Impact of thermal processing on sulforaphane yield from broccoli ( Brassica oleracea L. ssp. italica).

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Wang, Grace C; Farnham, Mark; Jeffery, Elizabeth H

2012-07-11

In broccoli, sulforaphane forms when the glucosinolate glucoraphanin is hydrolyzed by the endogenous plant thiohydrolase myrosinase. A myrosinase cofactor directs hydrolysis away from the formation of bioactive sulforaphane and toward an inactive product, sulforaphane nitrile. The cofactor is more heat sensitive than myrosinase, presenting an opportunity to preferentially direct hydrolysis toward sulforaphane formation through regulation of thermal processing. Four broccoli cultivars were microwave heated, boiled, or steamed for various lengths of time. Production of nitrile during hydrolysis of unheated broccoli varied among cultivars from 91 to 52% of hydrolysis products (Pinnacle > Marathon > Patriot > Brigadier). Boiling and microwave heating caused an initial loss of nitrile, with a concomitant increase in sulforaphane, followed by loss of sulforaphane, all within 1 min. In contrast, steaming enhanced sulforaphane yield between 1.0 and 3.0 min in all but Brigadier. These data are proof of concept that steaming for 1.0-3.0 min provides less nitrile and more sulforaphane yield from a broccoli meal.

Sulforaphane Bioavailability from Glucoraphanin-Rich Broccoli: Control by Active Endogenous Myrosinase

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Fahey, Jed W.; Holtzclaw, W. David; Wehage, Scott L.; Wade, Kristina L.; Stephenson, Katherine K.; Talalay, Paul

2015-01-01

Glucoraphanin from broccoli and its sprouts and seeds is a water soluble and relatively inert precursor of sulforaphane, the reactive isothiocyanate that potently inhibits neoplastic cellular processes and prevents a number of disease states. Sulforaphane is difficult to deliver in an enriched and stable form for purposes of direct human consumption. We have focused upon evaluating the bioavailability of sulforaphane, either by direct administration of glucoraphanin (a glucosinolate, or β-thioglucoside-N-hydroxysulfate), or by co-administering glucoraphanin and the enzyme myrosinase to catalyze its conversion to sulforaphane at economic, reproducible and sustainable yields. We show that following administration of glucoraphanin in a commercially prepared dietary supplement to a small number of human volunteers, the volunteers had equivalent output of sulforaphane metabolites in their urine to that which they produced when given an equimolar dose of glucoraphanin in a simple boiled and lyophilized extract of broccoli sprouts. Furthermore, when either broccoli sprouts or seeds are administered directly to subjects without prior extraction and consequent inactivation of endogenous myrosinase, regardless of the delivery matrix or dose, the sulforaphane in those preparations is 3- to 4-fold more bioavailable than sulforaphane from glucoraphanin delivered without active plant myrosinase. These data expand upon earlier reports of inter- and intra-individual variability, when glucoraphanin was delivered in either teas, juices, or gelatin capsules, and they confirm that a variety of delivery matrices may be equally suitable for glucoraphanin supplementation (e.g. fruit juices, water, or various types of capsules and tablets). PMID:26524341

Chemopreventive Activities of Sulforaphane and Its Metabolites in Human Hepatoma HepG2 Cells

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Peng Liu

2018-05-01

Full Text Available Sulforaphane (SFN exhibits chemopreventive effects through various mechanisms. However, few studies have focused on the bioactivities of its metabolites. Here, three metabolites derived from SFN were studied, known as sulforaphane glutathione, sulforaphane cysteine and sulforaphane-N-acetylcysteine. Their effects on cell viability, DNA damage, tumorigenicity, cell migration and adhesion were measured in human hepatoma HepG2 cells, and their anti-angiogenetic effects were determined in a 3D co-culture model of human umbilical vein endothelial cells (HUVECs and pericytes. Results indicated that these metabolites at high doses decreased cancer cell viability, induced DNA damage and inhibited motility, and impaired endothelial cell migration and tube formation. Additionally, pre-treatment with low doses of SFN metabolites protected against H2O2 challenge. The activation of the nuclear factor E2-related factor 2 (Nrf2-antioxidant response element (ARE pathway and the induction of intracellular glutathione (GSH played an important role in the cytoprotective effects of SFN metabolites. In conclusion, SFN metabolites exhibited similar cytotoxic and cytoprotective effects to SFN, which proves the necessity to study the mechanisms of action of not only SFN but also of its metabolites. Based on the different tissue distribution profiles of these metabolites, the most relevant chemical forms can be selected for targeted chemoprevention.

Optimisation of the Method for the Quantitative Determination of Sulforaphane in Broccoli

International Nuclear Information System (INIS)

Yi Yi Myint; Antal Bognar; Tauscher, B.

2002-02-01

Consumption of vegetables, especially crucifers, reduces the risk of developing cancer. Sulforaphane [l-isothiocyanato-4- (methylsulfinyl)-butane], a compound with the ability to inhibit carcinogenesis, is one of the degradation products of glucosinolates in cruciferous vegetables. Among available extraction methods, autolysis at room temperature is the most effective for Sulforaphane extraction (relatively higher purity and better yield). The research work undertaken at Federal Research Centre for Nutrition, Institute of Biology and Chemistry, Karlsruhe, Germany was isolation of Sulforaphane based on cruciferous vegetables like Broccoli (Brassica oleracea L. Cv. italica) employing autolysis - the yield being higher. The extracted Sulforaphane compound's purity and yield were accordingly examined with gas chromatography. (author)

Optimisation of the Method for the Quantitative Determination of Sulforaphane in Broccoli

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Myint, Yi Yi; Bognar, Antal; Tauscher, B

2002-02-15

Consumption of vegetables, especially crucifers, reduces the risk of developing cancer. Sulforaphane [l-isothiocyanato-4- (methylsulfinyl)-butane], a compound with the ability to inhibit carcinogenesis, is one of the degradation products of glucosinolates in cruciferous vegetables. Among available extraction methods, autolysis at room temperature is the most effective for Sulforaphane extraction (relatively higher purity and better yield). The research work undertaken at Federal Research Centre for Nutrition, Institute of Biology and Chemistry, Karlsruhe, Germany was isolation of Sulforaphane based on cruciferous vegetables like Broccoli (Brassica oleracea L. Cv. italica) employing autolysis - the yield being higher. The extracted Sulforaphane compound's purity and yield were accordingly examined with gas chromatography. (author)

Storage in high-barrier pouches increases the sulforaphane concentration in broccoli florets.

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Yoshio Makino

Full Text Available Sulforaphane is a phytochemical that is usually found in cruciferous vegetables and is known to have a depressive effect on gastric cancer. Preliminary investigations showed that the sulforaphane concentration in broccoli (Brassica oleracea var. italica florets increased under anoxia. Therefore, in the present study, we examined the effect of different atmospheric conditions on the sulforaphane concentration in broccoli and also tested whether there are concurrent effects on the concentration of ethanol, which is an unfavorable byproduct of fermentation. The sulforaphane concentration in broccoli florets was significantly elevated by 1.9- to 2.8-fold after 2 d of storage under hypoxia at ca. 0% O2 and ca. 24% CO2 at 20°C, whereas no such increase was observed following storage under normoxia at ca. 0% O2 without CO2 at 20°C. Furthermore, after 2 d, the sulforaphane concentration under hypoxia was 1.6- to 2.3-fold higher than that under normoxia. These results suggest that storage under hypoxia with high CO2 levels can elevate the sulforaphane concentration in broccoli florets. However, the elevated sulforaphane concentration could not be maintained beyond 2 d. There was no significant difference in the concentration of ethanol between florets that were stored under hypoxia with/without CO2 or normoxia at 2 d. However, the ethanol concentrations inside the pouches significantly increased between 2 d and 7 d. These findings indicate that the quality of broccoli florets can be improved through storage under hypoxia with high CO2 levels at 20°C for 2 d.

Storage in high-barrier pouches increases the sulforaphane concentration in broccoli florets.

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Makino, Yoshio; Nishimura, Yuto; Oshita, Seiichi; Mizosoe, Takaharu; Akihiro, Takashi

2018-01-01

Sulforaphane is a phytochemical that is usually found in cruciferous vegetables and is known to have a depressive effect on gastric cancer. Preliminary investigations showed that the sulforaphane concentration in broccoli (Brassica oleracea var. italica) florets increased under anoxia. Therefore, in the present study, we examined the effect of different atmospheric conditions on the sulforaphane concentration in broccoli and also tested whether there are concurrent effects on the concentration of ethanol, which is an unfavorable byproduct of fermentation. The sulforaphane concentration in broccoli florets was significantly elevated by 1.9- to 2.8-fold after 2 d of storage under hypoxia at ca. 0% O2 and ca. 24% CO2 at 20°C, whereas no such increase was observed following storage under normoxia at ca. 0% O2 without CO2 at 20°C. Furthermore, after 2 d, the sulforaphane concentration under hypoxia was 1.6- to 2.3-fold higher than that under normoxia. These results suggest that storage under hypoxia with high CO2 levels can elevate the sulforaphane concentration in broccoli florets. However, the elevated sulforaphane concentration could not be maintained beyond 2 d. There was no significant difference in the concentration of ethanol between florets that were stored under hypoxia with/without CO2 or normoxia at 2 d. However, the ethanol concentrations inside the pouches significantly increased between 2 d and 7 d. These findings indicate that the quality of broccoli florets can be improved through storage under hypoxia with high CO2 levels at 20°C for 2 d.

Separation and Purification of Sulforaphane from Broccoli by Solid Phase Extraction

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Kyung Ho Row

2011-03-01

Full Text Available A simple solid-phase extraction (SPE method for the determination of sulforaphane in broccoli has been developed. The optimal conditions were found to be use of a silica SPE cartridge, and ethyl acetate and dichloromethane as washing and eluting solvents, respectively, which could eliminate interferences originating from the broccoli matrix. The extracts were sufficiently clean to be directly injected into high-performance liquid chromatography (HPLC for further chromatographic analysis. Good linearity was obtained from 0.05 to 200 μg/mL (r = 0.998 for sulforaphane with the relative standard deviations less than 3.6%. The mean recoveries of sulforaphane from broccoli were more than 90.8% and the detection limit (S/N = 3:1 was 0.02 μg/mL. The SPE method provides a higher yield of sulforaphane from crude extracts compared to conventional liquid-liquid extraction.

Novel Gram-Scale Production of Enantiopure R-Sulforaphane from Tuscan Black Kale Seeds

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Gina Rosalinda De Nicola

2014-05-01

Full Text Available Dietary R-sulforaphane is a highly potent inducer of the Keap1/Nrf2/ARE pathway. Furthermore, sulforaphane is currently being used in clinical trials to assess its effects against different tumour processes. This study reports an efficient preparation of enantiopure R-sulforaphane based on the enzymatic hydrolysis of its natural precursor glucoraphanin. As an alternative to broccoli seeds, we have exploited Tuscan black kale seeds as a suitable source for gram-scale production of glucoraphanin. The defatted seed meal contained 5.1% (w/w of glucoraphanin that was first isolated through an anion exchange chromatographic process, and then purified by gel filtration. The availability of glucoraphanin (purity ≈ 95%, weight basis has allowed us to develop a novel simple hydrolytic process involving myrosinase (EC 3.2.1.147 in a biphasic system to directly produce R-sulforaphane. In a typical experiment, 1.09 g of enantiopure R-sulforaphane was obtained from 150 g of defatted Tuscan black kale seed meal.

Sulforaphane – a possible agent in prevention and therapy of cancer

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Joanna Tomczyk

2010-11-01

Full Text Available Sulforaphane (SFN is an isothiocyanate that is naturally present in cruciferous vegetables, with high concentration in broccoli. The results of the most recent studies indicate multi-targeted sulforaphane actions which may contribute to prevention and therapy of cancer. Protective properties of sulforaphane have been observed in every stage of carcinogenesis. The mechanism of protection against the initiation of carcinogenesis by SFN includes modulation of phase I and II xenobiotic-metabolizing enzymes, as well as direct blocking of specific binding sites of carcinogens with the DNA molecule. As a result, sulforaphane inhibits DNA adduct formation, thus reducing the risk of mutations. Further sulforaphane activity is targeted at cancer cells and prevents their expansion due to regulation of proliferation and induction of differentiation or apoptosis. In vitro studies using various types of cancer cells have revealed the ability of SFN to arrest the cell cycle, particularly in G2/M, while SFN at higher concentration is shown to activate apoptotic pathways. The possible SFN anticancer effect in the progression stage of carcinogenesis has been proved by only a few studies, which provide evidence for its antiangiogenic and antimetastatic influence. Additionally, SFN exhibits anti-inflammatory and antibacterial effects relevant to cancer prevention.Apart from the biological activity of SFN, this review also focuses on its bioavailability and tissue distribution as well as individuals’ genetic predispositions as significant factors influencing the potential efficiency of chemoprevention using this compound.

Sulforaphane (SFN: An Isothiocyanate in a Cancer Chemoprevention Paradigm

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Mohammad Fahad Ullah

2015-07-01

Full Text Available The International Agency for Research on Cancer (IARC in its latest World Cancer Report (2014 has projected the increase in the global cancer burden from 14 million (2012 to 22 million incidence annually within the next two decades. Such statistics warrant a collaborative engagement of conventional and complementary and alternative therapies to contain and manage cancer. In recent years, there has been a shift in the cancer chemoprevention paradigm with a significant focus turning towards bioactive components of human diets for their anticancer properties. Since diet is an integral part of lifestyle and given that an estimated one third of human cancers are believed to be preventable though appropriate lifestyle modification including dietary habits, the current shift in the conventional paradigm assumes significance. Several epidemiological studies have indicated that consumption of broccoli is associated with a lower risk of cancer incidence including breast, prostate, lung, stomach and colon cancer. The edible plant belonging to the family of cruciferae such as broccoli is a rich source of glucoraphanin, a precursor of isothiocyanate sulforaphane which is considered to be a potent anti-cancer agent. Plant-based dietary agents such as sulforaphane mimic chemotherapeutic drugs such as vorinostat, possessing histone deacetylase inhibition activity. Evidence from epidemiological and experimental studies have emerged, enhancing the clinical plausibility and translational value of sulforaphane in cancer chemoprevention. The present review provides the current understanding of the cancer chemopreventive pharmacology of sulforaphane towards its potential as an anticancer agent.

Defining futile life-prolonging treatments through Neo-Socratic Dialogue.

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Aizawa, Kuniko; Asai, Atsushi; Bito, Seiji

2013-12-09

In Japan, people are negative towards life-prolonging treatments. Laws that regulate withholding or discontinuing life-prolonging treatments and advance directives do not exist. Physicians, however, view discontinuing life-prolonging treatments negatively due to fears of police investigations. Although ministerial guidelines were announced regarding the decision process for end-of-life care in 2007, a consensus could not be reached on the definition of end-of-life and conditions for withholding treatment. We established a forum for extended discussions and consensus building on this topic. We used the Neo-Socratic Dialogue (NSD) method which promotes philosophical discussion based on a case-study to address a question and formulate a consensus and answer in a group. The question chosen for the dialogue was: "What is a life-prolonging treatment?" A series of dialogues took place over a period of one and a half days. It was carried out by three groups in 2010 and 2011. Seven participants with diverse backgrounds were recruited per group. We analyzed the content of the discussion. Based on three case studies concerning different opinions about treatment options for an older dementia patient, a patient demanding chemotherapy, and a severely ill neonate, conditions for futile life-prolonging treatment were elucidated through NSD. Such treatments are those carried out for the sole purpose of prolonging life and are detrimental to the patient, and should be decided based foremost on the patient's lack of desire for treatment, the consensus of those involved, and through social acceptance. These arguments are essentially consistent with ones on medical futility in the United States. By expressing the objective of healthcare and the requirement of social acceptance, participants were also able to elucidate issues related to the awareness of those involved and the medical environment. Compared to the end-of-life guidelines in Japan, the objective of treatment, its effects

High resolution mass spectrometry studies of sulforaphane and indole-3-carbinol in broccoli.

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Kokotou, Maroula G; Revelou, Panagiota-Kyriaki; Pappas, Christos; Constantinou-Kokotou, Violetta

2017-12-15

Broccoli is a rich source of bioactive compounds. Among them, sulforaphane and indole-3-carbinol have attracted a lot of attention, since their consumption is associated with reduced risk of cancer. In this work, the development of an efficient and direct method for the simultaneous determination of sulforaphane and indole-3-carbinol in broccoli using UPLC-HRMS/MS is described. The correlation coefficient, and limits of detection (LOD) and quantification (LOQ) were 0.993, 0.77mg/L and 2.35mg/L for sulforaphane and 0.997, 0.42mg/L, 1.29mg/L for indole-3-carbinol, respectively. The content of sulforaphane and indole-3-carbinol varied between 72±9-304±2mg and 77±1-117±3mg per 100g of fresh florets, respectively. Taking into consideration the differences in cultivar, geography, season and environmental factors, the results agreed with values published in the literature using other techniques. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cloning of genes related to aliphatic glucosinolate metabolism and the mechanism of sulforaphane accumulation in broccoli sprouts under jasmonic acid treatment.

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Guo, Liping; Yang, Runqiang; Gu, Zhenxin

2016-10-01

Cytochrome P450 79F1 (CYP79F1), cytochrome P450 83A1 (CYP83A1), UDP-glucosyltransferase 74B1 (UGT74B1), sulfotransferase 18 (ST5b) and flavin-containing monooxygenase GS-OX1 (FMOGS - OX1 ) are important enzymes in aliphatic glucosinolate biosynthesis. In this study, their full-length cDNA in broccoli was firstly cloned, then the mechanism of sulforaphane accumulation under jasmonic acid (JA) treatment was investigated. The full-length cDNA of CYP79F1, CYP83A1, UGT74B1, ST5b and FMOGS - OX1 comprised 1980, 1652, 1592, 1378 and 1623 bp respectively. The increase in aliphatic glucosinolate accumulation in broccoli sprouts treated with JA was associated with elevated expression of genes in the aliphatic glucosinolate biosynthetic pathway. Application of 100 µmol L(-1) JA increased myrosinase (MYR) activity but did not affect epithiospecifier protein (ESP) activity in broccoli sprouts, which was supported by the expression of MYR and ESP. Sulforaphane formation in 7-day-old sprouts treated with 100 µmol L(-1) JA was 3.36 and 1.30 times that in the control and 300 µmol L(-1) JA treatment respectively. JA enhanced the accumulation of aliphatic glucosinolates in broccoli sprouts via up-regulation of related gene expression. Broccoli sprouts treated with 100 µmol L(-1) JA showed higher sulforphane formation than those treated with 300 µmol L(-1) JA owing to the higher glucoraphanin content and myrosinase activity under 100 µmol L(-1) JA treatment. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Sulforaphane?induced apoptosis in Xuanwei lung adenocarcinoma cell line XWLC?05

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Zhou, Lan; Yao, Qian; Li, Yan; Huang, Yun?chao; Jiang, Hua; Wang, Chuan?qiong; Fan, Lei

2016-01-01

Background Xuanwei district in Yunnan Province has the highest incidence of lung cancer in China, especially among non?smoking women. Cruciferous vegetables can reduce lung cancer risk by prompting a protective mechanism against respiratory tract inflammation caused by air pollution, and are rich in sulforaphane, which can induce changes in gene expression. We investigated the effect of sulforaphane?induced apoptosis in Xuanwei lung adenocarcinoma cell line (XWCL?05) to explore the value of s...

Sulforaphane induces apoptosis in T24 human urinary bladder cancer cells through a reactive oxygen species-mediated mitochondrial pathway: the involvement of endoplasmic reticulum stress and the Nrf2 signaling pathway.

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Jo, Guk Heui; Kim, Gi-Young; Kim, Wun-Jae; Park, Kun Young; Choi, Yung Hyun

2014-10-01

Sulforaphane, a naturally occurring isothiocyanate found in cruciferous vegetables, has received a great deal of attention because of its ability to inhibit cell proliferation and induce apoptosis in cancer cells. In this study, we investigated the anticancer activity of sulforaphane in the T24 human bladder cancer line, and explored its molecular mechanism of action. Our results showed that treatment with sulforaphane inhibited cell viability and induced apoptosis in T24 cells in a concentration-dependent manner. Sulforaphane-induced apoptosis was associated with mitochondria dysfunction, cytochrome c release and Bcl-2/Bax dysregulation. Furthermore, the increased activity of caspase-9 and -3, but not caspase-8, was accompanied by the cleavage of poly ADP-ribose polymerase, indicating the involvement of the mitochondria-mediated intrinsic apoptotic pathway. Concomitant with these changes, sulforaphane triggered reactive oxygen species (ROS) generation, which, along with the blockage of sulforaphane-induced loss of mitochondrial membrane potential and apoptosis, was strongly attenuated by the ROS scavenger N-acetyl-L-cysteine. Furthermore, sulforaphane was observed to activate endoplasmic reticulum (ER) stress and the nuclear factor-E2-related factor-2 (Nrf2) signaling pathway, as demonstrated by the upregulation of ER stress‑related proteins, including glucose-regulated protein 78 and C/EBP-homologous protein, and the accumulation of phosphorylated Nrf2 proteins in the nucleus and induction of heme oxygenase-1 expression, respectively. Taken together, these results demonstrate that sulforaphane has antitumor effects against bladder cancer cells through an ROS-mediated intrinsic apoptotic pathway, and suggest that ER stress and Nrf2 may represent strategic targets for sulforaphane-induced apoptosis.

Prolonged sulforaphane treatment activates survival signaling in nontumorigenic NCM460 colon cells but apoptotic signaling in tumorigenic HCT116 colon cells.

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Zeng, Huawei; Trujillo, Olivia N; Moyer, Mary P; Botnen, James H

2011-01-01

Sulforaphane (SFN) is a naturally occurring chemopreventive agent; the induction of cell cycle arrest and apoptosis is a key mechanism by which SFN exerts its colon cancer prevention. However, little is known about the differential effects of SFN on colon cancer and normal cells. In this study, we demonstrated that SFN (15 μmol/L) exposure (72 h) inhibited cell proliferation by up to 95% in colon cancer cells (HCT116) and by 52% in normal colon mucosa-derived (NCM460) cells. Our data also showed that SFN exposure (5 and 10 μmol/L) led to the reduction of G1 phase cell distribution and an induction of apoptosis in HCT116 cells, but to a much lesser extent in NCM460 cells. Furthermore, the examination of mitogen-activated protein kinase (MAPK) signaling status revealed that SFN upregulated the phosphorylation of extracellular-regulated kinase 1/2 (ERK1/2) in NCM460 cells but not in HCT116 cells. In contrast, SFN enhanced the phosphorylation of stress-activated protein kinase (SAPK) and decreased cellular myelocytomatosis oncogene (c-Myc) expression in HCT116 cells but not NCM460 cells. Taken together, the activation of survival signaling in NCM460 cells and apoptotic signaling in HCT116 cells may play a critical role in SFN's stronger potential of inhibiting cell proliferation in colon cancer cells than in normal colon cells. Copyright © 2011, Taylor & Francis Group, LLC

Sulforaphane-induced transcription of thioredoxin reductase in lens: possible significance against cataract formation

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Varma SD

2013-10-01

Full Text Available Shambhu D Varma, Krish Chandrasekaran, Svitlana Kovtun Department of Ophthalmology and Visual Sciences, University of Maryland, Baltimore, MD, USA Purpose: Sulforaphane is a phytochemically derived organic isothiocyanate 1-isothiocyanato-4-methylsulfinyl-butane present naturally in crucifers, including broccoli and cauliflower. Biochemically, it has been reported to induce the transcription of several antioxidant enzymes. Since such enzymes have been implicated in preventing cataract formation triggered by the intraocular generation of oxy-radical species, the purpose of this investigation was to examine whether it could induce the formation of antioxidant enzymes in the eye lens. Thioredoxin reductase (TrxR was used as the target of such induction. Methods: Mice lenses were cultured for an overnight period of 17 hours in medium 199 fortified with 10% fetal calf serum. Incubation was conducted in the absence and presence of sulforaphane (5 µM. Subsequently, the lenses were homogenized in phosphate-buffered saline (PBS, followed by centrifugation. TrxR activity was determined in the supernatant by measuring the nicotinamide adenine dinucleotide phosphate (reduced (NADPH-dependent reduction of 5,5´-dithiobis-2-nitrobenzoic acid (DTNB. Non-specific reduction of DTNB was corrected for by conducting parallel determinations in the presence of aurothiomalate. The reduction of DTNB was followed spectrophotometrically at 410 nm. Results: The activity of TrxR in the lenses incubated with sulforaphane was found to be elevated to 18 times of that observed in lenses incubated without sulforaphane. It was also noticeably higher in the lenses incubated without sulforaphane than in the un-incubated fresh lenses. However, this increase was much lower than that observed for lenses incubated with sulforaphane. Conclusion: Sulforaphane has been found to enhance TrxR activity in the mouse lens in culture. In view of the protective effect of the antioxidant enzymes

Hydrogen sulfide mediates the anti-survival effect of sulforaphane on human prostate cancer cells

International Nuclear Information System (INIS)

Pei, Yanxi; Wu, Bo; Cao, Qiuhui; Wu, Lingyun; Yang, Guangdong

2011-01-01

Hydrogen sulfide (H 2 S) is a novel gasotransmitter that regulates cell proliferation and other cellular functions. Sulforaphane (SFN) is a sulfur-containing compound that exhibits anticancer properties, and young sprouts of broccoli are particularly rich in SFN. There is consistent epidemiological evidence that the consumption of sulfur-containing vegetables, such as garlic and cruciferous vegetables, may help reduce the occurrence of prostate cancer. Here we found that a large amount of H 2 S is released when SFN is added into cell culture medium or mixed with mouse liver homogenates, respectively. Both SFN and NaHS (a H 2 S donor) decreased the viability of PC-3 cells (a human prostate cancer cell line) in a dose-dependent manner, and supplement of methemoglobin or oxidized glutathione (two H 2 S scavengers) reversed SFN-reduced cell viability. We further found both cystathionine gamma-lyase (CSE) and cystathionine beta-synthase are expressed in PC-3 cells and mouse prostate tissues. H 2 S production in prostate tissues from CSE knockout mice was only 20% of that from wild-type mice, suggesting CSE is a major H 2 S-producing enzyme in prostate. CSE overexpression enhanced H 2 S production and inhibited cell viability in PC-3 cells. In addition, both SFN and NaHS activated p38 mitogen-activated protein kinases (MAPK) and c-Jun N-terminal kinase (JNK). Pre-treatment of PC-3 cells with methemoglobin decreased SFN-stimulated MAPK activities. Suppression of both p38 MAPK and JNK reversed H 2 S- or SFN-reduced viability of PC-3 cells. Our results demonstrated that H 2 S mediates the inhibitory effect of SFN on the proliferation of PC-3 cells, which suggests that H 2 S-releasing diet or drug might be beneficial in the treatment of prostate cancer. Highlights: ► A large amount of H 2 S is released from sulforaphane. ► H 2 S mediates the anti-survival effect of sulforaphane on human prostate cancer cells. ► Cystathionine gamma-lyase is a major H 2 S

Microencapsulation of sulforaphane from broccoli seed extracts by gelatin/gum arabic and gelatin/pectin complexes.

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García-Saldaña, Jesús S; Campas-Baypoli, Olga N; López-Cervantes, Jaime; Sánchez-Machado, Dalia I; Cantú-Soto, Ernesto U; Rodríguez-Ramírez, Roberto

2016-06-15

Sulforaphane is a phytochemical that has received attention in recent years due to its chemopreventive properties. However, the uses and applications of this compound are very limited, because is an unstable molecule that is degraded mainly by changes in temperature and pH. In this research, the use of food grade polymers for microencapsulation of sulforaphane was studied by a complex coacervation method using the interaction of oppositely charged polymers as gelatin/gum arabic and gelatin/pectin. The polymers used were previously characterized in moisture content, ash and nitrogen. The encapsulation yield was over 80%. The gelatin/pectin complex had highest encapsulation efficiency with 17.91%. The presence of sulforaphane in the complexes was confirmed by FTIR and UV/visible spectroscopy. The materials used in this work could be a new and attractive option for the protection of sulforaphane. Copyright © 2016 Elsevier Ltd. All rights reserved.

The potential to intensify sulforaphane formation in cooked broccoli (Brassica oleracea var. italica) using mustard seeds (Sinapis alba).

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Ghawi, Sameer Khalil; Methven, Lisa; Niranjan, Keshavan

2013-06-01

Sulforaphane, a naturally occurring cancer chemopreventive, is the hydrolysis product of glucoraphanin, the main glucosinolate in broccoli. The hydrolysis requires myrosinase isoenzyme to be present in sufficient activity; however, processing leads to its denaturation and hence reduced hydrolysis. In this study, the effect of adding mustard seeds, which contain a more resilient isoform of myrosinase, to processed broccoli was investigated with a view to intensify the formation of sulforaphane. Thermal inactivation of myrosinase from both broccoli and mustard seeds was studied. Thermal degradation of broccoli glucoraphanin was investigated in addition to the effects of thermal processing on the formation of sulforaphane and sulforaphane nitrile. Limited thermal degradation of glucoraphanin (less than 12%) was observed when broccoli was placed in vacuum sealed bag (sous vide) and cooked in a water bath at 100°C for 8 and 12 min. Boiling broccoli in water prevented the formation of any significant levels of sulforaphane due to inactivated myrosinase. However, addition of powdered mustard seeds to the heat processed broccoli significantly increased the formation of sulforaphane. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Sulforaphane and Other Nutrigenomic Nrf2 Activators: Can the Clinician's Expectation Be Matched by the Reality?

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Houghton, Christine A.; Fassett, Robert G.; Coombes, Jeff S.

2016-01-01

The recognition that food-derived nonnutrient molecules can modulate gene expression to influence intracellular molecular mechanisms has seen the emergence of the fields of nutrigenomics and nutrigenetics. The aim of this review is to describe the properties of nutrigenomic activators of transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2), comparing the potential for sulforaphane and other phytochemicals to demonstrate clinical efficacy as complementary medicines. Broccoli-derived sulforaphane emerges as a phytochemical with this capability, with oral doses capable of favourably modifying genes associated with chemoprevention. Compared with widely used phytochemical-based supplements like curcumin, silymarin, and resveratrol, sulforaphane more potently activates Nrf2 to induce the expression of a battery of cytoprotective genes. By virtue of its lipophilic nature and low molecular weight, sulforaphane displays significantly higher bioavailability than the polyphenol-based dietary supplements that also activate Nrf2. Nrf2 activation induces cytoprotective genes such as those playing key roles in cellular defense mechanisms including redox status and detoxification. Both its high bioavailability and significant Nrf2 inducer capacity contribute to the therapeutic potential of sulforaphane-yielding supplements. PMID:26881038

The effects of sulforaphane on the liver and remote organ damage in hepatic ischemia-reperfusion model formed with pringle maneuver in rats.

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Oguz, Abdullah; Kapan, Murat; Kaplan, Ibrahim; Alabalik, Ulas; Ulger, Burak Veli; Uslukaya, Omer; Turkoglu, Ahmet; Polat, Yilmaz

2015-06-01

The purpose of this study was to investigate the effect of Sulforaphane on ischemia/ reperfusion (IR) injury of the liver and distant organs resulting from liver blood flow arrest. Fourty Wistar rats were assigned into four groups, each included 10 rats were used. Group I as only laparatomy, Group II laparatomy and Sulforaphane application, Group III hepatic IR; and Group IV as hepatic IR and Sulforaphane application group. Animals were subjected to liver ischemia for 30 min and then reperfusion is started. 5 mg/kg Sulforaphane was applied via oral lavage 15 minutes before initiating the experimental study. Blood samples were taken from the animals for biochemical analysis at 60th minutes of the experiment in the first and second groups; 30 minutes after beginning reperfusion in the third and forth groups. Simultaneously, liver, lung and kidney tissues were sampled for biochemical and histopathological examinations. The administration of sulforaphane significantly reduced the serum TOA and liver TOA levels, increased the serum TAC and liver TAC levels and also decreased The OSI and liver OSI levels. In the histopathologic examination, the injury was reduced by the administration of sulforaphane. Administration of sulforaphane did not lead to any significant changes in any parameter including histopathological parameters in both the kidney and the lung. Sulforaphane reduced the liver oxidative stress from I/R injury. A histological injury in liver was reduced by sulforaphane administration. However, there were no significant effects of sulforaphane on the remote organ injuries induced by IR. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

Data on sulforaphane treatment mediated suppression of autoreactive, inflammatory M1 macrophages

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Sanjima Pal

2016-06-01

Full Text Available Any chronic, inflammatory, autoimmune disease (e.g. arthritis associated pathogenesis directs uncontrolled accumulation of both soluble forms of collagens in the synovial fluids and M1 macrophages around inflamed tissues. Despite of few studies demonstrating efficiency of Sulforaphane (SFN in suppressing arthritis associated collagen restricted T cells or fibroblasts, its effects on macrophage polarity and plasticity are less understood. Recently, we reported regulation of phenotypic and functional switching by SFN in induced and spontaneously differentiating human monocytes [1]. Here, flow cytometry, western blot and ELISA derived data demonstrated that SFN inhibited in vitro inflammatory responses developed by soluble human collagens (I–IV induced auto-reactive M1 type monocyte/macrophage model.

Interaction of sulforaphane with DNA and RNA.

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Farzaneh Abassi Joozdani

Full Text Available Sulforaphane (SFN is an isothiocyanate found in cruciferous vegetables with anti-inflammatory, anti-oxidant and anti-cancer activities. However, the antioxidant and anticancer mechanism of sulforaphane is not well understood. In the present research, we reported binding modes, binding constants and stability of SFN-DNA and -RNA complexes by Fourier transform infrared (FTIR and UV-Visible spectroscopic methods. Spectroscopic evidence showed DNA intercalation with some degree of groove binding. SFN binds minor and major grooves of DNA and backbone phosphate (PO2, while RNA binding is through G, U, A bases with some degree of SFN-phosphate (PO2 interaction. Overall binding constants were estimated to be K(SFN-DNA=3.01 (± 0.035×10(4 M(-1 and K(SFN-RNA= 6.63 (±0.042×10(3 M(-1. At high SFN concentration (SFN/RNA = 1/1, DNA conformation changed from B to A occurred, while RNA remained in A-family structure.

No de novo sulforaphane biosynthesis in broccoli seedlings

NARCIS (Netherlands)

Gorissen, Antonie; Kraut, Nicolai U.; de Visser, Ries; de Vries, Marcel; Roelofsen, Han; Vonk, Roel J.

2011-01-01

The isothiocyanate sulforaphane, present in significant amounts in broccoli (Brassica oleracea L.) seedlings in the form of its precursor glucoraphanin, has been identified as an inducer of quinine reductase, a phase-II detoxification enzyme known for its anticarcinogenic properties. Its

Hydrogen sulfide mediates the anti-survival effect of sulforaphane on human prostate cancer cells

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Pei, Yanxi [Department of Biology, Lakehead University, Thunder Bay (Canada); College of Life Science, Shanxi University, Taiyuan (China); Wu, Bo [Department of Biology, Lakehead University, Thunder Bay (Canada); Department of Pathophysiology, Harbin Medical University, Harbin (China); Cao, Qiuhui [Department of Biology, Lakehead University, Thunder Bay (Canada); Wu, Lingyun [Department of Pathophysiology, Harbin Medical University, Harbin (China); Department of Pharmacology, University of Saskatchewan, Saskatoon (Canada); Yang, Guangdong, E-mail: gyang@lakeheadu.ca [The School of Kinesiology, Lakehead University, Thunder Bay (Canada)

2011-12-15

Hydrogen sulfide (H{sub 2}S) is a novel gasotransmitter that regulates cell proliferation and other cellular functions. Sulforaphane (SFN) is a sulfur-containing compound that exhibits anticancer properties, and young sprouts of broccoli are particularly rich in SFN. There is consistent epidemiological evidence that the consumption of sulfur-containing vegetables, such as garlic and cruciferous vegetables, may help reduce the occurrence of prostate cancer. Here we found that a large amount of H{sub 2}S is released when SFN is added into cell culture medium or mixed with mouse liver homogenates, respectively. Both SFN and NaHS (a H{sub 2}S donor) decreased the viability of PC-3 cells (a human prostate cancer cell line) in a dose-dependent manner, and supplement of methemoglobin or oxidized glutathione (two H{sub 2}S scavengers) reversed SFN-reduced cell viability. We further found both cystathionine gamma-lyase (CSE) and cystathionine beta-synthase are expressed in PC-3 cells and mouse prostate tissues. H{sub 2}S production in prostate tissues from CSE knockout mice was only 20% of that from wild-type mice, suggesting CSE is a major H{sub 2}S-producing enzyme in prostate. CSE overexpression enhanced H{sub 2}S production and inhibited cell viability in PC-3 cells. In addition, both SFN and NaHS activated p38 mitogen-activated protein kinases (MAPK) and c-Jun N-terminal kinase (JNK). Pre-treatment of PC-3 cells with methemoglobin decreased SFN-stimulated MAPK activities. Suppression of both p38 MAPK and JNK reversed H{sub 2}S- or SFN-reduced viability of PC-3 cells. Our results demonstrated that H{sub 2}S mediates the inhibitory effect of SFN on the proliferation of PC-3 cells, which suggests that H{sub 2}S-releasing diet or drug might be beneficial in the treatment of prostate cancer. Highlights: Black-Right-Pointing-Pointer A large amount of H{sub 2}S is released from sulforaphane. Black-Right-Pointing-Pointer H{sub 2}S mediates the anti-survival effect of

Sulforaphane and Other Nutrigenomic Nrf2 Activators: Can the Clinician’s Expectation Be Matched by the Reality?

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Christine A. Houghton

2016-01-01

Full Text Available The recognition that food-derived nonnutrient molecules can modulate gene expression to influence intracellular molecular mechanisms has seen the emergence of the fields of nutrigenomics and nutrigenetics. The aim of this review is to describe the properties of nutrigenomic activators of transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2, comparing the potential for sulforaphane and other phytochemicals to demonstrate clinical efficacy as complementary medicines. Broccoli-derived sulforaphane emerges as a phytochemical with this capability, with oral doses capable of favourably modifying genes associated with chemoprevention. Compared with widely used phytochemical-based supplements like curcumin, silymarin, and resveratrol, sulforaphane more potently activates Nrf2 to induce the expression of a battery of cytoprotective genes. By virtue of its lipophilic nature and low molecular weight, sulforaphane displays significantly higher bioavailability than the polyphenol-based dietary supplements that also activate Nrf2. Nrf2 activation induces cytoprotective genes such as those playing key roles in cellular defense mechanisms including redox status and detoxification. Both its high bioavailability and significant Nrf2 inducer capacity contribute to the therapeutic potential of sulforaphane-yielding supplements.

Sulforaphane Protects against High Cholesterol-Induced Mitochondrial Bioenergetics Impairments, Inflammation, and Oxidative Stress and Preserves Pancreatic β-Cells Function

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Catalina Carrasco-Pozo

2017-01-01

Full Text Available Cholesterol plays an important role in inducing pancreatic β-cell dysfunction, leading to an impaired insulin secretory response to glucose. This study aimed to determine the protective effects of sulforaphane, a natural isothiocyanate Nrf2-inducer, against cholesterol-induced pancreatic β-cells dysfunction, through molecular and cellular mechanisms involving mitochondrial bioenergetics. Sulforaphane prevented cholesterol-induced alterations in the coupling efficiency of mitochondrial respiration, improving ATP turnover and spare capacity, and averted the impairment of the electron flow at complexes I, II, and IV. Sulforaphane also attenuated the cholesterol-induced activation of the NFκB pathway, normalizing the expression of pro- and anti-inflammatory cytokines. In addition, it also inhibited the decrease in sirtuin 1 expression and greatly increased Pgc-1α expression in Min6 cells. Sulforaphane increased the expression of antioxidant enzymes downstream of the Nrf2 pathway and prevented lipid peroxidation induced by cholesterol. The antioxidant and anti-inflammatory properties of sulforaphane and its ability to protect and improve mitochondrial bioenergetic function contribute to its protective action against cholesterol-induced pancreatic β-cell dysfunction. Our data provide a scientifically tested foundation upon which sulforaphane can be developed as nutraceutical to preserve β-cell function and eventually control hyperglycemia.

Prolonged Exposure: a Rapid Treatment for Phobias

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Watson, J. P.; Gaind, R.; Marks, I. M.

1971-01-01

Ten adult patients with long-standing specific phobias were treated by prolonged continuous exposure to their phobic objects in fantasy and reality without avoidance. All patients were greatly helped by four to five hours' treatment in two or three sessions, and all improved more after practice than after imaginal sessions. The treatment method is more economical and efficient than other methods described so far. PMID:5539135

HPLC Separation of Sulforaphane Enantiomers in Broccoli and Its Sprouts by Transformation into Diastereoisomers Using Derivatization with (S)-Leucine.

Science.gov (United States)

Okada, Makiko; Yamamoto, Atsushi; Aizawa, Sen-Ichi; Taga, Atsushi; Terashima, Hiroyuki; Kodama, Shuji

2017-01-11

Racemic sulforaphane, which was derivatized with (S)-leucine (l-leucine), was resolved by reversed phase HPLC with UV detection. The optimum mobile phase conditions were found to be 10 mM citric acid (pH 2.8) containing 22% methanol at 35 °C using detection at 254 nm. Sulforaphane enantiomers in florets and stems of five brands of broccoli and leaves and stems of three brands of broccoli sprouts were analyzed by the proposed HPLC method. Both sulforaphane enantiomers were detected in all of the samples. The S/R ratios of sulforaphane in broccoli samples were 1.5-2.6/97.4-98.5% for florets and 5.0-12.1/87.9-95.0% for stems. The S/R ratios in broccoli sprout samples were higher than those in broccoli samples and were found to be 8.3-19.7/80.3-91.7% for leaves and 37.0-41.8/58.2-63.0% for stems. (S)-Sulforaphane detected in the broccoli and its sprout samples was positively identified by separately using an HPLC with a chiral column (Chiralpak AD-RH) and mass spectrometry.

Sulforaphane inhibits osteoclast differentiation by suppressing the cell-cell fusion molecules DC-STAMP and OC-STAMP

International Nuclear Information System (INIS)

Takagi, Tomohiro; Inoue, Hirofumi; Takahashi, Nobuyuki; Katsumata-Tsuboi, Rie; Uehara, Mariko

2017-01-01

Sulforaphane (SFN), a kind of isothiocyanate, is derived from broccoli sprouts. It has anti-tumor, anti-inflammatory, and anti-oxidation activity. The molecular function of SFN in the inhibition of osteoclast differentiation is not well-documented. In this study, we assessed the effect of SFN on osteoclast differentiation in vitro. SFN inhibited osteoclast differentiation in both bone marrow cells and RAW264.7 cells. Key molecules involved in the inhibitory effects of SFN on osteoclast differentiation were determined using a microarray analysis, which showed that SFN inhibits osteoclast-associated genes, such as osteoclast-associated receptor (OSCAR), nuclear factor of activated T cells cytoplasmic-1, tartrate-resistant acid phosphatase, and cathepsin K. Moreover, the mRNA expression levels of the cell-cell fusion molecules dendritic cell specific transmembrane protein (DC-STAMP) and osteoclast stimulatory transmembrane protein (OC-STAMP) were strongly suppressed in cells treated with SFN. Furthermore, SFN increased the phosphorylation of signal transducer and activator of transcription 1 (STAT1), a regulator of macrophage and osteoclast cell fusion. Thus, our data suggested that SFN significantly inhibits the cell-cell fusion molecules DC-STAMP and OC-STAMP by inducing the phosphorylation of STAT1 (Tyr701), which might be regulated by interactions with OSCAR. - Highlights: • Sulforaphane inhibited osteoclast differentiation and osteoclast cell-fusion. • Sulforaphane suppressed not only NFATc1, but also cell-cell fusion molecules, DC-STAMP and OC-STAMP. • Sulforaphane decreased multinucleated osteoclasts, whereas increased mono-nucleated osteoclasts. • Sulforaphane inhibits the cell-cell fusion by inducing the phosphorylation of STAT1 (Tyr701).

Sulforaphane formation and bioaccessibility are more affected by steaming time than meal composition during in vitro digestion of broccoli

NARCIS (Netherlands)

Sarvan-Kruse, Irmela; Kramer, E.; Bouwmeester, Hans; Dekker, Matthijs; Verkerk, R.

2017-01-01

Broccoli is a rich source of the glucosinolate glucoraphanin (GR). After hydrolysis of GR by the endogenous enzyme myrosinase, sulforaphane (SF) or sulforaphane nitrile (SFN) are produced, depending on environmental conditions. How the conversion of GR and bioaccessibility of released breakdown

Characterization and antioxidant activity of bovine serum albumin and sulforaphane complex in different solvent systems

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Dong, Xueyan; Zhou, Rui; Jing, Hao, E-mail: h200521@cau.edu.cn

2014-02-15

Modes and influencing factors of bovine serum albumin (BSA) and sulforaphane (SFN) interaction will help us understand the interaction mechanisms and functional changes of bioactive small molecule and biomacromolecule. This study investigated interaction mechanisms of BSA and SFN and associated antioxidant activity in three solvent systems of deionized water (dH{sub 2}O), dimethyl sulfoxide (DMSO) and ethanol (EtOH), using Fourier transform infrared spectroscopy (FT-IR), fluorescence spectroscopy, synchronous fluorescence spectroscopy, DPPH and ABTS radical scavenging assays. The results revealed that SFN had ability to quench BSA's fluorescence in static modes, and to interact with BSA at both tyrosine (Tyr) and tryptophan (Trp) residues, while the Trp residues were highly sensitive, which was demonstrated by fluorescence at 340 nm. Hydrophobic forces, hydrogen bonds and van der Waals interactions were all involved in BSA and SFN interaction, which were not significantly changed by three solvents. The binding constant values and binding site numbers were in a descending order of dH{sub 2}O>DMSO>EtOH. The values of free energy change were in a descending order of dH{sub 2}O>DMSO>EtOH, which indicated that the binding forces were in a descending order of dH{sub 2}O>DMSO>EtOH. There was no significant difference in antioxidant activity between SFN and BSA–SFN. Moreover, three solvents had not significant influence on antioxidant activity of SFN and BSA–SFN. -- Highlights: • We report interaction mechanisms of BSA and sulforaphane in three solvent systems. • We report antioxidant activity of BSA–sulforaphane complex in three solvent systems. • Decreasing the solvent polarity will decrease the binding of BSA and sulforaphane. • Three solvents had not influence on antioxidant activity of BSA–sulforaphane.

The effect of nitrogen and sulphur fertilization on the yield and content of sulforaphane and nitrates in cauliflower

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Nina Čekey

2011-01-01

Full Text Available In the field experiment with cauliflower, we investigated the effect of four different variants of nitrogen and suplhur fertilization on quantity and quality of cauliflower in the term of sulforaphane content and nitrate accumulation. The influence of fertilization was statistically significant between control variant and fertilization variants and in both experimental years within all parameters of cauliflower yield. The highest yield of cauliflower was reached at the variant 4 when it was fertilized on the level of nutrients N:S = 250:60 kg.ha−1. The increase of yield against control variant represented value 26.6%. The applied fertilization positively affected on the accumulation sulforaphane in the cauliflower. Its highest content was determined at the variant 4 (N:S = 250:60 kg.ha−1. In comparison with control variant, the sulforaphane content was increased about 18.4%. On the other side, applied nutrition resulted in increased accumulation of nitrates in the cauliflower. The most increase of nitrate content, compared to the control variant, was also ascertained at the variant 4 (about 31.4%.The gathered data point towards to the possibility and way how we could effect on the increased accumulation of sulforaphane in cauliflower florets. This sphere of fertilization effect on the sulforaphane content is not sufficiently explored well. Our aim is to continue in this research subject and to find way how to cultivate vegetables with higher content of health-promoting compounds.

The effect of interruptions and prolonged treatment time in radiotherapy for nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Kwong, Dora L.W.; Sham, Jonathan S.T.; Chua, Daniel T.T.; Choy, Damon T.K.; Au, Gordon K.H.; Wu, P.M.

1997-01-01

Purpose: The effect of interruptions and prolonged overall treatment time in radiotherapy for nasopharyngeal carcinoma and the significance of timing of interruption was investigated. Methods and Materials: Treatment records of 229 patients treated with continuous course (CC) and 567 patients treated with split course (SC) radiotherapy for nonmetastatic NPC were reviewed. Overall treatment time without inclusion of time for boost was calculated. Treatment that extended 1 week beyond scheduled time was considered prolonged. Outcome in patients who completed treatment 'per schedule' were compared with those who had 'prolonged' treatment. Because of known patient selection bias between CC and SC, patients on the two schedules were analyzed separately. Multivariate analysis was performed for patients on SC. Total number of days of interruption, age, sex, T and N stage, and the use of boost were tested for the whole SC group. Analysis on the effect of timing of interruption was performed in a subgroup of 223 patients on SC who had a single unplanned interruption. Timing of interruption, either before or after the fourth week for the unplanned interruption, was tested in addition to the other variables in multivariate analysis for this subgroup of SC. Results: Twenty-seven (11.8%) patients on CC and 96 (16.9%) patients on SC had prolonged treatment. Patients on SC who had prolonged treatment had significantly poorer loco-regional control rate and disease free survival when compared with those who completed radiotherapy per schedule (p = 0.0063 and 0.001, respectively, with adjustment for stage). For CC, the effect of prolonged treatment on outcome was not significant. The small number of events for patients on CC probably account for the insignificant finding. The number of days of interruption was confirmed as prognostic factor, independent of T and N stages, for loco-regional control and disease-free survival in multivariate analysis for SC. The hazard rate for loco

Photothrombosis-Induced Infarction of the Mouse Cerebral Cortex Is Not Affected by the Nrf2-Activator Sulforaphane

OpenAIRE

Porritt, Michelle J.; Andersson, Helene C.; Hou, Linda; Nilsson, Åsa; Pekna, Marcela; Pekny, Milos; Nilsson, Michael

2012-01-01

Sulforaphane-induced activation of the transcription factor NF-E2 related factor 2 (Nrf2 or the gene Nfe2l2) and subsequent induction of the phase II antioxidant system has previously been shown to exert neuroprotective action in a transient model of focal cerebral ischemia. However, its ability to attenuate functional and cellular deficits after permanent focal cerebral ischemia is not clear. We assessed the neuroprotective effects of sulforaphane in the photothrombotic model of permanent fo...

Life-threatening asthma attack during prolonged fingolimod treatment: case report

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Zecca C

2014-07-01

Full Text Available Chiara Zecca,1,* Matteo Caporro,1,* Sandor Györik,2 Claudio Gobbi11Neurocenter of Southern Switzerland, Department of Neurology, Ospedale Regionale di Lugano, Lugano, Switzerland; 2Department of Internal Medicine, Ospedale Regionale di Bellinzona, Bellinzona, Switzerland*These authors contributed equally to this workBackground: Fingolimod (FTY mediates bronchoconstriction by interacting with sphingosine-1-phosphate receptors. The majority of the reported adverse respiratory events occur during the first weeks of treatment.Case presentation: A 49-year-old woman developed a life-threatening asthma attack after 6 months of continuous FTY treatment. The adverse event required prolonged hospitalization, and the patient recovered without sequelae after FTY interruption. A history of previous airway hyperreactivity and a concurrent viral respiratory infection possibly acted as predisposing factors.Conclusion: This first description of a severe, life-threatening asthma attack during prolonged FTY treatment suggests the need for long-term clinical surveillance, especially in patients with known predisposing factors.Keywords: multiple sclerosis, bronchial hyper-reactivity

Diverse definitions of prolonged labour and its consequences with sometimes subsequent inappropriate treatment

OpenAIRE

Nystedt, Astrid; Hildingsson, Ingegerd

2014-01-01

Background: Prolonged labour very often causes suffering from difficulties that may have lifelong implications. This study aimed to explore the prevalence and treatment of prolonged labour and to compare birth outcome and women's experiences of prolonged and normal labour. Method: Women with spontaneous onset of labour, living in a Swedish county, were recruited two months after birth, to a cross-sectional study. Women (n = 829) completed a questionnaire that investigated socio-demographic an...

Sulforaphane inhibits CYP1A1 activity and promotes genotoxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in vitro

Energy Technology Data Exchange (ETDEWEB)

Yang, Fangxing, E-mail: fxyang@zju.edu.cn [MOE Key Laboratory of Environmental Remediation and Ecosystem Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou, 310058 (China); Zhuang, Shulin [MOE Key Laboratory of Environmental Remediation and Ecosystem Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou, 310058 (China); Zhang, Chao; Dai, Heping [State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072 (China); Liu, Weiping, E-mail: wliu@zju.edu.cn [MOE Key Laboratory of Environmental Remediation and Ecosystem Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou, 310058 (China)

2013-06-15

Increasing environmental pollution by carcinogens such as some of persistent organic pollutants (POPs) has prompted growing interest in searching for chemopreventive compounds which are readily obtainable. Sulforaphane (SFN) is isolated from cruciferous vegetables and has the potentials to reduce carcinogenesis through various pathways. In this study, we studied the effects of SFN on CYP1A1 activity and genotoxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The results showed that SFN inhibited TCDD-induced CYP1A1 activity in H4IIE cells by directly inhibiting CYP1A1 activity, probably through binding to aryl hydrocarbon receptor and/or CYP1A1 revealed by molecular docking. However, SFN promoted TCDD-induced DNA damage in yeast cells and reduced the viability of initiated yeast cells. Besides, it is surprising that SFN also failed to reduce genotoxicity induced by other genotoxic reagents which possess different mechanisms to lead to DNA damage. Currently, it is difficult to predict whether SFN has the potentials to reduce the risk of TCDD based on the conflicting observations in the study. Therefore, further studies should be urgent to reveal the function and mechanism of SFN in the stress of such POPs on human health. - Highlights: • Sulforaphane inhibited TCDD-induced CYP1A1 activity in H4IIE cells. • Sulforaphane may bind to aryl hydrocarbon receptor and/or CYP1A1. • Sulforaphane promoted TCDD-induced DNA damage in yeast cells. • Sulforaphane may promote DNA damage by DNA strand breaks or DNA alkylation.

Streptococcus suis meningitis can require a prolonged treatment course

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Jean Dejace

2017-12-01

Full Text Available We report a case of recrudescent Streptococcus suis meningitis requiring a prolonged treatment course. A few similar cases can be found in the burgeoning literature on what remains a relatively uncommon disease in humans, and these patients should be monitored carefully upon completion of therapy. Keywords: Meningitis, Relapse, Duration, Streptococcus suis

Prolonged Remission in Neuromyelitis Optica Following Cessation of Rituximab Treatment.

Science.gov (United States)

Weinfurtner, Kelley; Graves, Jennifer; Ness, Jayne; Krupp, Lauren; Milazzo, Maria; Waubant, Emmanuelle

2015-09-01

Neuromyelitis optica is an autoimmune disease characterized by acute episodes of transverse myelitis and optic neuritis. Several small, open-label studies suggest rituximab, a monoclonal antibody against CD20, prevents relapses in neuromyelitis optica; however, there is little consensus on timing or duration of treatment. Here we report four patients with severe relapsing neuromyelitis optica who were stabilized on rituximab and, after discontinuing treatment, continued to experience prolonged remission of their disease. Remission ranged from 4.5 to 10.5 years total, including 3 to 9 years off all therapies. The patients had sustained clinical responses despite normal B-lymphocyte levels and, in at least 2 patients, continued seropositivity for aquaporin-4 antibodies. These cases suggest that rituximab may induce prolonged remission in certain neuromyelitis optica patients, and they highlight the need for further elucidation of rituximab's mechanism in neuromyelitis optica. © The Author(s) 2014.

Inhibition of class IIa histone deacetylase activity by gallic acid, sulforaphane, TMP269, and panobinostat.

Science.gov (United States)

Choi, Sin Young; Kee, Hae Jin; Jin, Li; Ryu, Yuhee; Sun, Simei; Kim, Gwi Ran; Jeong, Myung Ho

2018-05-01

Histone deacetylase (HDAC) inhibitors are gaining increasing attention as potential therapeutics for cardiovascular diseases as well as cancer. We recently reported that the class II HDAC inhibitor, MC1568, and the phytochemical, gallic acid, lowered high blood pressure in mouse models of hypertension. We hypothesized that class II HDACs may be involved in the regulation of hypertension. The aim of this study was to determine and compare the effects of well-known HDAC inhibitors (TMP269, panobinostat, and MC1568), phytochemicals (gallic acid, sulforaphane, and piceatannol), and anti-hypertensive drugs (losartan, carvedilol, and furosemide) on activities of class IIa HDACs (HDAC4, 5, 7, and 9). The selective class IIa HDAC inhibitor, TMP269, and the pan-HDAC inhibitor, panobinostat, but not MC1568, clearly inhibited class IIa HDAC activities. Among the three phytochemicals, gallic acid showed remarkable inhibition, whereas sulforaphane presented mild inhibition of class IIa HDACs. Piceatannol inhibited only HDAC7 activity. As expected, the anti-hypertensive drugs losartan, carvedilol, and furosemide did not affect the activity of any class IIa HDAC. In addition, we evaluated the inhibitory effect of several compounds on the activity of class l HDACs (HDAC1, 2, 3, and 8) and class IIb HDAC (HDAC6). MC1568 did not affect the activities of HDAC1, HDAC2, and HDAC3, but it reduced the activity of HDAC8 at concentrations of 1 and 10 μM. Gallic acid weakly inhibited HDAC1 and HDAC6 activities, but strongly inhibited HDAC8 activity with effectiveness comparable to that of trichostatin A. Inhibition of HDAC2 activity by sulforaphane was stronger than that by piceatnnaol. These results indicated that gallic acid is a powerful dietary inhibitor of HDAC8 and class IIa/b HDAC activities. Sulforaphane may also be used as a dietary inhibitor of HDAC2 and class IIa HDAC. Our findings suggest that the class II HDAC inhibitor, MC1568, does not inhibit class IIa HDAC, but inhibits

Effect of prolonged isothermal heat treatment on the mechanical behavior of advanced NANOBAIN steel

Science.gov (United States)

Avishan, Behzad

2017-09-01

The microstructural evolution and consequent changes in strength and ductility of advanced NANOBAIN steel during prolonged isothermal heat-treatment stages were investigated. The microstructure and mechanical properties of nanostructured bainite were not expected to be influenced by extending the heat-treatment time beyond the optimum value because of the autotempering phenomenon and high tempering resistance. However, experimental results indicated that the microstructure was thermodynamically unstable and that prolonged austempering resulted in carbon depletion from high-carbon retained austenite and carbide precipitations. Therefore, austenite became thermally less stable and partially transformed into martensite during cooling to room temperature. Prolonged austempering did not lead to the typical tempering sequence of bainite, and the sizes of the microstructural constituents were independent of the extended heat-treatment times. This independence, in turn, resulted in almost constant ultimate tensile strength values. However, microstructural variations enhanced the yield strength and the hardness of the material at extended isothermal heat-treatment stages. Finally, although microstructural changes decreased the total elongation and impact toughness, considerable combinations of mechanical properties could still be achieved.

QT interval prolongation associated with sibutramine treatment

Science.gov (United States)

Harrison-Woolrych, Mira; Clark, David W J; Hill, Geraldine R; Rees, Mark I; Skinner, Jonathan R

2006-01-01

Aims To investigate a possible association of sibutramine with QT interval prolongation. Methods Post-marketing surveillance using prescription event monitoring in the New Zealand Intensive Medicines Monitoring Programme (IMMP) identified a case of QT prolongation and associated cardiac arrest in a patient taking sibutramine for 25 days. This patient was further investigated, including genotyping for long QT syndrome. Other IMMP case reports suggesting arrhythmias associated with sibutramine were assessed and further reports were obtained from the World Health Organisation (WHO) adverse drug reactions database. Results The index case displayed a novel mutation in a cardiac potassium channel subunit gene, KCNQ1, which is likely to prolong cardiac membrane depolarization and increase susceptibility to long QT intervals. Assessment of further IMMP reports identified five additional patients who experienced palpitations associated with syncope or presyncopal symptoms, one of whom had a QTc at the upper limit of normal. Assessment of reports from the WHO database identified three reports of QT prolongation and one fatal case of torsade de pointes in a patient also taking cisapride. Conclusions This case series suggests that sibutramine may be associated with QT prolongation and related dysrhythmias. Further studies are required, but in the meantime we would recommend that sibutramine should be avoided in patients with long QT syndrome and in patients taking other medicines that may prolong the QT interval. PMID:16542208

The effect of duration of untreated psychosis and treatment delay on the outcomes of prolonged early intervention in psychotic disorders

DEFF Research Database (Denmark)

Albert, Nikolai; Melau, Marianne; Jensen, Heidi

2017-01-01

to the prolonged treatment with regards to disorganized and negative dimension. For participants with short duration from first symptom until start of SEI treatment there was a significant difference on the negative dimension favoring the prolonged OPUS treatment. The finding of an effect of prolonged treatment......The duration of untreated psychosis (DUP) has been shown to have an effect on outcome after first-episode psychosis. The premise of specialized early intervention (SEI) services is that intervention in the early years of illness can affect long-term outcomes. In this study, we investigate whether...... DUP affects treatment response after 5 years of SEI treatment compared to 2 years of SEI treatment. As part of a randomized controlled trial testing the effect of prolonged SEI treatment 400 participants diagnosed within the schizophrenia spectrum were recruited. For this specific study participants...

Sulforaphane Prevents Neuronal Apoptosis and Memory Impairment in Diabetic Rats

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Gengyin Wang

2016-08-01

Full Text Available Background/Aims: To explore the effects of sulforaphane (SFN on neuronal apoptosis in hippocampus and memory impairment in diabetic rats. Methods: Thirty male rats were randomly divided into normal control, diabetic model and SFN treatment groups (N = 10 in each group. Streptozotocin (STZ was applied to establish diabetic model. Water Morris maze task was applied to test learning and memory. Tunel assaying was used to detect apoptosis in hippocampus. The expressions of Caspase-3 and myeloid cell leukemia 1(MCL-1 were detected by western blotting. Neurotrophic factor levels and AKT/GSK3β pathway were also detected. Results: Compared with normal control, learning and memory were apparently impaired, with up-regulation of Caspase-3 and down-regulation of MCL-1 in diabetic rats. Apoptotic neurons were also found in CA1 region after diabetic modeling. By contrast, SFN treatment prevented the memory impairment, decreased the apoptosis of hippocampal neurons. SFN also attenuated the abnormal expression of Caspase-3 and MCL-1 in diabetic model. Mechanically, SFN treatment reversed diabetic modeling-induced decrease of p-Akt, p-GSK3β, NGF and BDNF expressions. Conclusion: SFN could prevent the memory impairment and apoptosis of hippocampal neurons in diabetic rat. The possible mechanism was related to the regulation of neurotropic factors and Akt/GSK3β pathway.

Prolonged methylprednisolone therapy after the pulse treatment for patients with moderate-to-severe paraquat poisoning: A retrospective analysis.

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Gao, Jie; Feng, ShunYi; Wang, Jian; Yang, SiYuan; Li, Yong

2017-06-01

This retrospective study aims to evaluate the effect of prolonged methylprednisolone (MP) therapy on the mortality of patients with moderate-to-severe paraquat (PQ) poisoning after the pulse treatment.We performed a retrospective analysis of patients with acute moderate-to-severe PQ poisoning that were admitted to the emergency department from May 2012 to August 2016. Out of 138 patients, 60 were treated with pulse treatment (15 mg kg day MP for 3 days) and 78 were treated with prolonged MP therapy after pulse treatment (15 mg kg day MP for 3 days; afterward, the dosage was reduced in half every 2 days, and the MP therapy was terminated until 0.47 mg kg day). Kaplan-Meier method was used to compare the mortality between the 2 groups. Cox proportional hazard models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI).The mortality of the prolonged MP therapy after pulse treatment group was lower than that of the pulse group (47.4% vs 63.3%; log-rank tests, P  =  .003). According to the multivariate Cox analysis, the prolonged MP therapy after pulse treatment was significantly associated with a lower mortality risk (HR: 0.31, 95% CI: 0.19-0.52, P treatment caused more incidences of leucopenia than the pulse treatment alone (25.6% vs 11.7%, P  =  .04).The prolonged MP therapy after pulse treatment can reduce the mortality of moderate-to-severe PQ poisoning patients.

Bioavailability and kinetics of sulforaphane in humans after consumption of cooked versus raw broccoli

NARCIS (Netherlands)

Vermeulen, M.; Klöpping-Ketelaars, I.W.A.A.; Berg, R. van den; Vaes, W.H.J.

2008-01-01

The aim of this study was to determine the bioavailability and kinetics of the supposed anticarcinogen sulforaphane, the hydrolysis product of glucoraphanin, from raw and cooked broccoli. Eight men consumed 200 g of crushed broccoli, raw or cooked, with a warm meal in a randomized, free-living, open

Diverse definitions of prolonged labour and its consequences with sometimes subsequent inappropriate treatment

Science.gov (United States)

2014-01-01

Background Prolonged labour very often causes suffering from difficulties that may have lifelong implications. This study aimed to explore the prevalence and treatment of prolonged labour and to compare birth outcome and women’s experiences of prolonged and normal labour. Method Women with spontaneous onset of labour, living in a Swedish county, were recruited two months after birth, to a cross-sectional study. Women (n = 829) completed a questionnaire that investigated socio-demographic and obstetric background, birth outcome and women’s feelings and experiences of birth. The prevalence of prolonged labour, as defined by a documented ICD-code and inspection of partogram was calculated. Four groups were identified; women with prolonged labour as identified by documented ICD-codes or by partogram inspection but no ICD-code; women with normal labour augmented with oxytocin or not. Results Every fifth woman experienced a prolonged labour. The prevalence with the documented ICD-code was (13%) and without ICD-code but positive partogram was (8%). Seven percent of women with prolonged labour were not treated with oxytocin. Approximately one in three women (28%) received oxytocin augmentation despite having no evidence of prolonged labour. The length of labour differed between the four groups of women, from 7 to 23 hours. Women with a prolonged labour had a negative birth experience more often (13%) than did women who had a normal labour (3%) (P women with prolonged labour were emergency Caesarean section (OR 9.0, 95% CI 1.2-3.0) and to strongly agree with the following statement ‘My birth experience made me decide not to have any more children’ (OR 41.3, 95% CI 4.9-349.6). The factors that contributed most strongly to a negative birth experience in women with normal labour were less agreement with the statement ‘It was exiting to give birth’ (OR 0.13, 95% CI 0.34-0.5). Conclusions There is need for increased clinical skill in identification and classification

SPBP is a sulforaphane induced transcriptional coactivator of NRF2 regulating expression of the autophagy receptor p62/SQSTM1.

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Sagar Ramesh Darvekar

Full Text Available Organisms exposed to oxidative stress respond by orchestrating a stress response to prevent further damage. Intracellular levels of antioxidant agents increase, and damaged components are removed by autophagy induction. The KEAP1-NRF2 signaling pathway is the main pathway responsible for cell defense against oxidative stress and for maintaining the cellular redox balance at physiological levels. Sulforaphane, an isothiocyanate derived from cruciferous vegetables, is a potent inducer of KEAP1-NRF2 signaling and antioxidant response element driven gene expression. In this study, we show that sulforaphane enhances the expression of the transcriptional coregulator SPBP. The expression curve peaks 6-8 hours post stimulation, and parallels the sulforaphane-induced expression of NRF2 and the autophagy receptor protein p62/SQSTM1. Reporter gene assays show that SPBP stimulates the expression of p62/SQSTM1 via ARE elements in the promoter region, and siRNA mediated knock down of SPBP significantly decreases the expression of p62/SQSTM1 and the formation of p62/SQSTM1 bodies in HeLa cells. Furthermore, SPBP siRNA reduces the sulforaphane induced expression of NRF2, and the expression of the autophagy marker protein LC3B. Both these proteins contain ARE-like elements in their promoter regions. Over-expressed SPBP and NRF2 acts synergistically on the p62/SQSTM1 promoter and colocalize in nuclear speckles in HeLa cells. Collectively, these results suggest that SPBP is a coactivator of NRF2, and hence may be important for securing enhanced and sustained expression of NRF2 induced genes such as proteins involved in selective autophagy.

Assessment of global proteome in LNCaP cells by 2D-RP/RP LC–MS/MS following sulforaphane exposure

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Gregory W. Watson

2015-12-01

Full Text Available The phytochemical sulforaphane can induce cell cycle arrest and apoptosis in metastatic prostate cancer cells, though the mechanism of action is not fully known. We conducted a global proteome analysis in LNCaP metastatic prostate cancer cells to characterize how global protein signature responds to sulforaphane. We conducted parallel analyses to evaluate semi-quantitative 1-dimensional versus 2-dimensional liquid chromatography tandem mass spectrometry (LC–MS/MS and their utility in characterizing whole cell lysate. We show that 2-dimensional LC–MS/MS can be a useful tool for characterizing global protein profiles and identify TRIAP1 as a novel regulator of cell proliferation in LNCaP metastatic prostate cancer cells.

Current health and preferences for life-prolonging treatments: an application of prospect theory to end-of-life decision making.

Science.gov (United States)

Winter, Laraine; Parker, Barbara

2007-10-01

As a substantial body of research attests, the acceptability of life-prolonging treatment (e.g., tube feeding) tends to be greater among people in worse health than among healthier ones. Because a decision for or against a life-prolonging treatment represents a choice between two prospects-life (usually in poor health) and death-we propose a decision model, Prospect Theory, as a theoretical account of this phenomenon. Prospect Theory postulates that pairs of distant prospects are less distinguishable than pairs of closer ones. Thus, to healthy individuals, the prospects of death and life in poor health would both be remote, and therefore, the distinction between them, small. To less healthy individuals, however, the difference between the same pairs of prospects would appear greater, and therefore, life-prolonging treatment may be more acceptable. In a cross-sectional study of 304 community-dwelling people, aged 60 years and over in the Philadelphia area, USA, preferences for 4 life-prolonging treatments in 9 health scenarios were examined in relation to participants' current health, operationalized as number of deficits in physical functioning. As predicted, less healthy people expressed stronger preferences for all life-prolonging treatments compared with healthier ones, with differences greatest in the worse-health scenarios. Preferences also varied by health scenario, with any treatment preferred in the better health scenarios. Treatment preferences did not differ by type of treatment, depressed mood or any demographic characteristic except race, with African-Americans expressing stronger treatment preferences. Implications for advance care planning are discussed.

The effects of sulforaphane on canine osteosarcoma proliferation and invasion.

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Rizzo, V L; Levine, C B; Wakshlag, J J

2017-09-01

Recent evidence in in vitro and in vivo models suggests that sulforaphane (SFN), found in raw cruciferous vegetables, may have utility in chemoprevention, as an antineoplastic agent and as a free radical scavenger. The effects of SFN alone or with doxorubicin on cell viability were examined, as well as cell cycle kinetics, invasion capabilities and apoptosis in three canine osteosarcoma cell line (D17, OS 2.4 and HMPOS). Results showed that SFN could not induce cell death at potentially physiological concentrations (canine osteosarcoma. © 2016 John Wiley & Sons Ltd.

Risk Factors for Prolonged Treatment of Whiplash-Associated Disorders.

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Hiroyuki Oka

Full Text Available Whiplash-associated disorders (WAD are the most common injuries that are associated with car collisions in Japan and many Western countries. However, there is no clear evidence regarding the potential risk factors for poor recovery from WAD. Therefore, we used an online survey of the Japanese population to examine the association between potential risk factors and the persistence of symptoms in individuals with WAD.An online survey was completed by 127,956 participants, including 4,164 participants who had been involved in a traffic collision. A random sample of the collision participants (n = 1,698 were provided with a secondary questionnaire. From among the 974 (57.4% respondents to the secondary questionnaire, we selected 183 cases (intractable neck pain that was treated over a period of 6 months and 333 controls (minor neck pain that was treated within 3 months. Multivariable logistic regression analysis was used to evaluate the potential risk factors for prolonged treatment of WAD.Female sex, the severity of the collision, poor expectations of recovery, victim mentality, dizziness, numbness or pain in the arms, and lower back pain were associated with a poor recovery from WAD.In the present study, the baseline symptoms (dizziness, numbness or pain in the arms, and lower back pain had the strongest associations with prolonged treatment for WAD, although the psychological and behavioral factors were also important. These risk factors should be considered when evaluating patients who may have the potential for poor outcomes.

Dietary agent, benzyl isothiocyanate inhibits signal transducer and activator of transcription 3 phosphorylation and collaborates with sulforaphane in the growth suppression of PANC-1 cancer cells

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Deangelis Stephanie

2009-08-01

Full Text Available Abstract The Signal Transducer and Activator of Transcription (STAT proteins comprise a family of latent transcription factors with diverse functions. STAT3 has well established roles in cell proliferation, growth and survival, and its persistent activation has been detected with high frequency in many human cancers. As constitutive activation of STAT3 appears to be vital for the continued survival of these cancerous cells, it has emerged as an attractive target for chemotherapeutics. We examined whether the inhibitory activities of bioactive compounds from cruciferous vegetables, such as Benzyl isothiocyanate (BITC and sulforaphane, extended to STAT3 activation in PANC-1 human pancreatic cancer cells. BITC and sulforaphane were both capable of inhibiting cell viability and inducing apoptosis in PANC-1. Sulforaphane had minimal effect on the direct inhibition of STAT3 tyrosine phosphorylation, however, suggesting its inhibitory activities are most likely STAT3-independent. Conversely, BITC was shown to inhibit the tyrosine phosphorylation of STAT3, but not the phosphorylation of ERK1/2, MAPK and p70S6 kinase. These results suggest that STAT3 may be one of the targets of BITC-mediated inhibition of cell viability in PANC-1 cancer cells. In addition, we show that BITC can prevent the induction of STAT3 activation by Interleukin-6 in MDA-MB-453 breast cancer cells. Furthermore, combinations of BITC and sulforaphane inhibited cell viability and STAT3 phosphorylation more dramatically than either agent alone. These findings suggest that the combination of the dietary agents BITC and sulforaphane has potent inhibitory activity in pancreatic cancer cells and that they may have translational potential as chemopreventative or therapeutic agents.

Sulforaphane is a Nrf2-independent inhibitor of mitochondrial fission

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Gary B. O'Mealey

2017-04-01

Full Text Available The KEAP1-Nrf2-ARE antioxidant system is a principal means by which cells respond to oxidative and xenobiotic stresses. Sulforaphane (SFN, an electrophilic isothiocyanate derived from cruciferous vegetables, activates the KEAP1-Nrf2-ARE pathway and has become a molecule-of-interest in the treatment of diseases in which chronic oxidative stress plays a major etiological role. We demonstrate here that the mitochondria of cultured, human retinal pigment epithelial (RPE-1 cells treated with SFN undergo hyperfusion that is independent of both Nrf2 and its cytoplasmic inhibitor KEAP1. Mitochondrial fusion has been reported to be cytoprotective by inhibiting pore formation in mitochondria during apoptosis, and consistent with this, we show Nrf2-independent, cytoprotection of SFN-treated cells exposed to the apoptosis-inducer, staurosporine. Mechanistically, SFN mitigates the recruitment and/or retention of the soluble fission factor Drp1 to mitochondria and to peroxisomes but does not affect overall Drp1 abundance. These data demonstrate that the beneficial properties of SFN extend beyond activation of the KEAP1-Nrf2-ARE system and warrant further interrogation given the current use of this agent in multiple clinical trials.

