaluation for the development of second primary malignancies (SPMs) was conducted, and no increase in incidence was noted in our cohort of patients who received frontline immunomodulatory therapy. BiRd remains a highly potent and safe regimen for frontline therapy in patients with MM without apparent increase in risk of SPMs. This trial was registered at www.clinicaltrials.gov as #NCT00151203.

Nippostronglylus brasiliensis infection in the rat: effect of iron and protein deficiency and dexamethasone on the efficacy of benzimidazole anthelmintics.

Science.gov (United States)

Duncombe, V M; Bolin, T D; Davis, A E; Kelly, J D

1977-01-01

Malnutrition, anaemia, and gut parasites are commonly interrelated. Using the Nippostrongylus brasiliensis-rat model, the effect of iron and protein deficiency on the efficacy of benzimidazole anthelmintics was studied. It was demonstrated that the anthelmintics mebendazole and fenbendazole were significantly less effective in eradicating parasites when animals were deficient in iron and protein. This decreased efficacy of anthelmintics in iron and protein deficiency could not be overcome by intraperitoneal administration of the drug. Since nutritional deficiencies may act via impairment of the immune response, anthelmintic efficacy was determined in adequately nourished rats treated with the immunosuppressive drug dexamethasone. A similar decrease in efficacy of mebendazole was shown when these animals were treated with dexamethasone. Thus it is possible that lowered anthelmintic efficacy in iron and protein deficient animals is mediated by immune deficiency. These findings may be relevant to anthelmintic programmes in malnourished communities. PMID:590849

Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study.

Science.gov (United States)

Rosiñol, Laura; Oriol, Albert; Teruel, Ana Isabel; Hernández, Dolores; López-Jiménez, Javier; de la Rubia, Javier; Granell, Miquel; Besalduch, Joan; Palomera, Luis; González, Yolanda; Etxebeste, María Asunción; Díaz-Mediavilla, Joaquín; Hernández, Miguel T; de Arriba, Felipe; Gutiérrez, Norma C; Martín-Ramos, María Luisa; Cibeira, María Teresa; Mateos, María Victoria; Martínez, Joaquín; Alegre, Adrián; Lahuerta, Juan José; San Miguel, Jesús; Bladé, Joan

2012-08-23

The Spanish Myeloma Group conducted a trial to compare bortezomib/thalidomide/dexamethasone (VTD) versus thalidomide/dexamethasone (TD) versus vincristine, BCNU, melphalan, cyclophosphamide, prednisone/vincristine, BCNU, doxorubicin, dexamethasone/bortezomib (VBMCP/VBAD/B) in patients aged 65 years or younger with multiple myeloma. The primary endpoint was complete response (CR) rate postinduction and post-autologous stem cell transplantation (ASCT). Three hundred eighty-six patients were allocated to VTD (130), TD (127), or VBMCP/VBAD/B (129). The CR rate was significantly higher with VTD than with TD (35% vs 14%, P = .001) or with VBMCP/VBAD/B (35% vs 21%, P = .01). The median progression-free survival (PFS) was significantly longer with VTD (56.2 vs 28.2 vs 35.5 months, P = .01). In an intention-to-treat analysis, the post-ASCT CR rate was higher with VTD than with TD (46% vs 24%, P = .004) or with VBMCP/VBAD/B (46% vs 38%, P = .1). Patients with high-risk cytogenetics had a shorter PFS and overall survival in the overall series and in all treatment groups. In conclusion, VTD resulted in a higher pre- and posttransplantation CR rate and in a significantly longer PFS although it was not able to overcome the poor prognosis of high-risk cytogenetics. Our results support the use of VTD as a highly effective induction regimen prior to ASCT. The study was registered with http://www.clinicaltrials.gov (NCT00461747) and Eudra CT (no. 2005-001110-41).

Multimodal analgesia with gabapentin, ketamine and dexamethasone in combination with paracetamol and ketorolac after hip arthroplasty: a preliminary study

DEFF Research Database (Denmark)

Rasmussen, Michael; Mathiesen, Ole; Dierking, Gerd

2010-01-01

It has been hypothesized that combinations of analgesics with different mechanisms of action may reduce or even prevent postoperative pain. We, therefore, investigated the analgesic effect of gabapentin, dexamethasone and low-dose ketamine in combination with paracetamol and ketorolac as compared...... with paracetamol and ketorolac alone after hip arthroplasty....

