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Sample records for long-term daily administration

  1. [Behavior of acid secretion under the long-term daily administration of omeprazol].

    PubMed

    Dammann, H G; Müller, P; Seitz, H K; Simon, B

    1983-06-18

    The effect of the substituted benzimidazole omeprazole on acid secretion after repeated administration to healthy volunteers has been studied. During repeated dosage of 30 mg once daily inhibition of basal and pentagastrin-stimulated acid output was increased from 30% after the first dose to about 60% after dose 4. The extent of inhibition did not further increase between day 5 and day 10. In four volunteers acid secretion returned to predose levels within 5 days after drug withdrawal. The 24-hour gastric acidity was reduced by about 72% and 82% after 9-day pretreatment with 30 mg and 60 mg omeprazole respectively. The antisecretory effect of omeprazole was independent of peak plasma concentrations. Omeprazole given once daily therefore possesses a long-lasting effect on gastric acid secretion, i.e. for more than 24 hours. This effect appears to be fully reversible since control levels of acid output are reached within 5 days.

  2. Lack of tissue accumulation of grape seed flavanols after daily long-term administration in healthy and cafeteria-diet obese rats.

    PubMed

    Margalef, Maria; Pons, Zara; Iglesias-Carres, Lisard; Bravo, Francisca Isabel; Muguerza, Begoña; Arola-Arnal, Anna

    2015-11-18

    After ingestion flavanols are metabolized by phase-II enzymes and the microbiota and are distributed throughout the body depending on several factors. Herein we aim to evaluate whether flavanols are tissue-accumulated after the long-term administration of a grape seed polyphenol extract (GSPE) in rats and to study if compounds present in tissues differ in a cafeteria-diet obesity state. For that, plasma, liver, mesenteric white adipose tissue (MWAT), brain, and aorta flavanol metabolites from standard chow-diet-fed (ST) and cafeteria-diet-fed (CAF) rats were analyzed by high-performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) 21 h after the last 12-week-daily GSPE (100 mg/kg) dosage. Results showed that long-term GSPE intake did not trigger a flavanol tissue accumulation, indicating a clearance of products at each daily dosage. Therefore, results suggest that polyphenol benefits in a disease state would be due to a daily pulsatile effect. Moreover, obesity induced by diet also influences the metabolism and bioavailability of flavanols in rats.

  3. Effects of Long-Term Daily Administration of Prostaglandin-E2 on Maintaining Elevated Proximal Tibial Metaphyseal Cancellous Bone Mass in Male Rats

    NASA Technical Reports Server (NTRS)

    Ke, Hua Zhu; Jee, Webster S. S.; Mori, Satoshi; Li, Xiao Jian; Kimmel, Donald B.

    1992-01-01

    The effects of long-term prostaglandin E(sub 2) (PGE(sub 2)) on cancellous bone in proximal tibial metaphysis were studied in 7 month old male Sprague-Dawley rats given daily subcutaneous injections of 0, 1, 3, and 6 mg PGE(sub 2)/kg/day and sacrificed after 60, 120, and 180 days. Histomorphometric analyses were performed on double fluorescent-labeled undecalcified bone specimens. After 60 days of treatment, PGE(sub 2) produced diffusely labeled trabecular bone area, increased trabecular bone area, eroded and labeled trabecular perimeter, mineral apposition rate, and bone formation rate at all dose levels when compared with age-matched controls. In rats given PGE(sub 2) for longer time periods (120 and 180 days), trabecular bone area, diffusely labeled trabecular bone area, labeled perimeter, mineral apposition, and bone formation rates were sustained at the elevated levels achieved earlier at 60-day treatment. The eroded perimeter continued to increase until 120 days, then plateau. The observation that continuous systemic PGE(sub 2) administration to adult male rats elevated metaphyseal cancellous bone mass to 3.5-fold of the control level within 60 days and maintained it for another 120 days indicates that the powerful skeletal anabolic effects of PGE2 can be sustained with continuous administration .

  4. A retrospective cohort study of long-term immediate-release hydrocodone/acetaminophen use and acetaminophen dosing above the Food and Drug Administration recommended maximum daily limit among commercially insured individuals in the United States (2008-2013).

    PubMed

    DeVeaugh-Geiss, Angela; Kadakia, Aditi; Chilcoat, Howard; Alexander, Louis; Coplan, Paul

    2015-06-01

    Immediate-release (IR) hydrocodone/acetaminophen is the most prescribed opioid in the United States; however, patterns of use, including long-term treatment and dose, are not well described. Duration of use, including the percentage of patients on long-term treatment (>90 days of continuous use), was assessed for patients newly prescribed IR hydrocodone/acetaminophen compared to other opioid analgesics in a national commercial insurance database (January 2008-September 2013). Though only a small percentage of IR hydrocodone/acetaminophen patients continued treatment long-term (1.7%), the number was large (104,839) and was nearly 5 times the number receiving extended-release (ER) morphine (n = 22,338) and nearly 4 times the number receiving ER oxycodone (n = 26,946) long-term. Using a less conservative allowable gap in treatment increased the number of patients meeting the criteria for long-term use (approximately 160,000 for IR hydrocodone/acetaminophen vs <30,000 for ER morphine and ER oxycodone). Most patients meeting these criteria received IR hydrocodone doses between >20 and ≤60 mg/d (n = 56,220, 53.6%) in month 4; 5.5% (n = 5,743) received doses >60 mg/d. Moreover, approximately 15% of IR hydrocodone/acetaminophen patients (n > 900,000) were prescribed total daily acetaminophen doses exceeding 4 g (the limit recommended by the U.S. Food and Drug Administration) at their initial IR hydrocodone/acetaminophen prescription or any time during therapy. Although most patients were prescribed IR hydrocodone/acetaminophen for acute pain, the number of patients prescribed long-term therapy exceeds the number of patients prescribed ER opioids. It is important to consider the benefits and risks inherent with long-term opioid therapy, whether with IR or ER opioids, to ensure safe use of these products. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Effects of Long-Term Ayahuasca Administration on Memory and Anxiety in Rats.

    PubMed

    Favaro, Vanessa Manchim; Yonamine, Maurício; Soares, Juliana Carlota Kramer; Oliveira, Maria Gabriela Menezes

    2015-01-01

    Ayahuasca is a hallucinogenic beverage that combines the action of the 5-HT2A/2C agonist N,N-dimethyltryptamine (DMT) from Psychotria viridis with the monoamine oxidase inhibitors (MAOIs) induced by beta-carbonyls from Banisteriopsis caapi. Previous investigations have highlighted the involvement of ayahuasca with the activation of brain regions known to be involved with episodic memory, contextual associations and emotional processing after ayahuasca ingestion. Moreover long term users show better performance in neuropsychological tests when tested in off-drug condition. This study evaluated the effects of long-term administration of ayahuasca on Morris water maze (MWM), fear conditioning and elevated plus maze (EPM) performance in rats. Behavior tests started 48h after the end of treatment. Freeze-dried ayahuasca doses of 120, 240 and 480 mg/kg were used, with water as the control. Long-term administration consisted of a daily oral dose for 30 days by gavage. The behavioral data indicated that long-term ayahuasca administration did not affect the performance of animals in MWM and EPM tasks. However the dose of 120 mg/kg increased the contextual conditioned fear response for both background and foreground fear conditioning. The tone conditioned response was not affected after long-term administration. In addition, the increase in the contextual fear response was maintained during the repeated sessions several weeks after training. Taken together, these data showed that long-term ayahuasca administration in rats can interfere with the contextual association of emotional events, which is in agreement with the fact that the beverage activates brain areas related to these processes.

  6. Effects of Long-Term Ayahuasca Administration on Memory and Anxiety in Rats

    PubMed Central

    Favaro, Vanessa Manchim; Yonamine, Maurício; Soares, Juliana Carlota Kramer; Oliveira, Maria Gabriela Menezes

    2015-01-01

    Ayahuasca is a hallucinogenic beverage that combines the action of the 5-HT2A/2C agonist N,N-dimethyltryptamine (DMT) from Psychotria viridis with the monoamine oxidase inhibitors (MAOIs) induced by beta-carbonyls from Banisteriopsis caapi. Previous investigations have highlighted the involvement of ayahuasca with the activation of brain regions known to be involved with episodic memory, contextual associations and emotional processing after ayahuasca ingestion. Moreover long term users show better performance in neuropsychological tests when tested in off-drug condition. This study evaluated the effects of long-term administration of ayahuasca on Morris water maze (MWM), fear conditioning and elevated plus maze (EPM) performance in rats. Behavior tests started 48h after the end of treatment. Freeze-dried ayahuasca doses of 120, 240 and 480 mg/kg were used, with water as the control. Long-term administration consisted of a daily oral dose for 30 days by gavage. The behavioral data indicated that long-term ayahuasca administration did not affect the performance of animals in MWM and EPM tasks. However the dose of 120 mg/kg increased the contextual conditioned fear response for both background and foreground fear conditioning. The tone conditioned response was not affected after long-term administration. In addition, the increase in the contextual fear response was maintained during the repeated sessions several weeks after training. Taken together, these data showed that long-term ayahuasca administration in rats can interfere with the contextual association of emotional events, which is in agreement with the fact that the beverage activates brain areas related to these processes. PMID:26716991

  7. The long-term safety of D-allulose administration in healthy dogs.

    PubMed

    Nishii, Naohito; Takashima, Satoshi; Kobatake, Yui; Tokuda, Masaaki; Kitagawa, Hitoshi

    2017-09-17

    The safety and biological effects of a long-term dose of D-allulose were evaluated in healthy dogs. For 12 weeks, the dogs were administered D-allulose (0.2 g/kg) or placebo daily. Plasma total cholesterol concentrations in the D-allulose group were significantly lower than those in the control group at and after week 2 (P<0.05). D-Allulose administration did not cause clinical signs or changes in hematological and biochemical levels, except for lipids. D-Allulose administration also did not influence body weight. Plasma glucose and insulin concentrations in the glucose tolerance test, performed one day after the termination of D-allulose administration, were not different between groups, suggesting no cumulative effects of D-allulose on glucose metabolism in healthy dogs. In conclusion, long-term administration of D-allulose caused no harmful effects in dogs.