Effects of prolonged agmatine treatment in aged male Sprague-Dawley rats.

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Rushaidhi, M; Zhang, H; Liu, P

2013-03-27

Increasing evidence suggests that altered arginine metabolism contributes to cognitive decline during ageing. Agmatine, decarboxylated arginine, has a variety of pharmacological effects, including the modulation of behavioural function. A recent study demonstrated the beneficial effects of short-term agmatine treatment in aged rats. The present study investigated how intraperitoneal administration of agmatine (40mg/kg, once daily) over 4-6weeks affected behavioural function and neurochemistry in aged Sprague-Dawley rats. Aged rats treated with saline displayed significantly reduced exploratory activity in the open field, impaired spatial learning and memory in the water maze and object recognition memory relative to young rats. Prolonged agmatine treatment improved animals' performance in the reversal test of the water maze and object recognition memory test, and significantly suppressed age-related elevation in nitric oxide synthase activity in the dentate gyrus of the hippocampus and prefrontal cortex. However, this prolonged supplementation was unable to improve exploratory activity and spatial reference learning and memory in aged rats. These findings further demonstrate that exogenous agmatine selectively improves behavioural function in aged rats. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Low liver stiffness among cirrhotic patients with hepatitis B after prolonged treatment with nucleoside analogs

DEFF Research Database (Denmark)

Andersen, Ellen Sloth; Weiland, Ola; Leutscher, Peter

2011-01-01

Case reports and short-term clinical trials have suggested that treatment for chronic hepatitis B (CHB) may lead to improvement of cirrhosis. The aim of the present study was to measure liver stiffness in patients diagnosed with advanced fibrosis or cirrhosis prior to prolonged treatment...

QT interval prolongation related to psychoactive drug treatment: a comparison of monotherapy versus polytherapy

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Piccinelli Marco

2005-01-01

Full Text Available Abstract Background Several antipsychotic agents are known to prolong the QT interval in a dose dependent manner. Corrected QT interval (QTc exceeding a threshold value of 450 ms may be associated with an increased risk of life threatening arrhythmias. Antipsychotic agents are often given in combination with other psychotropic drugs, such as antidepressants, that may also contribute to QT prolongation. This observational study compares the effects observed on QT interval between antipsychotic monotherapy and psychoactive polytherapy, which included an additional antidepressant or lithium treatment. Method We examined two groups of hospitalized women with Schizophrenia, Bipolar Disorder and Schizoaffective Disorder in a naturalistic setting. Group 1 was composed of nineteen hospitalized women treated with antipsychotic monotherapy (either haloperidol, olanzapine, risperidone or clozapine and Group 2 was composed of nineteen hospitalized women treated with an antipsychotic (either haloperidol, olanzapine, risperidone or quetiapine with an additional antidepressant (citalopram, escitalopram, sertraline, paroxetine, fluvoxamine, mirtazapine, venlafaxine or clomipramine or lithium. An Electrocardiogram (ECG was carried out before the beginning of the treatment for both groups and at a second time after four days of therapy at full dosage, when blood was also drawn for determination of serum levels of the antipsychotic. Statistical analysis included repeated measures ANOVA, Fisher Exact Test and Indipendent T Test. Results Mean QTc intervals significantly increased in Group 2 (24 ± 21 ms however this was not the case in Group 1 (-1 ± 30 ms (Repeated measures ANOVA p Conclusions No significant prolongation of the QT interval was found following monotherapy with an antipsychotic agent, while combination of these drugs with antidepressants caused a significant QT prolongation. Careful monitoring of the QT interval is suggested in patients taking a

Treatment of prolonged convulsive seizures in children; a single centre, retrospective, observational study

NARCIS (Netherlands)

Vlaskamp, Danique R. M.; Brouwer, Oebele F.; Callenbach, Petra M. C.

2014-01-01

Objectives: To evaluate treatment of children with Prolonged Convulsive Seizures (PCS) at the University Medical Centre Groningen (UMCG). Material and methods: PCS were identified from an UMCG database of children with epilepsy aged = 10 mm and occurred between January 2000 and October 2012 in

Unfavourable effect of prolonged treatment with antithyroid drugs on radioiodine therapy outcome in Graves' hyperthyroidism

OpenAIRE

Rajić, Milena; Vlajković, Marina; Ilić, Slobodan; Stević, Miloš; Sekulić, Vladan; Zečević, Mila

2014-01-01

Radioiodine therapy (RIT) of Graves' hyperthyroidism (GH) is usually recommended after failure of primary therapy with antithyroid drugs (ATDs), which are commonly prescribed for up to 18-24 months. However, in our region, the prolonged ATDs treatment of the disease is very common. Thus, we assessed the efficacy of RIT after prolonged continual pretreatment with ATDs in Graves' hyperthyroidism. Therapy outcome using a single dose of radioiodine was evaluated after one year in 91 patients (f/m...

Arsenic in an alkaline AMD treatment sludge: Characterization and stability under prolonged anoxic conditions

International Nuclear Information System (INIS)

Beauchemin, Suzanne; Fiset, Jean-Francois; Poirier, Glenn; Ablett, James

2010-01-01

Lime treatment of acid mine drainage (AMD) generates large volumes of neutralization sludge that are often stored under water covers. The sludge consists mainly of calcite, gypsum and a widespread ferrihydrite-like Fe phase with several associated species of metal(loid) contaminants. The long-term stability of metal(loid)s in this chemically ill-defined material remains unknown. In this study, the stability and speciation of As in AMD sludge subjected to prolonged anoxic conditions is determined. The total As concentration in the sludge is 300 mg kg -1 . In the laboratory, three distinct water cover treatments were imposed on the sludge to induce different redox conditions (100%N 2 , 100%N 2 + glucose, 95%N 2 :5%H 2 ). These treatments were compared against a control of oxidized, water-saturated sludge. Electron micro-probe (EMP) analysis and spatially resolved synchrotron X-ray fluorescence (SXRF) results indicate that As is dominantly associated with Fe in the sludge. In all treatments and throughout the experiment, measured concentrations of dissolved As were less than 5 μg L -1 . Dissolved Mn concentration in the N 2 + glucose treatment increased significantly compared to other treatments. Manganese and As K-edge X-ray absorption near edge structure spectroscopy (XANES) analyses showed that Mn was the redox-active element in the solid-phase, while As was stable. Arsenic(V) was still the dominant species in all water-covered sludges after 9 months of anoxic treatments. In contrast, Mn(IV) in the original sludge was partially reduced into Mn(II) in all water-covered sludges. The effect was most pronounced in the N 2 + glucose treatment, suggesting microbial reduction. Micro-scale SXRF and XANES analysis of the treated sludge showed that Mn(II) accumulated in areas already enriched in Fe and As. Overall, the study shows that AMD sludges remain stable under prolonged anoxic conditions. External sources of chemical reductants or soluble C were needed to induce

The effect of duration of untreated psychosis and treatment delay on the outcomes of prolonged early intervention in psychotic disorders.

Science.gov (United States)

Albert, Nikolai; Melau, Marianne; Jensen, Heidi; Hastrup, Lene Halling; Hjorthøj, Carsten; Nordentoft, Merete

2017-09-26

The duration of untreated psychosis (DUP) has been shown to have an effect on outcome after first-episode psychosis. The premise of specialized early intervention (SEI) services is that intervention in the early years of illness can affect long-term outcomes. In this study, we investigate whether DUP affects treatment response after 5 years of SEI treatment compared to 2 years of SEI treatment. As part of a randomized controlled trial testing the effect of prolonged SEI treatment 400 participants diagnosed within the schizophrenia spectrum were recruited. For this specific study participants were dichotomized based on DUP, treatment delay, and time from first symptom until start of SEI treatment. The groups were analyzed with regard to treatment response on psychopathology, level of functioning, and cognitive functioning. The participants with a short DUP had a tendency to respond better to the prolonged treatment with regards to disorganized and negative dimension. For participants with short duration from first symptom until start of SEI treatment there was a significant difference on the negative dimension favoring the prolonged OPUS treatment. The finding of an effect of prolonged treatment for participants with a short total treatment delay could mean that prolonged SEI treatment is more beneficial than treatment as usual (TAU) so long as it is provided in the early years of illness and not just in the early years after diagnosis. THE EARLIER THE BETTER: The duration of untreated psychosis influences the long-term outcomes of treatment. Nikolai Albert, at the Copenhagen Mental Health Centre, and a team of Danish researchers have investigated the effects of a specialized early intervention program (OPUS) in 400 patients diagnosed with schizophrenia spectrum disorders and compared the effects of OPUS after two and five years. Their findings suggest that five years of specialized early intervention was most beneficial when the total duration from symptom start to

Sulforaphane reverses glucocorticoid-induced apoptosis in osteoblastic cells through regulation of the Nrf2 pathway

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Lin H

2014-07-01

Full Text Available Hao Lin,1,* Bo Wei,1,* Guangsheng Li,1 Jinchang Zheng,1 Jiecong Sun,1 Jiaqi Chu,2 Rong Zeng,1 Yanru Niu21Department of Spinal Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang, People’s Republic of China; 2Laboratory Institute of Minimally Invasive Orthopedic Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang, People’s Republic of China *These authors contributed equally to this work Abstract: Apoptosis of osteoblasts triggered by high-dose glucocorticoids (GCs has been identified as a major cause of osteoporosis. However, the underlying molecular mechanisms accounting for this action remain elusive, which has impeded the prevention and cure of this side effect. Sulforaphane (SFP is a naturally occurring isothiocyanate that has huge health benefits for humans. In this study, by using osteoblastic MC3T3-E1 cells as a model, we demonstrate the protective effects of SFP against dexamethasone (Dex-induced apoptosis and elucidate the underlying molecular mechanisms. The results show that SFP could effectively inhibit the Dex-induced growth inhibition and release of lactate dehydrogenase in MC3T3-E1 cells. Treatment with Dex induced caspase-dependent apoptosis in MC3T3-E1 cells, as evidenced by an increase in the Sub-G1 phase, chromatin condensation, and deoxyribonucleic acid fragmentation, which were significantly suppressed by coincubation with SFP. Mitochondria-mediated apoptosis pathway contributed importantly to Dex-induced apoptosis, as revealed by the activation of caspase-3/-9 and subsequent cleavage of poly adenosine diphosphate ribose polymerase, which was also effectively blocked by SFP. Moreover, treatments of Dex strongly induced overproduction of reactive oxygen species and inhibited the expression of nuclear factor erythroid 2-related factor 2 (Nrf2 and the downstream effectors HO1 and NQO1. However, cotreatment with SFP effectively reversed this action of Dex. Furthermore, silencing of Nrf2 by

Sulforaphane protects against cytokine- and streptozotocin-induced β-cell damage by suppressing the NF-κB pathway

International Nuclear Information System (INIS)

Song, Mi-Young; Kim, Eun-Kyung; Moon, Woo-Sung; Park, Jin-Woo; Kim, Hyung-Jin; So, Hong-Seob; Park, Raekil; Kwon, Kang-Beom; Park, Byung-Hyun

2009-01-01

Sulforaphane (SFN) is an indirect antioxidant that protects animal tissues from chemical or biological insults by stimulating the expression of several NF-E2-related factor-2 (Nrf2)-regulated phase 2 enzymes. Treatment of RINm5F insulinoma cells with SFN increases Nrf2 nuclear translocation and expression of phase 2 enzymes. In this study, we investigated whether the activation of Nrf2 by SFN treatment or ectopic overexpression of Nrf2 inhibited cytokine-induced β-cell damage. Treatment of RIN cells with IL-1β and IFN-γ induced β-cell damage through a NF-κB-dependent signaling pathway. Activation of Nrf2 by treatment with SFN and induction of Nrf2 overexpression by transfection with Nrf2 prevented cytokine toxicity. The mechanism by which Nrf2 activation inhibited NF-κB-dependent cell death signals appeared to involve the reduction of oxidative stress, as demonstrated by the inhibition of cytokine-induced H 2 O 2 production. The protective effect of SFN was further demonstrated by the restoration of normal insulin secreting responses to glucose in cytokine-treated rat pancreatic islets. Furthermore, pretreatment with SFN blocked the development of type 1 diabetes in streptozotocin-treated mice

Contents of Sulforaphane and Total Isothiocyanates, Antimutagenic Activity, and Inhibition of Clastogenicity in Pulp Juices from Cruciferous Plants

Czech Academy of Sciences Publication Activity Database

Totušek, J.; Tříska, Jan; Lefnerová, D.; Strohalm, J.; Vrchotová, Naděžda; Zendulka, O.; Průchová, J.; Chaloupková, J.; Novotná, P.; Houška, M.

2011-01-01

Roč. 29, č. 5 (2011), s. 548-556 ISSN 1212-1800 R&D Projects: GA MZe QF3287 Institutional research plan: CEZ:AV0Z60870520 Keywords : cruciferous vegetables * juice * antimutagenic effects * sulforaphane * isothiocyanates Subject RIV: GM - Food Processing Impact factor: 0.522, year: 2011

Prolonged Exposure Treatment of Chronic PTSD in Juvenile Sex Offenders: Promising Results from Two Case Studies

Science.gov (United States)

Hunter, John A.

2010-01-01

Prolonged exposure (PE) was used to treat chronic PTSD secondary to severe developmental trauma in two adolescent male sex offenders referred for residential sex offender treatment. Both youth were treatment resistant prior to initiation of PE and showed evidence of long-standing irritability and depression/anxiety. Clinical observation and…

Sulforaphane, a cancer chemopreventive agent, induces pathways associated with membrane biosynthesis in response to tissue damage by aflatoxin B{sub 1}

Energy Technology Data Exchange (ETDEWEB)

Techapiesancharoenkij, Nirachara [Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Bangkok 10210 (Thailand); Fiala, Jeannette L.A. [Department of Biological Engineering and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Navasumrit, Panida [Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Bangkok 10210 (Thailand); Croy, Robert G.; Wogan, Gerald N. [Department of Biological Engineering and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Groopman, John D. [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205 (United States); Ruchirawat, Mathuros [Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Bangkok 10210 (Thailand); Essigmann, John M., E-mail: jessig@mit.edu [Department of Biological Engineering and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States)

2015-01-01

Aflatoxin B{sub 1} (AFB{sub 1}) is one of the major risk factors for liver cancer globally. A recent study showed that sulforaphane (SF), a potent inducer of phase II enzymes that occurs naturally in widely consumed vegetables, effectively induces hepatic glutathione S-transferases (GSTs) and reduces levels of hepatic AFB{sub 1}-DNA adducts in AFB{sub 1}-exposed Sprague Dawley rats. The present study characterized the effects of SF pre-treatment on global gene expression in the livers of similarly treated male rats. Combined treatment with AFB{sub 1} and SF caused reprogramming of a network of genes involved in signal transduction and transcription. Changes in gene regulation were observable 4 h after AFB{sub 1} administration in SF-pretreated animals and may reflect regeneration of cells in the wake of AFB{sub 1}-induced hepatotoxicity. At 24 h after AFB{sub 1} administration, significant induction of genes that play roles in cellular lipid metabolism and acetyl-CoA biosynthesis was detected in SF-pretreated AFB{sub 1}-dosed rats. Induction of this group of genes may indicate a metabolic shift toward glycolysis and fatty acid synthesis to generate and maintain pools of intermediate molecules required for tissue repair, cell growth and compensatory hepatic cell proliferation. Collectively, gene expression data from this study provide insights into molecular mechanisms underlying the protective effects of SF against AFB{sub 1} hepatotoxicity and hepatocarcinogenicity, in addition to the chemopreventive activity of this compound as a GST inducer. - Highlights: • This study revealed sulforaphane (SF)-deregulated gene sets in aflatoxin B{sub 1} (AFB{sub 1})-treated rat livers. • SF redirects biochemical networks toward lipid biosynthesis in AFB{sub 1}-dosed rats. • SF enhanced gene sets that would be expected to favor cell repair and regeneration.

Effect of prolonged and intermittent treatment on the clinical course of peptic ulcer.

Science.gov (United States)

Chornenka, Zhanetta A; Yasinska, Elvira Ts; Grytsiuk, Mariana I

2018-01-01

Introduction: The number of patients with peptic ulcer increases annually. According to published data, patients with peptic ulcer constitute about 15% of those hospitalized with gastrointestinal diseases. The aim: That is why we set the task to evaluate the methods of preventive treatment and to choose the most effective one. Materials and methods: For this purpose, we selected 103 patients with peptic ulcer without severe exacerbations and complications from one region (main group) and 101 patients from another region (control group) for observations. Making diagnosis was based on the study of complaints, anamnestic data, physical examination of the patient, evaluation of the functional state of the gastroduodenal system, as well as the X-ray and endoscopic examination. The sources of the study were medical records of outpatients, control cards for dispensary surveillance, registers of temporary disability records, sick leave records and others. Results: Most patients, from both the main and control groups, who were on prophylactic treatment, noticed that they had an increased working capacity, normalized sleep, better appetite and fewer dyspeptic disorders. Patients in the main group for two years were on prolonged prophylactic treatment according to the method that we had developed. by us. Patients in the control group received an intermittent preventive treatment twice a year (in spring and autumn). In the complex of therapeutic measures the following were used: dietary recommendations, antacids, cholinolytics, multivitamins, etc. Conclusions: Prolonged prophylactic treatment is an effective means to combat exacerbations and complications of peptic ulcer and can be recommended for implementation in practice.

Sulforaphane Prevents Testicular Damage in Kunming Mice Exposed to Cadmium via Activation of Nrf2/ARE Signaling Pathways

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Shu-Hua Yang

2016-10-01

Full Text Available Sulforaphane (SFN is a natural and highly effective antioxidant. Studies suggest that SFN protects cells and tissues against cadmium (Cd toxicity. This study investigated the protective effect of SFN against oxidative damage in the testes of Kunming mice exposed to cadmium, and explored the possible molecular mechanisms involved. Cadmium greatly reduced the serum testosterone levels in mice, reduced sperm motility, total sperm count, and increased the sperm deformity rate. Cadmium also reduces superoxide dismutase (T-SOD and glutathione (GSH levels and increases malondialdehyde (MDA concentrations. SFN intervention improved sperm quality, serum testosterone, and antioxidant levels. Both mRNA and protein expression of mouse testicular nuclear factor-erythroid 2-related factor 2 (Nrf2 was reduced in cadmium-treated group. Furthermore, the downstream genes of Nrf2, glutathione peroxidase (GSH-Px, γ-glutamyl cysteine synthetase (γ-GCS, heme oxygenase-1 (HO-1, and NAD(PH:quinone oxidoreductase-1 (NQO1 were also decreased in cadmium-treated group. SFN intervention increases the expression of these genes. Sulforaphane prevents cadmium-induced testicular damage, probably via activation of Nrf2/ARE signaling.

Sulforaphane composition, cytotoxic and antioxidant activity of crucifer vegetables

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Mohamed A. Farag

2010-01-01

Full Text Available Sulphur compounds in sulphur rich food have been shown to significantly reduce the risk of cancer development. One such compound is sulforaphane (SF, a cancer chemopreventive agent identified in broccoli (F. cruciferae. In this study, SF content was assessed in extracts of several crucifer vegetables including broccoli, brussels sprout, green cabbage, red cabbage, Chinese kale and turnip, in parallel with anticancer and antioxidant activity. Among tested crucifers, cabbage demonstrated a pronounced anticancer effect against A-549 lung cancer cells, with an IC50 value of 38 μg mL−1, and correlated with high SF levels at 540 μg g−1. Except for red cabbage and kale, crucifer extracts displayed moderate to weak activity in scavenging 2,2-diphenyl-1-picrylhydrazyl (DDPH free radicals relative to vitamin E standard.

Sonic hedgehog signaling inhibition provides opportunities for targeted therapy by sulforaphane in regulating pancreatic cancer stem cell self-renewal.

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Mariana Rodova

Full Text Available Dysregulation of the sonic hedgehog (Shh signaling pathway has been associated with cancer stem cells (CSC and implicated in the initiation of pancreatic cancer. Pancreatic CSCs are rare tumor cells characterized by their ability to self-renew, and are responsible for tumor recurrence accompanied by resistance to current therapies. The lethality of these incurable, aggressive and invasive pancreatic tumors remains a daunting clinical challenge. Thus, the objective of this study was to investigate the role of Shh pathway in pancreatic cancer and to examine the molecular mechanisms by which sulforaphane (SFN, an active compound in cruciferous vegetables, inhibits self-renewal capacity of human pancreatic CSCs. Interestingly, we demonstrate here that Shh pathway is highly activated in pancreatic CSCs and plays important role in maintaining stemness by regulating the expression of stemness genes. Given the requirement for Hedgehog in pancreatic cancer, we investigated whether hedgehog blockade by SFN could target the stem cell population in pancreatic cancer. In an in vitro model, human pancreatic CSCs derived spheres were significantly inhibited on treatment with SFN, suggesting the clonogenic depletion of the CSCs. Interestingly, SFN inhibited the components of Shh pathway and Gli transcriptional activity. Interference of Shh-Gli signaling significantly blocked SFN-induced inhibitory effects demonstrating the requirement of an active pathway for the growth of pancreatic CSCs. SFN also inhibited downstream targets of Gli transcription by suppressing the expression of pluripotency maintaining factors (Nanog and Oct-4 as well as PDGFRα and Cyclin D1. Furthermore, SFN induced apoptosis by inhibition of BCL-2 and activation of caspases. Our data reveal the essential role of Shh-Gli signaling in controlling the characteristics of pancreatic CSCs. We propose that pancreatic cancer preventative effects of SFN may result from inhibition of the Shh pathway

Neural changes in extinction recall following prolonged exposure treatment for PTSD: A longitudinal fMRI study

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Liat Helpman, PhD

2016-01-01

Conclusions: Prolonged exposure treatment appears to alter neural activation in PTSD patients during recall of fear extinction, and change in extinction recall (measured by SCR is associated with symptom reduction. We discuss results in the context of neural systems involved in response to affective stimuli.

New developments in the treatment of primary insomnia in elderly patients: focus on prolonged-release melatonin

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Vigo DE

2012-10-01

Full Text Available Daniel P Cardinali, María F Vidal, Daniel E VigoDepartment of Teaching and Research, Faculty of Medical Sciences, Pontificia Universidad Católica Argentina, Buenos Aires, ArgentinaAbstract: A temporal relationship between the nocturnal rise in melatonin secretion and the increase in sleep propensity at the beginning of the night, coupled with the sleep-promoting effects of exogenous melatonin, indicate that melatonin is involved in the regulation of sleep. This action is attributed to the MT1 and MT2 melatonin receptors present in the hypothalamic suprachiasmatic nucleus and other brain areas. The sleep-promoting actions of melatonin, which are demonstrable in healthy humans, have been found to be useful in subjects suffering from circadian rhythm sleep disorders and in elderly patients, who had low nocturnal melatonin production and secretion. The effectiveness of melatonin in treating sleep disturbances in these patients is relevant because the sleep-promoting compounds that are usually prescribed, such as benzodiazepines and related drugs, have many adverse effects, such as next-day hangover, dependence, and impairment of memory. Melatonin has been used for improving sleep in patients with insomnia mainly because it does not cause any hangover or show any addictive potential. However, there is a lack of consistency concerning its therapeutic value (partly because of its short half-life and the small quantities of melatonin used. Thus, attention has been focused either on the development of more potent melatonin analogs with prolonged effects or on the design of slow-release melatonin preparations. A prolonged-release preparation of melatonin 2 mg (Circadin® has been approved for the treatment of primary insomnia in patients aged ≥55 years in the European Union. This prolonged-release preparation of melatonin had no effect on psychomotor functions, memory recall, or driving skills during the night or the next morning relative to placebo

Interferon alfa for chronic hepatitis B infection: increased efficacy of prolonged treatment. The European Concerted Action on Viral Hepatitis (EUROHEP)

NARCIS (Netherlands)

Janssen, H. L.; Gerken, G.; Carreño, V.; Marcellin, P.; Naoumov, N. V.; Craxi, A.; Ring-Larsen, H.; Kitis, G.; van Hattum, J.; de Vries, R. A.; Michielsen, P. P.; ten Kate, F. J.; Hop, W. C.; Heijtink, R. A.; Honkoop, P.; Schalm, S. W.

1999-01-01

Interferon alfa (IFN-alpha) is the primary treatment for chronic hepatitis B. The standard duration of IFN-alpha therapy is considered 16 weeks; however, the optimal treatment length is still poorly defined. We evaluated the efficacy and acceptability of prolonged IFN-alpha treatment in patients

Work-related limitations and return-to-work experiences in prolonged fatigue: workers' perspectives before and after vocational treatment.

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Joosen, Margot C W; Frings-Dresen, Monique H W; Sluiter, Judith K

2011-01-01

To gain insight into fatigued workers' perspectives regarding work experience before and after receiving vocational rehabilitation (VR) treatments. A qualitative survey was conducted using semi-structured interviews with 21 fatigued workers who attended an outpatient multi-component VR treatment. Six months after treatment, work-related limitations and employed VR strategies at work before treatment were explored. Next, VR treatment experiences regarding return-to-work (RTW) were explored. Two researchers performed partially independent, qualitative analyses that revealed topics, discussed by the project team, and organised into domains, categories and sub-categories. Work-related limitations were: symptoms of prolonged fatigue, personal limitations (e.g. lack of self-reflection on individual capacity and limitations), interpersonal factors, activities and conditions at work and life/work imbalance. Before the treatment, VR strategies such as work adaptations, well-intentioned advice and support, and/or referral to psychological or physical care were employed. VR treatment experiences on RTW were: personal challenges (e.g. gained awareness and coping skills), improved activities during work, work adaptations and unresolved problems (e.g. remaining fatigue symptoms and sickness absence). New information about work experiences before and after multi-component VR treatments in workers with prolonged fatigue may help employers, occupational physicians and other caregivers to develop VR strategies that better meet individuals' needs.

Evaluating a patient's request for life-prolonging treatment: an ethical framework.

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Winkler, Eva C; Hiddemann, Wolfgang; Marckmann, Georg

2012-11-01

Contrary to the widespread concern about over-treatment at the end of life, today, patient preferences for palliative care at the end of life are frequently respected. However, ethically challenging situations in the current healthcare climate are, instead, situations in which a competent patient requests active treatment with the goal of life-prolongation while the physician suggests best supportive care only. The argument of futility has often been used to justify unilateral decisions made by physicians to withhold or withdraw life-sustaining treatment. However, we argue that neither the concept of futility nor that of patient autonomy alone is apt for resolving situations in which physicians are confronted with patients' requests for active treatment. Instead, we integrate the relevant arguments that have been put forward in the academic discussion about 'futile' treatment into an ethical algorithm with five guiding questions: (1) Is there a chance that medical intervention will be effective in achieving the patient's treatment goal? (2) How does the physician evaluate the expected benefit and the potential harm of the treatment? (3) Does the patient understand his or her medical situation? (4) Does the patient prefer receiving treatment after evaluating the benefit-harm ratio and the costs? (5) Does the treatment require many resources? This algorithm shall facilitate approaching patients' requests for treatments deemed futile by the physician in a systematic way, and responding to these requests in an ethically appropriate manner. It thereby adds substantive considerations to the current procedural approaches of conflict resolution in order to improve decision making among physicians, patients and families.

Sulforaphane ameliorates the development of experimental autoimmune encephalomyelitis by antagonizing oxidative stress and Th17-related inflammation in mice.

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Li, Bin; Cui, Wei; Liu, Jia; Li, Ru; Liu, Qian; Xie, Xiao-Hua; Ge, Xiao-Li; Zhang, Jing; Song, Xiu-Juan; Wang, Ying; Guo, Li

2013-12-01

Sulforaphane (SFN) is an organosulfur compound present in vegetables and has potent anti-oxidant and anti-inflammatory activities. This study was aimed at investigating the effect of treatment with SFN on inflammation and oxidative stress, and the potential mechanisms underlying the action of SFN in experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. Treatment with SFN significantly inhibited the development and severity of EAE in mice, accompanied by mitigating inflammatory infiltration and demyelination in the spinal cord of mice. The protective effect of SFN was associated with significantly improved distribution of claudin-5 and occludin, and decreased levels of MMP-9 expression, preserving the blood-brain barrier. Furthermore, the protection of SFN was also related to decreased levels of oxidative stress in the brains of mice by enhanced activation of the Nrf2/ARE pathway and increased levels of anti-oxidant HO-1 and NQO1 expression. In addition, treatment with SFN inhibited antigen-specific Th17 responses and enhanced IL-10 responses. Our data indicated that treatment with SFN inhibited EAE development and severity in mice by its anti-oxidant activity and antagonizing autoimmune inflammation. Our findings suggest that SFN and its analogues may be promising reagents for intervention of multiple sclerosis and other autoimmune diseases. © 2013.

Neural and behavioural changes in male periadolescent mice after prolonged nicotine-MDMA treatment.

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Adeniyi, Philip A; Ishola, Azeez O; Laoye, Babafemi J; Olatunji, Babawale P; Bankole, Oluwamolakun O; Shallie, Philemon D; Ogundele, Olalekan M

2016-02-01

The interaction between MDMA and Nicotine affects multiple brain centres and neurotransmitter systems (serotonin, dopamine and glutamate) involved in motor coordination and cognition. In this study, we have elucidated the effect of prolonged (10 days) MDMA, Nicotine and a combined Nicotine-MDMA treatment on motor-cognitive neural functions. In addition, we have shown the correlation between the observed behavioural change and neural structural changes induced by these treatments in BALB/c mice. We observed that MDMA (2 mg/Kg body weight; subcutaneous) induced a decline in motor function, while Nicotine (2 mg/Kg body weight; subcutaneous) improved motor function in male periadolescent mice. In combined treatment, Nicotine reduced the motor function decline observed in MDMA treatment, thus no significant change in motor function for the combined treatment versus the control. Nicotine or MDMA treatment reduced memory function and altered hippocampal structure. Similarly, a combined Nicotine-MDMA treatment reduced memory function when compared with the control. Ultimately, the metabolic and structural changes in these neural systems were seen to vary for the various forms of treatment. It is noteworthy to mention that a combined treatment increased the rate of lipid peroxidation in brain tissue.

QTc Prolongation in Veterans With Heroin Dependence on Methadone Maintenance Treatment.

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Hassamal, Sameer; Fernandez, Antony; Moradi Rekabdarkolaee, Hossein; Pandurangi, Ananda

2015-06-01

QTc prolongation and Torsade de Ppointes have been reported in patients on methadone maintenance. In this study, QTc was compared before and after the veteran (n = 49) was on a stable dosage of methadone for 8.72 ± 4.50 years to treat heroin dependence. Risk factors were correlated with the QTc once the veteran was on a stable dose of methadone. Differences in the clinical risk factors in subgroups of veterans with below and above mean QTc change was compared. ECG data was obtained from a 12-lead electrocardiogram (pre-methadone and on methadone) on 49 veterans. Data and risk factors were retrospectively collected from the medical records. The mean QTc at baseline (pre-methadone) was 426 ± 34 msec and after being on methadone for an average of 8.72 ± 4.50 years was significantly higher at 450 ± 35 msec. No significant relationships were found between QTc prolongation and risk factors except for calcium. The methadone dosage was significantly higher in veterans with a QTc change above the mean change of ≥ 24 msec (88.48 ± 27.20 mg v.s 68.96 ± 19.84 mg). None of the veterans experienced cardiac arrhythmias. The low complexity of medical co-morbidities may explain the lack of a significant correlation between any risk factor with the QTc except calcium and methadone dosage. The absence of TdP may be explained by the low prevalence of QTc values > 500 msec as well as the retrospective design of the study. During long-term methadone treatment, there was a slight increase in the QTc interval but we did not find evidence of increased cardiac toxicity as a reason for treatment termination.

The effect of shorter exposure versus prolonged exposure on treatment outcome in Tourette syndrome and chronic tic disorders - an open trial.

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van de Griendt, Jolande M T M; van Dijk, Maarten K; Verdellen, Cara W J; Verbraak, Marc J P M

2018-01-11

Exposure and response prevention has shown to be an effective strategy and is considered a first-line intervention in the behavioural treatment of tic disorders. Prior research demonstrated significant tic reduction after 12 two hour sessions. In this open trial, the question is addressed whether, relative to these prolonged sessions, exposure sessions of shorter duration yield differential outcome for patients with tic disorders. A total of 29 patients diagnosed with Tourette syndrome (TS) or chronic tic disorder were treated with shorter exposure sessions (1 h), and these data were compared to the data from a study about prolonged exposure (2 h, n = 21). Outcome was measured by the Yale Global Tic Severity Scale (YGTSS). Results suggest that after taking the difference in illness duration between the two groups into account, the effectiveness of shorter exposure sessions is not inferior to that of prolonged exposure. Results suggest that treatment with shorter exposure might be more efficient and more patients can be reached. Future research is needed to gain more insight into the mechanisms underlying the efficacy of behavioural treatments for tics.

Protection by sulforaphane from type 1 diabetes-induced testicular apoptosis is associated with the up-regulation of Nrf2 expression and function

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Jiang, Xin; Bai, Yang; Zhang, Zhiguo [The First Hospital of Jilin University, Changchun 130021 (China); KCHRI at the Department of Pediatrics, The University of Louisville, Louisville 40202 (United States); Xin, Ying, E-mail: xiny@jlu.edu.cn [KCHRI at the Department of Pediatrics, The University of Louisville, Louisville 40202 (United States); Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun 130021 (China); Cai, Lu, E-mail: l0cai001@louisville.edu [The First Hospital of Jilin University, Changchun 130021 (China); KCHRI at the Department of Pediatrics, The University of Louisville, Louisville 40202 (United States)

2014-09-01

Diabetes-induced testicular apoptosis is predominantly due to increased oxidative stress. The nuclear factor-erythroid 2-related factor 2 (Nrf2), as a master transcription factor in controlling anti-oxidative systems, is able to be induced by sulforaphane (SFN). To examine whether SFN prevents testicular apoptosis, type 1 diabetic mouse model was induced with multiple low-dose streptozotocin. Diabetic and age-matched control mice were treated with and without SFN at 0.5 mg/kg daily in five days of each week for 3 months and then kept until 6 months. Diabetes significantly increased testicular apoptosis that was associated with endoplasmic reticulum stress and mitochondrial cell death pathways, shown by the increased expression of C/EBP homologous protein (CHOP), cleaved caspase-12, Bax to Bcl2 expression ratio, and cleaved caspase-3. Diabetes also significantly increased testicular oxidative damage, inflammation and fibrosis, and decreased germ cell proliferation. All these diabetic effects were significantly prevented by SFN treatment for the first 3 months, and the protective effect could be sustained at 3 months after SFN treatment. SFN was able to up-regulate Nrf2 expression and function. The latter was reflected by the increased phosphorylation of Nrf2 at Ser40 and expression of Nrf2 downstream antioxidants at mRNA and protein levels. These results suggest that type 1 diabetes significantly induced testicular apoptosis and damage along with increasing oxidative stress and cell death and suppressing Nrf2 expression and function. SFN is able to prevent testicular oxidative damage and apoptosis in type 1 diabetes mice, which may be associated with the preservation of testicular Nrf2 expression and function under diabetic condition. - Highlights: • Sulforaphane (SFN) could attenuate diabetes-induced germ cell apoptosis. • SFN could preserve germ cell proliferation under diabetic conditions. • SFN testicular protection was sustained until 3 months after

Protection by sulforaphane from type 1 diabetes-induced testicular apoptosis is associated with the up-regulation of Nrf2 expression and function

International Nuclear Information System (INIS)

Jiang, Xin; Bai, Yang; Zhang, Zhiguo; Xin, Ying; Cai, Lu

2014-01-01

Diabetes-induced testicular apoptosis is predominantly due to increased oxidative stress. The nuclear factor-erythroid 2-related factor 2 (Nrf2), as a master transcription factor in controlling anti-oxidative systems, is able to be induced by sulforaphane (SFN). To examine whether SFN prevents testicular apoptosis, type 1 diabetic mouse model was induced with multiple low-dose streptozotocin. Diabetic and age-matched control mice were treated with and without SFN at 0.5 mg/kg daily in five days of each week for 3 months and then kept until 6 months. Diabetes significantly increased testicular apoptosis that was associated with endoplasmic reticulum stress and mitochondrial cell death pathways, shown by the increased expression of C/EBP homologous protein (CHOP), cleaved caspase-12, Bax to Bcl2 expression ratio, and cleaved caspase-3. Diabetes also significantly increased testicular oxidative damage, inflammation and fibrosis, and decreased germ cell proliferation. All these diabetic effects were significantly prevented by SFN treatment for the first 3 months, and the protective effect could be sustained at 3 months after SFN treatment. SFN was able to up-regulate Nrf2 expression and function. The latter was reflected by the increased phosphorylation of Nrf2 at Ser40 and expression of Nrf2 downstream antioxidants at mRNA and protein levels. These results suggest that type 1 diabetes significantly induced testicular apoptosis and damage along with increasing oxidative stress and cell death and suppressing Nrf2 expression and function. SFN is able to prevent testicular oxidative damage and apoptosis in type 1 diabetes mice, which may be associated with the preservation of testicular Nrf2 expression and function under diabetic condition. - Highlights: • Sulforaphane (SFN) could attenuate diabetes-induced germ cell apoptosis. • SFN could preserve germ cell proliferation under diabetic conditions. • SFN testicular protection was sustained until 3 months after

Sulforaphane enhances irradiation effects in terms of perturbed cell cycle progression and increased DNA damage in pancreatic cancer cells.

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Patrick Naumann

Full Text Available Sulforaphane (SFN, an herbal isothiocyanate enriched in cruciferous vegetables like broccoli and cauliflower, has gained popularity for its antitumor effects in cell lines such as pancreatic cancer. Antiproliferative as well as radiosensitizing properties were reported for head and neck cancer but little is known about its effects in pancreatic cancer cells in combination with irradiation (RT.In four established pancreatic cancer cell lines we investigated clonogenic survival, analyzed cell cycle distribution and compared DNA damage via flow cytometry and western blot after treatment with SFN and RT.Both SFN and RT show a strong and dose dependent survival reduction in clonogenic assays, an induction of a G2/M cell cycle arrest and an increase in γH2AX protein level indicating DNA damage. Effects were more pronounced in combined treatment and both cell cycle perturbation and DNA damage persisted for a longer period than after SFN or RT alone. Moreover, SFN induced a loss of DNA repair proteins Ku 70, Ku 80 and XRCC4.Our results suggest that combination of SFN and RT exerts a more distinct DNA damage and growth inhibition than each treatment alone. SFN seems to be a viable option to improve treatment efficacy of chemoradiation with hopefully higher rates of secondary resectability after neoadjuvant treatment for pancreatic cancer.

Prolonged utilization of proton pump inhibitors in patients with ischemic and valvular heart disease is associated with surgical treatments, weight loss and aggravates anemia.

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Boban, Marko; Zulj, Marinko; Persic, Viktor; Medved, Igor; Zekanovic, Drazen; Vcev, Aleksandar

2016-09-15

Proton pump inhibitors (PPIs) are among the commonest drugs used nowadays. The aim of our study was to analyze prolonged utilization of proton pump inhibitors in medical therapy of patients with ischemic and valvular heart disease. Secondly, profile of utilization was scrutinized to patient characteristics and type of cardiovascular treatments. The study included consecutive patients scheduled for cardiovascular rehabilitation 2-6months after index cardiovascular treatment. Two hundred ninety-four patients (n=294/604; 48.7%) have been using proton pump inhibitor in their therapy after index cardiovascular treatment. Cardiovascular treatments were powerfully connected with utilization of PPIs; surgery 5.77 (95%-confidence intervals [CI]: 4.05-8.22; pvalvular heart disease utilized proton pump inhibitor in prolonged courses. Prolonged courses of PPIs were connected with existence and worsening of red blood count indexes, older age, lesser weight of patients and underutilization of cardioprotective drugs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Virtual reality exposure versus prolonged exposure for PTSD: Which treatment for whom?

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Norr, Aaron M; Smolenski, Derek J; Katz, Andrea C; Rizzo, Albert A; Rothbaum, Barbara O; Difede, JoAnn; Koenen-Woods, Patricia; Reger, Mark A; Reger, Greg M

2018-06-01

The majority of studies comparing active psychological treatments for posttraumatic stress disorder (PTSD) do not find significant differences at posttreatment. This was the case in a recent trial examining prolonged exposure (PE) and virtual reality exposure (VRE) among active-duty soldiers with combat-related PTSD. Matching individual patients to specific treatments provides a potential avenue to improve significantly the public health impact of effective treatments for PTSD. A composite moderator approach was used to identify profiles of patients who would see superior PTSD symptom reduction in VRE or PE to inform future treatment matching. Active duty U.S. army soldiers (N = 108) were enrolled in a randomized clinical trial comparing VRE and PE in the treatment of PTSD stemming from deployments to Iraq or Afghanistan. Eighteen baseline variables were examined to identify treatment response heterogeneity in two patient groups: those with a superior response to PE and those with a superior response to VRE. The final composite moderator comprised four of 18 baseline variables. Results revealed that patients who were predicted to see greater PTSD symptom reduction in VRE were likely to be younger, not taking antidepressant medication, had greater PTSD hyperarousal symptoms, and were more likely to have greater than minimal suicide risk. Results suggest that treatment matching based on patient profiles could meaningfully improve treatment efficacy for combat-related PTSD. Future research can build on these results to improve our understanding of how to improve treatment matching for PTSD. © 2018 Wiley Periodicals, Inc.

Sulforaphane Protects the Liver against CdSe Quantum Dot-Induced Cytotoxicity.

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Wei Wang

Full Text Available The potential cytotoxicity of cadmium selenide (CdSe quantum dots (QDs presents a barrier to their use in biomedical imaging or as diagnostic and therapeutic agents. Sulforaphane (SFN is a chemoprotective compound derived from cruciferous vegetables which can up-regulate antioxidant enzymes and induce apoptosis and autophagy. This study reports the effects of SFN on CdSe QD-induced cytotoxicity in immortalised human hepatocytes and in the livers of mice. CdSe QDs induced dose-dependent cell death in hepatocytes with an IC50 = 20.4 μM. Pre-treatment with SFN (5 μM increased cell viability in response to CdSe QDs (20 μM from 49.5 to 89.3%. SFN induced a pro-oxidant effect characterized by depletion of intracellular reduced glutathione during short term exposure (3-6 h, followed by up-regulation of antioxidant enzymes and glutathione levels at 24 h. SFN also caused Nrf2 translocation into the nucleus, up-regulation of antioxidant enzymes and autophagy. siRNA knockdown of Nrf2 suggests that the Nrf2 pathway plays a role in the protection against CdSe QD-induced cell death. Wortmannin inhibition of SFN-induced autophagy significantly suppressed the protective effect of SFN on CdSe QD-induced cell death. Moreover, the role of autophagy in SFN protection against CdSe QD-induced cell death was confirmed using mouse embryonic fibroblasts lacking ATG5. CdSe QDs caused significant liver damage in mice, and this was decreased by SFN treatment. In conclusion, SFN attenuated the cytotoxicity of CdSe QDs in both human hepatocytes and in the mouse liver, and this protection was associated with the induction of Nrf2 pathway and autophagy.

Low liver stiffness among cirrhotic patients with hepatitis B after prolonged treatment with nucleoside analogs

DEFF Research Database (Denmark)

Andersen, Ellen Sloth; Weiland, Ola; Leutscher, Peter

2011-01-01

Abstract Objective. Case reports and short-term clinical trials have suggested that treatment for chronic hepatitis B (CHB) may lead to improvement of cirrhosis. The aim of the present study was to measure liver stiffness in patients diagnosed with advanced fibrosis or cirrhosis prior to prolonged...... treatment with nucleoside or nucleotide analogs (NUCs) for CHB. Materials and methods. Patients with CHB and advanced fibrosis or cirrhosis prior to treatment with NUCs for at least 1 year were offered inclusion in the study. We measured liver stiffness using transient elastography (TE) at follow-up. TE cut...... duration was 50.5 months. Among patients with cirrhosis prior to treatment, 26 (49%) had liver stiffness below 11.0 kPa at follow-up, suggesting regression of cirrhosis. Among patients with advanced fibrosis (F3) prior to treatment, 10 (77%) had liver stiffness below 8.1 kPa after treatment, suggesting...

Prolonged response without prolonged chemotherapy: a lesson from PCV chemotherapy in low-grade gliomas

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Peyre, Matthieu; Cartalat-Carel, Stéphanie; Meyronet, David; Ricard, Damien; Jouvet, Anne; Pallud, Johan; Mokhtari, Karima; Guyotat, Jacques; Jouanneau, Emmanuel; Sunyach, Marie-Pierre; Frappaz, Didier; Honnorat, Jérôme; Ducray, François

2010-01-01

Previous studies with temozolomide suggest that a prolonged duration of chemotherapy is important for treating low-grade gliomas (LGGs). PCV (procarbazine, CCNU, vincristine) chemotherapy has demonstrated efficacy in treating LGGs, but this therapy cannot be used for a prolonged period because of the cumulative toxicity. The aim of the present study was to evaluate the impact of first-line PCV chemotherapy on LGGs growth kinetics. The mean tumor diameter (MTD) of 21 LGGs was measured on serial magnetic resonance images before (n=13), during, and after PCV onset (n=21). During PCV treatment, a decrease in the MTD was observed in all patients. After PCV discontinuation, an ongoing decrease in MTD was observed in 20 of the 21 patients. Median duration of the MTD decrease was 3.4 years (range, 0.8–7.7) after PCV onset and 2.7 years (range, 0–7) after the end of PCV treatment with 60% of LGGs, demonstrating an ongoing and prolonged (>2 years) response despite chemotherapy no longer being administered. According to McDonald's criteria, the rates of partial and minor responses were 5% and 38% at the end of PCV but 38% and 42% at the time of maximal MTD decrease, which occurred after a median period of 3.4 years after PCV onset. These results challenge the idea that a prolonged duration of chemotherapy is necessary for treating LGGs and raise the issue of understanding the mechanisms involved in the persistent tumor volume decrease once chemotherapy is terminated. PMID:20488959

Influence of prolonged storage process, pasteurization, and heat treatment on biologically-active human milk proteins.

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Chang, Jih-Chin; Chen, Chao-Huei; Fang, Li-Jung; Tsai, Chi-Ren; Chang, Yu-Chuan; Wang, Teh-Ming

2013-12-01

The bioactive proteins in human milk may be influenced by prolonged storage process, pasteurization, and heat treatment. This study was conducted to evaluate the effects of these procedures. Three forms of human milk - freshly expressed, frozen at -20°C for a prolonged duration, and pasteurized milk - were collected from 14 healthy lactating mothers and a milk bank. The concentrations of major bioactive proteins (secretory immunoglobulin A, lactoferrin, lysozyme, and leptin) were quantified using enzyme-linked immunosorbent assay kits. Changes in these proteins by heat treatment at 40°C or 60°C for 30 minutes were further evaluated. The mean concentrations of lactoferrin and secretory immunoglobulin A were significantly reduced by 66% and 25.9%, respectively, in pasteurized milk compared with those in freshly-expressed milk. Heat treatment at 40°C or 60°C did not cause significant changes in lactoferrin and secretory immunoglobulin A, but there was an apparent increase in lysozyme (p = 0.016). There were no significant differences in leptin level among these three forms of milk prior to (p = 0.153) or after heat treatment (p = 0.053). Various freezing/heating/pasteurization processes applied to human milk prior to delivery to neonates could affect the concentration of immunomodulatory proteins, especially lactoferrin, secretory immunoglobulin A, and lysozyme. Leptin was unaffected by the various handling processes tested. Fresh milk was found to be the best food for neonates. Further studies are warranted to evaluate the functional activity of these proteins and their effects on infants' immunological status. Copyright © 2013. Published by Elsevier B.V.

Short vs prolonged dual antiplatelet treatment upon endovascular stenting of peripheral arteries

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Kronlage M

2017-10-01

Full Text Available Mariya Kronlage,1 Maximilian Wassmann,1 Britta Vogel,1 Oliver J Müller,1 Erwin Blessing,2 Hugo Katus,1,3 Christian Erbel1 1Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, Heidelberg, 2SRH Klinikum Karlsbad Langensteinbach, Karlsbad, 3DZHK German Center for Cardiovascular Research, Partner Site Heidelberg/Mannheim, Mannheim, Germany Introduction: Peripheral artery disease (PAD is a highly prevalent disorder with a substantial economical burden. Dual antiplatelet treatment (DAPT upon endovascular stenting to prevent acute thrombotic reocclusions is an universally accepted practice for postinterventional management of PAD patients. However, the optimal period of time for DAPT upon endovascular stenting is not known.Methods: In the current nonrandomized, retrospective monocentric study, we evaluated the duration of DAPT upon endovascular stenting. A total of 261 endovascular SFA and iliac stenting procedures were performed on 214 patients and these patients were subdivided into a short (4–6 weeks or a prolonged (8–12 weeks DAPT regime group. More than 65% of the patients included were male, approximately 35% were diabetic, and 61% had a history of smoking. Of all the patients, 90% exhibited a Rutherford stage 2–3, and approximately half of the patients had a moderate-to-severe calcified target lesion with a length of >13 cm. Major safety end points were defined as any bleeding, compartment syndrome, and ischemic events. In addition to this, patency, all-cause mortality, as well as amputation were followed up over a period of 12 months upon intervention.Results: Twelve months after endovascular stenting, primary patency in our cohort was comparable between the groups (83.94% short vs 79.8% long DAPT, P>0.05. Major bleeding occurred in 18 cases without any difference between the groups (P>0.05. In addition, during the 12-month follow-up, 6 (3.4% patients in the short and 3 (3.5% in the prolonged DAPT regime

Effect of NaCl treatments on glucosinolate metabolism in broccoli sprouts*

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Guo, Rong-fang; Yuan, Gao-feng; Wang, Qiao-mei

2013-01-01

To understand the regulation mechanism of NaCl on glucosinolate metabolism in broccoli sprouts, the germination rate, fresh weight, contents of glucosinolates and sulforaphane, as well as myrosinase activity of broccoli sprouts germinated under 0, 20, 40, 60, 80, and 100 mmol/L of NaCl were investigated in our experiment. The results showed that glucoerucin, glucobrassicin, and 4-hydroxy glucobrassicin in 7-d-old broccoli sprouts were significantly enhanced and the activity of myrosinase was inhibited by 100 mmol/L of NaCl. However, the total glucosinolate content in 7-d-old broccoli sprouts was markedly decreased although the fresh weight was significantly increased after treatment with NaCl at relatively low concentrations (20, 40, and 60 mmol/L). NaCl treatment at the concentration of 60 mmol/L for 5 d maintained higher biomass and comparatively higher content of glucosinolates in sprouts of broccoli with decreased myrosinase activity. A relatively high level of NaCl treatment (100 mmol/L) significantly increased the content of sulforaphane in 7-d-old broccoli sprouts compared with the control. These results indicate that broccoli sprouts grown under a suitable concentration of NaCl could be desirable for human nutrition. PMID:23365011

Smoking prolongs the infectivity of patients with tuberculosis.

LENUS (Irish Health Repository)

Siddiqui, U A

2010-10-01

We sought to establish if smokers on anti-tuberculosis treatment are more likely to have a prolonged period of infectivity, compared to non-smoking tuberculosis patients, in a low tuberculosis prevalence country. We conducted a cross-sectional, retrospective study in Ireland that recruited 53 microbiologically confirmed cases of pulmonary tuberculosis (PTB). The age-sex adjusted odds ratios (AOR) suggest that the infectivity status of PTB on treatment was four times more likely to be prolonged beyond 6-8 weeks, if the cases had a smoking history (AOR: 4.42; 95% CI: 1.23; 15.9). Smoking was associated with delayed sputum smear conversion in PTB patients on treatment.

Epigenetic Regulation by Sulforaphane: Opportunities for Breast and Prostate Cancer Chemoprevention.

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Atwell, Lauren L; Beaver, Laura M; Shannon, Jackilen; Williams, David E; Dashwood, Roderick H; Ho, Emily

2015-04-01

Sulforaphane (SFN) is a phytochemical derived from cruciferous vegetables that has multiple molecular targets and anti-cancer properties. Researchers have demonstrated several chemopreventive benefits of SFN consumption, such as reductions in tumor growth, increases in cancer cell apoptosis, and disruption of signaling within tumor microenvironments both in vitro and in vivo . Emerging evidence indicates that SFN exerts several of its chemopreventive effects by altering epigenetic mechanisms. This review summarizes evidence of the impact of SFN on epigenetic events and how they relate to the chemopreventive effects of SFN observed in preclinical and clinical studies of breast and prostate cancers. Specific areas of focus include the role of SFN in the regulation of cell cycle, apoptosis, inflammation, antioxidant defense, and cancer cell signaling and their relationships to epigenetic mechanisms. Finally, remaining challenges and research needs for translating mechanistic work with SFN into human studies and clinical intervention trials are discussed.

Protective effect of sulforaphane against retinal degeneration in the Pde6rd10 mouse model of retinitis pigmentosa.

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Kang, Kai; Yu, Minzhong

2017-12-01

Retinitis pigmentosa (RP) is a group of inherited diseases characterized by the death of rod photoreceptors, followed by the death of cone photoreceptors, progressively leading to partial or complete blindness. Currently no specific treatment is available for RP patients. Sulforaphane (SFN) has been confirmed to be an effective antioxidant in the treatment of many diseases. In this study, we tested the therapeutic effects of SFN against photoreceptor degeneration in Pde6b rd10 mice. rd10 mice and C57/BL6 wild-type (WT) mice were treated with SFN and saline, respectively, from P6 to P20. Electroretinography (ERG), terminal deoxynucleotidyl transferase dUTP nick end labeling and western blot were tested, respectively, at P21 for the analysis of retinal function, retinal cell apoptosis or death and the protein express of GRP78/BiP (TUNEL) as a marker of endoplasmic reticulum (ER) stress. Compared with the saline group, the SFN-treated group showed significantly higher ERG a-wave and b-wave amplitudes, less photoreceptor death, and the downregulation of GRP78/BiP. Our data showed that SFN ameliorated the retinal degeneration of rd10 mice, which is possibly related to the downregulation of GRP78 expression.

Urease from Helicobacter pylori is inactivated by sulforaphane and other isothiocyanates

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Fahey, Jed W.; Stephenson, Katherine K.; Wade, Kristina L.; Talalay, Paul

2013-01-01

Infections by Helicobacter pylori are very common, causing gastroduodenal inflammation including peptic ulcers, and increasing the risk of gastric neoplasia. The isothiocyanate (ITC) sulforaphane [SF; 1-isothiocyanato-4-(methylsulfinyl)butane] derived from edible crucifers such as broccoli is potently bactericidal against Helicobacter, including antibiotic-resistant strains, suggesting a possible dietary therapy. Gastric H. pylori infections express high urease activity which generates ammonia, neutralizes gastric acidity, and promotes inflammation. The finding that SF inhibits (inactivates) urease (jack bean and Helicobacter) raised the issue of whether these properties might be functionally related. The rates of inactivation of urease activity depend on enzyme and SF concentrations and show first order kinetics. Treatment with SF results in time-dependent increases in the ultraviolet absorption of partially purified Helicobacter urease in the 280–340 nm region. This provides direct spectroscopic evidence for the formation of dithiocarbamates between the ITC group of SF and cysteine thiols of urease. The potencies of inactivation of Helicobacter urease by isothiocyanates structurally related to SF were surprisingly variable. Natural isothiocyanates closely related to SF, previously shown to be bactericidal (berteroin, hirsutin, phenethyl isothiocyanate, alyssin, and erucin), did not inactivate urease activity. Furthermore, SF is bactericidal against both urease positive and negative H. pylori strains. In contrast, some isothiocyanates such as benzoyl-ITC, are very potent urease inactivators, but are not bactericidal. The bactericidal effects of SF and other ITC against Helicobacter are therefore not obligatorily linked to urease inactivation, but may reduce the inflammatory component of Helicobacter infections. PMID:23583386

Methyl Jasmonate and 1-Methylcyclopropene Treatment Effects on Quinone Reductase Inducing Activity and Post-Harvest Quality of Broccoli

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Ku, Kang Mo; Choi, Jeong Hee; Kim, Hyoung Seok; Kushad, Mosbah M.; Jeffery, Elizabeth H.; Juvik, John A.

2013-01-01

Effect of pre-harvest methyl jasmonate (MeJA) and post-harvest 1-methylcyclopropene (1-MCP) treatments on broccoli floret glucosinolate (GS) concentrations and quinone reductase (QR, an in vitro anti-cancer biomarker) inducing activity were evaluated two days prior to harvest, at harvest and at 10, 20, and 30 days of post-harvest storage at 4 °C. MeJA treatments four days prior to harvest of broccoli heads was observed to significantly increase floret ethylene biosynthesis resulting in chlorophyll catabolism during post-harvest storage and reduced product quality. Post-harvest treatment with 1-methylcyclopropene (1-MCP), which competitively binds to protein ethylene receptors, maintained post-harvest floret chlorophyll concentrations and product visual quality in both control and MeJA-treated broccoli. Transcript abundance of BoPPH, a gene which is responsible for the synthesis of pheophytinase, the primary enzyme associated with chlorophyll catabolism in broccoli, was reduced by 1-MCP treatment and showed a significant, negative correlation with floret chlorophyll concentrations. The GS, glucobrassicin, neoglucobrassicin, and gluconasturtiin were significantly increased by MeJA treatments. The products of some of the GS from endogenous myrosinase hydrolysis [sulforaphane (SF), neoascorbigen (NeoASG), N-methoxyindole-3-carbinol (NI3C), and phenethyl isothiocyanate (PEITC)] were also quantified and found to be significantly correlated with QR. Sulforaphane, the isothiocyanate hydrolysis product of the GS glucoraphanin, was found to be the most potent QR induction agent. Increased sulforaphane formation from the hydrolysis of glucoraphanin was associated with up-regulated gene expression of myrosinase (BoMyo) and the myrosinase enzyme co-factor gene, epithiospecifier modifier1 (BoESM1). This study demonstrates the combined treatment of MeJA and 1-MCP increased QR activity without post-harvest quality loss. PMID:24146962

Prolonged vertigo and ataxia after mandibular nerve block for treatment of trigeminal neuralgia.

Science.gov (United States)

Chaturvedi, Arvind; Dash, Hh

2011-07-01

Common complications of neurolytic mandibular nerve block are hypoesthesia, dysesthesia, and chemical neuritis. We report a rare complication, prolonged severe vertigo and ataxia, after neurolytic mandibular blockade in a patient suffering from trigeminal neuralgia. Coronoid approach was used for right sided mandibular block. After successful test injection with local anesthetic, absolute alcohol was given for neurolytic block. Immediately after alcohol injection, patient developed nausea and vomiting along with severe vertigo, ataxia and hypertension. Neurological evaluation was normal except for the presence of vertigo and ataxia. Computerised tomography scan brain was also normal. Patient was admitted for observation and symptomatic treatment was given. Vertigo and ataxia gradually improved over 24 hours.

Phase 1 Study of a Sulforaphane-Containing Broccoli Sprout Homogenate for Sickle Cell Disease.

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Jennifer F Doss

Full Text Available Sickle cell disease (SCD is the most common inherited hemoglobinopathy worldwide. Our previous results indicate that the reduced oxidative stress capacity of sickle erythrocytes may be caused by decreased expression of NRF2 (Nuclear factor (erythroid-derived 2-like 2, an oxidative stress regulator. We found that activation of NRF2 with sulforaphane (SFN in erythroid progenitors significantly increased the expression of NRF2 targets HMOX1, NQO1, and HBG1 (subunit of fetal hemoglobin in a dose-dependent manner. Therefore, we hypothesized that NRF2 activation with SFN may offer therapeutic benefits for SCD patients by restoring oxidative capacity and increasing fetal hemoglobin concentration. To test this hypothesis, we performed a Phase 1, open-label, dose-escalation study of SFN, contained in a broccoli sprout homogenate (BSH that naturally contains SFN, in adults with SCD. The primary and secondary study endpoints were safety and physiological response to NRF2 activation, respectively. We found that BSH was well tolerated, and the few adverse events that occurred during the trial were not likely related to BSH consumption. We observed an increase in the mean relative whole blood mRNA levels for the NRF2 target HMOX1 (p = 0.02 on the last day of BSH treatment, compared to pre-treatment. We also observed a trend toward increased mean relative mRNA levels of the NRF2 target HBG1 (p = 0.10 from baseline to end of treatment, but without significant changes in HbF protein. We conclude that BSH, in the provided doses, is safe in stable SCD patients and may induce changes in gene expression levels. We therefore propose investigation of more potent NRF2 inducers, which may elicit more robust physiological changes and offer clinical benefits to SCD patients. Trial registration: ClinicalTrials.gov NCT01715480.

Changes in SeMSC, glucosinolates and sulforaphane levels, and in proteome profile in broccoli (Brassica oleracea var. Italica) fertilized with sodium selenate.

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Sepúlveda, Ignacio; Barrientos, Herna; Mahn, Andrea; Moenne, Alejandra

2013-05-07

The aim of this work was to analyze the effect of sodium selenate fortification on the content of selenomethyl selenocysteine (SeMSC), total glucosinolates and sulforaphane, as well as the changes in protein profile of the inflorescences of broccoli (Brassica oleracea var. Italica). Two experimental groups were considered: plants treated with 100 μmol/L sodium selenate (final concentration in the pot) and control plants treated with water. Fortification began 2 weeks after transplantation and was repeated once a week during 10 weeks. Broccoli florets were harvested when they reached appropriate size. SeMSC content in broccoli florets increased significantly with sodium selenate fortification; but total glucosinolates and sulforaphane content as well as myrosinase activity were not affected. The protein profile of broccoli florets changed due to fortification with sodium selenate. Some proteins involved in general stress-responses were up-regulated, whereas down-regulated proteins were identified as proteins involved in protection against pathogens. This is the first attempt to evaluate the physiological effect of fortification with sodium selenate on broccoli at protein level. The results of this work will contribute to better understanding the metabolic processes related with selenium uptake and accumulation in broccoli.

Changes in SeMSC, Glucosinolates and Sulforaphane Levels, and in Proteome Profile in Broccoli (Brassica oleracea var. Italica Fertilized with Sodium Selenate

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Alejandra Moenne

2013-05-01

Full Text Available The aim of this work was to analyze the effect of sodium selenate fortification on the content of selenomethyl selenocysteine (SeMSC, total glucosinolates and sulforaphane, as well as the changes in protein profile of the inflorescences of broccoli (Brassica oleracea var. Italica. Two experimental groups were considered: plants treated with 100 mmol/L sodium selenate (final concentration in the pot and control plants treated with water. Fortification began 2 weeks after transplantation and was repeated once a week during 10 weeks. Broccoli florets were harvested when they reached appropriate size. SeMSC content in broccoli florets increased significantly with sodium selenate fortification; but total glucosinolates and sulforaphane content as well as myrosinase activity were not affected. The protein profile of broccoli florets changed due to fortification with sodium selenate. Some proteins involved in general stress-responses were up-regulated, whereas down-regulated proteins were identified as proteins involved in protection against pathogens. This is the first attempt to evaluate the physiological effect of fortification with sodium selenate on broccoli at protein level. The results of this work will contribute to better understanding the metabolic processes related with selenium uptake and accumulation in broccoli.

Sulforaphane Protects against Cardiovascular Disease via Nrf2 Activation

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Yang Bai

2015-01-01

Full Text Available Cardiovascular disease (CVD causes an unparalleled proportion of the global burden of disease and will remain the main cause of mortality for the near future. Oxidative stress plays a major role in the pathophysiology of cardiac disorders. Several studies have highlighted the cardinal role played by the overproduction of reactive oxygen or nitrogen species in the pathogenesis of ischemic myocardial damage and consequent cardiac dysfunction. Isothiocyanates (ITC are sulfur-containing compounds that are broadly distributed among cruciferous vegetables. Sulforaphane (SFN is an ITC shown to possess anticancer activities by both in vivo and epidemiological studies. Recent data have indicated that the beneficial effects of SFN in CVD are due to its antioxidant and anti-inflammatory properties. SFN activates NF-E2-related factor 2 (Nrf2, a basic leucine zipper transcription factor that serves as a defense mechanism against oxidative stress and electrophilic toxicants by inducing more than a hundred cytoprotective proteins, including antioxidants and phase II detoxifying enzymes. This review will summarize the evidence from clinical studies and animal experiments relating to the potential mechanisms by which SFN modulates Nrf2 activation and protects against CVD.

The Relationship between Posttraumatic and Depressive Symptoms during Prolonged Exposure with and without Cognitive Restructuring for the Treatment of Posttraumatic Stress Disorder

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Aderka, Idan M.; Gillihan, Seth J.; McLean, Carmen P.; Foa, Edna B.

2013-01-01

Objective: In the present study, we examined the relationship between posttraumatic and depressive symptoms during prolonged exposure (PE) treatment with and without cognitive restructuring (CR) for the treatment of posttraumatic stress disorder (PTSD). Method: Female assault survivors (N = 153) with PTSD were randomized to either PE alone or PE…

Prolonged vertigo and ataxia after mandibular nerve block for treatment of trigeminal neuralgia

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Arvind Chaturvedi

2011-01-01

Full Text Available Common complications of neurolytic mandibular nerve block are hypoesthesia, dysesthesia, and chemical neuritis. We report a rare complication, prolonged severe vertigo and ataxia, after neurolytic mandibular blockade in a patient suffering from trigeminal neuralgia. Coronoid approach was used for right sided mandibular block. After successful test injection with local anesthetic, absolute alcohol was given for neurolytic block. Immediately after alcohol injection, patient developed nausea and vomiting along with severe vertigo, ataxia and hypertension. Neurological evaluation was normal except for the presence of vertigo and ataxia. Computerised tomography scan brain was also normal. Patient was admitted for observation and symptomatic treatment was given. Vertigo and ataxia gradually improved over 24 hours.

The effect of sulforaphane on the levels of serum cystatin-c in acetaminophen- induced nephrotoxicity in rats

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Eda Dokumacioglu

2016-09-01

Full Text Available Objective: The exposure of living creatures to drugs and chemicals often results in toxicity of liver and kidney. Drugs constitute an important and big part of the commu­nity and hospital-acquired kidney diseases. In this study, we investigated the effect of sulforaphane (SFN on the levels of cystatin-C and lipid peroxidation on acetamino­phen (APAP- induced nephrotoxicity in rats. Methods: Thirty-six Sprague-Dawley rats were separat­ed equally into four experimental groups: control group, SFN group, APAP group, and APAP + SFN group. In the experimental treatment groups APAP was administered oral gavage at 1 g/kg 3 h after SFN treatment in last day and, in the APAP + SFN group, SFN was administered oral gavage at a dose of 500 μg/kg exactly for three days. Rats were euthanized and sacrificed 24 h after APAP ad­ministration. Results: APAP administration showed to significant in­crease in serum BUN, creatinine, urea and LDH concen­trations as compared to the control datas indicating the induction of severe nephrotoxicity (p<0.001. SFN treat­ment significantly decreased the cystatin-C levels and lipid peroxidation compared to APAP group (p<0.05. Conclusion: The present study demonstrate that the at­tachment of SFN to the nephrotoxicity treatment protocol will be beneficial and further studies should be conducted for cystatin C which plays an important role in kidney tox­icity and disease to be routinized as a biomarker.

Ways to Optimize Therapy of Prolonged Conjugation Jaundice in Infants

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O.G. Shadrin

2015-09-01

Full Text Available The article is devoted to the optimization of the treatment of prolonged conjugation jaundice. Inclusion of ursodeoxycholic acid in the treatment of neonatal prolonged conjugation jaundice in a dose of 15–20 mg/kg of body mass per day increases the terms of regression of clinical and paraclinical signs of jaundice as much as 2 times and leads to cytolysis normalization. The preparation has a sufficient level of safety, there were not revealed side effects whilst its application.

d,l-Sulforaphane Induces ROS-Dependent Apoptosis in Human Gliomablastoma Cells by Inactivating STAT3 Signaling Pathway

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Ziwei Miao

2017-01-01

Full Text Available d,l-Sulforaphane (SFN, a synthetic analogue of broccoli-derived isomer l-SFN, exerts cytotoxic effects on multiple tumor cell types through different mechanisms and is more potent than the l-isomer at inhibiting cancer growth. However, the means by which SFN impairs glioblastoma (GBM cells remains poorly understood. In this study, we investigated the anti-cancer effect of SFN in GBM cells and determined the underlying molecular mechanisms. Cell viability assays, flow cytometry, immunofluorescence, and Western blot results revealed that SFN could induced apoptosis of GBM cells in a dose- and time-dependent manner, via up-regulation of caspase-3 and Bax, and down-regulation of Bcl-2. Mechanistically, SFN treatment led to increase the intracellular reactive oxygen species (ROS level in GBM cells. Meanwhile, SFN also suppressed both constitutive and IL-6-induced phosphorylation of STAT3, and the activation of upstream JAK2 and Src tyrosine kinases, dose- and time-dependently. Moreover, blockage of ROS production by using the ROS inhibitor N-acetyl-l-cysteine totally reversed SFN-mediated down-regulation of JAK2/Src-STAT3 signaling activation and the subsequent effects on apoptosis by blocking the induction of apoptosis-related genes in GBM cells. Taken together, our data suggests that SFN induces apoptosis in GBM cells via ROS-dependent inactivation of STAT3 phosphorylation. These findings motivate further evaluation of SFN as a cancer chemopreventive agent in GBM treatment.

Combination of carbonic anhydrase inhibitor, acetazolamide, and sulforaphane, reduces the viability and growth of bronchial carcinoid cell lines

International Nuclear Information System (INIS)

Mokhtari, Reza Bayat; Kumar, Sushil; Islam, Syed S; Yazdanpanah, Mehrdad; Adeli, Khosrow; Cutz, Ernest; Yeger, Herman

2013-01-01

Bronchial carcinoids are pulmonary neuroendocrine cell-derived tumors comprising typical (TC) and atypical (AC) malignant phenotypes. The 5-year survival rate in metastatic carcinoid, despite multiple current therapies, is 14-25%. Hence, we are testing novel therapies that can affect the proliferation and survival of bronchial carcinoids. In vitro studies were used for the dose–response (AlamarBlue) effects of acetazolamide (AZ) and sulforaphane (SFN) on clonogenicity, serotonin-induced growth effect and serotonin content (LC-MS) on H-727 (TC) and H-720 (AC) bronchial carcinoid cell lines and their derived NOD/SCID mice subcutaneous xenografts. Tumor ultra structure was studied by electron microscopy. Invasive fraction of the tumors was determined by matrigel invasion assay. Immunohistochemistry was conducted to study the effect of treatment(s) on proliferation (Ki67, phospho histone-H3) and neuroendocrine phenotype (chromogranin-A, tryptophan hydroxylase). Both compounds significantly reduced cell viability and colony formation in a dose-dependent manner (0–80 μM, 48 hours and 7 days) in H-727 and H-720 cell lines. Treatment of H-727 and H-720 subcutaneous xenografts in NOD/SCID mice with the combination of AZ + SFN for two weeks demonstrated highly significant growth inhibition and reduction of 5-HT content and reduced the invasive capacity of H-727 tumor cells. In terms of the tumor ultra structure, a marked reduction in secretory vesicles correlated with the decrease in 5-HT content. The combination of AZ and SFN was more effective than either single agent. Since the effective doses are well within clinical range and bioavailability, our results suggest a potential new therapeutic strategy for the treatment of bronchial carcinoids

Identifying Molecular Targets For PTSD Treatment Using Single Prolonged Stress

Science.gov (United States)

2014-10-01

Post - traumatic stress disorder ( PTSD ) is a chronic, debilitating psychiatric disorder that can...SPS animals. Post - traumatic stress disorder ( PTSD ) is associated with neurocognitive impairments that have been attributed to functional deficits...and resilience. 2. KEYWORDS Post - traumatic stress disorder , Single Prolonged Stress , Neurobiological Mechanisms 5 3. ACCOMPLISHMENTS

One-Year Outcome of Geriatric Hip-Fracture Patients following Prolonged ICU Treatment

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Daphne Eschbach

2016-01-01

Full Text Available Purpose. Incidence of geriatric fractures is increasing. Knowledge of outcome data for hip-fracture patients undergoing intensive-care unit (ICU treatment, including invasive ventilatory management (IVM and hemodiafiltration (CVVHDF, is sparse. Methods. Single-center prospective observational study including 402 geriatric hip-fracture patients. Age, gender, the American Society of Anesthesiologists (ASA classification, and the Barthel index (BI were documented. Underlying reasons for prolonged ICU stay were registered, as well as assessed procedures like IVM and CVVHDF. Outcome parameters were in-hospital, 6-month, and 1-year mortality and need for nursing care. Results. 15% were treated > 3 days and 68% 3d cohort were significantly increased (p=0.001. Most frequent indications were cardiocirculatory pathology followed by respiratory failure, renal impairment, and infection. 18% of patients needed CVVHDF and 41% IVM. In these cohorts, 6-month mortality ranged > 80% and 12-month mortality > 90%. 100% needed nursing care after 6 and 12 months. Conclusions. ICU treatment > 3 days showed considerable difference in mortality and nursing care needed after 6 and 12 months. Particularly, patients requiring CVVHDF or IVM had disastrous long-term results. Our study may add one further element in complex decision making serving this vulnerable patient cohort.

Enhancement of Cisplatin-Mediated Apoptosis in Ovarian Cancer Cells through Potentiating G2/M Arrest and p21 Upregulation by Combinatorial Epigallocatechin Gallate and Sulforaphane

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Huaping Chen

2013-01-01

Full Text Available Advanced-stage ovarian cancer is characterized by high mortality due to development of resistance to conventional chemotherapy. Novel compounds that can enhance the efficacy of conventional chemotherapy in ovarian cancer may overcome this drug resistance. Consumption of green tea (epigallocatechin gallate, EGCG and cruciferous vegetables (sulforaphane, SFN is inversely associated with occurrence of ovarian cancer and has anticancer effects through targeting multiple molecules in cancer cells. However, the effects of EGCG and SFN combinational treatment on ovarian cancer cells and on efficacy of cisplatin to these cells are unknown. In this study, EGCG or SFN was used to treat both cisplatin-sensitive (A2780 and cisplatin-resistant (A2780/CP20 ovarian cancer cells alone or in combination with cisplatin. We found that EGCG and SFN combinational treatment can reduce cell viability of both ovarian cancer cell lines time- and dose-dependently. Furthermore, EGCG and SFN combinational treatment can enhance cisplatin-induced apoptosis and G2/M phase arrest, thereby enhancing the efficacy of cisplatin on both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. EGCG and SFN combinational treatment upregulated p21 expression induced by cisplatin in cisplatin-sensitive ovarian cancer cells, while p27 expression was not regulated by these treatments. Collectively, these studies provide novel approaches to overcoming cisplatin chemotherapy resistance in ovarian cancer.