Histopatologi Usus Halus Tikus Putih Jantan yang Diberikan Deksametason dan Vitamin E (HISTOPATHOLOGY SMALL INSTESTINE OF MALE WHITE RATS THAT WERE DEXAMETHASONE AND VITAMINE E SUPLEMENTED

Directory of Open Access Journals (Sweden)

Kadek Karina Dewi Wijayanthi

2017-02-01

Full Text Available Deksametason telah diketahui sebagai obat kortikosteroid sintetik yang banyak digunakan oleh masyarakat. Jika deksametason digunakan dalam jangka waktu panjang dan pemakaian dosis besar, menyebabkan stres oksidatif pada sel akibat akumulasi radikal bebas yang menyebabkan kematian sel pada jaringan organ tubuh. Vitamin E diketahui memiliki peran yang baik sebagai antioksidan. Saat ini belum diketahui efek samping pemberian deksametason dan vitamin E terhadap kerusakan usus halus tikus putih (Rattus norvegicus. Penelitian ini menggunakan sampel 25 ekor tikus putih jantan, dibagi dalam 5 kelompok perlakuan, yaitu kontrol negatif (P0, kontrol positif (P1 diberikan deksametason Harsen  0.13 mg/kg, dan perlakuan diberikan deksametason Harsen 0.13 mg/kg dengan variasi vitamin E (Natur-E bertingkat yaitu P2 (100 mg/kg, P3 (150 mg/kg, dan P4 (200 mg/kg. Setelah perlakuan diberikan selama 2 minggu, tikus dinekropsi dan usus halus diambil untuk selanjutnya dibuat sediaan histopatologi dengan pewarnaan hematoksilin-eosin (HE. Hasil menunjukkan perlakuan P1 terlihat nekrosis berat (kaseosa pada usus halus, sedangkan seluruh perlakuan P2, P3, dan P4 berpengaruh terhadap perbaikan kerusakan akibat efek samping deksametason. Perlakuan 4 (P4 sebagai hasil paling baik dalam mengurangi efek samping deksametason.   Dexamethasone it’s in period a synthetic corticosteroid drug that widely used by the public. If  it used for long time and the use of large doses, causing oxidative stress in cells due to the accumulation of free radicals which may cause cell death in the body organs tissues. Vitamin E was known to have a good role as an antioxidant effect. Currently, unknown effects of dexamethasone and vitamin E administration on damage of the small intestine of rat (Rattus norvegicus. This study used an experimental design. Samples 25 male rats were divided into 5 groups, namely the negative control or no treatment (P0, positive control (P1 was given

Comparative Efficacy of Daratumumab Monotherapy and Pomalidomide Plus Low-Dose Dexamethasone in the Treatment of Multiple Myeloma: A Matching Adjusted Indirect Comparison.

Science.gov (United States)

Van Sanden, Suzy; Ito, Tetsuro; Diels, Joris; Vogel, Martin; Belch, Andrew; Oriol, Albert

2018-03-01

Daratumumab (a human CD38-directed monoclonal antibody) and pomalidomide (an immunomodulatory drug) plus dexamethasone are both relatively new treatment options for patients with heavily pretreated multiple myeloma. A matching adjusted indirect comparison (MAIC) was used to compare absolute treatment effects of daratumumab versus pomalidomide + low-dose dexamethasone (LoDex; 40 mg) on overall survival (OS), while adjusting for differences between the trial populations. The MAIC method reduces the risk of bias associated with naïve indirect comparisons. Data from 148 patients receiving daratumumab (16 mg/kg), pooled from the GEN501 and SIRIUS studies, were compared separately with data from patients receiving pomalidomide + LoDex in the MM-003 and STRATUS studies. The MAIC-adjusted hazard ratio (HR) for OS of daratumumab versus pomalidomide + LoDex was 0.56 (95% confidence interval [CI], 0.38-0.83; p  = .0041) for MM-003 and 0.51 (95% CI, 0.37-0.69; p  < .0001) for STRATUS. The treatment benefit was even more pronounced when the daratumumab population was restricted to pomalidomide-naïve patients (MM-003: HR, 0.33; 95% CI, 0.17-0.66; p  = .0017; STRATUS: HR, 0.41; 95% CI, 0.21-0.79; p  = .0082). An additional analysis indicated a consistent trend of the OS benefit across subgroups based on M-protein level reduction (≥50%, ≥25%, and <25%). The MAIC results suggest that daratumumab improves OS compared with pomalidomide + LoDex in patients with heavily pretreated multiple myeloma. This matching adjusted indirect comparison of clinical trial data from four studies analyzes the survival outcomes of patients with heavily pretreated, relapsed/refractory multiple myeloma who received either daratumumab monotherapy or pomalidomide plus low-dose dexamethasone. Using this method, daratumumab conferred a significant overall survival benefit compared with pomalidomide plus low-dose dexamethasone. In the absence of head-to-head trials, these