  8. Thiamin metabolism in the rat during long term alcohol administration.

    PubMed

    Bitsch, R; Hansen, J; Hötzel, D

    1982-01-01

    In order to test the effect of a long term alcohol administration on the thiamin metabolism in blood, heart and liver under suboptimal supply, an experiment with rats was carried out over a period of 16 weeks. The suboptimal thiamin supply became visible mainly in the liver stores which were lowered during the whole test period. The unphosphorylated thiamin (T) of liver and heart was not detectable after 4 weeks up to the end of experiment. On the other hand the total thiamin concentration in the erythrocytes increased from the beginning due to an enhanced thiamin-diphosphate (TDP) and thiamintriphosphate (TTP) pool and T was lowered to undetectable amounts only after 16 weeks. In contrast, the alpha-TK in blood and liver was enhanced only after 2 and 4 weeks and tended to become normal by the end of the test period indicating an apoenzyme degeneration. Alcohol ingestion resulted in a general diminution of the total thiamin and the thiamin phosphates in blood, heart and liver and a reduced thiamin excretion in urine. An alcohol induced shift of the phosphorylation status could be observed only in the liver, but not in the heart and the erythrocytes, leading to a lowered concentration of T and TMP. The results demonstrate that the level of thiamin and thiamin phosphates in blood and organs under suboptimal thiamin supply seems to be more sensitive to chronic alcohol administration than the transketolase activity and the alpha-TK value.

  9. Long-term administration of mifepristone (RU486): clinical tolerance during extended treatment of meningioma.

    PubMed

    Grunberg, Steven M; Weiss, Martin H; Russell, Christy A; Spitz, Irving M; Ahmadi, Jamshid; Sadun, Alfredo; Sitruk-Ware, Regine

    2006-12-01

    Mifepristone (RU486) is an oral antiprogestational and, to a lesser extent, antiglucocorticoid agent commonly used for short-term (single-day) therapy. However, treatment of neoplasms or chronic conditions will require long-term administration. Meningioma is a benign central nervous system tumor that is often progesterone-but not estrogen-receptor positive, making long-term antiprogestational therapy a logical treatment strategy. Patients with unresectable meningioma were treated with oral mifepristone 200 mg/day. This dose was selected to provide significant antiprogestational but not antiglucocorticoid activity. Patients also received oral dexamethasone 1 mg/day for the first 14 days. Serial follow-up allowed evaluation for tolerability and side effects of long-term therapy as well as observation for efficacy (tumor shrinkage or improvement in visual fields). Twenty-eight patients received daily oral mifepristone for a total of 1,626 patient-months of treatment. The median duration of therapy was 35 months (range 2-157 months). Repeated oral administration was well tolerated with mild fatigue (22 patients), hot flashes (13 patients), and gynecomastia/breast tenderness (6 patients) being the most common side effects. However, endometrial hyperplasia or polyps were documented in 3 patients and one patient developed peritoneal adenocarcinoma after 9 years of therapy. Minor responses (improved automated visual field examination or improved CT or MRI scan) were noted in 8 patients, 7 of whom were male or premenopausal female. Long-term administration of mifepristone is feasible and clinically well tolerated, with generally mild toxicity. However, endometrial hyperplasia was noted in several patients. In view of the association between long-term treatment with tamoxifen (another agent that can induce an unopposed estrogen effect) and endometrial cancer, this observation will require further investigation and screening. Minor regression of meningioma that can result in

  10. Long-term oxytocin administration enhances the experience of attachment.

    PubMed

    Bernaerts, Sylvie; Prinsen, Jellina; Berra, Emmely; Bosmans, Guy; Steyaert, Jean; Alaerts, Kaat

    2017-04-01

    The neuropeptide 'oxytocin' (OT) is known to play a pivotal role in a variety of complex social behaviors by promoting a prosocial attitude and interpersonal bonding. Previous studies showed that a single-dose of exogenously administered OT can affect trust and feelings of attachment insecurity. With the present study, we explored the effects of two weeks of daily OT administration on measures of state and trait attachment using a double-blind between-subjects randomized placebo-controlled design. In 40 healthy young adult men state and trait attachment were assessed before and after two weeks of daily intranasal OT (24 IU) or placebo using the State Adult Attachment Scale and the Inventory of Parent and Peer Attachment. Mood, social responsiveness and quality of life were additionally assessed as secondary outcome measures. Reductions in attachment avoidance and increases in reports of attachment toward peers were reported after two weeks of OT treatment. Further, treatment-induced changes were most pronounced for participants with less secure attachment towards their peers. indicating that normal variance at baseline modulated treatment response. OT treatment was additionally associated with changes in mood, indicating decreases in feelings of tension and (tentatively) anger in the OT group, not in the placebo group. Further, at the end of the two-week trial, both treatment groups (OT, placebo) reported to experience an increase in social responsiveness and quality of life, but the effects were only specific to the OT-treatment in terms of reports on 'social motivation'. In summary, the observed improvements on state and trait dimensions of attachment after a multiple-dose treatment with OT provide further evidence in support of a pivotal role of OT in promoting the experience of attachment.

  11. Interest in Long-Term Care among Health Services Administration Students

    ERIC Educational Resources Information Center

    Temple, April; Thompson, Jon M.

    2011-01-01

    The aging of the population has created increased opportunities for health administrators in long-term care. This study consisted of a cross-sectional survey of 68 undergraduate health services administration students to explore factors related to interest in a career in long-term care administration. One third expressed interest working in the…

  12. Interest in Long-Term Care among Health Services Administration Students

    ERIC Educational Resources Information Center

    Temple, April; Thompson, Jon M.

    2011-01-01

    The aging of the population has created increased opportunities for health administrators in long-term care. This study consisted of a cross-sectional survey of 68 undergraduate health services administration students to explore factors related to interest in a career in long-term care administration. One third expressed interest working in the…

  13. Growth hormone response to long-term GH-RH administration in lambs.

    PubMed

    Pérez-Romero, A; Rol De Lama, M A; Granados, B; Vara, E; Vázquez González, I; Ariznavarreta, C; Tresguerres, J A

    2000-06-01

    The pattern of long-term GHRH administration capable of stimulating GH release without depleting pituitary GH content has been investigated using two experimental approaches. In experiment 1, recently weaned male lambs were treated for 3 weeks as follows: Group A) control; B) subcutaneous (sc) continuous infusion of GHRH (1200 mg/day) using a slow release pellet; C) the same as B plus 1 daily sc injection of long acting somatostatin (SS) (octreotide, 20 mg) ; D) 3 daily sc GHRH (250 mg) injections ; E) 2 daily sc injections of GHRH (250 mg) and 2 of natural SS (250 mg). In experiment 2, recently weaned male lambs were continuously GHRH-treated using sc osmotic minipumps (900 mg/day) alone or combined with a daily sc injection of octreotide (20 mg) for 4 weeks. Basal plasma GH levels were increased after chronic pulsatile GHRH treatment but not after any kind of continuous GHRH administration. This increment was maintained during the 3 weeks of experimentation and appeared accompanied by a pituitary GH content similar to controls. A marked GH response to the iv GHRH challenge was observed in controls and in lambs receiving both types of continuous sc GHRH infusions, whereas pulsatile sc GHRH-treated animals did not respond to the iv GHRH challenge in the first and second weeks of the study but did so in the third week of treatment. These data demonstrate that long-term pulsatile GHRH administration is capable of stimulating GH release in growing male lambs, without producing pituitary desensitization.

  14. Cardiotoxicity in rabbits after long-term nandrolone decanoate administration.

    PubMed

    Vasilaki, Fotini; Tsitsimpikou, Christina; Tsarouhas, Konstantinos; Germanakis, Ioannis; Tzardi, Marias; Kavvalakis, Matthaios; Ozcagli, Eren; Kouretas, Dimitrios; Tsatsakis, Aristidis M

    2016-01-22

    Abuse of anabolic androgenic steroids is linked to a variety of cardiovascular complications. The aim of our study was to investigate the possible cardiovascular effects of nandrolone decanoate on young rabbits using echocardiography, histology and monitoring of telomerase activity, oxidative stress and biochemical markers. Fourteen rabbits were divided into three administration groups and the control group. Doses of 4mg/kg and 10mg/kg of nandrolone decanoate, given intramuscularly and subcutaneously, two days per week for six months were applied. A 4-months wash-out period followed. Focal fibrosis and inflammatory infiltrations of cardiac tissue were observed in the high dose groups. Thiobarbituric acid-reactive species (TBARS) levels were significantly increased in the high dose groups, while catalase activity decreased. Myocardial Performance Index (MPI) is the main echocardiographic index primarily affected by nandrolone administration in rabbits. Despite the preserved systolic performance, histological lesions observed associated with distorted MPI values, point to diastolic impairment of the thickened myocardium due to nandrolone treatment. Oxidative stress accumulates and telomerase activity in cardiac tissue rises. Subcutaneous administration seems to be more deleterious to the cardiovascular system, as oxidative stress, telomerase activity and biochemical markers do not appear to return into normal values in the wash-out period.