Sulforaphane Analogues with Heterocyclic Moieties: Syntheses and Inhibitory Activities against Cancer Cell Lines

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Ye-Hui Shi

2016-04-01

Full Text Available Recent studies have shown that sulforaphane (SFN selectively inhibits the growth of ALDH+ breast cancer stem-like cells.Herein, a series of SFN analogues were synthesized and evaluated against breast cancer cell lines MCF-7 and SUM-159, and the leukemia stem cell-like cell line KG-1a. These SFN analogues were characterized by the replacement of the methyl group with heterocyclic moieties, and the replacement of the sulfoxide group with sulfide or sulfone. A growth inhibitory assay indicated that the tetrazole analogs 3d, 8d and 9d were significantly more potent than SFN against the three cancer cell lines. Compound 14c, the water soluble derivative of tetrazole sulfide 3d, demonstrated higher potency against KG-1a cell line than 3d. SFN, 3d and 14c significantly induced the activation of caspase-3, and reduced the ALDH+ subpopulation in the SUM159 cell line, while the marketed drug doxrubicin(DOX increased the ALDH+ subpopulation.

[Prolonged blockade of nervus ischiadicus in a system of complex treatment of patients, suffering complicated diabetic foot syndrome].

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Shapoval, S D; Savon, I L; Sofilkanych, M M

2015-03-01

General principles of treatment in patients, suffering diabetic foot syndrome, are adduced. There was proved, that reconvalescence of the patients depends not only on quality of complex treatment, but from optimal choice of anesthesia method, its impact on postoperative period course. Application of prolonged blockade of n. ischiadicus gives possibility to perform operative intervention on the lower extremity in full volume, guarantees sufficient motor and sensory block, permits patients to reject from application of narcotic analgetics, to reduce the dose of strong nonnarcotic analgetics, the terms of transition of the wound process phase I into phase II, promotes early activization of patients postoperatively, constitutes alternative for other methods of anesthesiological support.

Sulforaphane Modifies Histone H3, Unpacks Chromatin, and Primes Defense.

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Schillheim, Britta; Jansen, Irina; Baum, Stephani; Beesley, Alexander; Bolm, Carsten; Conrath, Uwe

2018-03-01

Modern crop production calls for agrochemicals that prime plants for enhanced defense. Reliable test systems for spotting priming-inducing chemistry, however, are rare. We developed an assay for the high-throughput search for compounds that prime microbial pattern-induced secretion of antimicrobial furanocoumarins (phytoalexins) in cultured parsley cells. The screen produced 1-isothiocyanato-4-methylsulfinylbutane (sulforaphane; SFN), a secondary metabolite in many crucifers, as a novel defense priming compound. While elucidating SFN's mode of action in defense priming, we found that in Arabidopsis ( Arabidopsis thaliana ) the isothiocyanate provokes covalent modification (K4me3, K9ac) of histone H3 in the promoter and promoter-proximal region of defense genes WRKY6 and PDF1 2 , but not PR1 SFN-triggered H3K4me3 and H3K9ac coincide with chromatin unpacking in the WRKY6 and PDF1 2 regulatory regions, primed WRKY6 expression, unprimed PDF1 2 activation, and reduced susceptibility to downy mildew disease ( Hyaloperonospora arabidopsidis ). Because SFN also directly inhibits H arabidopsidis and other plant pathogens, the isothiocyanate is promising for the development of a plant protectant with a dual mode of action. © 2018 American Society of Plant Biologists. All Rights Reserved.

Prolonged QRS Widening After Aripiprazole Overdose.

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Mazer-Amirshahi, Maryann; Porter, Robert; Dewey, Kayla

2018-05-05

Aripiprazole is an atypical antipsychotic with a long half-life. Overdose can result in protracted somnolence and cardiac disturbances, particularly QT interval prolongation. This is a single case report of a 14-year-old boy who took an overdose of aripiprazole and developed QRS widening. A 14-year-old boy intentionally ingested 20 tablets of aripiprazole (5 mg). He was brought to the emergency department when his ingestion was discovered. The patient's vital signs were as follows: temperature, 37.7°C; heart rate, 108 beats/min; blood pressure, 138/98 mm Hg; and respirations, 16 breaths/min. Activated charcoal was administered within 90 minutes of ingestion. Initial electrocardiogram (EKG) showed sinus tachycardia, with a QRS of 138 ms and QT interval of 444 ms. QRS duration was 90 ms on an EKG performed 3 months earlier. A bolus of sodium bicarbonate was administered, and the patient was transferred to the pediatric intensive care unit. Repeat EKG demonstrated a QRS of 156 ms, and a sodium bicarbonate infusion was initiated. The patient continued to have QRS prolongation for the next 8 days, reaching a peak of 172 ms 3 days postingestion. Despite aggressive treatment with sodium bicarbonate, there was persistent QRS prolongation; however, the patient did not have any dysrhythmias and remained hemodynamically stable. The patient was discharged 9 days postingestion when the QRS duration normalized to 82 ms. Genetic testing revealed that the patient was a CYP2D6 poor metabolizer. This case suggests that aripiprazole toxicity may possibly be associated with QRS prolongation without associated dysrhythmias or cardiovascular compromise. In addition, toxicity may be prolonged in patients who are CYP2D6 poor metabolizers.

Sulforaphane restores cellular glutathione levels and reduces chronic periodontitis neutrophil hyperactivity in vitro.

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Irundika H K Dias

Full Text Available The production of high levels of reactive oxygen species by neutrophils is associated with the local and systemic destructive phenotype found in the chronic inflammatory disease periodontitis. In the present study, we investigated the ability of sulforaphane (SFN to restore cellular glutathione levels and reduce the hyperactivity of circulating neutrophils associated with chronic periodontitis. Using differentiated HL60 cells as a neutrophil model, here we show that generation of extracellular O2 (. - by the nicotinamide adenine dinucleotide (NADPH oxidase complex is increased by intracellular glutathione depletion. This may be attributed to the upregulation of thiol regulated acid sphingomyelinase driven lipid raft formation. Intracellular glutathione was also lower in primary neutrophils from periodontitis patients and, consistent with our previous findings, patients neutrophils were hyper-reactive to stimuli. The activity of nuclear factor erythroid-2-related factor 2 (Nrf2, a master regulator of the antioxidant response, is impaired in circulating neutrophils from chronic periodontitis patients. Although patients' neutrophils exhibit a low reduced glutathione (GSH/oxidised glutathione (GSSG ratio and a higher total Nrf2 level, the DNA-binding activity of nuclear Nrf2 remained unchanged relative to healthy controls and had reduced expression of glutamate cysteine ligase catalytic (GCLC, and modifier (GCLM subunit mRNAs, compared to periodontally healthy subjects neutrophils. Pre-treatment with SFN increased expression of GCLC and GCM, improved intracellular GSH/GSSG ratios and reduced agonist-activated extracellular O2 (. - production in both dHL60 and primary neutrophils from patients with periodontitis and controls. These findings suggest that a deficiency in Nrf2-dependent pathways may underpin susceptibility to hyper-reactivity in circulating primary neutrophils during chronic periodontitis.

Sulforaphane restores cellular glutathione levels and reduces chronic periodontitis neutrophil hyperactivity in vitro.

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Dias, Irundika H K; Chapple, Ian L C; Milward, Mike; Grant, Melissa M; Hill, Eric; Brown, James; Griffiths, Helen R

2013-01-01

The production of high levels of reactive oxygen species by neutrophils is associated with the local and systemic destructive phenotype found in the chronic inflammatory disease periodontitis. In the present study, we investigated the ability of sulforaphane (SFN) to restore cellular glutathione levels and reduce the hyperactivity of circulating neutrophils associated with chronic periodontitis. Using differentiated HL60 cells as a neutrophil model, here we show that generation of extracellular O2 (. -) by the nicotinamide adenine dinucleotide (NADPH) oxidase complex is increased by intracellular glutathione depletion. This may be attributed to the upregulation of thiol regulated acid sphingomyelinase driven lipid raft formation. Intracellular glutathione was also lower in primary neutrophils from periodontitis patients and, consistent with our previous findings, patients neutrophils were hyper-reactive to stimuli. The activity of nuclear factor erythroid-2-related factor 2 (Nrf2), a master regulator of the antioxidant response, is impaired in circulating neutrophils from chronic periodontitis patients. Although patients' neutrophils exhibit a low reduced glutathione (GSH)/oxidised glutathione (GSSG) ratio and a higher total Nrf2 level, the DNA-binding activity of nuclear Nrf2 remained unchanged relative to healthy controls and had reduced expression of glutamate cysteine ligase catalytic (GCLC), and modifier (GCLM) subunit mRNAs, compared to periodontally healthy subjects neutrophils. Pre-treatment with SFN increased expression of GCLC and GCM, improved intracellular GSH/GSSG ratios and reduced agonist-activated extracellular O2 (. -) production in both dHL60 and primary neutrophils from patients with periodontitis and controls. These findings suggest that a deficiency in Nrf2-dependent pathways may underpin susceptibility to hyper-reactivity in circulating primary neutrophils during chronic periodontitis.

Prolonged Exposure Therapy For Post Traumatic Stress Disorder

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Levent SÜTÇİGİL

2012-07-01

Full Text Available Post-traumatic Stress Disorder (PTSD is a psychiatric illness that usually develops after an event that threatens one’s life and body integrity and it affects quality of life and impairs social functioning significantly. Many studies have shown therapeutic effect of cognitive behavioral therapies on posttraumatic stress disorder, so that these therapies take part in the first step of treatment guides. Exposure is a practice that is generally used to reduce pathological fear and related emotions common in posttraumatic stress disorder (PTSD and other anxiety disorders. During exposure, patients intentionally confront with feared objects, situations, thoughts and similar stimuli in order to reduce anxiety level. Exposure can be divided into two main techniques as in vivo exposure and imaginal exposure. Prolonged exposure therapy is a specialized treatment program configured for the treatment of posttraumatic stress disorder and it is based on emotional processing theory. Program is comprised of four main components: (a Psycho-education about trauma and posttraumatic disorders, (b Training for breathing exercises, (c repeated facing with objects, persons, situations and thoughts which causes re-experience about trauma, (d Patient are instructed for telling repeatedly and loudly about traumatic experiences . Prolonged exposure usually involves 9 to 12 sessions, each lasting about 60-90 minutes, administered once or twice a week. Prolonged exposure therapy was started to be implemented since the 1980s, during this period the effectiveness of the therapy has been shown in various empirical studies.

Notch activation is dispensable for D, L-sulforaphane-mediated inhibition of human prostate cancer cell migration.

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Eun-Ryeong Hahm

Full Text Available D, L-Sulforaphane (SFN, a synthetic racemic analog of broccoli constituent L-sulforaphane, is a highly promising cancer chemopreventive agent with in vivo efficacy against chemically-induced as well as oncogene-driven cancer in preclinical rodent models. Cancer chemopreventive effect of SFN is characterized by G(2/M phase cell cycle arrest, apoptosis induction, and inhibition of cell migration and invasion. Moreover, SFN inhibits multiple oncogenic signaling pathways often hyperactive in human cancers, including nuclear factor-κB, Akt, signal transducer and activator of transcription 3, and androgen receptor. The present study was designed to determine the role of Notch signaling, which is constitutively active in many human cancers, in anticancer effects of SFN using prostate cancer cells as a model. Exposure of human prostate cancer cells (PC-3, LNCaP, and/or LNCaP-C4-2B to SFN as well as its naturally-occurring thio-, sulfinyl-, and sulfonyl-analogs resulted in cleavage (activation of Notch1, Notch2, and Notch4, which was accompanied by a decrease in levels of full-length Notch forms especially at the 16- and 24-hour time points. The SFN-mediated cleavage of Notch isoforms was associated with its transcriptional activation as evidenced by RBP-Jk-, HES-1A/B- and HEY-1 luciferase reporter assays. Migration of PC-3 and LNCaP cells was decreased significantly by RNA interference of Notch1 and Notch2, but not Notch4. Furthermore, SFN-mediated inhibition of PC-3 and LNCaP cell migration was only marginally affected by knockdown of Notch1 and Notch2. Strikingly, SFN administration to Transgenic Adenocarcinoma of Mouse Prostate transgenic mice failed to increase levels of cleaved Notch1, cleaved Notch2, and HES-1 proteins in vivo in prostatic intraepithelial neoplasia, well-differentiated carcinoma or poorly-differentiated prostate cancer lesions. These results indicate that Notch activation is largely dispensable for SFN-mediated inhibition of cell

Therapeutic evaluation of prolonged infusions of β-lactam antibiotics in the treatment and management of critically ill patients

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Jorge S. Amador

2017-04-01

Full Text Available Context: Critically ill patients has a large number of pathophysiological changes product of commitment and organ systems. Therefore, knowledge of the pharmacological properties of antimicrobials is essential to choose the best treatment. In order to optimize the response of antibiotic therapy and these drugs, new strategies have been proposed dosage, the most used drug application of the model, called: Pharmacokinetics/Pharmacodynamics (PK/PD. In the case of β-lactam antibiotics, the PK/PD model is known as time-dependent on the Minimum Inhibitory Concentration (Time > MIC. For optimal concentrations in β-lactam antibiotics, prolonged or continuous infusions, thus exposing the drug on the pathogen is achieved in a longer optimal concentrations through are used. Aims: To evaluate the therapeutic response of β-lactam antibiotics in critically ill patients with prolonged infusions by applying the model PK/ PD. Methods: Prospective observational study (concurrent cohort, taking as a control non-concurrent historic cohort, conducted for a period of seven months in the intensive care unit of the Hospital Clínico San Borja Arriarán (HCSBA, Santiago, Chile. Results: It was found a significant difference in number of days of hospitalization in ICU for the group bolus versus infusion group (12.5 ± 5.4 vs. 18 ± 9.7 days, IC: 1.5-9.5; p = 0.009. Conclusions: This study suggests that there would be a therapeutic advantage in the use of prolonged infusion in ICU stay duration.

Prolonged Exposure Therapy For Post Traumatic Stress Disorder

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Levent SÜTÇÝGÝL

2012-08-01

Full Text Available Post-traumatic Stress Disorder (PTSD is a psychiatric illness that usually develops after an event that threatens one’s life and body integrity and it affects quality of life and impairs social functioning significantly. Many studies have shown therapeutic effect of cognitive behavioral therapies on posttraumatic stress disorder, so that these therapies take part in the first step of treatment guides. Exposure is a practice that is generally used to reduce pathological fear and related emotions common in posttraumatic stress disorder (PTSD and other anxiety disorders. During exposure, patients intentionally confront with feared objects, situations, thoughts and similar stimuli in order to reduce anxiety level. Exposure can be divided into two main techniques as in vivo exposure and imaginal exposure. Prolonged exposure therapy is a specialized treatment program configured for the treatment of posttraumatic stress disorder and it is based on emotional processing theory. Program is comprised of four main components: (a Psycho-education about trauma and posttraumatic disorders, (b Training for breathing exercises, (c repeated facing with objects, persons, situations and thoughts which causes re-experience about trauma, (d Patient are instructed for telling repeatedly and loudly about traumatic experiences . Prolonged exposure usually involves 9 to 12 sessions, each lasting about 60-90 minutes, administered once or twice a week. Prolonged exposure therapy was started to be implemented since the 1980s, during this period the effectiveness of the therapy has been shown in various empirical studies. [JCBPR 2012; 1(2.000: 98-104

Sulforaphane is not an effective antagonist of the human pregnane X-receptor in vivo

International Nuclear Information System (INIS)

Poulton, Emma Jane; Levy, Lisa; Lampe, Johanna W.; Shen, Danny D.; Tracy, Julia; Shuhart, Margaret C.; Thummel, Kenneth E.; Eaton, David L.

2013-01-01

Sulforaphane (SFN), is an effective in vitro antagonist of ligand activation of the human pregnane and xenobiotic receptor (PXR). PXR mediated CYP3A4 up-regulation is implicated in adverse drug-drug interactions making identification of small molecule antagonists a desirable therapeutic goal. SFN is not an antagonist to mouse or rat PXR in vitro; thus, normal rodent species are not suitable as in vivo models for human response. To evaluate whether SFN can effectively antagonize ligand activation of human PXR in vivo, a three-armed, randomized, crossover trial was conducted with 24 healthy adults. The potent PXR ligand — rifampicin (300 mg/d) was given alone for 7 days in arm 1, or in daily combination with 450 μmol SFN (Broccoli Sprout extract) in arm 2; SFN was given alone in arm 3. Midazolam as an in vivo phenotype marker of CYP3A was administered before and after each treatment arm. Rifampicin alone decreased midazolam AUC by 70%, indicative of the expected increase in CYP3A4 activity. Co-treatment with SFN did not reduce CYP3A4 induction. Treatment with SFN alone also did not affect CYP3A4 activity in the cohort as a whole, although in the subset with the highest basal CYP3A4 activity there was a statistically significant increase in midazolam AUC (i.e., decrease in CYP3A4 activity). A parallel study in humanized PXR mice yielded similar results. The parallel effects of SFN between humanized PXR mice and human subjects demonstrate the predictive value of humanized mouse models in situations where species differences in ligand-receptor interactions preclude the use of a native mouse model for studying human ligand-receptor pharmacology. -- Highlights: ► The effects of SFN on PXR mediated CYP3A4 induction in humanized PXR mice and humans were examined. ► SFN had no effect on rifampicin mediated CYP3A4 induction in humans or humanized mice. ► SFN had a modest effect on basal CYP3A4 activity among subjects with higher baseline activity. ► Humanized PXR

Efficacy of prolonged antimicrobial chemotherapy for brucellar spondylodiscitis.

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Ioannou, S; Karadima, D; Pneumaticos, S; Athanasiou, H; Pontikis, J; Zormpala, A; Sipsas, N V

2011-05-01

The standard treatment of brucellar spondylitis with a combination of two antibiotics for 6-12 weeks is associated with high rates of treatment failure and relapse. The present study aimed to assess the safety and efficacy of a treatment strategy based on the prolonged administration of a triple combination of suitable antibiotics. Eighteen patients with brucellar spondylitis were treated with a combination of at least three suitable antibiotics (doxycycline, rifampin, plus intramuscular streptomycin or cotrimoxazole or ciprofloxacin) until the completion of at least 6 months of treatment, when clinical, radiological and serology re-evaluation was performed. If necessary, the treatment was continued with additional 6-month cycles, until resolution or significant improvement of clinical and radiological findings, or for a maximum of 18 months. At presentation, the median age was 66 years (range, 42-85 years) with male predominance. The median duration of therapy was 48 weeks (range 24-72 weeks). Treatment was discontinued early because of side-effects in only one patient. Surgical intervention was required for three patients. At the end of treatment all patients had a complete response. After completion of treatment, all patients were followed up with regular visits. During the follow-up period (duration 1-96 months, median 36.5 months), no relapses were observed. In conclusion, prolonged (at least 6 months) administration of a triple combination of suitable antibiotics appears to be an effective treatment for brucellar spondylitis. © 2010 The Authors. Clinical Microbiology and Infection © 2010 European Society of Clinical Microbiology and Infectious Diseases.

Cultural Adaptations of Prolonged Exposure Therapy for Treatment and Prevention of Posttraumatic Stress Disorder in African Americans

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Monnica T. Williams

2014-05-01

Full Text Available Posttraumatic stress disorder (PTSD is a highly disabling disorder, afflicting African Americans at disproportionately higher rates than the general population. When receiving treatment, African Americans may feel differently towards a European American clinician due to cultural mistrust. Furthermore, racism and discrimination experienced before or during the traumatic event may compound posttrauma reactions, impacting the severity of symptoms. Failure to adapt treatment approaches to encompass cultural differences and racism-related traumas may decrease treatment success for African American clients. Cognitive behavioral treatment approaches are highly effective, and Prolonged Exposure (PE in particular has the most empirical support for the treatment of PTSD. This article discusses culturally-informed adaptations of PE that incorporates race-related trauma themes specific to the Black experience. These include adding more sessions at the front end to better establish rapport, asking directly about race-related themes during the assessment process, and deliberately bringing to the forefront race-related experiences and discrimination during treatment when indicated. Guidelines for assessment and the development of appropriate exposures are provided. Case examples are presented demonstrating adaptation of PE for a survivor of race-related trauma and for a woman who developed internalized racism following a sexual assault. Both individuals experienced improvement in their posttrauma reactions using culturally-informed adaptations to PE.

Prolonged conservative treatment or 'early' surgery in sciatica caused by a lumbar disc herniation: rationale and design of a randomized trial [ISRCT 26872154

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Peul, Wilco C; van Houwelingen, Hans C; van der Hout, Wilbert B; Brand, Ronald; Eekhof, Just AH; Tans, Joseph ThJ; Thomeer, Ralph TWM; Koes, Bart W

2005-01-01

Background The design of a randomized multicenter trial is presented on the effectiveness of a prolonged conservative treatment strategy compared with surgery in patients with persisting intense sciatica (lumbosacral radicular syndrome). Methods/design Patients presenting themselves to their general practitioner with disabling sciatica lasting less than twelve weeks are referred to the neurology outpatient department of one of the participating hospitals. After confirmation of the diagnosis and surgical indication MRI scanning is performed. If a distinct disc herniation is discerned which in addition covers the clinically expected site the patient is eligible for randomization. Depending on the outcome of the randomization scheme the patient will either be submitted to prolonged conservative care or surgery. Surgery will be carried out according to the guidelines and between six and twelve weeks after onset of complaints. The experimental therapy consists of a prolonged conservative treatment under supervision of the general practitioner, which may be followed by surgical intervention in case of persisting or progressive disability. The main primary outcome measure is the disease specific disability of daily functioning. Other primary outcome measures are perceived recovery and intensity of legpain. Secondary outcome measures encompass severity of complaints, quality of life, medical consumption, absenteeism, costs and preference. The main research question will be answered at 12 months after randomization. The total follow-up period covers two years. Discussion Evidence is lacking concerning the optimal treatment of lumbar disc induced sciatica. This pragmatic randomized trial, focusses on the 'timing' of intervention, and will contribute to the decision of the general practictioner and neurologist, regarding referral of patients for surgery. PMID:15707491

Glycyrrhizin Treatment Facilitates Extinction of Conditioned Fear Responses After a Single Prolonged Stress Exposure in Rats

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Shuhua Lai

2018-03-01

Full Text Available Background/Aims: Impaired fear memory extinction is widely considered a key mechanism of post-traumatic stress disorder (PTSD. Recent studies have suggested that neuroinflammation after a single prolonged stress (SPS exposure may play a critical role in the impaired fear memory extinction. Studies have shown that high mobility group box chromosomal protein 1 (HMGB-1 is critically involved in neuroinflammation. However, the role of HMGB-1 underlying the development of impairment of fear memory extinction is still not known. Methods: Thus, we examined the levels of HMGB-1 in the basolateral amygdala (BLA following SPS using Western blot and evaluated the levels of microglia and astrocytes activation in the BLA after SPS using immunohistochemical staining. We then examined the effects of pre-SPS intra-BLA administration of glycyrrhizin, an HMGB1 inhibitor, or LPS-RS, a competitive TLR4 antagonist, on subsequent post-SPS fear extinction. Results: We found that SPS treatment prolonged the extinction of contextual fear memory after the SPS. The impairment of SPS-induced extinction of contextual fear memory was associated with increased HMGB1 and Toll-like receptor 4 (TLR4 levels in the BLA. Additionally, the impairment of SPS-induced extinction of contextual fear memory was associated with increased activation of microglia and astrocyte in the BLA. Intra-BLA administrations of glycyrrhizin (HMGB-1 inhibitor or LPS-RS (TLR4 antagonist can prevent the development of SPS-induced fear extinction impairment. Conclusion: Taken together, these results suggested that SPS treatment may not only produce short term effects on the HMGB1/TLR4-mediated pro-inflammation, but alter the response of microglia and astrocytes to the exposure to fear associated contextual stimuli.

Glycyrrhizin Treatment Facilitates Extinction of Conditioned Fear Responses After a Single Prolonged Stress Exposure in Rats.

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Lai, Shuhua; Wu, Gangwei; Jiang, Zhixian

2018-01-01

Impaired fear memory extinction is widely considered a key mechanism of post-traumatic stress disorder (PTSD). Recent studies have suggested that neuroinflammation after a single prolonged stress (SPS) exposure may play a critical role in the impaired fear memory extinction. Studies have shown that high mobility group box chromosomal protein 1 (HMGB-1) is critically involved in neuroinflammation. However, the role of HMGB-1 underlying the development of impairment of fear memory extinction is still not known. Thus, we examined the levels of HMGB-1 in the basolateral amygdala (BLA) following SPS using Western blot and evaluated the levels of microglia and astrocytes activation in the BLA after SPS using immunohistochemical staining. We then examined the effects of pre-SPS intra-BLA administration of glycyrrhizin, an HMGB1 inhibitor, or LPS-RS, a competitive TLR4 antagonist, on subsequent post-SPS fear extinction. We found that SPS treatment prolonged the extinction of contextual fear memory after the SPS. The impairment of SPS-induced extinction of contextual fear memory was associated with increased HMGB1 and Toll-like receptor 4 (TLR4) levels in the BLA. Additionally, the impairment of SPS-induced extinction of contextual fear memory was associated with increased activation of microglia and astrocyte in the BLA. Intra-BLA administrations of glycyrrhizin (HMGB-1 inhibitor) or LPS-RS (TLR4 antagonist) can prevent the development of SPS-induced fear extinction impairment. Taken together, these results suggested that SPS treatment may not only produce short term effects on the HMGB1/TLR4-mediated pro-inflammation, but alter the response of microglia and astrocytes to the exposure to fear associated contextual stimuli. © 2018 The Author(s). Published by S. Karger AG, Basel.

The Winter Procedure as Management for Prolonged Low-Flow Priapism: A Case Report

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Hsi-Lin Hsiao

2007-10-01

Full Text Available Priapism is a prolonged penile erection that is not associated with sexual stimulation. Although the time course has not been formally defined, it is usually considered to be one that lasts for more than 4–6 hours. Low-flow (ischemic priapism is usually associated with sickle cell disease, hemoglobinopathies, neoplastic syndrome, anticoagulant therapy, psychotropic medication or idiopathic causes. Here, we report a case of prolonged low-flow priapism lasting for 2 weeks, which was successfully treated with the Winter procedure after several attempts of conservative treatment. Although the potency remains unclear and the patient needs a longer period of follow-up, the case reported here still shows that prolonged low-flow priapism can be successfully treated with the Winter procedure when conservative treatments fail.

Disseminated Mycobacterium celatum disease with prolonged pulmonary involvement

DEFF Research Database (Denmark)

Patsche, Cecilie Blenstrup; Svensson, Erik; Wejse, Christian

2014-01-01

Mycobacterium celatum is a rare cause of human infection, causing disseminated disease in immunosuppressed individuals. Infections localized to the lungs and the lymph nodes have also been reported in immunocompetent individuals. The existing literature on the subject is limited as are experiences...... with treatment regimens and durations. In the case presented herein, two different treatment regimens were applied to an immunocompromised HIV-negative patient with primary skin involvement and extensive pulmonary involvement due to suspected relapse on isoniazid, ethambutol, and clarithromycin treatment....... The treatment regimen was changed to azithromycin, ciprofloxacin, and pyrazinamide and the treatment duration was prolonged to a total of 24 months, with good effect....

Severe bradycardia and prolonged hypotension in ciguatera.

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Chan, Thomas Yan Keung

2013-06-01

Ciguatera results when ciguatoxin-contaminated coral reef fish from tropical or subtropical waters are consumed. The clinical features that present in affected persons are mainly gastrointestinal, neurological, general, and much less commonly, cardiovascular. We report the case of a 50-year-old man who developed the characteristic combination of acute gastrointestinal and neurological symptoms after the consumption of an unidentified coral reef fish head. In addition to those symptoms, he developed dizziness, severe bradycardia (46 bpm) and prolonged hypotension, which required the administration of intravenous atropine and over three days of intravenous fluid replacement with dopamine infusion. Patients with ciguatera can develop severe bradycardia and prolonged hypotension. Physicians should recognise the possible cardiovascular complications of ciguatera and promptly initiate treatment with intravenous atropine, intravenous fluid replacement and inotropic therapy if such complications are observed.

Cardiovascular drugs inducing QT prolongation: facts and evidence.

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Taira, Carlos A; Opezzo, Javier A W; Mayer, Marcos A; Höcht, Christian

2010-01-01

Acquired QT syndrome is mainly caused by the administration of drugs that prolong ventricular repolarization. On the other hand, the risk of drug-induced torsades de pointes is increased by numerous predisposing factors, such as genetic predisposition, female sex, hypokalemia and cardiac dysfunction. This adverse reaction is induced by different chemical compounds used for the treatment of a variety of pathologies, including arrhythmias. As it is known, antiarrhythmic agents and other cardiovascular drugs can prolong the QT interval, causing this adverse reaction. Of the 20 most commonly reported drugs, 10 were cardiovascular agents and these appeared in 348 of the reports (46%). Class Ia antiarrhythmic agents have frequently been linked to inducing arrhythmia, including torsades de pointes. Sotalol and amiodarone, class III antiarrhythmics, are known to prolong the QT interval by blocking I(Kr). Due to the severity of events caused by the therapeutic use of these drugs, in this work of revision the cardiovascular drugs that present this property and the factors and evidence will be mentioned.

Cell cycle effects of L-sulforaphane, a major antioxidant from cruciferous vegetables: The role of the anaphase promoting complex.

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Shelley, Zhaoping; Royce, Simon G; Ververis, Katherine; Karagiannis, Tom C

2014-01-01

L-sulforaphane (LSF) is a natural isothiocyanate found in cruciferous vegetables particularly broccoli. LSF has been identified as a potent antioxidant and anti-cancer agent and is widely known to regulate phase II detoxifying enzymes and induce cell cycle arrest or apoptosis in malignant cells in vitro and in vivo. Previous studies have found significant G2/M cell cycle arrest in response to LSF in various model of cancer and results have mainly been attributed to increased cyclin B1 protein levels and increased p21expression. Using genome-wide mRNA-Seq analysis we provide insights into the molecular mechanisms of action of LSF to identify a key pathway in cell cycle progression - the role of the anaphase promoting complex (APC) pathway. We evaluated gene expression changes in human erythroleukemic K562 cells following treatment with 15 μM LSF for 48h and compared them to immortalized human keratinocytes, human microvascular endothelial cells (HMEC-1) cells and normal human umbilical endothelial cells (HUVEC). We identified disparate gene expression changes in response to LSF between malignant and normal cells and immortalized cell lines. The results highlight significant down-regulation of kinase CDK1 which is suggestive that the existence and activity of APC/CDC20 complex will be inhibited along with its associated down-stream degradation of key cell cycle regulators preventing cell cycle progression from mitotic exit.

Psychotropic Pharmacotherapy Associated With QT Prolongation Among Veterans With Posttraumatic Stress Disorder.

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Stock, Eileen M; Zeber, John E; McNeal, Catherine J; Banchs, Javier E; Copeland, Laurel A

2018-04-01

In 2012, the Food and Drug Administration issued Drug Safety Communications on several drugs associated with QT prolongation and fatal ventricular arrhythmias. Among these was citalopram, a selective serotonin reuptake inhibitor (SSRI) approved for depression and commonly used for posttraumatic stress disorder (PTSD). Evaluation of the risk for QT prolongation among other psychotropic drugs for individuals with PTSD remains limited. Explore psychotropic drugs associated with QT prolongation among veterans with PTSD. Patients in the Veterans Health Administration in 2006-2009 with PTSD and QT prolongation (176 cases) were matched 1:4 on age, gender, visit date and setting, and physical comorbidity. Classification trees assessed QT prolongation risk among prescribed medications (n=880). Receipt of any drug with known risk of QT prolongation varied by group (23% QT cases vs 15% control, prisks included ziprasidone (3% vs 1%, p=0.02) and buspirone (6% vs 2%, p=0.01). Increased risk was not observed for the SSRIs, citalopram and fluoxetine. Classification trees found that sotalol and amitriptyline carried greater risk among cardiac patients and methadone, especially if prescribed with quetiapine, among noncardiac patients. Per adjusted survival model, patients with QT prolongation were at increased risk for death (hazard ratio=1.60; 95% CI=1.04-2.44). Decision models are particularly advantageous when exploring nonlinear relationships or nonadditive interactions. These findings may potentially affect clinical decision-making concerning treatment for PTSD. For patients at higher risk of QT prolongation, antidepressants other than amitriptyline should be considered. Medications for comorbid conditions should also be closely monitored for heightened QT prolongation risk.

The parents' ability to take care of their baby as a factor in decisions to withhold or withdraw life-prolonging treatment in two Dutch NICUs

NARCIS (Netherlands)

Moratti, Sofia

In The Netherlands, it is openly acknowledged that the parents' ability to take care of their child plays a role in the decision-making process over administration of life-prolonging treatment to severely defective newborn babies. Unlike other aspects of such decision-making process up until the

Colorectal Transit and Volume During Treatment With Prolonged-release Oxycodone/Naloxone Versus Oxycodone Plus Macrogol 3350.

Science.gov (United States)

Poulsen, Jakob L; Mark, Esben B; Brock, Christina; Frøkjær, Jens B; Krogh, Klaus; Drewes, Asbjørn M

2018-01-30

Opioid-induced constipation (OIC) is the most common gastrointestinal (GI) side effect to opioid treatment. Opioid receptor antagonists against OIC have been introduced, but their efficacy has not been directly compared to conventional laxatives. Our aim was to compare symptoms and objective parameters of gut function in an experimental model of OIC during treatment with the opioid antagonist naloxone and oxycodone in prolonged-release (PR) formulation versus oxycodone plus macrogol 3350. In this randomized, double-blind, crossover trial 20 healthy men received a 5-day treatment of combined PR oxycodone/naloxone or PR oxycodone plus macrogol 3350. Regional GI transit times and segmental colorectal transit were assessed with the Motilis 3D-Transit electromagnetic capsule system. Colorectal volumes were determined by MRI. OIC symptoms were assessed with validated questionnaires, along with stool frequency and consistency. Total colorectal volume did not change after 5 days' treatment with PR oxycodone/naloxone (941 vs 1036 mL; P = 0.091), but increased significantly after PR oxycodone plus macrogol treatment (912 vs 1123 mL; P transit times nor segmental colorectal transit differed between the treatments (all P > 0.05). The Patient Assessment of Constipation Symptom Questionnaire abdominal symptoms score was lower during PR oxycodone/naloxone compared to PR oxycodone plus macrogol (0.2 vs 3.2; P = 0.002). Stool frequency was lower during PR oxycodone/naloxone compared to PR oxycodone plus macrogol (4.2 vs 5.4; P = 0.035). PR oxycodone plus macrogol increases colorectal volume, but does not improve GI transit compared to PR oxycodone/naloxone. However, PR oxycodone/naloxone results in a lower abdominal symptom burden, despite higher stool frequency during macrogol treatment.

Prolonged treatment with N-acetylcysteine and L-arginine restores gonadal function in patients with polycystic ovary syndrome.

Science.gov (United States)

Masha, A; Manieri, C; Dinatale, S; Bruno, G A; Ghigo, E; Martina, V

2009-12-01

Nitric oxide (NO) plays a wide spectrum of biological actions including a positive role in oocyte maturation and ovulation. Free radicals levels have been shown elevated in polycystic ovary syndrome (PCOS) and therefore would be responsible for quenching NO that, in turn, would play a role in determining oligo- or amenorrhea connoting PCOS. Eight patients with PCOS displaying oligo-amenorrhea from at least 1 yr underwent a combined treatment with N-acetylcysteine (NAC) (1200 mg/die) plus L-arginine (ARG) (1600 mg/die) for 6 months. Menstrual function, glucose and insulin levels, and, in turn, homeostasis model assessment (HOMA) index were monitored. Menstrual function was at some extent restored as indicated by the number of uterine bleedings under treatment (3.00, 0.18-5.83 vs 0.00, 0.00-0.83; p<0.02). Also, a well-defined biphasic pattern in the basal body temperature suggested ovulatory cycles. The HOMA index decreased under treatment (2.12, 1.46-4.42 vs 3.48, 1.62-5.95; p<0.05). In conclusion, this preliminary, open study suggests that prolonged treatment with NAC+ARG might restore gonadal function in PCOS. This effect seems associated to an improvement in insulin sensitivity.

Experimental therapy of epilepsy with transcranial magnetic stimulation: lack of additional benefit with prolonged treatment

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Brasil-Neto Joaquim P.

2004-01-01

Full Text Available OBJECTIVE: To investigate the effect of three months of low-frequency repetitive transcranial magnetic stimulation (rTMS treatment in intractable epilepsy. METHODS: Five patients (four males, one female; ages 6 to 50 years, were enrolled in the study; their epilepsy could not be controlled by medical treatment and surgery was not indicated. rTMS was performed twice a week for three months; patients kept records of seizure frequency for an equal period of time before, during, and after rTMS sessions. rTMS was delivered to the vertex with a round coil, at an intensity 5 % below motor threshold. During rTMS sessions, 100 stimuli (five series of 20 stimuli, with one-minute intervals between series were delivered at a frequency of 0.3 Hz. RESULTS: Mean daily number of seizures (MDNS decreased in three patients and increased in two during rTMS- one of these was treated for only one month; the best result was achieved in a patient with focal cortical dysplasia (reduction of 43.09 % in MDNS. In the whole patient group, there was a significant (p<0.01 decrease in MDNS of 22.8 %. CONCLUSION: Although prolonged rTMS treatment is safe and moderately decreases MDNS in a group of patients with intractable epilepsy, individual patient responses were mostly subtle and clinical relevance of this method is probably low. Our data suggest, however, that patients with focal cortical lesions may indeed benefit from this novel treatment. Further studies should concentrate on that patient subgroup.

Incidence and risk of QTc interval prolongation among cancer patients treated with vandetanib: a systematic review and meta-analysis.

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Jiajie Zang

Full Text Available Vandetanib is a multikinase inhibitor that is under assessment for the treatment of various cancers. QTc interval prolongation is one of the major adverse effects of this drug, but the reported incidence varies substantially among clinical trials. We performed a systematic review and meta-analysis to obtain a better understanding in the risk of QTc interval prolongation among cancer patients administered vandetanib.Eligible studies were phase II and III prospective clinical trials that involved cancer patients who were prescribed vandetanib 300 mg/d and that included data on QTc interval prolongation. The overall incidence and risk of QTc interval prolongation were calculated using random-effects or fixed-effects models, depending on the heterogeneity of the included studies. Nine trials with 2,188 patients were included for the meta-analysis. The overall incidence of all-grade and high-grade QTc interval prolongation was 16.4% (95% CI, 8.1-30.4% and 3.7% (8.1-30.4%, respectively, among non-thyroid cancer patients, and 18.0% (10.7-28.6% and 12.0% (4.5-28.0%, respectively, among thyroid cancer patients. Patients with thyroid cancer who had longer treatment duration also had a higher incidence of high-grade events, with a relative risk of 3.24 (1.57-6.71, than patients who had non-thyroid cancer. Vandetanib was associated with a significantly increased risk of all-grade QTc interval prolongation with overall Peto odds ratios of 7.26 (4.36-12.09 and 5.70 (3.09-10.53 among patients with non-thyroid cancer and thyroid cancer, respectively, compared to the controls.Treatment with vandetanib is associated with a significant increase in the overall incidence and risk of QTc interval prolongation. Different cancer types and treatment durations may affect the risk of developing high-grade QTc interval prolongation.

Pre-treatment Predictors of Dropout from Prolonged Exposure Therapy in Patients with Chronic Posttraumatic Stress Disorder and Comorbid Substance Use Disorders

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Belleau, Emily L.; Chin, Eu Gene; Wanklyn, Sonya G.; Zambrano-Vazquez, Laura; Schumacher, Julie A.; Coffey, Scott F.

2017-01-01

Posttraumatic stress disorder (PTSD) and substance use disorders (SUDs) are commonly co-occurring disorders associated with more adverse consequences than PTSD alone. Prolonged exposure therapy (PE) is one of the most efficacious treatments for PTSD. However, among individuals with PTSD-SUD, 35–62% of individuals drop out of trauma-focused exposure treatments. Thus, it is important to identify predictors of PTSD treatment dropout among substance abusers with PTSD in order to gain information about adapting treatment strategies to enhance retention and outcomes. The current study explored pre-treatment predictors of early termination from PE treatment in a sample of 85 individuals receiving concurrent treatment for PTSD and a SUD in a residential treatment facility as part of a randomized controlled trial. The results indicated that less education and more anxiety sensitivity uniquely predicted PE treatment dropout. Demographic variables, PTSD severity, SUD severity, mental health comorbidities, and emotion regulation difficulties did not predict treatment dropout. These results suggest that adding pre-treatment interventions that address anxiety sensitivity, and promote social adjustment and cognitive flexibility, could possibly improve PE retention rates in clients with high anxiety or low education. PMID:28147254

Sulforaphane induces cell cycle arrest by protecting RB-E2F-1 complex in epithelial ovarian cancer cells

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Morris Robert

2010-03-01

Full Text Available Abstract Background Sulforaphane (SFN, an isothiocyanate phytochemical present predominantly in cruciferous vegetables such as brussels sprout and broccoli, is considered a promising chemo-preventive agent against cancer. In-vitro exposure to SFN appears to result in the induction of apoptosis and cell-cycle arrest in a variety of tumor types. However, the molecular mechanisms leading to the inhibition of cell cycle progression by SFN are poorly understood in epithelial ovarian cancer cells (EOC. The aim of this study is to understand the signaling mechanisms through which SFN influences the cell growth and proliferation in EOC. Results SFN at concentrations of 5 - 20 μM induced a dose-dependent suppression of growth in cell lines MDAH 2774 and SkOV-3 with an IC50 of ~8 μM after a 3 day exposure. Combination treatment with chemotherapeutic agent, paclitaxel, resulted in additive growth suppression. SFN at ~8 μM decreased growth by 40% and 20% on day 1 in MDAH 2774 and SkOV-3, respectively. Cells treated with cytotoxic concentrations of SFN have reduced cell migration and increased apoptotic cell death via an increase in Bak/Bcl-2 ratio and cleavage of procaspase-9 and poly (ADP-ribose-polymerase (PARP. Gene expression profile analysis of cell cycle regulated proteins demonstrated increased levels of tumor suppressor retinoblastoma protein (RB and decreased levels of E2F-1 transcription factor. SFN treatment resulted in G1 cell cycle arrest through down modulation of RB phosphorylation and by protecting the RB-E2F-1 complex. Conclusions SFN induces growth arrest and apoptosis in EOC cells. Inhibition of retinoblastoma (RB phosphorylation and reduction in levels of free E2F-1 appear to play an important role in EOC growth arrest.

Subtleties in practical application of prolonged infusion of β-lactam antibiotics.

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De Waele, Jan J; Lipman, Jeffrey; Carlier, Mieke; Roberts, Jason A

2015-05-01

Prolonged infusion (PI) of β-lactam antibiotics is increasingly used in order to optimise antibiotic exposure in critically ill patients. Physicians are often not aware of a number of subtleties that may jeopardise the treatment. In this clinically based paper, we stress pragmatic issues, such as the importance of a loading dose before PI, and discuss a number of important practicalities that are mandatory to benefit from the pharmacokinetic advantages of prolonged β-lactam antibiotic administration. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Sulforaphane Induces Cell Death Through G2/M Phase Arrest and Triggers Apoptosis in HCT 116 Human Colon Cancer Cells.

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Liu, Kuo-Ching; Shih, Ting-Ying; Kuo, Chao-Lin; Ma, Yi-Shih; Yang, Jiun-Long; Wu, Ping-Ping; Huang, Yi-Ping; Lai, Kuang-Chi; Chung, Jing-Gung

2016-01-01

Sulforaphane (SFN), an isothiocyanate, exists exclusively in cruciferous vegetables, and has been shown to possess potent antitumor and chemopreventive activity. However, there is no available information that shows SFN affecting human colon cancer HCT 116 cells. In the present study, we found that SFN induced cell morphological changes, which were photographed by contrast-phase microscopy, and decreased viability. SFN also induced G2/M phase arrest and cell apoptosis in HCT 116 cells, which were measured with flow cytometric assays. Western blotting indicated that SFN increased Cyclin A, cdk 2, Cyclin B and WEE1, but decreased Cdc 25C, cdk1 protein expressions that led to G2/M phase arrest. Apoptotic cell death was also confirmed by Annexin V/PI and DAPI staining and DNA gel electrophoresis in HCT 116 cells after exposure to SFN. The flow cytometric assay also showed that SFN induced the generation of reactive oxygen species (ROS) and Ca[Formula: see text] and decreased mitochondria membrane potential and increased caspase-8, -9 and -3 activities in HCT 116 cell. Western blotting also showed that SFN induced the release of cytochrome c, and AIF, which was confirmed by confocal microscopy examination. SFN induced ER stress-associated protein expression. Based on those observations, we suggest that SFN may be used as a novel anticancer agent for the treatment of human colon cancer in the future.

Sulforaphane, a Dietary Isothiocyanate, Induces G2/M Arrest in Cervical Cancer Cells through CyclinB1 Downregulation and GADD45β/CDC2 Association

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Ya-Min Cheng

2016-09-01

Full Text Available Globally, cervical cancer is the most common malignancy affecting women. The main treatment methods for this type of cancer include conization or hysterectomy procedures. Sulforaphane (SFN is a natural, compound-based drug derived from dietary isothiocyanates which has previously been shown to possess potent anti-tumor and chemopreventive effects against several types of cancer. The present study investigated the effects of SFN on anti-proliferation and G2/M phase cell cycle arrest in cervical cancer cell lines (Cx, CxWJ, and HeLa. We found that cytotoxicity is associated with an accumulation of cells in the G2/M phases of the cell-cycle. Treatment with SFN led to cell cycle arrest as well as the down-regulation of Cyclin B1 expression, but not of CDC2 expression. In addition, the effects of GADD45β gene activation in cell cycle arrest increase proportionally with the dose of SFN; however, mitotic delay and the inhibition of proliferation both depend on the dosage of SFN used to treat cancer cells. These results indicate that SFN may delay the development of cancer by arresting cell growth in the G2/M phase via down-regulation of Cyclin B1 gene expression, dissociation of the cyclin B1/CDC2 complex, and up-regulation of GADD45β proteins.

Sulforaphane Modulates Joint Inflammation in a Murine Model of Complete Freund’s Adjuvant-Induced Mono-Arthritis

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João Francisco Silva Rodrigues

2018-04-01

Full Text Available Rheumatoid arthritis (RA is characterized by inflammation of one or more joints, and affects ~1% of the adult population worldwide. Sulforaphane (SFN is a natural compound that has been suggested as an antioxidant. Here, SFN’s effects were evaluated in a murine mono-arthritis model. Mono-arthritis was induced in mice by a single intra-articular injection of Complete Freund’s Adjuvant (CFA-10 µg/joint, in 10 µL into the ipsilateral joint. The contralateral joint received an equal volume of PBS. On the 4th day post-joint inflammation induction, animals received either SFN (10 mg/kg or vehicle (3% DMSO in saline, intraperitoneally (i.p., twice a day for 3 days. Joint swelling and secondary mechanical allodynia and hyperalgesia were evaluated over 7 days post-CFA. After this period, animals were culled and their blood and synovial fluid samples were collected for analysis of cell populations, cytokine release and thioredoxin reductase (TrxR activity. Knee joint samples were also collected for histology. SFN reduced joint swelling and damage whilst increasing the recruitment of Ly6C+ and Ly6G+ cells to CFA-injected joints. SFN-treated animals presented down-regulation of CD11b and CD62L on synovial fluid Ly6G+ cells. Synovial fluid samples obtained from CFA-injected joints and plasma samples of SFN-treated mice presented higher levels of IL-6 and increased activity of TrxR, in comparison with controls. These results indicate that SFN reduces knee joint damage by modulating cell activation/migration to the joints, cytokine production and increasing the activity of TrxR, and therefore, may represent an alternative treatment to joint inflammation.

Chemical pleurodesis for prolonged postoperative air leak in primary spontaneous pneumothorax

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Cheng-Hung How

2014-05-01

Conclusion: Chemical pleurodesis using OK-432 or minocycline is safe and convenient for prolonged air leak after thoracoscopic treatment for PSP. Our experience suggested that OK-432 may be more effective than minocycline in reducing air leak.

Prolonged first-line PEG-asparaginase treatment in pediatric acute lymphoblastic leukemia in the NOPHO ALL2008 protocol-Pharmacokinetics and antibody formation

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Tram Henriksen, Louise; Gottschalk Højfeldt, Sofie; Schmiegelow, Kjeld

2017-01-01

BACKGROUND: As pegylated asparaginase is becoming the preferred first-line asparaginase preparation in the chemotherapy regimens of childhood acute lymphoblastic leukemia (ALL), there is a need to evaluate this treatment. METHODS: The aim of this study was to evaluate the pharmacokinetics...... of prolonged upfront biweekly PEG-asparaginase (where PEG is polyethylene glycol) treatment by measuring serum l-asparaginase activity and formation of anti-PEG-asparaginase antibodies. A total of 97 evaluable patients (1-17 years), diagnosed with ALL, and treated according to the NOPHO ALL2008 protocol (where...... NOPHO is Nordic Society of Paediatric Haematology and Oncology) were included. In the NOPHO ALL2008 protocol, patients are randomized to 8 or 15 doses of intramuscular PEG-asparaginase (Oncaspar(®) ) 1,000 IU/m²/dose, at 2-week or 6-week intervals with a total of 30-week treatment (Clinical trials...

Physiological response of rabbit bucks to prolonged feeding of ...

African Journals Online (AJOL)

Sixty-four (64) weanling rabbit bucks, 5 to 6 weeks old, were involved in a 2 x 4 factorial experiment to evaluate the effects of prolonged feeding of cottonseed cake (CSC) – based diets with or without vitamin E supplementation on the physiological response of the bucks. There were eight treatment combinations comprising ...

Effectiveness of Cognitive Processing Therapy and Prolonged Exposure in the Department of Veterans Affairs.

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Rutt, Benjamin T; Oehlert, Mary E; Krieshok, Thomas S; Lichtenberg, James W

2018-04-01

Objective This study evaluated the effectiveness of cognitive processing therapy and prolonged exposure in conditions reflective of current clinical practice within the Veterans Health Administration. Method This study involved a retrospective review of 2030 charts. A total of 750 veterans from 10 U.S. states who received cognitive processing therapy or prolonged exposure in individual psychotherapy were included in the study (participants in cognitive processing therapy, N = 376; participants in prolonged exposure, N = 374). The main dependent variable was self-reported posttraumatic stress disorder symptoms as measured by total scores on the Posttraumatic Stress Disorder Checklist. The study used multilevel modeling to evaluate the absolute and relative effectiveness of both treatments and determine the relationship between patient-level variables and total Posttraumatic Stress Disorder Checklist scores during treatment. Results Cognitive processing therapy and prolonged exposure were equally effective at reducing total Posttraumatic Stress Disorder Checklist scores. Veterans who completed therapy reported significantly larger reductions in the Posttraumatic Stress Disorder Checklist than patients who did not complete therapy. There were no significant differences in the improvement of posttraumatic stress disorder symptoms with respect to age and three racial/ethnic groups (Caucasian, African American, and Hispanic). Conclusions Cognitive processing therapy and prolonged exposure were shown to be effective in conditions highly reflective of clinical practice and with a highly diverse sample of veterans. Challenges related to dropout from trauma focused therapy should continue to be researched.

Licence prolongations of US nuclear power plants; Les prolongations de licence des centrales nucleaires americaines

Energy Technology Data Exchange (ETDEWEB)

NONE

2004-04-01

Licences of US nuclear reactors were initially attributed for a 40 years duration. However, the vast majority of the reactors can benefit of a licence prolongation for a period of 20 years maximum. This article recalls first the procedure to follow for the licence prolongation demands (safety analysis, components aging, environmental impact statement), and then it makes a status of the accepted prolongations, of the demands under examination, and of the demands that should be presented in the next 5 years. (J.S.)

Efficacy and Safety of Prolonged Rituximab Treatment in Patients with Systemic Juvenile Idiopathic Arthritis

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E. I. Alexeeva

2013-01-01

Full Text Available Aim: to assess efficacy and safety of rituximab treatment in children with systemic juvenile idiopathic arthritis under prolonged follow-up. Patients and methods: results of treatment of 60 children (33 girls and 27 boys with systemic variant of juvenile idiopathic arthritis being followed-up in rheumatology department of the Federal State Institution «Scientific Centre of Children Health» of RAMS (FSI «SCCH» RAMS were analyzed. The mean age of children was 8,7 years. The mean duration of disease course at the moment of first rituximab administration was 5,3 years. At the beginning of rituximab therapy all children had active articular syndrome, severe systemic manifestations and significantly increased laboratory markers of activity. As the signs of improvement the authors used pediatric criteria of the American College of Rheumatology. The treatment was approved by the local ethic committee of the FSI «SCCH» RAMS; the patients’ representatives and patients older than 14 years old had signed informed agreement. Results: remission was induced in 26 of 60 (43% patients: in 9 of them after the 1st course of treatment, in 8 — after the 2nd, in 6 — after the 3d and in 3 — after the 4th. The maximal duration of remission was 5 years 4 months, minimal — 6 months. Other genetically engineered drugs were administered to 34 (57% of the patients: due to the primary inefficiency in 15, secondary inefficiency — in 10; due to partial inefficiency — in 9 children. The drug was well-tolerated in most of the patients. Undesirable effects were represented by transfusional reactions to the rituximab infusion, infections with different severity and granulocytopenia. Conclusions: rituximab has high efficiency in patients with severe systemic variant of juvenile idiopathic arthritis. The drug induced remission in patients who had been considered almost incurable, with low status of physical and social adaptation.

[Diagnosis of congenital endocrinological disease in newborns with prolonged jaundice and hypoglycaemia].

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Braslavsky, D; Keselman, A; Chiesa, A; Bergadá, I

2012-03-01

The association of prolonged neonatal jaundice and hypoglycaemia may be secondary to an endocrinological disease. Pituitary insufficiency and primary adrenal insufficiency are the most likely endocrine diseases that need to be ruled out. We retrospectively analysed the clinical and laboratory characteristics of thirteen patients referred to the Hospital de Niños Ricardo Gutiérrez between years 2003 and 2008 due to prolonged neonatal jaundice and hypoglycaemia secondary to pituitary insufficiency in twelve patients, and in one secondary to primary adrenal insufficiency. All patients had a history of neonatal hypoglycaemia. Ten patients had conjugated hyperbilirubinaemia and six also had elevated transaminases. Combined pituitary hormone deficiency was observed in the twelve hypopituitarism patients. Hormonal replacement normalised liver function and resolved the prolonged jaundice in all the patients. None of them underwent liver biopsy. Hypoglycaemia also remitted after hormonal therapy. Prolonged or cholestatic jaundice associated with neonatal hypoglycaemia is highly likely to be due to pituitary hormone deficiency or primary adrenal insufficiency. Early diagnosis and treatment of these children reverts the prolonged jaundice and prevents morbidity and mortality due to recurrent hypoglycaemia and hormone deficiencies. Copyright © 2011 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Causes of prolonged hospitalization among general internal medicine patients of a tertiary care center.

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Ruangkriengsin, Darat; Phisalprapa, Pochamana

2014-03-01

Unnecessary days of prolonged hospitalization may lead to the increase in hospital-related complications and costs, especially in tertiary care center Currently, there have not been many studies about the causes of prolonged hospitalization. Some identified causes could, however, be prevented and improved. To identify the prevalence, causes, predictive factors, prognosis, and economic burden of prolonged hospitalization in patients who had been in general internal medicine wards of the tertiary care center for 7 days or more. Retrospective chart review study was conducted among all patients who were admitted for 7 days or more in general internal medicine wards of Siriraj Hospital, the largest tertiary care center in Thailand. The period of this study was from 1 August 2012 to 30 September 2012. Demographic data, principle diagnosis, comorbid diseases, complications, discharge status, total costs of admission and percentage of reimbursement were collected. The causes of prolonged hospitalization at day 7, 14, 30, and 90 were assessed. Five hundred and sixty-two charts were reviewed. The average length of stay was 25.9 days. The two most common causes of prolonged admission at day 7 were treatment of main diagnosed disease with stable condition (27.6%) and waiting for completion of intravenous antibiotics administration with stable condition (19.5%). The causes of prolonged hospitalization at day 14 were unstable condition from complications (22.6%) and those waiting for completion of intravenous antibiotics administration with stable condition (15.8%). The causes of prolonged admission at day 30 were unstable conditions from complications (25.6%), difficulty weaning or ventilator dependence (17.6%), and caregiver problems (15.2%). The causes of prolonged hospitalization at day 90 were unstable condition from complications (30.0%), caregiver problems (30.0%), and palliative care (25.0%). Poor outcomes were shown in the patients admitted more than 90 days. Percentage

Quality of drug label information on QT interval prolongation

DEFF Research Database (Denmark)

Warnier, Miriam J; Holtkamp, Frank A; Rutten, Frans H

2014-01-01

BACKGROUND: Information regarding QT-prolongation in the drug label may vary between products. This could lead to suboptimal risk minimization strategies. OBJECTIVE: To systematically assess the variation in the extent and content of information on QT prolongation in the summary of product......-prolongation'/'QT-prolongation') and the advice on cautionary measures pertaining to QT-prolongation in the label were examined, as well as their association. RESULTS: Of the 175 screened products, 44 contained information on QT in the SPC ('no QT-prolongation': 23%, 'unclear drug-QT association': 43%, 'possibly QT-prolongation': 16%, 'QT......-prolongation': 18%). 62% contained advices to act with caution in patients with additional risk factors for QT-prolongation. Products that more likely to have QT-prolonging properties according to the SPC provided more information on QT-prolongation in the SPC ('no prolongation': 10% and for the category 'QT...

Prolonged Hypocalcemia Following a Single Dose of Denosumab for Diffuse Bone Metastasis of Gastric Cancer after Total Gastrectomy.

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Iizumi, Sakura; Shimoi, Tatsunori; Nishikawa, Tadaaki; Kitano, Atsuko; Sasada, Shinsuke; Shimomura, Akihiko; Noguchi, Emi; Yunokawa, Mayu; Yonemori, Kan; Shimizu, Chikako; Fujiwara, Yasuhiro; Tamura, Kenji

2017-11-01

Hypocalcemia is a significant adverse effect of denosumab. We herein report a case of prolonged hypocalcemia in a patient with multiple risk factors for hypocalcemia, including gastrectomy, increased bone turnover, and a poor performance status. Hypocalcemia developed after denosumab treatment for diffuse bone metastasis of gastric cancer, despite oral supplementation with vitamin D and calcium. To avoid serious prolonged hypocalcemia, a thorough assessment of the bone calcium metabolism is required before initiating denosumab treatment.

Sulforaphane protects cortical neurons against 5-S-cysteinyl-dopamine-induced toxicity through the activation of ERK1/2, Nrf-2 and the upregulation of detoxification enzymes.

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Vauzour, David; Buonfiglio, Maria; Corona, Giulia; Chirafisi, Joselita; Vafeiadou, Katerina; Angeloni, Cristina; Hrelia, Silvana; Hrelia, Patrizia; Spencer, Jeremy P E

2010-04-01

The degeneration of dopaminergic neurons in the substantia nigra has been linked to the formation of the endogenous neurotoxin 5-S-cysteinyl-dopamine. Sulforaphane (SFN), an isothiocyanate derived from the corresponding precursor glucosinolate found in cruciferous vegetables has been observed to exert a range of biological activities in various cell populations. In this study, we show that SFN protects primary cortical neurons against 5-S-cysteinyl-dopamine induced neuronal injury. Pre-treatment of cortical neurons with SFN (0.01-1 microM) resulted in protection against 5-S-cysteinyl-dopamine-induced neurotoxicity, which peaked at 100 nM. This protection was observed to be mediated by the ability of SFN to modulate the extracellular signal-regulated kinase 1 and 2 and the activation of Kelch-like ECH-associated protein 1/NF-E2-related factor-2 leading to the increased expression and activity of glutathione-S-transferase (M1, M3 and M5), glutathione reductase, thioredoxin reductase and NAD(P)H oxidoreductase 1. These data suggest that SFN stimulates the NF-E2-related factor-2 pathway of antioxidant gene expression in neurons and may protect against neuronal injury relevant to the aetiology of Parkinson's disease.

Serum proteomic changes after randomized prolonged erythropoietin treatment and/or endurance training: detection of novel biomarkers.

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Britt Christensen

Full Text Available Despite implementation of the biological passport to detect erythropoietin abuse, a need for additional biomarkers remains. We used a proteomic approach to identify novel serum biomarkers of prolonged erythropoiesis-stimulating agent (ESA exposure (Darbepoietin-α and/or aerobic training.Thirty-six healthy young males were randomly assigned to the following groups: Sedentary-placebo (n = 9, Sedentary-ESA (n = 9, Training-placebo (n = 10, or Training-ESA (n = 8. They were treated with placebo/Darbepoietin-α subcutaneously once/week for 10 weeks followed by a 3-week washout period. Training consisted of supervised biking 3/week for 13 weeks at the highest possible intensity. Serum was collected at baseline, week 3 (high dose Darbepoietin-α, week 10 (reduced dose Darbepoietin-α, and after a 3-week washout period.Serum proteins were separated according to charge and molecular mass (2D-gel electrophoresis. The identity of proteins from spots exhibiting altered intensity was determined by mass spectrometry.Six protein spots changed in response to Darbepoietin-α treatment. Comparing all 4 experimental groups, two protein spots (serotransferrin and haptoglobin/haptoglobin related protein showed a significant response to Darbepoietin-α treatment. The haptoglobin/haptoglobin related protein spot showed a significantly lower intensity in all subjects in the training-ESA group during the treatment period and increased during the washout period.An isoform of haptoglobin/haptoglobin related protein could be a new anti-doping marker and merits further research.ClinicalTrials.gov NCT01320449.

Potentiation of ghrelin signaling attenuates cancer anorexia–cachexia and prolongs survival

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Fujitsuka, N; Asakawa, A; Uezono, Y; Minami, K; Yamaguchi, T; Niijima, A; Yada, T; Maejima, Y; Sedbazar, U; Sakai, T; Hattori, T; Kase, Y; Inui, A

2011-01-01

Cancer anorexia–cachexia syndrome is characterized by decreased food intake, weight loss, muscle tissue wasting and psychological distress, and this syndrome is a major source of increased morbidity and mortality in cancer patients. This study aimed to clarify the gut–brain peptides involved in the pathogenesis of the syndrome and determine effective treatment for cancer anorexia–cachexia. We show that both ghrelin insufficiency and resistance were observed in tumor-bearing rats. Corticotropin-releasing factor (CRF) decreased the plasma level of acyl ghrelin, and its receptor antagonist, α-helical CRF, increased food intake of these rats. The serotonin 2c receptor (5-HT2cR) antagonist SB242084 decreased hypothalamic CRF level and improved anorexia, gastrointestinal (GI) dysmotility and body weight loss. The ghrelin receptor antagonist (D-Lys3)-GHRP-6 worsened anorexia and hastened death in tumor-bearing rats. Ghrelin attenuated anorexia–cachexia in the short term, but failed to prolong survival, as did SB242084 administration. In addition, the herbal medicine rikkunshito improved anorexia, GI dysmotility, muscle wasting, and anxiety-related behavior and prolonged survival in animals and patients with cancer. The appetite-stimulating effect of rikkunshito was blocked by (D-Lys3)-GHRP-6. Active components of rikkunshito, hesperidin and atractylodin, potentiated ghrelin secretion and receptor signaling, respectively, and atractylodin prolonged survival in tumor-bearing rats. Our study demonstrates that the integrated mechanism underlying cancer anorexia–cachexia involves lowered ghrelin signaling due to excessive hypothalamic interactions of 5-HT with CRF through the 5-HT2cR. Potentiation of ghrelin receptor signaling may be an attractive treatment for anorexia, muscle wasting and prolong survival in patients with cancer anorexia–cachexia. PMID:22832525

Restless legs syndrome: a new entity of neuropathic pain? Treatment with prolonged release oxycodone/naloxone combination

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Gemignani F

2016-04-01

Full Text Available Franco Gemignani,1 Andrea Melpignano,1,2 Giulia Milioli,1,2 Silvia Riccardi,1,2 Liborio Parrino1,2 1Neurology Unit, Department of Neurosciences, University of Parma, Parma, Italy; 2Sleep Disorders Center, Department of Neurosciences, University of Parma, Parma, Italy Abstract: Restless legs syndrome (RLS is a disorder of sensorimotor integration characterized by an urge to move the legs when at rest, especially at night or in the evening, which is relieved by movement. Sensory symptoms may be prominent, often exhibiting features consistent with neuropathic pain. Iron deficiency and genetic factors are implicated in RLS causation in most patients. The pathogenetic model of impaired circadian dopaminergic modulation of sensorimotor integration circuitry at the spinal level is fitting with the co-occurrence of movement disorders, sensory symptoms, and sleep disruption in RLS. Accordingly, levodopa and dopamine agonists are effective for RLS symptoms, which compensate for the impaired descending control by diencephalo-spinal dopa(minergic pathway. Dopamine agonists are usually indicated as the first-line therapy, but their use in long-term treatment is often complicated by augmentation and impulse control disorder, thus alpha-2-delta ligands also are now considered the first line of treatment. It has been recognized that endogenous opioid system is also involved in the mechanisms generating RLS, possibly through an impaired modulation of pain pathways. Opioids can be considered as an alternative therapy, particularly in patients with augmentation and/or refractory to other treatments. Recently introduced prolonged-release oxycodone–naloxone was efficacious for short-term treatment of patients with severe RLS inadequately controlled with previous treatment. It will be important to assess whether opioids, as well as other drugs, are especially effective in definite RLS subtypes such as the painful phenotype. Keywords: small fiber neuropathy

MANAGEMENT OF ENDOCRINE DISEASE: Arguments for the prolonged use of antithyroid drugs in children with Graves' disease.

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Léger, Juliane; Carel, Jean-Claude

2017-08-01

Graves' disease is an autoimmune disorder. It is the leading cause of hyperthyroidism, but is rare in children. Patients are initially managed with antithyroid drugs (ATDs), such as methimazole/carbimazole. A major disadvantage of treatment with ATD is the high risk of relapse, exceeding 70% of children treated for duration of 2 years, and the potential major side effects of the drug reported in exceptional cases. The major advantage of ATD treatment is that normal homeostasis of the hypothalamus-pituitary-thyroid axis may be restored, with periods of drug treatment followed by freedom from medical intervention achieved in approximately 40-50% of cases after prolonged treatment with ATD, for several years, in recent studies. Alternative ablative treatments such as radioactive iodine and, less frequently and mostly in cases of very high volume goiters or in children under the age of 5 years, thyroidectomy, performed by pediatric surgeons with extensive experience should be proposed in cases of non-compliance, intolerance to medical treatment or relapse after prolonged medical treatment. Ablative treatments are effective against hyperthyroidism, but they require the subsequent administration of levothyroxine throughout the patient's life. This review considers data relating to the prognosis for Graves' disease remission in children and explores the limitations of study designs and results; and the emerging proposal for management through the prolonged use of ATD drugs. © 2017 European Society of Endocrinology.

Presymptomatic Treatment with Acetylcholinesterase Antisense Oligonucleotides Prolongs Survival in ALS (G93A-SOD1 Mice

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Gotkine Marc

2013-01-01

Full Text Available Objective. Previous research suggests that acetylcholinesterase (AChE may be involved in ALS pathogenesis. AChE enzyme inhibitors can upregulate AChE transcription which in certain contexts can have deleterious (noncatalytic effects, making them theoretically harmful in ALS, whilst AChE antisense-oligonucleotides (mEN101, which downregulate AChE may be beneficial. Our aim was to investigate whether downregulation of AChE using mEN101 is beneficial in an ALS mouse model. Methods. ALS (G93A-SOD1 mice received saline, mEN101, inverse-EN101, or neostigmine. Treatments were administered from 5 weeks. Disease-onset and survival were recorded. Additional mice were sacrificed for pathological analysis at 15 weeks of age. In a follow-up experiment treatment was started at the symptomatic stage at a higher dose. Results. mEN101 given at the presymptomatic (but not symptomatic stage prolonged survival and attenuated motor-neuron loss in ALS mice. In contrast, neostigmine exacerbated the clinical parameters. Conclusions. These results suggest that AChE may be involved in ALS pathogenesis. The accelerated disease course with neostigmine suggests that any beneficial effects of mEN101 occur through a non-catalytic rather than cholinergic mechanism.

Prolonged pregnancy: Methods, Causal Determinants and Outcome

DEFF Research Database (Denmark)

Olesen, Annette Wind

Summary Prolonged pregnancy, defined as a pregnancy with a gestational length of 294 days or more, is a frequent condition. It is associated with an increased risk of fetal and maternal complications. Little is known about the aetiology of prolonged pregnancy. The aims of the thesis were 1......) to study the incidence of prolonged pregnancy as a function of methods for determining gestational age; 2) to determine the risk of obstetrical and fetal complications in prolonged pregnancy; 3) to validate the self-reported gestational age in the National Birth Cohort; 4) to determine whether...... the risk of recurrence of prolonged pregnancy as a function of change in male partner and social conditions (IV). The National Birth Cohort provided data for the study on prenatal risk indicators of prolonged pregnancy in a follow-up design (V). The self-reported gestational ages from this database...

Prolonged CT urography in duplex kidney.

Science.gov (United States)

Gong, Honghan; Gao, Lei; Dai, Xi-Jian; Zhou, Fuqing; Zhang, Ning; Zeng, Xianjun; Jiang, Jian; He, Laichang

2016-05-13

Duplex kidney is a common anomaly that is frequently associated with multiple complications. Typical computed tomography urography (CTU) includes four phases (unenhanced, arterial, parenchymal and excretory) and has been suggested to considerably aid in the duplex kidney diagnosi. Unfortunately, regarding duplex kidney with prolonged dilatation, the affected parenchyma and tortuous ureters demonstrate a lack of or delayed excretory opacification. We used prolonged-delay CTU, which consists of another prolonged-delay phase (1- to 72-h delay; mean delay: 24 h) to opacify the duplicated ureters and affected parenchyma. Seventeen patients (9 males and 8 females; age range: 2.5-56 y; mean age: 40.4 y) with duplex kidney were included in this study. Unenhanced scans did not find typical characteristics of duplex kidney, except for irregular perirenal morphology. Duplex kidney could not be confirmed on typical four-phase CTU, whereas it could be easily diagnosed in axial and CT-3D reconstruction using prolonged CTU (prolonged-delay phase). Between January 2005 and October 2010, in this review board-approved study (with waived informed consent), 17 patients (9 males and 8 females; age range: 2.5 ~ 56 y; mean age: 40.4 y) with suspicious duplex kidney underwent prolonged CTU to opacify the duplicated ureters and confirm the diagnosis. Our results suggest the validity of prolonged CTU to aid in the evaluation of the function of the affected parenchyma and in the demonstration of urinary tract malformations.

Sulforaphane Reverses the Expression of Various Tumor Suppressor Genes by Targeting DNMT3B and HDAC1 in Human Cervical Cancer Cells

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Munawwar Ali Khan

2015-01-01

Full Text Available Sulforaphane (SFN may hinder carcinogenesis by altering epigenetic events in the cells; however, its molecular mechanisms are unclear. The present study investigates the role of SFN in modifying epigenetic events in human cervical cancer cells, HeLa. HeLa cells were treated with SFN (2.5 µM for a period of 0, 24, 48, and 72 hours for all experiments. After treatment, expressions of DNMT3B, HDAC1, RARβ, CDH1, DAPK1, and GSTP1 were studied using RT-PCR while promoter DNA methylation of tumor suppressor genes (TSGs was studied using MS-PCR. Inhibition assays of DNA methyl transferases (DNMTs and histone deacetylases (HDACs were performed at varying time points. Molecular modeling and docking studies were performed to explore the possible interaction of SFN with HDAC1 and DNMT3B. Time-dependent exposure to SFN decreases the expression of DNMT3B and HDAC1 and significantly reduces the enzymatic activity of DNMTs and HDACs. Molecular modeling data suggests that SFN may interact directly with DNMT3B and HDAC1 which may explain the inhibitory action of SFN. Interestingly, time-dependent reactivation of the studied TSGs via reversal of methylation in SFN treated cells correlates well with its impact on the epigenetic alterations accumulated during cancer development. Thus, SFN may have significant implications for epigenetic based therapy.

Risk management of QTc-prolongation in patients receiving haloperidol: an epidemiological study in a University hospital in Belgium.

Science.gov (United States)

Vandael, Eline; Vandenberk, Bert; Vandenberghe, Joris; Spriet, Isabel; Willems, Rik; Foulon, Veerle

2016-04-01

Many drugs, including haloperidol, are linked with a risk of QTc-prolongation, which can lead to Torsade de Pointes and sudden cardiac death. To investigate the prevalence of concomitant risk factors for QTc-prolongation in patients treated with haloperidol, and the use of safety measures to minimize this risk. University Hospitals of Leuven, Belgium. Methods A retrospective epidemiological study was performed. On 15 consecutive Mondays, all patients with a prescription for haloperidol were included. A risk score for QTc-prolongation, inspired by the pro-QTc score of Haugaa et al., was calculated based on gender, comorbidities, lab results and concomitant QTc-prolonging drugs (each factor counting for one point). Available electrocardiograms before and during the treatment of haloperidol were registered. Management of the risk of QTc-prolongation. Two hundred twenty-two patients were included (59.0 % men, median age 77 years) of whom 26.6 % had a risk score of ≥4 (known to significantly increase the mortality). Overall, 24.3 % received haloperidol in combination with other drugs with a known risk of Torsade de Pointes. Half of the patients had an electrocardiogram in the week before the start of haloperidol; only in one-third a follow-up electrocardiogram during haloperidol treatment was performed. Of the patients with a moderately (n = 41) or severely (n = 14) prolonged QTc-interval before haloperidol, 48.8 % and 42.9 % respectively had a follow-up electrocardiogram. In patients with a risk score ≥4, significantly more electrocardiograms were taken before starting haloperidol (p = 0.020). Although many patients had risk factors for QTc-prolongation (including the use of other QTc-prolonging drugs) or had a prolonged QTc on a baseline electrocardiogram, follow-up safety measures were limited. Persistent efforts should be taken to develop decision support systems to manage this risk.

Prolonged Exposure Therapy for a Vietnam Veteran with PTSD and Early-Stage Dementia

Science.gov (United States)

Duax, Jeanne M.; Waldron-Perrine, Brigid; Rauch, Sheila A. M.; Adams, Kenneth M.