The effect of addition of dexamethasone to levobupivacaine in parturients receiving combined spinal-epidural for analgesia for vaginal delivery

Directory of Open Access Journals (Sweden)

Amr Samir Wahdan

2017-01-01

Full Text Available Background and Aims: Regional analgesia is commonly used for the relief of labour pain, Prolongation of analgesia can be achieved by adjuvant medications. The aim of this randomised controlled trial was to evaluate the efficacy of intrathecal levobupivacaine with dexamethasone for labour analgesia. Methods: A total of 80 females were included in this study, all were primigravidas undergoing vaginal delivery with cervical dilatation ≥4 cm and 50% or more effacement. Forty females were included randomly in either Group L (received intrathecal levobupivacaine 0.25% in 2 mL or Group LD (received intrathecal levobupivacaine 0.25% combined with dexamethasone 4 mg in 2 mL. The primary outcome was the duration of spinal analgesia. Secondary outcomes included the total dose of epidural local anaesthetic given, time to delivery, neonatal outcome and adverse effects. Results: The duration of spinal analgesia was significantly longer in the LD group compared with L group (80.5 ± 12.4 min vs. 57.1 ± 11.5 min, respectively; P< 0.001. In Group LD compared with Group L, time from spinal analgesia to delivery was significantly lower (317.4 ± 98.9 min vs. 372.4 ± 118.8 min, respectively; P = 0.027, and total epidural levobupivacaine consumption was significantly lower (102.4 ± 34.8 mg vs. 120.1 ± 41.9 mg, respectively; P = 0.027. The two groups were comparable with respect to characteristics of sensory and motor block, haemodynamic parameters, pain scores, neonatal outcome and frequency of adverse effects. Conclusion: Intrathecal dexamethasone plus levobupivacaine prolongs the duration of spinal analgesia during combined spinal-epidural CSE for labour analgesia.

Monitoring-induced disruption in skilled typewriting.

Science.gov (United States)

Snyder, Kristy M; Logan, Gordon D

2013-10-01

It is often disruptive to attend to the details of one's expert performance. The current work presents four experiments that utilized a monitor to report protocol to evaluate the sufficiency of three accounts of monitoring-induced disruption. The inhibition hypothesis states that disruption results from costs associated with preparing to withhold inappropriate responses. The dual-task hypothesis states that disruption results from maintaining monitored information in working memory. The implicit-explicit hypothesis states that disruption results from explicitly monitoring details of performance that are normally implicit. The findings suggest that all three hypotheses are sufficient to produce disruption, but inhibition and dual-task costs are not necessary. Experiment 1 showed that monitoring to report was disruptive even when there was no requirement to inhibit. Experiment 2 showed that maintaining information in working memory caused some disruption but much less than monitoring to report. Experiment 4 showed that monitoring to inhibit was more disruptive than monitoring to report, suggesting that monitoring is more disruptive when it is combined with other task requirements, such as inhibition. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Disruptive Intelligence - How to gather Information to deal with disruptive innovations

NARCIS (Netherlands)

Vriens, D.J.; Solberg Søilen, K.

2014-01-01

Disruptive innovations are innovations that have the capacity to transform a whole business into one with products that are more accessible and affordable (cf. Christensen et al. 2009). As Christensen et al. argue no business is immune to such disruptive innovations. If these authors are right, it

Simultaneous Determination of Ciprofloxacin Hydrochloride and Dexamethasone Sodium Phosphate in Eye Drops by HPLC

OpenAIRE

Katakam, Prakash; Sireesha, Karanam R.

2012-01-01

A liquid chromatographic method was developed and validated for the simultaneous determination of ciprofloxacin hydrochloride and dexamethasone sodium phosphate in bulk and pharmaceutical formulations. Optimum separation was achieved in less than 5 min using a C18 column (250 mmx4.6 mm i.d, 5μ particle size) by isocratic elution. The mobile phase consisting of a mixture of mixed phosphate buffer (pH 4) and acetonitrile (65:35, v/v) was used. Column effluents were monitored at 254 nm at a flow...

Regulation of intercellular tight junctions by zonula occludens toxin and its eukaryotic analogue zonulin.