  15. Paradoxical enhancement of active cochlear mechanics in long-term administration of salicylate.

    PubMed

    Huang, Zhi-Wu; Luo, Yanyun; Wu, Zhanyuan; Tao, Zhezhang; Jones, Raleigh O; Zhao, Hong-Bo

    2005-04-01

    Aspirin (salicylate) is a common drug and frequently used long term in the clinic. It has been well documented that salicylate can cause reversible hearing loss and tinnitus and diminish outer hair cell (OHC) electromotility, which is capable of actively boosting the basilar membrane vibration and producing acoustic emission. However, aspirin's ototoxic mechanisms still remain largely unclear. In this experiment, the effects of long-term salicylate administration on cochlear hearing functions were investigated by measuring distortion product otoacoustic emissions (DPOAEs) in awake guinea pigs. A single injection of sodium salicylate (200 mg/kg) could reduce the amplitude of the cubic distortion product of 2f1-f2 within 2 h. The reduction was significant at 20-50 dB SPL stimulus levels and recovered after 8 h. However, following daily injections of sodium salicylate (200 mg/kg, b.i.d.), the distortion product of 2f1-f2 progressively increased. After injection for 14 days, the distortion product increased about 2-3.5 dB SPL. The increase rate was about 0.2 dB SPL/day. The DP-I/O function remained nonlinear. The increase was greater at 40-70 dB SPL primary sound intensities and reversible. After cessation of salicylate treatment for 4 wk, the increased distortion product returned to the initial normal levels. The rate of recovery was 0.1 dB SPL/day. In the control animals with saline injection, there was no change in DPOAEs. The data revealed that long-term administration of salicylate could paradoxically enhance active cochlear mechanics. The data also suggested that salicylate-induced tinnitus might be generated at the OHC level.

  16. Action Planning for Daily Mouth Care in Long-Term Care: The Brushing Up on Mouth Care Project

    PubMed Central

    McNally, Mary E.; Martin-Misener, Ruth; Wyatt, Christopher C. L.; McNeil, Karen P.; Crowell, Sandra J.; Matthews, Debora C.; Clovis, Joanne B.

    2012-01-01

    Research focusing on the introduction of daily mouth care programs for dependent older adults in long-term care has met with limited success. There is a need for greater awareness about the importance of oral health, more education for those providing oral care, and organizational structures that provide policy and administrative support for daily mouth care. The purpose of this paper is to describe the establishment of an oral care action plan for long-term care using an interdisciplinary collaborative approach. Methods. Elements of a program planning cycle that includes assessment, planning, implementation, and evaluation guided this work and are described in this paper. Findings associated with assessment and planning are detailed. Assessment involved exploration of internal and external factors influencing oral care in long-term care and included document review, focus groups and one-on-one interviews with end-users. The planning phase brought care providers, stakeholders, and researchers together to design a set of actions to integrate oral care into the organizational policy and practice of the research settings. Findings. The establishment of a meaningful and productive collaboration was beneficial for developing realistic goals, understanding context and institutional culture, creating actions suitable and applicable for end-users, and laying a foundation for broader networking with relevant stakeholders and health policy makers. PMID:22550572

  17. Action planning for daily mouth care in long-term care: the brushing up on mouth care project.

    PubMed

    McNally, Mary E; Martin-Misener, Ruth; Wyatt, Christopher C L; McNeil, Karen P; Crowell, Sandra J; Matthews, Debora C; Clovis, Joanne B

    2012-01-01

    Research focusing on the introduction of daily mouth care programs for dependent older adults in long-term care has met with limited success. There is a need for greater awareness about the importance of oral health, more education for those providing oral care, and organizational structures that provide policy and administrative support for daily mouth care. The purpose of this paper is to describe the establishment of an oral care action plan for long-term care using an interdisciplinary collaborative approach. Methods. Elements of a program planning cycle that includes assessment, planning, implementation, and evaluation guided this work and are described in this paper. Findings associated with assessment and planning are detailed. Assessment involved exploration of internal and external factors influencing oral care in long-term care and included document review, focus groups and one-on-one interviews with end-users. The planning phase brought care providers, stakeholders, and researchers together to design a set of actions to integrate oral care into the organizational policy and practice of the research settings. Findings. The establishment of a meaningful and productive collaboration was beneficial for developing realistic goals, understanding context and institutional culture, creating actions suitable and applicable for end-users, and laying a foundation for broader networking with relevant stakeholders and health policy makers.

  18. Long-term drug administration in the adult zebrafish using oral gavage for cancer preclinical studies

    PubMed Central

    Dang, Michelle; Henderson, Rachel E.; Garraway, Levi A.

    2016-01-01

    ABSTRACT Zebrafish are a major model for chemical genetics, and most studies use embryos when investigating small molecules that cause interesting phenotypes or that can rescue disease models. Limited studies have dosed adults with small molecules by means of water-borne exposure or injection techniques. Challenges in the form of drug delivery-related trauma and anesthesia-related toxicity have excluded the adult zebrafish from long-term drug efficacy studies. Here, we introduce a novel anesthetic combination of MS-222 and isoflurane to an oral gavage technique for a non-toxic, non-invasive and long-term drug administration platform. As a proof of principle, we established drug efficacy of the FDA-approved BRAFV600E inhibitor, Vemurafenib, in adult zebrafish harboring BRAFV600E melanoma tumors. In the model, adult casper zebrafish intraperitoneally transplanted with a zebrafish melanoma cell line (ZMEL1) and exposed to daily sub-lethal dosing at 100 mg/kg of Vemurafenib for 2 weeks via oral gavage resulted in an average 65% decrease in tumor burden and a 15% mortality rate. In contrast, Vemurafenib-resistant ZMEL1 cell lines, generated in culture from low-dose drug exposure for 4 months, did not respond to the oral gavage treatment regimen. Similarly, this drug treatment regimen can be applied for treatment of primary melanoma tumors in the zebrafish. Taken together, we developed an effective long-term drug treatment system that will allow the adult zebrafish to be used to identify more effective anti-melanoma combination therapies and opens up possibilities for treating adult models of other diseases. PMID:27482819

  19. Evaluation of a Baccalaureate External Degree Program in Health Services Administration with a Major in Long Term Care Administration.

    ERIC Educational Resources Information Center

    Kleppick, Annabelle L.; And Others

    The development and evaluation of a nontraditional program with a major in Long Term Care Administration is presented. Part 1 presents an evaluation of the impact of the program on students, faculty, the curricula for long term care administration, and in the field of practice. Student characteristics are established and the performance of the…

  20. Cardiovascular effects of long-term caffeine administration in aged rats.

    PubMed

    El Agaty, S M T; Seif, A A

    2015-06-01

    To evaluate the possible beneficial effect of long-term caffeine administration on cardiovascular system in aged rats. This study was carried out on 20 senile male albino rats, aged 18-20 months. Rats were divided into caffeine-treated group, which received 25 mg/kg caffeine by gavage daily for 6 weeks, and control group. All rats were subjected to the following in vivo measurements: body weight, arterial blood pressure, heart rate and ECG recording. In vitro measurements included studying isolated hearts in a Langendorff apparatus for their intrinsic properties as well as plasma levels of lipids, malondialdehyde and nitrate. Caffeine administration to aged rats significantly enhanced the baseline and maximum values achieved in response to isoproterenol infusion in isolated heart preparation for both maximum rate of tension development (dT/dt max) and time to peak tension (TPT). The responses of hearts isolated from caffeine group to the three doses of isoproterenol infusion also showed a significantly higher dT/dt max with shorter TPT and half relaxation time (1/2 RT) compared to controls. Plasma nitrate was significantly increased and ECG recording was nonsignificantly affected in caffeine group. The plasma levels of total cholesterol, LDL cholesterol as well as in vivo heart rate and systolic, diastolic and mean arterial blood pressures were all significantly increased associated with a significant decrease in HDL cholesterol in caffeine group. Long-term caffeine administration in aged rats increased cardiac inotropy, lusitropy and preserved NO level, which points to a promising potential favorable effect on cardiac intrinsic properties.

  1. An Educational Needs Assessment of Long Term Care Administrative Personnel in the Commonwealth of Pennsylvania.

    ERIC Educational Resources Information Center

    Kleppick, Annabelle L.; Costanzo, Nancy L.

    The Graduate School of Public Health, University of Pittsburgh, directed its efforts towards providing continuing education courses to enable long term care administrators to qualify for relicensure in accordance with Pennsylvania's requirements. Because of the diversity of administrators' educational background, more data were needed to establish…

  2. 1989 Management Seminars for the New York Association of Long Term Care Administrators.

    ERIC Educational Resources Information Center

    Towne, Violet A.