2013-01-01

Although prolonged exposure therapy (PE) is considered an evidence-based treatment for PTSD, there has been little published about the use of this treatment for older adults with comorbid early-stage dementia. As the number of older adults in the United States continues to grow, so will their unique mental health needs. The present article…

Sulforaphane Prevents Angiotensin II-Induced Testicular Cell Death via Activation of NRF2

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Yonggang Wang

2017-01-01

Full Text Available Although angiotensin II (Ang II was reported to facilitate sperm motility and intratesticular sperm transport, recent findings shed light on the efficacy of Ang II in stimulating inflammatory events in testicular peritubular cells, effect of which may play a role in male infertility. It is still unknown whether Ang II can induce testicular apoptotic cell death, which may be a more direct action of Ang II in male infertility. Therefore, the present study aims to determine whether Ang II can induce testicular apoptotic cell death and whether this action can be prevented by sulforaphane (SFN via activating nuclear factor (erythroid-derived 2-like 2 (NRF2, the governor of antioxidant-redox signalling. Eight-week-old male C57BL/6J wild type (WT and Nrf2 gene knockout mice were treated with Ang II, in the presence or absence of SFN. In WT mice, SFN activated testicular NRF2 expression and function, along with a marked attenuation in Ang II-induced testicular oxidative stress, inflammation, endoplasmic reticulum stress, and apoptotic cell death. Deletion of the Nrf2 gene led to a complete abolishment of these efficacies of SFN. The present study indicated that Ang II may result in testicular apoptotic cell death, which can be prevented by SFN via the activation of NRF2.

Prolonging the duration of masseter muscle reduction by adjusting the masticatory movements after the treatment of masseter muscle hypertrophy with botulinum toxin type a injection.

Science.gov (United States)

Wei, Jiao; Xu, Hua; Dong, Jiasheng; Li, Qingfeng; Dai, Chuanchang

2015-01-01

Botulinum toxin type A (BTX-A) is widely used for the clinical treatment of masseteric hypertrophy. Until now, few reports have discussed how to prolong the duration of its effectiveness. This study evaluated that purposely adjusting the masticatory movements is possible of postponing the masseter muscle rehypertrophy. Ninety-eight patients were randomly and equally divided into 2 groups, and 35 U BTX-A per side was injected into the masseters. The thickness and volume of the masticatory muscles were measured by ultrasound and computerized tomography, respectively. Patients in Group 1 were instructed to strengthen their masticatory effort during the denervated atrophic stage of the masseter (the interval was evaluated by real-time ultrasound monitoring), whereas patients in Group 2 were not given this instruction. When the masseter muscle began to recover, patients in both groups were instructed to reduce their chewing. The duration of the masseter muscle rehypertrophy was significantly prolonged in Group 1 patients. The thickness and the volume of the other masticatory muscles were significantly increased in Group 1 but were either slightly decreased or insignificantly different in Group 2. Purposely strengthening masticatory muscle movement during the denervated atrophic stage of the masseter can prolong the duration of masseter rehypertrophy.

[Brain function recovery after prolonged posttraumatic coma].

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Klimash, A V; Zhanaidarov, Z S

2016-01-01

To explore the characteristics of brain function recovery in patients after prolonged posttraumatic coma and with long-unconscious states. Eighty-seven patients after prolonged posttraumatic coma were followed-up for two years. An analysis of a clinical/neurological picture after a prolonged episode of coma was based on the dynamics of vital functions, neurological status and patient's reactions to external stimuli. Based on the dynamics of the clinical/neurological picture that shows the recovery of functions of the certain brain areas, three stages of brain function recovery after a prolonged episode of coma were singled out: brain stem areas, diencephalic areas and telencephalic areas. These functional/anatomic areas of brain function recovery after prolonged coma were compared to the present classifications.

Antibiotic-eluting hydrophilized PMMA bone cement with prolonged bactericidal effect for the treatment of osteomyelitis.

Science.gov (United States)

Oh, Eun Jo; Oh, Se Heang; Lee, In Soo; Kwon, Oh Soo; Lee, Jin Ho

2016-05-01

Osteomyelitis is still considered to be one of the major challenges for orthopedic surgeons despite advanced antiseptic surgical procedures and pharmaceutical therapeutics. In this study, hydrophilized poly(methyl methacrylate) (PMMA) bone cements containing Pluronic F68 (EG79PG28EG79) as a hydrophilic additive and vancomycin (F68-VAcements) were prepared to allow the sustained release of the antibiotic for adequate periods of time without any significant loss of mechanical properties. The compressive strengths of the bone cements with Pluronic F68 compositions less than 7 wt% were not significantly different compared with the control vancomycin-loaded bone cement (VAcement). TheF68 (7 wt%)-VAcement showed sustained release of the antibiotic for up to 11 weeks and almost 100% release from the bone cement. It also prohibited the growth ofS. aureus(zone of inhibition) over six weeks (the required period to treat osteomyelitis), and it did not show any notable cytotoxicity. From an animal study using a femoral osteomyelitis rat model, it was observed that theF68 (7 wt%)-VAcement was effective for the treatment of osteomyelitis, probably as a result of the prolonged release of antibiotic from the PMMA bone cement. On the basis of these findings, it can be suggested that the use of Pluronic F68 as a hydrophilic additive for antibiotic-eluting PMMA bone cement can be a promising strategy for the treatment of osteomyelitis. © The Author(s) 2016.

[Pathophysiology of prolonged hypokinesia].

Science.gov (United States)

Kovalenko, E A

1976-01-01

Hypokinesia is an important problem in modern medicine. In the pathogenetic effect of prolonged hypokinesia the main etiological factor is diminished motor activity; of major importance are disorders in the energy and plastic metabolism which affect the muscle system; the contributing factors are cardiovascular deconditioning and orthostatic intolerance. This is attributed to a decreased oxygen supply and eliminated hydrostatic influences during a prolonged recumbency. Blood redistribution in the vascular bed is related to the Gauer-Henry reflex and subsequent changes in the fluid-electrolyte balance. Decreased load on the bone system induces changes in the protein-phosphate-calcium metabolism, diminished bone density and increased calcium content in the blood and urine. Changes in the calcium metabolism are systemic. The activity of the higher nervous system and reflex functions is lowered. Changes in the function of the autonomic nervous system which include a noticeable decline of its adaptive-trophic role as a result of the decrease of afferent and efferent impulsation are of great importance. Changes in the hormonal function involve a peculiar stress-reaction which develops at an early stage of hypokinesia as a response to an unusual situation. Prolonged hypokinesia may result in a disturbed function of the pituitary-adrenal system. It is assumed that prolonged hypokinesia may induce a specific disease of hypokinesia during which man cannot lead a normal mode of life and work.

Prolonged vertigo and ataxia after mandibular nerve block for treatment of trigeminal neuralgia

OpenAIRE

Arvind Chaturvedi; H H Dash

2011-01-01

Common complications of neurolytic mandibular nerve block are hypoesthesia, dysesthesia, and chemical neuritis. We report a rare complication, prolonged severe vertigo and ataxia, after neurolytic mandibular blockade in a patient suffering from trigeminal neuralgia. Coronoid approach was used for right sided mandibular block. After successful test injection with local anesthetic, absolute alcohol was given for neurolytic block. Immediately after alcohol injection, patient developed nausea and...

Prolonged-release melatonin versus placebo for benzodiazepine discontinuation in patients with schizophrenia: a randomized clinical trial - the SMART trial protocol

DEFF Research Database (Denmark)

Baandrup, Lone; Fagerlund, Birgitte; Jennum, Poul

2011-01-01

Treatment of schizophrenia frequently includes prolonged benzodiazepine administration despite a lack of evidence of its use. It is often difficult to discontinue benzodiazepines because of the development of dependence. We aim to assess if melatonin can facilitate the withdrawal of prolonged...

QT Prolongation due to Graves’ Disease

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Zain Kulairi

2017-01-01

Full Text Available Hyperthyroidism is a highly prevalent disease affecting over 4 million people in the US. The disease is associated with many cardiac complications including atrial fibrillation and also less commonly with ventricular tachycardia and fibrillation. Many cardiac pathologies have been extensively studied; however, the relationship between hyperthyroidism and rate of ventricular repolarization manifesting as a prolonged QTc interval is not well known. Prolonged QTc interval regardless of thyroid status is a risk factor for cardiovascular mortality and life-threatening ventricular arrhythmia. The mechanism regarding the prolongation of the QT interval in a hyperthyroid patient has not been extensively investigated although its clinical implications are relevant. Herein, we describe a case of prolonged QTc in a patient who presented with signs of hyperthyroidism that was corrected with return to euthyroid status.

Internalized stigma in adults with early phase versus prolonged psychosis.

Science.gov (United States)

Firmin, Ruth L; Lysaker, Paul H; Luther, Lauren; Yanos, Philip T; Leonhardt, Bethany; Breier, Alan; Vohs, Jenifer L

2018-03-30

Although internalized stigma is associated with negative outcomes among those with prolonged psychosis, surprisingly little work has focused on when in the course of one's illness stigma is internalized and the impact of internalization on symptoms or social functioning over the course of the illness. Therefore, this study investigated whether (1) internalized stigma is greater among those later in the course of psychosis and (2) whether internalized stigma has a stronger negative relationship with social functioning or symptoms among those with prolonged compared to early phase psychosis. Individuals with early phase (n = 40) and prolonged psychosis (n = 71) who were receiving outpatient services at an early-intervention clinic and a VA medical center, respectively, completed self-report measures of internalized stigma and interview-rated measures of symptoms and social functioning. Controlling for education, race and sex differences, internalized stigma was significantly greater among those with prolonged psychosis compared to early phase. Internalized stigma was negatively related to social functioning and positively related to symptoms in both groups. Furthermore, the magnitude of the relationship between cognitive symptoms and internalized stigma was significantly greater among those with early phase. Stereotype endorsement, discrimination experiences and social withdrawal also differentially related to symptoms and social functioning across the 2 samples. Findings suggest that internalized stigma is an important variable to incorporate into models of early psychosis. Furthermore, internalized stigma may be a possible treatment target among those with early phase psychosis. © 2018 John Wiley & Sons Australia, Ltd.

High-dose radiation therapy alone for inoperable non-small cell lung cancer. Experience with prolonged overall treatment times

International Nuclear Information System (INIS)

Willers, H.; Wuerschmidt, F.; Buenemann, H.; Heilmann, H.P.

1998-01-01

The purpose of this study was to determine the impact of overall treatment time on long-term survival after high-dose radiation therapy alone for inoperable non-small cell lung cancer (NSCLC). Between 1978 and 1990, 229 patients with stage I-III disease and Karnofsky Performance Scores of 80-100 received a conventionally fractionated total dose of 70 Gy through a split-course technique. After a first treatment course of 40 or 50 Gy, a rest aging was performed and only patients without any contraindications, such as newly diagnosed distant metastases or serious deterioration of performance status, were given a second course. In 83% of patients this break lasted for 4-6 weeks. Overall treatment time ranged between 7 and 24 weeks (median 12 weeks). Median follow-up time was 6.6 years (range 4.0-9.3 years). Actuarial overall survival rates at 2 and 5 years were 28% and 7% respectively. Complete radiological tumor response was observed in 31% of patients, and was found to be the strongest positive predictor of survival with 2- and 5-year rates of 50% and 12% respectively compared with 17% and 4% for patients without complete response. Treatment duration was not found to be a significant prognostic factor in univariate or multivariate analysis. For overall treatment times of 7-11 weeks (n=50), 12 weeks (n=79) and >12 weeks (n=100), 5-year survival was 4%, 6%, and 8%, respectively (p=0.6). To conclude, in our experience and in contrast to other studies, prolonged overall treatment times in radiation therapy alone for inoperable NSCLC had no negative impact on long-term survival. It is hypothesized that accelerated tumor cell repopulation is absent in a significant number of these patients with the time-factor playing no apparent role for outcome of treatment. (orig.)

Exhaustion from prolonged gambling

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Fatimah Lateef

2013-01-01

Full Text Available Complaints of fatigue and physical exhaustion are frequently seen in the acute medical setting, especially amongst athletes, army recruits and persons involved in strenuous and exertional physical activities. Stress-induced exhaustion, on the other hand, is less often seen, but can present with very similar symptoms to physical exhaustion. Recently, three patients were seen at the Department of Emergency Medicine, presenting with exhaustion from prolonged involvement in gambling activities. The cases serve to highlight some of the physical consequences of prolonged gambling.

What prolongs a butterfly's life?: Trade-offs between dormancy, fecundity and body size.

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Elena Haeler

Full Text Available In butterflies, life span often increases only at the expense of fecundity. Prolonged life span, on the other hand, provides more opportunities for oviposition. Here, we studied the association between life span and summer dormancy in two closely related species of Palearctic Meadow Brown butterflies, the endemic Maniola nurag and the widespread M. jurtina, from two climatic provenances, a Mediterranean and a Central European site, and tested the relationships between longevity, body size and fecundity. We experimentally induced summer dormancy and hence prolonged the butterflies' life in order to study the effects of such a prolonged life. We were able to modulate longevity only in Mediterranean females by rearing them under summer photoperiodic conditions (light 16 h : dark 8 h, thereby more than doubling their natural life span, to up to 246 days. Central European individuals kept their natural average live span under all treatments, as did Mediterranean individuals under autumn treatment (light 11: dark 13. Body size only had a significant effect in the smaller species, M. nurag, where it affected the duration of dormancy and lifetime fecundity. In the larger species, M. jurtina, a prolonged adult life span did, surprisingly, not convey any fecundity loss. In M. nurag, which generally deposited fewer eggs, extended life had a fecundity cost. We conclude that Mediterranen M. jurtina butterflies have an extraordinary plasticity in aging which allows them to extend life span in response to adverse environmental conditions and relieve the time limitation on egg-laying while maintaining egg production at equal levels.

Deciding about treatments that prolong life

Science.gov (United States)

... you are receiving or may need in the future. Learn about the treatments and how they would ... patients and their families. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 25th ed. Philadelphia, PA: ...

9. Nuclear power plant service life prolongation

International Nuclear Information System (INIS)

Evropin, S.V.

1998-01-01

The problem of prolongation of nuclear power plant service life duration is discussed. A schematic diagram of the program developed in the course of activities dealing with NPP service time prolongation is shown and analyzed in details. It is shown that the basic moment when determining the strategy for NPP service time prolongation is the positive confirmation of the agreement between the NPP safety provisions and modern safety requirements. The other very important aspect of the problem is engineering substantiation of the measures assuring the reactor operation prolongation. The conclusion is made that available methods of recovering reactor materials properties, main components repair and replacement, the modern techniques for nondestructive testing of metals and NPP pipelines, as well as the developed approaches to reactor facility safety improvements make the prolongation of the Russian NPP service lifetimes possible from engineering viewpoint and economically desirable

A Comparison of Cognitive-Processing Therapy With Prolonged Exposure and a Waiting Condition for the Treatment of Chronic Posttraumatic Stress Disorder in Female Rape Victims

Science.gov (United States)

Resick, Patricia A.; Nishith, Pallavi; Weaver, Terri L.; Astin, Millie C.; Feuer, Catherine A.

2010-01-01

The purpose of this study was to compare cognitive-processing therapy (CPT) with prolonged exposure and a minimal attention condition (MA) for the treatment of posttraumatic stress disorder (PTSD) and depression. One hundred seventy-one female rape victims were randomized into 1 of the 3 conditions, and 121 completed treatment. Participants were assessed with the Clinician-Administered PTSD Scale, the PTSD Symptom Scale, the Structured Clinical Interview for DSM–IV, the Beck Depression Inventory, and the Trauma-Related Guilt Inventory. Independent assessments were made at pretreatment, posttreatment, and 3 and 9 months posttreatment. Analyses indicated that both treatments were highly efficacious and superior to MA. The 2 therapies had similar results except that CPT produced better scores on 2 of 4 guilt subscales. PMID:12182270

Agitation during prolonged mechanical ventilation at a long-term acute care hospital: risk factors, treatments, and outcomes.

Science.gov (United States)

O'Connor, Heidi; Al-Qadheeb, Nada S; White, Alexander C; Thaker, Vishal; Devlin, John W

2014-01-01

The prevalence, risk factors, treatment practices, and outcomes of agitation in patients undergoing prolonged mechanical ventilation (PMV) in the long-term acute care hospital (LTACH) setting are not well understood. We compared agitation risk factors, management strategies, and outcomes between patients who developed agitation and those who did not, in LTACH patients undergoing PMV. Patients admitted to an LTACH for PMV over a 1-year period were categorized into agitated and nonagitated groups. The presence of agitation risk factors, management strategies, and relevant outcomes were extracted and compared between the 2 groups. A total of 80 patients were included, 41% (33) with agitation and 59% (47) without. Compared to the nonagitated group, the agitated group had a lower Sequential Organ Failure Assessment score (P agitated group, use of benzodiazepines (P = .16), opioids (P = .11), or psychiatric evaluation (P = .90) was not. Weaning success, duration of LTACH stay, and daily costs were similar. Agitation among the LTACH patients undergoing PMV is associated with greater delirium and use of antipsychotics and restraints but does not influence weaning success or LTACH stay. Strategies focused on agitation prevention and treatment in this population need to be developed and formally evaluated. © The Author(s) 2013.

The effects of sodium bicarbonate during prolonged cardiopulmonary resuscitation.

Science.gov (United States)

Weng, Yi-Ming; Wu, Shih-Hao; Li, Wen-Cheng; Kuo, Chan-Wei; Chen, Shou-Yen; Chen, Jih-Chang

2013-03-01

This study was performed to determine the effects of sodium bicarbonate injection during prolonged cardiopulmonary resuscitation (for >15 minutes). The retrospective cohort study consisted of adult patients who presented to the emergency department (ED) with the diagnosis of cardiac arrest in 2009. Data were retrieved from the institutional database. A total of 92 patients were enrolled in the study. Patients were divided into 2 groups based on whether they were treated (group1, n = 30) or not treated (group 2, n = 62) with sodium bicarbonate. There were no significant differences in demographic characteristics between groups. The median time interval between the administration of CPR and sodium bicarbonate injection was 36.0 minutes (IQR: 30.5-41.8 minutes). The median amount of bicarbonate injection was 100.2 mEq (IQR: 66.8-104.4). Patients who received a sodium bicarbonate injection during prolonged CPR had a higher percentage of return of spontaneous circulation, but not statistical significant (ROSC, 40.0% vs. 32.3%; P = .465). Sustained ROSC was achieved by 2 (6.7%) patients in the sodium bicarbonate treatment group, with no survival to discharge. No significant differences in vital signs after ROSC were detected between the 2 groups (heart rate, P = .124; systolic blood pressure, P = .094). Sodium bicarbonate injection during prolonged CPR was not associated with ROSC after adjust for variables by regression analysis (Table 3; P = .615; odds ratio, 1.270; 95% confidence interval: 0.501-3.219) The administration of sodium bicarbonate during prolonged CPR did not significantly improve the rate of ROSC in out-of-hospital cardiac arrest. Copyright © 2013 Elsevier Inc. All rights reserved.

Life Threatening Severe QTc Prolongation in Patient with Systemic Lupus Erythematosus due to Hydroxychloroquine

Directory of Open Access Journals (Sweden)

John P. O’Laughlin

2016-01-01

Full Text Available We present a case of a syncopal episode resulting from significant QT interval prolongation in a patient on hydroxychloroquine for the treatment of systemic lupus erythematosus and end stage renal disease. The patient had been treated with hydroxychloroquine for two years prior to presentation. After thorough workup for secondary causes of QT interval prolongation hydroxychloroquine was discontinued and the patient’s QT interval shortened. The patient was treated with mexiletine to prevent sudden ventricular arrhythmias, which was unique compared to other documented cases in which lidocaine was used. The patient was noted to have mild prolongation of the QT interval on electrocardiogram prior to initiation of hydroxychloroquine therapy which was exacerbated by its use and may have been caused due to toxicity from underlying renal failure.

Safety information on QT-interval prolongation

DEFF Research Database (Denmark)

Warnier, Miriam J; Holtkamp, Frank A; Rutten, Frans H

2014-01-01

Prolongation of the QT interval can predispose to fatal ventricular arrhythmias. Differences in QT-labeling language can result in miscommunication and suboptimal risk mitigation. We systematically compared the phraseology used to communicate on QT-prolonging properties of 144 drugs newly approve...

Chemical pleurodesis for prolonged postoperative air leak in primary spontaneous pneumothorax.

Science.gov (United States)

How, Cheng-Hung; Tsai, Tung-Ming; Kuo, Shuenn-Wen; Huang, Pei-Ming; Hsu, Hsao-Hsun; Lee, Jang-Ming; Chen, Jin-Shing; Lai, Hong-Shiee

2014-05-01

Prolonged air leak is the most common complication after thoracoscopic operation for primary spontaneous pneumothorax (PSP), and the role of chemical pleurodesis in treating air leaks remains unclear. This study evaluated the safety and efficacy of chemical pleurodesis with a comparison between minocycline and OK-432. Between 1994 and 2011, 1083 PSP patients were treated by thoracoscopic operation. After the operation, patients with persistent air leak for 3 days or more were managed by minocycline or OK-432 pleurodesis. The demographic and outcome data for these patients were collected by retrospective chart review. Seventy-nine patients (7.3%) with prolonged air leak after thoracoscopy underwent minocycline pleurodesis (60 patients) or OK-432 pleurodesis (19 patients) as the primary treatment. The primary success rate was 63% (38/60) for minocycline pleurodesis and 95% (18/19) for OK-432 pleurodesis (p = 0.009). Postpleurodesis pain was common and comparable between the two groups. No major complications were noted after a total of 121 treatments. Patients undergoing primary OK-432 pleurodesis had shorter durations of postpleurodesis chest drainage (mean 8.5 vs. 2.3 days; p < 0.001) and postoperative hospital stay (mean 11.9 vs. 6.8 days; p < 0.001) than those undergoing primary minocycline pleurodesis. After a median follow-up of 16 months, recurrence was noted in one patient in the OK-432 group and none in the minocycline group. Long-term pulmonary function in the two groups was comparable. Chemical pleurodesis using OK-432 or minocycline is safe and convenient for prolonged air leak after thoracoscopic treatment for PSP. Our experience suggested that OK-432 may be more effective than minocycline in reducing air leak. Copyright © 2013. Published by Elsevier B.V.

Prolonged treatment with transcutaneous electrical nerve stimulation (TENS) modulates neuro-gastric motility and plasma levels of vasoactive intestinal peptide (VIP), motilin and interleukin-6 (IL-6) in systemic sclerosis.

Science.gov (United States)

McNearney, Terry A; Sallam, Hanaa S; Hunnicutt, Sonya E; Doshi, Dipti; Chen, Jiande D Z

2013-01-01

We assessed the effects of transcutaneous electrical nerve stimulation (TENS) on neurogastric functioning in scleroderma patients. Seventeen SSc patients underwent 30 min TENS treatment >10Hz at GI acupuncture points PC6 and ST36, once (acute TENS) and then after two weeks of TENS sessions for 30 min twice daily (prolonged TENS). Data collected at Visits 1 and 2 included gastric myoelectrical activity (GMA) by surface electrogastrography (EGG), heart rate variability (HRV) by surface electrocardiography (EKG), GI specific symptoms and health related SF-36 questionnaires. Plasma VIP, motilin and IL-6 levels were determined. Statistical analyses were performed by Student's t-test, Spearman Rank and p-values TENS, the percentages of normal slow waves and average slow wave coupling (especially channels 1, 2 reflecting gastric pacemaker and corpus regions) were significantly increased; 2. the percentage of normal slow waves was significantly correlated to sympathovagal balance; 3. Mean plasma VIP and motilin levels were significantly decreased after acute TENS, (vs. baseline), generally maintained in the prolonged TENS intervals. Compared to baseline, mean plasma IL-6 levels were significantly increased after acute TENS, but significantly decreased after prolonged TENS. 4. After prolonged TENS, the frequency of awakening due to abdominal pain and abdominal bloating were significantly and modestly decreased, respectively. In SSc patients, two weeks of daily TENS improved patient GMA scores, lowered plasma VIP, motilin and IL-6 levels and improved association between GMA and sympathovagal balance. This supports the therapeutic potential of prolonged TENS to enhance gastric myoelectrical functioning in SSc.

Genetic influence on prolonged gestation

DEFF Research Database (Denmark)

Laursen, Maja; Bille, Camilla; Olesen, Annette Wind

2004-01-01

OBJECTIVE: The purpose of this study was to test a possible genetic component to prolonged gestation. STUDY DESIGN: The gestational duration of single, first pregnancies by both female and male twins was obtained by linking the Danish Twin Registry, The Danish Civil Registration System, and the D...... factors. CONCLUSION: Maternal genes influence prolonged gestation. However, a substantial paternal genetic influence through the fetus was not found....

Treatment of hemodialysis vascular access rupture irresponsive to prolonged balloon tamponade: Retrospective evaluation of the effectiveness of N-butyl cyanoacrylate seal-off technique

Energy Technology Data Exchange (ETDEWEB)

Weng, Mei Jul; Liang, Huei Lung; Pan, Huay Ben [Dept. of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung (China); Chen, Matt Chiung Yu [Dept. of Radiology, Yuan' s General Hospital, Kaohsiung (China)

2013-01-15

The current study retrospectively evaluated whether the percutaneous N-butyl cyanoacrylate (NBCA) seal-off technique is an effective treatment for controlling the angioplasty-related ruptures, which are irresponsive to prolonged balloon tamponade, during interventions for failed or failing hemodialysis vascular accesses. We reviewed 1588 interventions performed during a 2-year period for dysfunction and/or failed hemodialysis vascular access sites in 1569 patients. For the angioplasty-related ruptures, which could not be controlled with repeated prolonged balloon tamponade, the rupture sites were sealed off with an injection of a glue mixture (NBCA and lipiodol), via a needle/needle sheath to the rupture site, under a sonographic guidance. Technical success rate, complications and clinical success rate were reported. The post-seal-off primary and secondary functional patency rates were calculated by a survival analysis with the Kaplan-Meier method. Twenty ruptures irresponsive to prolonged balloon tamponade occurred in 1588 interventions (1.3%). Two technical failures were noted; one was salvaged with a bailout stent-graft insertion and the other was lost after access embolization. Eighteen accesses (90.0%) were salvaged with the seal-off technique; of them, 16 ruptures were completely sealed off, and two lesions were controlled as acute pseudoaneurysms. Acute pseudoaneurysms were corrected with stentgraft insertion in one patient, and access ligation in the other. The most significant complication during the follow-up was delayed pseudoaneurysm, which occurred in 43.8% (7 of 16) of the completely sealed off accesses. Delayed pseudoaneurysms were treated with surgical revision (n = 2), access ligation (n = 2) and observation (n = 3). During the follow-up, despite the presence of pseudoaneurysms (acute = 1, delayed = 7), a high clinical success rate of 94.4% (17 of 18) was achieved, and they were utilized for hemodialysis at the mean of 411.0 days. The post

Prolonged Minocycline Treatment Impairs Motor Neuronal Survival and Glial Function in Organotypic Rat Spinal Cord Cultures

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Pinkernelle, Josephine; Fansa, Hisham; Ebmeyer, Uwe; Keilhoff, Gerburg

2013-01-01

Background Minocycline, a second-generation tetracycline antibiotic, exhibits anti-inflammatory and neuroprotective effects in various experimental models of neurological diseases, such as stroke, Alzheimer’s disease, amyotrophic lateral sclerosis and spinal cord injury. However, conflicting results have prompted a debate regarding the beneficial effects of minocycline. Methods In this study, we analyzed minocycline treatment in organotypic spinal cord cultures of neonatal rats as a model of motor neuron survival and regeneration after injury. Minocycline was administered in 2 different concentrations (10 and 100 µM) at various time points in culture and fixed after 1 week. Results Prolonged minocycline administration decreased the survival of motor neurons in the organotypic cultures. This effect was strongly enhanced with higher concentrations of minocycline. High concentrations of minocycline reduced the number of DAPI-positive cell nuclei in organotypic cultures and simultaneously inhibited microglial activation. Astrocytes, which covered the surface of the control organotypic cultures, revealed a peripheral distribution after early minocycline treatment. Thus, we further analyzed the effects of 100 µM minocycline on the viability and migration ability of dispersed primary glial cell cultures. We found that minocycline reduced cell viability, delayed wound closure in a scratch migration assay and increased connexin 43 protein levels in these cultures. Conclusions The administration of high doses of minocycline was deleterious for motor neuron survival. In addition, it inhibited microglial activation and impaired glial viability and migration. These data suggest that especially high doses of minocycline might have undesired affects in treatment of spinal cord injury. Further experiments are required to determine the conditions for the safe clinical administration of minocycline in spinal cord injured patients. PMID:23967343

Promoter de-methylation of cyclin D2 by sulforaphane in prostate cancer cells

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Hsu Anna

2011-10-01

Full Text Available Abstract Sulforaphane (SFN, an isothiocyanate derived from cruciferous vegetables, induces potent anti-proliferative effects in prostate cancer cells. One mechanism that may contribute to the anti-proliferative effects of SFN is the modulation of epigenetic marks, such as inhibition of histone deacetylase (HDAC enzymes. However, the effects of SFN on other common epigenetic marks such as DNA methylation are understudied. Promoter hyper-methylation of cyclin D2, a major regulator of cell cycle, is correlated with prostate cancer progression, and restoration of cyclin D2 expression exerts anti-proliferative effects on LnCap prostate cancer cells. Our study aimed to investigate the effects of SFN on DNA methylation status of cyclin D2 promoter, and how alteration in promoter methylation impacts cyclin D2 gene expression in LnCap cells. We found that SFN significantly decreased the expression of DNA methyltransferases (DNMTs, especially DNMT1 and DNMT3b. Furthermore, SFN significantly decreased methylation in cyclin D2 promoter regions containing c-Myc and multiple Sp1 binding sites. Reduced methlyation of cyclin D2 promoter corresponded to an increase in cyclin D2 transcript levels, suggesting that SFN may de-repress methylation-silenced cyclin D2 by impacting epigenetic pathways. Our results demonstrated the ability of SFN to epigenetically modulate cyclin D2 expression, and provide novel insights into the mechanisms by which SFN may regulate gene expression as a prostate cancer chemopreventive agent.

Withaferin A and sulforaphane regulate breast cancer cell cycle progression through epigenetic mechanisms.

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Royston, Kendra J; Paul, Bidisha; Nozell, Susan; Rajbhandari, Rajani; Tollefsbol, Trygve O

2018-07-01

Little is known about the effects of combinatorial dietary compounds on the regulation of epigenetic mechanisms involved in breast cancer prevention. The human diet consists of a multitude of components, and there is a need to elucidate how certain compounds interact in collaboration. Withaferin A (WA), found in the Indian winter cherry and documented as a DNA methyltransferase (DNMT) inhibitor, and sulforaphane (SFN), a well-known histone deacetylase (HDAC) inhibitor found in cruciferous vegetables, are two epigenetic modifying compounds that have only recently been studied in conjunction. The use of DNMT and HDAC inhibitors to reverse the malignant expression of certain genes in breast cancer has shown considerable promise. Previously, we found that SFN + WA synergistically promote breast cancer cell death. Herein, we determined that these compounds inhibit cell cycle progression from S to G2 phase in MDA-MB-231 and MCF-7 breast cancer. Furthermore, we demonstrate that this unique combination of epigenetic modifying compounds down-regulates the levels of Cyclin D1 and CDK4, and pRB; conversely, the levels of E2F mRNA and tumor suppressor p21 are increased independently of p53. We find these events coincide with an increase in unrestricted histone methylation. We propose SFN + WA-induced breast cancer cell death is attributed, in part, to epigenetic modifications that result in the modulated expression of key genes responsible for the regulation of cancer cell senescence. Copyright © 2018 Elsevier Inc. All rights reserved.

Risk Factors of Prolonged Hospitalization in Patients with Hyperemesis Gravidarum

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Hasan Onur Topcu

2015-03-01

Conclusion: Number of vomiting per day and maternal serum TSH levels could help physicians to estimate the risk of prolonged hospitalization; however further investigations are needed in large population studies. Identifying the high risk patients is important both for prevention of HEG and beginning appropriate antiemetic treatment to avoid complications to reduce the economic costs. [Cukurova Med J 2015; 40(1.000: 113-118

Prolonged infusion versus intermittent boluses of β-lactam antibiotics for treatment of acute infections: a meta-analysis.

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Teo, Jocelyn; Liew, Yixin; Lee, Winnie; Kwa, Andrea Lay-Hoon

2014-05-01

The clinical advantages of prolonged (extended/continuous) infusion remain controversial. Previous studies and reviews have failed to show consistent clinical benefits of extending the infusion time. This meta-analysis sought to determine whether prolonged β-lactam infusions were associated with a reduction in mortality and improvement in clinical success. A search of PubMed, EMBASE and The Cochrane Library for randomised controlled trials (RCTs) and observational studies comparing prolonged infusion with intermittent bolus administration of the same antibiotic in hospitalised adult patients was conducted. Primary outcomes evaluated were mortality and clinical success. A total of 29 studies with 2206 patients (18 RCTs and 11 observational studies) were included in the meta-analysis. Compared with intermittent boluses, use of prolonged infusion appeared to be associated with a significant reduction in mortality [pooled relative risk (RR) = 0.66, 95% confidence interval (CI) 0.53-0.83] and improvement in clinical success (RR = 1.12, 95% CI 1.03-1.21). Statistically significant benefit was supported by non-randomised studies (mortality, RR = 0.57, 95% CI 0.43-0.76; clinical success, RR = 1.34, 95% CI 1.02-1.76) but not by RCTs (mortality, RR = 0.83, 95% CI 0.57-1.21; clinical success, RR = 1.05, 95% CI 0.99-1.12). The positive results from observational studies, especially in the face of increasing antibiotic resistance, serve to justify the imperative need to conduct a large-scale, well-designed, multicentre RCT involving critically ill patients infected with high minimum inhibitory concentration pathogens to clearly substantiate this benefit. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Risk factors for QTc interval prolongation

NARCIS (Netherlands)

Heemskerk, Charlotte P.M.; Pereboom, Marieke; van Stralen, Karlijn; Berger, Florine A.; van den Bemt, Patricia M.L.A.; Kuijper, Aaf F.M.; van der Hoeven, Ruud T M; Mantel-Teeuwisse, Aukje K.; Becker, Matthijs L

2018-01-01

Purpose: Prolongation of the QTc interval may result in Torsade de Pointes, a ventricular arrhythmia. Numerous risk factors for QTc interval prolongation have been described, including the use of certain drugs. In clinical practice, there is much debate about the management of the risks involved. In

[Beta lactam antibiotics and the question of dose regimen for severe infection. Prolonged infusion theoretically appealing--yet no evidence of clinical benefit].

Science.gov (United States)

Leander, Gunilla; Eliasson, Erik; Hanberger, Håkan; Giske, Christian

2015-03-24

Patients with severe sepsis/septic shock have a high mortality. Beta-lactam antibiotics are normally first line treatment. This antimicrobial class has been associated with time-dependent efficacy. It is therefore plausible that administration as prolonged infusion will increase the therapeutic effect, as compared to short term bolus injections, which is the most common practice today. We have reviewed 14 randomized controlled studies to investigate whether prolonged infusion provides lower mortality and/or increased clinical cure. In summary, convincing advantages with prolonged infusion could not be found, however randomized studies are heterogeneous, and it cannot be excluded that some subgroups of critically ill patients could benefit from such treatment.

Sulforaphane attenuates di-N-butylphthalate-induced reproductive damage in pubertal mice: Involvement of the Nrf2-antioxidant system.

Science.gov (United States)

Jiang, Xu-Ping; Tang, Jing-Yuan; Xu, Zhen; Han, Peng; Qin, Zhi-Qiang; Yang, Cheng-di; Wang, Shang-Qian; Tang, Min; Wang, Wei; Qin, Chao; Xu, Yang; Shen, Bai-Xin; Zhou, Wei-Min; Zhang, Wei

2017-07-01

di-N-butylphthalate (DBP) is a ubiquitous environmental pollutant used for plastic coating and in the cosmetics industry. It has toxic effects on body health, especially the male reproductive system. Here, we investigated the effects of DBP on the male reproductive system of pubertal mice and explored the protective role of sulforaphane (SFN). The results showed that DBP significantly reduced the anogenital distance, testicular weight, sperm count and motility, and plasma and testicular testosterone levels and significantly increased the oxidative stress, sperm abnormalities, and testicular cell apoptosis. SFN supplementation ameliorated these effects. After DBP stimulation, the transcription factor nuclear factor erythroid-related factor 2 (Nrf2) was adaptively increased together with its target genes, such as HO-1 and NQO1. Upregulation of Nrf2 by SFN reduced the DBP-mediated intracellular oxidative toxicity and also increased testosterone secretion and spermatogenesis, which were decreased by DBP. These findings indicate that SFN can attenuate DBP-induced reproductive damage in pubertal mice via Nrf2-associated pathways. © 2017 Wiley Periodicals, Inc.

Prolonged grief: where to after Diagnostic and Statistical Manual of Mental Disorders, 5th Edition?

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Bryant, Richard A

2014-01-01

Although there is much evidence for the construct of prolonged grief, there was much controversy over the proposal to introduce a prolonged grief diagnosis into Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), and it was finally rejected as a diagnosis in DSM-5. This review outlines the evidence for and against the diagnosis, and highlights the implications of the DSM-5 decision. Convergent evidence indicates that prolonged grief characterized by persistently severe yearning for the deceased is a distinct construct from bereavement-related depression and anxiety, is associated with marked functional impairment, is responsive to targeted treatments for prolonged grief, and has been validated across different cultures, age groups, and types of bereavement. Although DSM-5 has rejected the construct as a formal diagnosis, evidence continues to emerge on related mechanisms, including maladaptive appraisals, memory and attentional processes, immunological and arousal responses, and neural circuitry. It is most likely that the International Classification of Diseases (ICD-11) will introduce a diagnosis to recognize prolonged grief, even though DSM-5 has decided against this option. It is probable that the DSM-5 decision may result in more prolonged grief patients being incorrectly diagnosed with depression after bereavement and possibly incorrectly treated. The DSM-5 decision is unlikely to impact on future research agendas.

Prolonged antibiotics for non-cystic fibrosis bronchiectasis in children and adults.

Science.gov (United States)

Hnin, Khin; Nguyen, Chau; Carson, Kristin V; Evans, David J; Greenstone, Michael; Smith, Brian J

2015-08-13

The vicious cycle hypothesis for bronchiectasis predicts that bacterial colonisation of the respiratory tract perpetuates inflammatory change. This damages the mucociliary escalator, preventing bacterial clearance and allowing persistence of pro-inflammatory mediators. Conventional treatment with physiotherapy and intermittent antibiotics is believed to improve the condition of people with bronchiectasis, although no conclusive data show that these interventions influence the natural history of the condition. Various strategies have been tried to interrupt this cycle of infection and inflammation, including prolonging antibiotic treatment with the goal of allowing the airway mucosa to heal. To determine the benefits of prolonged antibiotic therapy in the treatment of patients with bronchiectasis. We searched the Cochrane Airways Group Trials Register and reference lists of identified articles. Searches were current as of February 2014. Randomised trials examining the use of prolonged antibiotic therapy (for four or more weeks) in the treatment of bronchiectasis compared with placebo or usual care. Two review authors independently assessed trial quality and extracted data. We contacted study authors to ask for missing information. Eighteen trials met the inclusion criteria, randomly assigning a total of 1157 participants. Antibiotics were given for between four weeks and 83 weeks. Limited meta-analysis was possible because of the diversity of outcomes reported in these trials. Based on the number of participants with at least one exacerbation, the meta-analysis showed significant effects in favour of the intervention (odds ratio (OR) 0.31, 95% confidence interval (CI) 0.19 to 0.52; P value antibiotics with a moderate quality grade of supporting evidence (37 per 1000 in the intervention arm (95% CI 13 to 96) and 87 per 1000 in control (OR 0.40, 95% CI 0.14 to 1.11; P value = 0.08). Drug resistance developed in 36 of 220 participants taking antibiotics compared with

Prolongation of islet allograft survival

International Nuclear Information System (INIS)

Lacy, P.E.; Davie, J.M.; Finke, E.H.; Scharp, D.W.

1979-01-01

Pretreatment of donor rats with irradiation and silica followed by in vitro culture of the islets for 1 to 2 days prolonged survival of allografts across a minor histocompatibility barrier if hand-picked, clean islets were used for transplantation. Pretreatment of donor rats with irradiation and silica in conjunction with a single injection of antilymphocyte serum (ALS) into the recipient produced a prolongation of survival of hand-picked islets transplanted across a major histocompatibility barrier

Sulforaphane-rich broccoli sprout extract improves hepatic abnormalities in male subjects

Science.gov (United States)

Kikuchi, Masahiro; Ushida, Yusuke; Shiozawa, Hirokazu; Umeda, Rumiko; Tsuruya, Kota; Aoki, Yudai; Suganuma, Hiroyuki; Nishizaki, Yasuhiro

2015-01-01

AIM: To evaluate effects of dietary supplementation of sulforaphane (SF)-rich broccoli sprout (BS) extract on hepatic abnormalities in Japanese male participants. METHODS: In a randomized, placebo-controlled, double blind trial, male participants with fatty liver received either BS capsules containing glucoraphanin [GR; a precursor of SF (n = 24)] or placebo (n = 28) for 2 mo. Liver function markers, serum levels of aspartate and alanine aminotransferases (AST and ALT, respectively) and γ-glutamyl transpeptidase (γ-GTP) and an oxidative stress marker, urinary levels of 8-hydroxydeoxyguanosine (8-OHdG), were measured and compared in participants before and after the trial period. In an animal model, chronic liver failure was induced in Sprague-Dawley rats by successive intraperitoneal injection with N-nitrosodimethylamine (NDMA) for 4 wk. Concomitantly, rats received AIN-76 diets supplemented with or without BS extract. Thereafter, rats were sacrificed, and their sera and livers were collected to measure serum liver function markers and hepatic levels of thiobarbituric acid reactive substances (TBARS) levels and hepatic glutathione S-transferase (GST) activity, a prototypical phase 2 antioxidant enzyme. RESULTS: Dietary supplementation with BS extract containing SF precursor GR for 2 mo significantly decreased serum levels of liver function markers, ALT [median (interquartile range), before: 54.0 (34.5-79.0) vs after supplementation: 48.5 (33.3-65.3) IU/L, P NDMA-induced chronic liver failure in rats, which was attributable to the suppression of the increase in TBARS through induction of hepatic phase 2 antioxidant enzymes including hepatic GST (86.6 ± 95.2 vs 107.8 ± 7.7 IU/g, P < 0.01). CONCLUSION: Dietary supplementation with BS extract containing the SF precursor GR is likely to be highly effective in improving liver function through reduction of oxidative stress. PMID:26604653

Prolonged pain and disability are common after rib fractures.

Science.gov (United States)

Fabricant, Loic; Ham, Bruce; Mullins, Richard; Mayberry, John

2013-05-01

The contribution of rib fractures to prolonged pain and disability may be underappreciated and undertreated. Clinicians are traditionally taught that the pain and disability of rib fractures resolves in 6 to 8 weeks. This study was a prospective observation of 203 patients with rib fractures at a level 1 trauma center. Chest wall pain was evaluated by the McGill Pain Questionnaire (MPQ) pain rating index (PRI) and present pain intensity (PPI). Prolonged pain was defined as a PRI of 8 or more at 2 months after injury. Prolonged disability was defined as a decrease in 1 or more levels of work or functional status at 2 months after injury. Predictors of prolonged pain and disability were determined by multivariate analysis. One hundred forty-five male patients and 58 female patients with a mean injury severity score (ISS) of 20 (range, 1 to 59) had a mean of 5.4 rib fractures (range, 1 to 29). Forty-four (22%) patients had bilateral fractures, 15 (7%) had flail chest, and 92 (45%) had associated injury. One hundred eighty-seven patients were followed 2 months or more. One hundred ten (59%) patients had prolonged chest wall pain and 142 (76%) had prolonged disability. Among 111 patients with isolated rib fractures, 67 (64%) had prolonged chest wall pain and 69 (66%) had prolonged disability. MPQ PPI was predictive of prolonged pain (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.4 to 2.5), and prolonged disability (OR, 2.2; 95% CI, 1.5 to 3.4). The presence of significant associated injuries was predictive of prolonged disability (OR, 5.9; 95% CI, 1.4 to 29). Prolonged chest wall pain is common, and the contribution of rib fractures to disability is greater than traditionally expected. Further investigation into more effective therapies that prevent prolonged pain and disability after rib fractures is needed. Copyright © 2013 Elsevier Inc. All rights reserved.

Prolonged delirium misdiagnosed as a mood disorder.

Science.gov (United States)

Cao, Fei; Salem, Haitham; Nagpal, Caesa; Teixeira, Antonio L

2017-01-01

Delirium can be conceptualized as an acute decline in cognitive function that typically lasts from hours to a few days. Prolonged delirium can also affect patients with multiple predisposing and/or precipitating factors. In clinical practice, prolonged delirium is often unrecognized, and can be misdiagnosed as other psychiatric disorders. We describe a case of a 59-year-old male presenting with behavioral and cognitive symptoms that was first misdiagnosed as a mood disorder in a general hospital setting. After prolonged delirium due to multiple factors was confirmed, the patient was treated accordingly with symptomatic management. He evolved with progressive improvement of his clinical status. Early diagnosis and management of prolonged delirium are important to improve patient prognosis and avoid iatrogenic measures.

Sulforaphane causes epigenetic repression of hTERT expression in human breast cancer cell lines.

Directory of Open Access Journals (Sweden)

Syed M Meeran

Full Text Available BACKGROUND: Sulforaphane (SFN, an isothiocyanate found in cruciferous vegetables, is a common dietary component that has histone deacetylase inhibition activity and exciting potential in cancer prevention. The mechanisms by which SFN imparts its chemopreventive properties are of considerable interest and little is known of its preventive potential for breast cancer. PRINCIPAL FINDINGS: We found that SFN significantly inhibits the viability and proliferation of breast cancer cells in vitro while it has negligible effects on normal breast cells. Inhibition of telomerase has received considerable attention because of its high expression in cancer cells and extremely low level of expression in normal cells. SFN treatment dose- and time-dependently inhibited human telomerase reverse transcriptase (hTERT, the catalytic regulatory subunit of telomerase, in both MCF-7 and MDA-MB-231 human breast cancer cells. DNA methyltransferases (DNMTs, especially DNMT1 and DNMT3a, were also decreased in SFN-treated breast cancer cells suggesting that SFN may repress hTERT by impacting epigenetic pathways. Down-regulation of DNMTs in response to SFN induced site-specific CpG demethylation occurring primarily in the first exon of the hTERT gene thereby facilitating CTCF binding associated with hTERT repression. Chromatin immunoprecipitation (ChIP analysis of the hTERT promoter revealed that SFN increased the level of active chromatin markers acetyl-H3, acetyl-H3K9 and acetyl-H4, whereas the trimethyl-H3K9 and trimethyl-H3K27 inactive chromatin markers were decreased in a dose-dependent manner. SFN-induced hyperacetylation facilitated the binding of many hTERT repressor proteins such as MAD1 and CTCF to the hTERT regulatory region. Depletion of CTCF using siRNA reduced the SFN-induced down-regulation of hTERT mRNA transcription in these breast cancer cells. In addition, down-regulation of hTERT expression facilitated the induction of cellular apoptosis in human breast

Significant prolongation of hamster liver transplant survival in Lewis rats by total-lymphoid irradiation, cyclosporine, and splenectomy

International Nuclear Information System (INIS)

Yamaguchi, Y.; Halperin, E.C.; Harland, R.C.; Wyble, C.; Bollinger, R.R.

1990-01-01

The effects of total lymphoid irradiation, cyclosporine and splenectomy alone and in combination have been studied in liver transplants from the LVG hamster to the LEW rat. Neither CsA alone, splenectomy alone, nor TLI alone prolonged graft survival. CsA/splenectomy and TLI/CsA produced significant prolongation of graft survival. TLI/CsA/splenectomy prolonged graft survival by over sixfold compared with controls. While CsA alone was ineffective in reducing lymphocytotoxic antidonor antibody, splenectomy alone or CsA/splenectomy did significantly suppress production of antibody. Only very low levels of antibody could be detected in animals treated with TLI/CsA/splenectomy. TLI/CsA/splenectomy has an immunosuppressive effect sufficient to significantly prolong liver graft survival in the LVG hamster to LEW rat combination and may represent a promising treatment protocol in experimental cross-species transplantation

[Prolonged desensitization pretreatment for in vitro fertilization in women with polycystic ovary].

Science.gov (United States)

Kuczyński, W; Czech, R; Redźko, S; Wasilewski, T; Mrugacz, G; Wołczyński, S; Pietrewicz, P; Grochowski, D; Szamatowicz, M

2000-09-01

To analyse the outcome of intracytoplasmic sperm injection (ICSI) in women with severe polycystic ovary disease (PCD), stimulated after prolonged pituitary desensitization in comparison with regular long protocol therapy. The results of controlled ovarian hyperstimulation (COH), fertilization rate, early embryo development parameters and clinical pregnancy rates were compared depending on the duration of pituitary desensitization before gonadotropin administration. A total of 60 patients with severe PCOD were desensitized with GnRH agonist up to 30 days before COH. The results were compared with the group of 213 patients with mild PCOD treated with regular long protocol (control). We observed a slightly higher rate of mature oocytes MII as well as the number of embryos obtained in the control group, however the pregnancy rate in the group with prolonged desensitization was significantly higher (50%) in comparison to the control group (33.8%). The prolonged pituitary desensitization before controlled ovarian hyperstimulation gives better chance for obtaining pregnancy in patients with severe PCOD. It could be recommended facing previous treatment failure.

Limitation of life-sustaining treatment in patients with prolonged admission to the ICU. Current situation in Spain as seen from the EPIPUSE Study.

Science.gov (United States)

Hernández-Tejedor, A; Martín Delgado, M C; Cabré Pericas, L; Algora Weber, A

2015-10-01

Limitation of life-sustaining treatment (LLST) is a recommended practice in certain circumstances. Limitation practices are varied, and their application differs from one center to another. The present study evaluates the current situation of LLST practices in patients with prolonged admission to the ICU who suffer worsening of their condition. A prospective, observational cohort study was carried out. Seventy-five Spanish ICUs. A total of 589 patients suffering 777 complications or adverse events with organ function impairment after day 7 of admission, during a three-month recruitment period. The timing of limitation, the subject proposing LLST, the degree of agreement within the team, the influence of LLST upon the doctor-patient-family relationship, and the way in which LLST is implemented. LLST was proposed in 34.3% of the patients presenting prolonged admission to the ICU with severe complications. The incidence was higher in patients with moderate to severe lung disease, cancer, immunosuppressive treatment or dependence for basic activities of daily living. LLST was finally implemented in 97% of the cases in which it was proposed. The decision within the medical team was unanimous in 87.9% of the cases. The doctor-patient-family relationship usually does not change or even improves in this situation. LLST in ICUs is usually carried out under unanimous decision of the medical team, is performed more frequently in patients with severe comorbidity, and usually does not have a negative impact upon the relationship with the patients and their families. Copyright © 2013 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

Endoscopic stent suture fixation for prevention of esophageal stent migration during prolonged dilatation for achalasia treatment.

Science.gov (United States)

Rieder, E; Asari, R; Paireder, M; Lenglinger, J; Schoppmann, S F

2017-04-01

The aim of this study is to compare endoscopic stent suture fixation with endoscopic clip attachment or the use of partially covered stents (PCS) regarding their capability to prevent stent migration during prolonged dilatation in achalasia. Large-diameter self-expanding metal stents (30 mm × 80 mm) were placed across the gastroesophageal junction in 11 patients with achalasia. Stent removal was scheduled after 4 to 7 days. To prevent stent dislocation, endoscopic clip attachment, endoscopic stent suture fixation, or PCS were used. The Eckardt score was evaluated before and 6 months after prolonged dilatation. After endoscopic stent suture fixation, no (0/4) sutured stent migrated. When endoscopic clips were used, 80% (4/5) clipped stents migrated (p = 0.02). Of two PCS (n = 2), one migrated and one became embedded leading to difficult stent removal. Technical adverse events were not seen in endoscopic stent suture fixation but were significantly correlated with the use of clips or PCS (r = 0.828, p = 0.02). Overall, 72% of patients were in remission regarding their achalasia symptoms 6 months after prolonged dilatation. Endoscopic suture fixation of esophageal stents but not clip attachment appears to be the best method of preventing early migration of esophageal stents placed at difficult locations such as at the naive gastroesophageal junction. © The Authors 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Safety and Efficacy of BAY 94-9027, a Prolonged-Half-Life Factor VIII

DEFF Research Database (Denmark)

Reding, M T; Ng, H J; Poulsen, Lone Hvitfeldt

2017-01-01

BACKGROUND: BAY 94-9027 is a B-domain-deleted prolonged-half-life recombinant factor VIII (FVIII) conjugates in a site-specific manner with polyethylene glycol. OBJECTIVE: Assess efficacy and safety of BAY 94-9027 for prophylaxis and treatment of bleeds in patients with severe hemophilia A PATIEN...

Licence prolongations of US nuclear power plants

International Nuclear Information System (INIS)

2004-04-01

Licences of US nuclear reactors were initially attributed for a 40 years duration. However, the vast majority of the reactors can benefit of a licence prolongation for a period of 20 years maximum. This article recalls first the procedure to follow for the licence prolongation demands (safety analysis, components aging, environmental impact statement), and then it makes a status of the accepted prolongations, of the demands under examination, and of the demands that should be presented in the next 5 years. (J.S.)

Sulforaphane modulates telomerase activity via epigenetic regulation in prostate cancer cell lines.

Science.gov (United States)

Abbas, Ata; Hall, J Adam; Patterson, William L; Ho, Emily; Hsu, Anna; Al-Mulla, Fahd; Georgel, Philippe T

2016-02-01

Epidemiologic studies have revealed that diets rich in sulforaphane (SFN), an isothiocyanate present in cruciferous vegetables, are associated with a marked decrease in prostate cancer incidence. The chemo-preventive role of SFN is associated with its histone de-acetylase inhibitor activity. However, the effect of SFN on chromatin composition and dynamic folding, especially in relation to HDAC inhibitor activity, remains poorly understood. In this study, we found that SFN can inhibit the expression and activity of human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase, in 2 prostate cancer cell lines. This decrease in gene expression is correlated with SFN-induced changes in chromatin structure and composition. The SFN-mediated changes in levels of histone post-translational modifications, more specifically acetylation of histone H3 lysine 18 and di-methylation of histone H3 lysine 4, 2 modifications linked with high risk of prostate cancer recurrence, were associated with regulatory elements within the hTERT promoter region. Chromatin condensation may also play a role in SFN-mediated hTERT repression, since expression and recruitment of MeCP2, a known chromatin compactor, were altered in SFN treated prostate cancer cells. Chromatin immuno-precipitation (ChIP) of MeCP2 showed enrichment over regions of the hTERT promoter with increased nucleosome density. These combined results strongly support a role for SFN in the mediation of epigenetic events leading to the repression of hTERT in prostate cancer cells. This ability of SFN to modify chromatin composition and structure associated with target gene expression provides a new model by which dietary phytochemicals may exert their chemoprevention activity.

Diclofenac Prolongs Repolarization in Ventricular Muscle with Impaired Repolarization Reserve

Science.gov (United States)

Kristóf, Attila; Husti, Zoltán; Koncz, István; Kohajda, Zsófia; Szél, Tamás; Juhász, Viktor; Biliczki, Péter; Jost, Norbert; Baczkó, István; Papp, Julius Gy; Varró, András; Virág, László

2012-01-01

Background The aim of the present work was to characterize the electrophysiological effects of the non-steroidal anti-inflammatory drug diclofenac and to study the possible proarrhythmic potency of the drug in ventricular muscle. Methods Ion currents were recorded using voltage clamp technique in canine single ventricular cells and action potentials were obtained from canine ventricular preparations using microelectrodes. The proarrhythmic potency of the drug was investigated in an anaesthetized rabbit proarrhythmia model. Results Action potentials were slightly lengthened in ventricular muscle but were shortened in Purkinje fibers by diclofenac (20 µM). The maximum upstroke velocity was decreased in both preparations. Larger repolarization prolongation was observed when repolarization reserve was impaired by previous BaCl2 application. Diclofenac (3 mg/kg) did not prolong while dofetilide (25 µg/kg) significantly lengthened the QTc interval in anaesthetized rabbits. The addition of diclofenac following reduction of repolarization reserve by dofetilide further prolonged QTc. Diclofenac alone did not induce Torsades de Pointes ventricular tachycardia (TdP) while TdP incidence following dofetilide was 20%. However, the combination of diclofenac and dofetilide significantly increased TdP incidence (62%). In single ventricular cells diclofenac (30 µM) decreased the amplitude of rapid (IKr) and slow (IKs) delayed rectifier currents thereby attenuating repolarization reserve. L-type calcium current (ICa) was slightly diminished, but the transient outward (Ito) and inward rectifier (IK1) potassium currents were not influenced. Conclusions Diclofenac at therapeutic concentrations and even at high dose does not prolong repolarization markedly and does not increase the risk of arrhythmia in normal heart. However, high dose diclofenac treatment may lengthen repolarization and enhance proarrhythmic risk in hearts with reduced repolarization reserve. PMID:23300901

Drug-Induced QTc Interval Prolongation: A Multicenter Study to Detect Drugs and Clinical Factors Involved in Every Day Practice.

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Keller, Guillermo A; Alvarez, Paulino A; Ponte, Marcelo L; Belloso, Waldo H; Bagnes, Claudia; Sparanochia, Cecilia; Gonzalez, Claudio D; Villa Etchegoyen, M Cecilia; Diez, Roberto A; Di Girolamo, Guillermo

2016-01-01

The actual prevalence of drug induced QTc prolongation in clinical practice is unknown. Our objective was to determine the occurrence and characteristics of drug-induced QT prolongation in several common clinical practices. Additionally, a subgroup of patients treated with dextropropoxyphene of particular interest for the regulatory authority was analysed. Medical history and comorbidities predisposing to QT interval prolongation were registered for 1270 patient requiring medical assistance that involved drug administration. Three ionograms and ECGs were performed: baseline, intra- and after treatment; QT interval was corrected with Bazzet formula. Among patients, 9.9% presented QTc >450/470 ms, 3% QTc > 500 ms, 12.7% ΔQTc >30 ms and 5.2% ΔQTc >60 ms. QTc prolongation associated with congestive heart failure, ischemic cardiopathy, diabetes, renal failure, arrhythmias, hypothyroidism, and bradycardia. At univariate analysis, clarithromycin, haloperidol, tramadol, amiodarone, glyceryl trinitrate, amoxicillin + clavulanic acid, amoxicillin + sulbactam, ampicillin + sulbactam, fentanyl, piperacillin + tazobactam, and diazepam prolonged QTc. Prolongation remained significantly associated with furosemide, clarithromycin, glyceryl trinitrate and betalactamase inhibitors after multivariate analysis. QT interval prolongation in everyday practice is frequent, in association to clinical factors and drugs that can be easily identified for monitoring and prevention strategies.

Prenatal risk indicators of a prolonged pregnancy

DEFF Research Database (Denmark)

Olesen, Annette Wind; Westergaard, Jes Grabow; Olsen, Jørn

2006-01-01

BACKGROUND: Few prenatal risk factors of prolonged pregnancy, a pregnancy of 42 weeks or more, are known. The objective was to examine whether sociodemographic, reproductive, toxicologic, or medical health conditions were associated with the risk of prolonged pregnancy. METHODS: Data from...

An unusual case of prolonged post-endoscopic retrograde cholangiopancreatography jaundice.

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Tziatzios, Georgios; Gkolfakis, Paraskevas; Papanikolaou, Ioannis S; Dimitriadis, George; Triantafyllou, Konstantinos

2016-04-01

Despite the effectiveness of endoscopic retrograde cholangiopancreatography (ERCP) for the treatment of choledocholithiasis, various complications have been described. We herein report the first case of prolonged post-ERCP jaundice due to toxicity of the contrast agent Iobitridol (®XENETIX, Guerbet, Roissy CdG Cedex, France) in a patient who underwent ERCP with sphincterectomy and common bile duct stone removal. While clinical improvement and normalization of aminotransferases and cholestatic enzymes after the procedure, an unexplained increase of direct bilirubin was noticed. A second ERCP was performed one week later, excluding possible remaining choledocholithiasis. Nevertheless, serum direct bilirubin increased further up to 15 mg/dL. Other potential causes of direct hyperbilirubinemia were ruled out and patient's liver biopsy was compatible with drug-induced liver toxicity. Additionally, the cause-result time connection between the use of Iobitridol and bilirubin increase indicated the possibility of a toxic effect related to the repeated use of the particular contrast agent. Iobitridol, a contrast agent, can induce prolonged direct hyperbilirubinemia.

Does UTI cause prolonged jaundice in otherwise well infants?

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Chowdhury, Tanzila; Kisat, Hamudi; Tullus, Kjell

2015-07-01

The symptoms of urinary tract infections in infants are very non-specific and have historically included prolonged hyperbilirubinaemia. We studied the results of routine urine samples in 319 infants with prolonged jaundice. Convincing findings of UTI was not found in any of these children even if one of them was treated with antibiotics after four consecutive urine cultures with different bacteria. A urine culture might thus not be an appropriate investigation in a child with prolonged jaundice without any other symptoms of UTI. • The symptoms of UTI in infancy are very non-specific. • Old studies suggest that prolonged hyperbilirubinaemia is one such symptom; more modern studies give more conflicting results. What is New: • Our study could not confirm that children with prolonged jaundice have an increased risk of UTI. • Routine urine testing is thus not needed in otherwise healthy infants with prolonged jaundice.

Mixed models for data from thorough QT studies: part 2. One-step assessment of conditional QT prolongation.

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Schall, Robert

2011-01-01

We investigate mixed analysis of covariance models for the 'one-step' assessment of conditional QT prolongation. Initially, we consider three different covariance structures for the data, where between-treatment covariance of repeated measures is modelled respectively through random effects, random coefficients, and through a combination of random effects and random coefficients. In all three of those models, an unstructured covariance pattern is used to model within-treatment covariance. In a fourth model, proposed earlier in the literature, between-treatment covariance is modelled through random coefficients but the residuals are assumed to be independent identically distributed (i.i.d.). Finally, we consider a mixed model with saturated covariance structure. We investigate the precision and robustness of those models by fitting them to a large group of real data sets from thorough QT studies. Our findings suggest: (i) Point estimates of treatment contrasts from all five models are similar. (ii) The random coefficients model with i.i.d. residuals is not robust; the model potentially leads to both under- and overestimation of standard errors of treatment contrasts and therefore cannot be recommended for the analysis of conditional QT prolongation. (iii) The combined random effects/random coefficients model does not always converge; in the cases where it converges, its precision is generally inferior to the other models considered. (iv) Both the random effects and the random coefficients model are robust. (v) The random effects, the random coefficients, and the saturated model have similar precision and all three models are suitable for the one-step assessment of conditional QT prolongation. Copyright © 2010 John Wiley & Sons, Ltd.

Prolonged fever and involuntary weight loss as manifestations of bacterial endocarditis: A case report

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Sukmawati, N. M. D. D.; Merati, T. P.; Somia, A.; Utama, S.; Gayatri, Y.

2018-03-01

We reported an unusual presentation of prolonged fever and involuntary weight loss in older adult as a manifestation of infective bacterial endocarditis. The patient had pre-existing compensated asymptomatic valvular heart disease without treatment. A positive fecal occult blood test is prompting an investigation of malignancy of gastrointestinal as one of other possible cause of prolonged fever with wasting, evaluation of HIV serostatus shows seronegative. The case fulfilled criteria for definitive infective endocarditis: one major criterion of positive blood culture for Streptococcus mitis, which was one of viridans group streptococci and three minor criteria of fever at least 38°Celsius, immunologic phenomena in the form of glomerulonephritis, and a predisposing heart condition. One course of third-generation cephalosporin successfully cleared the Streptococcus mitis infection proven by culture. Infective endocarditis should be considered as one of the causes of prolonged fever with wasting, especially in cases with the previous history of heart disease.

Peculiarities of prolonged neonatal jaundice and possibility of their pharmacological correction

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Yablon O.

2017-03-01

Full Text Available Purpose: to study of peculiarities of prolonged neonatal jaundice and the possibility of pharmacological correction based on ursodeoxycholic acid. Patients and methods. Were examined 42 children (29 boys and 13 girls with prolonged neonatal jaundice. The study group included 22 children, who in complex of pharmacological treatment received the ursodeoxycholic acid, the comparison group comprised 20 children who received only basic treatment such as phototherapy. The effectiveness of the treatment was evaluated by biochemical parameters of blood (bilirubin and its fractions, liver transaminase, the level of serum alpha&fetoprotein, epidermal growth factor were determined by ELISA. Results. All children were full term. The mean age of children in the study group was 20.8±1.9 days in the control group and 22±1.5 days. In the main group indirect bilirubin was above on 35 μmol/l, but significant differences in the level of indirect bilirubin were absent at the beginning of treatment in both groups of children included in the study, respectively, 286±14,3 μmol/l and 250±16.4 μmol/l (p>0.05. The average indirect bilirubin after treatment significantly decreased in both groups but in the main group, a decline of 49% in the comparison group decrease of bilirubin was on 30%. It was also noted signs of neonatal cholestasis: every fifth child had the increased level of direct bilirubin, every third child had elevated liver transaminase. Also, there were no significant differenses in the mean levels of serum AFP and EGF, there were higher in children of both study groups, respectively, mean level of serum AFP in the main group was 834±28 ng/ml in the comparison group — 809±26 ng/ml(p>0.05; mean level of serum EGF in the main group 651±57,2 ng/ml in the comparison group — 714±27 ng/ml(p>0.05. However, in children who were treated with ursodeoxycholic acid (UkrlivR suspension the levels of serum AFP and EGF were significantly decreased, in

Diclofenac prolongs repolarization in ventricular muscle with impaired repolarization reserve.

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Attila Kristóf

Full Text Available BACKGROUND: The aim of the present work was to characterize the electrophysiological effects of the non-steroidal anti-inflammatory drug diclofenac and to study the possible proarrhythmic potency of the drug in ventricular muscle. METHODS: Ion currents were recorded using voltage clamp technique in canine single ventricular cells and action potentials were obtained from canine ventricular preparations using microelectrodes. The proarrhythmic potency of the drug was investigated in an anaesthetized rabbit proarrhythmia model. RESULTS: Action potentials were slightly lengthened in ventricular muscle but were shortened in Purkinje fibers by diclofenac (20 µM. The maximum upstroke velocity was decreased in both preparations. Larger repolarization prolongation was observed when repolarization reserve was impaired by previous BaCl(2 application. Diclofenac (3 mg/kg did not prolong while dofetilide (25 µg/kg significantly lengthened the QT(c interval in anaesthetized rabbits. The addition of diclofenac following reduction of repolarization reserve by dofetilide further prolonged QT(c. Diclofenac alone did not induce Torsades de Pointes ventricular tachycardia (TdP while TdP incidence following dofetilide was 20%. However, the combination of diclofenac and dofetilide significantly increased TdP incidence (62%. In single ventricular cells diclofenac (30 µM decreased the amplitude of rapid (I(Kr and slow (I(Ks delayed rectifier currents thereby attenuating repolarization reserve. L-type calcium current (I(Ca was slightly diminished, but the transient outward (I(to and inward rectifier (I(K1 potassium currents were not influenced. CONCLUSIONS: Diclofenac at therapeutic concentrations and even at high dose does not prolong repolarization markedly and does not increase the risk of arrhythmia in normal heart. However, high dose diclofenac treatment may lengthen repolarization and enhance proarrhythmic risk in hearts with reduced repolarization reserve.

Multifactorial QT Interval Prolongation and Takotsubo Cardiomyopathy

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Michael Gysel

2014-01-01

Full Text Available A 71-year-old woman collapsed while working as a grocery store cashier. CPR was performed and an AED revealed torsades de pointes (TdP. She was subsequently defibrillated resulting in restoration of sinus rhythm with a QTc interval of 544 msec. Further evaluation revealed a diagnosis of Takotsubo Cardiomyopathy (TCM contributing to the development of a multifactorial acquired long QT syndrome (LQTS. The case highlights the role of TCM as a cause of LQTS in the setting of multiple risk factors including old age, female gender, hypokalemia, and treatment with QT prolonging medications. It also highlights the multifactorial nature of acquired LQTS and lends support to growing evidence of an association with TCM.

Prolonged labour as indication for emergency caesarean section

DEFF Research Database (Denmark)

Maaløe, Nanna; Sorensen, B L; Onesmo, R

2012-01-01

To audit the quality of obstetric management preceding emergency caesarean sections for prolonged labour.......To audit the quality of obstetric management preceding emergency caesarean sections for prolonged labour....

Prolonged Pregnancy: Methods, Causal Determinants and Outcome

DEFF Research Database (Denmark)

Olesen, Annette Wind

) to study the incidence of prolonged pregnancy as a function of methods for determining gestational age; 2) to determine the risk of obstetrical and fetal complications in prolonged pregnancy; 3) to validate the self-reported gestational age in the National Birth Cohort; 4) to determine whether...... an ultrasound scan in the first or second trimester, or menstrual history was best at predicting the day of delivery; 5) to study the risk of recurrence of prolonged pregnancy as a function of change in male partner, social status and municipality; and 6) to detect prenatal risk indicators of prolonged...... of perinatal and obstetrical complications was high in post-term delivery compared to term delivery (OR between 1.2 and 3.1). The risk of perinatal death (OR=1.36 (1.08-1.72)) was also higher in the post-term group (I). The self-reported gestational ages in the National Birth Cohort correlated well with data...

Effects of prolonged treatment with memantine in the MRL model of CNS lupus.

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Marcinko, Katarina; Parsons, Tiffany; Lerch, Jason P; Sled, John G; Sakic, Boris

2012-09-01

Neuropsychiatric manifestations and brain atrophy of unknown etiology are common and severe complications of systemic lupus erythematosus (SLE). An autoantibody that binds to N-methyl-D-aspartate (NMDA) receptor NR2 has been proposed as a key factor in the etiology of central nervous system (CNS) SLE. This hypothesis was supported by evidence suggesting memantine (MEM), an uncompetitive NMDA receptor antagonist, prevents behavioral dysfunction and brain pathology in healthy mice immunized with a peptide similar to an epitope on the NR2 receptor. Given that SLE is a chronic condition, we presently examine the effects of MEM in MRL/lpr mice, which develop behavioral deficits alongside SLE-like disease. A broad behavioral battery and 7-Tesla MRI were used to examine whether prolonged treatment with MEM (~25 mg/kg b.w. in drinking water) prevents CNS involvement in this spontaneous model of SLE. Although MEM increased novel object exploration in MRL/lpr mice, it did not show other beneficial, substrain-specific effects. Conversely, MEM was detrimental to spontaneous activity in control MRL +/+ mice and had a negative effect on body mass gain. Similarly, MRI revealed comparable increases in the volume of periventricular structures in MEM-treated groups. Sustained exposure to MEM affects body growth, brain morphology, and behavior primarily by pharmacological, and not autoimmunity-dependant mechanisms. Substrain-specific improvement in exploratory behavior of MEM-treated MRL/lpr mice may indicate that the NMDA system is merely a constituent of a complex pathogenenic cascade. However, it was evident that chronic administration of MEM is unable to completely prevent the development of a CNS SLE-like syndrome.

Inhibition of spontaneous recovery of fear by mGluR5 after prolonged extinction training.

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Sheng-Chun Mao

Full Text Available Fear behavior is vital for survival and involves learning contingent associations of non-threatening cues with aversive stimuli. In contrast, excessive levels of fear can be maladaptive and lead to anxiety disorders. Generally, extensive sessions of extinction training correlates with reduced spontaneous recovery. The molecular mechanisms underlying the long-term inhibition of fear recovery following repeated extinction training are not fully understood. Here we show that in rats, prolonged extinction training causes greater reduction in both fear-potentiated startle and spontaneous recovery. This effect was specifically blocked by metabotropic glutamate receptor 5 (mGluR5, but not by mGluR1 antagonists and by a protein synthesis inhibitor. Similar inhibition of memory recovery following prolonged extinction training was also observed in mice. In agreement with the instrumental role of mGluR5 in the prolonged inhibition of fear recovery, we found that FMR1-/- mice which exhibit enhanced mGluR5-mediated signaling exhibit lower spontaneous recovery of fear after extinction training than wild-type littermates. At the molecular level, we discovered that prolonged extinction training reversed the fear conditioning-induced increase in surface expression of GluR1, AMPA/NMDA ratio, postsynaptic density-95 (PSD-95 and synapse-associated protein-97 (SAP97. Accordingly, delivery of Tat-GluR2(3Y, a synthetic peptide that blocks AMPA receptor endocytosis, inhibited prolonged extinction training-induced inhibition of fear recovery. Together, our results demonstrate that prolonged extinction training results in the mGluR5-dependent long-term inhibition of fear recovery. This effect may involve the degradation of original memory and may explain the beneficial effects of prolonged exposure therapy for the treatment of phobias.

Inhibition of spontaneous recovery of fear by mGluR5 after prolonged extinction training.

Science.gov (United States)

Mao, Sheng-Chun; Chang, Chih-Hua; Wu, Chia-Chen; Orejarena, M Juliana; Orejanera, Maria Juliana; Manzoni, Olivier J; Gean, Po-Wu

2013-01-01

Fear behavior is vital for survival and involves learning contingent associations of non-threatening cues with aversive stimuli. In contrast, excessive levels of fear can be maladaptive and lead to anxiety disorders. Generally, extensive sessions of extinction training correlates with reduced spontaneous recovery. The molecular mechanisms underlying the long-term inhibition of fear recovery following repeated extinction training are not fully understood. Here we show that in rats, prolonged extinction training causes greater reduction in both fear-potentiated startle and spontaneous recovery. This effect was specifically blocked by metabotropic glutamate receptor 5 (mGluR5), but not by mGluR1 antagonists and by a protein synthesis inhibitor. Similar inhibition of memory recovery following prolonged extinction training was also observed in mice. In agreement with the instrumental role of mGluR5 in the prolonged inhibition of fear recovery, we found that FMR1-/- mice which exhibit enhanced mGluR5-mediated signaling exhibit lower spontaneous recovery of fear after extinction training than wild-type littermates. At the molecular level, we discovered that prolonged extinction training reversed the fear conditioning-induced increase in surface expression of GluR1, AMPA/NMDA ratio, postsynaptic density-95 (PSD-95) and synapse-associated protein-97 (SAP97). Accordingly, delivery of Tat-GluR2(3Y), a synthetic peptide that blocks AMPA receptor endocytosis, inhibited prolonged extinction training-induced inhibition of fear recovery. Together, our results demonstrate that prolonged extinction training results in the mGluR5-dependent long-term inhibition of fear recovery. This effect may involve the degradation of original memory and may explain the beneficial effects of prolonged exposure therapy for the treatment of phobias.