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Fasano, A

2000-01-01

The intestinal epithelium represents the largest interface between the external environment and the internal host milieu and constitutes the major barrier through which molecules can either be absorbed or secreted. There is now substantial evidence that tight junctions (tj) play a major role in regulating epithelial permeability by influencing paracellular flow of fluid and solutes. Tj are one of the hallmarks of absorptive and secretory epithelia. Evidence now exists that tj are dynamic rather than static structures and readily adapt to a variety of developmental, physiological, and pathological circumstances. These adaptive mechanisms are still incompletely understood. Activation of PKC either by Zonula occludens toxin (Zot) or by phorbol esters increases paracellular permeability. Alteration of epithelial tj is a recently described property for infectious agents. Clostridium difficile toxin A and B and influenza and vesicular stomatitis viruses have been shown to loosen tj in tissue culture monolayers. Unlike what occurs after the Zot stimulus, these changes appear to be irreversible and are associated with destruction of the tj complex. On the basis of this observation, we postulated that Zot may mimic the effect of a functionally and immunologically related endogenous modulator of epithelial tj. We were able to identify an intestinal Zot analogue, which we named zonulin. It is conceivable that the zonulins participate in the physiological regulation of intercellular tj not only in the small intestine, but also throughout a wide range of extraintestinal epithelia as well as the ubiquitous vascular endothelium, including the blood-brain barrier. Disregulation of this hypothetical zonulin model may contribute to disease states that involve disordered intercellular communication, including developmental and intestinal disorders, tissue inflammation, malignant transformation, and metastasis.

Politisk disruption

DEFF Research Database (Denmark)

Tække, Jesper

2018-01-01

Dette blogindlæg giver en kort analyse af hvordan de sociale medier ved at give en ny tid har åbnet for den disruption af de politiske processer som især Trump stå som et eksempel på.......Dette blogindlæg giver en kort analyse af hvordan de sociale medier ved at give en ny tid har åbnet for den disruption af de politiske processer som især Trump stå som et eksempel på....

Towards a Disruptive Digital Platform Model

DEFF Research Database (Denmark)

Kazan, Erol

that digital platforms leverage on three strategic design elements (i.e., business, architecture, and technology design) to create supportive conditions for facilitating disruption. To shed light on disruptive digital platforms, I opted for payment platforms as my empirical context and unit of analysis......Digital platforms are layered modular information technology architectures that support disruption. Digital platforms are particularly disruptive, as they facilitate the quick release of digital innovations that may replace established innovations. Yet, despite their support for disruption, we have...... not fully understood how such digital platforms can be strategically designed and configured to facilitate disruption. To that end, this thesis endeavors to unravel disruptive digital platforms from the supply perspective that are grounded on strategic digital platform design elements. I suggest...

Dexamethasone attenuates grain sorghum dust extract-induced increase in macromolecular efflux in vivo.

Science.gov (United States)

Akhter, S R; Ikezaki, H; Gao, X P; Rubinstein, I

1999-05-01

The purpose of this study was to determine whether dexamethasone attenuates grain sorghum dust extract-induced increase in macromolecular efflux from the in situ hamster cheek pouch and, if so, whether this response is specific. By using intravital microscopy, we found that an aqueous extract of grain sorghum dust elicited significant, concentration-dependent leaky site formation and increase in clearance of FITC-labeled dextran (FITC-dextran; mol mass, 70 kDa) from the in situ hamster cheek pouch (P grain sorghum dust extract- and substance P-induced increases in macromolecular efflux from the in situ hamster cheek pouch in a specific fashion.

Haloperidol plus dexamethasone versus dexamethasone alone to prevent postoperative nausea and vomiting in patients undergoing ambulatory surgery: a randomized, controlled and double-blind study

Directory of Open Access Journals (Sweden)

Nelson Javier González

2008-02-01

Full Text Available

BACKGROUND AND GOAL OF THE STUDY: haloperidol is an effective antiemetic drug. We sought to determine whether haloperidol and dexamethasone prophylaxis schemes decrease the incidence of postoperative nausea and vomiting (PONV in patients undergoing ambulatory surgery.

MATERIALS AND METHODS: we enrolled 160 non-smoking females who received a standardized anesthesia technique including 8 mg of dexamethasone at the beginning of surgery. They were then randomized to receive either 1.5 mg of haloperidol (DH group or placebo (DP group 30 minutes before the end of surgery. The incidence of PONV was assessed by a blinded investigator at 30 minutes and at 2, 6 and 24 hours in the postoperative period. Analgesic requirements, ocular opening time and sedation were also assessed. The quantitative variables of normal distribution were evaluated with the t-student test and the ones with abnormal distribution, with the U-Mann Whitney test. Qualitative variables were evaluated with the Fisher test.