    The collaboration between the continuing education arm of the State University of New York Institute of Technology at Utica/Rome and the New York Association for Long Term Care Administrators in the design, development and delivery of educational programs for nursing home and adult home administrators in New York State is reported. Program content…

  3. Effect of acute and long-term administration of gold nanoparticles on biochemical parameters in rat brain.

    PubMed

    Ferreira, Gabriela K; Cardoso, Eria; Vuolo, Francieli Silva; Galant, Letícia Selinger; Michels, Monique; Gonçalves, Cinara L; Rezin, Gislaine Tezza; Dal-Pizzol, Felipe; Benavides, Roberto; Alonso-Núñez, Gabriel; Andrade, Vanessa Moraes; Streck, Emilio L; da Silva Paula, Marcos Marques

    2017-10-01

    The present study investigated stress oxidative parameters and activities of enzymes of the energy metabolism in various brain structures. Rats were subjected to acute and long-term administration of gold nanoparticles (GNPs) with mean diameters of 10nm and 30nm. Adult (60days old) male Wistar rats received a single intraperitoneal injection (acute administration; 70μg·kg(-1)) or repeated injections once daily for 28days (long-term administration; 70μg·kg(-1)) of saline solution or GNPs (10nm or 30nm). Twenty-four hours after administration of the final dose, the animals were killed and the cerebral structures were isolated for enzyme analysis. In this study, we observed that the thiobarbituric acid-reactive species and carbonyl protein levels were decreased after acute administration of GNPs, whereas the superoxide dismutase activity was increased after acute and long-term of GNPs. The catalase activity was affected by the administration of GNPs. Furthermore, we have not found change in the citrate synthase activity. The succinate dehydrogenase, malate dehydrogenase, complexes I, II, II-III and IV, and creatine kinase activities were altered. These results indicate that inhibition energy metabolism can be caused by oxidative stress. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Chronic alcohol self-administration in monkeys shows long-term quantity/frequency categorical stability.

    PubMed

    Baker, Erich J; Farro, Jonathan; Gonzales, Steven; Helms, Christa; Grant, Kathleen A

    2014-11-01

    The current criteria for alcohol use disorders (AUDs) do not include consumption (quantity/frequency) measures of alcohol intake, in part due to the difficulty of these measures in humans. Animal models of ethanol (EtOH) self-administration have been fundamental in advancing our understanding of the neurobiological basis of AUD and can address quantity/frequency measures with accurate measurements over prolonged periods of time. The nonhuman primate model of voluntary oral alcohol self-administration has documented both binge drinking and drinking to dependence and can be used to test the stability of consumption measures over time. Here, an extensive set of alcohol intakes (g/kg/d) was analyzed from a large multi-cohort population of Rhesus (Macaca mulatta) monkeys (n = 31). Daily EtOH intake was uniformly distributed over chronic (12 months) access for all animals. Underlying this distribution of intakes were subpopulations of monkeys that exhibited distinctive clustering of drinking patterns, allowing us to categorically define very heavy drinking (VHD), heavy drinking (HD), binge drinking (BD), and low drinking (LD). These categories were stable across the 12 months assessed by the protocol, but exhibited fluctuations when examined at shorter intervals. The establishment of persistent drinking categories based on quantity/frequency suggests that consumption variables can be used to track long-term changes in behavioral, molecular, or physiochemical mechanisms related to our understanding of diagnosis, prevention, intervention, and treatment efficacies. Copyright © 2014 by the Research Society on Alcoholism.

  5. Chronic alcohol self-administration in monkeys shows long-term quantity/frequency categorical stability

    PubMed Central

    Baker, Erich J.; Farro, Jonathan; Gonzales, Steven; Helms, Christa; Grant, Kathleen A.

    2014-01-01

    Background The current criteria for alcohol use disorders (AUD) do not include consumption (quantity/frequency) measures of alcohol intake, in part due to the difficulty of these measures in humans. Animal models of ethanol self-administration have been fundamental in advancing our understanding of the neurobiological basis of (AUD) and can address quantity/frequency measures with accurate measurements over prolonged periods of time. The non-human primate (NHP) model of voluntary oral alcohol self-administration has documented both binge drinking and drinking to dependence and can be used to test the stability of consumption measures over time. Methods and Results Here, an extensive set of alcohol intakes (g/kg/day) was analyzed from a large multi-cohort population of Rhesus (Macaca mulatta) monkeys (n=31). Daily ethanol intake was uniformly distributed over chronic (12 months) access for all animals. Underlying this distribution of intakes were subpopulations of monkeys that exhibited distinctive clustering of drinking patterns, allowing us to categorically define very heavy drinking (VHD), heavy drinking (HD), binge drinking (BD), and low drinking (LD). These categories were stable across the 12-month assessed by the protocol, but exhibited fluctuations when examined at shorter intervals. Conclusions The establishment of persistent drinking categories based on quantity/frequency suggests that consumption variables can be used to track long-term changes in behavioral, molecular or physiochemical mechanisms related to our understanding of diagnosis, prevention, intervention and treatment efficacies. PMID:25421519

  6. Daily life physical activity in long-term survivors of nephroblastoma and neuroblastoma.

    PubMed

    van Waas, Marjolein; Wijnen, Mark; Hartman, Annelies; de Vries, Andrica C H; Pieters, Rob; Neggers, Sebastian J C M M; van den Heuvel-Eibrink, Marry M

    2013-07-01

    The risk of metabolic late effects after childhood cancer, such as obesity, hypertension, and diabetes, can be positively influenced by a healthy lifestyle with sufficient physical activity. Nevertheless, studies on physical activity in adult survivors of childhood cancer are scarce and involve different and often nonvalidated questionnaires. We used the Short QUestionnaire to ASsess Health-enhancing physical activity (SQUASH), which was developed and validated to assess daily life physical activity in the Dutch adult population. The aim of the study was to assess daily life physical activity in Dutch adult long-term nephroblastoma and neuroblastoma survivors. Sixty-seven nephroblastoma and 36 neuroblastoma survivors (median age, 30 y; range, 18 to 51 y) and 60 sociodemographically similar healthy control subjects (median age, 32 y; range, 18 to 62 y) were asked to complete the SQUASH during their regular follow-up visit. The adjusted mean physical activity score in male neuroblastoma survivors (mean, 7155; P=0.004) was significantly lower than in male controls (mean, 10,574), whereas it was not significantly lower in male nephroblastoma survivors (mean, 9122; P=0.108). Adjusted means for physical activity scores in females were not different from their controls. In conclusions, male neuroblastoma survivors were identified as performing less daily physical activity.

  7. Adverse performance effects of acute lorazepam administration in elderly long-term users: pharmacokinetic and clinical predictors

    PubMed Central

    Pomara, Nunzio; Lee, Sang Han; Bruno, Davide; Silber, Timothy; Greenblatt, David J.; Petkova, Eva; Sidtis, John J.

    2014-01-01

    Background The benzodiazepine lorazepam is widely utilized in the treatment of elderly individuals with anxiety disorders and related conditions. Negative effects of acute lorazepam administration on cognitive performance, especially memory, have been reported in both previously untreated elderly and in individuals who have received short term (up to three weeks) treatment with therapeutic doses. However, it remains unclear if these adverse cognitive effects also persist after long-term use, which is frequently found in clinical practice. Methods Cognitively intact elderly individuals (n=37) on long-term (at least three months) daily treatment with lorazepam were studied using a double-blind placebo-controlled cross-over study design. Subjects were administered their highest daily unit dose of lorazepam (0.25 – 3.00 mg) orplacebo on different days, approximately 1 week apart in a random order, and were assessed on memory, psychomotor speed, and subjective mood states Results Subjects had significantly poorer recall and slowed psychomotor performance following acute lorazepam administration. There were no significant effects on self-ratings of mood, sedation, or anxiety in the whole group, but secondary analyses suggested a differential response in subjects with Generalized Anxiety Disorder. Conclusions The reduced recall and psychomotor slowing that we observed, along with an absence of significant therapeutic benefits, following acute lorazepam administration in elderly long-term users reinforces the importance of cognitive toxicity as a clinical factor in benzodiazepine use, especially in this population. PMID:25195839

  8. Development of a Self-Assessment Tool to Facilitate Decision-Making in Choosing a Long Term Care Administration Major

    ERIC Educational Resources Information Center

    Johs-Artisensi, Jennifer L.; Olson, Douglas M.; Nahm, Abraham Y.

    2016-01-01

    Long term care administrators need a broad base of knowledge, skills, and interests to provide leadership and be successful in managing a fiscally responsible, quality long term care organization. Researchers developed a tool to help students assess whether a long term care administration major is a compatible fit. With input from professionals in…

  9. Development of a Self-Assessment Tool to Facilitate Decision-Making in Choosing a Long Term Care Administration Major

    ERIC Educational Resources Information Center

    Johs-Artisensi, Jennifer L.; Olson, Douglas M.; Nahm, Abraham Y.

    2016-01-01

    Long term care administrators need a broad base of knowledge, skills, and interests to provide leadership and be successful in managing a fiscally responsible, quality long term care organization. Researchers developed a tool to help students assess whether a long term care administration major is a compatible fit. With input from professionals in…

  10. Assessment of the appropriateness of naloxone administration to patients receiving long-term opioid therapy.

    PubMed

    Facey, Caroline; Brooks, David; Boland, Jason W

    2016-01-01

    The most dangerous adverse effect of opioids is respiratory depression. Naloxone is used to reverse this, although in patients receiving long-term opioid therapy it can cause acute opioid withdrawal and opioid-refractory pain. To determine if naloxone is appropriately administered to patients receiving long-term opioid therapy. This retrospective case series based on chart reviews systematically identified patients over one year in a district general hospital. All patients aged 18 years or older receiving long-term opioid therapy admitted to medicine, surgery or the high dependency unit who were administered naloxone during their admission were included. A total of 1206 patient drug administration records were reviewed. Sixteen patients receiving long-term opioid therapy were administered naloxone. Twelve of these did not have opioid-induced respiratory depression and four did not have respiratory rate and oxygen saturations documented in the medical notes. All naloxone doses administered were higher than those recommended by national guidelines for this patient group. No patient receiving long-term opioid therapy who was administered naloxone had evidence of respiratory depression. More thorough assessment and documentation are needed. Verbal and physical stimulation as well as oxygenation should be considered prior to naloxone administration; this should be followed by close observation, hydration, renal function tests and opioid dose review.