Levo-α-acetylmethadol (LAAM induced QTc-prolongation - results from a controlled clinical trial

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Wieneke H

2009-01-01

Full Text Available Abstract Background Due to potential proarrhythmic side-effects levo-α-Acetylmethadol (LAAM is currently not available in EU countries as maintenance drug in the treatment of opiate addiction. However, recent studies and meta-analyses underline the clinical advantages of LAAM with respect to the reduction of heroin use. Thus a reappraisal of LAAM has been demanded. The aim of the present study was to evaluate the relative impact of LAAM on QTc-interval, as a measure of pro-arrhythmic risk, in comparison to methadone, the current standard in substitution therapy. Methods ECG recordings were analysed within a randomized, controlled clinical trial evaluating the efficacy and tolerability of maintenance treatment with LAAM compared with racemic methadone. Recordings were done at two points: 1 during a run-in period with all patients on methadone and 2 24 weeks after randomisation into methadone or LAAM treatment group. These ECG recordings were analysed with respect to QTc-values and QTc-dispersion. Mean values as well as individual changes compared to baseline parameters were evaluated. QTc-intervals were classified according to CPMP-guidelines. Results Complete ECG data sets could be obtained in 53 patients (31 LAAM-group, 22 methadone-group. No clinical cardiac complications were observed in either group. After 24 weeks, patients receiving LAAM showed a significant increase in QTc-interval (0.409 s ± 0.022 s versus 0.418 s ± 0.028 s, p = 0.046, whereas no significant changes could be observed in patients remaining on methadone. There was no statistically significant change in QTc-dispersion in either group. More patients with borderline prolonged and prolonged QTc-intervals were observed in the LAAM than in the methadone treatment group (n = 7 vs. n = 1; p = 0.1. Conclusions In this controlled trial LAAM induced QTc-prolongation in a higher degree than methadone. Given reports of severe arrhythmic events, careful ECG-monitoring is recommended

IL-7 treatment augments and prolongs sepsis-induced expansion of IL-10-producing B lymphocytes and myeloid-derived suppressor cells.

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Kulkarni, Upasana; Herrmenau, Christoph; Win, Stephanie J; Bauer, Michael; Kamradt, Thomas

2018-01-01

Immunological dysregulation in sepsis is associated with often lethal secondary infections. Loss of effector cells and an expansion of immunoregulatory cell populations both contribute to sepsis-induced immunosuppression. The extent and duration of this immunosuppression are unknown. Interleukin 7 (IL-7) is important for the maintenance of lymphocytes and can accelerate the reconstitution of effector lymphocytes in sepsis. How IL-7 influences immunosuppressive cell populations is unknown. We have used the mouse model of peritoneal contamination and infection (PCI) to investigate the expansion of immunoregulatory cells as long-term sequelae of sepsis with or without IL-7 treatment. We analysed the frequencies and numbers of regulatory T cells (Tregs), double negative T cells, IL-10 producing B cells and myeloid-derived suppressor cells (MDSCs) for 3.5 months after sepsis induction. Sepsis induced an increase in IL-10+ B cells, which was enhanced and prolonged by IL-7 treatment. An increased frequency of MDSCs in the spleen was still detectable 3.5 months after sepsis induction and this was more pronounced in IL-7-treated mice. MDSCs from septic mice were more potent at suppressing T cell proliferation than MDSCs from control mice. Our data reveal that sepsis induces a long lasting increase in IL-10+ B cells and MDSCs. Late-onset IL-7 treatment augments this increase, which should be relevant for clinical interventions.

Selective lymphoid irradiation: III. Prolongation of cardiac xenografts and allografts in presensitized rats

International Nuclear Information System (INIS)

Hardy, M.A.; Oluwole, S.; Fawwaz, R.; Satake, K.; Nowygrod, R.; Reemtsma, K.

1982-01-01

Selective lymphoid irradiation (SLI) with palladium-109-hematoporphyrin (Pd-H) combined with antilymphocyte globulin (ALG) induces either donor-specific permanent rat heart allograft acceptance or significant allograft prolongation depending on the degree of donor-recipient matching. The purpose of this study was to determine if SLI combined with ALG can affect ACI heart allograft survival in Lewis recipients presensitized to ACI, and of hamster heart xenografts of Lewis rats. SLI combined with ALG delays allograft and xenograft rejection in the presence of induced or preformed antidonor antibodies, and converts primarily a humoral rejection into a cellular rejection by mechanisms as yet uncertain. Such peritransplant treatment had significant effect on the levels of antidonor complement-dependent cytotoxic antibody titers but did not correlate directly with graft survival. Histological analysis of rejected hearts in all groups demonstrated primarily a humoral hyperacute rejection in control animals and in recipients treated with ALG alone, while peritransplant treatment with Pd-H and ALG resulted not only in prolonged graft survival but histologically, primarily a cellular rejection of the graft

QTc interval prolongation in children with Turner syndrome: the results of exercise testing and 24-h ECG.

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Dalla Pozza, Robert; Bechtold, Susanne; Urschel, Simon; Netz, Heinrich; Schwarz, Hans-Peter

2009-01-01

Turner syndrome (TS) is the most common sex chromosome abnormality in females. Recently, a prolongation of the rate-corrected QT (QTc) interval in the electrocardiogram (ECG) of TS patients has been reported. A prolonged QTc interval has been correlated to an increased risk for sudden cardiac death, and medical treatment is warranted in patients with congenital long QT syndrome (LQTS). Additionally, several drugs of common use are contraindicated in LQTS because of their effects on myocardial repolarization. The importance of the QTc prolongation in TS patients is not known at present. Eighteen TS patients with a prolonged QTc interval (group 1) and 11 TS patients with a normal QTc interval (group 2) (mean age 12.6+/-3.1 vs. 11.8+/-2.1 years, respectively) were tested. The QTc interval was calculated during exercise testing and during 24-h ECG recordings. None of the patients experienced adverse cardiac events during the tests. The mean QTc interval decreased from 0.467 to 0.432 s in group 1 and from 0.432 to 0.412 s in group 2. During the 24-h ECG, the maximum QTc interval was significantly prolonged in group 1 (0.51 vs. 0.465 s, pinformation about the cardiac risk in the single TS patient with a prolonged QTc interval. This helps in counseling these girls, as clear therapeutic guidelines are currently lacking.

[Representation of Internal Medicine in G-DRG System - Analysis of Reasons for Prolonged Length of Stay].

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Siam, Kristina; Roeder, Norbert; Fölsch, Ulrich R; Spies, Hans-Friedrich

2017-08-01

Background  There is an ongoing discussion within the German Society of Internal Medicine (DGIM) and the Professional Association of German Internists (BDI) about the appropriate depiction and remuneration of internal medicine in the G-DRG. Method  Therefore, cases with a significantly prolonged length of stay were analyzed in a multicenter study. 124 cases from 6 hospitals were collected for evaluation. Results  The results show that the observed prolongation of hospitalization was mainly due to medical reasons. Discussion  Thus, patients with unclear symptoms and consequently need for a thorough workup could not be identified to cause longer inpatient stay. Instead, treatment complications and comorbidities led to extended hospitalization. The results also reveal prolonged hospitalization as a consequence of unsettled or delayed postdischarge care e. g. in rehabilitation facilities. © Georg Thieme Verlag KG Stuttgart · New York.

In vivo relaxation time measurements on a murine tumor model--prolongation of T1 after photodynamic therapy.

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Liu, Y H; Hawk, R M; Ramaprasad, S

1995-01-01

RIF tumors implanted on mice feet were investigated for changes in relaxation times (T1 and T2) after photodynamic therapy (PDT). Photodynamic therapy was performed using Photofrin II as the photosensitizer and laser light at 630 nm. A home-built proton solenoid coil in the balanced configuration was used to accommodate the tumors, and the relaxation times were measured before, immediately after, and up to several hours after therapy. Several control experiments were performed untreated tumors, tumors treated with Photofrin II alone, or tumors treated with laser light alone. Significant increases in T1s of water protons were observed after PDT treatment. In all experiments, 31P spectra were recorded before and after the therapy to study the tumor status and to confirm the onset of PDT. These studies show significant prolongation of T1s after the PDT treatment. The spin-spin relaxation measurements, on the other hand, did not show such prolongation in T2 values after PDT treatment.

SU119. Internalized Stigma in Adults With Early-Phase vs Prolonged Psychosis

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Firmin, Ruth; Vohs, Jenifer; Luther, Lauren; Yanos, Philip; Leonhardt, Bethany; Lysaker, Paul

2017-01-01

Abstract Background: While internalized stigma is associated with negative outcomes among those with prolonged psychosis, surprisingly little work has focused on when in the course of one’s illness stigma is internalized and the impact of internalization on symptoms or quality of life over the course of the illness. Therefore, this study investigated whether (1) internalized stigma is greater among those later in the course of psychosis and (2) whether internalized stigma has a stronger negative relationship with quality of life or symptoms among those with prolonged compared to early-phase psychosis. Methods: Individuals with early-phase (n = 40) and prolonged psychosis (n = 71) who were receiving outpatient services at an early-intervention clinic and a VA medical center, respectively, completed self-report measures of internalized stigma and interview-rated measures of symptoms and quality of life. Results: Controlling for education, race, and sex differences, internalized stigma was significantly greater among those with prolonged compared to early-phase psychosis. Internalized stigma was negatively related to quality of life and positively related to symptoms in both groups. Furthermore, the magnitude of the relationship between cognitive symptoms and internalized stigma was significantly greater among those with early-phase psychosis. Stereotype endorsement, discrimination experiences, and social withdrawal also deferentially related to symptoms and quality of life across the 2 samples. Conclusion: Findings suggest that internalized stigma is an important variable to incorporate into models of early psychosis. Further, internalized stigma may be a possible treatment target among those in their early phase of psychosis.

Prolonged preconditioning with natural honey against myocardial infarction injuries.

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Eteraf-Oskouei, Tahereh; Shaseb, Elnaz; Ghaffary, Saba; Najafi, Moslem

2013-07-01

Potential protective effects of prolonged preconditioning with natural honey against myocardial infarction were investigated. Male Wistar rats were pre-treated with honey (1%, 2% and 4%) for 45 days then their hearts were isolated and mounted on a Langendorff apparatus and perfused with a modified Krebs-Henseleit solution during 30 min regional ischemia fallowed by 120 min reperfusion. Two important indexes of ischemia-induced damage (infarction size and arrhythmias) were determined by computerized planimetry and ECG analysis, respectively. Honey (1% and 2%) reduced infarct size from 23±3.1% (control) to 9.7±2.4 and 9.5±2.3%, respectively (Phoney (1%) significantly reduced (PHoney (1% and 2%) also significantly decreased number of ventricular ectopic beats (VEBs). In addition, incidence and duration of reversible ventricular fibrillation (Rev VF) were lowered by honey 2% (Phoney produced significant reduction in the incidences of VT, total and Rev VF, duration and number of VT. The results showed cardioprotective effects of prolonged pre-treatment of rats with honey following myocardial infarction. Maybe, the existence of antioxidants and energy sources (glucose and fructose) in honey composition and improvement of hemodynamic functions may involve in those protective effects.

Long-Term Haloperidol Treatment Prolongs QT Interval and Increases Expression of Sigma 1 and IP3 Receptors in Guinea Pig Hearts.

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Stracina, Tibor; Slaninova, Iva; Polanska, Hana; Axmanova, Martina; Olejnickova, Veronika; Konecny, Petr; Masarik, Michal; Krizanova, Olga; Novakova, Marie

2015-07-01

Haloperidol is a neuroleptic drug used for a medication of various psychoses and deliria. Its administration is frequently accompanied by cardiovascular side effects, expressed as QT interval prolongation and occurrence of even lethal arrhythmias. Despite these side effects, haloperidol is still prescribed in Europe in clinical practice. Haloperidol binds to sigma receptors that are coupled with inositol 1,4,5-trisphosphate (IP3) receptors. Sigma receptors are expressed in various tissues, including heart muscle, and they modulate potassium channels. Together with IP3 receptors, sigma receptors are also involved in calcium handling in various tissues. Therefore, the present work aimed to study the effects of long-term haloperidol administration on the cardiac function. Haloperidol (2 mg/kg once a day) or vehiculum was administered by intraperitoneal injection to guinea pigs for 21 consecutive days. We measured the responsiveness of the hearts isolated from the haloperidol-treated animals to additional application of haloperidol. Expression of the sigma 1 receptor and IP3 receptors was studied by real time-PCR and immunohistochemical analyses. Haloperidol treatment caused the significant decrease in the relative heart rate and the prolongation of QT interval of the isolated hearts from the haloperidol-treated animals, compared to the hearts isolated from control animals. The expression of sigma 1 and IP3 type 1 and type 2 receptors was increased in both atria of the haloperidol-treated animals but not in ventricles. The modulation of sigma 1 and IP3 receptors may lead to altered calcium handling in cardiomyocytes and thus contribute to changed sensitivity of cardiac cells to arrhythmias.

Prolonged acid rain facilitates soil organic carbon accumulation in a mature forest in Southern China.

Science.gov (United States)

Wu, Jianping; Liang, Guohua; Hui, Dafeng; Deng, Qi; Xiong, Xin; Qiu, Qingyan; Liu, Juxiu; Chu, Guowei; Zhou, Guoyi; Zhang, Deqiang

2016-02-15

With the continuing increase in anthropogenic activities, acid rain remains a serious environmental threat, especially in the fast developing areas such as southern China. To detect how prolonged deposition of acid rain would influence soil organic carbon accumulation in mature subtropical forests, we conducted a field experiment with simulated acid rain (SAR) treatments in a monsoon evergreen broadleaf forest at Dinghushan National Nature Reserve in southern China. Four levels of SAR treatments were set by irrigating plants with water of different pH values: CK (the control, local lake water, pH ≈ 4.5), T1 (water pH=4.0), T2 (water pH=3.5), and T3 (water pH=3.0). Results showed reduced pH measurements in the topsoil exposed to simulated acid rains due to soil acidification. Soil respiration, soil microbial biomass and litter decomposition rates were significantly decreased by the SAR treatments. As a result, T3 treatment significantly increased the total organic carbon by 24.5% in the topsoil compared to the control. Furthermore, surface soil became more stable as more recalcitrant organic matter was generated under the SAR treatments. Our results suggest that prolonged acid rain exposure may have the potential to facilitate soil organic carbon accumulation in the subtropical forest in southern China. Copyright © 2015 Elsevier B.V. All rights reserved.

Valsartan Attenuates Atherosclerosis via Upregulating the Th2 Immune Response in Prolonged Angiotensin II–Treated ApoE−/− Mice

Science.gov (United States)

Meng, Kai; Zeng, Qiutang; Lu, Qinghua; Lin, Yingzhong; Wu, Bangwei; Yu, Kunwu; Dong, Zhaoqiang; Zhang, Jianwei; Chai, Meng; Liu, Yuyang; Ji, Qingwei; Zhou, Yujie

2015-01-01

Valsartan has a protective effect against hypertension and atherosclerosis in humans and experimental animal models. This study aimed to determine the effect of prolonged treatment with angiotensin II (Ang II) on atherosclerosis and the effect of valsartan on the activity of CD4+ T lymphocyte subsets. The results showed that prolonged treatment (8 wks) with exogenous Ang II resulted in an increased atherosclerotic plaque size and a switch of stable-to-unstable plaque via modulating on CD4+ T lymphocyte activity, including an increase in the T helper cell type 1 (Th1) and Th17 cells and a decrease in Th2 and regulatory T (Treg) cells. In contrast, valsartan treatment efficiently reversed the imbalance in CD4+ T lymphocyte activity, ameliorated atherosclerosis and elicited a stable plaque phenotype in addition to controlling blood pressure. In addition, treatment with anti-interleukin (IL)-5 monoclonal antibodies weakened the antiatherosclerotic effects of valsartan without affecting blood pressure. PMID:25685964

Studies on Relationship between Serum Nitric Oxide and Plasma Cyclic Guanosine Monophosphate and Prolonged Bleeding after Medical Abortion as well as Prophylaxis and Treatment of Bleeding with Traditional Chinese Medicine

Institute of Scientific and Technical Information of China (English)

廖玎玲; 谭布珍; 辛华; 贺晓菊

1999-01-01

Objectives To study the relationship between serum nitric oxide(NO and plasma cyclic guanosine monophosphate(cGMP)and prolonged bleeding after medical abortion.Methods A total of 120women having received medical abortions at random were recruited and divided into two groups:the one(Group A,n=60) taking “Gong-Fu Mixture(Uterus-Recovering Mixture)”and the other(Group B,n=60)not taking it after abortion.On d 10,20 and 30 after medical abortion,serum NO and plasma cGMP were tested before and after mifepristone administration and 10 d later by Gresis reac-tion method and radioimmunoassay respectively.Results NO concentration in serum and cGMP concentration in plasma decreased signifi-cantly after taking mifeprlstone given(P＜0. 05).Ten days later,the number of thos ewith bleeding discontinuation in the group A was significantly greater than that in the group B(P＜0.05).Serum NO level and plasma cGMP level in the group A de-creased more significantly than those in the group B(P＜0. 05).Conclusion The slow decrease of serum NO and plasma cGMP is closely related to prolonged bleeding after medical abortion.“Gong-Fu Mixture(uterus-recovering mixture)”is effective in prevention and treatment of prolonged bleeding.

Systemic treatment with CAR-engineered T cells against PSCA delays subcutaneous tumor growth and prolongs survival of mice

International Nuclear Information System (INIS)

Hillerdal, Victoria; Ramachandran, Mohanraj; Leja, Justyna; Essand, Magnus

2014-01-01

Adoptive transfer of T cells genetically engineered with a chimeric antigen receptor (CAR) has successfully been used to treat both chronic and acute lymphocytic leukemia as well as other hematological cancers. Experimental therapy with CAR-engineered T cells has also shown promising results on solid tumors. The prostate stem cell antigen (PSCA) is a protein expressed on the surface of prostate epithelial cells as well as in primary and metastatic prostate cancer cells and therefore a promising target for immunotherapy of prostate cancer. We developed a third-generation CAR against PSCA including the CD28, OX-40 and CD3 ζ signaling domains. T cells were transduced with a lentivirus encoding the PSCA-CAR and evaluated for cytokine production (paired Student’s t-test), proliferation (paired Student’s t-test), CD107a expression (paired Student’s t-test) and target cell killing in vitro and tumor growth and survival in vivo (Log-rank test comparing Kaplan-Meier survival curves). PSCA-CAR T cells exhibit specific interferon (IFN)-γ and interleukin (IL)-2 secretion and specific proliferation in response to PSCA-expressing target cells. Furthermore, the PSCA-CAR-engineered T cells efficiently kill PSCA-expressing tumor cells in vitro and systemic treatment with PSCA-CAR-engineered T cells significantly delays subcutaneous tumor growth and prolongs survival of mice. Our data confirms that PSCA-CAR T cells may be developed for treatment of prostate cancer

Prolonged-release melatonin versus placebo for benzodiazepine discontinuation in patients with schizophrenia: a randomized clinical trial - the SMART trial protocol

DEFF Research Database (Denmark)

Baandrup, Lone; Fagerlund, Birgitte; Jennum, Poul

2011-01-01

Treatment of schizophrenia frequently includes prolonged benzodiazepine administration despite a lack of evidence of its use. It is often difficult to discontinue benzodiazepines because of the development of dependence. We aim to assess if melatonin can facilitate the withdrawal of prolonged...... benzodiazepine administration in patients with schizophrenia. Furthermore, we aim to investigate the association of benzodiazepine dose reduction with the following clinically important variables: sleep, psychophysiology, cognition, social function, and quality of life....

Pharmacometabolomic approach to predict QT prolongation in guinea pigs.

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Jeonghyeon Park

Full Text Available Drug-induced torsades de pointes (TdP, a life-threatening arrhythmia associated with prolongation of the QT interval, has been a significant reason for withdrawal of several medicines from the market. Prolongation of the QT interval is considered as the best biomarker for predicting the torsadogenic risk of a new chemical entity. Because of the difficulty assessing the risk for TdP during drug development, we evaluated the metabolic phenotype for predicting QT prolongation induced by sparfloxacin, and elucidated the metabolic pathway related to the QT prolongation. We performed electrocardiography analysis and liquid chromatography-mass spectroscopy-based metabolic profiling of plasma samples obtained from 15 guinea pigs after administration of sparfloxacin at doses of 33.3, 100, and 300 mg/kg. Principal component analysis and partial least squares modelling were conducted to select the metabolites that substantially contributed to the prediction of QT prolongation. QTc increased significantly with increasing dose (r = 0.93. From the PLS analysis, the key metabolites that showed the highest variable importance in the projection values (>1.5 were selected, identified, and used to determine the metabolic network. In particular, cytidine-5'-diphosphate (CDP, deoxycorticosterone, L-aspartic acid and stearic acid were found to be final metabolomic phenotypes for the prediction of QT prolongation. Metabolomic phenotypes for predicting drug-induced QT prolongation of sparfloxacin were developed and can be applied to cardiac toxicity screening of other drugs. In addition, this integrative pharmacometabolomic approach would serve as a good tool for predicting pharmacodynamic or toxicological effects caused by changes in dose.

Potential New Pharmacological Agents Derived From Medicinal Plants for the Treatment of Pancreatic Cancer.

Science.gov (United States)

Azimi, Haniye; Khakshur, Ali Asghar; Abdollahi, Mohammad; Rahimi, Roja

2015-01-01

In the present article, we reviewed plants and phytochemical compounds demonstrating beneficial effects in pancreatic cancer to find new sources of pharmaceutical agents. For this purpose, Scopus, PubMed, Web of Science, and Google scholar were searched for plants or herbal components with beneficial effects in the treatment of pancreatic cancer. Data were collected up to January 2013. The search terms were "plant," "herb," "herbal therapy," or "phytotherapy" and "pancreatic cancer" or "pancreas." All of the human in vivo and in vitro studies were included. According to studies, among diverse plants and phytochemicals, 12 compounds including apigenin, genistein, quercetin, resveratrol, epigallocatechin gallate, benzyl isothiocyanate, sulforaphane, curcumin, thymoquinone, dihydroartemisinin, cucurbitacin B, and perillyl alcohol have beneficial action against pancreatic cancer cells through 4 or more mechanisms. Applying their plausible synergistic effects can be an imperative approach for finding new efficient pharmacological agents in the treatment of pancreatic cancer.

Prolonged operative time increases infection rate in tibial plateau fractures.

Science.gov (United States)

Colman, Matthew; Wright, Adam; Gruen, Gary; Siska, Peter; Pape, Hans-Christoph; Tarkin, Ivan

2013-02-01

Fractures of the tibial plateau present a treatment challenge and are susceptible to both prolonged operative times and high postoperative infection rates. For those fractures treated with open plating, we sought to identify the relationship between surgical site infection and prolonged operative time as well as to identify other surgical risk factors. We performed a retrospective controlled analysis of 309 consecutive unicondylar and bicondylar tibial plateau fractures treated with open plate osteosynthesis at our institution's level I trauma centre during a recent 5-year period. We recorded operative times, injury characteristics, surgical treatment, and need for operative debridement due to infection. Operative times of infected cases were compared to uncomplicated surgical cases. Multivariable logistic regression analysis was performed to identify independent risk factors for postoperative infection. Mean operative time in the infection group was 2.8h vs. 2.2h in the non-infected group (p=0.005). 15 fractures (4.9%) underwent four compartment fasciotomies as part of their treatment, with a significantly higher infection rate than those not undergoing fasciotomy (26.7% vs. 6.8%, p=0.01). Open fracture grade was also significantly related to infection rate (closed fractures: 5.3%, grade 1: 14.3%, grade 2: 40%, grade 3: 50%, pinfection rates (13.9% vs. 8.7%, p=0.36). Multivariable logistic regression analysis of the entire study group identified longer operative times (OR 1.78, p=0.013) and open fractures (OR 7.02, psite infection. Operative times approaching 3h and open fractures are related to an increased overall risk for surgical site infection after open plating of the tibial plateau. Dual incision approaches with bicolumnar plating do not appear to expose the patient to increased risk compared to single incision approaches. Copyright © 2012 Elsevier Ltd. All rights reserved.

The effect of chewing on oral glucoraphanin hydrolysis in raw and steamed broccoli

NARCIS (Netherlands)

Sarvan, Irmela; Klauw, van der Michelle; Oliviero, Teresa; Dekker, Matthijs; Verkerk, Ruud

2018-01-01

Chewing disrupts broccoli cells, and myrosinase can effectively hydrolyze the glucosinolate glucoraphanin into the biological active sulforaphane. The influence of chewing time and steaming time on glucoraphanin hydrolysis as well as sulforaphane and sulforaphane nitrile formation in broccoli was

Prolonged exposure therapy for the treatment of patients diagnosed with psychogenic non-epileptic seizures (PNES) and post-traumatic stress disorder (PTSD).

Science.gov (United States)

Myers, Lorna; Vaidya-Mathur, Urmi; Lancman, Marcelo

2017-01-01

Although there is general consensus that psychogenic non-epileptic seizures (PNES) are treated with psychotherapy, the effectiveness of most psychotherapeutic modalities remains understudied. In this treatment series of 16 patients dually diagnosed with PNES and post-traumatic stress disorder (PTSD), we evaluated the effect of prolonged exposure therapy (PE) on reduction of PNES. Secondary measures included Beck Depression Inventory (BDI-II) and Post-Traumatic Disorder Diagnostic Scale (PDS). Subjects diagnosed with video EEG-confirmed PNES and PTSD confirmed through neuropsychological testing and clinical interview were treated with traditional PE psychotherapy with certain modifications for the PNES. Treatment was conducted over the course of 12-15 weekly sessions. Seizure frequency was noted in each session by examining the patients' seizure logs, and mood and PTSD symptomatology was assessed at baseline and on the final session. Eighteen subjects enrolled, and 16 (88.8%) completed the course of treatment. Thirteen of the 16 (81.25%) therapy completers reported no seizures by their final PE session, and the other three reported a decline in seizure frequency (Z=-3.233, p=0.001). Mean scores on scales of depression (M=-13.56, SD=12.27; t (15)=-4.420, pPTSD symptoms (M=-17.1875, SD=13.01; t (15)=-5.281, pPTSD reduced the number of PNES and improved mood and post traumatic symptomatology. Follow-up revealed that gains made in seizure control on the last day of treatment were maintained over time. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

RD50 Prolongation Request 2018

CERN Document Server

Casse, Gianluigi

2018-01-01

With this document, we request the prolongation of the CERN RD50 research program for 5 years. A very brief historical review of the RD50 research program since the RD50 project approval by the Research Board in the year 2002 is presented and the biggest RD50 achievements are highlighted. The present composition of the collaboration, its organizational structure, and the research methodology are described. The role of RD50 in the present various upgrade and research programs of the LHC Experiments community is given and the overall work plan explained. Finally, a detailed 5-years work program with precise milestones and deliverables for the various research activities is presented. We conclude with our prolongation request towards the LHCC.

Predictive factors for oropharyngeal dysphagia after prolonged orotracheal intubation.

Science.gov (United States)

Oliveira, Ana Carolina Martins de; Friche, Amélia Augusta de Lima; Salomão, Marina Silva; Bougo, Graziela Chamarelli; Vicente, Laélia Cristina Caseiro

2017-09-13

Lesions in the oral cavity, pharynx and larynx due to endotracheal intubation can cause reduction in the local motility and sensitivity, impairing the swallowing process, resulting in oropharyngeal dysphagia. To verify the predictive factors for the development of oropharyngeal dysphagia and the risk of aspiration in patients with prolonged orotracheal intubation admitted to an intensive care unit. This is an observational, analytical, cross-sectional and retrospective data collection study of 181 electronic medical records of patients submitted to prolonged orotracheal intubation. Data on age; gender; underlying disease; associated comorbidities; time and reason for orotracheal intubation; Glasgow scale on the day of the Speech Therapist assessment; comprehension; vocal quality; presence and severity of dysphagia; risk of bronchoaspiration; and the suggested oral route were collected. The data were analyzed through logistic regression. The level of significance was set at 5%, with a 95% Confidence Interval. The prevalence of dysphagia in this study was 35.9% and the risk of aspiration was 24.9%. As the age increased, the altered vocal quality and the degree of voice impairment increased the risk of the presence of dysphagia by 5-; 45.4- and 6.7-fold, respectively, and of aspiration by 6-; 36.4- and 4.8-fold. The increase in the time of orotracheal intubation increased the risk of aspiration by 5.5-fold. Patients submitted to prolonged intubation who have risk factors associated with dysphagia and aspiration should be submitted to an early speech-language/audiology assessment and receive appropriate and timely treatment. The recognition of these predictive factors by the entire multidisciplinary team can minimize the possibility of clinical complications inherent to the risk of dysphagia and aspiration in extubated patients. Copyright © 2017. Published by Elsevier Editora Ltda.

Fermionic covariant prolongation structure theory for supernonlinear evolution equation

International Nuclear Information System (INIS)

Cheng Jipeng; Wang Shikun; Wu Ke; Zhao Weizhong

2010-01-01

We investigate the superprincipal bundle and its associated superbundle. The super(nonlinear)connection on the superfiber bundle is constructed. Then by means of the connection theory, we establish the fermionic covariant prolongation structure theory of the supernonlinear evolution equation. In this geometry theory, the fermionic covariant fundamental equations determining the prolongation structure are presented. As an example, the supernonlinear Schroedinger equation is analyzed in the framework of this fermionic covariant prolongation structure theory. We obtain its Lax pairs and Baecklund transformation.

Changes in quality and biochemical parameters in 'Idared' apples during prolonged shelf life and 1-MCP treatment.

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Bizjak, Jan; Slatnar, Ana; Stampar, Franci; Veberic, Robert

2012-12-01

In this study, changes in quality and various biochemical parameters of 'Idared' apples during prolonged shelf life period after ultra-low oxygen (ULO) storage were investigated. Additionally, the impact of the postharvest application of 1-methylcyclopropene (1-MCP) on different parameters was evaluated. After the harvest, apples were stored in the ULO storage for 6 months and then exposed to room temperature. Fruit firmness, peel color, and changes in sugars, organic acids and phenolics were monitored during the 3 weeks of shelf life. Malic acid, sugars and firmness decreased at room temperature. However, the color of the apples remained unchanged. The level of citric and ascorbic acid remained constant. Levels of phenolics in the peel increased significantly, whereas remained constant in the pulp of apples. 1-MCP treatment resulted in higher amounts of fructose and glucose, malic acid and greater firmness of apples. However, 1-MCP did not influence the phenolic content, ascorbic acid or color. The results obtained indicate that the content of different health-promoting compounds of apples does not change dramatically at room temperature. At the same time these results suggest that 1-MCP could be useful for maintaining certain quality and biochemical parameters and might extend the shelf life of apples.

Prophylactic effects of sulforaphane on depression-like behavior and dendritic changes in mice after inflammation.

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Zhang, Ji-Chun; Yao, Wei; Dong, Chao; Yang, Chun; Ren, Qian; Ma, Min; Han, Mei; Wu, Jin; Ushida, Yusuke; Suganuma, Hiroyuki; Hashimoto, Kenji

2017-01-01

Inflammation plays a role in the pathophysiology of depression. Sulforaphane (SFN), an isothiocyanate compound derived from broccoli, is a potent activator of the NF-E2-related factor-2 (Nrf2), which plays a role in inflammation. In this study, we examined whether the prevention effects of SFN in lipopolysaccharide (LPS) induced depression-like behavior in mice. Pretreatment with SFN significantly blocked an increase in the serum tumor necrosis factor-α (TNF-α) level and an increase in microglial activation of brain regions after a single administration of LPS (0.5 mg/kg). Furthermore, SFN significantly potentiated increased serum levels of IL-10 after LPS administration. In the tail-suspension test and forced swimming test, SFN significantly attenuated an increase of the immobility time after LPS administration. In addition, SFN significantly recovered to control levels for LPS-induced alterations in the proteins such as brain-derived neurotrophic factor, postsynaptic density protein 95 and AMPA receptor 1 (GluA1) and dendritic spine density in the brain regions. Finally, dietary intake of 0.1% glucoraphanin (a glucosinolate precursor of SFN) food during the juvenile and adolescence could prevent the onset of LPS-induced depression-like behaviors and dendritic spine changes in the brain regions at adulthood. In conclusion, these findings suggest that dietary intake of SFN-rich broccoli sprout has prophylactic effects on inflammation-related depressive symptoms. Therefore, supplementation of SFN-rich broccoli sprout could be prophylactic vegetable to prevent or minimize the relapse by inflammation in the remission state of depressed patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Prolonged hypoxic culture and trypsinization increase the pro-angiogenic potential of human adipose tissue-derived stem cells

DEFF Research Database (Denmark)

Rasmussen, Jeppe Grøndahl; Frøbert, Ole; Pilgaard, Linda

2011-01-01

Transplantation of mesenchymal stromal cells (MSC), including adipose tissue-derived stem cells (ASC), is a promising option in the treatment of vascular disease. Short-term hypoxic culture of MSC augments secretion of anti-apoptotic and angiogenic cytokines. We hypothesized that prolonged hypoxi...

Sulforaphane and alpha-lipoic acid upregulate the expression of the pi class of glutathione S-transferase through c-jun and Nrf2 activation.

Science.gov (United States)

Lii, Chong-Kuei; Liu, Kai-Li; Cheng, Yi-Ping; Lin, Ai-Hsuan; Chen, Haw-Wen; Tsai, Chia-Wen

2010-05-01

The anticarcinogenic effect of dietary organosulfur compounds has been partly attributed to their modulation of the activity and expression of phase II detoxification enzymes. Our previous studies indicated that garlic allyl sulfides upregulate the expression of the pi class of glutathione S-transferase (GSTP) through the activator protein-1 pathway. Here, we examined the modulatory effect of sulforaphane (SFN) and alpha-lipoic acid (LA) or dihydrolipoic acid (DHLA) on GSTP expression in rat Clone 9 liver cells. Cells were treated with LA or DHLA (50-600 micromol/L) or SFN (0.2-5 micromol/L) for 24 h. Immunoblots and real-time PCR showed that SFN, LA, and DHLA dose dependently induced GSTP protein and mRNA expression. Compared with the induction by the garlic organosulfur compound diallyl trisulfide (DATS), the effectiveness was in the order of SFN > DATS > LA = DHLA. The increase in GSTP enzyme activity in cells treated with 5 micromol/L SFN, 50 micromol/L DATS, and 600 micromol/L LA and DHLA was 172, 75, 122, and 117%, respectively (P GPEI) was required for GSTP induction by the organosulfur compounds. Electromobility gel shift assays showed that the DNA binding of GPEI to nuclear proteins reached a maximum at 0.5-1 h after SFN, LA, and DHLA treatment. Super-shift assay revealed that the transcription factors c-jun and nuclear factor erythroid-2 related factor 2 (Nrf2) were bound to GPEI. These results suggest that SFN and LA in either its oxidized or reduced form upregulate the transcription of the GSTP gene by activating c-jun and Nrf2 binding to the enhancer element GPEI.

Activation of Nrf2 Reduces UVA-Mediated MMP-1 Upregulation via MAPK/AP-1 Signaling Cascades: The Photoprotective Effects of Sulforaphane and Hispidulin

Science.gov (United States)

Chaiprasongsuk, Anyamanee; Lohakul, Jinaphat; Soontrapa, Kitipong; Sampattavanich, Somponnat; Akarasereenont, Pravit

2017-01-01

UVA irradiation plays a role in premature aging of the skin through triggering oxidative stress-associated stimulation of matrix metalloproteinase-1 (MMP-1) responsible for collagen degradation, a hallmark of photoaged skin. Compounds that can activate nuclear factor E2-related factor 2 (Nrf2), a transcription factor regulating antioxidant gene expression, should therefore serve as effective antiphotoaging agents. We investigated whether genetic silencing of Nrf2 could relieve UVA-mediated MMP-1 upregulation via activation of mitogen-activated protein kinase (MAPK)/activator protein 1 (AP-1) signaling using human keratinocyte cell line (HaCaT). Antiphotoaging effects of hispidulin (HPD) and sulforaphane (SFN) were assessed on their abilities to activate Nrf2 in controlling MMP-1 and collagen expressions in association with phosphorylation of MAPKs (extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38), c-Jun, and c-Fos, using the skin of BALB/c mice subjected to repetitive UVA irradiation. Our findings suggested that depletion of Nrf2 promoted both mRNA expression and activity of MMP-1 in the UVA-irradiated HaCaT cells. Treatment of Nrf2 knocked-down HaCaT cells with MAPK inhibitors significantly suppressed UVA-induced MMP-1 and AP-1 activities. Moreover, pretreatment of the mouse skin with HPD and SFN, which could activate Nrf2, provided protective effects against UVA-mediated MMP-1 induction and collagen depletion in correlation with the decreased levels of phosphorylated MAPKs, c-Jun, and c-Fos in the mouse skin. In conclusion, Nrf2 could influence UVA-mediated MMP-1 upregulation through the MAPK/AP-1 signaling cascades. HPD and SFN may therefore represent promising antiphotoaging candidates. PMID:28011874

Lumbosacral Plexus Injury and Brachial Plexus Injury Following Prolonged Compression

Directory of Open Access Journals (Sweden)

Chung-Lan Kao

2006-11-01

Full Text Available We report the case of a 36-year-old woman who developed right upper and lower limb paralysis with sensory deficit after sedative drug overdose with prolonged immobilization. Due to the initial motor and sensory deficit pattern, brachial plexus injury or C8/T1 radiculopathy was suspected. Subsequent nerve conduction study/electromyography proved the lesion level to be brachial plexus. Painful swelling of the right buttock was suggestive of gluteal compartment syndrome. Elevation of serum creatine phosphokinase and urinary occult blood indicated rhabdomyolysis. The patient received medical treatment and rehabilitation; 2 years after the injury, her right upper and lower limb function had recovered nearly completely. As it is easy to develop complications such as muscle atrophy and joint contracture during the paralytic period of brachial plexopathy and lumbosacral plexopathy, early intervention with rehabilitation is necessary to ensure that the future limb function of the patient can be recovered. Our patient had suspected gluteal compartment syndrome that developed after prolonged compression, with the complication of concomitant lumbosacral plexus injury and brachial plexus injury, which is rarely reported in the literature. A satisfactory outcome was achieved with nonsurgical management.

Prolonged heart xenograft survival using combined total lymphoid irradiation and cyclosporine

International Nuclear Information System (INIS)

Knechtle, S.J.; Halperin, E.C.; Saad, T.; Bollinger, R.R.

1986-01-01

Total lymphoid irradiation and cyclosporine have profound immunosuppressive properties and permit successful heart allotransplantation. Cyclosporine used alone has not permitted consistently successful transplantation between species in all cases. Total lymphoid irradiation has not been applied to xenotransplantation. The efficacy of total lymphoid irradiation alone and in combination with cyclosporine was examined using an animal model of heart xenotransplantation. Heterotopic heart transplants were performed using inbred Syrian hamsters as donors and Lewis rats as recipients. Total lymphoid irradiation was administered preoperatively over 3 weeks for a total dose of 15 gray. Cyclosporine was started on the day of surgery and was given as a daily intramuscular injection of 2.5, 5, or 10 mg/kg/day until rejection was complete. Neither total lymphoid irradiation nor cyclosporine alone markedly prolonged graft survival. However, combined total lymphoid irradiation and cyclosporine, 5 or 10 mg/kg/day, dramatically prolonged graft survival to greater than 100 days in most recipients. There were no treatment-related deaths. In conclusion, combined total lymphoid irradiation and cyclosporine permit successful long-term survival of heart xenotransplants in this hamster-to-rat model

Study On Irradiated Vietnam Java Rambutan Fruit Which Was Postharvested Treatment To Prolong The Shelflife For Export Purposes

International Nuclear Information System (INIS)

Nguyen Thuy Khanh; Nguyen Thi Ly; Doan Thi The; Cao Van Chung; Nguyen Van Phong

2014-01-01

The research - Study on irradiated Vietnam Java rambutan fruit which was postharvested treatment to prolong the shelflife for export purposes - was conducted at Research and Development Center for Radiation Technology and Southern Horticultural Research Institute for 12 months. On the one hand, the theme was to study the effects of low-dose radiation in the range (200-500 Gy) combined with two types of packaging: carton boxes and carton boxes + PE perforated cover 0.5% of the area bags. After 13 days monitoring in 13 o C, RH= 85-90% the results showed that Java rambutan fruit which was packed in carton boxes combined PE bags then irradiated at 300 Gy dose could limit the browning pericarp, dehydration through the rate of browning, browning level and the percentage of weight loss. Irradiated ramtuban also remains their pulp quality when testing the soluble solids, the titratable acidity and the ascorbic acid content. Irradiation did not affect the cell structure of pericarp and pulp by investigating the total ion leakage. On the other hand, the topics also examined the influence of some postharvest handling and low-dose radiation on Java rambutan. The results showed that pre-irradiation processing: hot water treatment at 43 o C in 6 minute, dipping in cloruacalxi 0.4% + citric acid 0.5% solution in 3 minutes, packed in carton boxes + PE bags and irradiated at 300 Gy dose capable of maintaining the quality which extends the shelflife of Java rambutan more 4 days when kept under conditions of 13 o C, RH= 85-90%. (author)

Prolonged-release fampridine treatment improved subject-reported impact of multiple sclerosis: Item-level analysis of the MSIS-29.

Science.gov (United States)

Gasperini, Claudio; Hupperts, Raymond; Lycke, Jan; Short, Christine; McNeill, Manjit; Zhong, John; Mehta, Lahar R

2016-11-15

Prolonged-release (PR) fampridine is approved to treat walking impairment in persons with multiple sclerosis (MS); however, treatment benefits may extend beyond walking. MOBILE was a phase 2, 24-week, double-blind, placebo-controlled exploratory study to assess the impact of 10mg PR-fampridine twice daily versus placebo on several subject-assessed measures. This analysis evaluated the physical and psychological health outcomes of subjects with progressing or relapsing MS from individual items of the Multiple Sclerosis Impact Scale (MSIS-29). PR-fampridine treatment (n=68) resulted in greater improvements from baseline in the MSIS-29 physical (PHYS) and psychological (PSYCH) impact subscales, with differences of 89% and 148% in mean score reduction from baseline (n=64) at week 24 versus placebo, respectively. MSIS-29 item analysis showed that a higher percentage of PR-fampridine subjects had mean improvements in 16/20 PHYS and 6/9 PSYCH items versus placebo after 24weeks. Post hoc analysis of the 12-item Multiple Sclerosis Walking Scale (MSWS-12) improver population (≥8-point mean improvement) demonstrated differences in mean reductions from baseline of 97% and 111% in PR-fampridine MSIS-29 PHYS and PSYCH subscales versus the overall placebo group over 24weeks. A higher percentage of MSWS-12 improvers treated with PR-fampridine showed mean improvements in 20/20 PHYS and 8/9 PSYCH items versus placebo at 24weeks. In conclusion, PR-fampridine resulted in physical and psychological benefits versus placebo, sustained over 24weeks. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Prolonged Treatment Duration is Required for Successful Helicobacter pylori Eradication with Proton Pump Inhibitor Triple Therapy in Canada

Directory of Open Access Journals (Sweden)

Carlo A Fallone

2013-01-01

Full Text Available BACKGROUND: Traditional seven-day proton pump inhibitor triple therapy for Helicobacter pylori eradication has recently shown disappointing results outside of Canada. Prolonging therapy may be associated with poorer compliance and, hence, may not have a better outcome in a real-world setting.

Sulforaphane protects rodent retinas against ischemia-reperfusion injury through the activation of the Nrf2/HO-1 antioxidant pathway.

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Hong Pan

Full Text Available Retinal ischemia-reperfusion (I/R injury induces oxidative stress, leukocyte infiltration, and neuronal cell death. Sulforaphane (SF, which can be obtained in cruciferous vegetables such as broccoli, exerts protective effects in response to oxidative stress in various tissues. These effects can be initiated through nuclear factor E2-related factor 2 (Nrf2-mediated induction of heme oxygenase-1 (HO-1. This investigation was designed to elucidate the neural protective mechanisms of SF in the retinal I/R rat model. Animals were intraperitoneally (i.p. injected with SF (12.5 mg/kg or vehicle (corn oil once a day for 7 consecutive days. Then, retinal I/R was made by elevating the intraocular pressure (IOP to 130 mmHg for 1 h. To determine if HO-1 was involved in the Nrf2 antioxidant pathway, rats were subjected to protoporphyrin IX zinc (II (ZnPP, 30 mg/kg, i.p. treatments at 24 h before retinal ischemia. The neuroprotective effects of SF were assessed by determining the morphology of the retina, counting the infiltrating inflammatory cells and the surviving retinal ganglion cells (RGCs and amacrine cells, and measuring apoptosis in the retinal layers. The expression of Nrf2 and HO-1 was studied by immunofluorescence analysis and western blotting. I/R induced a marked increase of ROS generation, caused pronounced inflammation, increased the apoptosis of RGCs and amacrine cells and caused the thinning of the inner retinal layer (IRL, and these effects were diminished or abolished by SF pretreatment. Meanwhile, SF pretreatment significantly elevated the nuclear accumulation of Nrf2 and the level of HO-1 expression in the I/R retinas; however, ZnPP reversed the protective effects of SF on I/R retinas. Together, we offer direct evidence that SF had protective effects on I/R retinas, which could be attributed, at least in part, to the activation of the Nrf2/HO-1 antioxidant pathway.

Management of prolonged pregnancy

International Nuclear Information System (INIS)

Iqbal, S.

2004-01-01

Objective: To compare two strategies for management of prolonged pregnancy (= or >294 days) i.e. induction (intervention) versus expectant management (non-intervention) and evaluate the associated feto-maternal risks. Subjects and Methods: One hundred cases of uncomplicated prolonged gestation were selected. The gestational age was confirmed by ultrasound in first trimester. One group (50 patients) was managed by intervention i.e. induction of labour (group A) and other group (50 patients) by non-intervention i.e. expectant management (group B). In group A intervention was done at 42 weeks. In expectant group, the methods of monitoring were fetal kick charting recorded daily by the patient, and ultrasound for amniotic fluid index. The biophysical profile score and NST (non stress test) were performed once a week till 42 weeks and then twice weekly. Results: The frequency of prolonged pregnancy was found to be 10.9%. There was no significant difference in the number of spontaneous vaginal deliveries between the two groups. The rate of LSCS (lower segment caesarean section) was higher in intervention group ( 30% versus 18% ). The neonatal depression at birth was more in group B ( 10% versus 4%) and at 5 minutes almost same between two groups (4% versus 2%). There were 11 cases of meconium aspiration syndrome, leading to one neonatal death. Among nine perinatal deaths two were neonatal deaths. Seven cases of intrauterine deaths in which antepartum deaths occurred because of non compliance of patients. No cause could be detected for the other three fetuses. Conclusion: There was increased LSCS rate in group A. However in expectant group B perinatal mortality was about twice more as compared to intervention group. Active early intervention at 42 weeks is warranted to reduce perinatal morbidity and mortality. (author)

Drug therapy for congestive heart failure:appropriate choices can prolong life

International Nuclear Information System (INIS)

Sorrentino, M

1997-01-01

Between one purpose of the insufficiency congestive heart is improve and prolong the quality life. A good multidisciplinary health equipment can help to the improving patients with this disease referred to effective handling interned and ambulatory patients groups. The inhibition mechanism compensate that perpetuate heart congestive insufficiency are a way for reach treatment purposes. Between patients with symptomatic cardiac insufficiency and overload volume is indicated digoxin(Lanoxin) and vasodilators. The enzyme inhibition angiotensin converted improve over life range more than an others vasodilators and is preferred for the systole dysfunction patients

PROLONGED MULTIPLE SPASMS OF SMOOTH CORONARY ARTERIES PRESENTING AS ACUTE MIOCARDIAL INFARCTION, COMPLETE AV BLOCK AND SYNCOPE

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Franci Cesar

2004-11-01

Full Text Available Background. A variant form of angina pectoris (VAP is caused by coronary vessel spasm and occures in patients with and without varying degrees of obstructive coronary artery disease. Although the prognosis of VAP without significant organic stenosis is generally good, multivessel spasm is associated with a high risk of life-threatening abnormalities of rhythm and conduction.Patient and methods. We describe a patient who presented with prolonged chest pain, associated with hypotension, lost of consciousness, complete AV block and widespread ST segment elevations consistent with inferoanterior acute myocardial infarction. Urgent selective coronary angiography revealed spasms in right coronary artery and in left circumflex artery that were relieved by intracoronary injection of nitroglycerin. All coronary arteries were otherwise patient, without signs of atherosclerosis. The patient was treated with diltiazem and nitrates. She made a complete recovery and resumed her normal activities.Conclusions. Simultaneous multiple spasms of native coronary arteries represent a rare syndrome characterized by significantly higher incidence of potentially life-threatening arrhythmia. Less commonly, prolonged coronary spasm may mimic acute myocardial infarction. Modern management of acute coronary syndromes, including urgent coronarography, enables a prompt differentiation between prolonged coronary spasm and atherosclerotic coronary disease, warranting different treatment strategies. Medical treatment with nitrates and calcium channel blockers in most cases prevents recurrence of vasospasms and arrhythmias.

Predictors of Prolonged TB Treatment in a Dutch Outpatient Setting.

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Natasha Van't Boveneind-Vrubleuskaya

Full Text Available Standard treatment duration for drug-susceptible tuberculosis (TB treatment is 6 months. Treatment duration is often extended-and for various different reasons. The aim of this study was to determine the prevalence and to assess risk factors associated with extended TB treatment.A cross-sectional study was conducted. Data including demographic, clinical, radiological and microbiological information from the Netherlands TB Register (NTR of 90 patients with smear and culture positive pulmonary TB of the region Haaglanden, The Netherlands, was eligible for analysis.Treatment was extended to ≥ 200 days by 46 (51% patients. Extended TB treatment was associated with a higher frequency of symptoms, presumed to be due to adverse drug reactions (ADR; OR 2.39 95% CI: 1.01-5.69, drug-induced liver injury (DILI (OR: 13.51; 95% CI: 1.66-109.82 and longer than 2 month smear and culture conversion rate (OR: 11.00; 95% CI: 1.24-97.96 and OR: 8.56; 95% CI: 1.53-47.96. In the multivariable logistic analysis, development of DILI emerged as the single statistically strong risk factor necessitating extension of TB treatment.This finding will need further confirmation in a prospective study, exploring the possible mutual role of pharmacokinetic and pharmacogenetic determinants of DILI among TB patients.

Effectiveness of prolonged use of continuous passive motion (CPM, as an adjunct to physiotherapy, after total knee arthroplasty

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Geesink Ruud JT

2008-04-01

Full Text Available Abstract Background Adequate and intensive rehabilitation is an important requirement for successful total knee arthroplasty. Although research suggests that Continuous Passive Motion (CPM should be implemented in the first rehabilitation phase after surgery, there is substantial debate about the duration of each session and the total period of CPM application. A Cochrane review on this topic concluded that short-term use of CPM leads to greater short-term range of motion. It also suggested, however, that future research should concentrate on the treatment period during which CPM should be administered. Methods In a randomised controlled trial we investigated the effectiveness of prolonged CPM use in the home situation as an adjunct to standardised PT. Efficacy was assessed in terms of faster improvements in range of motion (RoM and functional recovery, measured at the end of the active treatment period, 17 days after surgery. Sixty patients with knee osteoarthritis undergoing TKA and experiencing early postoperative flexion impairment were randomised over two treatment groups. The experimental group received CPM + PT for 17 consecutive days after surgery, whereas the usual care group received the same treatment during the in-hospital phase (i.e. about four days, followed by PT alone (usual care in the first two weeks after hospital discharge. From 18 days to three months after surgery, both groups received standardised PT. The primary focus of rehabilitation was functional recovery (e.g. ambulation and regaining RoM in the knee. Results Prolonged use of CPM slightly improved short-term RoM in patients with limited RoM at the time of discharge after total knee arthroplasty when added to a semi-standard PT programme. Assessment at 6 weeks and three months after surgery found no long-term effects of this intervention Neither did we detect functional benefits of the improved RoM at any of the outcome assessments. Conclusion Although results

Effectiveness of prolonged use of continuous passive motion (CPM), as an adjunct to physiotherapy, after total knee arthroplasty

Science.gov (United States)

Lenssen, Ton AF; van Steyn, Mike JA; Crijns, Yvonne HF; Waltjé, Eddie MH; Roox, George M; Geesink, Ruud JT; Brandt, Piet A van den; De Bie, Rob A

2008-01-01

Background Adequate and intensive rehabilitation is an important requirement for successful total knee arthroplasty. Although research suggests that Continuous Passive Motion (CPM) should be implemented in the first rehabilitation phase after surgery, there is substantial debate about the duration of each session and the total period of CPM application. A Cochrane review on this topic concluded that short-term use of CPM leads to greater short-term range of motion. It also suggested, however, that future research should concentrate on the treatment period during which CPM should be administered. Methods In a randomised controlled trial we investigated the effectiveness of prolonged CPM use in the home situation as an adjunct to standardised PT. Efficacy was assessed in terms of faster improvements in range of motion (RoM) and functional recovery, measured at the end of the active treatment period, 17 days after surgery. Sixty patients with knee osteoarthritis undergoing TKA and experiencing early postoperative flexion impairment were randomised over two treatment groups. The experimental group received CPM + PT for 17 consecutive days after surgery, whereas the usual care group received the same treatment during the in-hospital phase (i.e. about four days), followed by PT alone (usual care) in the first two weeks after hospital discharge. From 18 days to three months after surgery, both groups received standardised PT. The primary focus of rehabilitation was functional recovery (e.g. ambulation) and regaining RoM in the knee. Results Prolonged use of CPM slightly improved short-term RoM in patients with limited RoM at the time of discharge after total knee arthroplasty when added to a semi-standard PT programme. Assessment at 6 weeks and three months after surgery found no long-term effects of this intervention Neither did we detect functional benefits of the improved RoM at any of the outcome assessments. Conclusion Although results indicate that prolonged CPM use

Effectiveness of prolonged use of continuous passive motion (CPM), as an adjunct to physiotherapy, after total knee arthroplasty.

Science.gov (United States)

Lenssen, Ton A F; van Steyn, Mike J A; Crijns, Yvonne H F; Waltjé, Eddie M H; Roox, George M; Geesink, Ruud J T; van den Brandt, Piet A; De Bie, Rob A

2008-04-29

Adequate and intensive rehabilitation is an important requirement for successful total knee arthroplasty. Although research suggests that Continuous Passive Motion (CPM) should be implemented in the first rehabilitation phase after surgery, there is substantial debate about the duration of each session and the total period of CPM application. A Cochrane review on this topic concluded that short-term use of CPM leads to greater short-term range of motion. It also suggested, however, that future research should concentrate on the treatment period during which CPM should be administered. In a randomised controlled trial we investigated the effectiveness of prolonged CPM use in the home situation as an adjunct to standardised PT. Efficacy was assessed in terms of faster improvements in range of motion (RoM) and functional recovery, measured at the end of the active treatment period, 17 days after surgery. Sixty patients with knee osteoarthritis undergoing TKA and experiencing early postoperative flexion impairment were randomised over two treatment groups. The experimental group received CPM + PT for 17 consecutive days after surgery, whereas the usual care group received the same treatment during the in-hospital phase (i.e. about four days), followed by PT alone (usual care) in the first two weeks after hospital discharge. From 18 days to three months after surgery, both groups received standardised PT. The primary focus of rehabilitation was functional recovery (e.g. ambulation) and regaining RoM in the knee. Prolonged use of CPM slightly improved short-term RoM in patients with limited RoM at the time of discharge after total knee arthroplasty when added to a semi-standard PT programme. Assessment at 6 weeks and three months after surgery found no long-term effects of this intervention Neither did we detect functional benefits of the improved RoM at any of the outcome assessments. Although results indicate that prolonged CPM use might have a small short-term effect

SALIVARY ANTIMICROBIAL PROTEIN RESPONSE TO PROLONGED RUNNING

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Suzanne Schneider

2013-01-01

Full Text Available Prolonged exercise may compromise immunity through a reduction of salivary antimicrobial proteins (AMPs. Salivary IgA (IgA has been extensively studied, but little is known about the effect of acute, prolonged exercise on AMPs including lysozyme (Lys and lactoferrin (Lac. Objective: To determine the effect of a 50-km trail race on salivary cortisol (Cort, IgA, Lys, and Lac. Methods: 14 subjects: (6 females, 8 males completed a 50km ultramarathon. Saliva was collected pre, immediately after (post and 1.5 hrs post race ( 1.5. Results: Lac concentration was higher at 1.5 hrs post race compared to post exercise (p0.05. IgA concentration, secretion rate, and IgA/Osm were lower 1.5 hrs post compared to pre race (p<0.05. Cort concentration was higher at post compared to 1.5 (p<0.05, but was unaltered from pre race levels. Subjects finished in 7.81 ± 1.2 hrs. Saliva flow rate did not differ between time points. Saliva Osm increased at post (p<0.05 compared to pre race. Conclusions: The intensity could have been too low to alter Lys and Lac secretion rates and thus, may not be as sensitive as IgA to changes in response to prolonged running. Results expand our understanding of the mucosal immune system and may have implications for predicting illness after prolonged running.

Locally advanced pancreatic cancer: association between prolonged preoperative treatment and lymph-node negativity and overall survival.

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Kadera, Brian E; Sunjaya, Dharma B; Isacoff, William H; Li, Luyi; Hines, O Joe; Tomlinson, James S; Dawson, David W; Rochefort, Matthew M; Donald, Graham W; Clerkin, Barbara M; Reber, Howard A; Donahue, Timothy R

2014-02-01

), also correlated with OS. On multivariate Cox proportional hazard modeling of HP and prognostic biomarkers, only SMAD4 protein loss was significant (hazard ratio, 9.3; P=.004). Our approach to patients with LA/BR PDAC, which includes prolonged preoperative chemotherapy, is associated with a high incidence of LN-negative disease and excellent OS. After surgical resection, HP treatment response, perineural invasion, and SMAD4 status should help determine who should receive adjuvant therapy in this select subset of patients.

Safety and tolerability of flexible dosages of prolonged-release OROS methylphenidate in adults with attention-deficit/hyperactivity disorder.

NARCIS (Netherlands)

Buitelaar, J.K.; Ramos-Quiroga, J.A.; Casas, M.; Kooij, J.J.; Niemela, A.; Konofal, E.; Dejonckheere, J.; Challis, B.H.; Medori, R.

2009-01-01

The osmotic release oral system (OROS) methylphenidate formulation is a prolonged-release medication for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children, adolescents, and adults. We conducted a seven-week open-label extension of a double-blind study to assess the safety

Prolonged administration of recombinant human erythropoietin increases submaximal performance more than maximal aerobic capacity

DEFF Research Database (Denmark)

Thomsen, J J; Rentsch, R L; Robach, P

2007-01-01

HuEpo treatment VO2max increased (Ptime-to-exhaustion (80% VO2max) was increased by 54.0 and 54.3% (Ptime point...... week 11), TTE was decreased by 26.8% as compared to pre rHuEpo administration. In conclusion, in healthy non-athlete subjects rHuEpo administration prolongs submaximal exercise performance by about 54% independently of the approximately 12% increase in VO2max....

Tolerance and withdrawal from prolonged opioid use in critically ill children.

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Anand, Kanwaljeet J S; Willson, Douglas F; Berger, John; Harrison, Rick; Meert, Kathleen L; Zimmerman, Jerry; Carcillo, Joseph; Newth, Christopher J L; Prodhan, Parthak; Dean, J Michael; Nicholson, Carol

2010-05-01

After prolonged opioid exposure, children develop opioid-induced hyperalgesia, tolerance, and withdrawal. Strategies for prevention and management should be based on the mechanisms of opioid tolerance and withdrawal. Relevant manuscripts published in the English language were searched in Medline by using search terms "opioid," "opiate," "sedation," "analgesia," "child," "infant-newborn," "tolerance," "dependency," "withdrawal," "analgesic," "receptor," and "individual opioid drugs." Clinical and preclinical studies were reviewed for data synthesis. Mechanisms of opioid-induced hyperalgesia and tolerance suggest important drug- and patient-related risk factors that lead to tolerance and withdrawal. Opioid tolerance occurs earlier in the younger age groups, develops commonly during critical illness, and results more frequently from prolonged intravenous infusions of short-acting opioids. Treatment options include slowly tapering opioid doses, switching to longer-acting opioids, or specifically treating the symptoms of opioid withdrawal. Novel therapies may also include blocking the mechanisms of opioid tolerance, which would enhance the safety and effectiveness of opioid analgesia. Opioid tolerance and withdrawal occur frequently in critically ill children. Novel insights into opioid receptor physiology and cellular biochemical changes will inform scientific approaches for the use of opioid analgesia and the prevention of opioid tolerance and withdrawal.

The Significance of Prolonged and Saddleback Fever in Hospitalised Adult Dengue.

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Deborah Hl Ng

Full Text Available Dengue fever is gaining importance in Singapore with an increase in the number of cases and mortality in recent years. Although prolonged and saddleback fever have been reported in dengue fever, there are no specific studies on their significance in dengue. This study aims to examine the prevalence of prolonged and saddleback fever in dengue as well as their associations with dengue severity. A total of 2843 polymerase-chain reaction (PCR confirmed dengue patients admitted to Tan Tock Seng Hospital from 2004 to 2008 were included in the study. Sixty-nine percent of them were male with a median age of 34 years. Prolonged fever (fever > 7 days duration was present in 572 (20.1% of patients. Dengue hemorrhagic fever (DHF, dengue shock syndrome (DSS and severe dengue (SD were significantly more likely to occur in patients with prolonged fever. Mucosal bleeding, anorexia, diarrhea, abdominal pain, nausea or vomiting, lethargy, rash, clinical fluid accumulation, hepatomegaly, nosocomial infection, leukopenia, higher neutrophil count, higher hematocrit, higher alanine transaminase (ALT and aspartate transaminase (AST, higher creatinine, lower protein and prolonged activated partial thromboplastin time (APTT were significantly associated with prolonged fever but not platelet count or prothrombin time (PT. Saddleback fever was present in 165 (5.8%. Although DHF and SD were more likely to occur in patients in those with saddleback fever, DSS was not. Compared with prolonged fever, saddleback fever did not show many significant associations except for diarrhea, abdominal pain, clinical fluid accumulation, hematocrit and platelet change, and lower systolic blood pressure. This study demonstrates that prolonged fever may be associated with various warning signs and more severe forms of dengue (SD, DSS, DHF, while saddleback fever showed associations with DHF and SD but not DSS. The presence of prolonged or saddleback fever in dengue patients should therefore

Circulating levels of pegvisomant and endogenous growth hormone during prolonged pegvisomant therapy in patients with acromegaly

DEFF Research Database (Denmark)

Madsen, Michael; Fisker, Sanne; Feldt-Rasmussen, Ulla

2014-01-01

OBJECTIVE: To investigate whether pegvisomant treatment in acromegaly induces gradual elevations in endogenous serum growth hormone (GH) levels and whether serum pegvisomant levels predict the therapeutic outcome. PATIENTS AND METHODS: Seventeen patients (6 women), mean age 46·3 years (range: 23...... correlated with baseline growth hormone levels, whereas no associations between serum pegvisomant and either dose, gender, age or body weight were found. CONCLUSIONS: (1) Serum GH levels increased initially, but remained stable during prolonged pegvisomant treatment in patients with acromegaly, (2) serum...

Prolonged social withdrawal disorder: a hikikomori case in Spain.

Science.gov (United States)

Ovejero, Santiago; Caro-Cañizares, Irene; de León-Martínez, Victoria; Baca-Garcia, Enrique

2014-09-01

The Japanese term hikikomori means literally 'to be confined'. Social withdrawal can be present in severe psychiatric disorders; however, in Japan, hikikomori is a defined nosologic entity. There have been only a few reported cases in occidental culture. We present a case report of a Spanish man with prolonged social withdrawal lasting for 4 years. This is a case of prolonged social withdrawal not bound to culture, as well as the second case of hikikomori reported in Spain. We propose prolonged social withdrawal disorder as a disorder not linked to culture, in contrast to hikikomori. Further documentation of this disorder is still needed to encompass all cases reported in Japan and around the world. © The Author(s) 2013.

Ventricular Cycle Length Characteristics Estimative of Prolonged RR Interval during Atrial Fibrillation

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CIACCIO, EDWARD J.; BIVIANO, ANGELO B.; GAMBHIR, ALOK; EINSTEIN, ANDREW J.; GARAN, HASAN

2014-01-01

Background When atrial fibrillation (AF) is incessant, imaging during a prolonged ventricular RR interval may improve image quality. It was hypothesized that long RR intervals could be predicted from preceding RR values. Methods From the PhysioNet database, electrocardiogram RR intervals were obtained from 74 persistent AF patients. An RR interval lengthened by at least 250 ms beyond the immediately preceding RR interval (termed T0 and T1, respectively) was considered prolonged. A two-parameter scatterplot was used to predict the occurrence of a prolonged interval T0. The scatterplot parameters were: (1) RR variability (RRv) estimated as the average second derivative from 10 previous pairs of RR differences, T13–T2, and (2) Tm–T1, the difference between Tm, the mean from T13 to T2, and T1. For each patient, scatterplots were constructed using preliminary data from the first hour. The ranges of parameters 1 and 2 were adjusted to maximize the proportion of prolonged RR intervals within range. These constraints were used for prediction of prolonged RR in test data collected during the second hour. Results The mean prolonged event was 1.0 seconds in duration. Actual prolonged events were identified with a mean positive predictive value (PPV) of 80% in the test set. PPV was >80% in 36 of 74 patients. An average of 10.8 prolonged RR intervals per 60 minutes was correctly identified. Conclusions A method was developed to predict prolonged RR intervals using two parameters and prior statistical sampling for each patient. This or similar methodology may help improve cardiac imaging in many longstanding persistent AF patients. PMID:23998759

Women's experiences of becoming a mother after prolonged labour.

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Nystedt, Astrid; Högberg, Ulf; Lundman, Berit

2008-08-01

This paper is a report of a study to explore women's experiences of becoming a mother after prolonged labour. The negativity associated with a complicated labour such as prolonged labour can lead to a struggle to become a healthy mother and could restrict the process of becoming a mother. Interviews were conducted in 2004 with 10 mothers who had been through a prolonged labour with assisted vaginal or caesarean delivery 1-3 months previously. Thematic content analysis was used. Three themes were formulated, describing women's experiences as fumbling in the dark, struggling for motherhood and achieving confidence in being a mother. The difficulties and suffering involved in becoming a mother after a prolonged labour were interpreted to be like 'fumbling in the dark'. Women experienced bodily fatigue, accompanied by feelings of illness and detachment from the child. Having the child when in this condition entailed a struggle to become a mother. In spite of these experiences and the desire to achieve confidence in being a mother, the reassurance of these women regarding their capacity for motherhood was crucial: it was central to their happiness as mothers, encouraged interaction and relationship with the child, and contributed to their adaptation to motherhood. Women experiencing prolonged labour may be comparable with the experience of and recovery from illness, which could contribute to difficulties transitioning to motherhood and limit a woman's ability to be emotionally available for the child.

Prolonged unexplained fatigue in paediatrics

NARCIS (Netherlands)

Bakker, R.J.

2010-01-01

Prolonged Unexplained Fatigue in Paediatrics. Fatigue, as the result of mental or physical exertion, will disappear after rest, drinks and food. Fatigue as a symptom of illness will recover with the recovering of the illness. But when fatigue is ongoing for a long time, and not the result of

Complete Restoration of Refractory Mandibular Osteoradionecrosis by Prolonged Treatment with a Pentoxifylline-Tocopherol-Clodronate Combination (PENTOCLO): A Phase II Trial

International Nuclear Information System (INIS)

Delanian, Sylvie; Chatel, Cecile; Porcher, Raphael; Depondt, Joel; Lefaix, Jean-Louis

2011-01-01

Purpose: Osteoradionecrosis (ORN) is a nonhealing wound of the bone that is difficult to manage. Combined treatment with pentoxifylline and vitamin E reduces radiation-induced fibrosis and ORN with a good prognosis. We previously showed that the combination of pentoxifylline and vitamin E with clodronate (PENTOCLO) is useful in healing sternocostal and some mandibular ORN. Is PENTOCLO effective in ORN of poor prognosis? Methods: 54 eligible patients previously irradiated for head and neck cancer (among 72 treated) a mean 5 years previously received exteriorized refractory mandibular ORN for 1.4 ± 1.8 years, mainly after local surgery and hyperbaric oxygen had been ineffective. The mean length of exposed bone (D) was 17 ± 8 mm as primary endpoint, and the mean Subjective, Objective, Management, and Analytic evaluation of injury (SOMA) score was 16 ± 4. Between August 2000 and August 2008, all patients were given daily oral PENTOCLO: 800 mg pentoxifylline, 1,000 IU vitamin E, and 1,600 mg clodronate 5 days per week alternating with 20 mg prednisone and 1,000 mg ciprofloxacin 2 days per week. The duration of treatment was related to consolidated healing. Results: Prolonged treatment (16 ± 9 months) was safe and well tolerated. All patients improved, with an exponential progressive-(f[t] = a.exp(-b.t)-and significant (p 2 -42%, D 4 -62%, D 6 -77%, D 12 -92%, and D 18 -96%, combined with iterative spontaneous sequestrectomies in 36 patients. All patients experienced complete recovery in a median of 9 months. Clinical improvement was measured in terms of discontinuation of analgesics, new fracture, closed skin fistulae, and delayed radiologic improvement: SOMA 6 -64%, SOMA 12 -89%, and SOMA 30 -96%. Conclusion: Long-term PENTOCLO treatment is effective, safe, and curative for refractory ORN and induces mucosal and bone healing with significant symptom improvement. These findings will need to be confirmed in a randomized trial.

[The prevention and treatment of suppurative-inflammatory complications in the bronchopulmonary system during prolonged artificial ventilation].

Science.gov (United States)

Mozhaev, G A; Tikhonovskiĭ, I Iu

1992-01-01

The use of physical methods, namely low frequency magnetic field in critically ill patients under respiratory therapy made it possible to prevent and in case of their development to effectively treat pyoinflammatory bronchopulmonary complications that accompany prolonged controlled lung ventilation. The results obtained were due to the elimination of an unfavourable effect of controlled lung ventilation on natural resistance and immune response of the respiratory tract because of normalization of physicochemical properties of the tracheobronchial tree secretion, enhanced functional capacities of phagocytes, repaired bonds between cellular and humoral local immunity in the lungs.

Factors associated with prolonged length of stay following cardiac surgery in a major referral hospital in Oman: a retrospective observational study.

Science.gov (United States)

Almashrafi, Ahmed; Alsabti, Hilal; Mukaddirov, Mirdavron; Balan, Baskaran; Aylin, Paul

2016-06-08

Two objectives were set for this study. The first was to identify factors influencing prolonged postoperative length of stay (LOS) following cardiac surgery. The second was to devise a predictive model for prolonged LOS in the cardiac intensive care unit (CICU) based on preoperative factors available at admission and to compare it against two existing cardiac stratification systems. Observational retrospective study. A tertiary hospital in Oman. All adult patients who underwent cardiac surgery at a major referral hospital in Oman between 2009 and 2013. 30.5% of the patients had prolonged LOS (≥11 days) after surgery, while 17% experienced prolonged ICU LOS (≥5 days). Factors that were identified to prolong CICU LOS were non-elective surgery, current congestive heart failure (CHF), renal failure, combined coronary artery bypass graft (CABG) and valve surgery, and other non-isolated valve or CABG surgery. Patients were divided into three groups based on their scores. The probabilities of prolonged CICU LOS were 11%, 26% and 28% for group 1, 2 and 3, respectively. The predictive model had an area under the curve of 0.75. Factors associated with prolonged overall postoperative LOS included the body mass index, the type of surgery, cardiopulmonary bypass machine use, packed red blood cells use, non-elective surgery and number of complications. The latter was the most important determinant of postoperative LOS. Patient management can be tailored for individual patient based on their treatments and personal attributes to optimise resource allocation. Moreover, a simple predictive score system to enable identification of patients at risk of prolonged CICU stay can be developed using data that are routinely collected by most hospitals. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Naloxone fails to prolong seizure length in ECT.

Science.gov (United States)

Rasmussen, K G; Pandurangi, A K

1999-12-01

Electroconvulsive shock (ECS) in animals has been shown to enhance endogenous opiate systems. The anticonvulsant effects of ECS are also partially blocked by the opiate receptor antagonist naloxone, leading some investigators to postulate that the anticonvulsant effects of ECS are mediated by activation of endogenous opiates. If such a phenomenon occurs in humans, then naloxone might prolong seizure length in electroconvulsive therapy (ECT). In the present study, nine patients were given 2.0 mg intravenous (i.v.) naloxone 2 minutes prior to one-half of their ECT treatments. Motor seizure length was measured via the cuff technique. EEG tracings were read by an investigator blind to naloxone status. There was no difference between the two groups in either EEG or nonblindly evaluated motor seizure length. It is concluded that a dose of 2 mg naloxone does not effectively increase seizure length in ECT.

Does a 'tight' hamstring predict low back pain reporting during prolonged standing?

Science.gov (United States)

Raftry, Sean M; Marshall, Paul W M

2012-06-01

The purpose of this study was to investigate the relationship between hamstring passive stiffness and extensibility in asymptomatic individuals with the reporting of low back pain during 2-h prolonged standing. Twenty healthy participants with no history of low back pain (mean±SD, age 22.6±2.7 years, height 1.74±0.09 m, weight 76.2±14.8 kg). Low back pain (VAS score; mm) was continuously monitored during 2-h prolonged standing. Hamstring extensibility, passive stiffness, and stretch tolerance were measured before and after prolonged standing using an instrumented straight leg raise (iSLR). Ten participants reported a clinically relevant increase (Δ VAS>10mm) in low back pain during prolonged standing. Hamstring extensiblity (leg°(max)), passive stiffness (Nm.°(-1)), and stretch tolerance (VAS; mm) were no different between pain developers and non-pain developers. No changes in hamstring measures were observed following 2-h prolonged standing. No relationship was observed in this study between measures of hamstring extensibility and the reporting of low back pain during prolonged standing. There is no evidence to recommend hamstring extensibility interventions (i.e. passive stretching) as a means of reducing pain reporting in occupations requiring prolonged standing. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cocaine Hydrolase Gene Transfer Demonstrates Cardiac Safety and Efficacy against Cocaine-Induced QT Prolongation in Mice

OpenAIRE

Murthy, Vishakantha; Reyes, Santiago; Geng, Liyi; Gao, Yang; Brimijoin, Stephen

2016-01-01

Cocaine addiction is associated with devastating medical consequences, including cardiotoxicity and risk-conferring prolongation of the QT interval. Viral gene transfer of cocaine hydrolase engineered from butyrylcholinesterase offers therapeutic promise for treatment-seeking drug users. Although previous preclinical studies have demonstrated benefits of this strategy without signs of toxicity, the specific cardiac safety and efficacy of engineered butyrylcholinesterase viral delivery remains...