RESULTS AND DISCUSSION: both groups were homogeneous in demographic characteristics (30.1 vs. 29.5 years, 55.9 vs. 56 kg and history of PONV in 21.5% vs. 21.2% in DH group vs. DP group, respectively. At 6 hours postoperatively we found no difference in the incidence of nausea (22.5% vs. 27.5%; RR: 0.81, CI 95%: 0.56 -1

Thigmotaxis Mediates Trail Odour Disruption.

Science.gov (United States)

Stringer, Lloyd D; Corn, Joshua E; Sik Roh, Hyun; Jiménez-Pérez, Alfredo; Manning, Lee-Anne M; Harper, Aimee R; Suckling, David M

2017-05-10

Disruption of foraging using oversupply of ant trail pheromones is a novel pest management application under investigation. It presents an opportunity to investigate the interaction of sensory modalities by removal of one of the modes. Superficially similar to sex pheromone-based mating disruption in moths, ant trail pheromone disruption lacks an equivalent mechanistic understanding of how the ants respond to an oversupply of their trail pheromone. Since significant compromise of one sensory modality essential for trail following (chemotaxis) has been demonstrated, we hypothesised that other sensory modalities such as thigmotaxis could act to reduce the impact on olfactory disruption of foraging behaviour. To test this, we provided a physical stimulus of thread to aid trailing by Argentine ants otherwise under disruptive pheromone concentrations. Trail following success was higher using a physical cue. While trail integrity reduced under continuous over-supply of trail pheromone delivered directly on the thread, provision of a physical cue in the form of thread slightly improved trail following and mediated trail disruption from high concentrations upwind. Our results indicate that ants are able to use physical structures to reduce but not eliminate the effects of trail pheromone disruption.

Dexamethasone, all trans retinoic acid and interferon alpha 2a in patients with refractory multiple myeloma.

Science.gov (United States)

Avilés, A; Rosas, A; Huerta-Guzmán, J; Talavera, A; Cleto, S

1999-02-01

Few effective regimen are available for patients with refractory multiple myeloma (RMM). Generally, responses are scarce and disease free survival is very short. We developed a new therapeutic option in these patients using dexamethasone (40 mg/m2, i.v., daily, days 1 to 4), all-trans retinoic acid (45 mg/m2, po, daily, days 5 to 14) and interferon alpha 2a (9.0 MU, daily, subcutaneously, days 5 to 14). The treatment was administered every 21 days for 6 cycles. In a pilot study, 12 patients, heavily treated with chemotherapy and radiotherapy and in some cases with interferon, were allocated to receive the afore mentioned treatment. Response was observed in 10 patients (83%). With a median follow-up of 36.1 months (range 27 to 41), seven patients remain alive and disease-free without any treatment. Two patients were failures and have died due to tumor progression. Toxicity was mild and all patients received treatment according to the planned doses of drugs. The use of biological modifiers in combination with dexamethasone offer a safe and effective therapeutic option in patients with refractory multiple myeloma. More studies are warranted to define the role of this type of treatment.

Differentiation of malignant and degenerative bone lesions using dexamethasone interventional 3- and 24-hour bone scintigraphy

International Nuclear Information System (INIS)

Bhatnagar, A.; Mondal, A.; Kashyap, R.; Sharma, R.K.; Sharma, R.; Chakravarty, S.K.; Bihari, V.; Sawroop, K.; Chopra, M.K.; Soni, N.L.

1994-01-01

Seventy-seven adult patients with suspected skeletal metastases were divided into two groups. In group A (n=30), following intravenous administration of 20 mCi (740 MBq) of technetium-99m methylene diphosphonate ( 99m Tc-MDP), 3- and 24-h scintigraphy of bone lesions was performed. The 24/3 h lesion to bone background radiouptake ratio (RUR) was calculated for each lesion. In group B (n=47), the same procedure was followed with dexamethasone intervention (10 mg in 24 h) following the 3-h acquisition. In group A, after determination of the critical point, malignant and degenerative bone lesions could be separated with a sensitivity, specificity and accuracy of 0.76, 0.72 and 0.73, respectively. The mean RUR of the malignant lesions was 1.20± 0.23, and that of the benign lesions, 0.95± 0.15. In group B cases, significantly increased sensitivity, specificity and accuracy of 0.87, 0.94 and 0.92, respectively, were found (P<0.001). The mean RUR of the malignant lesions was 1.48± 0.34, and that of degenerative lesions, 0.88± 0.19. Dexamethasone interventional bone scintigraphy seems to be a new cost-effective method for differentiating malignant from degenerative bone lesions using the RUR. (orig.)