  11. Myocardial lesions after long-term administration of methamphetamine in rats.

    PubMed

    Yi, Shao-hua; Ren, Liang; Yang, Tian-tong; Liu, Liang; Wang, Han; Liu, Qian

    2008-12-01

    To demonstrate the myocardial lesion associated with long-term administration of methamphetamine in rats. The experimental models of intoxication of methamphetamine were established in Sprague-Dawley rats. Methamphetamine hydrochloride (3 mg x kg(-1) x d(-1)) was subcutaneously injected to rats in methamphetamine-treated group (n = 16), and normal saline at the same dose was injected to rats in control group (n = 16). After 1 week and 8 weeks of injection, 8 rats in each group were sacrificed and their hearts were examined with light microscopy and electron microscopy, respectively. After 1 week of methamphetamine exposure, foci of contraction band and cellular degeneration were present in subendocardial myocardium. Cellular degeneration, myocytolysis, and contraction band necrosis became prominent and extensive in methamphetamine-treated rats after 8 weeks. Hypertrophy, intracellular vacuolization, and fibrosis were also observed. The ultrastructural feature showed marked swelling and degeneration of mitochondria, enlargement of sarcoplasmic reticulum, and dissolution of myofilaments. No obvious cardiac myocyte lesions were observed in rats of control group. Methamphetamine abuse daily for a long time may result in an increased risk of cardiovascular lesions similar to cardiomyopathy.

  12. 42 CFR 488.446 - Administrator sanctions: long-term care facility closures.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 false Administrator sanctions: long-term care facility closures. 488.446 Section 488.446 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) STANDARDS AND CERTIFICATION SURVEY, CERTIFICATION, AND...

  13. Cessation of Long-term Naltrexone Administration: Longitudinal Follow-Ups.

    ERIC Educational Resources Information Center

    Crews, W. David, Jr.; Rhodes, Robert D.; Bonaventura, Sharon H.; Rowe, Frederick B.; Goering, Aaron M.

    1999-01-01

    Longitudinal follow-ups of the cessation of long-term Naltrexone administration were conducted with a women with profound mental retardation who had previously displayed dramatic decreases in self-injurious behavior (SIB). After two and four years post-Naltrexone therapy, the subject exhibited near-zero rates of SIB despite changes in staff and in…

  14. Long-term effects of daily postprandial physical activity on blood glucose: a randomized controlled trial.

    PubMed

    Nygaard, Håvard; Grindaker, Eirik; Rønnestad, Bent Ronny; Holmboe-Ottesen, Gerd; Høstmark, Arne Torbjørn

    2017-04-01

    Previous studies have shown that a bout of moderate or light postprandial physical activity effectively blunts the postprandial increase in blood glucose. The objective of this study was to test whether regular light postprandial physical activity can improve glycemia in persons with hyperglycemia or with a high risk of hyperglycemia. We randomized 56 participants to an intervention or a control group. They were diagnosed as hyperglycemic, not using antidiabetics, or were categorized as high-risk individuals for type 2 diabetes. The intervention group was instructed to undertake a minimum 30 min of daily light physical activity, starting a maximum of 30 min after a meal in addition to their usual physical activity for 12 weeks. The control group maintained their usual lifestyle. Blood samples were taken pre- and post-test. Forty participants completed the study and are included in the results. The self-reported increase in daily physical activity from before to within the study period was higher in the intervention group compared with control (41 ± 25 vs. 2 ± 16 min, p < 0.001). Activity diaries and accelerometer recordings supported this observation. The activity in the intervention group started earlier after the last meal compared with control (30 ± 13 vs. 100 ± 57 min, p = 0.001). There were no within- or between-group differences in any glycemic variable from pre- to post-test. In conclusion, the present study does not seem to support the notion that regular light postprandial physical activity improves blood glucose in the long term in persons with hyperglycemia or with high risk of hyperglycemia.

  15. Long-term oxytocin administration improves social behaviors in a girl with autistic disorder

    PubMed Central

    2012-01-01

    Background Patients with autism spectrum disorders (ASDs) exhibit core autistic symptoms including social impairments from early childhood and mostly show secondary disabilities such as irritability and aggressive behavior based on core symptoms. However, there are still no radical treatments of social impairments in these patients. Oxytocin has been reported to play important roles in multiple social behaviors dependent on social recognition, and has been expected as one of the effective treatments of social impairments of patients with ASDs. Case presentation We present a case of a 16-year-old girl with autistic disorder who treated by long-term administration of oxytocin nasal spray. Her autistic symptoms were successfully treated by two month administration; the girl’s social interactions and social communication began to improve without adverse effects. Her irritability and aggressive behavior also improved dramatically with marked decreases in aberrant behavior checklist scores from 69 to 7. Conclusion This case is the first to illustrate long-term administration of oxytocin nasal spray in the targeted treatment of social impairments in a female with autistic disorder. This case suggests that long-term nasal oxytocin spray is promising and well-tolerated for treatment of social impairments of patients with ASDs. PMID:22888794

  16. Long-term oxytocin administration improves social behaviors in a girl with autistic disorder.

    PubMed

    Kosaka, Hirotaka; Munesue, Toshio; Ishitobi, Makoto; Asano, Mizuki; Omori, Masao; Sato, Makoto; Tomoda, Akemi; Wada, Yuji

    2012-08-13

    Patients with autism spectrum disorders (ASDs) exhibit core autistic symptoms including social impairments from early childhood and mostly show secondary disabilities such as irritability and aggressive behavior based on core symptoms. However, there are still no radical treatments of social impairments in these patients. Oxytocin has been reported to play important roles in multiple social behaviors dependent on social recognition, and has been expected as one of the effective treatments of social impairments of patients with ASDs. We present a case of a 16-year-old girl with autistic disorder who treated by long-term administration of oxytocin nasal spray. Her autistic symptoms were successfully treated by two month administration; the girl's social interactions and social communication began to improve without adverse effects. Her irritability and aggressive behavior also improved dramatically with marked decreases in aberrant behavior checklist scores from 69 to 7. This case is the first to illustrate long-term administration of oxytocin nasal spray in the targeted treatment of social impairments in a female with autistic disorder. This case suggests that long-term nasal oxytocin spray is promising and well-tolerated for treatment of social impairments of patients with ASDs.

  17. The steps that can take us miles: Examining the short-term dynamics of long-term daily goal pursuit.

    PubMed

    Wilkowski, Benjamin M; Ferguson, Elizabeth Louise

    2016-04-01

    Cybernetic models suggest that to achieve one's long-term goals, one must create specific plans, enact these plan, monitor progress toward the goal, and resist temptations. Although many studies have examined these proposals in laboratory settings, few studies have examined such processes in daily life. This was the explicit purpose of the current investigation. Participants identified 4 long-term goals during an orientation session. They then completed a diary protocol in which they reported on these self-regulatory processes. The results were largely consistent with predictions. Of the 20 hypotheses examined, 17 were significant in the expected direction. For example, testing led to the initiation of long-term goal operations, which in turn led to goal progress. Likewise, temptations led to self-control operations, which in turn led to the successful resistance of temptations. The investigation thus suggests that cybernetic principles have broad relevance to understanding goal pursuit in daily life. (c) 2016 APA, all rights reserved).

  18. Withdrawal from long-term methamphetamine self-administration 'normalizes' neurometabolites in rhesus monkeys: a (1) H MR spectroscopy study.

    PubMed

    Yang, Shaolin; Belcher, Annabelle M; Chefer, Svetlana; Vaupel, D Bruce; Schindler, Charles W; Stein, Elliot A; Yang, Yihong

    2015-01-01

    (1) H magnetic resonance spectroscopy has demonstrated alterations in several neurometabolites in methamphetamine (METH)-dependent individuals in brain regions implicated in addiction. Yet, it is unclear whether these neurochemicals return to homeostatic levels after an individual abstains from drug use, a difficult question to address due to high recidivism and poor study retention in human subjects. We thus utilized a non-human primate model of addiction to explore the effects of long-term drug exposure and withdrawal on brain neurochemistry. Ten rhesus macaque monkeys on an active METH self-administration protocol (average use 4.6 ± 0.8 years, average daily intake between 0.4 and 1.2 mg/kg) and 10 age- and sex-matched drug-naive controls (CONT) served as subjects. Concentrations of several neurochemicals were evaluated at several timepoints following withdrawal from drug availability (10 monkeys at 1 week and 1 and 3 months, and 6 monkeys at 6 and 12 months; CONT examined at one timepoint). At 1 week following METH withdrawal, we found increases in myo-inositol in anterior cingulate cortex in the METH group relative to CONT. These alterations showed a linear pattern of decreased levels ('normalization') by 1 year of abstinence. We also found decreases in glutamine and Glx (composed mainly of glutamate and glutamine) in the caudate-putamen of the same animals at early withdrawal that showed a similar linear pattern of increasing concentration by 1 year. These results demonstrate that despite protracted, long-term use, neurochemical changes seen following long-term drug administration do not persist following prolonged abstinence, suggesting therapeutic effects of long-term withdrawal from drug use. © 2013 Society for the Study of Addiction.