Subchondral insufficiency fracture of the knee: a non-traumatic injury with prolonged recovery time.

Science.gov (United States)

Gourlay, Margaret L; Renner, Jordan B; Spang, Jeffrey T; Rubin, Janet E

2015-06-08

Subchondral insufficiency fractures are non-traumatic fractures that occur immediately below the cartilage of a joint. Although low bone density may be present concurrently, it is not the underlying cause of subchondral insufficiency fractures in the majority of patients. Patients with subchondral insufficiency fracture characteristically have unremarkable plain radiographs, while MRI examination may reveal extensive bone marrow oedema and subchondral bone collapse. This article presents a 51-year-old postmenopausal woman, a physician, who had subchondral insufficiency fractures of the knee associated with prolonged standing during clinical work. She was treated with partial weight bearing on crutches until 14 months after the injury, viscosupplementation at 4 months to treat osteoarthritis and teriparatide treatment to improve bone healing at 7 months. By 26 months after the injury, she tolerated independent walking with a fabric knee support but still experienced mild posterolateral knee pain and numbness on prolonged standing. 2015 BMJ Publishing Group Ltd.

Studies on Prolonging Storage life and Maintaining Fruit Quality Parameters of Zaghloul Dates

International Nuclear Information System (INIS)

ElSalhy, F.T.

2011-01-01

This study was carried out to investigate the effect of gamma irradiation ( 1, 2 and 3 kGy) and some natural plant extracts i.e. aloe, ambrosia, cinnamon, chamomile, clove or nigella on prolonging the storage life and some parameters of Zaghloul dates quality under cold storage (5 ±2 C, 90-95 % RH). The weight loss %, decay %, T.S.S. %, total sugars and non-reducing sugars % of Zaghloul dates were increased in most cases with prolonging the storage time. Meanwhile, titratable acidity %, reducing sugars % and tannins content were decreased during storage period (56 days). However, the lowest values of weight loss % and decay % were recorded by aloe extract treatment while the highest values of T.S.S., total sugars, non-reducing sugars, titratable acidity %, reducing sugars % and tannins content were scored by gamma irradiation at 3 kGy. It could be concluded that using irradiation at 3 kGy, aloe, cinnamon or clove can keep the dates (Zaghloul variety) fresh even after 56 days at cold storage with good quality and safety levels of microbes

Phytochemicals from cruciferous vegetables, epigenetics, and prostate cancer prevention.

Science.gov (United States)

W Watson, Gregory; M Beaver, Laura; E Williams, David; H Dashwood, Roderick; Ho, Emily

2013-10-01

Epidemiological evidence has demonstrated a reduced risk of prostate cancer associated with cruciferous vegetable intake. Follow-up studies have attributed this protective activity to the metabolic products of glucosinolates, a class of secondary metabolites produced by crucifers. The metabolic products of glucoraphanin and glucobrassicin, sulforaphane, and indole-3-carbinol respectively, have been the subject of intense investigation by cancer researchers. Sulforaphane and indole-3-carbinol inhibit prostate cancer by both blocking initiation and suppressing prostate cancer progression in vitro and in vivo. Research has largely focused on the anti-initiation and cytoprotective effects of sulforaphane and indole-3-carbinol through induction of phases I and II detoxification pathways. With regards to suppressive activity, research has focused on the ability of sulforaphane and indole-3-carbinol to antagonize cell signaling pathways known to be dysregulated in prostate cancer. Recent investigations have characterized the ability of sulforaphane and indole-3-carbinol derivatives to modulate the activity of enzymes controlling the epigenetic status of prostate cancer cells. In this review, we will summarize the well-established, "classic" non-epigenetic targets of sulforaphane and indole-3-carbinol, and highlight more recent evidence supporting these phytochemicals as epigenetic modulators for prostate cancer chemoprevention.

Prolonged fasting activates Nrf2 in post-weaned elephant seals.

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Vázquez-Medina, José Pablo; Soñanez-Organis, José G; Rodriguez, Ruben; Viscarra, Jose A; Nishiyama, Akira; Crocker, Daniel E; Ortiz, Rudy M

2013-08-01

Elephant seals naturally experience prolonged periods of absolute food and water deprivation (fasting). In humans, rats and mice, prolonged food deprivation activates the renin-angiotensin system (RAS) and increases oxidative damage. In elephant seals, prolonged fasting activates RAS without increasing oxidative damage likely due to an increase in antioxidant defenses. The mechanism leading to the upregulation of antioxidant defenses during prolonged fasting remains elusive. Therefore, we investigated whether prolonged fasting activates the redox-sensitive transcription factor Nrf2, which controls the expression of antioxidant genes, and if such activation is potentially mediated by systemic increases in RAS. Blood and skeletal muscle samples were collected from seals fasting for 1, 3, 5 and 7 weeks. Nrf2 activity and nuclear content increased by 76% and 167% at week 7. Plasma angiotensin II (Ang II) and transforming growth factor β (TGF-β) were 5000% and 250% higher at week 7 than at week 1. Phosphorylation of Smad2, an effector of Ang II and TGF signaling, increased by 120% at week 7 and by 84% in response to intravenously infused Ang II. NADPH oxidase 4 (Nox4) mRNA expression, which is controlled by smad proteins, increased 430% at week 7, while Nox4 protein expression, which can activate Nrf2, was 170% higher at week 7 than at week 1. These results demonstrate that prolonged fasting activates Nrf2 in elephant seals and that RAS stimulation can potentially result in increased Nox4 through Smad phosphorylation. The results also suggest that Nox4 is essential to sustain the hormetic adaptive response to oxidative stress in fasting seals.

AORN Ergonomic Tool 4: Solutions for Prolonged Standing in Perioperative Settings.

Science.gov (United States)

Hughes, Nancy L; Nelson, Audrey; Matz, Mary W; Lloyd, John

2011-06-01

Prolonged standing during surgical procedures poses a high risk of causing musculoskeletal disorders, including back, leg, and foot pain, which can be chronic or acute in nature. Ergonomic Tool 4: Solutions for Prolonged Standing in Perioperative Settings provides recommendations for relieving the strain of prolonged standing, including the use of antifatigue mats, supportive footwear, and sit/stand stools, that are based on well-accepted ergonomic safety concepts, current research, and access to new and emerging technology. Published by Elsevier Inc.

Tetrodotoxin-Bupivacaine-Epinephrine Combinations for Prolonged Local Anesthesia

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Christina Bognet

2011-12-01

Full Text Available Currently available local anesthetics have analgesic durations in humans generally less than 12 hours. Prolonged-duration local anesthetics will be useful for postoperative analgesia. Previous studies showed that in rats, combinations of tetrodotoxin (TTX with bupivacaine had supra-additive effects on sciatic block durations. In those studies, epinephrine combined with TTX prolonged blocks more than 10-fold, while reducing systemic toxicity. TTX, formulated as Tectin, is in phase III clinical trials as an injectable systemic analgesic for chronic cancer pain. Here, we examine dose-duration relationships and sciatic nerve histology following local nerve blocks with combinations of Tectin with bupivacaine 0.25% (2.5 mg/mL solutions, with or without epinephrine 5 µg/mL (1:200,000 in rats. Percutaneous sciatic blockade was performed in Sprague-Dawley rats, and intensity and duration of sensory blockade was tested blindly with different Tectin-bupivacaine-epinephrine combinations. Between-group comparisons were analyzed using ANOVA and post-hoc Sidak tests. Nerves were examined blindly for signs of injury. Blocks containing bupivacaine 0.25% with Tectin 10 µM and epinephrine 5 µg/mL were prolonged by roughly 3-fold compared to blocks with bupivacaine 0.25% plain (P < 0.001 or bupivacaine 0.25% with epinephrine 5 µg/mL (P < 0.001. Nerve histology was benign for all groups. Combinations of Tectin in bupivacaine 0.25% with epinephrine 5 µg/mL appear promising for prolonged duration of local anesthesia.

MRI findings of prolonged post-traumatic sternal pain

International Nuclear Information System (INIS)

Grosse, Alexandra; Grosse, Claudia; Anderson, Suzanne; Steinbach, Lynne

2007-01-01

The objective of this study was to characterize the different causes of prolonged sternal pain following thoracic trauma with involvement of the sternum and to define criteria for sternal nonunion diagnosis using MRI. Five patients with abnormalities of the sternum were evaluated for prolonged sternal pain following thoracic trauma using MRI. MR images were evaluated by two radiologists in consensus. The patients were selected from the radiology database, which included 8 patients with post-traumatic prolonged sternal pain. Two patients (n = 2) revealed a sternal nonunion after sternal fracture. One patient had a sternal fracture with delayed union and minor displacement of the sternal halves. Abnormal signal intensity alterations adjacent to and within the manubrio-sternal joint were evident in 2 patients and considered due to trauma-related changes in the manubrio-sternal joint. The 3 patients who were not included in the study had no abnormalities of the sternum: 1 of them proved to have a well-healed sternal fracture and nonunion of a rib fracture, 1 had subtle Tietze's syndrome, and 1 patient revealed no pathological findings on imaging. Various factors may be responsible for prolonged sternal pain following thoracic trauma, and these can be viewed with MRI. In cases of sternal nonunion there was common fluid-like signal in the fracture interspace between the bony edges, and the bone marrow adjacent to the nonunion showed altered signal intensity. MRI identified sternal nonunion and other trauma-related abnormalities of the sternum following chest trauma. (orig.)

Psidium guajava and Piper betle leaf extracts prolong vase life of cut carnation (Dianthus caryophyllus) flowers.

Science.gov (United States)

Rahman, M M; Ahmad, S H; Lgu, K S

2012-01-01

The effect of leaf extracts of Psidium guajava and Piper betle on prolonging vase life of cut carnation flowers was studied. "Carola" and "Pallas Orange" carnation flowers, at bud stage, were pulsed 24 hours with a floral preservative. Then, flowers were placed in a vase solution containing sprite and a "germicide" (leaf extracts of P. guajava and P. betle, 8-HQC, or a copper coin). Flowers treated with 8-HQC, copper coin, and leaf extracts had longer vase life, larger flower diameter, and higher rate of water uptake compared to control (tap water). The leaf extracts of P. guajava and P. betle showed highest antibacterial and antifungal activities compared to the other treatments. Both showed similar effects on flower quality as the synthetic germicide, 8-HQC. Therefore, these extracts are likely natural germicides to prolong vase life of cut flowers.

[Prolonged diarrhea and weight loss after a biking trip from Tibet to Nepal: infection with Cyclospora].

Science.gov (United States)

Dekker, E; Kager, P A

2002-08-10

A 39-year-old man, who had made a cycling tour from Tibet to Nepal, visited the outpatients' clinic one month later because of prolonged diarrhoea, abdominal complaints and serious weight loss. Parasitological examination of the stool revealed oocysts of Cyclospora cayetanensis and the patient was treated with trimethoprim-sulfamethoxazole (co-trimoxazole) with good result. C. cayetanensis has only recently been discovered as a protozoal cause of diarrhoea. Infections are primarily reported from areas with a low hygienic standard e.g. Central and South America, the Indian subcontinent (Nepal), Indonesia and South-East Asia. Clinical symptoms of infection are diarrhoea (usually watery), abdominal cramps and discomfort. The infection can have a prolonged course. Diagnosis is made by parasitological examination of the stool (one should be cautious not to confuse with cryptosporidia) and treatment with trimethoprim-sulfamethoxazole is effective.

Pretransplant portal venous administration of donor antigen and portal venous allograft drainage synergistically prolong rat cardiac allograft survival

International Nuclear Information System (INIS)

Kamei, T.; Callery, M.P.; Flye, M.W.

1990-01-01

The effect of antigen given through the portal vein (PV) before transplantation or continuous drainage of a graft into the PV results in moderate prolongation of allograft survival. This study examines these treatment modalities further. Pretransplant donor antigen as 25 x 10(6) ultraviolet B-irradiated (12,000 joules/m2) donor spleen cells was given 7 days before heart transplantation through either the PV or systemic venous (IV) routes. On day 0, Lewis-to-Buffalo rat cardiac allografts were drained either into the PV or IV. Pretransplant PV donor antigen administration (p less than 0.005), but not by IV administration, significantly prolonged cardiac allograft survival across the strong RT 1 rat histoincompatibility barrier. Similarly PV, but not IV, drainage of the graft prolonged graft survival (p less than 0.005). Pretransplant IV antigen administration had no additive effect on PV drainage graft survival. In contrast, when pretransplant PV donor antigen was combined with PV drainage, 11 of 14 allografts (p less than 0.001) continued to function, free of rejection, after 150 days. Therefore for rat cardiac transplants a clearly synergistic graft-prolonging effect results when pretransplant PV donor antigen is combined with PV drainage of the allografts. These data clarify the potent tolerogenic effects of alloantigen not only administered into the PV but also continuously shed intraportally so that it is first processed by the liver

Prolonged blockade of the brachial plexus for the early rehabilitation of children with posttraumatic elbow contractures

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D. V. Zabolotsky

2015-01-01

Full Text Available Objective. Improvement of surgical treatment outcomes in children with post-traumatic elbow contractures. Materials and methods. The study is based on the diagnostic findings of 48 children with post-traumatic elbow contractures who were treated at the Turner Scientific and Research Institute for Children’s Orthopedics. All children underwent complex rehabilitation after reconstructive intra-articular surgery to work out passive motions in the elbow using ARTROMOT-E2 device. The patients of the study group started rehabilitation in the first days after reconstructive intra-articular surgery in the background of prolonged blockade of the brachial plexus. In the control group, the rehabilitation was carried out traditionally on the 6th day after surgery without regional anesthesia. The patients of the study group were supplied with Contiplex SU perinural catheters for prolonged blockade of the brachial plexus using ultrasound (Edge SonoSite and neurostimulation (Stimuplex® HNS12 before surgery. For perioperative blockade of the brachial plexus we used intermittent injection of 0.5% ropivacaine (2 mg / kg. The severity of pain at the stages of rehabilitation was assessed using 10-point grading scale (FPS-R. The range of active and passive motions in the joints was evaluated by measuring the range of motions with a fleximeter. Results. Intermittent injection of ropivacaine before rehabilitation allowed to correct post-traumatic elbow contractures in children in the first days after surgery associated with the minimum subjective pain level and stable hemodynamic parameteres, accompanied with a significant increase of the elbow motion range in comparison with the group of the patients who were not performed regional anesthesia . Conclusion. Prolonged blockade of the brachial plexus in rehabilitation treatment of children with post-traumatic contractures provides appropriate analgesic and myoneural block components from the 1st day after intra

Physiology Of Prolonged Bed Rest

Science.gov (United States)

Greenleaf, John E.

1991-01-01

Report describes physiological effects of prolonged bed rest. Rest for periods of 24 hours or longer deconditions body to some extent; healing proceeds simultaneously with deconditioning. Report provides details on shifts in fluid electrolytes and loss of lean body mass, which comprises everything in body besides fat - that is, water, muscle, and bone. Based on published research.

Uremic retention solute indoxyl sulfate level is associated with prolonged QTc interval in early CKD patients.

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Wei-Hua Tang

Full Text Available Total mortality and sudden cardiac death is highly prevalent in patients with chronic kidney disease (CKD. In CKD patients, the protein-bound uremic retention solute indoxyl sulfate (IS is independently associated with cardiovascular disease. However, the underlying mechanisms of this association have yet to be elucidated. The relationship between IS and cardiac electrocardiographic parameters was investigated in a prospective observational study among early CKD patients. IS arrhythmogenic effect was evaluated by in vitro cardiomyocyte electrophysiological study and mathematical computer simulation. In a cohort of 100 early CKD patients, patients with corrected QT (QTc prolongation had higher IS levels. Furthermore, serum IS level was independently associated with prolonged QTc interval. In vitro, the delay rectifier potassium current (IK was found to be significantly decreased after the treatment of IS in a dose-dependent manner. The modulation of IS to the IK was through the regulation of the major potassium ion channel protein Kv 2.1 phosphorylation. In a computer simulation, the decrease of IK by IS could prolong the action potential duration (APD and induce early afterdepolarization, which is known to be a trigger mechanism of lethal ventricular arrhythmias. In conclusion, serum IS level is independently associated with the prolonged QTc interval in early CKD patients. IS down-regulated IK channel protein phosphorylation and the IK current activity that in turn increased the cardiomyocyte APD and QTc interval in vitro and in the computer ORd model. These findings suggest that IS may play a role in the development of arrhythmogenesis in CKD patients.

Prolonged fatigue is associated with sickness absence in men but not in women: prospective study with 1-year follow-up of white-collar employees.

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Roelen, Corné A M; van Rhenen, Willem; Groothoff, Johan W; van der Klink, Jac J L; Bültmann, Ute

2014-04-01

Prolonged fatigue adversely affects an individual's performance and functioning. The present study investigated the prospective associations between prolonged fatigue and sickness absence (SA) during 1-year follow-up. At baseline, a convenience sample of white-collar employees received the 20-item Checklist Individual Strength (CIS), which measures prolonged fatigue by covering the dimensions fatigue severity, reduced concentration, reduced motivation, and reduced physical activity. SA episodes were registered during the 1-year follow-up distinguishing between short-term (1-7 days) and long-term ( 7 days) SA episodes. Baseline CIS scores were linked to SA during follow-up by negative binomial regression models in which age, gender, job grade, and prior SA were controlled for. Six hundred and thirty-three (56 %) employees participated in the study of which 598 had complete data and were eligible for analysis. Gender was a significant effect modifier of the relationship between prolonged fatigue and SA. Therefore, the results were stratified for men (N = 365) and women (N = 233). In white-collar men, fatigue severity and reduced concentration were positively associated with the number of long-term SA episodes, while other fatigue dimensions were not significantly related to SA. In white-collar women, prolonged fatigue was not associated with SA during 1-year follow-up. The results of this study warrant more attention for prolonged fatigue in occupational healthcare practice and research. Early identification of and treatment for prolonged fatigue might prevent future health problems and SA, especially in white-collar men.

Treatment preferences of psychotherapy patients with chronic PTSD.

Science.gov (United States)

Markowitz, John C; Meehan, Kevin B; Petkova, Eva; Zhao, Yihong; Van Meter, Page E; Neria, Yuval; Pessin, Hayley; Nazia, Yasmin

2016-03-01

Patient treatment preference may moderate treatment effect in major depressive disorder (MDD) studies. Little research has addressed preference in posttraumatic stress disorder (PTSD); almost none has assessed actual patients' PTSD psychotherapy preferences. From a 14-week trial of chronic PTSD comparing prolonged exposure, relaxation therapy, and interpersonal psychotherapy, we report treatment preferences of the 110 randomized patients, explore preference correlates, and assess effects on treatment outcome. Patients recruited between 2008 and 2013 with chronic DSM-IV PTSD (Clinician-Administered PTSD Scale [CAPS] score ≥ 50) received balanced, scripted psychotherapy descriptions prerandomization and indicated their preferences. Analyses assessed relationships of treatment attitudes to demographic and clinical factors. We hypothesized that patients randomized to preferred treatments would have better outcomes, and to unwanted treatment worse outcomes. Eighty-seven patients (79%) voiced treatment preferences or disinclinations: 29 (26%) preferred prolonged exposure, 29 (26%) preferred relaxation therapy, and 56 (50%) preferred interpersonal psychotherapy (Cochran Q = 18.46, P psychotherapy (Cochran Q = 22.71, P psychotherapy preferences to outcome. Despite explanations emphasizing prolonged exposure's greater empirical support, patients significantly preferred interpersonal psychotherapy. Preference subtly affected psychotherapy outcome; depression appeared an important moderator of the effect of unwanted treatment on outcome. Potential biases to avoid in future research are discussed. ClinicalTrials.gov identifier: NCT00739765. © Copyright 2015 Physicians Postgraduate Press, Inc.

Sulforaphane Suppresses Hepatitis C Virus Replication by Up-Regulating Heme Oxygenase-1 Expression through PI3K/Nrf2 Pathway.

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Jung-Sheng Yu

Full Text Available Hepatitis C virus (HCV infection-induced oxidative stress is a major risk factor for the development of HCV-associated liver disease. Sulforaphane (SFN is an antioxidant phytocompound that acts against cellular oxidative stress and tumorigenesis. However, there is little known about its anti-viral activity. In this study, we demonstrated that SFN significantly suppressed HCV protein and RNA levels in HCV replicon cells and infectious system, with an IC50 value of 5.7 ± 0.2 μM. Moreover, combination of SFN with anti-viral drugs displayed synergistic effects in the suppression of HCV replication. In addition, we found nuclear factor erythroid 2-related factor 2 (Nrf2/HO-1 induction in response to SFN and determined the signaling pathways involved in this process, including inhibition of NS3 protease activity and induction of IFN response. In contrast, the anti-viral activities were attenuated by knockdown of HO-1 with specific inhibitor (SnPP and shRNA, suggesting that anti-HCV activity of SFN is dependent on HO-1 expression. Otherwise, SFN stimulated the phosphorylation of phosphoinositide 3-kinase (PI3K leading Nrf2-mediated HO-1 expression against HCV replication. Overall, our results indicated that HO-1 is essential in SFN-mediated anti-HCV activity and provide new insights in the molecular mechanism of SFN in HCV replication.

Impact of Azithromycin on Pregnancy Prolongation in Women at Risk of Preterm Labor: A Time-to-Event Analysis.

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Goyer, Isabelle; Ferland, Gabrielle; Ruo, Ni; Morin, Caroline; Brochet, Marie-Sophie; Morin, Lucie; Ferreira, Ema

2016-09-13

Since 2006, the empiric use of azithromycin in women at risk of premature birth has become prevalent in our institution without any evidence of its efficacy. Although antibiotics can prolong pregnancy in preterm prolonged rupture of membranes, no published data are available for women with intact membranes. To describe the purpose of adding azithromycin to the usual treatments (cerclage, tocolysis, rest, etc.) to prolong pregnancy in women with intact membranes who are at risk of or already in preterm labour. A retrospective observational cohort study was done at a Mother-Child University Hospital Centre. Patients admitted to obstetric ward who received azithromycin between January 1 st , 2006 and August 1 st , 2010 were included. A total of 127 exposed women were matched to 127 controls through medical records and pharmacy software. A time-to-event analysis was done to compare gestational age at the time of the recorded composite event (delivery, or rupture of membranes, or second intervention to prolong pregnancy). To compare proportions of composite event at different time points, χ 2 tests were used. Patients who received azithromycin had a more severe condition at presentation. Once adjusted for confounding factors, prolongation of pregnancy (HR =1.049; CI 95%: 0.774-1.421 [p=0.758]) and gestational age at the event (HR=1.200; CI 95%: 0.894-1.609 [p=0.225]) did not differ between the groups. The proportions of women with an event ≥7 days post-diagnosis or ≥37 gestational weeks were similar. Azithromycin was added to medical therapy in a more at-risk population and no clear benefit was measured.

MRI findings of prolonged post-traumatic sternal pain

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Grosse, Alexandra; Grosse, Claudia; Anderson, Suzanne [University Hospital of Berne, Department of Diagnostic, Pediatric and Interventional Radiology, Berne (Switzerland); Steinbach, Lynne [University of California San Francisco, Department of Radiology, San Francisco, CA (United States)

2007-05-15

The objective of this study was to characterize the different causes of prolonged sternal pain following thoracic trauma with involvement of the sternum and to define criteria for sternal nonunion diagnosis using MRI. Five patients with abnormalities of the sternum were evaluated for prolonged sternal pain following thoracic trauma using MRI. MR images were evaluated by two radiologists in consensus. The patients were selected from the radiology database, which included 8 patients with post-traumatic prolonged sternal pain. Two patients (n = 2) revealed a sternal nonunion after sternal fracture. One patient had a sternal fracture with delayed union and minor displacement of the sternal halves. Abnormal signal intensity alterations adjacent to and within the manubrio-sternal joint were evident in 2 patients and considered due to trauma-related changes in the manubrio-sternal joint. The 3 patients who were not included in the study had no abnormalities of the sternum: 1 of them proved to have a well-healed sternal fracture and nonunion of a rib fracture, 1 had subtle Tietze's syndrome, and 1 patient revealed no pathological findings on imaging. Various factors may be responsible for prolonged sternal pain following thoracic trauma, and these can be viewed with MRI. In cases of sternal nonunion there was common fluid-like signal in the fracture interspace between the bony edges, and the bone marrow adjacent to the nonunion showed altered signal intensity. MRI identified sternal nonunion and other trauma-related abnormalities of the sternum following chest trauma. (orig.)

The incidence of hyponatremia during prolonged ultraendurance exercise.

Science.gov (United States)

Noakes, T D; Norman, R J; Buck, R H; Godlonton, J; Stevenson, K; Pittaway, D

1990-04-01

Recent studies have shown that potentially fatal hyponatremia can develop during prolonged exercise. To determine the incidence of hyponatremia in athletes competing in ultradistance events, we measured serum sodium levels in 315 of 626 (50%) runners who were treated for collapse after two 90 km ultramarathon footraces (total starters 20,335; total finishers 18,031) and in 101 of 147 (69%) finishers in a 186 km ultratriathlon. In both races the athletes drank fluids with low sodium chloride content (less than 6.8 mmol.l-1). Hyponatremia (serum sodium level less than 130 mmol.l-1) was identified in 27 of 315 (9%) collapsed runners in the 90 km races and in none of the triathletes. In response to diuretic therapy, the runner with the most severe hyponatremia (serum sodium level = 112 mmol.l-1) excreted in excess of 7.5 l dilute urine during the first 17 h of hospitalization. These data suggest that, although symptomatic hyponatremia occurs in less than 0.3% of competitors during prolonged exercise even when they ingest little sodium chloride, it is found in a significant proportion (9%) of collapsed runners. A regulated contraction of the extracellular fluid volume would explain why the majority of athletes maintain normal serum sodium levels even though they develop a significant sodium chloride deficit during prolonged exercise. Alternatively, sodium chloride losses during prolonged exercise may be substantially less than are currently believed. Physicians treating collapsed ultradistance athletes need to be aware that as many as 10% or more of such patients may be hyponatremic.

Prolonged sitting in cars: prevalence, socio-demographic variations, and trends.

Science.gov (United States)

Sugiyama, Takemi; Merom, Dafna; van der Ploeg, Hidde P; Corpuz, Grace; Bauman, Adrian; Owen, Neville

2012-10-01

Prolonged sitting is detrimentally associated with health outcomes. However, the prevalence and characteristics of those who sit in cars for long periods are not well understood. This study examined the population prevalence, socio-demographic variations, and trends for prolonged sitting in cars among adults. Using the Sydney Greater Metropolitan Area Household Travel Survey, the prevalence of prolonged sitting time in cars (≥2 h/day) was calculated for four 3-year periods (1997-99, 2000-02, 2003-05, and 2006-08) for each population subgroup. Trends were calculated as the mean change in prevalence between adjacent survey periods. Cars were used for 66% of the total trips recorded (n=336,505). The prevalence of prolonged sitting time in cars was 16-18% in men, and 10-12% in women. Relatively higher prevalence rates were found among middle-age groups (men: 20-22%, women: 12-15%), full-time workers (men: 21-24%, women: 14-15%), those with higher income (men: 21-25%, women: 14-16%), couples with children (men: 20-21%, women: 12-14%), and those living in outer suburbs (men: 20-23%, women: 12-13%). Trends were stable in men, but increasing in women. Several subgroups (older age; living in regional suburbs) also showed increasing trends. These findings provide evidence to inform integrated approaches to measurement and policy development on prolonged car use among the public health, urban planning, and transport sectors. Copyright © 2012 Elsevier Inc. All rights reserved.

Management of children with prolonged diarrhea [version 1; referees: 3 approved

Directory of Open Access Journals (Sweden)

Antonietta Giannattasio

2016-02-01

Full Text Available Prolonged diarrhea is usually defined as acute-onset diarrhea lasting 7 days or more, but less than 14 days. Its trend has been declining in recent years because of improvement in the management of acute diarrhea, which represents the ideal strategy to prevent prolonged diarrhea. The pathogenesis of prolonged diarrhea is multifactorial and essentially based on persistent mucosal damage due to specific infections or sequential infections with different pathogens, host-related factors including micronutrient and/or vitamin deficiency, undernutrition and immunodeficiency, high mucosal permeability due to previous infectious processes and nutrient deficiency with consequential malabsorption, and microbiota disruption. Infections seem to play a major role in causing prolonged diarrhea in both developing and developed areas. However, single etiologic pathogens have not been identified, and the pattern of agents varies according to settings, host risk factors, and previous use of antibiotics and other drugs. The management of prolonged diarrhea is complex. Because of the wide etiologic spectrum, diagnostic algorithms should take into consideration the age of the patient, clinical and epidemiological factors, and the nutritional status and should always include a search for enteric pathogens. Often, expensive laboratory evaluations are of little benefit in guiding therapy, and an empirical approach may be effective in the majority of cases. The presence or absence of weight loss is crucial for driving the initial management of prolonged diarrhea. If there is no weight loss, generally there is no need for further evaluation. If weight loss is present, empiric anti-infectious therapy or elimination diet may be considered once specific etiologies have been excluded.

Integrating Dialectical Behavior Therapy and Prolonged Exposure to Treat Co-Occurring Borderline Personality Disorder and PTSD: Two Case Studies

Science.gov (United States)

Harned, Melanie S.; Linehan, Marsha M.

2008-01-01

Despite the high rate of trauma and PTSD among individuals with borderline personality disorder (BPD), no studies have specifically evaluated the treatment of PTSD in a BPD population. These case studies illustrate the use of a protocol based on prolonged exposure therapy that can be integrated into standard dialectical behavior therapy to treat…

Psidium guajava and Piper betle Leaf Extracts Prolong Vase Life of Cut Carnation (Dianthus caryophyllus Flowers

Directory of Open Access Journals (Sweden)

M. M. Rahman

2012-01-01

Full Text Available The effect of leaf extracts of Psidium guajava and Piper betle on prolonging vase life of cut carnation flowers was studied. “Carola” and “Pallas Orange” carnation flowers, at bud stage, were pulsed 24 hours with a floral preservative. Then, flowers were placed in a vase solution containing sprite and a “germicide” (leaf extracts of P. guajava and P. betle, 8-HQC, or a copper coin. Flowers treated with 8-HQC, copper coin, and leaf extracts had longer vase life, larger flower diameter, and higher rate of water uptake compared to control (tap water. The leaf extracts of P. guajava and P. betle showed highest antibacterial and antifungal activities compared to the other treatments. Both showed similar effects on flower quality as the synthetic germicide, 8-HQC. Therefore, these extracts are likely natural germicides to prolong vase life of cut flowers.

Levofloxacin-Induced QTc Prolongation Depends on the Time of Drug Administration

NARCIS (Netherlands)

Kervezee, L; Gotta, V; Stevens, J; Birkhoff, W; Kamerling, Imc; Danhof, M; Meijer, J H; Burggraaf, J

2016-01-01

Understanding the factors influencing a drug's potential to prolong the QTc interval on an electrocardiogram is essential for the correct evaluation of its safety profile. To explore the effect of dosing time on drug-induced QTc prolongation, a randomized, crossover, clinical trial was conducted in

Dose-dependent effects of R-sulforaphane isothiocyanate on the biology of human mesenchymal stem cells, at dietary amounts, it promotes cell proliferation and reduces senescence and apoptosis, while at anti-cancer drug doses, it has a cytotoxic effect.

Science.gov (United States)

Zanichelli, Fulvia; Capasso, Stefania; Cipollaro, Marilena; Pagnotta, Eleonora; Cartenì, Maria; Casale, Fiorina; Iori, Renato; Galderisi, Umberto

2012-04-01

Brassica vegetables are attracting a great deal of attention as healthy foods because of the fact that they contain substantial amounts of secondary metabolite glucosinolates that are converted into isothiocyanates, such as sulforaphane [(-)1-isothiocyanato-4R-(methylsulfinyl)-butane] (R-SFN), through the actions of chopping or chewing the vegetables. Several studies have analyzed the biological and molecular mechanisms of the anti-cancer activity of synthetic R,S-sulforaphane, which is thought to be a result of its antioxidant properties and its ability to inhibit histone deacetylase enzymes (HDAC). Few studies have addressed the possible antioxidant effects of R-SFN, which could protect cells from the free radical damage that strongly contribute to aging. Moreover, little is known about the effect of R-SFN on stem cells whose longevity is implicated in human aging. We evaluated the effects of R-SFN on the biology on human mesenchymal stem cells (MSCs), which, in addition to their ability to differentiate into mesenchymal tissues, support hematopoiesis, and contribute to the homeostatic maintenance of many organs and tissues. Our investigation found evidence that low doses of R-SFN promote MSCs proliferation and protect them from apoptosis and senescence, while higher doses have a cytotoxic effect, leading to the induction of cell cycle arrest, programmed cell death and senescence. The beneficial effects of R-SFN may be ascribed to its antioxidant properties, which were observed when MSC cultures were incubated with low doses of R-SFN. Its cytotoxic effects, which were observed after treating MSCs with high doses of R-SFN, could be attributed to its HDAC inhibitory activity. In summary, we found that R-SFN, like many other dietary supplements, exhibits a hormetic behavior; it is able to induce biologically opposite effects at different doses.

Effect of 34 kinds of traditional Japanese herbal medicines on prolongation of cardiac allograft survival.

Science.gov (United States)

Jin, X; Uchiyama, M; Zhang, Q; Harada, T; Otsuka, K; Shimokawa, T; Niimi, M

2014-05-01

Herbal medicines have been used for over 3,000 years in Asian as alternative therapy for their variety effects and have recently become popular in Europe and the United States. In the last 30 years, Japanese herbal medicines were widely used for treatment of diseases after been recognized officially by Japanese government. In this study, we investigated the effect of 34 kinds of traditional Japanese herbal medicines on alloimmune responses in a murine model of cardiac allograft transplantation. CBA mice (H2(k)) underwent transplantation of a C57BL/6 (H2(b)) heart and received oral administration of 2 g/kg/d of the 34 kinds of herbal medicines from the day of transplantation until 7 days afterward. Naïve CBA mice rejected B6 cardiac grafts acutely (median survival time [MST], 7 days). CBA transplant recipients given 2 g/kg/d of Sairei-to (TJ-114) and Tokishakuyaku-san (TJ-23) had prolonged C57BL/6 allograft survival indefinitely (both MSTs > 100 days). Moreover, CBA transplant recipients given Seisinrensiin (TJ-111), Tokishigyakukagoshuyushokyoto (TJ-38), Rikkunshito (TJ-43), Maobushisaishinto (TJ-127), Ninjin-yoei-to (TJ-108), Ryokan-kyomi-shinge-nin-to (TJ-119), Inchingorei-san (TJ-117), Hochuekkito (TJ-41), Kihi-to (TJ-65), and Sinbu-to (TJ-30) had also prolonged C57BL/6 allograft survival significantly (MSTs of 28, 22, 16, 14, 14, 13, 12, 9.5, 9 and 9 days, respectively). However, none of other 22 kinds of herbal medicines could prolong the allograft survival. Furthermore, oral administration of 2 g/kg/d of Daikenchuto (TJ-100) induced sudden death (within 1 minute) in CBA mice. In conclusion, 12 kinds of Japanese herbal medicines prolonged allograft survival and one showed toxic effect in mice. Copyright © 2014 Elsevier Inc. All rights reserved.

Daptomycin in the treatment of prosthetic joint infection by Enterococcus faecalis: safety and efficacy of high-dose and prolonged therapy

OpenAIRE

José Ramón Yuste; Milena Quesada; Pablo Díaz-Rada; José Luis Del Pozo

2014-01-01

Enterococci are implicated in less than 2.3% of prosthetic joint infections. These infections can be difficult to treat and therapeutic failures are not uncommon. In these situations, daptomycin is a safe and effective alternative. We present a clinical case with a successful response to the prolonged use of high-dose daptomycin.

In vitro chemo-sensitivity assay guided chemotherapy is associated with prolonged overall survival in cancer patients.

Science.gov (United States)

Udelnow, Andrej; Schönfęlder, Manfred; Würl, Peter; Halloul, Zuhir; Meyer, Frank; Lippert, Hans; Mroczkowski, Paweł

2013-06-01

The overall survival (OS) of patients suffering From various tumour entities was correlated with the results of in vitro-chemosensitivity assay (CSA) of the in vivo applied drugs. Tumour specimen (n=611) were dissected in 514 patients and incubated for primary tumour cell culture. The histocytological regression assay was performed 5 days after adding chemotherapeutic substances to the cell cultures. n=329 patients undergoing chemotherapy were included in the in vitro/in vivo associations. OS was assessed and in vitro response groups compared using survival analysis. Furthermore Cox-regression analysis was performed on OS including CSA, age, TNM classification and treatment course. The growth rate of the primary was 73-96% depending on tumour entity. The in-vitro response rate varied with histology and drugs (e.g. 8-18% for methotrexate and 33-83% for epirubicine). OS was significantly prolonged for patients treated with in vitro effective drugs compared to empiric therapy (log-rank-test, p=0.0435). Cox-regression revealed that application of in vitro effective drugs, residual tumour and postoperative radiotherapy determined the death risk independently. When patients were treated with drugs effective in our CSA, OS was significantly prolonged compared to empiric therapy. CSA guided chemotherapy should be compared to empiric treatment by a prospective randomized trial.

Multimodal actions of the phytochemical sulforaphane suppress both AR and AR-V7 in 22Rv1 cells: Advocating a potent pharmaceutical combination against castration-resistant prostate cancer.

Science.gov (United States)

Khurana, Namrata; Kim, Hogyoung; Chandra, Partha K; Talwar, Sudha; Sharma, Pankaj; Abdel-Mageed, Asim B; Sikka, Suresh C; Mondal, Debasis

2017-11-01

Prostate cancer (PCa) cells expressing full-length androgen receptor (AR-FL) are susceptible to androgen deprivation therapy (ADT). However, outgrowth of castration-resistant prostate cancer (CRPC) can occur due to the expression of constitutively active (ligand-independent) AR splice variants, particularly AR-V7. We previously demonstrated that sulforaphane (SFN), an isothiocyanate phytochemical, can decrease AR-FL levels in the PCa cell lines, LNCaP and C4-2B. Here, we examined the efficacy of SFN in targeting both AR-FL and AR-V7 in the CRPC cell line, CWR22Rv1 (22Rv1). MTT cell viability, wound-heal assay, and colony forming unit (CFU) measurements revealed that 22Rv1 cells are resistant to the anti-androgen, enzalutamide (ENZ). However, co-exposure to SFN sensitized these cells to the potent anticancer effects of ENZ (PAR-FL and AR-V7 levels, and immunofluorescence microscopy (IFM) depicted decreased AR in both cytoplasm and nucleus with SFN treatment. SFN increased both ubiquitination and proteasomal activity in 22Rv1 cells. Studies using a protein synthesis inhibitor (cycloheximide) or a proteasomal inhibitor (MG132) indicated that SFN increases both ubiquitin-mediated aggregation and subsequent proteasomal-degradation of AR proteins. Previous studies reported that SFN inhibits the chaperone activity of heat-shock protein 90 (Hsp90) and induces the nuclear factor erythroid-2-like 2 (Nrf2) transcription factor. Therefore, we investigated whether the Hsp90 inhibitor, ganetespib (G) or the Nrf2 activator, bardoxolone methyl (BM) can similarly suppress AR levels in 22Rv1 cells. Low doses of G and BM, alone or in combination, decreased both AR-FL and AR-V7 levels, and combined exposure to G+BM sensitized 22Rv1 cells to ENZ. Therefore, adjunct treatment with the phytochemical SFN or a safe pharmaceutical combination of G+BM may be effective against CRPC cells, especially those expressing AR-V7.

Variation in Definition of Prolonged Mechanical Ventilation.

Science.gov (United States)

Rose, Louise; McGinlay, Michael; Amin, Reshma; Burns, Karen Ea; Connolly, Bronwen; Hart, Nicholas; Jouvet, Philippe; Katz, Sherri; Leasa, David; Mawdsley, Cathy; McAuley, Danny F; Schultz, Marcus J; Blackwood, Bronagh

2017-10-01

Consistency of definitional criteria for terminology applied to describe subject cohorts receiving mechanical ventilation within ICU and post-acute care settings is important for understanding prevalence, risk stratification, effectiveness of interventions, and projections for resource allocation. Our objective was to quantify the application and definition of terms for prolonged mechanical ventilation. We conducted a scoping review of studies (all designs except single-case study) reporting a study population (adult and pediatric) using the term prolonged mechanical ventilation or a synonym. We screened 5,331 references, reviewed 539 full-text references, and excluded 120. Of the 419 studies (representing 38 countries) meeting inclusion criteria, 297 (71%) reported data on a heterogeneous subject cohort, and 66 (16%) included surgical subjects only (46 of those 66, 70% cardiac surgery). Other studies described COPD (16, 4%), trauma (22, 5%), neuromuscular (17, 4%), and sepsis (1, 0.2%) cohorts. A total of 741 terms were used to refer to the 419 study cohorts. The most common terms were: prolonged mechanical ventilation (253, 60%), admission to specialized unit (107, 26%), and long-term mechanical ventilation (79, 19%). Some authors (282, 67%) defined their cohorts based on duration of mechanical ventilation, with 154 studies (55%) using this as the sole criterion. We identified 37 different durations of ventilation ranging from 5 h to 1 y, with > 21 d being the most common (28 of 282, 7%). For studies describing a surgical cohort, minimum ventilation duration required for inclusion was ≥ 24 h for 20 of 66 studies (30%). More than half of all studies (237, 57%) did not provide a reason/rationale for definitional criteria used, with only 28 studies (7%) referring to a consensus definition. We conclude that substantial variation exists in the terminology and definitional criteria for cohorts of subjects receiving prolonged mechanical ventilation. Standardization of

Acute Right Ventricular Dysfunction Complicating Prolonged ...

African Journals Online (AJOL)

We report a case of transient right ventricular dysfunction associated with prolonged cardiac tamponade, an unusual complication of uncertain etiology. We believe that in this case dynamic coronary flow restriction resulted in ischemic injury and stunning of the right ventricle. Other possible causes are briefly reviewed. Right ...

Primary Sjögren syndrome that initially presented with repeated hypergammaglobulinemic purpura after prolonged sitting: A case report.

Science.gov (United States)

Zhou, Zhihua; Jiang, Weiqiang; Wang, Ming; Liu, Yongyuan; Zhang, Wei; Huang, Manping; Liang, Donghui

2017-12-01

Purpura is a common dermatologic manifestation in Sjögren syndrome (SS). When a patient presents with sicca symptoms, the diagnosis of SS is not difficult. Here, we reported a case of a 52-year-old Chinese woman who initially presented with nonpalpable purpura on both lower extremities, and these lesions had developed soon after prolonged sitting. In the past 2 years, she had repeated cutaneous nonpalpable purpura 4 times. She had no sicca symptoms, dry eyes, or dry mouth. Combining the laboratory findings, Schirmer test, and labial gland biopsy, primary SS was confirmed. The patient was placed on a trial of hydroxychloroquine (200 mg once daily). The purpura on both lower extremities had faded at the sixth day after onset and at the third day after hydroxychloroquine treatment. These case was not easy to diagnosis primary SS because she had no sicca symptoms. A patient with primary SS who initially presented with recurrent purpura associated with prolonged sitting. Prolonged sitting had been a possible aggravating factor for the cutaneous purpura of this patient with primary SS. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Sulforaphane Treatment of Children with Autism Spectrum Disorder

Science.gov (United States)

2017-07-01

the results disseminated to communities of interest? Preliminary report of progress in the study was presented at Pediatric Grand Rounds at UMass on...Publications, conference papers, and presentations A progress report of the study was presented at Pediatric Grand Rounds at UMass on May 26, 2017...Instructor in Pediatrics Researcher Identifier: None Nearest person month worked: Contribution to Project: Dr. Singh assists the PI in the planning

Sulforaphane Treatment of Children with Autism Spectrum Disorder

Science.gov (United States)

2016-07-01

Unclassified 19b. TELEPHONE NUMBER (include area code) Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 Page 2 Table of Contents...Advertisement CLEAN 111815.doc UMass Institutional Biosafety Committee approval SFN Study Medication Diary 041415.doc SFN Study Study Diary Side Effects

The efficacy of antipsychotics for prolonged delirium with renal dysfunction

Directory of Open Access Journals (Sweden)

Asano S

2017-11-01

Full Text Available Satoko Asano, Yasuto Kunii, Hiroshi Hoshino, Yusuke Osakabe, Tetsuya Shiga, Shuntaro Itagaki, Itaru Miura, Hirooki Yabe Department of Neuropsychiatry, School of Medicine Fukushima Medical University, Fukushima, Japan Aim: Delirium is commonly encountered in daily clinical practice. To identify predictors influencing outcomes, we retrospectively examined the characteristics of inpatients with delirium who required psychiatric medication during hospitalization.Methods: We extracted all new inpatients (n=523 consulted for psychiatric symptoms at Fukushima Medical University Hospital between October 2011 and September 2013. We selected 203 inpatients with delirium diagnosed by psychiatrists. We analyzed data from 177 inpatients with delirium who received psychiatric medication. We defined an “early improvement group” in which delirium resolved in ≤3 days after starting psychiatric medication, and a “prolonged group” with delirium lasting for >3 days. Among the 83 inpatients with renal dysfunction (estimated glomerular filtration rate <60 mL/min/1.73 m2, we defined an “early improvement group with renal dysfunction” in which delirium resolved in ≤3 days after starting psychiatric medication and a “prolonged group with renal dysfunction” with delirium lasting for >3 days. We then examined differences between groups for different categorical variables.Results: Dose of antipsychotic medication at end point was significantly lower in the prolonged group with renal dysfunction than in the early improvement group with renal dysfunction.Conclusion: The results suggest that maintaining a sufficient dose of antipsychotics from an early stage may prevent prolongation of delirium even in inpatients with renal dysfunction. Keywords: antipsychotic, prolonged delirium, chronic kidney disease, pharmacokinetics 

The in vivo study on the radiobiologic effect of prolonged delivery time to tumor control in C57BL mice implanted with Lewis lung cancer

International Nuclear Information System (INIS)

Wang, Xin; Xiong, Xiao-Peng; Lu, Jiade; Zhu, Guo-Pei; He, Shao-Qin; Hu, Chao-Su; Ying, Hong-Mei

2011-01-01

High-precision radiation therapy techniques such as IMRT or sterotactic radiosurgery, delivers more complex treatment fields than conventional techniques. The increased complexity causes longer dose delivery times for each fraction. The purpose of this work is to explore the radiobiologic effect of prolonged fraction delivery time on tumor response and survival in vivo. 1-cm-diameter Lewis lung cancer tumors growing in the legs of C57BL mice were used. To evaluate effect of dose delivery prolongation, 18 Gy was divided into different subfractions. 48 mice were randomized into 6 groups: the normal control group, the single fraction with 18 Gy group, the two subfractions with 30 min interval group, the seven subfractions with 5 min interval group, the two subfractions with 60 min interval group and the seven subfractions with 10 min interval group. The tumor growth tendency, the tumor growth delay and the mice survival time were analyzed. The tumor growth delay of groups with prolonged delivery time was shorter than the group with single fraction of 18 Gy (P < 0.05). The tumor grow delay of groups with prolonged delivery time 30 min was longer than that of groups with prolonged delivery time 60 min P < 0.05). There was no significant difference between groups with same delivery time (P > 0.05). Compared to the group with single fraction of 18 Gy, the groups with prolonged delivery time shorten the mice survival time while there was no significant difference between the groups with prolonged delivery time 30 min and the groups with prolonged delivery time 60 min. The prolonged delivery time with same radiation dose shorten the tumor growth delay and survival time in the mice implanted with Lewis lung cancer. The anti-tumor effect decreased with elongation of the total interfractional time

Dynamics of heterogeneous liners with prolonged plasma creation

International Nuclear Information System (INIS)

Aleksandrov, V.V.; Branitskii, A.V.; Volkov, G.S.; Grabovskii, E.V.; Zurin, M.V.; Nedoseev, S.L.; Oleinik, G.M.; Samokhin, A.A.; Smirnov, V.P.; Fedulov, M.V.; Frolov, I.N.; Sasorov, P.V.

2001-01-01

Prolonged plasma creation in heterogeneous liners, in which the liner substance is separated into two phase states (a hot plasma and a cold skeleton), is investigated both experimentally and theoretically. This situation is typical of multiwire, foam, and even gas liners in high-current high-voltage facilities. The main mechanisms governing the rate at which the plasma is created are investigated, and the simplest estimates of the creation rate are presented. It is found that, during prolonged plasma creation, the electric current flows through the entire cross section of the produced plasma shell, whose thickness is comparable with the liner radius; in other words, a current skin layer does not form. During compression, such a shell is fairly stable because of its relatively high resilience. It is shown that, under certain conditions, even a thick plasma shell can be highly compressed toward the discharge axis. A simplified numerical simulation of the compression of a plasma shell in a liner with prolonged plasma creation is employed in order to determine the conditions for achieving regimes of fairly compact and relatively stable radial compression of the shell

Daptomycin in the treatment of prosthetic joint infection by Enterococcus faecalis: safety and efficacy of high-dose and prolonged therapy

Directory of Open Access Journals (Sweden)

José Ramón Yuste

2014-10-01

Full Text Available Enterococci are implicated in less than 2.3% of prosthetic joint infections. These infections can be difficult to treat and therapeutic failures are not uncommon. In these situations, daptomycin is a safe and effective alternative. We present a clinical case with a successful response to the prolonged use of high-dose daptomycin.

Vision and Vestibular System Dysfunction Predicts Prolonged Concussion Recovery in Children.

Science.gov (United States)

Master, Christina L; Master, Stephen R; Wiebe, Douglas J; Storey, Eileen P; Lockyer, Julia E; Podolak, Olivia E; Grady, Matthew F

2018-03-01

Up to one-third of children with concussion have prolonged symptoms lasting beyond 4 weeks. Vision and vestibular dysfunction is common after concussion. It is unknown whether such dysfunction predicts prolonged recovery. We sought to determine which vision or vestibular problems predict prolonged recovery in children. A retrospective cohort of pediatric patients with concussion. A subspecialty pediatric concussion program. Four hundred thirty-two patient records were abstracted. Presence of vision or vestibular dysfunction upon presentation to the subspecialty concussion program. The main outcome of interest was time to clinical recovery, defined by discharge from clinical follow-up, including resolution of acute symptoms, resumption of normal physical and cognitive activity, and normalization of physical examination findings to functional levels. Study subjects were 5 to 18 years (median = 14). A total of 378 of 432 subjects (88%) presented with vision or vestibular problems. A history of motion sickness was associated with vestibular dysfunction. Younger age, public insurance, and presence of headache were associated with later presentation for subspecialty concussion care. Vision and vestibular problems were associated within distinct clusters. Provocable symptoms with vestibulo-ocular reflex (VOR) and smooth pursuits and abnormal balance and accommodative amplitude (AA) predicted prolonged recovery time. Vision and vestibular problems predict prolonged concussion recovery in children. A history of motion sickness may be an important premorbid factor. Public insurance status may represent problems with disparities in access to concussion care. Vision assessments in concussion must include smooth pursuits, saccades, near point of convergence (NPC), and accommodative amplitude (AA). A comprehensive, multidomain assessment is essential to predict prolonged recovery time and enable active intervention with specific school accommodations and targeted rehabilitation.

Histone deacetylase turnover and recovery in sulforaphane-treated colon cancer cells: competing actions of 14-3-3 and Pin1 in HDAC3/SMRT corepressor complex dissociation/reassembly

Directory of Open Access Journals (Sweden)

Williams David E

2011-05-01

Full Text Available Abstract Background Histone deacetylase (HDAC inhibitors are currently undergoing clinical evaluation as anti-cancer agents. Dietary constituents share certain properties of HDAC inhibitor drugs, including the ability to induce global histone acetylation, turn-on epigenetically-silenced genes, and trigger cell cycle arrest, apoptosis, or differentiation in cancer cells. One such example is sulforaphane (SFN, an isothiocyanate derived from the glucosinolate precursor glucoraphanin, which is abundant in broccoli. Here, we examined the time-course and reversibility of SFN-induced HDAC changes in human colon cancer cells. Results Cells underwent progressive G2/M arrest over the period 6-72 h after SFN treatment, during which time HDAC activity increased in the vehicle-treated controls but not in SFN-treated cells. There was a time-dependent loss of class I and selected class II HDAC proteins, with HDAC3 depletion detected ahead of other HDACs. Mechanism studies revealed no apparent effect of calpain, proteasome, protease or caspase inhibitors, but HDAC3 was rescued by cycloheximide or actinomycin D treatment. Among the protein partners implicated in the HDAC3 turnover mechanism, silencing mediator for retinoid and thyroid hormone receptors (SMRT was phosphorylated in the nucleus within 6 h of SFN treatment, as was HDAC3 itself. Co-immunoprecipitation assays revealed SFN-induced dissociation of HDAC3/SMRT complexes coinciding with increased binding of HDAC3 to 14-3-3 and peptidyl-prolyl cis/trans isomerase 1 (Pin1. Pin1 knockdown blocked the SFN-induced loss of HDAC3. Finally, SFN treatment for 6 or 24 h followed by SFN removal from the culture media led to complete recovery of HDAC activity and HDAC protein expression, during which time cells were released from G2/M arrest. Conclusion The current investigation supports a model in which protein kinase CK2 phosphorylates SMRT and HDAC3 in the nucleus, resulting in dissociation of the corepressor

Left Ventricular Function After Prolonged Exercise in Equine Endurance Athletes

DEFF Research Database (Denmark)

Flethøj, M.; Schwarzwald, C. C.; Haugaard, M. M.

2016-01-01

Doppler imaging, and two-dimensional speckle tracking. Correlation between echocardiographic variables and cardiac troponin I was evaluated. Results: Early diastolic myocardial velocities decreased significantly in longitudinal (baseline: −17.4 ± 2.4cm/s; end of ride: −15.8 ± 3.2cm/s (P = .013); morning......Background: Prolonged exercise in human athletes is associated with transient impairment of left ventricular (LV) function, known as cardiac fatigue. Cardiac effects of prolonged exercise in horses remain unknown. Objectives :To investigate the effects of prolonged exercise on LV systolic...... and diastolic function in horses. Animals: Twenty-six horses competing in 120–160 km endurance rides. Methods: Cross-sectional field study. Echocardiography was performed before and after rides, and the following morning, and included two-dimensional echocardiography, anatomical M-mode, pulsed-wave tissue...

Down-regulation of dopamine D-2, 5-HT2 receptors and β-adrenoceptors in rat brain after prolonged treatment with a new potential antidepressant, Lu 19-005

International Nuclear Information System (INIS)

Nowak, G.; Arnt, J.; Hyttel, J.; Svendsen, O.

1985-01-01

Lu 19-005 is a new phenylindan derivative with strong and equipotent inhibitory effect on dopamine (DA), noradrenaline (NA) and serotonin (5-HT) uptake. The adaptive effects of 2 weeks treatment with Lu 19-005, on receptor binding in vitro and on d-amphetamine responsiveness in vivo have been investigated in rats. One or 3 days after the final dose the number of β-adrenoceptors and of 5-HT 2 and DA D-2 receptors was decreased by 20-30%, whereas αsub1-adrenoceptor number was slightly decreased only 1 day after withdrawal. The DA D-2 receptor number remained decreased at 7 days withdrawal, but returned to normal after another 3 days. The brain levels of DA, NA and 5-HT were not changed by 2 weeks' Lu 19-005 treatment. The down-regulation of DA D-2 receptors was accompanied by tolerance to d-amphetamine-induced hypermotility (after low doses) and stereotyped licking or biting (after a high dose). The tolerance to d-amphetamine-induced hypermotility was maximal 3-5 days withdrawal time, and remained significant also 15 days after the last dose. The results are discussed in relation to the effect of prolonged treatment with other antidepressant drugs. (Author)

Diet-consumer nitrogen isotope fractionation for prolonged fasting arthropods.

Science.gov (United States)

Mizota, Chitoshi; Yamanaka, Toshiro

2011-12-01

Nitrogen acquisition for cellular metabolism during diapause is a primary concern for herbivorous arthropods. Analyses of naturally occurring stable isotopes of nitrogen help elucidate the mechanism. Relevant articles have cited (58 times up to mid-June 2011) anomalously elevated δ(15)N (per mil deviation of (15)N/(14)N, relative to atmospheric nitrogen=0 ‰) values (diet-consumer nitrogen isotope fractionation; up to 12 ‰) for a prolonged fasting raspberry beetle (Byturus tomentosus Degeer (Coleoptera: Byturidae)), which feeds on red raspberries (Rubus idaeus: δ(15)N= ~ +2 ‰). Biologists have hypothesised that extensive recycling of amino acid nitrogen is responsible for the prolonged fasting. Since this hypothesis was proposed in 1995, scientists have integrated biochemical and molecular knowledge to support the mechanism of prolonged diapausing of animals. To test the validity of the recycling hypothesis, we analysed tissue nitrogen isotope ratios for four Japanese arthropods: the shield bug Parastrachia japonensis Scott (Hemiptera: Cydnidae), the burrower bug Canthophorus niveimarginatus Scott (Hemiptera: Cydnidae), leaf beetle Gastrophysa atrocyanea Motschulsky (Coleoptera: Chrysomelidae) and the Japanese oak silkworm Antheraea yamamai (Lepidoptera: Saturniidae), all of which fast for more than 6 months as part of their life-history strategy. Resulting diet-consumer nitrogen isotope discrimination during fasting ranged from 0 to 7‰, as in many commonly known terrestrial arthropods. We conclude that prolonged fasting of arthropods does not always result in anomalous diet-consumer nitrogen isotope fractionation, since the recycling process is closed or nearly closed with respect to nitrogen isotopes.

Hyperglycemia and subsequent torsades de pointes with marked QT prolongation during refeeding.

Science.gov (United States)

Nakashima, Takashi; Kubota, Tomoki; Takasugi, Nobuhiro; Kitagawa, Yuichiro; Yoshida, Takahiro; Ushikoshi, Hiroaki; Kawasaki, Masanori; Nishigaki, Kazuhiko; Ogura, Shinji; Minatoguchi, Shinya

2017-01-01

A fatal cardiac complication can occasionally present in malnourished patients during refeeding; this is known as refeeding syndrome. However, to our knowledge, hyperglycemia preceding torsades de pointes with QT prolongation during refeeding has not been reported. In the present study, we present a case in which hyperglycemia preceded torsades de pointes with QT prolongation during refeeding. The aim of this study was to determine the possible mechanism underlying QT prolongation during refeeding and indicate how to prevent it. A 32-y-old severely malnourished woman (body mass index 14.57 kg/m 2 ) was admitted to the intensive care unit of our institution after resuscitation from cardiopulmonary arrest due to ventricular fibrillation. She was diagnosed with anorexia nervosa. Although no obvious electrolyte abnormalities were observed, her blood glucose level was 11 mg/dL. A 12-lead electrocardiogram at admission showed sinus rhythm with normal QT interval (QTc 0.448). Forty mL of 50% glucose (containing 20 g of glucose) was intravenously injected, followed by a drip infusion of glucose to maintain blood glucose level within normal range. After 9 h, the patient's blood glucose level increased to 569 mg/dL. However, after 38 h, an episode of marked QT prolongation (QTc 0.931) followed by torsades de pointes developed. Hyperglycemia during refeeding can present with QT prolongation; consequently, monitoring blood glucose levels may be useful in avoiding hyperglycemia, which can result in QT prolongation. Furthermore, additional monitoring of QT intervals using a 12-lead electrocardiogram should allow the early detection of QT prolongation when glucose solution is administered to a malnourished patient with (severe) hypoglycemia. Copyright © 2016 Elsevier Inc. All rights reserved.

pH-dependent inhibition of K2P3.1 prolongs atrial refractoriness in whole hearts

DEFF Research Database (Denmark)

Skarsfeldt, Mark A; Jepps, Thomas A; Bomholtz, Sofia H

2016-01-01

In isolated human atrial cardiomyocytes, inhibition of K2P3.1 K(+) channels results in action potential (action potential duration (APD)) prolongation. It has therefore been postulated that K2P3.1 (KCNK3), together with K2P9.1 (KCNK9), could represent novel drug targets for the treatment of atrial...... fibrillation (AF). However, it is unknown whether these findings in isolated cells translate to the whole heart. The purposes of this study were to investigate the expression levels of KCNK3 and KCNK9 in human hearts and two relevant rodent models and determine the antiarrhythmic potential of K2P3.1 inhibition...... displayed a more uniform expression of KCNK3 between atria and ventricle. In voltage-clamp experiments, ML365 and A293 were found to be potent and selective inhibitors of K2P3.1, but at pH 7.4, they failed to prolong atrial APD and refractory period (effective refractory period (ERP)) in isolated perfused...

Prolonged hypoxic culture and trypsinization increase the pro-angiogenic potential of human adipose tissue-derived stem cells

DEFF Research Database (Denmark)

Rasmussen, Jeppe Grøndahl; Frøbert, Ole; Pilgaard, Linda

2011-01-01

Transplantation of mesenchymal stromal cells (MSC), including adipose tissue-derived stem cells (ASC), is a promising option in the treatment of vascular disease. Short-term hypoxic culture of MSC augments secretion of anti-apoptotic and angiogenic cytokines. We hypothesized that prolonged hypoxic...... (1% and 5% oxygen) culture and trypsinization would augment ASC expression of anti-apoptotic and angiogenic cytokines and increase the angiogenic potential of ASC-conditioned media....

Prolonged parenteral nutrition after neonatal gastrointestinal surgery

DEFF Research Database (Denmark)

Estmann, Anne; Qvist, Niels; Husby, Steffen

2002-01-01

to diagnosis and clinical course. METHODOLOGY: This study reviews the clinical course of infants with gastrointestinal disease (gastroschisis, intestinal atresia, omphalocele, volvulus, Hirschsprung's disease and necrotizing enterocolitis) with a prolonged need for parenteral nutrition in the Western part...

Prevention of Pazopanib-Induced Prolonged Cardiac Repolarization and Proarrhythmic Effects

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Tulay Akman

2014-11-01

Full Text Available Background: Pazopanib (PZP may induce prolonged cardiac repolarization and proarrhythmic effects, similarly to other tyrosine kinase inhibitors. Objectives: To demonstrate PZP-induced prolonged cardiac repolarization and proarrhythmic electrophysiological effects and to investigate possible preventive effects of metoprolol and diltiazem on ECG changes (prolonged QT in an experimental rat model. Methods: Twenty-four Sprague-Dawley adult male rats were randomly assigned to 4 groups (n = 6. The first group (normal group received 4 mL of tap water and the other groups received 100 mg/kg of PZP (Votrient® tablet perorally, via orogastric tubes. After 3 hours, the following solutions were intraperitoneally administered to the animals: physiological saline solution (SP, to the normal group and to the second group (control-PZP+SP group; 1 mg/kg metoprolol (Beloc, Ampule, AstraZeneca, to the third group (PZP+metoprolol group; and 1mg/kg diltiazem (Diltiazem, Mustafa Nevzat, to the fourth group (PZP+diltiazem group. One hour after, and under anesthesia, QTc was calculated by recording ECG on lead I. Results: The mean QTc interval values were as follows: normal group, 99.93 ± 3.62 ms; control-PZP+SP group, 131.23 ± 12.21 ms; PZP+metoprolol group, 89.36 ± 3.61 ms; and PZP+diltiazem group, 88.86 ± 4.04 ms. Both PZP+metoprolol and PZP+diltiazem groups had significantly shorter QTc intervals compared to the control-PZP+SP group (p < 0.001. Conclusion: Both metoprolol and diltiazem prevented PZP-induced QT interval prolongation. These drugs may provide a promising prophylactic strategy for the prolonged QTc interval associated with tyrosine kinase inhibitor use.

Intrinsic motivation and amotivation in first episode and prolonged psychosis.

Science.gov (United States)

Luther, Lauren; Lysaker, Paul H; Firmin, Ruth L; Breier, Alan; Vohs, Jenifer L

2015-12-01

The deleterious functional implications of motivation deficits in psychosis have generated interest in examining dimensions of the construct. However, there remains a paucity of data regarding whether dimensions of motivation differ over the course of psychosis. Therefore, this study examined two motivation dimensions, trait-like intrinsic motivation, and the negative symptom of amotivation, and tested the impact of illness phase on the 1) levels of these dimensions and 2) relationship between these dimensions. Participants with first episode psychosis (FEP; n=40) and prolonged psychosis (n=66) completed clinician-rated measures of intrinsic motivation and amotivation. Analyses revealed that when controlling for group differences in gender and education, the FEP group had significantly more intrinsic motivation and lower amotivation than the prolonged psychosis group. Moreover, intrinsic motivation was negatively correlated with amotivation in both FEP and prolonged psychosis, but the magnitude of the relationship did not statistically differ between groups. These findings suggest that motivation deficits are more severe later in the course of psychosis and that low intrinsic motivation may be partially independent of amotivation in both first episode and prolonged psychosis. Clinically, these results highlight the importance of targeting motivation in early intervention services. Copyright © 2015 Elsevier B.V. All rights reserved.

Safety and tolerability of prolonged-release nicotinic acid in statin-treated patients

NARCIS (Netherlands)

Birjmohun, R. S.; Kastelein, J. J. P.; Poldermans, D.; Stroes, E. S. G.; Hostalek, U.; Assmann, G.

2007-01-01

Objective: To evaluate the safety and tolerability of prolonged -release nicotinic acid (Niaspan*) added to statin therapy in patients at increased cardiovascular risk. Methods: This was a 6-month, prospective, observational, multicentre, open-label evaluation of prolonged-release nicotinic acid

Mesenteric venous thrombosis after prolonged air travel-a case report

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Joaquín Salas-Coronas

2014-07-01

Full Text Available We present a case of acute mesenteric venous thrombosis after a long distance flight in a traveller presenting with abdominal pain, diarrhoea and vomiting within 48 h of prolonged immobility situation. Venous thrombosis in the lower limbs and venous thromboembolism has been clearly associated with prolonged air travel (economy class syndrome. Thrombosis was diagnosed by computed tomography of the abdomen, and after starting anticoagulant therapy with acenocumarol, symptoms yielded completely in a few weeks. The study of thrombophilia was negative, although the existence of two first-degree relatives (mother and grandmother with a history of venous thrombosis with a history of venous thrombosis makes it likely a situation of inherited thrombophilia. Although exceptional, mesenteric venous thrombosis should be considered in travellers with acute abdominal pain after prolonged air travel when there are thrombophilic conditions.

Laryngotracheal Injury following Prolonged Endotracheal Intubation

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J. Mehdizadeh

2006-07-01

Full Text Available Background: Prolonged endotracheal intubation is a growing method for supporting ventilation in patients who require intensive care. Despite considerable advancement in endotracheal intubation, this method still has some complications; the most important is laryngo-tracheal injuries. Methods: Over a 2-year period, this retrospective study was conducted on 57 patients with history of prolonged intubation who were referred to the ENT Department of Amir Alam Hospital. For each patient, a complete evaluation including history, physical examination, and direct laryngoscopy and bronchoscopy was done under general anesthesia. Results: Fifty-seven patients (44 male; mean age, 23.014.7 years were studied. Mean intubation period was 15.88 days. The most common presenting symptom was dyspnea (62%. Head trauma was responsible for most cases of intubation (72.4%. The most common types of tracheal and laryngeal lesions were tracheal (56.9% and subglottic (55.2% stenosis, respectively. Mean length of tracheal stenosis was 0.810.83 cm. There was a statistically significant relationship between length of tracheal stenosis and intubation period (P=0.0001 but no relation was observed between tracheal stenosis and age, sex, and etiology of intubation (All P=NS. Among the glottic lesions, inter- arytenoids adhesion was the most common lesion (25.9%. No statistically significant relation was found between glottic and subglottic lesions and age, sex and intubation period (all P=NS. Length of stenosis and intubation period was significantly greater in tracheal/ subglottic lesions than those in glottic/ supraglottic lesions (all P=NS. Conclusion: After prolonged endotracheal intubation, laryngo-tracheal lesions had no relation with patient’s age, sex, and cause of intubation.There was direct relation between length of tracheal stenosis and intubation period. Glottic lesions were more commonly observed in head trauma patients. Lesion length and intubation

Grading of Emphysema Is Indispensable for Predicting Prolonged Air Leak After Lung Lobectomy.

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Murakami, Junichi; Ueda, Kazuhiro; Tanaka, Toshiki; Kobayashi, Taiga; Hamano, Kimikazu

2018-04-01

The aim of this study was to assess the utility of quantitative computed tomography-based grading of emphysema for predicting prolonged air leak after thoracoscopic lobectomy. A consecutive series of 284 patients undergoing thoracoscopic lobectomy for lung cancer was retrospectively reviewed. Prolonged air leak was defined as air leaks lasting 7 days or longer. The grade of emphysema (emphysema index) was defined by the proportion of the emphysematous lung volume (less than -910 HU) to the total lung volume (-600 to -1,024 HU) by a computer-assisted histogram analysis of whole-lung computed tomography scans. The mean length of chest tube drainage was 1.5 days. Fifteen patients (5.3%) presented with prolonged air leak. According to a receiver-operating characteristics curve analysis, the emphysema index was the best predictor of prolonged air leak, with an area under the curve of 0.85 (95% confidence interval: 0.73 to 0.98). An emphysema index of 35% or greater was the best cutoff value for predicting prolonged air leak, with a negative predictive value of 0.99. The emphysema index was the only significant predictor for the length of postoperative chest tube drainage among conventional variables, including the pulmonary function and resected lobe, in both univariate and multivariate analyses. Prolonged air leak resulted in an increased duration of hospitalization (p leak that adversely influences early postoperative outcomes. We must take new measures against prolonged air leak in quantitative computed tomography-based high-risk patients. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Narrative reconstruction therapy for prolonged grief disorder—rationale and case study

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Tuvia Peri

2016-05-01

Full Text Available Background: Prolonged grief disorder (PGD is a potentially disabling condition affecting approximately 10% of bereaved people. It has been suggested that the impaired integration of the loss memory, as expressed in recurrent memories of the loss and disorganization of memory, is involved in the development of PGD. Narrative reconstruction (NR, originally designed for the treatment of posttraumatic stress disorder (PTSD in an integrative therapy module, and consisting of exposure to the loss memory, detailed written reconstruction of the loss memory narrative and an elaboration of the personal significance of that memory for the bereaved, has been shown to be effective in the treatment of intrusion symptoms. Objective: In light of findings that cognitive behavior therapy (CBT, including cognitive restructuring and exposure, is effective in the treatment of PGD, we suggest the implementation of a somewhat novel therapy module, NR, for the treatment of intrusive phenomena in bereaved patients. Method: The rationale for the implementation of NR for PGD and a case study of the treatment of a woman suffering from PGD after the death of her father are presented. Therapy took place in a university outpatient training clinic. Results: Evaluations conducted before and after treatment and at a 3-month follow-up demonstrated the effectiveness of NR in reducing symptoms of PGD and depression. The analysis of spontaneous narratives recorded before and after treatment showed an increased organization of the narratives. Conclusions: This case report demonstrates an adaptation of NR for the treatment of PGD. The results provide preliminary support for the effectiveness of NR for PGD. The significance of the study and its limitations are discussed.

Prolonged Mechanical Ventilation as a Predictor of Mortality After Cardiac Surgery.

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Fernandez-Zamora, Maria Dolores; Gordillo-Brenes, Antonio; Banderas-Bravo, Esther; Arboleda-Sánchez, José Andrés; Hinojosa-Pérez, Rafael; Aguilar-Alonso, Eduardo; Herruzo-Aviles, Ángel; Curiel-Balsera, Emilio; Sánchez-Rodríguez, Ángel; Rivera-Fernández, Ricardo

2018-05-01

Mortality among the small percentage of cardiac surgery patients receiving prolonged mechanical ventilation is high, but this issue appears to be inadequately addressed in guidelines. This study is a retrospective analysis of prospective, multi-center, and observational study in Spain including all adults undergoing cardiac surgery in 3 Andalusian hospitals between June 2008 and December 2012. The study included 3,588 adults with mean ± SD age of 63.5 ± 12.8 y and with median (interquartile range) EuroSCORE of 5 (3-7) points. Prolonged mechanical ventilation (> 24 h) was required by 415 subjects (11.6%), with ICU mortality of 44.3% (184 subjects), and was not required by 3,173 subjects (88.4%), with ICU mortality of 3.1% (99 subjects, P mechanical ventilation was associated with more complications and was required by 4.5% of subjects with a EuroSCORE 10. In the multivariable analysis, ICU mortality was associated with illness severity, duration of bypass surgery, surgery type, and prolonged mechanical ventilation (odds ratio 15.19, 95% CI 11.56-22.09). The main cause of death was multiple organ failure and sepsis in subjects who required prolonged mechanical ventilation (50.3%) and cardiogenic shock in those who did not (59.2%). Prolonged postoperative mechanical ventilation was required by 10-20% of cardiac surgery subjects, who constitute a specific group that represents most of the postoperative mortality, which is associated with multiple organ failure and sepsis. Copyright © 2018 by Daedalus Enterprises.

Features of History, Anthropometric Data and Individual Functions of the Liver in Children with Prolonged Jaundice

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O.V. Tyajka

2016-11-01

Full Text Available Background. Neonatal jaundice is one of the urgent problems in neonatology. There is a tendency to increase the incidence of prolonged jaundice. The aim of our study was to explore the features of history, anthropometric data and some liver functions in children with prolonged jaundice. Materials and methods. The study involved 111 children with prolonged jaundice aged from 3 weeks to 3 months. In all children with prolonged jaundice, we have examined complete blood count, urinalysis, blood chemistry (determination of total bilirubin and fractions, total protein, albumin, glucose and used instrumental methods of examination — ultrasound of the abdominal cavity and cranial ultrasonography, electrocardiography. Most children with prolonged jaundice were breastfed and were term infants. Results. Indicators of physical development at birth (body weight, body length, head circumference, chest circumference in children with prolonged jaundice and in healthy children had not statistically significant differences. Neonatal jaundice was prolonged in children, who were born from the first pregnancy, — 60 children (54.1 %. A high level of total and indirect bilirubin was accompanied by a low level of albumin in the blood serum of children with prolonged jaundice. Protein-synthesis function of the liver was reduced in children with prolonged jaundice.

Bryostatin and its synthetic analog, picolog rescue dermal fibroblasts from prolonged stress and contribute to survival and rejuvenation of human skin equivalents.