MMP-8 Is Critical for Dexamethasone Therapy in Alkali-Burned Corneas Under Dry Eye Conditions

Science.gov (United States)

BIAN, FANG; WANG, CHANGJUN; TUKLER-HENRIKSSON, JOHANNA; PFLUGFELDER, STEPHEN C.; CAMODECA, CATERINA; NUTI, ELISA; ROSSELLO, ARMANDO; LI, DE-QUAN; DE PAIVA, CINTIA S.

2016-01-01

Our previous studies have shown that Dexamethasone (Dex) reduced the expression of matrix-metalloproteinases (MMPs -1,-3,-9,-13), IL-1β and IL-6, while it significantly increased MMP-8 mRNA transcripts in a concomitant dry eye and corneal alkali burn murine model (CM). To investigate if MMP-8 induction is responsible for some of the protective effects of Dex in CM, MMP-8 knock out mice (MMP-8KO) were subjected to the CM for 2 or 5 days and topically treated either with 2 μl of 0.1% Dexamethasone (Dex), or saline QID. A separate group of C57BL/6 mice were topically treated with Dex or BSS and received either 100 nM CAM12 (MMP-8 inhibitor) or vehicle IP, QD. Here we demonstrate that topical Dex treated MMP-8KO mice subjected to CM showed reduced corneal clarity, increased expression of inflammatory mediators (IL-6, CXCL1, and MMP-1 mRNA) and increased neutrophil infiltration at 2D and 5D compared to Dex treated WT mice. C57BL/6 mice topically treated with Dex and CAM12 IP recapitulated findings seen with MMP-8KO mice. These results suggest that some of the anti-inflammatory effects of Dex are mediated through increased MMP-8 expression. PMID:26923552

Supply disruption cost for power network planning

International Nuclear Information System (INIS)

Kjoelle, G.H.

1992-09-01

A description is given of the method of approach to calculate the total annual socio-economic cost of power supply disruption and non-supplied energy, included the utilities' cost for planning. The total socio-economic supply disruption cost is the sum of the customers' disruption cost and the utilities' cost for failure and disruption. The mean weighted disruption cost for Norway for one hour disruption is NOK 19 per kWh. The customers' annual disruption cost is calculated with basis in the specific disruption cost referred to heavy load (January) and dimensioning maximum loads. The loads are reduced by factors taking into account the time variations of the failure frequency, duration, the loads and the disruption cost. 6 refs

Disrupting the Industry with Play

DEFF Research Database (Denmark)

Lund, Henrik Hautop

2016-01-01

or two ago. This is significantly disrupting the industry in several market sectors. This paper describes the components of the playware and embodied artificial intelligence research that has led to disruption in the industrial robotics sector, and which points to the next disruption of the health care...

Cell disruption for microalgae biorefineries.

Science.gov (United States)

Günerken, E; D'Hondt, E; Eppink, M H M; Garcia-Gonzalez, L; Elst, K; Wijffels, R H

2015-01-01

Microalgae are a potential source for various valuable chemicals for commercial applications ranging from nutraceuticals to fuels. Objective in a biorefinery is to utilize biomass ingredients efficiently similarly to petroleum refineries in which oil is fractionated in fuels and a variety of products with higher value. Downstream processes in microalgae biorefineries consist of different steps whereof cell disruption is the most crucial part. To maintain the functionality of algae biochemicals during cell disruption while obtaining high disruption yields is an important challenge. Despite this need, studies on mild disruption of microalgae cells are limited. This review article focuses on the evaluation of conventional and emerging cell disruption technologies, and a comparison thereof with respect to their potential for the future microalgae biorefineries. The discussed techniques are bead milling, high pressure homogenization, high speed homogenization, ultrasonication, microwave treatment, pulsed electric field treatment, non-mechanical cell disruption and some emerging technologies. Copyright © 2015 Elsevier Inc. All rights reserved.

Inhibition of luminescence and virulence in the black tiger prawn (Penaeus monodon) pathogen Vibrio harveyi by intercellular signal antagonists.