  19. Long-term administration of inulin-type fructans has no significant lipid-lowering effect in normolipidemic humans.

    PubMed

    Forcheron, Fabien; Beylot, Michel

    2007-08-01

    Short-term studies have shown that the addition to diet of inulin-type fructans, a nondigestible carbohydrate, may have a plasma lipid-lowering effect in humans. Whether this beneficial effect persists during long-term administration has not been determined. The study was aimed at determining whether a prolonged (6 months) administration of inulin-type fructans to healthy subjects has a lipid-lowering action. In a double-blind, randomized, placebo-controlled study, 17 healthy subjects were studied before and after 6 months of daily administration of placebo (8 subjects) or 10 g of a mix of inulin and oligofructose (9 subjects). During this 6-month period, they consumed their usual diet and did not modify their everyday way of life. We measured plasma lipid concentrations; cholesterol synthesis and hepatic lipogenesis; and adipose tissue and circulating mononuclear cell messenger RNA concentrations of key regulatory genes of cholesterol metabolism. Compared with the administration of placebo, the administration of inulin-type fructans had no effect on plasma triacylglycerol concentrations and hepatic lipogenesis and induced only a nonsignificant trend for decreased plasma total and low-density lipoprotein cholesterol levels and increased high-density lipoprotein cholesterol concentration. Cholesterol synthesis was not significantly modified. Of all the messenger RNA concentrations measured, none was significantly modified by the administration of inulin-type fructans. In conclusion, contrary to what was observed in short-term studies, we observed no significant beneficial effect of a long-term (6-month) administration of inulin-type fructans on plasma lipids in healthy human subjects.

  20. Nurses' perceptions of and satisfaction with the medication administration system in long-term-care homes.

    PubMed

    Kaasalainen, Sharon; Agarwal, Gina; Dolovich, Lisa; Papaioannou, Alexandra; Brazil, Kevin; Akhtar-Danesh, Noori

    2010-12-01

    The purpose of this study was to explore nurses' perceptions of and level of satisfaction with the medication administration system in long-term care (LTC). The cross-sectional survey design included both quantitative and open-ended questions. Data were collected from licensed registered nurses (RNs) and registered practical nurses (RPNs) at 9 LTC residences in southwestern Ontario, Canada. Using independent sample t tests, the researchers found that RNs were significantly less satisfied than RPNs with their medication administration system, particularly with respect to safety issues. RNs identified a number of related barriers, including time constraints, poor packaging, insufficient drug information, prescription changes, lack of staff competency, and unwieldy medication carts. Implications for practice and policy are discussed, including recommendations for improving medication administration practices and for addressing the workload demands of LTC nurses.

  1. Time management and leadership styles: an empirical study of long-term health care administrators.

    PubMed

    Hartley, H J; Kramer, J A

    1991-01-01

    Is there a relationship between the type of leadership style employed by long-term health care administrators and the effective use and management of time? This paper describes a 1989 study of 188 administrators of skilled nursing facilities and intermediate care facilities in Connecticut. Two self-rating instruments were employed: the Executive Time Management Inventory (Hartley, Kramer, et al.) and the LEAD-Self instrument (Hersey and Blanchard). Four hypotheses were tested at the .05 level of significance to examine relationships among time management, leadership style, size of facility, administrator experience, and cost factors. Statistical procedures included Pearson Product-Moment correlations, analysis of variance, t-tests, and partial correlations. Results of the study included (1) time management effectiveness increased as administrators gained more experience; (2) no significant relationship existed between type of leadership style and time management effectiveness; (3) women administrators perceived themselves as significantly more effective time managers than men did; (4) most health care administrators employed the same primary leadership style: "selling," which is defined as high relationship/high task; and (5) institutional size was not related to the time management effectiveness of the administrator. The findings have implications for pre-service and in-service training and for future studies in health administration education.

  2. 41 CFR 301-11.14 - How is my daily lodging rate computed when I rent lodging on a long-term basis?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... rate computed when I rent lodging on a long-term basis? 301-11.14 Section 301-11.14 Public Contracts... computed when I rent lodging on a long-term basis? When you obtain lodging on a long-term basis (e.g., weekly or monthly) your daily lodging rate is computed by dividing the total lodging cost by the...

  3. Intrahippocampal glutamine administration inhibits mTORC1 signaling and impairs long-term memory

    PubMed Central

    Rozas, Natalia S.; Redell, John B.; Pita-Almenar, Juan D.; Mckenna, James; Moore, Anthony N.; Gambello, Michael J.

    2015-01-01

    The mechanistic Target of Rapamycin Complex 1 (mTORC1), a key regulator of protein synthesis and cellular growth, is also required for long-term memory formation. Stimulation of mTORC1 signaling is known to be dependent on the availability of energy and growth factors, as well as the presence of amino acids. In vitro studies using serum- and amino acid-starved cells have reported that glutamine addition can either stimulate or repress mTORC1 activity, depending on the particular experimental system that was used. However, these experiments do not directly address the effect of glutamine on mTORC1 activity under physiological conditions in nondeprived cells in vivo. We present experimental results indicating that intrahippocampal administration of glutamine to rats reduces mTORC1 activity. Moreover, post-training administration of glutamine impairs long-term spatial memory formation, while coadministration of glutamine with leucine had no influence on memory. Intracellular recordings in hippocampal slices showed that glutamine did not alter either excitatory or inhibitory synaptic activity, suggesting that the observed memory impairments may not result from conversion of glutamine to either glutamate or GABA. Taken together, these findings indicate that glutamine can decrease mTORC1 activity in the brain and may have implications for treatments of neurological diseases associated with high mTORC1 signaling. PMID:25878136

  4. Repeated Neonatal Propofol Administration Induces Sex-Dependent Long-Term Impairments on Spatial and Recognition Memory in Rats

    PubMed Central

    Gonzales, Edson Luck T.; Yang, Sung Min; Choi, Chang Soon; Mabunga, Darine Froy N.; Kim, Hee Jin; Cheong, Jae Hoon; Ryu, Jong Hoon; Koo, Bon-Nyeo; Shin, Chan Young

    2015-01-01

    Propofol is an anesthetic agent that gained wide use because of its fast induction of anesthesia and rapid recovery post-anesthesia. However, previous studies have reported immediate neurodegeneration and long-term impairment in spatial learning and memory from repeated neonatal propofol administration in animals. Yet, none of those studies has explored the sex-specific long-term physical changes and behavioral alterations such as social (sociability and social preference), emotional (anxiety), and other cognitive functions (spatial working, recognition, and avoidance memory) after neonatal propofol treatment. Seven-day-old Wistar-Kyoto (WKY) rats underwent repeated daily intraperitoneal injections of propofol or normal saline for 7 days. Starting fourth week of age and onwards, rats were subjected to behavior tests including open-field, elevated-plus-maze, Y-maze, 3-chamber social interaction, novel-object-recognition, passive-avoidance, and rotarod. Rats were sacrificed at 9 weeks and hippocampal protein expressions were analyzed by Western blot. Results revealed long-term body weight gain alterations in the growing rats and sex-specific impairments in spatial (female) and recognition (male) learning and memory paradigms. A markedly decreased expression of hippocampal NMDA receptor GluN1 subunit in female- and increased expression of AMPA GluR1 subunit protein expression in male rats were also found. Other aspects of behaviors such as locomotor activity and coordination, anxiety, sociability, social preference and avoidance learning and memory were not generally affected. These results suggest that neonatal repeated propofol administration disrupts normal growth and some aspects of neurodevelopment in rats in a sex-specific manner. PMID:25995824

  5. Long-term administration of fluvoxamine attenuates neuropathic pain and involvement of spinal serotonin receptors in diabetic model rats.

    PubMed

    Kato, Takahiro; Kajiyama, Seiji; Hamada, Hiroshi; Kawamoto, Masashi

    2013-12-01

    Diabetic neuropathic pain management is difficult even with non-steroidal anti-inflammatory drugs and narcotic analgesics such as morphine. Fluvoxamine, a class of selective serotonin reuptake inhibitors (SSRIs), is widely used to treat depression. Its analgesic effects are also documented for diabetic neuropathic pain, but they are limited because it is administered as a single-dose. In this study, we examined the time course of the antiallodynic effect of fluvoxamine in a rat model of diabetic neuropathic pain, which was induced by a single intraperitoneal administration of streptozotocin (75 mg/kg). In addition, the involvement of spinal serotonin (5-HT) receptors in long-term fluvoxamine treatment was studied by intrathecal administration of 5-HT receptor antagonists. In this study the development of mechanical hyperalgesia was assessed by measuring the hind paw withdrawal threshold using von Frey filaments. The results demonstrated that daily oral administration of fluvoxamine (10, 30, and 100 mg/kg) to diabetic rats from 3 to 8 weeks after streptozotocin administration resulted in a dose-dependent antiallodynic effect. The antiallodynic effect was sustained from 2 to 5 weeks after fluvoxamine administration. The antiallodynic effect of fluvoxamine in the diabetic rats was attenuated by WAY-100635 (a 5-HT(1A) receptor antagonist) intrathecally administered 1 week after the onset of daily administration of fluvoxamine, whereas no significant attenuation was seen when the antagonist was administered 3 and 5 weeks after fluvoxamine administration. The antiallodynic effect of fluvoxamine was also attenuated by ketanserin (a 5-HT(2A/2C) receptor antagonist) and ondansetron (a 5-HT3 receptor antagonist) intrathecally administered 1 and 3 weeks after the onset of daily fluvoxamine administration. However, no significant attenuation was observed when the antagonist was administered 5 weeks after fluvoxamine administration. This study demonstrated that daily oral

  6. Long-term administration of rifaximin improves the prognosis of patients with decompensated alcoholic cirrhosis.

    PubMed

    Vlachogiannakos, Jiannis; Viazis, Nikos; Vasianopoulou, Panagiota; Vafiadis, Irene; Karamanolis, Dimitrios G; Ladas, Spiros D