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Khan, Tapan K; Wender, Paul A; Alkon, Daniel L

2018-02-01

Skin health is associated with the day-to-day activity of fibroblasts. The primary function of fibroblasts is to synthesize structural proteins, such as collagen, extracellular matrix proteins, and other proteins that support the structural integrity of the skin and are associated with younger, firmer, and more elastic skin that is better able to resist and recover from injury. At sub-nanomolar concentrations (0.03-0.3 nM), bryostatin-1 and its synthetic analog, picolog (0.1-10 nM) sustained the survival and activation of human dermal fibroblasts cultured under the stressful condition of prolonged serum deprivation. Bryostatin-1 treatment stabilized human skin equivalents (HSEs), a bioengineered combination of primary human skin cells (keratinocytes and dermal fibroblasts) on an extracellular matrix composed of mainly collagen. Fibroblasts activated by bryostatin-1 protected the structural integrity of HSEs. Bryostatin-1 and picolog prolonged activation of Erk in fibroblasts to promote cell survival. Chronic stress promotes the progression of apoptosis. Dermal fibroblasts constitutively express all components of Fas associated apoptosis, including caspase-8, an initiator enzyme of apoptosis. Prolong bryostatin-1 treatment reduced apoptosis by decreasing caspase-8 and protected dermal fibroblasts. Our data suggest that bryostatin-1 and picolog could be useful in anti-aging skincare, and could have applications in tissue engineering and regenerative medicine. © 2017 Wiley Periodicals, Inc.

Prolonged Cholestatic Jaundice Associated With Flurbiprofen.

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Dogan, Serkan; Celikbilek, Mehmet; Demirkan, Kutay; Yilmaz, Semih; Deniz, Kemal; Gursoy, Sebnem; Yucesoy, Mehmet

2014-08-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely consumed drugs throughout the world for pain relief. Although the adverse effects of NSAIDs to the liver are well known, flurbiprofen-induced liver cholestasis is extremely rare. Herein, we present a patient with prolonged icterus that is associated with the use of flurbiprofen without causing ductopenia. © The Author(s) 2013.

Electrocardiographic PR prolongation and atrial fibrillation risk: a meta-analysis of prospective cohort studies.

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Cheng, Min; Lu, Xiangfeng; Huang, Jianfeng; Zhang, Shu; Gu, Dongfeng

2015-01-01

Electrocardiographic PR interval prolongation is considered a benign condition, but recent studies have challenged the notion by demonstrating that prolonged PR interval is associated with an increased risk of atrial fibrillation (AF). The purpose of this study was to perform a meta-analysis of prospective cohort studies to evaluate the evidence supporting an association of prolonged PR interval with AF incidence. We searched the MEDLINE and EMBASE database (from inception to May 2014) supplemented by manual searches of references of relevant retrieved articles. Prospective cohort studies were included with hazard ratio (HR) of prolonged PR interval for incident AF. The search strategy yielded 6 cohort studies meeting eligibility criteria. A total of 328,932 participants were included, with 14,191 participants suffering from AF during follow-up. Pooled HRs of prolonged PR interval for incident AF was 1.30 (95% CI: 1.13 to 1.49) using random-effect model (I(2) = 30%). There was a significant difference of combined HRs between studies with and without adjustment for taking of AV nodal blocking agents in subgroup analysis. Sensitivity analysis supported the robustness of the results. Prolonged PR interval is not a totally benign condition but an independent risk factor for AF incidence. The mechanisms underlying the association of prolonged PR interval with AF incidence need further research. © 2014 Wiley Periodicals, Inc.

High frequency components of tracheal sound are emphasized during prolonged flow limitation

International Nuclear Information System (INIS)

Tenhunen, M; Huupponen, E; Saastamoinen, A; Kulkas, A; Himanen, S-L; Rauhala, E

2009-01-01

A nasal pressure transducer, which is used to study nocturnal airflow, also provides information about the inspiratory flow waveform. A round flow shape is presented during normal breathing. A flattened, non-round shape is found during hypopneas and it can also appear in prolonged episodes. The significance of this prolonged flow limitation is still not established. A tracheal sound spectrum has been analyzed further in order to achieve additional information about breathing during sleep. Increased sound frequencies over 500 Hz have been connected to obstruction of the upper airway. The aim of the present study was to examine the tracheal sound signal content of prolonged flow limitation and to find out whether prolonged flow limitation would consist of abundant high frequency activity. Sleep recordings of 36 consecutive patients were examined. The tracheal sound spectral analysis was performed on 10 min episodes of prolonged flow limitation, normal breathing and periodic apnea-hypopnea breathing. The highest total spectral amplitude, implicating loudest sounds, occurred during flow-limited breathing which also presented loudest sounds in all frequency bands above 100 Hz. In addition, the tracheal sound signal during flow-limited breathing constituted proportionally more high frequency activities compared to normal breathing and even periodic apnea-hypopnea breathing

Qt interval prolongation and ventricular arrhythmias in patients with chronic heart failure

International Nuclear Information System (INIS)

Sarwar, M.; Majeed, S.M.I.; Khan, M.A.; Majeed, S.M.

2014-01-01

To determine the association of QTc interval prolongation with ventricular arrhythmias in patients with chronic heart failure. Study Design: Descriptive study. Place and Duration of Study: This study was conducted at Armed Forces Institute of Cardiology/National Institute of Heart Diseases, Rawalpindi, Pakistan from April 2013 to August 2013. Patients and Methods: Fifty three heart failure patients were monitored for 48 hours using ambulatory holter electrocardiography recorders. Digital ECG data was analyzed for QTc interval along with frequency and severity of arrhythmias. Association of prolonged QTc interval with ventricular arrhythmias and severity of arrhythmias was analyzed. Results: Cardiac arrhythmias were observed in 79.2% patients. QT analysis revealed that 69.8% patients had prolonged QTc interval, 86.4% patients with prolonged QTc had ventricular arrhythmias. Of these 66% patients were found to have severe ventricular arrhythmias. Comparison of mean QTc interval of our study population with a reference value showed significantly higher QTc interval of our study group than the test value. Conclusion: Arrhythmia frequency and severity significantly increases with an increase in QTc interval in heart failure demonstrating association of prolonged QTc interval with high risk of severe ventricular arrhythmias and sudden cardiac death in chronic heart failure. (author)

Differential cellular responses to prolonged LDR-IR in MLH1-proficient and MLH1-deficient colorectal cancer HCT116 cells.

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Yan, Tao; Seo, Yuji; Kinsella, Timothy J

2009-11-15

MLH1 is a key DNA mismatch repair (MMR) protein involved in maintaining genomic stability by participating in the repair of endogenous and exogenous mispairs in the daughter strands during S phase. Exogenous mispairs can result following treatment with several classes of chemotherapeutic drugs, as well as with ionizing radiation. In this study, we investigated the role of the MLH1 protein in determining the cellular and molecular responses to prolonged low-dose rate ionizing radiation (LDR-IR), which is similar to the clinical use of cancer brachytherapy. An isogenic pair of MMR(+) (MLH1(+)) and MMR(-) (MLH1(-)) human colorectal cancer HCT116 cells was exposed to prolonged LDR-IR (1.3-17 cGy/h x 24-96 h). The clonogenic survival and gene mutation rates were examined. Cell cycle distribution was analyzed with flow cytometry. Changes in selected DNA damage repair proteins, DNA damage response proteins, and cell death marker proteins were examined with Western blotting. MLH1(+) HCT116 cells showed greater radiosensitivity with enhanced expression of apoptotic and autophagic markers, a reduced HPRT gene mutation rate, and more pronounced cell cycle alterations (increased late-S population and a G(2)/M arrest) following LDR-IR compared with MLH1(-) HCT116 cells. Importantly, a progressive increase in MLH1 protein levels was found in MLH1(+) cells during prolonged LDR-IR, which was temporally correlated with a progressive decrease in Rad51 protein (involved in homologous recombination) levels. MLH1 status significantly affects cellular responses to prolonged LDR-IR. MLH1 may enhance cell radiosensitivity to prolonged LDR-IR through inhibition of homologous recombination (through inhibition of Rad51).

Prolonged displacement may compromise resilience in Eritrean ...

African Journals Online (AJOL)

Objective: to assess the impact of prolonged displacement on the resilience of Eritrean mothers. Methods: an adapted SOC scale (short form) was administered. Complementary qualitative data were gathered from study participants' spontaneous reactions to and commentaries on the SOC scale. Results: Displaced ...

Prolonged-release melatonin versus placebo for benzodiazepine discontinuation in patients with schizophrenia: a randomized clinical trial - the SMART trial protocol

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Oranje Bob

2011-10-01

Full Text Available Abstract Background Treatment of schizophrenia frequently includes prolonged benzodiazepine administration despite a lack of evidence of its use. It is often difficult to discontinue benzodiazepines because of the development of dependence. We aim to assess if melatonin can facilitate the withdrawal of prolonged benzodiazepine administration in patients with schizophrenia. Furthermore, we aim to investigate the association of benzodiazepine dose reduction with the following clinically important variables: sleep, psychophysiology, cognition, social function, and quality of life. Methods/Design Randomized, blinded, two-armed, parallel superiority trial. We plan to include 80 consenting outpatients diagnosed with schizophrenia or schizoaffective disorder, 18-55 years of age, treated with antipsychotic drug(s and at least one benzodiazepine derivative for the last three months before inclusion. Exclusion criteria: currently under treatment for alcohol or drug abuse, aggressive or violent behavior, known mental retardation, pervasive developmental disorder, dementia, epilepsy, terminal illness, severe co morbidity, inability to understand Danish, allergy to melatonin, lactose, starch, gelatin, or talc, hepatic impairment, pregnancy or nursing, or lack of informed consent. After being randomized to prolonged-release melatonin (Circadin® 2 mg daily or matching placebo, participants are required to slowly taper off their benzodiazepine dose. The primary outcome measure is benzodiazepine dose at 6 months follow-up. Secondary outcome measures include sleep, psychophysiological, and neurocognitive measures. Data are collected at baseline and at 6 months follow-up regarding medical treatment, cognition, psychophysiology, sleep, laboratory tests, adverse events, psychopathology, social function, and quality of life. Data on medical treatment, cognition, psychophysiology, adverse events, social function, and quality of life are also collected at 2 and 4

Physiological Stress Responses to Prolonged Exposure to MS-222 and Surgical Implantation in Juvenile Chinook Salmon

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Wagner, Katie A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Woodley, Christa M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Seaburg, Adam [Univ. of Washington, Seattle, WA (United States); Skalski, John R. [Univ. of Washington, Seattle, WA (United States); Eppard, Matthew B. [U.S. Army Corps of Engineers, Portland, OR (United States)

2014-07-17

While many studies have investigated the effects of transmitters on fish condition, behavior, and survival, to our knowledge, no studies have taken into account anesthetic exposure time in addition to tag and surgery effects. We investigated stress responses to prolonged MS-222 exposure after stage 4 induction in surgically implanted juvenile Chinook salmon (Oncorhynchus tshawytscha). Survival, tag loss, plasma cortisol concentration, and blood Na⁺, K⁺, Ca²⁺, and pH were measured immediately following anesthetic exposure and surgical implantation and 1, 7, and 14 days post-treatment. Despite the prolonged anesthetic exposure, 3-15 minutes post Stage 4 induction, there were no mortalities or tag loss in any treatment. MS-222 was effective at delaying immediate cortisol release during surgical implantation; however, osmotic disturbances resulted, which were more pronounced in longer anesthetic time exposures. From day 1 to day 14, Na⁺, Ca²⁺, and pH significantly decreased, while cortisol significantly increased. The cortisol increase was exacerbated by surgical implantation. There was a significant interaction between MS-222 time exposure and observation day for Na⁺, Ca²⁺, K⁺, and pH; variations were seen in the longer time exposures, although not consistently. In conclusion, stress response patterns suggest stress associated with surgical implantation is amplified with increased exposure to MS-222.

BONE TURNOVER IN OSTEOPOROTIC WOMEN DURING LONG-TERM ORAL BISPHOSPHONATES TREATMENT: IMPLICATIONS FOR TREATMENT FAILURE AND "DRUG HOLIDAY" IN THE REAL WORLD.

Science.gov (United States)

Liel, Yair; Plakht, Ygal; Tailakh, Muhammad Abu

2017-07-01

Little data exist to support concerns over bone turnover suppression during prolonged oral bisphosphonate treatment and on consequences of the recommended "drug holiday." This study was performed to assess bone resorption rates in postmenopausal osteoporotic women on prolonged oral bisphosphonate treatment and in response to switching to "drug holiday" intravenous bisphosphonate, or continuation of oral bisphosphonates. The frequency distribution of the bone resorption marker urinary deoxypyridinoline crosslinks (uDPD), was obtained retrospectively from 211 osteoporotic women attended at an academic hospital endocrine clinic, treated for >2 years with oral bisphosphonates. In some patients, uDPD was re-assessed following modification or continuation of treatment. The mean duration of oral bisphosphonates treatment was 7.2 ± 3.1 years. uDPD was within reference range for premenopausal women in 61.6% of the patients, below in 7.6% of the patients, and above upper limit in 30.8%. uDPD decreased significantly following intravenous zoledronic acid, increased significantly during "drug holiday," and slightly decreased in those continued on oral bisphosphonate treatment. In this real-world study, the majority of women on prolonged oral bisphosphonates maintained bone resorption rates within the normal reference range for premenopausal women. The likelihood for inadequate suppression was considerably greater than that of over-suppression. Implementing a "drug holiday" resulted in a marked increase in bone resorption rates. Additional studies should explore the potential role of bone turnover markers in the evaluation of patients on prolonged oral bisphosphonates and during "drug holiday" in different settings and using additional markers. BMD = bone mineral density; IQR = interquartile range; uDPD = urinary deoxypyridinoline crosslinks.

Impaired Neonatal Outcome after Emergency Cerclage Adds Controversy to Prolongation of Pregnancy.

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Ruben-J Kuon

Full Text Available Emergency cervical cerclage is one of the treatment options for the reduction of preterm birth. The aim of this study is to assess neonatal outcome after cerclage with special focus on adverse effects in very low birth weight infants.Retrospective cohort study. Classification of cerclages in history-indicated (HIC, n = 38, ultrasound-indicated (UIC, n = 29 and emergency/ physical examination-indicated (PEIC, n = 33 cerclage. Descriptive analysis of pregnancy and neonatal outcome (admission to NICU, duration of hospitalization, respiratory outcome (intubation, CPAP, FiO2max, neonatal complications (ROP, IVH. Statistical comparison of perinatal parameters and outcome of neonates <1500 g after cerclage with a birth weight matched control group.Neonates <1500 g after PEIC show significantly impaired outcome, i.e. prolonged respiratory support (total ventilation in days, CPAP, FiO2max and higher rates of neonatal complications (IVH ≥ II, ROP ≥ 2. Placental pathologic evaluation revealed a significantly higher rate of chorioamnionitis (CAM after PEIC. Neonates <1500 g after UIC or HIC show no significant difference in neonatal complications or CAM.In our study PEIC is associated with adverse neonatal outcome in infants <1500 g. The high incidence of CAM indicates a potential inflammatory factor in the pathogenesis. Large well-designed RCTs are required to give conclusive answers to the question whether to prolong or to deliver.

Synbiotic approach restores intestinal homeostasis and prolongs survival in leukaemic mice with cachexia.

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Bindels, Laure B; Neyrinck, Audrey M; Claus, Sandrine P; Le Roy, Caroline I; Grangette, Corinne; Pot, Bruno; Martinez, Inés; Walter, Jens; Cani, Patrice D; Delzenne, Nathalie M

2016-06-01

Cancer cachexia is a multifactorial syndrome that includes muscle wasting and inflammation. As gut microbes influence host immunity and metabolism, we investigated the role of the gut microbiota in the therapeutic management of cancer and associated cachexia. A community-wide analysis of the caecal microbiome in two mouse models of cancer cachexia (acute leukaemia or subcutaneous transplantation of colon cancer cells) identified common microbial signatures, including decreased Lactobacillus spp. and increased Enterobacteriaceae and Parabacteroides goldsteinii/ASF 519. Building on this information, we administered a synbiotic containing inulin-type fructans and live Lactobacillus reuteri 100-23 to leukaemic mice. This treatment restored the Lactobacillus population and reduced the Enterobacteriaceae levels. It also reduced hepatic cancer cell proliferation, muscle wasting and morbidity, and prolonged survival. Administration of the synbiotic was associated with restoration of the expression of antimicrobial proteins controlling intestinal barrier function and gut immunity markers, but did not impact the portal metabolomics imprinting of energy demand. In summary, this study provided evidence that the development of cancer outside the gut can impact intestinal homeostasis and the gut microbial ecosystem and that a synbiotic intervention, by targeting some alterations of the gut microbiota, confers benefits to the host, prolonging survival and reducing cancer proliferation and cachexia.

High frequency of pertussis in older children and adolescents with prolonged cough in Turkey.

Science.gov (United States)

Aslan, Aslı; Kurugöl, Zafer; Aydemir, Şöhret; Gürsel, Derya; Koturoğlu, Güldane

2016-01-01

This study aimed to determine the frequency of B. pertussis infection among Turkish children with prolonged cough. Nasopharyngeal specimens were collected from 7-18 year old children, presenting with prolonged cough of two to four weeks' duration. Specimens were examined for B. pertussis by PCR. Of 101 children with prolonged cough, 20 (19.8%) had a positive PCR testing for B. pertussis. Children who were vaccinated ≥5 years previously had a 6.13-fold higher risk of PCR-confirmed pertussis than those who were vaccinated pertussis (paroxysmal cough, whooping and post-tussive vomiting) were seen in 30%, 15% and 25% of the patients with positive PCR, respectively; 55% of them had only a prolonged cough without any classic symptoms. Pertussis is common among Turkish children with prolonged cough, even after implementation of a fifth dose of pertussis vaccination and despite high vaccination coverage.

Are shame and self-esteem risk factors in prolonged grief after death of a spouse?

Science.gov (United States)

Dellmann, Thomas

2018-07-01

Although many single factors of prolonged grief have been identified in the literature, a comprehensive understanding of predictors is still lacking. This article argues that shame and low self-esteem, present risk factors in prolonged grief after spousal loss, based on a review of correlational studies. Using a practitioner-scientist approach, a developmental model of shame as a core factor in prolonged grief is proposed, outlining the progression from childhood relational trauma, to insecure attachment, shame, self-esteem contingent on spousal approval to eventual prolonged grief.

Hippocampal Abnormalities after Prolonged Febrile Convulsions

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J Gordon Millichap

2003-11-01

Full Text Available Hippocampal volume and T2 relaxation times were determined in an MRI study of 14 children with prolonged febrile convulsions (PFC who were investigated, 1 within 5 days of a PFC, and 2 at follow-up 4-8 months after the acute study, at the Institute of Child Health, University College, and Great Ormond Street Hospital, London, UK.

The in vivo study on the radiobiologic effect of prolonged delivery time to tumor control in C57BL mice implanted with Lewis lung cancer

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Zhu Guo-Pei

2011-01-01

Full Text Available Abstract Background High-precision radiation therapy techniques such as IMRT or sterotactic radiosurgery, delivers more complex treatment fields than conventional techniques. The increased complexity causes longer dose delivery times for each fraction. The purpose of this work is to explore the radiobiologic effect of prolonged fraction delivery time on tumor response and survival in vivo. Methods 1-cm-diameter Lewis lung cancer tumors growing in the legs of C57BL mice were used. To evaluate effect of dose delivery prolongation, 18 Gy was divided into different subfractions. 48 mice were randomized into 6 groups: the normal control group, the single fraction with 18 Gy group, the two subfractions with 30 min interval group, the seven subfractions with 5 min interval group, the two subfractions with 60 min interval group and the seven subfractions with 10 min interval group. The tumor growth tendency, the tumor growth delay and the mice survival time were analyzed. Results The tumor growth delay of groups with prolonged delivery time was shorter than the group with single fraction of 18 Gy (P 0.05. Compared to the group with single fraction of 18 Gy, the groups with prolonged delivery time shorten the mice survival time while there was no significant difference between the groups with prolonged delivery time 30 min and the groups with prolonged delivery time 60 min. Conclusions The prolonged delivery time with same radiation dose shorten the tumor growth delay and survival time in the mice implanted with Lewis lung cancer. The anti-tumor effect decreased with elongation of the total interfractional time.

Extracorporeal Treatment in Phenytoin Poisoning

DEFF Research Database (Denmark)

Anseeuw, Kurt; Mowry, James B; Burdmann, Emmanuel A

2016-01-01

The Extracorporeal Treatments in Poisoning (EXTRIP) Workgroup conducted a systematic literature review using a standardized process to develop evidence-based recommendations on the use of extracorporeal treatment (ECTR) in patients with phenytoin poisoning. The authors reviewed all articles......) despite its high protein binding and made the following recommendations. ECTR would be reasonable in select cases of severe phenytoin poisoning (neutral recommendation, 3D). ECTR is suggested if prolonged coma is present or expected (graded 2D) and it would be reasonable if prolonged incapacitating ataxia...... is present or expected (graded 3D). If ECTR is used, it should be discontinued when clinical improvement is apparent (graded 1D). The preferred ECTR modality in phenytoin poisoning is intermittent hemodialysis (graded 1D), but hemoperfusion is an acceptable alternative if hemodialysis is not available...

Ageing is associated with a prolonged fever response in human endotoxemia

DEFF Research Database (Denmark)

Krabbe, Karen S.; Kemp Bruunsgaard, Helle; Hansen, Christian Muff

2017-01-01

The purpose of this study was to investigate whether an age-associated impaired acute-phase response exists. Nine healthy elderly volunteers (median, 66 years; range, 61 to 69 years) and eight young controls (median, 24 years; range, 20 to 27 years) were given an intravenous bolus of endotoxin (2......-alpha and sTNFR-I levels and prolonged increased levels of sTNFR-I. Monocyte concentrations decreased in both groups, with the elderly group showing a more rapid decrease and a slower subsequent increase than did the young group. Furthermore, the elderly group had a more rapid increase in C-reactive protein...... levels than did the young group. In conclusion, ageing is associated with an altered acute-phase response including initial hyperreactivity, prolonged inflammatory activity, and prolonged fever response....

Primiparous women's preferences for care during a prolonged latent phase of labour.

Science.gov (United States)

Ängeby, Karin; Wilde-Larsson, Bodil; Hildingsson, Ingegerd; Sandin-Bojö, Ann-Kristin

2015-10-01

To investigate primiparous women's preferences for care during a prolonged latent phase of labour. A qualitative study based on focus groups and individual interviews and analysed with inductive content analysis. Sixteen primiparous women with a prolonged latent phase of labour >18 hours were interviewed in five focus groups (n = 11) or individually (n = 5). One main category emerged "Beyond normality - a need of individual adapted guidance in order to understand and manage an extended latent phase of labour" which covers the women's preferences during the prolonged latent phase. Five categories were generated from the data: "A welcoming manner and not being rejected", "Individually adapted care", "Important information which prepares for reality and coping", "Participation and need for feedback" and "Staying nearby the labour ward or being admitted for midwifery support". Women with a prolonged latent phase of labour sought to use their own resources, but their needs for professional support increased as time passed. A welcoming attitude from an available midwife during the latent phase created a feeling of security, and personally adapted care was perceived positively. Women with a prolonged latent phase of labour preferred woman-centred care. Midwives play an important role in supporting these women. Women's need for midwifery-support increases as the time spent in latent phase increases. Copyright © 2015 Elsevier B.V. All rights reserved.

Prolonged analgesic effect of PLGA-encapsulated bee venom on formalin-induced pain in rats.

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Jeong, Injae; Kim, Beom-Soo; Lee, Hyejung; Lee, Kang-Min; Shim, Insop; Kang, Sung-Keel; Yin, Chang-Shick; Hahm, Dae-Hyun

2009-10-01

To enhance the medicinal activity of bee venom (BV) acupuncture, bee venom was loaded into biodegradable poly(D,L-lactide-co-glycolide) nanoparticles (BV-PLGA-NPs) by a water-in-oil-in-water-emulsion/solvent-evaporation technique. Rat formalin tests were performed after subcutaneous injection of BV-PLGA-NPs to the Zusanli acupuncture point (ST36) at 0.5, 1, 2, 6, 12, 24, and 48 h before plantar injection of 2% formalin. BV-PLGA-NPs treatment showed comparable analgesic activity to typical BV acupuncture during the late phase, compared with saline-treated controls, and the analgesic effect lasted for 12h. PLGA-encapsulation was also effective in alleviating the edema induced by allergens in bee venom. These results indicate that PLGA-encapsulation provided a more prolonged effect of BV acupuncture treatment, while maintaining a comparable therapeutic effect.

Rituximab administration within 6 months of T cell-depleted allogeneic SCT is associated with prolonged life-threatening cytopenias.

Science.gov (United States)

McIver, Zachariah; Stephens, Nicole; Grim, Andrew; Barrett, A John

2010-11-01

The monoclonal anti-CD20 antibody Rituximab (RTX) is increasingly used in allogeneic stem cell transplantation (SCT) to treat lymphoproliferative disorders and chronic graft-versus-host disease (GVHD). RTX administration can be complicated by delayed and prolonged neutropenia, but the mechanism is unclear. We report the occurrence of profound cytopenias following RTX given in the conditioning regimen or early after T cell-deplete SCT to treat B cell lymphoproliferative disorders or chronic GVHD (cGVHD). Between 2006 and 2009, 102 patients (median age: 43 years, range: 13-68 years), received a myeloablative matched-sibling T cell-deplete SCT for lymphoid or myeloid hematologic disorders. Neutropenia occurring within 4 weeks of treatment developed in 16 of 17 patients given RTX within the first 190 days after SCT. Fourteen patients developed severe neutropenia (count SCT compared to patients with cGVHD not treated with early RTX (P SCT experienced only moderate neutropenia 3 to 5 months after treatment lasting 10 to 20 days while maintaining absolute neutrophil count (ANC) >1.0 × 10⁹/L. Although RTX rapidly controlled cGVHD, we conclude that its administration early after T cell-deplete SCT is associated with prolonged profound and life-threatening cytopenias, and should be avoided. Published by Elsevier Inc.

Hepatic scar in a case of healed candidiasis showing prolonged enhancement on CT

Energy Technology Data Exchange (ETDEWEB)

Itai, Yuji; Yashiro, Naobumi

1987-08-01

A patient with acute myelocytic leukemia recovering from hepatic candidiasis after long-term administration of amphotericin B had large scar in the liver which showed prominent prolonged enhancement on postcontrast CT. Prolonged enhancement can occur in regions other than hepatic masses.

A thorough QT study to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine and escitalopram, in healthy volunteers.

Science.gov (United States)

Kim, Anhye; Lim, Kyoung Soo; Lee, Howard; Chung, Hyewon; Yoon, Seo Hyun; Yu, Kyung-Sang; Cho, Joo-Youn; Jang, In-Jin; Chung, Jae-Yong

2016-07-01

Prolongation of the QT interval on an ECG is a surrogate marker for predicting the proarrhythmic potential of a drug under development. The aim of this study was to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine immediate release (IR) and escitalopram, in healthy individuals. This was a randomized, open-label, 4×4 Williams crossover study, with four single-dose treatments [placebo, 400 mg moxifloxacin (positive control), 20 mg escitalopram, and 100 mg quetiapine IR], conducted in 40 healthy volunteers. Serial blood samples for pharmacokinetics and ECG were collected. Individually, RR-corrected QTc intervals (QTcI) and placebo-adjusted changes from baseline values of QTcI (ΔΔQTcI) were evaluated. Lower-bound values of the one-sided 95% confidence interval for ΔΔQTcI of moxifloxacin with more than 5 ms confirmed the sensitivity of the assay. The maximum upper bound 95% confidence interval for the ΔΔQTcI of quetiapine IR and escitalopram was 13.7 and 10.5 ms, with mean estimates of 10.2 and 6.9 ms, respectively. Peak effects of moxifloxacin and quetiapine IR on ΔΔQTcI were observed at approximately time to maximum concentration (Tmax), whereas that of escitalopram was observed 3 h after Tmax. The concentration-ΔΔQTcI relationships of quetiapine IR and escitalopram were relatively flat, as compared with that of moxifloxacin. The results demonstrated the validity of trial methodology and that quetiapine IR and escitalopram caused QT prolongation in healthy individuals. In addition, hysteresis of escitalopram-induced QTc prolongation. These results indicate that higher doses of these drugs could lead to greater QT prolongation in a dose-response manner.

Transient impairments in single muscle fibre contractile function after prolonged cycling in elite endurance athletes

DEFF Research Database (Denmark)

Hvid, L G; Gejl, Kasper Degn; Bech, R D

2013-01-01

Prolonged muscle activity impairs whole-muscle performance and function. However, little is known about the effects of prolonged muscle activity on the contractile function of human single muscle fibres. The purpose of this study was to investigate the effects of prolonged exercise and subsequent...... recovery on the contractile function of single muscle fibres obtained from elite athletes....

The impact of bevacizumab treatment on survival and quality of life in newly diagnosed glioblastoma patients

DEFF Research Database (Denmark)

Poulsen, Hans Skovgaard; Urup, Thomas; Michaelsen, Signe Regner

2014-01-01

in newly diagnosed GBM patients have been performed during recent years to test the hypothesis that newly diagnosed GBM patients should be treated with standard multimodality treatment, in combination with bevacizumab, in order to prolong life and maintain or improve quality of life. The results...... treatment is therefore to prolong life, with a maintenance or improvement of quality of life. GBM is a highly vascular tumor and overexpresses the vascular endothelial growth factor A, which promotes angiogenesis. Preclinical data have suggested that anti-angiogenic treatment efficiently inhibits tumor...... growth. Bevacizumab is a humanized monoclonal antibody against vascular endothelial growth factor A, and treatment has shown impressive response rates in recurrent GBM. In addition, it has been shown that response is correlated to prolonged survival and improved quality of life. Several investigations...

Correlation of prolonged QT interval and severity of cirrhosis of liver

International Nuclear Information System (INIS)

Tarique, S.; Sarwar, S.

2011-01-01

To determine correlation between prolonged QT interval and severity of disease in patients of cirrhosis of liver. Study Design: Descriptive cross sectional study. Patients and Methods: One hundred and seventeen patients of cirrhosis were included. Baseline haematological and biochemical parameters were determined. Model for end stage liver disease (MELD) score was determined for all patients to document stage of liver disease. Corrected QT interval was determined from electrocardiography of each patient using QT cirrhosis formula. Correlation between QT interval and MELD score was determined using Pearson correlation and Receiver Operating Characteristic (ROC) curve. Results: One hundred and seventeen included patients had mean age of 53.58 (+- 12.11) while male to female ratio was 1.78/1 (75 / 42). Mean MELD score was 17.08 (+- 6.54) in study patients varying between 6 and 37 while mean corrected QT interval was 0.44 seconds (+- 0.06). Pearson correlation revealed no significant relation between severity of liver disease as determined with MELD score and prolonged QT interval (p value 0.18) Area under curve with ROC curve for correlation between prolonged QT interval and severity of liver disease was 0.42. Conclusion: Prolonged QT interval is not an indicator of severity of disease in cirrhosis of liver. (author)

Coexistence of Ureaplasma and chorioamnionitis is associated with prolonged mechanical ventilation.

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Jung, Euiseok; Choi, Chang Won; Kim, Su Yeong; Sung, Tae-Jung; Kim, Haeryoung; Park, Kyoung Un; Kim, Han-Suk; Kim, Beyong Il; Choi, Jung-Hwan

2017-01-01

Both histologic chorioamnionitis (HCAM) and Ureaplasma infection are considered important contributors to perinatal lung injury. We tested the hypothesis that coexistence of maternal HCAM and perinatal Ureaplasma exposure increases the risk of prolonged mechanical ventilation in extremely low-birthweight (ELBW) infants. A retrospective cohort study was carried out of all ELBW infants born between January 2008 and December 2013 at a single academic center. Placental pathology and gastric fluid Ureaplasma data were available for all infants. Culture and polymerase chain reaction were used to detect Ureaplasma in gastric fluid. Prolonged mechanical ventilation was defined as mechanical ventilation that began within 28 days after birth and continued. Of 111 ELBW infants enrolled, 84 survived beyond 36 weeks of postmenstrual age (PMA) and were included in the analysis. Eighteen infants (21.4%) had both HCAM and Ureaplasma exposure. Seven infants (8.3%) required mechanical ventilation beyond 36 weeks of PMA. Coexistence of HCAM and Ureaplasma in gastric fluid was significantly associated with prolonged mechanical ventilation after adjustment for gestational age, sex, mode of delivery, and use of macrolide antibiotics (OR, 8.7; 95%CI: 1.1-67.2). Coexistence of maternal HCAM and perinatal Ureaplasma exposure significantly increases the risk of prolonged mechanical ventilation in ELBW infants. © 2016 Japan Pediatric Society.

Using best interests meetings for people in a prolonged disorder of consciousness to improve clinical and ethical management.

Science.gov (United States)

Wade, Derick T

2018-05-01

Current management of people with prolonged disorders of consciousness is failing patients, families and society. The causes include a general lack of concern, knowledge and expertise; a legal and professional framework which impedes timely and appropriate decision-making and/or enactment of the decision; and the exclusive focus on the patient, with no legitimate means to consider the broader consequences of healthcare decisions. This article argues that a clinical pathway based on the principles of (a) the English Mental Capacity Act 2005 and (b) using time-limited treatment trials could greatly improve patient management and reduce stress on families. There needs to be early and continuing use of formal best interests meetings, starting between 7 and 21 days after onset of unconsciousness (from any cause, including progressive disorders). The treatment options need to evolve as the clinical state and prognosis becomes more certain. A formal discussion of treatment withdrawal should occur when the upper bound of predicted recovery falls below a level the patient would have considered acceptable, and it should always be discussed when the condition is considered permanent. Any decision to stop treatment should be contingent on a formal second opinion from an independent expert who should review the clinical situation and expected prognosis, but not the best interests decision. The article also asks how, if at all, the adverse effects on the family and the resource implications of long-term care of people left in a prolonged state of unconsciousness should be incorporated in the process. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Hepatic scar in a case of healed candidiasis showing prolonged enhancement on CT

International Nuclear Information System (INIS)

Itai, Yuji; Yashiro, Naobumi

1987-01-01

A patient with acute myelocytic leukemia recovering from hepatic candidiasis after long-term administration of amphotericin B had large scar in the liver which showed prominent prolonged enhancement on postcontrast CT. Prolonged enhancement can occur in regions other than hepatic masses. (author)

Kinetics of hemopoietic stem cells and survival of mice treated with hydroxyurea and exposed to prolonged γ-radiation

International Nuclear Information System (INIS)

Chertkov, K.S.; Rogozkin, V.D.; Dikovenko, E.A.; Mosina, Z.M.

1979-01-01

A study was made of radioprotective efficiency of hydroxyurea in relation to mice exposed to prolonged 137 Cs-γ-radiation. It was found that a 30-day survival rate, under optimal conditions of treatment with hydroxyurea, was more than 40 per cent higher than that of the controls. The protective effect of hydroxyurea was manifested at the level of hemopoietic stem cells due to a quicker onset and accelerated rate of the repopulation process

Prolonged QTc interval and risk of sudden cardiac death in a population of older adults

DEFF Research Database (Denmark)

Straus, Sabine M J M; Kors, Jan A; De Bruin, Marie L

2006-01-01

OBJECTIVES: This study sought to investigate whether prolongation of the heart rate-corrected QT (QTc) interval is a risk factor for sudden cardiac death in the general population. BACKGROUND: In developed countries, sudden cardiac death is a major cause of cardiovascular mortality. Prolongation...... of the QTc interval has been associated with ventricular arrhythmias, but in most population-based studies no consistent association was found between QTc prolongation and total or cardiovascular mortality. Only very few of these studies specifically addressed sudden cardiac death. METHODS: This study......). The association between a prolonged QTc interval and sudden cardiac death was estimated using Cox proportional hazards analysis. RESULTS: During an average follow-up period of 6.7 years (standard deviation, 2.3 years) 125 patients died of sudden cardiac death. An abnormally prolonged QTc interval (>450 ms in men...

Sulforaphane suppresses the growth of glioblastoma cells, glioblastoma stem cell-like spheroids, and tumor xenografts through multiple cell signaling pathways.

Science.gov (United States)

Bijangi-Vishehsaraei, Khadijeh; Reza Saadatzadeh, M; Wang, Haiyan; Nguyen, Angie; Kamocka, Malgorzata M; Cai, Wenjing; Cohen-Gadol, Aaron A; Halum, Stacey L; Sarkaria, Jann N; Pollok, Karen E; Safa, Ahmad R

2017-12-01

OBJECTIVE Defects in the apoptotic machinery and augmented survival signals contribute to drug resistance in glioblastoma (GBM). Moreover, another complexity related to GBM treatment is the concept that GBM development and recurrence may arise from the expression of GBM stem cells (GSCs). Therefore, the use of a multifaceted approach or multitargeted agents that affect specific tumor cell characteristics will likely be necessary to successfully eradicate GBM. The objective of this study was to investigate the usefulness of sulforaphane (SFN)-a constituent of cruciferous vegetables with a multitargeted effect-as a therapeutic agent for GBM. METHODS The inhibitory effects of SFN on established cell lines, early primary cultures, CD133-positive GSCs, GSC-derived spheroids, and GBM xenografts were evaluated using various methods, including GSC isolation and the sphere-forming assay, analysis of reactive oxygen species (ROS) and apoptosis, cell growth inhibition assay, comet assays for assessing SFN-triggered DNA damage, confocal microscopy, Western blot analysis, and the determination of in vivo efficacy as assessed in human GBM xenograft models. RESULTS SFN triggered the significant inhibition of cell survival and induced apoptotic cell death, which was associated with caspase 3 and caspase 7 activation. Moreover, SFN triggered the formation of mitochondrial ROS, and SFN-triggered cell death was ROS dependent. Comet assays revealed that SFN increased single- and double-strand DNA breaks in GBM. Compared with the vehicle control cells, a significantly higher amount of γ-H2AX foci correlated with an increase in DNA double-strand breaks in the SFN-treated samples. Furthermore, SFN robustly inhibited the growth of GBM cell-induced cell death in established cell cultures and early-passage primary cultures and, most importantly, was effective in eliminating GSCs, which play a major role in drug resistance and disease recurrence. In vivo studies revealed that SFN

Local delivery of nimodipine by prolonged-release microparticles-feasibility, effectiveness and dose-finding in experimental subarachnoid hemorrhage.

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Daniel Hänggi

Full Text Available BACKGROUND AND PURPOSE: To investigate the effect of locally applied nimodipine prolonged-release microparticles on angiographic vasospasm and secondary brain injury after experimental subarachnoid hemorrhage (SAH. METHODS: 70 male Wistar rats were categorized into three groups: 1 sham operated animals (control, 2 animals with SAH only (control and the 3 treatment group. SAH was induced using the double hemorrhage model. The treatment group received different concentrations (20%, 30% or 40% of nimodipine microparticles. Angiographic vasospasm was assessed 5 days later using digital subtraction angiography (DSA. Histological analysis of frozen sections was performed using H&E-staining as well as Iba1 and MAP2 immunohistochemistry. RESULTS: DSA images were sufficient for assessment in 42 animals. Severe angiographic vasospasm was present in group 2 (SAH only, as compared to the sham operated group (p<0.001. Only animals within group 3 and the highest nimodipine microparticles concentration (40% as well as group 1 (sham demonstrated the largest intracranial artery diameters. Variation in vessel calibers, however, did not result in differences in Iba-1 or MAP2 expression, i.e. in histological findings for secondary brain injury. CONCLUSIONS: Local delivery of high-dose nimodipine prolonged-release microparticles at high concentration resulted in significant reduction in angiographic vasospasm after experimental SAH and with no histological signs for matrix toxicity.

Prolonged storage of packed red blood cells for blood transfusion.

Science.gov (United States)

Martí-Carvajal, Arturo J; Simancas-Racines, Daniel; Peña-González, Barbra S

2015-07-14

A blood transfusion is an acute intervention, used to address life- and health-threatening conditions on a short-term basis. Packed red blood cells are most often used for blood transfusion. Sometimes blood is transfused after prolonged storage but there is continuing debate as to whether transfusion of 'older' blood is as beneficial as transfusion of 'fresher' blood. To assess the clinical benefits and harms of prolonged storage of packed red blood cells, in comparison with fresh, on recipients of blood transfusion. We ran the search on 1st May 2014. We searched the Cochrane Injuries Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE (OvidSP), Embase (OvidSP), CINAHL (EBSCO Host) and two other databases. We also searched clinical trials registers and screened reference lists of the retrieved publications and reviews. We updated this search in June 2015 but these results have not yet been incorporated. Randomised clinical trials including participants assessed as requiring red blood cell transfusion were eligible for inclusion. Prolonged storage was defined as red blood cells stored for ≥ 21 days in a blood bank. We did not apply limits regarding the duration of follow-up, or country where the study took place. We excluded trials where patients received a combination of short- and long-stored blood products, and also trials without a clear definition of prolonged storage. We independently performed study selection, risk of bias assessment and data extraction by at least two review authors. The major outcomes were death from any cause, transfusion-related acute lung injury, and adverse events. We estimated relative risk for dichotomous outcomes. We measured statistical heterogeneity using I(2). We used a random-effects model to synthesise the findings. We identified three randomised clinical trials, involving a total of 120 participants, comparing packed red blood cells with ≥ 21 days storage

The parents' ability to take care of their baby as a factor in decisions to withhold or withdraw life-prolonging treatment in two Dutch NICUs.

Science.gov (United States)

Moratti, Sofia

2010-06-01

In The Netherlands, it is openly acknowledged that the parents' ability to take care of their child plays a role in the decision-making process over administration of life-prolonging treatment to severely defective newborn babies. Unlike other aspects of such decision-making process up until the present time, the 'ability to take care' has not received specific attention in regulation or in empirical research. The present study is based on interviews with neonatologists in two Dutch NICUs concerning their definition of the ability to take care and its relevance in non-treatment decisions. All of the respondents think that the ability to take care consists of more than one factor. Most doctors mention the parents' emotional state, social network and cognitive abilities. Some doctors mention the presence of psychological conditions in the parents, their financial situation and physical condition. A few refer to the parents' experience and age, their chances to have another baby and their cultural background. Most doctors think the ability to take care has a secondary relevance in the decision-making process, while the primary concern is assessing the condition of the child. A substantial minority thinks the ability to take care does not play any role, while one doctor thinks it is a factor of primary importance. The study constitutes an important stepping-stone for future research in The Netherlands and elsewhere.

The Association between Job-Related Psychosocial Factors and Prolonged Fatigue among Industrial Employees in Taiwan.

Directory of Open Access Journals (Sweden)

Feng-Cheng Tang

Full Text Available Prolonged fatigue is common among employees, but the relationship between prolonged fatigue and job-related psychosocial factors is seldom studied. This study aimed (1 to assess the individual relations of physical condition, psychological condition, and job-related psychosocial factors to prolonged fatigue among employees, and (2 to clarify the associations between job-related psychosocial factors and prolonged fatigue using hierarchical regression when demographic characteristics, physical condition, and psychological condition were controlled.A cross-sectional study was employed. A questionnaire was used to obtain information pertaining to demographic characteristics, physical condition (perceived physical health and exercise routine, psychological condition (perceived mental health and psychological distress, job-related psychosocial factors (job demand, job control, and workplace social support, and prolonged fatigue.A total of 3,109 employees were recruited. Using multiple regression with controlled demographic characteristics, psychological condition explained 52.0% of the variance in prolonged fatigue. Physical condition and job-related psychosocial factors had an adjusted R2 of 0.370 and 0.251, respectively. Hierarchical multiple regression revealed that, among job-related psychosocial factors, job demand and job control showed significant associations with fatigue.Our findings highlight the role of job demand and job control, in addition to the role of perceived physical health, perceived mental health, and psychological distress, in workers' prolonged fatigue. However, more research is required to verify the causation among all the variables.

Safety and efficacy of prolonged epidural analgesia after oncologic colorectal surgery

Directory of Open Access Journals (Sweden)

R. V. Garyaev

2012-01-01

Full Text Available This study demonstrates effective thoracic epidural analgesia by ropivacain 0.2 %, phentanyl 2 mkg/ml, adrenaline 2 mkg/ml in single-use infusion pumps in 124 patients, who underwent surgery for colorectal cancer. Safe, effective and controllable analgesia was observed during surgery and postoperative period. Prolonged analgesia facilitates early rehabilitation and improves gastrointestinal peristaltic activity.  Prolonged epidural analgesia is the recommended method of analgesia in this group of patients.

Translating QT interval prolongation from conscious dogs to humans.

Science.gov (United States)

Dubois, Vincent F S; Smania, Giovanni; Yu, Huixin; Graf, Ramona; Chain, Anne S Y; Danhof, Meindert; Della Pasqua, Oscar

2017-02-01

In spite of screening procedures in early drug development, uncertainty remains about the propensity of new chemical entities (NCEs) to prolong the QT/QTc interval. The evaluation of proarrhythmic activity using a comprehensive in vitro proarrhythmia assay does not fully account for pharmacokinetic-pharmacodynamic (PKPD) differences in vivo. In the present study, we evaluated the correlation between drug-specific parameters describing QT interval prolongation in dogs and in humans. Using estimates of the drug-specific parameter, data on the slopes of the PKPD relationships of nine compounds with varying QT-prolonging effects (cisapride, sotalol, moxifloxacin, carabersat, GSK945237, SB237376 and GSK618334, and two anonymized NCEs) were analysed. Mean slope estimates varied between -0.98 ms μM -1 and 6.1 ms μM -1 in dogs and -10 ms μM -1 and 90 ms μM -1 in humans, indicating a wide range of effects on the QT interval. Linear regression techniques were then applied to characterize the correlation between the parameter estimates across species. For compounds without a mixed ion channel block, a correlation was observed between the drug-specific parameter in dogs and humans (y = -1.709 + 11.6x; R 2  = 0.989). These results show that per unit concentration, the drug effect on the QT interval in humans is 11.6-fold larger than in dogs. Together with information about the expected therapeutic exposure, the evidence of a correlation between the compound-specific parameter in dogs and in humans represents an opportunity for translating preclinical safety data before progression into the clinic. Whereas further investigation is required to establish the generalizability of our findings, this approach can be used with clinical trial simulations to predict the probability of QT prolongation in humans. © 2016 The British Pharmacological Society.

Effects of prolonged exposure to perchlorate on thyroid and reproductive function in zebrafish

Science.gov (United States)

Mukhi, S.; Patino, R.

2007-01-01

The objectives of this study were to determine the effects of prolonged exposure to perchlorate on (1) thyroid status and reproductive performance of adult zebrafish (Danio rerio) and (2) F1 embryo survival and early larval development. Using a static-renewal procedure, mixed sex populations of adult zebrafish were exposed to 0, 10, and 100 mg/l nominal concentrations of waterborne perchlorate for 10 weeks. Thyroid histology was qualitatively assessed, and females and males were separated and further exposed to their respective treatments for six additional weeks. Eight females in each tank replicate (n = 3) were paired weekly with four males from the same respective treatment, and packed-egg (spawn) volume (PEV) was measured each of the last five weeks. At least once during weeks 14-16 of exposure, other end points measured included fertilization rate, fertilized egg diameter, hatching rate, standard length, and craniofacial development of 4-day-postfertilization larvae and thyroid hormone content of 3.5-h embryos and of exposed mothers. At 10 weeks of exposure, perchlorate at both concentrations caused thyroidal hypertrophy and colloid depletion. A marked reduction in PEV was observed toward the end of the 6-week spawning period, but fertilization and embryo hatching rates were unaffected. Fertilized egg diameter and larval length were increased by parental exposure to perchlorate. Larval head depth was unaffected but the forward protrusion of the lower jaw-associated cartilage complexes, Meckel's and ceratohyal, was decreased. Exposure to both concentrations of perchlorate inhibited whole-body thyroxine content in mothers and embryos, but triiodothyronine content was unchanged. In conclusion, prolonged exposure of adult zebrafish to perchlorate not only disrupts their thyroid endocrine system but also impairs reproduction and influences early F1 development. ?? 2007 Oxford University Press.

Ultraviolet light immunomodulation of canine islets for prolongation of allograft survival

International Nuclear Information System (INIS)

Kenyon, N.S.; Strasser, S.; Alejandro, R.

1990-01-01

Ultraviolet (UV) light treatment of donor islets has been shown to be effective for the prolongation of islet allograft survival in rodent models. This study evaluated UV as an immunomodulator of canine islets. The effects of UV irradiation on islet secretory function in vitro revealed a trend of increasing basal insulin release with increasing doses of UV and a corresponding significant decrease in glucose-mediated insulin release (expressed as percentage of basal fractional insulin release) beginning at UV light exposures of 200-300 J/m2 (n = 3, P less than 0.05). Proliferative responses to UV-irradiated allogeneic peripheral blood leukocytes and islets were significantly decreased by 53-112% (P less than 0.05) in 27 of 29 mixed-lymphocyte cultures and by 35-74% (P less than 0.05) in 4 of 5 mixed-lymphocyte islet culture experiments, respectively, beginning at 200-600 J/m2. Autotransplantation of nonirradiated (n = 8) and irradiated islets (600 J/m2, n = 6) resulted in a 1-mo graft survival rate of 75% for the control group and 50% for the irradiated group. Allotransplantation of irradiated islets (600 J/m2) into either nonimmunosuppressed recipients (1 donor to 1 recipient, n = 8) or recipients of subimmunosuppressive doses of cyclosporin (2 donors to 1 recipient, n = 4) resulted in 100% rejection by day 10. In contrast, when islets were cultured for 24 h postirradiation and transplanted into cyclosporin-treated pancreatectomized recipients (2 donors to 1 recipient), 3 of 7 grafts were prolonged beyond day 10 to days 16, 26, and greater than 100

Prolonged jaundice in newborns is associated with low antioxidant capacity in breast milk.

Science.gov (United States)

Uras, Nurdan; Tonbul, Alpaslan; Karadag, Ahmet; Dogan, Derya G; Erel, Ozcan; Tatli, Mustafa M

2010-10-01

In breastfeeding newborns who are otherwise healthy, the mechanism of prolonged jaundice remains unclear. The aim of this study was to investigate relations between prolonged jaundice and oxidative parameters in breast milk. Full-term, otherwise healthy newborns with jaundice lasting more than 2 weeks were enrolled prospectively in the study. As a control group, newborns in the same age group but without prolonged jaundice were selected. All newborns in the study were exclusively breastfed. In the newborns with prolonged jaundice, investigations of the etiology of the jaundice included complete blood count, peripheral blood smear, blood typing, direct Coombs test, measurement of serum levels of total and direct bilirubin, tests for liver and thyroid function (TSH, free T4, total T4), urine culture and measurement of urine reducing substances, and determination of glucose 6 phosphate dehydrogenase enzyme levels. Breast milk was collected from the mothers of the newborns in both groups. The antioxidant status of the breast milk was assessed via determination of total antioxidant capacity (TAC). Oxidative stress was also assessed in breast milk by measurement of total oxidation status (TOS) and calculation of the oxidative stress index (OSI). The prolonged jaundice group differed significantly from the control group in terms of mean TAC and OSI (p antioxidant capacity was found to be decreased.

Nanoparticle tumor localization, disruption of autophagosomal trafficking, and prolonged drug delivery improve survival in peritoneal mesothelioma.

Science.gov (United States)

Liu, Rong; Colby, Aaron H; Gilmore, Denis; Schulz, Morgan; Zeng, Jialiu; Padera, Robert F; Shirihai, Orian; Grinstaff, Mark W; Colson, Yolonda L

2016-09-01

The treatment outcomes for malignant peritoneal mesothelioma are poor and associated with high co-morbidities due to suboptimal drug delivery. Thus, there is an unmet need for new approaches that concentrate drug at the tumor for a prolonged period of time yielding enhanced antitumor efficacy and improved metrics of treatment success. A paclitaxel-loaded pH-responsive expansile nanoparticle (PTX-eNP) system is described that addresses two unique challenges to improve the outcomes for peritoneal mesothelioma. First, following intraperitoneal administration, eNPs rapidly and specifically localize to tumors. The rate of eNP uptake by tumors is an order of magnitude faster than the rate of uptake in non-malignant cells; and, subsequent accumulation in autophagosomes and disruption of autophagosomal trafficking leads to prolonged intracellular retention of eNPs. The net effect of these combined mechanisms manifests as rapid localization to intraperitoneal tumors within 4 h of injection and persistent intratumoral retention for >14 days. Second, the high tumor-specificity of PTX-eNPs leads to delivery of greater than 100 times higher concentrations of drug in tumors compared to PTX alone and this is maintained for at least seven days following administration. As a result, overall survival of animals with established mesothelioma more than doubled when animals were treated with multiple doses of PTX-eNPs compared to equivalent dosing with PTX or non-responsive PTX-loaded nanoparticles. Copyright © 2016 Elsevier Ltd. All rights reserved.

QTc-prolonging drugs and hospitalizations for cardiac arrhythmias

DEFF Research Database (Denmark)

De Bruin, Marie L; Hoes, Arno W; Leufkens, Hubert G M

2003-01-01

Cardiac arrhythmia as an adverse effect of noncardiac drugs has been an issue of growing importance during the past few years. In this population-based study, we evaluated the risk for serious cardiac arrhythmias during the use of several noncardiac QTc-prolonging drugs in day-to-day practice......, and subsequently focused on several specific groups of patients who could be extremely vulnerable for drug-induced arrhythmias. We performed a case-control study in which patients (cases), hospitalized for nonatrial cardiac arrhythmias from 1987 to 1998, were compared with their matched controls regarding current...... use of QTc-prolonging drugs. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariate conditional logistic regression, adjusting for potential confounding factors. Data were obtained from the PHARMO record linkage system. We identified 501 cases, 39 of whom used QTc...

Human amnion as a biological dressing used to prevent prolonged air leakage in thoracic surgery

International Nuclear Information System (INIS)

Mijewski, M.; Uhrynowska-Tyszkiewicz, I.; Piech, K.; Gogowski, M.

2008-01-01

Full text: Prolonged air leakage lasting 7 days or more is one of the most common complications in thoracic surgery. This complication may result in increased morbidity and prolonged hospital stay. Amnion allografts have been used to minimise this complication. The aim of our study was to evaluate the usefulness of human amnion grafts in the treatment of air leakage following thoracic surgery. Deep-frozen, radiation-sterilized (35 kGy) human amnion grafts prepared at the Central Tissue Bank in Warsaw (Poland) were used. Amnion allografts were applied to 69 patients who had surgery: 36 thoracotomies, and 33 rethoracotomies had been performed. During lung ventilation the air leakage sites were identified and covered by the amnion flap. Air leakage were evaluated during the postoperative period. Retrospectively we analysed air leakage duration in 170 thoracothomies and rethoracotomies without amnion transplantation. The separation of lung tissue and the liberation of pleural adhesions may be result in the lung and visceral pleura injury. Deep-frozen and radiation-sterilized human amnion is biocompatible, flexible, strong and airtight. It may be easily attached to the lung parenchyma and allows coverage of the area of the lung parenchyma deprived of the visceral pleura. The use of human amnion allografts is simple and safe. After treatment with amnion in 85% of the cases air leakage last less than 7 days, and only its traces were observed. Our results suggest that the human amnion grafts applied for the prevention of air leakage in lung surgery is a safe, simple and effective method. (Author)

The Importance of Prolonged Provocation in Drug Allergy - Results From a Danish Allergy Clinic.

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Fransson, Sara; Mosbech, Holger; Kappel, Mogens; Hjortlund, Janni; Poulsen, Lars K; Kvisselgaard, Ask D; Garvey, Lene H

Drug provocation is the "Gold Standard" in drug allergy investigation. Recent studies suggest that a negative drug provocation on first dose should be followed by a prolonged provocation over several days. To evaluate drug allergy investigations on the basis of drug provocation, including prolonged provocation. Data from adult patients investigated for drug allergy in a Danish Allergy Clinic during the period 2010 to 2014 were entered into a database. Data included clinical details and results of provocations with suspected culprit drug (for penicillins performed only in specific IgE-negative patients). If provocation was negative on first dose, treatment was continued for 3 to 10 days. A total of 1,913 provocations were done in 1,659 patients, median age 46 years, of whom 1,237 (74.6%) were females. Drugs investigated were antibiotics, 1,776 (92.8%), of which 1,590 (89.5%) were penicillins; analgesics, 59 (3.1%); local anesthetics, 33 (1.7%); and other drugs, 45 (2.4%). In total, 211 of 1,913 (11.0%) provocations were positive. Causes were antibiotics, 198 (93.8%), of which 167 (84.3%) were penicillins; analgesics, 7 (3.3%); local anesthetics, 0; and other drugs, 6 (2.8%). Only 43 (20.4%) provocations were positive on first dose, whereas 95 (45.0%) turned positive more than 3 days later. Only 11.0% of the provocations were positive. Importantly, only 1 of 5 patients tested positive on the first dose, indicating that prolonged exposure should always be considered when drug provocation is included in allergy investigations. Most provocations were with penicillins, reflecting the pattern of antibiotic use in Denmark, which differs from that in other countries, especially outside Northern Europe. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Extended ankle and foot fasciotomy as an enhancement to the surgical treatment of patients with prolonged ischemia of the lower extremities

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Mišović Sidor

2005-01-01

Full Text Available Aim. To present the technique and efficacy of extended ankle and foot fasciotomy, as a surgical limb-salvage procedure associated with the successful revascularization after the gold interval. Method. A retrospective review of six patients at the age of 16−79 years (mean 39 in the period from 1996 to 2003, treated with the extended ankle and foot fasciotomy. There were four males undergoing the delayed treatment of war injuries to the lower extremity, and two females with atherosclerotic occlusive disease (a. illiacae dex and a. poplitealis dex.. The average ishemic time in the wounded patients was 22 hours (range, 14−30 hours, and ischemic time in occlusive disease (range, 48−72 hours. Clinical signs, indications, surgical access and the technique of extended ankle and foot fasciotomy was reported. Results. The obtained results were classified as early and late. There was no cases with lethal outcome. Incisional wounds closed 15 days after the intervention, using secondary suture or skin transplant sec. Thiersch. The satisfactory functional results were achieved in 4 of the patients, 1 had a small edema, while amputation was performed in 1 patient. Conclusion. In cases of prolonged foot ischemia with edema and paresthesia in the toes, extended ankle and foot fasciotomy should be performed as a surgical limb-salvage procedure.

Prolonged Response and Restoration of Functional Independence with Bevacizumab plus Vinorelbine as Third-Line Treatment for Breast Cancer-Related Leptomeningeal Metastases

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Emilie Le Rhun

2015-02-01

Full Text Available Background: Survival of patients with leptomeningeal metastases (LM and impaired functional status is limited to several months, and rarely does neurological function improve with treatment. Case Report: A 34-year-old female with hormone-negative and HER2-positive metastatic breast cancer was diagnosed with bulky radiographic LM 45 months after initial diagnosis. She was treated with intra-CSF trastuzumab followed by intra-CSF liposomal cytarabine; however, the cancer progressed 8 months after the diagnosis of LM. At the time of the third LM progression, the patient presented with a cauda equina syndrome and cerebellar impairment resulting in an inability to walk. She was treated with CNS-directed radiotherapy (lumbosacral and cerebellar and bevacizumab plus vinorelbine. Rapid functional improvement occurred, and the patient regained the ability to walk and independently manage her daily activities. Twelve months later, she presented with rapid progression of the LM resulting in death within several weeks. Conclusion: In radiographically defined bulky LM, the combination of systemic therapy and CNS-directed radiotherapy likely is more active than intra-CSF therapy only. In lieu of the rapid and significant improvement in neurological function combined with the prolonged response, bevacizumab alone or in combination with chemotherapy and CNS-directed radiotherapy may be considered in select patients with radiographically bulky breast cancer-related LM.

Levofloxacin?Induced QTc Prolongation Depends on the Time of Drug Administration

OpenAIRE

Kervezee, L; Gotta, V; Stevens, J; Birkhoff, W; Kamerling, IMC; Danhof, M; Meijer, JH; Burggraaf, J

2016-01-01

Understanding the factors influencing a drug's potential to prolong the QTc interval on an electrocardiogram is essential for the correct evaluation of its safety profile. To explore the effect of dosing time on drug-induced QTc prolongation, a randomized, crossover, clinical trial was conducted in which 12 healthy male subjects received levofloxacin at 02:00, 06:00, 10:00, 14:00, 18:00, and 22:00. Using a pharmacokinetic-pharmacodynamic (PK-PD) modeling approach to account for variations in ...

The hemodynamic effects of prolonged respiratory alkalosis in anesthetized newborn piglets.

Science.gov (United States)

Jundi, K; Barrington, K J; Henderson, C; Allen, R G; Finer, N N

2000-04-01

To test the hypothesis that prolonged alkalosis decreases cardiac output and, furthermore, exacerbates hypoxic pulmonary vasoconstriction, as respiratory alkalosis is frequently induced as a therapy for persistent pulmonary hypertension of the newborn despite a lack of controlled evidence of improved outcomes. Potential adverse effects of prolonged alkalosis have been demonstrated. Two groups (control, n = 6, and hypocapnic alkalosis, n = 6) of 1-3 day old fentanyl-anesthetized, vecuronium-paralyzed piglets were instrumented to measure cardiac index (CI) and mean systemic (MAP) and pulmonary (PAP) arterial pressures. Baseline values were recorded. Alveolar hypoxia was then induced to achieve an arterial oxygen saturation of between 50 and 60% for 15 min. Respiratory alkalosis was then induced, by increasing ventilation to achieve a pH between 7.55-7.60, and was continued for 240 min. Inspired carbon dioxide was used with hyperventilation in the control group to maintain pressure of arterial carbon dioxide (PaCO2) at 35-45 mmHg and pH of 7.35-7.45. Hypoxia was induced again at 15 and 240 min. Pulmonary and systemic vascular resistances (PVR and SVR) were calculated. Prolonged alkalosis led to a significant and progressive fall in mean MAP from 61 (SD 7) mmHg at the start of the study falling to 50 (SD 6.9, p = 0.043), with no effect on CI. Calculated SVR decreased (0.45 SD 0.03 vs 0.36 SD 0.05). There were no statistically significant changes in any of the variables in the control group. Neither acute nor prolonged respiratory alkalosis had a significant effect on hypoxic pulmonary vasoconstriction. Prolonged hyperventilation leads to systemic hypotension, however it does not exacerbate hypoxic pulmonary vasoconstriction.

Post-traumatic stress disorder after weaning from prolonged mechanical ventilation.

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Jubran, Amal; Lawm, Gerald; Duffner, Lisa A; Collins, Eileen G; Lanuza, Dorothy M; Hoffman, Leslie A; Tobin, Martin J

2010-12-01

Weaning from prolonged mechanical ventilation may be associated with mental discomfort. It is not known whether such discomfort is linked with the development of post-traumatic stress disorder (PTSD). Accordingly, we investigated whether PTSD occurs in patients after weaning from prolonged ventilation. We also determined whether administering a questionnaire would identify patients at risk for developing PTSD. A prospective longitudinal study of patients transferred to a long-term acute-care hospital for weaning from prolonged ventilation was undertaken: 72 patients were studied 1 week after weaning, and 41 patients were studied again 3 months later. An experienced psychologist conducted a structured clinical interview 3 months after weaning to establish a diagnosis of PTSD. To assess for the presence of PTSD-related symptoms, the post-traumatic stress syndrome (PTSS-10) questionnaire was administered 1 week after weaning and 3 months later. The psychologist diagnosed PTSD in 12% of patients 3 months after ventilator weaning. Patients who developed PTSD were more likely to have a previous history of psychiatric disorders (P 20 one week after weaning reliably identified patients who were diagnosed with PTSD 3 months later: sensitivity 1.0; specificity 0.76; area under the receiver-operating characteristic curve 0.91. PTSD was diagnosed in 12% of patients who were weaned from prolonged ventilation. A PTSS-10 score >20 one week after weaning identified patients diagnosed with PTSD 3 months later. This finding suggests that a simple questionnaire administered before hospital discharge can identify patients at risk for developing PTSD.

Sidestep and crossover lower limb kinematics during a prolonged sport-like agility test.

Science.gov (United States)

Potter, Danielle; Reidinger, Kellie; Szymialowicz, Rebecca; Martin, Thomas; Dione, Donald; Feinn, Richard; Wallace, David; Garbalosa, Juan C

2014-10-01

Non-contact anterior cruciate ligament (ACL) injuries in athletes occur more often towards the end of athletic competitions. However, the exact mechanisms of how prolonged activity increases the risk for ACL injuries are not clear. To determine the effect of prolonged activity on the hip and knee kinematics observed during self-selected cutting maneuvers performed in a timed agility test. Nineteen female Division I collegiate soccer players completed a self-selected cutting agility test until they were unable to meet a set performance time (one standard deviation of the average baseline trial). Using the 3D dimensional coordinate data the cut type was identified by the principle investigators. The 3D hip and knee angles at 32ms post heel strike were analyzed using a two-factor, linear mixed model to assess the effect of prolonged activity and cut type on the recorded mean hip and knee angles. Athletes performed either sidestep or crossover cuts. An effect of cut type and prolonged activity was seen at the hip and knee. During the prolonged activity trials, the knee was relatively more adducted and both the hip and knee were less flexed than during the baseline trials regardless of cut type. Regardless of activity status, during sidestep cuts, the hip was more internally rotated and abducted, and less flexed than during crossover cuts while the knee was more abducted and less flexed during the sidestep than crossover cuts. During a sport-like agility test, prolonged activity appears to predispose the athlete to position their knee in a more extended and abducted posture and their hip in a more extended posture. This position has been suggested to place stress on the ACL and potentially increase the risk for injury. Clinicians may want to consider the effects of prolonged activity on biomechanical risk factors for sustaining ACL injuries in the design of intervention strategies to prevent ACL injuries. Level 4.

A Multicenter Evaluation of Prolonged Empiric Antibiotic Therapy in Adult ICUs in the United States.

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Thomas, Zachariah; Bandali, Farooq; Sankaranarayanan, Jayashri; Reardon, Tom; Olsen, Keith M

2015-12-01

The purpose of this study is to determine the rate of prolonged empiric antibiotic therapy in adult ICUs in the United States. Our secondary objective is to examine the relationship between the prolonged empiric antibiotic therapy rate and certain ICU characteristics. Multicenter, prospective, observational, 72-hour snapshot study. Sixty-seven ICUs from 32 hospitals in the United States. Nine hundred ninety-eight patients admitted to the ICU between midnight on June 20, 2011, and June 21, 2011, were included in the study. None. Antibiotic orders were categorized as prophylactic, definitive, empiric, or prolonged empiric antibiotic therapy. Prolonged empiric antibiotic therapy was defined as empiric antibiotics that continued for at least 72 hours in the absence of adjudicated infection. Standard definitions from the Centers for Disease Control and Prevention were used to determine infection. Prolonged empiric antibiotic therapy rate was determined as the ratio of the total number of empiric antibiotics continued for at least 72 hours divided by the total number of empiric antibiotics. Univariate analysis of factors associated with the ICU prolonged empiric antibiotic therapy rate was conducted using Student t test. A total of 660 unique antibiotics were prescribed as empiric therapy to 364 patients. Of the empiric antibiotics, 333 of 660 (50%) were continued for at least 72 hours in instances where Centers for Disease Control and Prevention infection criteria were not met. Suspected pneumonia accounted for approximately 60% of empiric antibiotic use. The most frequently prescribed empiric antibiotics were vancomycin and piperacillin/tazobactam. ICUs that utilized invasive techniques for the diagnosis of ventilator-associated pneumonia had lower rates of prolonged empiric antibiotic therapy than those that did not, 45.1% versus 59.5% (p = 0.03). No other institutional factor was significantly associated with prolonged empiric antibiotic therapy rate. Half of all

[Lung abscess: changes in treatment?].

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Clottu, E; Nicod, L P

2015-11-18

Lung abscess occurs in very pleomorphic according to germs initially involved. The mechanism commonly found is an aspiration of the oropharyngeal flora in patients with disorders of consciousness or swallowing. The infection is polymicrobial, with presence of anaerobic germs in 2/3 of the cases. The support consists of a prolonged antibiotic treatment, as well as anaerobic until resolution or stability of the radiological image. In case of prolonged toxic state, drainage of the abscess is to be discussed especially if there is no airways drainage. Surgical sanctions is rarely needed regardless of the size of the abscess, unless underlying carcinoma is present.

The Association between Job-Related Psychosocial Factors and Prolonged Fatigue among Industrial Employees in Taiwan

Science.gov (United States)

Tang, Feng-Cheng; Li, Ren-Hau; Huang, Shu-Ling

2016-01-01

Background and Objectives Prolonged fatigue is common among employees, but the relationship between prolonged fatigue and job-related psychosocial factors is seldom studied. This study aimed (1) to assess the individual relations of physical condition, psychological condition, and job-related psychosocial factors to prolonged fatigue among employees, and (2) to clarify the associations between job-related psychosocial factors and prolonged fatigue using hierarchical regression when demographic characteristics, physical condition, and psychological condition were controlled. Methods A cross-sectional study was employed. A questionnaire was used to obtain information pertaining to demographic characteristics, physical condition (perceived physical health and exercise routine), psychological condition (perceived mental health and psychological distress), job-related psychosocial factors (job demand, job control, and workplace social support), and prolonged fatigue. Results A total of 3,109 employees were recruited. Using multiple regression with controlled demographic characteristics, psychological condition explained 52.0% of the variance in prolonged fatigue. Physical condition and job-related psychosocial factors had an adjusted R2 of 0.370 and 0.251, respectively. Hierarchical multiple regression revealed that, among job-related psychosocial factors, job demand and job control showed significant associations with fatigue. Conclusion Our findings highlight the role of job demand and job control, in addition to the role of perceived physical health, perceived mental health, and psychological distress, in workers’ prolonged fatigue. However, more research is required to verify the causation among all the variables. PMID:26930064

Prolonged controlled delivery of nerve growth factor using porous silicon nanostructures.

Science.gov (United States)

Zilony, Neta; Rosenberg, Michal; Holtzman, Liran; Schori, Hadas; Shefi, Orit; Segal, Ester

2017-07-10

Although nerve growth factor (NGF) is beneficial for the treatment of numerous neurological and non-neurological diseases, its therapeutic administration represents a significant challenge, due to the difficulty to locally deliver relevant doses in a safe and non-invasive manner. In this work, we employ degradable nanostructured porous silicon (PSi) films as carriers for NGF, allowing its continuous and prolonged release, while retaining its bioactivity. The PSi carriers exhibit high loading efficacy (up to 90%) of NGF and a continuous release, with no burst, over a period of>26days. The released NGF bioactivity is compared to that of free NGF in both PC12 cells and dissociated dorsal root ganglion (DRG) neurons. We show that the NGF has retained its bioactivity and induces neurite outgrowth and profound differentiation (of >50% for PC12 cells) throughout the period of release within a single administration. Thus, this proof-of-concept study demonstrates the immense therapeutic potential of these tunable carriers as long-term implants of NGF reservoirs and paves the way for new localized treatment strategies of neurodegenerative diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

FEASIBILITY AND EFFECTIVENESS OF DYADIC PROLONGED EXPOSURE INTERVENTION FOR PREVENTING POSTTRAUMATIC GRIEF IN YOUNG CHILDREN: A CASE REPORT OF TWO SIBLINGS.

Science.gov (United States)

Rachamim, Lilach

2017-09-01

This article highlights the feasibility of a dyadic prolonged exposure (DPE) intervention (L. Rachamim, I. Mirochnik, L. Helpman, N. Nacasch, & E. Yadin, ) in a 3-year-old preschooler and in a 6-year-old kindergartener immediately following the traumatic death of their younger sibling. It presents a detailed case description of the DPE treatment addressing traumatic grief and includes transcribed treatment dialogue. At the time of treatment termination, both children and caregivers resumed normal functioning. The results suggest that DPE intervention may ameliorate posttraumatic grief symptoms in young children. Controlled studies of preventive interventions for this population are clearly warranted. © 2017 Michigan Association for Infant Mental Health.

Etiologies of Prolonged Unconjugated Hyperbilirubinemia in Neonates Admitted to Neonatal Wards

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Mohammad Kazem Sabzehei

2015-12-01

Full Text Available Background: Jaundice is a common condition among neonates. Prolonged unconjugated hyperbilirubinemia occurs when jaundice persists beyond two weeks in term neonates and three weeks in preterm neonates. This study aimed to determine the etiologies of prolonged unconjugated hyperbilirubinemia in infants admitted to the neonatal ward of Besat Hospital in Hamadan, Iran. Methods: This study was conducted on all infants diagnosed with prolonged unconjugated hyperbilirubinemia during 2007-2012 in the neonatal ward of Besat Hospital in Hamadan, Iran. Demographic characteristics of infants, physical examination and laboratory findings were collected and analyzed to determine the etiologies of neonatal hyperbilirubinemia. Results: In total, 100 infants diagnosed with neonatal hyperbilirubinemia were enrolled in this study, including 49 male and 51 female neonates with mean age of 20±1 days and mean bilirubin level of 17.5±4.0 mg/dL. Main causes of hyperbilirubinemia were urinary tract infection, ABO incompatibility, hypothyroidism and glucose-6-phosphate dehydrogenase deficiency in 14%, 5%, 6% and 5% of neonates, respectively. Moreover, unknown etiologies, such as breastfeeding, were detected in 70% of the studied infants. Conclusion: According to the results of this study, determining the main causes of prolonged unconjugated hyperbilirubinemia in neonates is of paramount importance. In the majority of cases, neonatal hyperbilirubinemia is associated with physiological factors, such as breastfeeding.

Marked QTc prolongation and Torsades de Pointes in patients with chronic inflammatory arthritis

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Pietro Enea Lazzerini

2016-09-01

Full Text Available Mounting evidence indicates that in chronic inflammatory arthritis (CIA, QTc prolongation is frequent and correlates with systemic inflammatory activation. Notably, basic studies demonstrated that inflammatory cytokines induce profound changes in potassium and calcium channels resulting in a prolonging effect on cardiomyocyte action potential duration (APD, thus on the QT interval on the electrocardiogram. Moreover, it has been demonstrated that in RA patients the risk of SCD is significantly increased when compared to non-RA subjects. Conversely, to date no data are available about Torsades de Pointes (TdP prevalence in CIA, and the few case reported considered CIA only an incidental concomitant disease, not contributing factor to TdP development.We report three patients with active CIA developing marked QTc prolongation, in two cases complicated with TdP degenerating to cardiac arrest. In these patients, a blood sample was obtained within 24h from TdP/marked QTc prolongation occurrence and levels of IL-6, TNF-alpha and IL-1 were evaluated. In all three cases, IL-6 was markedly elevated, ~10 to 100 times more than reference values. Moreover, one patient also showed high circulating levels of TNF-alpha and IL-1. In conclusion, active CIA may represent a currently overlooked QT-prolonging risk factor, potentially contributing in the presence of other classical risk factors to TdP occurrence. In particular, a relevant role may be played by elevated circulating IL-6 levels via direct electrophysiological effects on the heart. This observation should be carefully kept in mind, particularly when recognizable risk factors are already present and/or the addition of QT-prolonging drugs is required.

Reduced transpiration response to precipitation pulses precedes mortality in a piñon-juniper woodland subject to prolonged drought.

Science.gov (United States)

Plaut, Jennifer A; Wadsworth, W Duncan; Pangle, Robert; Yepez, Enrico A; McDowell, Nate G; Pockman, William T

2013-10-01

Global climate change is predicted to alter the intensity and duration of droughts, but the effects of changing precipitation patterns on vegetation mortality are difficult to predict. Our objective was to determine whether prolonged drought or above-average precipitation altered the capacity to respond to the individual precipitation pulses that drive productivity and survival. We analyzed 5 yr of data from a rainfall manipulation experiment in piñon-juniper (Pinus edulis-Juniperus monosperma) woodland using mixed effects models of transpiration response to event size, antecedent soil moisture, and post-event vapor pressure deficit. Replicated treatments included irrigation, drought, ambient control and infrastructure control. Mortality was highest under drought, and the reduced post-pulse transpiration in the droughted trees that died was attributable to treatment effects beyond drier antecedent conditions and reduced event size. In particular, trees that died were nearly unresponsive to antecedent shallow soil moisture, suggesting reduced shallow absorbing root area. Irrigated trees showed an enhanced response to precipitation pulses. Prolonged drought initiates a downward spiral whereby trees are increasingly unable to utilize pulsed soil moisture. Thus, the additive effects of future, more frequent droughts may increase drought-related mortality. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

The Importance of Prolonged Provocation in Drug Allergy

DEFF Research Database (Denmark)

Fransson, Sara; Mosbech, Holger; Kappel, Mogens

2017-01-01

BACKGROUND: Drug provocation is the "Gold Standard" in drug allergy investigation. Recent studies suggest that a negative drug provocation on first dose should be followed by a prolonged provocation over several days. OBJECTIVE: To evaluate drug allergy investigations on the basis of drug...

Mitigating prolonged QT interval in cancer nanodrug development for accelerated clinical translation.

Science.gov (United States)

Ranjan, Amalendu P; Mukerjee, Anindita; Helson, Lawrence; Vishwanatha, Jamboor K

2013-12-14

Cardiac toxicity is the foremost reason for drug discontinuation from development to clinical evaluation and post market surveillance [Fung 35:293-317, 2001; Piccini 158:317-326 2009]. The Food and Drug Administration (FDA) has rejected many potential pharmaceutical agents due to QT prolongation effects. Since drug development and FDA approval takes an enormous amount of time, money and effort with high failure rates, there is an increased focus on rescuing drugs that cause QT prolongation. If these otherwise safe and potent drugs were formulated in a unique way so as to mitigate the QT prolongation associated with them, these potent drugs may get FDA approval for clinical use. Rescuing these compounds not only benefit the patients who need them but also require much less time and money thus leading to faster clinical translation. In this study, we chose curcumin as our drug of choice since it has been shown to posses anti-tumor properties against various cancers with limited toxicity. The major limitations with this pharmacologically active drug are (a) its ability to prolong QT by inhibiting the hERG channel and (b) its low bioavailability. In our previous studies, we found that lipids have protective actions against hERG channel inhibition and therefore QT prolongation. Results of the manual patch clamp assay of HEK 293 cells clearly illustrated that our hybrid nanocurcumin formulation prevented the curcumin induced inhibition of hERG K+ channel at concentrations higher than the therapeutic concentrations of curcumin. Comparing the percent inhibition, the hybrid nanocurcumin limited inhibition to 24.8% at a high curcumin equivalent concentration of 18 μM. Liposomal curcumin could only decrease this inhibition upto 30% only at lower curcumin concentration of 6 μM but not at 18 μM concentration. Here we show a curcumin encapsulated lipopolymeric hybrid nanoparticle formulation which could protect against QT prolongation and also render increased

Prolonged minor allograft survival in intravenously primed mice--a test of the veto hypothesis

International Nuclear Information System (INIS)

Johnson, L.L.

1987-01-01

Experiments were performed to test the hypothesis that veto cells are responsible for the prolonged survival of minor allografts of skin that is observed in recipients primed intravenously with spleen cells from mice syngeneic with the skin donors. This prolonged survival was observed for each of several minor histocompatibility (H) antigens and is antigen-specific. Gamma radiation (3300 rads) abolished the ability of male spleen cells infused i.v. to delay the rejection of male skin grafts (H-Y antigen) on female recipients. However, depletion of Thy-1+ cells from the i.v. infusion failed to abolish the ability to prolong male skin graft survival. Furthermore, the prolonged survival accorded to B6 (H-2b) male skin grafts on CB6F1 (H-2b/H-2d) female recipients given i.v. infusions of B6 male spleen cells extended to BALB/c (H-2d) male skin grafts as well, indicating a lack of MHC restriction. Thus, prolongation of minor allograft survival by i.v. infusion of minor H antigen-bearing spleen cells appears not to depend on veto T cells that others have found to be responsible for the suppression of CTL generation

Prolonged radioprotective activity of WR-2721 linked to dextran

International Nuclear Information System (INIS)

Moenig, H.; Konermann, G.; Oehlert, W.

1990-01-01

The radioprotective agent WR-2721 was linked to dextran and poly(glutamic acid) respectively, to obtain a prolonged radioprotective ability. Male mice were administered these water soluble polymer conjugates one to 72 hours prior to a whole body irradiation with X-rays. A prolongation of radioprotective efficiency was achieved with two dextran-(WR-2721)-conjugates. For a period of 24 hours between administration, and irradiation dose reduction factors of 1.14±0.04 and 1.10±0.03 respectively were found. After 72 hours, no protective effect was observed. Histopathological investigations of the liver for formation of tumors 200 to 600 days after irradiation seems to indicate that a protective effect is not produced by the dextran-(WR-2721)-conjugats. (orig.) [de

Prolonged endoplasmic reticulum stress alters placental morphology and causes low birth weight

International Nuclear Information System (INIS)

Kawakami, Takashige; Yoshimi, Masaki; Kadota, Yoshito; Inoue, Masahisa; Sato, Masao; Suzuki, Shinya

2014-01-01

The role of endoplasmic reticulum (ER) stress in pregnancy remains largely unknown. Pregnant mice were subcutaneously administered tunicamycin (Tun), an ER stressor, as a single dose [0, 50, and 100 μg Tun/kg/body weight (BW)] on gestation days (GDs) 8.5, 12.5, and 15.5. A high incidence (75%) of preterm delivery was observed only in the group treated with Tun 100 μg/kg BW at GD 15.5, indicating that pregnant mice during late gestation are more susceptible to ER stress on preterm delivery. We further examined whether prolonged in utero exposure to ER stress affects fetal development. Pregnant mice were subcutaneously administered a dose of 0, 20, 40, and 60 μg Tun/kg from GD 12.5 to 16.5. Tun treatment decreased the placental and fetal weights in a dose-dependent manner. Histological evaluation showed the formation of a cluster of spongiotrophoblast cells in the labyrinth zone of the placenta of Tun-treated mice. The glycogen content of the fetal liver and placenta from Tun-treated mice was lower than that from control mice. Tun treatment decreased mRNA expression of Slc2a1/glucose transporter 1 (GLUT1), which is a major transporter for glucose, but increased placental mRNA levels of Slc2a3/GLUT3. Moreover, maternal exposure to Tun resulted in a decrease in vascular endothelial growth factor receptor-1 (VEGFR-1), VEGFR-2, and placental growth factor. These results suggest that excessive and exogenous ER stress may induce functional abnormalities in the placenta, at least in part, with altered GLUT and vascular-related gene expression, resulting in low infant birth weight. - Highlights: • Maternal exposure to excessive ER stress induced preterm birth and IUGR. • Prolonged excessive ER stress altered the formation of the placental labyrinth. • ER stress decreased GLUT1 mRNA expression in the placenta, but increased GLUT3. • ER stress-induced IUGR causes decreased glycogen and altered glucose transport

Prolonged endoplasmic reticulum stress alters placental morphology and causes low birth weight

Energy Technology Data Exchange (ETDEWEB)

Kawakami, Takashige, E-mail: tkawakami@ph.bunri-u.ac.jp; Yoshimi, Masaki; Kadota, Yoshito; Inoue, Masahisa; Sato, Masao; Suzuki, Shinya

2014-03-01

The role of endoplasmic reticulum (ER) stress in pregnancy remains largely unknown. Pregnant mice were subcutaneously administered tunicamycin (Tun), an ER stressor, as a single dose [0, 50, and 100 μg Tun/kg/body weight (BW)] on gestation days (GDs) 8.5, 12.5, and 15.5. A high incidence (75%) of preterm delivery was observed only in the group treated with Tun 100 μg/kg BW at GD 15.5, indicating that pregnant mice during late gestation are more susceptible to ER stress on preterm delivery. We further examined whether prolonged in utero exposure to ER stress affects fetal development. Pregnant mice were subcutaneously administered a dose of 0, 20, 40, and 60 μg Tun/kg from GD 12.5 to 16.5. Tun treatment decreased the placental and fetal weights in a dose-dependent manner. Histological evaluation showed the formation of a cluster of spongiotrophoblast cells in the labyrinth zone of the placenta of Tun-treated mice. The glycogen content of the fetal liver and placenta from Tun-treated mice was lower than that from control mice. Tun treatment decreased mRNA expression of Slc2a1/glucose transporter 1 (GLUT1), which is a major transporter for glucose, but increased placental mRNA levels of Slc2a3/GLUT3. Moreover, maternal exposure to Tun resulted in a decrease in vascular endothelial growth factor receptor-1 (VEGFR-1), VEGFR-2, and placental growth factor. These results suggest that excessive and exogenous ER stress may induce functional abnormalities in the placenta, at least in part, with altered GLUT and vascular-related gene expression, resulting in low infant birth weight. - Highlights: • Maternal exposure to excessive ER stress induced preterm birth and IUGR. • Prolonged excessive ER stress altered the formation of the placental labyrinth. • ER stress decreased GLUT1 mRNA expression in the placenta, but increased GLUT3. • ER stress-induced IUGR causes decreased glycogen and altered glucose transport.

Extensive deep vein thrombosis following prolonged gaming ('gamer's thrombosis'): a case report.

Science.gov (United States)

Chang, Hsien-Cheng Leon; Burbridge, Hayley; Wong, Conroy

2013-10-08

The average time spent playing video games is increasing. Prolonged immobility associated with gaming may therefore be an important risk factor for venous thromboembolism. We report a case of deep vein thrombosis associated with prolonged playing of PlayStation® games. A 31-year-old Caucasian man, an exterior painter, presented with a three-day history of left leg pain and swelling after playing PlayStation® games for almost eight hours a day for four consecutive days. Doppler ultrasound of the left leg confirmed extensive left leg deep venous thrombosis requiring thrombolysis and anticoagulation. Video gaming should be considered a risk factor for venous thromboembolism. Further studies are needed to estimate the degree of risk associated with prolonged periods of playing video games, and education for preventing venous thrombosis should be provided to gamers.

Correlates of prolonged television viewing time in older Japanese men and women.

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Kikuchi, Hiroyuki; Inoue, Shigeru; Sugiyama, Takemi; Owen, Neville; Oka, Koichiro; Shimomitsu, Teruichi

2013-03-09

In addition to insufficient moderate-to-vigorous physical activity (MVPA), prolonged sitting time is also a health risk for older adults. An understanding of population subgroups who have prolonged television viewing (TV) time, a predominant sedentary behavior, can aid in the development of relevant health promotion initiatives; however, few such studies have focused on older adults, the most sedentary segment of the population as a whole. The aim of this study is to examine the socio-demographic attributes associated with TV time among community-dwelling Japanese older men and women. A population-based, cross-sectional mail survey was used to collect data on TV time, MVPA, and socio-demographic characteristics. The survey was conducted from February through March 2010. Participants were 2700 community-dwelling older adults (aged 65-74 years, 50% men) who were randomly selected from the registry of residential addresses of three cities in Japan. Data from 1665 participants (mean age: 69.5 years, 52% men) who completed all variables for the present study were analyzed. Multivariate logistic regression analyses were used to calculate the odds ratios (ORs) of prolonged TV time (>2 hours/day) for each socio-demographic attribute, stratified by gender. Of the 1665 participants, 810 (48.6%) watched TV for more than 2 hours/day. The median television viewing time (25th, 75th percentile) was 2.00 (1.07, 3.50) hours/day. Prolonged TV time was associated with not in full-time employment, lower educational attainment, weight status, living in regional areas and low MVPA for the whole sample. For men, prolonged TV time was associated with lower educational attainment; (OR = 1.53, 95% CI: 1.12-2.07), underweight (OR = 1.63, 95% CI: 1.02-2.60), overweight (OR = 1.57, 95% CI: 1.11-2.21), and low MVPA (OR = 1.43, 95% CI: 1.02-2.02). For women, living in regional areas (OR = 2.02, 95% CI: 1.33-3.08), living alone (OR = 1.61, 95% CI: 1.03-2.49), not driving

Efficacy and safety of intravenous sodium valproate versus phenobarbital in controlling convulsive status epilepticus and acute prolonged convulsive seizures in children: a randomised trial.

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Malamiri, Reza Azizi; Ghaempanah, Mahdieh; Khosroshahi, Nahid; Nikkhah, Ali; Bavarian, Behrouz; Ashrafi, Mahmoud Reza

2012-09-01

Status epilepticus and acute prolonged seizures are the most commonly occurring neurological emergencies in children. Such events have high morbidity and mortality rates along with poor long-term outcomes, depending on their duration and causes. Therefore, such seizures warrant urgent treatment using appropriate doses of anticonvulsants. Benzodiazepines, phenobarbital, and phenytoin are the most commonly used anticonvulsants for controlling status epilepticus and acute prolonged seizures. However, these medications have several well-known adverse effects. Previous studies on both adults and children have shown the efficacy and safety of rapid infusion of valproate in controlling status epilepticus. However, few well-designed randomised trials have been carried out in children, and there remains a paucity of data regarding intravenous sodium valproate use in children. Therefore, our aim was to compare the efficacy and safety of rapid loading of valproate with those of intravenous phenobarbital in children with status epilepticus and acute prolonged seizures. Sixty children (30 in each group) with convulsive status epilepticus and acute prolonged seizures were enrolled and randomly assigned to receive either valproate or phenobarbital. The main outcome variable was termination of all convulsive activity within 20 min of starting anticonvulsant infusion. Intravenous rapid loading of valproate was successful in seizure termination in (27/30, 90%) of patients compared to phenobarbital (23/30, 77%) (p = 0.189). Clinically significant adverse effects occurred in 74% patients of the phenobarbital group and 24% patients of the valproate group (p < 0.001). In conclusion, rapid loading of valproate is effective and safe in controlling convulsive status epilepticus and acute prolonged convulsive seizures in children. Intravenous valproate should be considered as a suitable choice for terminating status epilepticus and acute prolonged seizures in children. Copyright �

Safely prolonging single breath-holds to >5 min in patients with cancer; feasibility and applications for radiotherapy

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Green, Stuart; Stevens, Andrea M; Parveen, Sophia; Stephens, Rebecca; Clutton-Brock, Thomas H

2016-01-01

Objective: Multiple, short and deep inspiratory breath-holds with air of approximately 20 s are now used in radiotherapy to reduce the influence of ventilatory motion and damage to healthy tissue. There may be further clinical advantages in delivering each treatment session in only one single, prolonged breath-hold. We have previously developed techniques enabling healthy subjects to breath-hold for 7 min. Here, we demonstrate their successful application in patients with cancer. Methods: 15 patients aged 37–74 years undergoing radiotherapy for breast cancer were trained to breath-hold safely with pre-oxygenation and mechanically induced hypocapnia under simulated radiotherapy treatment conditions. Results: The mean breath-hold duration was 5.3 ± 0.2 min. At breakpoint, all patients were normocapnic and normoxic [mean end-tidal partial pressure of carbon dioxide was 36 ± 1 standard error millimetre of mercury, (mmHg) and mean oxygen saturation was 100 ± 0 standard error %]. None were distressed, nor had gasping, dizziness or disturbed breathing in the post-breath-hold period. Mean blood pressure had risen significantly from 125 ± 3 to 166 ± 4 mmHg at breakpoint (without heart rate falling), but normalized within approximately 20 s of the breakpoint. During breath-holding, the mean linear anteroposterior displacement slope of the L breast marker was radiotherapy treatment conditions for longer than the typical beam-on time of a single fraction. We discuss the important applications of this technique for radiotherapy. Advances in knowledge: We demonstrate for the first time a technique enabling patients with cancer to deliver safely a single prolonged breath-hold of >5 min (10 times longer than currently used in radiotherapy practice), under simulated radiotherapy treatment conditions. PMID:27168468

Prolongation of rapacuronium neuromuscular blockade by clindamycin and magnesium.

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Sloan, Paul A; Rasul, Mazhar

2002-01-01

We report a prolonged neuromuscular block with the nondepolarizing muscle relaxant rapacuronium in the presence of clindamycin. Even when using "short-acting" muscle relaxants, the anesthesiologist must routinely monitor the neuromuscular function.

Hydroelectrolytic and hormonal modifications related to prolonged bedrest in antiorthostatic position

Science.gov (United States)

Güell, A.; Dupui, Ph.; Fanjaud, G.; Bes, A.; Moatti, J. P.; Gharrib, Cl.

The effects of prolonged bedrest in antiorthostatic position (-4° head down) on electrolyte balance were studied in 4 young volunteers. An increase was noted in sodium excretion during the first 4 days. Plasma renin activity and plasma aldosterone varied in parallel manner during the same period. Potassium balance and creatinine clearance were not significantly modified. In light of these data we feel that prolonged bedrest in antiorthostatic position constitutes an effective way to simulate on earth metabolic and hormonal modifications occurring in man under weightlessness conditions.

Effect of meal glycemic load and caffeine consumption on prolonged monotonous driving performance.

Science.gov (United States)

Bragg, Christopher; Desbrow, Ben; Hall, Susan; Irwin, Christopher

2017-11-01

Monotonous driving involves low levels of stimulation and high levels of repetition and is essentially an exercise in sustained attention and vigilance. The aim of this study was to determine the effects of consuming a high or low glycemic load meal on prolonged monotonous driving performance. The effect of consuming caffeine with a high glycemic load meal was also examined. Ten healthy, non-diabetic participants (7 males, age 51±7yrs, mean±SD) completed a repeated measures investigation involving 3 experimental trials. On separate occasions, participants were provided one of three treatments prior to undertaking a 90min computer-based simulated drive. The 3 treatment conditions involved consuming: (1) a low glycemic load meal+placebo capsules (LGL), (2) a high glycemic load meal+placebo capsules (HGL) and (3) a high glycemic load meal+caffeine capsules (3mgkg -1 body weight) (CAF). Measures of driving performance included lateral (standard deviation of lane position (SDLP), average lane position (AVLP), total number of lane crossings (LC)) and longitudinal (average speed (AVSP) and standard deviation of speed (SDSP)) vehicle control parameters. Blood glucose levels, plasma caffeine concentrations and subjective ratings of sleepiness, alertness, mood, hunger and simulator sickness were also collected throughout each trial. No difference in either lateral or longitudinal vehicle control parameters or subjective ratings were observed between HGL and LGL treatments. A significant reduction in SDLP (0.36±0.20m vs 0.41±0.19m, p=0.004) and LC (34.4±31.4 vs 56.7±31.5, p=0.018) was observed in the CAF trial compared to the HGL trial. However, no differences in AVLP, AVSP and SDSP or subjective ratings were detected between these two trials (p>0.05). Altering the glycemic load of a breakfast meal had no effect on measures of monotonous driving performance in non-diabetic adults. Individuals planning to undertake a prolonged monotonous drive following consumption of a

Prolonged ultraviolet light-induced erythema and the cutaneous carcinoma phenotype

International Nuclear Information System (INIS)

Tanenbaum, L.; Parrish, J.A.; Haynes, H.A.; Fitzpatrick, T.B.; Pathak, M.A.

1976-01-01

A considerable amount of evidence exists in support of the role of ultraviolet radiation as a major etiologic factor in human skin cancer, both melanoma and carcinoma types. On the basis of epidemiologic studies a phenotype has been described which helps to identify the persons who are more susceptible to skin cancer. In an attempt to further define this population, patients with cutaneous carcinoma and a normal control group were exposed to artificial ultraviolet light (UVL) and the erythema and tanning responses of each group were measured over a 21-day period. UVL-induced erythema was prolonged in a significantly higher percentage of patients with skin cancer than in control patients, lasting two to three weeks after single exposures to 6 and 8 times the patient's minimal erythema dose. The presence of prolonged erythema correlated with this history of previous skin cancer but did not correlate with other established risk factors for cutaneous carcinoma, i.e., fair skin, light hair and light eyes, easy sunburning and poor tanning, and Celtic ancestry. Prolonged erythema following UVL radiation may therefore represent an additional risk factor and help to identify the skin cancer-susceptible population

Systemic administration of bevacizumab prolongs survival in an in vivo model of platinum pre-treated ovarian cancer

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REIN, DANIEL T.; VOLKMER, ANNE KATHRIN; VOLKMER, JENS; BEYER, INES M.; JANNI, WOLFGANG; FLEISCH, MARKUS C.; WELTER, ANNE KATHRIN; BAUERSCHLAG, DIRK; SCHÖNDORF, THOMAS; BREIDENBACH, MARTINA

2012-01-01

Ovarian cancer patients often suffer from malignant ascites and pleural effusion. Apart from worsening the outcome, this condition frequently impairs the quality of life in patients who are already distressed by ovarian cancer. This study investigated whether single intraperitoneal administration of the anti-VEGF antibody bevacizumab is capable of reducing the ascites-related body surface and prolonging survival. The study was performed in an orthotopic murine model of peritoneal disseminated platin-resistant ovarian cancer. Mice were treated with bevacizumab and/or paclitaxel or buffer (control). Reduction of body surface and increased survival rates were assessed as therapeutic success. Survival of mice in all treatment groups was significantly enhanced when compared to the non-treatment control group. The combination of paclitaxel plus bevacizumab significantly improved body surface as well as overall survival in comparison to a treatment with only one of the drugs. Treatment of malignant effusion with a single dose of bevacizumab as an intraperitoneal application, with or without cytostatic co-medication, may be a powerful alternative to systemic treatment. PMID:22740945

H2O2 homeostasis in wild-type and ethylene-insensitive Never ripe tomato in response to salicylic acid treatment in normal photoperiod and in prolonged darkness.

Science.gov (United States)

Takács, Zoltán; Poór, Péter; Borbély, Péter; Czékus, Zalán; Szalai, Gabriella; Tari, Irma

2018-05-01

Ethylene proved to be an important modulator of salicylic acid (SA) signalling pathway. Since SA may regulate both the production and scavenging of hydrogen peroxide (H 2 O 2 ), which show light-dependency, the aim of this study was to compare H 2 O 2 metabolism in the leaves of SA-treated wild-type (WT) tomato (Solanum lycopersicum L. cv. Ailsa Craig) and in ethylene receptor Never-ripe (Nr) mutants grown in normal photoperiod or in prolonged darkness. H 2 O 2 accumulation was higher in the WT than in the mutants in normal photoperiod after 1 mM SA treatment, while Nr leaves contained more H 2 O 2 after light deprivation. The expression of certain superoxide dismutase (SOD) genes and activity of the enzyme followed the same tendency as H 2 O 2 , which was scavenged by different enzymes in the two genotypes. Catalase (CAT, EC 1.11.1.6) activity was inhibited by SA in WT, while the mutants maintained enhanced enzyme activity in the dark. Thus, in WT, CAT inhibition was the major component of the H 2 O 2 accumulation elicited by 1 mM SA in a normal photoperiod, since the expression and/or activity of ascorbate (APX, EC 1.11.1.11) and guaiacol peroxidases (POD, EC 1.11.1.7) were induced in the leaves. The absence of APX and POD activation in mutant plants suggests that the regulation of these enzymes by SA needs functional ethylene signalling. While the block of ethylene perception in Nr mutants was overwritten in the transcription and activity of certain SOD and CAT isoenzymes during prolonged darkness, the low APX and POD activities led to H 2 O 2 accumulation in these tissues. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Cerebral ammonia uptake and accumulation during prolonged exercise in humans

DEFF Research Database (Denmark)

Nybo, Lars; Dalsgaard, Mads K.; Steensberg, Adam

2005-01-01

We evaluated whether peripheral ammonia production during prolonged exercise enhances the uptake and subsequent accumulation of ammonia within the brain. Two studies determined the cerebral uptake of ammonia (arterial and jugular venous blood sampling combined with Kety-Schmidt-determined cerebral...... blood flow; n = 5) and the ammonia concentration in the cerebrospinal fluid (CSF; n = 8) at rest and immediately following prolonged exercise either with or without glucose supplementation. There was a net balance of ammonia across the brain at rest and at 30 min of exercise, whereas 3 h of exercise...... exercise with glucose, and further to 16.1 ± 3.3 µM after the placebo trial (P

Effectiveness of prolonged-release melatonin in Improving Quality of Sleep in Patients Aged 55 or Over

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G. V. Kovrov

2016-01-01

Full Text Available Objective: to evaluate the efficacy of prolonged-release melatonin used in routine practice to improve sleep quality in Russian patients over 55 years of age.Patients and methods. The results of the multicenter open-label observational study of Circadin (prolonged-release melatonin efficiency for treatment of insomnia in 36 patients older than 55 yeare presented. The drug was administered at a dose of 2 mg one-two hours before bedtime for 3 weeks.Results. Treatment with Circadin resulted in statistically significant (p<0.0001 according to pared t-test (95% CI: 4.8; 7.3 improvement of the sleep quality: the mean value of the modified subjective sleep characteristics scale increased from 11.8±2.6 points at baseline to 17.8±2.3 points after 3 weeks of treatment. The modified Questionnaire Scoring Subjective Characteristics of Sleep was grade from 0 (very bad to 20 (very good taking into account: the amount of time required to fall asleep, the sleep duration, the number of night awakenings and the general well-being in the morning. An increase of 6 points on a scale from 0 to 20 was considered as clinically relevant. A greater effect was observed in patients with severely impaired sleep quality as well as with low level of depression and anxiety and absence of cognitive impairment. Upon completion of Circadin treatment there were statistically significant improvement (p<0.0001 of attention (the mean value of the symbol-digit coding test increased from 34.2±9.7 to 37.3±10.6 points and memory (the median value of the short-term verbal memory test increased from 4 points at baseline to 5 points at the study end, p=0.0069.The drug had a good safety profile; only one adverse event related to study medication (allergic rush was registered in the study. The absolute majority (91.7% of the study patients considered Circadin treatment as either effective or very effective.Conclusion. Taking into consideration the good safety profile of this drug

Current status and prospects of HIV treatment.

Science.gov (United States)

Cihlar, Tomas; Fordyce, Marshall

2016-06-01

Current antiviral treatments can reduce HIV-associated morbidity, prolong survival, and prevent HIV transmission. Combination antiretroviral therapy (cART) containing preferably three active drugs from two or more classes is required for durable virologic suppression. Regimen selection is based on virologic efficacy, potential for adverse effects, pill burden and dosing frequency, drug-drug interaction potential, resistance test results, comorbid conditions, social status, and cost. With prolonged virologic suppression, improved clinical outcomes, and longer survival, patients will be exposed to antiretroviral agents for decades. Therefore, maximizing the safety and tolerability of cART is a high priority. Emergence of resistance and/or lack of tolerability in individual patients require availability of a range of treatment options. Development of new drugs is focused on improving safety (e.g. tenofovir alafenamide) and/or resistance profile (e.g. doravirine) within the existing drug classes, combination therapies with improved adherence (e.g. single-tablet regimens), novel mechanisms of action (e.g. attachment inhibitors, maturation inhibitors, broadly neutralizing antibodies), and treatment simplification with infrequent dosing (e.g. long-acting injectables). In parallel with cART innovations, research and development efforts focused on agents that target persistent HIV reservoirs may lead to prolonged drug-free remission and HIV cure. Copyright © 2016 Gilead Sciences, Inc. Published by Elsevier B.V. All rights reserved.

Histone Deacetylase Inhibitors Prolong Cardiac Repolarization through Transcriptional Mechanisms.

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Spence, Stan; Deurinck, Mark; Ju, Haisong; Traebert, Martin; McLean, LeeAnne; Marlowe, Jennifer; Emotte, Corinne; Tritto, Elaine; Tseng, Min; Shultz, Michael; Friedrichs, Gregory S

2016-09-01

Histone deacetylase (HDAC) inhibitors are an emerging class of anticancer agents that modify gene expression by altering the acetylation status of lysine residues of histone proteins, thereby inducing transcription, cell cycle arrest, differentiation, and cell death or apoptosis of cancer cells. In the clinical setting, treatment with HDAC inhibitors has been associated with delayed cardiac repolarization and in rare instances a lethal ventricular tachyarrhythmia known as torsades de pointes. The mechanism(s) of HDAC inhibitor-induced effects on cardiac repolarization is unknown. We demonstrate that administration of structurally diverse HDAC inhibitors to dogs causes delayed but persistent increases in the heart rate corrected QT interval (QTc), an in vivo measure of cardiac repolarization, at timepoints far removed from the Tmax for parent drug and metabolites. Transcriptional profiling of ventricular myocardium from dogs treated with various HDAC inhibitors demonstrated effects on genes involved in protein trafficking, scaffolding and insertion of various ion channels into the cell membrane as well as genes for specific ion channel subunits involved in cardiac repolarization. Extensive in vitro ion channel profiling of various structural classes of HDAC inhibitors (and their major metabolites) by binding and acute patch clamp assays failed to show any consistent correlations with direct ion channel blockade. Drug-induced rescue of an intracellular trafficking-deficient mutant potassium ion channel, hERG (G601S), and decreased maturation (glycosylation) of wild-type hERG expressed by CHO cells in vitro correlated with prolongation of QTc intervals observed in vivo The results suggest that HDAC inhibitor-induced prolongation of cardiac repolarization may be mediated in part by transcriptional changes of genes required for ion channel trafficking and localization to the sarcolemma. These data have broad implications for the development of these drug classes and

Prolongation Structure of Semi-discrete Nonlinear Evolution Equations

International Nuclear Information System (INIS)

Bai Yongqiang; Wu Ke; Zhao Weizhong; Guo Hanying

2007-01-01

Based on noncommutative differential calculus, we present a theory of prolongation structure for semi-discrete nonlinear evolution equations. As an illustrative example, a semi-discrete model of the nonlinear Schroedinger equation is discussed in terms of this theory and the corresponding Lax pairs are also given.

Prolonged Screen Viewing Times and Sociodemographic Factors among Pregnant Women: A Cross-Sectional Survey in China.

Science.gov (United States)

Xu, Xianglong; Liu, Dengyuan; Rao, Yunshuang; Zeng, Huan; Zhang, Fan; Wang, Lu; Xie, Yaojie; Sharma, Manoj; Zhao, Yong

2018-02-27

Objectives: This study aimed to assess the prevalence of prolonged television, computer, and mobile phone viewing times and examined related sociodemographic factors among Chinese pregnant women. Methods: In this study, a cross-sectional survey was implemented among 2400 Chinese pregnant women in 16 hospitals of 5 provinces from June to August in 2015, and the response rate of 97.76%. We excluded women with serious complications and cognitive disorders. The women were asked about their television, computer, and mobile phone viewing during pregnancy. Prolonged television watching or computer viewing was defined as spending more than two hours on television or computer viewing per day. Prolonged mobile phone viewing was watching more than one hour on mobile phone per day. Results: Among 2345 pregnant women, about 25.1% reported prolonged television viewing, 20.6% reported prolonged computer viewing, and 62.6% reported prolonged mobile phone viewing. Pregnant women with long mobile phone viewing times were likely have long TV (Estimate = 0.080, Standard Error ( SE ) = 0.016, p women with long TV (Estimate = 0.134, SE = 0.027, p women with long TV viewing times were less likely to have long computer viewing times (Estimate = -0.032, SE = 0.015, p = 0.035), and pregnant women with long computer viewing times were less likely have long TV viewing times (Estimate = -0.059, SE = 0.028, p = 0.035). Pregnant women in their second pregnancy had lower prolonged computer viewing times than those in their first pregnancy (Odds Ratio (OR) 0.56, 95% Confidence Interval (CI) 0.42-0.74). Pregnant women in their second pregnancy were more likely have longer prolonged mobile phone viewing times than those in their first pregnancy ( OR 1.25, 95% CI 1.01-1.55). Conclusions: The high prevalence rate of prolonged TV, computer, and mobile phone viewing times was common for pregnant women in their first and second pregnancy. This study preliminarily explored the relationship between

Romidepsin for the treatment of relapsed/refractory peripheral T cell lymphoma: prolonged stable disease provides clinical benefits for patients in the pivotal trial

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Francine Foss

2016-03-01

Full Text Available Abstract Background Achievement of durable responses in patients with relapsed/refractory peripheral T cell lymphoma (PTCL is challenging with current therapies, and there are few data regarding the potential benefits of continuing treatment in patients with the best response of stable disease (SD. Histone deacetylase inhibitors are a novel class of drugs with activity in T cell malignancies. Romidepsin was approved by the US Food and Drug Administration for the treatment of relapsed/refractory PTCL based on a pivotal trial demonstrating an objective response rate of 25 % (33/130, including 15 % with confirmed/unconfirmed complete response and a median duration of response of 28 months. Our objective was to further study the clinical benefits of romidepsin in patients that had the best response of SD. Methods Patients with PTCL relapsed/refractory to ≥1 prior therapy were treated with the approved dose of 14 mg/m2 romidepsin on days 1, 8, and 15 of six 28-day cycles; patients with SD or response after cycle 6 were allowed to continue on study until progression. By protocol amendment, patients treated for ≥12 cycles could receive maintenance dosing twice per cycle; after cycle 24, dosing could be further reduced to once per cycle in those who had received maintenance dosing for ≥6 months. Results Of the 32 patients (25 % with the best response of SD, 22 had SD for ≥90 days (SD90; cycle 4 response assessment. The longest SD was >3 years in a patient who received maintenance dosing of 14 mg/m2 on days 1 and 15 beginning in cycle 13. Patients with the best response of SD90 or partial response achieved similar overall and progression-free survival. Prolonged dosing of romidepsin was well tolerated. Conclusions We concluded that patients who achieve SD may consider continuing treatment because the clinical benefits of romidepsin may extend beyond objective responses. Trial registration NCT00426764

Dietary Intake of Sulforaphane-Rich Broccoli Sprout Extracts during Juvenile and Adolescence Can Prevent Phencyclidine-Induced Cognitive Deficits at Adulthood.

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Yumi Shirai

Full Text Available Oxidative stress and inflammation play a role in cognitive impairment, which is a core symptom of schizophrenia. Furthermore, a hallmark of the pathophysiology of this disease is the dysfunction of cortical inhibitory γ-aminobutyric acid (GABA neurons expressing parvalbumin (PV, which is also involved in cognitive impairment. Sulforaphane (SFN, an isothiocyanate derived from broccoli, is a potent activator of the transcription factor Nrf2, which plays a central role in the inducible expressions of many cytoprotective genes in response to oxidative stress. Keap1 is a cytoplasmic protein that is essential for the regulation of Nrf2 activity. Here, we found that pretreatment with SFN attenuated cognitive deficits, the increase in 8-oxo-dG-positive cells, and the decrease in PV-positive cells in the medial prefrontal cortex and hippocampus after repeated administration of phencyclidine (PCP. Furthermore, PCP-induced cognitive deficits were improved by the subsequent subchronic administration of SFN. Interestingly, the dietary intake of glucoraphanin (a glucosinolate precursor of SFN during the juvenile and adolescence prevented the onset of PCP-induced cognitive deficits as well as the increase in 8-oxo-dG-positive cells and the decrease in PV-positive cells in the brain at adulthood. Moreover, the NRF2 gene and the KEAP1 gene had an epistatic effect on cognitive impairment (e.g., working memory and processing speed in patients with schizophrenia. These findings suggest that SFN may have prophylactic and therapeutic effects on cognitive impairment in schizophrenia. Therefore, the dietary intake of SFN-rich broccoli sprouts during the juvenile and adolescence may prevent the onset of psychosis at adulthood.

Using the Single Prolonged Stress Model to Examine the Pathophysiology of PTSD

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Rimenez R. Souza

2017-09-01

Full Text Available The endurance of memories of emotionally arousing events serves the adaptive role of minimizing future exposure to danger and reinforcing rewarding behaviors. However, following a traumatic event, a subset of individuals suffers from persistent pathological symptoms such as those seen in posttraumatic stress disorder (PTSD. Despite the availability of pharmacological treatments and evidence-based cognitive behavioral therapy, a considerable number of PTSD patients do not respond to the treatment, or show partial remission and relapse of the symptoms. In controlled laboratory studies, PTSD patients show deficient ability to extinguish conditioned fear. Failure to extinguish learned fear could be responsible for the persistence of PTSD symptoms such as elevated anxiety, arousal, and avoidance. It may also explain the high non-response and dropout rates seen during treatment. Animal models are useful for understanding the pathophysiology of the disorder and the development of new treatments. This review examines studies in a rodent model of PTSD with the goal of identifying behavioral and physiological factors that predispose individuals to PTSD symptoms. Single prolonged stress (SPS is a frequently used rat model of PTSD that involves exposure to several successive stressors. SPS rats show PTSD-like symptoms, including impaired extinction of conditioned fear. Since its development by the Liberzon lab in 1997, the SPS model has been referred to by more than 200 published papers. Here we consider the findings of these studies and unresolved questions that may be investigated using the model.

Lung transplantation for idiopathic pulmonary arterial hypertension on intraoperative and postoperatively prolonged extracorporeal membrane oxygenation provides optimally controlled reperfusion and excellent outcome.

Science.gov (United States)

Moser, Bernhard; Jaksch, Peter; Taghavi, Shahrokh; Muraközy, Gabriella; Lang, Georg; Hager, Helmut; Krenn, Claus; Roth, Georg; Faybik, Peter; Bacher, Andreas; Aigner, Clemens; Matilla, José R; Hoetzenecker, Konrad; Hacker, Philipp; Lang, Irene; Klepetko, Walter

2018-01-01

Lung transplantation for idiopathic pulmonary arterial hypertension has the highest reported postoperative mortality of all indications. Reasons lie in the complexity of treatment of these patients and the frequent occurrence of postoperative left ventricular failure. Transplantation on intraoperative extracorporeal membrane oxygenation support instead of cardiopulmonary bypass and even more the prolongation of extracorporeal membrane oxygenation into the postoperative period helps to overcome these problems. We reviewed our experience with this concept. All patients undergoing bilateral lung transplantation for idiopathic pulmonary arterial hypertension on intraoperative extracorporeal membrane oxygenation with or without prophylactic extracorporeal membrane oxygenation prolongation into the postoperative period between January 2000 and December 2014 were retrospectively analysed. Forty-one patients entered the study. Venoarterial extracorporeal membrane oxygenation support was prolonged into the postoperative period for a median of 2.5 days (range 1-40). Ninety-day, 1-, 3- and 5-year survival rates for the patient collective were 92.7%, 90.2%, 87.4% and 87.4%, respectively. When compared with 31 patients with idiopathic pulmonary arterial hypertension transplanted in the same period of time without prolongation of extracorporeal membrane oxygenation into the postoperative period, the results compared favourably (83.9%, 77.4%, 77.4%, and 77.4%; P = 0.189). Furthermore, these results are among the best results ever reported for this particularly difficult patient population. Bilateral lung transplantation for idiopathic pulmonary arterial hypertension with intraoperative venoarterial extracorporeal membrane oxygenation support seems to provide superior outcome compared with the results reported about the use of cardiopulmonary bypass. Prophylactic prolongation of venoarterial extracorporeal membrane oxygenation into the early postoperative period provides

QTc-prolonging drugs and hospitalizations for cardiac arrhythmias

NARCIS (Netherlands)

De Bruin, ML; Hoes, AW; Leufkens, HGM

2003-01-01

Cardiac arrhythmia as an adverse effect of noncardiac drugs has been an issue of growing importance during the past few years. In this population-based study, we evaluated the risk for serious cardiac arrhythmias during the use of several noncardiac QTc-prolonging drugs in day-to-day practice, and

Qingyihuaji Formula Inhibits Pancreatic Cancer and Prolongs Survival by Downregulating Hes-1 and Hey-1

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Yanli Xu

2015-01-01

Full Text Available The dire prognosis of pancreatic cancer has not markedly improved during past decades. The present study was carried out to explore the effect of Qingyihuaji formula (QYHJ on inhibiting pancreatic cancer and prolonging survival in related Notch signaling pathway. Proliferation of pancreatic cancer cells (SW1990 and PANC-1 was detected by MTT assay at 24, 48, and 72 h with exposure to various concentrations (0.08–50 mg/mL of QYHJ water extract. Pancreatic tumor models of nude mice were divided into three groups randomly (control, QYHJ, and gemcitabine. mRNA and protein expression of Notch target genes (Hes-1, Hey-1, Hey-2, and Hey-L in dissected tumor tissue were detected. Results showed that proliferation of SW1990 cells and PANC-1 cells was inhibited by QYHJ water extract in a dose-dependent and time-dependent manner. QYHJ effectively inhibited tumor growth and prolonged survival time in nude mice. Expression of both Hes-1 and Hey-1 was decreased significantly in QYHJ group, suggesting that Hes-1 and Hey-1 in Notch signaling pathway might be potential targets for QYHJ treatment. This research could help explain the clinical effectiveness of QYHJ and may provide advanced pancreatic cancer patients with a new therapeutic option.

Patients with prolonged effect of succinylcholine or mivacurium had novel mutations in the butyrylcholinesterase gene

DEFF Research Database (Denmark)

Wichmann, Sine; Færk, Gitte; Bundgaard, Jens R.

2016-01-01

with prolonged duration of action to succinylcholine and mivacurium. Patients were studied if they had equivocal phenotypes on the basis of BChE activity, biochemical inhibitor reactions and with pedigree if possible. Complete nucleotide sequencing was performed to describe the genotype and pedigree was used......Introduction Mutations in the butyrylcholinesterase enzyme (BChE) can result in prolonged duration of action of the neuromuscular blocking agents, succinylcholine and mivacurium, as BChE hydrolyses these drugs. Hereditary low BChE activity can cause extensively prolonged apnoea during general...... anaesthesia when these drugs are used. The aim of this study was to describe novel mutations in the butyrylcholinesterase gene (BCHE) in patients who have experienced prolonged duration of action of mivacurium or succinylcholine. Methods The Danish Cholinesterase Research Unit registers patients...

Depressive disorders during weaning from prolonged mechanical ventilation.

Science.gov (United States)

Jubran, Amal; Lawm, Gerald; Kelly, Joanne; Duffner, Lisa A; Gungor, Gokay; Collins, Eileen G; Lanuza, Dorothy M; Hoffman, Leslie A; Tobin, Martin J

2010-05-01

Patients who require mechanical ventilation are at risk of emotional stress because of total dependence on a machine for breathing. The stress may negatively impact ventilator weaning and survival. The purpose of this study was to determine whether depressive disorders in patients being weaned from prolonged mechanical ventilation are linked to weaning failure and decreased survival. A prospective study of 478 consecutive patients transferred to a long-term acute care hospital for weaning from prolonged ventilation was undertaken. A clinical psychologist conducted a psychiatric interview to assess for the presence of depressive disorders. Of the 478 patients, 142 had persistent coma or delirium and were unable to be evaluated for depressive disorders. Of the remaining 336 patients, 142 (42%) were diagnosed with depressive disorders. In multivariate analysis, co-morbidity score [odds ratio (OR), 1.23; P = 0.007], functional dependence before the acute illness (OR, 1.70, P = 0.03) and history of psychiatric disorders (OR, 3.04, P = 0.0001) were independent predictors of depressive disorders. The rate of weaning failure was higher in patients with depressive disorders than in those without such disorders (61 vs. 33%, P = 0.0001), as was mortality (24 vs. 10%, P = 0.0008). The presence of depressive disorders was independently associated with mortality (OR, 4.3; P = 0.0002); age (OR, 1.06; P = 0.001) and co-morbidity score (OR, 1.24; P = 0.02) also predicted mortality. Depressive disorders were diagnosed in 42% of patients who were being weaned from prolonged ventilation. Patients with depressive disorders were more likely to experience weaning failure and death.

Pharmacokinetics of prolonged-release tacrolimus and implications for use in solid organ transplant recipients.

Science.gov (United States)

Tanzi, Maria G; Undre, Nasrullah; Keirns, James; Fitzsimmons, William E; Brown, Malcolm; First, M Roy

2016-08-01

Prolonged-release tacrolimus was developed as a once-daily formulation with ethylcellulose as the excipient, resulting in slower release and reduction in peak concentration (Cmax ) for a given dose compared with immediate-release tacrolimus, which is administered twice daily. This manuscript reviews pharmacokinetic information on prolonged-release tacrolimus in healthy subjects, in transplant recipients converted from immediate-release tacrolimus, and in de novo kidney and liver transplant recipients. As with the immediate-release formulation, prolonged-release tacrolimus shows a strong correlation between trough concentration (Cmin ) and area under the 24-hour time-concentration curve (AUC24 ), indicating that trough whole blood concentrations provide an accurate measure of drug exposure. We present the pharmacokinetic similarities and differences between the two formulations, so that prescribing physicians will have a better understanding of therapeutic drug monitoring in patients receiving prolonged-release tacrolimus. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Sequential Proximal Tibial Stress Fractures associated with Prolonged usage of Methotrexate and Corticosteroids: A Case Report

Directory of Open Access Journals (Sweden)

Tan TJL

2015-11-01

Full Text Available Stress fractures of the proximal tibia metaphysis are rare in the elderly. We present a case of a 65-year old male who developed sequential proximal tibia stress fractures associated with prolonged usage of methotrexate and prednisolone within a span of 18 months. Magnetic Resonance Imaging revealed an incomplete stress fracture involving the medial proximal tibial region. The patient was treated with stemmed total knee arthroplasty (TKA bilaterally. Stress fractures should be considered in patients with atypical knee pain who have a history of methotrexate and prednisolone usage. TKA is an effective treatment in stress fractures of the proximal tibia.

Ciprofloxacin does not Prolong the QTc Interval : A Clinical Study in ICU Patients and Review of the Literature

NARCIS (Netherlands)

Heemskerk, Charlotte P.M.; Woldman, Evelien; Pereboom, Marieke; van der Hoeven, Ruud T M; Mantel-Teeuwisse, Aukje; Van Gemeren, Claudia; Becker, Matthijs Lambertus

2017-01-01

PURPOSE: Ciprofloxacin may prolong the QT interval and increase the risk of Torsade de Pointes (TdP). Intravenous administration of ciprofloxacin in patients with additional risks may elevate the risk of QTc interval prolongation. We prospectively assessed whether intravenous ciprofloxacin prolongs

Glucocorticoid augmentation of prolonged exposure therapy: rationale and case report

Directory of Open Access Journals (Sweden)

Laura Pratchett

2010-12-01

Full Text Available Rationale: Prolonged exposure (PE therapy has been found to reduce symptoms of posttraumatic stress disorder (PTSD; however, it is difficult for many patients to engage fully in the obligatory retelling of their traumatic experiences. This problem is compounded by the fact that habituation and cognitive restructuring – the main mechanisms through which PE is hypothesized to work – are not instantaneous processes, and often require several weeks before the distress associated with imaginal exposure abates. Case reports: Two cases are described that respectively illustrate the use of hydrocortisone and placebo, in combination with PE, for the treatment of combat-related PTSD. Based on known effects of glucocorticoids on learning and memory performance, we hypothesized that augmentation with hydrocortisone would improve the therapeutic effects of PE by hastening “new” learning and facilitating decreases in the emotional impact of fear memories during the course of treatment. The veteran receiving hydrocortisone augmentation of PE displayed an accelerated and ultimately greater decline in PTSD symptoms than the veteran receiving placebo. Conclusions: While no general conclusion can be derived from comparison of two patients, the findings are consistent with the rationale for augmentation. These case reports support the potential for an appropriately designed and powered clinical trial to examine the efficacy of glucocorticoids in augmenting the effects of psychotherapy for PTSD.

Influence of prolonged cold ischemia in renal transplantation.

NARCIS (Netherlands)

Vliet, J.A. van der; Warle, M.C.; Cheung, C.L.; Teerenstra, S.; Hoitsma, A.J.

2011-01-01

van der Vliet JA, Warle MC, Cheung CLS, Teerenstra S, Hoitsma AJ. Influence of prolonged cold ischemia in renal transplantation. Clin Transplant 2011: 25: E612-E616. (c) 2011 John Wiley & Sons A/S. Abstract: Aim: To determine to what extent current cold ischemia times (CITs) affect the results of

Effect Of Prolonged Monocular Occlusion On Latent Nystagms

NARCIS (Netherlands)

H.J. Simonsz (Huib); G. Kommerell (Guntram)

1992-01-01

textabstractThe authors recorded nystagmus during seeing with one eye in eight patients with latent nystagmus (LN) before and after two or three days of prolonged occlusion of the better eye (POBE). Before POBE, the slow-phase speed of the nystagmus (SPS) was usually higher when the better eye was

Secondary bacteraemia in adult patients with prolonged dengue fever.

Science.gov (United States)

Premaratna, R; Dissanayake, D; Silva, F H D S; Dassanayake, M; de Silva, H J

2015-03-01

Although dengue management guidelines do not advice on use of antibiotics in dengue shock syndrome, unrecognised bactraemia is likely to contribute to morbidity and mortality. To assess the occurance of secondary bacteraemia in adult patients with prolonged dengue fever. A prospective study was conducted recruiting patients with confirmed acute dengue infection who had prolonged fever (>5 days). Two sets of blood cultures were taken in such patients prior to institution of antibiotic therapy. Demographic, clinical, haematological and biochemical parameters were recorded. Development of ascites and pleural effusions were detected using ultrasonography. Fourty patients (52.5% males) with a mean age of 29.8 years (SD 13.6) were studied. The average duration of fever was 7.9 days (SD 1.8). Ten patients (25%) had bacterial isolates in their blood cultures; Staphylococcus aureus (n=2), coliforms (n=3), pseudomonas (n=1) and 4 had mixed growths. The culture positive group had severe body aches at admission and higher fever, third space fluid accumulation, a significant drop in platelets and a higher CRP. A quarter of dengue patients with prolonged fever had a bacterial isolate. Culture positive patients appeared more ill with body aches and had higher degrees of fever during the latter part of the illness. Increased vascular permeability may predispose to bacterial seepage into blood. Although white cell count is not helpful in detecting bacteraemia, low platelet count and elevation of CRP seem to be helpful.

Prolonged Screen Viewing Times and Sociodemographic Factors among Pregnant Women: A Cross-Sectional Survey in China

Directory of Open Access Journals (Sweden)

Xianglong Xu

2018-02-01

Full Text Available Objectives: This study aimed to assess the prevalence of prolonged television, computer, and mobile phone viewing times and examined related sociodemographic factors among Chinese pregnant women. Methods: In this study, a cross-sectional survey was implemented among 2400 Chinese pregnant women in 16 hospitals of 5 provinces from June to August in 2015, and the response rate of 97.76%. We excluded women with serious complications and cognitive disorders. The women were asked about their television, computer, and mobile phone viewing during pregnancy. Prolonged television watching or computer viewing was defined as spending more than two hours on television or computer viewing per day. Prolonged mobile phone viewing was watching more than one hour on mobile phone per day. Results: Among 2345 pregnant women, about 25.1% reported prolonged television viewing, 20.6% reported prolonged computer viewing, and 62.6% reported prolonged mobile phone viewing. Pregnant women with long mobile phone viewing times were likely have long TV (Estimate = 0.080, Standard Error (SE = 0.016, p < 0.001 and computer viewing times (Estimate = 0.053, SE = 0.022, p = 0.015. Pregnant women with long TV (Estimate = 0.134, SE = 0.027, p < 0.001 and long computer viewing times (Estimate = 0.049, SE = 0.020, p = 0.015 were likely have long mobile phone viewing times. Pregnant women with long TV viewing times were less likely to have long computer viewing times (Estimate = −0.032, SE = 0.015, p = 0.035, and pregnant women with long computer viewing times were less likely have long TV viewing times (Estimate = −0.059, SE = 0.028, p = 0.035. Pregnant women in their second pregnancy had lower prolonged computer viewing times than those in their first pregnancy (Odds Ratio (OR 0.56, 95% Confidence Interval (CI 0.42–0.74. Pregnant women in their second pregnancy were more likely have longer prolonged mobile phone viewing times than those in their first pregnancy (OR 1.25, 95

Prolonged bone marrow T1-relaxation in patients with polycythemia vera

DEFF Research Database (Denmark)

Jensen, K E; Grube, T; Thomsen, C

1988-01-01

In vitro as well as in vivo studies have shown prolonged T1 relaxation times in patients with acute leukemia. The mechanism behind this finding is not known. In order to evaluate if this was specific for leukemia we examined eight patients with polycythemia vera, representing a condition with a r......In vitro as well as in vivo studies have shown prolonged T1 relaxation times in patients with acute leukemia. The mechanism behind this finding is not known. In order to evaluate if this was specific for leukemia we examined eight patients with polycythemia vera, representing a condition...

Prognostic Significance Of QT Interval Prolongation In Adult ...

African Journals Online (AJOL)

Prognostic survival studies for heart-rate corrected QT interval in patients with chronic heart failure are few; although these patients are known to have a high risk of sudden cardiac death. This study was aimed at determining the mortality risk associated with prolonged QTc in Nigerians with heart failure. Ninety-six ...

Emerging drugs and alternative possibilities in the treatment of tuberculosis

NARCIS (Netherlands)

Hofman, S.; Segers, M.M.; Ghimire, S.; Bolhuis, M.S.; Sturkenboom, M.G.; Soolingen, D. van; Alffenaar, J.W.

2016-01-01

INTRODUCTION: Tuberculosis (TB) remains a global health problem. Drug resistance, treatment duration, complexity, and adverse drug reactions associated with anti-TB regimens are associated with treatment failure, prolonged infectiousness and relapse. With the current set of anti-TB drugs the goal to

Emerging drugs and alternative possibilities in the treatment of tuberculosis

NARCIS (Netherlands)

Hofman, S.; Segers, M. M.; Ghimire, S.; Bolhuis, M. S.; Sturkenboom, M. G. G.; Van Soolingen, D.; Alffenaar, J. W. C.

2016-01-01

Introduction: Tuberculosis (TB) remains a global health problem. Drug resistance, treatment duration, complexity, and adverse drug reactions associated with anti-TB regimens are associated with treatment failure, prolonged infectiousness and relapse. With the current set of anti-TB drugs the goal to

A tumor-targeting p53 nanodelivery system limits chemoresistance to temozolomide prolonging survival in a mouse model of glioblastoma multiforme.

Science.gov (United States)

Kim, Sang-Soo; Rait, Antonina; Kim, Eric; Pirollo, Kathleen F; Chang, Esther H

2015-02-01

Development of temozolomide (TMZ) resistance contributes to the poor prognosis for glioblastoma multiforme (GBM) patients. It was previously demonstrated that delivery of exogenous wild-type tumor suppressor gene p53 via a tumor-targeted nanocomplex (SGT-53) which crosses the blood-brain barrier could sensitize highly TMZ-resistant GBM tumors to TMZ. Here we assessed whether SGT-53 could inhibit development of TMZ resistance. SGT-53 significantly chemosensitized TMZ-sensitive human GBM cell lines (U87 and U251), in vitro and in vivo. Furthermore, in an intracranial GBM tumor model, two cycles of concurrent treatment with systemically administered SGT-53 and TMZ inhibited tumor growth, increased apoptosis and most importantly, significantly prolonged median survival. In contrast TMZ alone had no significant effect on median survival compared to a single cycle of TMZ. These results suggest that combining SGT-53 with TMZ appears to limit development of TMZ resistance, prolonging its anti-tumor effect and could be a more effective therapy for GBM. Using human glioblastoma multiforma cell lines, this research team demonstrated that the delivery of exogenous wild-type tumor suppressor gene p53 via a tumor-targeted nanocomplex limited the development of temozolomide resistance and prolonged its anti-tumor effect, which may enable future human application of this or similar techniques. Copyright © 2015 Elsevier Inc. All rights reserved.

Ringer's lactate, but not hydroxyethyl starch, prolongs the food intolerance time after major abdominal surgery; an open-labelled clinical trial.

Science.gov (United States)

Li, Yuhong; He, Rui; Ying, Xiaojiang; Hahn, Robert G

2015-05-06

The infusion of large amounts of Ringer's lactate prolongs the functional gastrointestinal recovery time and increases the number of complications after open abdominal surgery. We performed an open-labelled clinical trial to determine whether hydroxyethyl starch or Ringer's lactate exerts these adverse effects when the surgery is performed by laparoscopy. Eighty-eight patients scheduled for major abdominal cancer surgery (83% by laparoscopy) received a first-line fluid treatment with 9 ml/kg of either 6% hydroxyethyl starch 130/0.4 (Voluven) or Ringer's lactate, just after induction of anaesthesia; this was followed by a second-line infusion with 12 ml/kg of either starch or Ringer's lactate over 1 hour. Further therapy was managed at the discretion of the attending anaesthetist. Outcome data consisted of postoperative gastrointestinal recovery time, complications and length of hospital stay. The order of the infusions had no impact on the outcome. Both the administration of ≥ 2 L of Ringer's lactate and the development of a surgical complication were associated with a longer time period of paralytic ileus and food intolerance (two-way ANOVA, P food intolerance time amounted to 2 days each. The infusion of ≥ 1 L of hydroxyethyl starch did not adversely affect gastrointestinal recovery. Ringer's lactate, but not hydroxyethyl starch, prolonged the gastrointestinal recovery time in patients undergoing laparoscopic cancer surgery. Surgical complications prolonged the hospital stay.

"Prolonged grief disorder" and "persistent complex bereavement disorder", but not "complicated grief", are one and the same diagnostic entity : an analysis of data from the Yale Bereavement Study

NARCIS (Netherlands)

Maciejewski, Paul K; Maercker, Andreas; Boelen, Paul A|info:eu-repo/dai/nl/174011954; Prigerson, Holly G

2016-01-01

There exists a general consensus that prolonged grief disorder (PGD), or some variant of PGD, represents a distinct mental disorder worthy of diagnosis and treatment. Nevertheless, confusion remains over whether different names and proposed symptom criteria for this disorder identify the same or

Safety information on QT-interval prolongation : comparison of European Union and United States drug labeling

NARCIS (Netherlands)

Warnier, Miriam J.; Holtkamp, Frank A.; Rutten, Frans H.; Hoes, Arno W.; de Boer, Anthonius; Mol, Peter G M; De Bruin, Marie L.

Prolongation of the QT interval can predispose to fatal ventricular arrhythmias. Differences in QT-labeling language can result in miscommunication and suboptimal risk mitigation. We systematically compared the phraseology used to communicate on QT-prolonging properties of 144 drugs newly approved

Safety information on QT-interval prolongation : Comparison of European Union and United States drug labeling

NARCIS (Netherlands)

Warnier, Miriam J.; Holtkamp, Frank A.; Rutten, Frans H.; Hoes, Arno W.; de Boer, Anthonius; Mol, Peter G. M.; De Bruin, Marie L.

Prolongation of the QT interval can predispose to fatal ventricular arrhythmias. Differences in QT-labeling language can result in miscommunication and suboptimal risk mitigation. We systematically compared the phraseology used to communicate on QT-prolonging properties of 144 drugs newly approved

Public stigma of prolonged grief disorder : An experimental study

NARCIS (Netherlands)

Eisma, Maarten C.

Prolonged grief disorder (PGD), characterized by severe, persistent and disabling grief, is being considered for inclusion in the International Classification of Diseases’ 11 (ICD-11) and a related disorder, Persistent Complex Bereavement Disorder (PCBD), is included for further investigation in the

Protection of Dentate Hilar Cells from Prolonged Stimulation by Intracellular Calcium Chelation

Science.gov (United States)

Scharfman, Helen E.; Schwartzkroin, Philip A.

1989-10-01

Prolonged afferent stimulation of the rat dentate gyrus in vivo leads to degeneration only of those cells that lack immunoreactivity for the calcium binding proteins parvalbumin and calbindin. In order to test the hypothesis that calcium binding proteins protect against the effects of prolonged stimulation, intracellular recordings were made in hippocampal slices from cells that lack immunoreactivity for calcium binding proteins. Calcium binding protein--negative cells showed electrophysiological signs of deterioration during prolonged stimulation; cells containing calcium binding protein did not. When neurons without calcium binding proteins were impaled with microelectrodes containing the calcium chelator BAPTA, and BAPTA was allowed to diffuse into the cells, these cells showed no deterioration. These results indicate that, in a complex tissue of the central nervous system, an activity-induced increase in intracellular calcium can trigger processes leading to cell deterioration, and that increasing the calcium binding capacity of a cell decreases its vulnerability to damage.

Prolonged Intrauterine Retention of Foetal Bones after Midtrimester ...

African Journals Online (AJOL)

Prolonged retention of foetal bones in the uterus is a rare complication of induced abortion. We present the case of a 37 year old nullipara with retained foetal bones following a second trimester induced abortion. Accurate diagnosis and removal of the bony fragments led to restoration of fertility and subsequent delivery of a ...

Characterizing prolonged heat effects on mortality in a sub-tropical high-density city, Hong Kong

Science.gov (United States)

Ho, Hung Chak; Lau, Kevin Ka-Lun; Ren, Chao; Ng, Edward

2017-11-01

Extreme hot weather events are likely to increase under future climate change, and it is exacerbated in urban areas due to the complex urban settings. It causes excess mortality due to prolonged exposure to such extreme heat. However, there is lack of universal definition of prolonged heat or heat wave, which leads to inadequacies of associated risk preparedness. Previous studies focused on estimating temperature-mortality relationship based on temperature thresholds for assessing heat-related health risks but only several studies investigated the association between types of prolonged heat and excess mortality. However, most studies focused on one or a few isolated heat waves, which cannot demonstrate typical scenarios that population has experienced. In addition, there are limited studies on the difference between daytime and nighttime temperature, resulting in insufficiency to conclude the effect of prolonged heat. In sub-tropical high-density cities where prolonged heat is common in summer, it is important to obtain a comprehensive understanding of prolonged heat for a complete assessment of heat-related health risks. In this study, six types of prolonged heat were examined by using a time-stratified analysis. We found that more consecutive hot nights contribute to higher mortality risk while the number of consecutive hot days does not have significant association with excess mortality. For a day after five consecutive hot nights, there were 7.99% [7.64%, 8.35%], 7.74% [6.93%, 8.55%], and 8.14% [7.38%, 8.88%] increases in all-cause, cardiovascular, and respiratory mortality, respectively. Non-consecutive hot days or nights are also found to contribute to short-term mortality risk. For a 7-day-period with at least five non-consecutive hot days and nights, there was 15.61% [14.52%, 16.70%] increase in all-cause mortality at lag 0-1, but only -2.00% [-2.83%, -1.17%] at lag 2-3. Differences in the temperature-mortality relationship caused by hot days and hot nights

Antioxidant dietary approach in treatment of fatty liver: New insights and updates.

Science.gov (United States)

Ferramosca, Alessandra; Di Giacomo, Mariangela; Zara, Vincenzo

2017-06-21

Non-alcoholic fatty liver disease (NAFLD) is a common clinicopathological condition, encompassing a range of conditions caused by lipid deposition within liver cells. To date, no approved drugs are available for the treatment of NAFLD, despite the fact that it represents a serious and growing clinical problem in the Western world. Identification of the molecular mechanisms leading to NAFLD-related fat accumulation, mitochondrial dysfunction and oxidative balance impairment facilitates the development of specific interventions aimed at preventing the progression of hepatic steatosis. In this review, we focus our attention on the role of dysfunctions in mitochondrial bioenergetics in the pathogenesis of fatty liver. Major data from the literature about the mitochondrial targeting of some antioxidant molecules as a potential treatment for hepatic steatosis are described and critically analysed. There is ample evidence of the positive effects of several classes of antioxidants, such as polyphenols ( i.e ., resveratrol, quercetin, coumestrol, anthocyanins, epigallocatechin gallate and curcumin), carotenoids ( i.e ., lycopene, astaxanthin and fucoxanthin) and glucosinolates ( i.e ., glucoraphanin, sulforaphane, sinigrin and allyl-isothiocyanate), on the reversion of fatty liver. Although the mechanism of action is not yet fully elucidated, in some cases an indirect interaction with mitochondrial metabolism is expected. We believe that such knowledge will eventually translate into the development of novel therapeutic approaches for fatty liver.

Sodium valproate for the treatment of mania in a patient with Charcot ...

African Journals Online (AJOL)

and the treatment thereof with sodium valproate. Mr. L, a 28 ... prolonged distal latencies, decreased compound muscle action ... 1000mg per day for treatment of mania. ... dystrophy, facio-scapulo-humeral dystrophy, and hereditary motor and.

Nationwide analysis of prolonged hospital stay and readmission after elective ventral hernia repair

DEFF Research Database (Denmark)

Helgstrand, Frederik; Rosenberg, Jacob; Kehlet, Henrik

2011-01-01

Early outcome after elective ventral hernia repair is unsatisfactory, but detailed analyses are lacking. The aim of this study was to describe the aetiology of prolonged hospital stay (LOS), readmission and death <30 days after elective ventral hernia repair.......Early outcome after elective ventral hernia repair is unsatisfactory, but detailed analyses are lacking. The aim of this study was to describe the aetiology of prolonged hospital stay (LOS), readmission and death

Topical Drug Formulations for Prolonged Corneal Anesthesia

Science.gov (United States)

Wang, Liqiang; Shankarappa, Sahadev A.; Tong, Rong; Ciolino, Joseph B.; Tsui, Jonathan H.; Chiang, Homer H.; Kohane, Daniel S.

2013-01-01

Purpose Ocular local anesthetics (OLA’s) currently used in routine clinical practice for corneal anesthesia are short acting and their ability to delay corneal healing makes them unsuitable for long-term use. In this study, we examined the effect on the duration of corneal anesthesia of the site-1 sodium channel blocker tetrodotoxin (TTX), applied with either proparacaine or the chemical permeation enhancer OTAB. The effect of test solutions on corneal healing was also studied. Methods Solutions of TTX, proparacaine, and OTAB, singly or in combination were applied topically to the rat cornea. The blink response, an indirect measure of corneal sensitivity, was recorded using a Cochet-Bonnet esthesiometer, and the duration of corneal anesthesia calculated. The effect of test compounds on the rate of corneal epithelialization was studied in vivo following corneal debridement. Results Combination of TTX and proparacaine resulted in corneal anesthesia that was 8–10 times longer in duration than that from either drug administered alone, while OTAB did not prolong anesthesia. The rate of corneal healing was moderately delayed following co-administration of TTX and proparacaine. Conclusion Co-administration of TTX and proparacaine significantly prolonged corneal anesthesia but in view of delayed corneal re-epithelialization, caution is suggested in use of the combination. PMID:23615270

The peculiarity of aerobic energy supply of rat tissues of different age upon prolonged ionizing and thermal exposure

International Nuclear Information System (INIS)

Tsyhun, G.F.

1998-01-01

Energy-producing functions of brain, myocardium, and hepatic mitochondria in mature and immature rats in remote period after prolonged ionizing X-ray at total dose 12,9 m C/kg and thermal exposure (4 hours, 37 degrees centigrade, 25 times) were studied. Dehydrogenase activities (pyruvate-, isocitrate-, 2-oxy glutarate-, succinate- and malate dehydrogenases) were reduced in mitochondria of different tissues of adult rats and it was especially considerable after combined influence. A higher resistance of young rats, as compared to adult ones, to combined radiation-thermal treatments was established

ESCHARS TREATMENT

Directory of Open Access Journals (Sweden)

Cioc Liliana

2012-02-01

Full Text Available This article carry out a modern research and principles of the main solutions for the treatment of eschars, including cleaning solutions for wound debridement, dressings, antibiotics, surgery and adjuvant therapies. The approach taken to achieve the research is justified by the fact that, despite current interest and progress in medicine, surgery, medical care and education for self-care, pressure sores remain a major cause of morbidity and mortality, affecting in particular, people with prolonged immobilization and the elderly. The conclusions of the paper are oriented towards to analysis of the efficiency of each treatment solutions presented in active control eschars and negative effects they generate.

Preferences for Prolonging Life: A Prospect Theory Approach

Science.gov (United States)

Winter, Laraine; Lawton, M. Powell; Ruckdeschel, Katy

2003-01-01

Kahneman and Tversky's (1979) Prospect theory was tested as a model of preferences for prolonging life under various hypothetical health statuses. A sample of 384 elderly people living in congregate housing (263 healthy, 131 frail) indicated how long (if at all) they would want to live under each of nine hypothetical health conditions (e.g.,…

Differential modulation of dibenzo[def,p]chrysene transplacental carcinogenesis: Maternal diets rich in indole-3-carbinol versus sulforaphane

Energy Technology Data Exchange (ETDEWEB)

Shorey, Lyndsey E.; Madeen, Erin P. [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR, 97331 (United States); Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331 (United States); Atwell, Lauren L.; Ho, Emily [Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331 (United States); School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, 97331 (United States); Löhr, Christiane V. [Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331 (United States); College of Veterinary Medicine, Oregon State University, Corvallis, OR, 97331 (United States); Pereira, Clifford B. [Department of Statistics, Oregon State University, Corvallis, OR, 97331 (United States); Dashwood, Roderick H. [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR, 97331 (United States); Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331 (United States); Williams, David E., E-mail: david.williams@oregonstate.edu [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR, 97331 (United States); Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331 (United States)

2013-07-01

Cruciferous vegetable components have been documented to exhibit anticancer properties. Targets of action span multiple mechanisms deregulated during cancer progression, ranging from altered carcinogen metabolism to the restoration of epigenetic machinery. Furthermore, the developing fetus is highly susceptible to changes in nutritional status and to environmental toxicants. Thus, we have exploited a mouse model of transplacental carcinogenesis to assess the impact of maternal dietary supplementation on cancer risk in offspring. In this study, transplacental and lactational exposure to a maternal dose of 15 mg/Kg B.W. of dibenzo[def,p]chrysene (DBC) resulted in significant morbidity of offspring due to an aggressive T-cell lymphoblastic lymphoma. As in previous studies, indole-3-carbinol (I3C, feed to the dam at 100, 500 or 1000 ppm), derived from cruciferous vegetables, dose-dependently reduced lung tumor multiplicity and also increased offspring survival. Brussels sprout and broccoli sprout powders, selected for their relative abundance of I3C and the bioactive component sulforaphane (SFN), respectively, surprisingly enhanced DBC-induced morbidity and tumorigenesis when incorporated into the maternal diet at 10% wt/wt. Purified SFN, incorporated in the maternal diet at 400 ppm, also decreased the latency of DBC-dependent morbidity. Interestingly, I3C abrogated the effect of SFN when the two purified compounds were administered in equimolar combination (500 ppm I3C and 600 ppm SFN). SFN metabolites measured in the plasma of neonates positively correlated with exposure levels via the maternal diet but not with offspring mortality. These findings provide justification for further study of the safety and bioactivity of cruciferous vegetable phytochemicals at supplemental concentrations during the perinatal period. - Highlights: • Dietary supplementation may modulate cancer risk in a mouse model of lymphoma. • Cruciferous vegetables may not contain sufficient I3C

Differential modulation of dibenzo[def,p]chrysene transplacental carcinogenesis: Maternal diets rich in indole-3-carbinol versus sulforaphane

International Nuclear Information System (INIS)

Shorey, Lyndsey E.; Madeen, Erin P.; Atwell, Lauren L.; Ho, Emily; Löhr, Christiane V.; Pereira, Clifford B.; Dashwood, Roderick H.; Williams, David E.

2013-01-01

Cruciferous vegetable components have been documented to exhibit anticancer properties. Targets of action span multiple mechanisms deregulated during cancer progression, ranging from altered carcinogen metabolism to the restoration of epigenetic machinery. Furthermore, the developing fetus is highly susceptible to changes in nutritional status and to environmental toxicants. Thus, we have exploited a mouse model of transplacental carcinogenesis to assess the impact of maternal dietary supplementation on cancer risk in offspring. In this study, transplacental and lactational exposure to a maternal dose of 15 mg/Kg B.W. of dibenzo[def,p]chrysene (DBC) resulted in significant morbidity of offspring due to an aggressive T-cell lymphoblastic lymphoma. As in previous studies, indole-3-carbinol (I3C, feed to the dam at 100, 500 or 1000 ppm), derived from cruciferous vegetables, dose-dependently reduced lung tumor multiplicity and also increased offspring survival. Brussels sprout and broccoli sprout powders, selected for their relative abundance of I3C and the bioactive component sulforaphane (SFN), respectively, surprisingly enhanced DBC-induced morbidity and tumorigenesis when incorporated into the maternal diet at 10% wt/wt. Purified SFN, incorporated in the maternal diet at 400 ppm, also decreased the latency of DBC-dependent morbidity. Interestingly, I3C abrogated the effect of SFN when the two purified compounds were administered in equimolar combination (500 ppm I3C and 600 ppm SFN). SFN metabolites measured in the plasma of neonates positively correlated with exposure levels via the maternal diet but not with offspring mortality. These findings provide justification for further study of the safety and bioactivity of cruciferous vegetable phytochemicals at supplemental concentrations during the perinatal period. - Highlights: • Dietary supplementation may modulate cancer risk in a mouse model of lymphoma. • Cruciferous vegetables may not contain sufficient I3C

Intravenous Poison Hemlock Injection Resulting in Prolonged Respiratory Failure and Encephalopathy.

Science.gov (United States)

Brtalik, Douglas; Stopyra, Jason; Hannum, Jennifer

2017-06-01

Poison hemlock (Conium maculatum) is a common plant with a significant toxicity. Data on this toxicity is sparse as there have been few case reports and never a documented poisoning after intravenous injection. We present a case of intravenous poison hemlock injection encountered in the emergency department. We describe a 30-year-old male who presented to the emergency department after a brief cardiac arrest after injecting poison hemlock. The patient had return of spontaneous circulation in the emergency department but had prolonged muscular weakness and encephalopathy later requiring tracheostomy. Intravenous injection of poison hemlock alkaloids can result in significant toxicity, including cardiopulmonary arrest, prolonged weakness, and encephalopathy.

Feasibility of proton pencil beam scanning treatment of free-breathing lung cancer patients

NARCIS (Netherlands)

Jakobi, Annika; Perrin, Rosalind; Knopf, Antje; Richter, Christian

BACKGROUND: The interplay effect might degrade the dose of pencil beam scanning proton therapy to a degree that free-breathing treatment might be impossible without further motion mitigation techniques, which complicate and prolong the treatment. We assessed whether treatment of free-breathing

Effects of strict prolonged bed rest on cardiorespiratory fitness