    2013-03-01

    Cirrhotic patients are predisposed to intestinal bacterial overgrowth with translocation of bacterial products which may deteriorate liver hemodynamics. Having shown that short-term administration of rifaximin improves liver hemodynamics in decompensated cirrhosis, we conducted this study to investigate the effect of intestinal decontamination with rifaximin on the long-term prognosis of patients with alcohol-related decompensated cirrhosis (Child-Pugh > 7) and ascites. Patients who had received rifaximin and showed improved liver hemodynamics were enrolled in the current study and continued to receive rifaximin (1200 mg/day). Each patient was matched by age, sex, and Child-Pugh grade to two controls and followed up for up to 5 years, death or liver transplantation. Survival and risk of developing portal hypertension-related complications were compared between rifaximin group and controls. Twenty three patients fulfilled the inclusion criteria and matched with 46 controls. Patients who received rifaximin had a significant lower risk of developing variceal bleeding (35% vs. 59.5%, P = 0.011), hepatic encephalopathy (31.5% vs. 47%, P = 0.034), spontaneous bacterial peritonitis (4.5% vs. 46%, P = 0.027), and hepatorenal syndrome (4.5% vs. 51%, P = 0.037) than controls. Five-year cumulative probability of survival was significantly higher in patients receiving rifaximin than in controls (61% vs. 13.5%, P = 0.012). In the multivariate analysis, rifaximin administration was independently associated with lower risk of developing variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, hepatorenal syndrome, and higher survival. In patients with alcohol-related decompensated cirrhosis, long-term rifaximin administration is associated with reduced risk of developing complications of portal hypertension and improved survival. © 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  7. The effects of long-term leptin administration on morphometrical changes of mice testicular tissue

    PubMed Central

    Esmaili-Nejad, Mohammad-Reza; Babaei, Homayoon; Kheirandish, Reza

    2015-01-01

    Objective(s): Leptin is a novel and interesting hormone for anyone trying to lose weight, but its effects on male gonad structure in longitudinal study is unknown. The present study was designed to explore morphometrical changes of mouse testicular tissue after long-term administration of leptin. Materials and Methods: Thirty healthy mature male mice were randomly assigned to either control (n=15) or treatment (n=15) groups. Leptin was intraperitoneally injected to the treatment group (0.1 µg/100 µl of physiological saline) once a day for 30 consecutive days, and control animals received normal saline with the same volume and route. Five mice from each experimental group were sacrificed at 15, 30 and 60 days after the beginning of treatments. Left testes were removed, weighted and then fixed in 10% buffered formalin, and stained with hematoxylin and eosine for morphometrical assays. Results: Except for sertoli cell nucleus diameter, which was affected from 30th day, evaluation of other morphometrical parameters such as Johnsen’s score, meiotic index, spermatogenesis, epithelial height, seminiferous tubules diameter and spermatogonial nucleus diameter revealed significant decrease from 15th day after leptin administration compare to those of the control group (P<0.05). Thus, meiotic index and spermatogonial cell nucleus diameter were two parameters that were further disturbed on 30th day compare to the day 15 (3.09±0.03 vs. 3.23±0.03, P=0.006 and 5.50±0.09 vs. 6.08±0.14, P=0.007, respectively). Conclusion: Our results showed that long-term administration of leptin could disturb testicular tissue structure and delay spermatogenesis process. PMID:26877846

  8. National Nuclear Security Administration Service Center Environmental Programs Long-Term Environmental Stewardship Baseline Handbook

    SciTech Connect

    Griswold, D. D.; Rohde, K.

    2003-02-26

    As environmental restoration (ER) projects move toward completion, the planning, integration, and documentation of long-term environmental stewardship (LTES) activities is increasingly important for ensuring smooth transition to LTES. The Long-Term Environmental Stewardship Baseline Handbook (Handbook) prepared by the National Nuclear Security Administration (NNSA) Service Center Environmental Programs Department (EPD) outlines approaches for integrating site-specific LTES planning and implementation into site ER baseline documentation. Since LTES will vary greatly from site to site, the Handbook also provides for flexibility in addressing LTES in ER Project life-cycle baselines, while clearly identifying Environmental Management (EM) requirements. It provides suggestions for enacting LTES principles and objectives through operational activities described in site-specific LTES plans and life cycle ER Project baseline scope, cost, and schedule documentation and tools for more thorough planning, better quantification, broader understanding of risk and risk management factors, and more comprehensive documentation. LTES planning applied to baselines in a phased approach will facilitate seamlessly integrating LTES into site operational activities, thereby minimizing the use of resources.

  9. [Long-term administration of calcium-heparin in thromboembolism (author's transl)].

    PubMed

    Hiltenbrand, C; Didier, A; Lantrade, P; Ille, H; Le Barbu, M; Lesbordes, J L; Xavier, J L

    1980-01-01

    The profound importance of thrombosis in natural history of venous and arterial thromboembolism justifies long-term use of heparin, the best antithrombotic agent. Through the study of 88 cases concerning patients treated by subcutaneous calcium-heparin for a time from 3 months to 6 years, in several indications of venous and arterial thromboembolism, we can bring the following results: - The treatment is easily accepted when patients are inquired and trained. The doses must be adapted according to clotting assays, which do no more restrain patients than during oral anticoagulant treatment. - The frequency of hemorrhagic complications is the same than during antivitamine K treatments. - Thrombosis occur rarely during heparin therapy, but with high frequency during oral anticoagulant treatments. - Osteoporosis is a real but acceptable risk (10 p. cent) of long-term heparin prescription. - The true limit of treatment is the frequency (34 p. cent) of cutaneous hypersensibility reactions with high blood eosinophilia rate. Always mild, this reaction is related to the subcutaneous administration, and heparin is likely not the single impeached substance. These undesirable effects bind us to their thorough study, in order to obtain better tolerated drugs.

  10. Clinical effects of long-term (36-month) lanthanum carbonate administration in hemodialysis patients in Japan.

    PubMed

    Kishi, Yuichiro; Obara, Yoshihiro; Hara, Keiko; Yamashiro, Hiromitsu; Kurosawa, Norio; Takada, Daisuke

    2014-06-01

    In this study, we investigated the clinical effects of long-term administration of the phosphorus (P) binder lanthanum carbonate (LC), which was launched in Japan in 2009. The subjects were 58 dialysis patients who began receiving LC, and we evaluated the clinical effects for up to 36 months after treatment initiation. The average serum P concentration remained low during the 36-month study period, with a significant reduction from 6.25 mg/dL at the start of the study to 4.94 mg/dL after 36 months (P < 0.001). A significant reduction was also observed in the average serum calcium concentration after 36 months (P < 0.05), but not in the serum intact parathyroid hormone concentration. Significant reductions were also observed in the average serum total protein, albumin and potassium concentrations (P < 0.05). The dosages of LC increased by approximately 1.9-fold after 36 months, in contrast, the dosages of concomitantly used sevelamer hydrochloride and Ca carbonate preparations decreased. These results indicate that LC could be used to treat hyperphosphatemia without causing hypercalcemia, and would be useful for long-term treatment with hemodialysis patients.

  11. Coronary angiogenic effect of long-term administration of Nigella sativa.

    PubMed

    Al Asoom, Lubna I

    2017-06-13

    Coronary angiogenesis is one of the preferable adaptive responses of aerobic training. Previous studies found inotropic and hypertrophic cardiac effects for long-term administration of Nigella sativa (NS), but no studies have explored its coronary angiogenic effect. The present study compared the effect of long-term NS- administration and exercise training on the induction of coronary angiogenesis. Fifteen adult male Wistar rats were divided into three groups: control, NS-fed, and exercise-trained (Ex). The NS-fed rats were administered 800 mg/Kg NS orally for eight weeks. The (Ex) rats were trained on a five-lane treadmill at a speed of 18 m/min and a grade of 32° for two hour/day for eight weeks. After the experiment, the hearts were extracted and immunohistological slides were prepared using rat vascular endothelial growth factor (VEGF), platelet endothelial cell adhesion molecule-1 (PECAM-1), Von Willebrand factor (VWF) and nitric oxide synthase-2 (NOS-2) antibodies (Ab). Photomicrographs were analysed using ImageJ software, and the % of the immunostained-area of 10 fields per specimen was recorded. VEGF was significantly higher in the NS- (2.59±1.37%) and Ex rats (2.51±1.86%) compared to the control group (1.58±0.78%) with P<0.01. The VWF was significantly lower in the two experimental groups (1.57±0.83%, 1.07±0.72%) for NS and Ex groups respectively, compared to the controls (2.38±1.72) with p<0.01. Only Ex group had a higher PECAM-1 (1.79±0.78%) and lower NOS-2 (0.83±0.57%) than the control group (1.19±1.17%, 1.25±1.19%) for PECAM-1 and NOS-2 with P<0.01 and P<0.05 respectively. The present study demonstrated an increase in VEGF and a decrease of the VWF in the hearts of Nigella-fed and exercise-trained rats. This might indicate the potentiality for induction of coronary angiogenesis via long-term administration of NS and exercise training. NS effect on coronary angiogenesis needs to be explored further as it might lead to a new promising

  12. Methodology for Using Long-Term Accelerometry Monitoring to Describe Daily Activity Patterns in COPD

    PubMed Central

    Hecht, Ariel; Ma, Shuyi; Porszasz, Janos; Casaburi, Richard

    2010-01-01

    We sought to develop procedures for computerized analysis of long-term, high-resolution activity monitoring data that allow accurate assessment of the time course of activity levels suitable for use in chronic obstructive pulmonary disease (COPD) patients. Twenty-two COPD patients utilizing long-term oxygen recruited from 5 sites of the COPD Clinical Research Network wore a triaxial accelerometer (RT3, Stayhealthy, Monrovia, CA) during waking hours over a14 day period. Computerized algorithms were composed allowing minute-by-minute activity data to be analyzed to determine, for each minute, whether the monitor was being worn. Temporal alignment allowed determination of average time course of activity level, expressed as average vector magnitude units (VMU, the vectorial sum of activity counts in three orthogonal directions) per minute, for each hour of the day. Mid-day activity was quantified as average VMU/minute between 10AM and 4PM for minutes the monitor was worn. Over the 14 day monitoring period, subjects wore the monitor an average of 11.4±3.0 hours·day−1. During midday hours, subjects wore the monitor 76.3% of the time and generated an average activity level of 112±55 VMU·min−1. Increase in precision of activity estimates with longer monitoring periods was demonstrated. This analysis scheme allows a detailed temporal pattern of activity to be defined from triaxial accelerometer recordings and has the potential to facilitate comparisons among subjects and between subject groups. This trial is registered at ClinicalTrials.gov (NCT00325754). PMID:19378225

  13. The metabolism of cyclamate to cyclohexylamine in humans during long-term administration.

    PubMed

    Renwick, A G; Thompson, J P; O'Shaughnessy, M; Walter, E J

    2004-05-01

    A group of 14 subjects, who had been identified from 261 volunteers in a 1-week screen as being able to metabolize the sweetener cyclamate to cyclohexylamine (>0.2% of a daily dose), and 31 nonconverters (<0.2% metabolism) were given calcium cyclamate tablets (equivalent to 250 mg cyclamic acid, 3 times daily) for a period of 13 weeks. The metabolism of cyclamate to cyclohexylamine was determined using twice-weekly timed (3 h) urine collections during week 1-3 and 7-13. Urine specimens were collected on all other study days to investigate day-to-day fluctuations in cyclohexylamine excretion. Analyses of the twice weekly timed urine collections showed that subjects recruited as nonconverters essentially remained nonconverters. Of the converters, three showed consistently low metabolism, five showed erratic metabolism, five showed low metabolism initially, which increased during the latter part of the study, and one subject showed consistently high metabolism throughout the study. Analysis of the day-to-day urine specimens showed marked intrasubject variability. The plasma concentrations of cyclohexylamine measured on weeks 1-3 and 7-13 reflected the urine profiles. The highest individual long-term average steady-state excretion values based on the 3-h urine collections and daily samples were 21%, 23%, 25%, 29%, 34%, and 38%. The maximum % metabolism detected in the high converters occasionally reached the value of 60% reported in previous short-term studies, but this high activity was not maintained, and was followed by periods of lower metabolism. The results of this metabolism study support an acceptable daily intake (ADI) of 0-11 mg/kg body weight per day.

  14. ACTIVITY AND ISOZYME CONTENT OF LACTATE DEHYDROGENASE UNDER LONG-TERM ORAL TAURINE ADMINISTRATION TO RATS.

    PubMed

    Ostapiv, R D; Humenyuk, S L; Manko, V V

    2015-01-01

    The effect of long-term oral taurine administration to rats on activity of lactate dehydrogenase (LDH), its isozyme content and activity in the whole blood, liver, thigh muscle, brain and testes tissues were studied in the present work. For this purpose male Wistar rats with body weight 190-220 g were randomly divided into three groups, they were orally administered drinking water (control group) or taurine solution 40 and 100 mg per kg of body weight ( groups I and II, respectively). The total lactate dehydrogenase activity was measured spectrophotometrically, the percentage content of isozymes was determined by electrophoresis in 7.5% poliacrylamide gel withfurther staining according to J. Garbus. It was found that the total lactate dehydrogenase activity increased in all studied tissues. In testes of animals of both groups and in brain of group I animals, the total percentage contents of isozymes that are responsible for lactate production (LDH4+LDH5) increased. In liver of animals of both groups and in whole blood of group II animals, the total percentage content of isozymes that produce pyruvate (LDH1+LDH2) increased. In thigh muscle of both groups and in brain of group II animals the balance between LDH1+LDH2 and LDH4+LDH5 content did not differ from control values, though total lactate dehydrogenase activity was significantly higher, than that in the control group. Thus, the increase in the lactate dehydrogenase activity under long-term oral taurine administration in different rat tissues was found to be tissue- and dose-dependent and was caused by the increase in the content of different isozymes. Such increase in group I animals might be explained by adaptive mechanisms to hypoxia caused by high doses of taurine. For group II animals high doses of taurine were toxic and directly affected metabolic processes in the animal bodies.

  15. Daily cognitive appraisals, daily affect, and long-term depressive symptoms: the role of self-esteem and self-concept clarity in the stress process.

    PubMed

    Lee-Flynn, Sharon C; Pomaki, Georgia; Delongis, Anita; Biesanz, Jeremy C; Puterman, Eli

    2011-02-01

    The current study investigated how self-esteem and self-concept clarity are implicated in the stress process both in the short and long term. Initial and 2-year follow-up interviews were completed by 178 participants from stepfamily unions. In twice-daily structured diaries over 7 days, participants reported their main family stressor, cognitive appraisals (perceived stressor threat and stressor controllability), and negative affect. Results of multilevel modeling indicated that high self-esteem ameliorated the effect of daily negative cognitive appraisals on daily negative affect. Self-concept clarity also buffered the effect of low self-self-esteem on depressive symptoms 2 years later. Our findings point to the vulnerability of those having low self-esteem or low self-concept clarity in terms of both short- and long-term adaptation to stress. They indicate the need for the consideration of such individual differences in designing stress management interventions.

  16. A new, long-term daily satellite-based rainfall dataset for operational monitoring in Africa

    PubMed Central

    Maidment, Ross I.; Grimes, David; Black, Emily; Tarnavsky, Elena; Young, Matthew; Greatrex, Helen; Allan, Richard P.; Stein, Thorwald; Nkonde, Edson; Senkunda, Samuel; Alcántara, Edgar Misael Uribe

    2017-01-01

    Rainfall information is essential for many applications in developing countries, and yet, continually updated information at fine temporal and spatial scales is lacking. In Africa, rainfall monitoring is particularly important given the close relationship between climate and livelihoods. To address this information gap, this paper describes two versions (v2.0 and v3.0) of the TAMSAT daily rainfall dataset based on high-resolution thermal-infrared observations, available from 1983 to the present. The datasets are based on the disaggregation of 10-day (v2.0) and 5-day (v3.0) total TAMSAT rainfall estimates to a daily time-step using daily cold cloud duration. This approach provides temporally consistent historic and near-real time daily rainfall information for all of Africa. The estimates have been evaluated using ground-based observations from five countries with contrasting rainfall climates (Mozambique, Niger, Nigeria, Uganda, and Zambia) and compared to other satellite-based rainfall estimates. The results indicate that both versions of the TAMSAT daily estimates reliably detects rainy days, but have less skill in capturing rainfall amount—results that are comparable to the other datasets. PMID:28534868

  17. A new, long-term daily satellite-based rainfall dataset for operational monitoring in Africa

    NASA Astrophysics Data System (ADS)

    Maidment, Ross I.; Grimes, David; Black, Emily; Tarnavsky, Elena; Young, Matthew; Greatrex, Helen; Allan, Richard P.; Stein, Thorwald; Nkonde, Edson; Senkunda, Samuel; Alcántara, Edgar Misael Uribe

    2017-05-01

    Rainfall information is essential for many applications in developing countries, and yet, continually updated information at fine temporal and spatial scales is lacking. In Africa, rainfall monitoring is particularly important given the close relationship between climate and livelihoods. To address this information gap, this paper describes two versions (v2.0 and v3.0) of the TAMSAT daily rainfall dataset based on high-resolution thermal-infrared observations, available from 1983 to the present. The datasets are based on the disaggregation of 10-day (v2.0) and 5-day (v3.0) total TAMSAT rainfall estimates to a daily time-step using daily cold cloud duration. This approach provides temporally consistent historic and near-real time daily rainfall information for all of Africa. The estimates have been evaluated using ground-based observations from five countries with contrasting rainfall climates (Mozambique, Niger, Nigeria, Uganda, and Zambia) and compared to other satellite-based rainfall estimates. The results indicate that both versions of the TAMSAT daily estimates reliably detects rainy days, but have less skill in capturing rainfall amount—results that are comparable to the other datasets.

  18. Long-term melatonin administration increases polyunsaturated fatty acid percentage in plasma lipids of hypercholesterolemic rats.

    PubMed

    Pita, Maria L; Hoyos, Marta; Martin-Lacave, Inés; Osuna, Carmen; Fernández-Santos, Jose M; Guerrero, Juan M

    2002-04-01

    This study was designed to investigate the effect of melatonin on the fatty acid composition of plasma and tissue lipids. Melatonin administration to rats fed with a standard diet only increased long-chain n-6 polyunsaturated fatty acids (PUFA) in total plasma lipids and liver phospholipids but induced significant changes in hypercholesterolemic rats. In plasma, palmitoleic and oleic acids increased and n-6 and n-3 PUFA decreased in hypercholesterolemic rats; theses changes were reversed by melatonin administration. The analysis of lipid fractions revealed that only the cholesteryl ester fraction was affected by melatonin. Histological studies of the carotid artery intima revealed the appearance, in hypercholesterolemic rats, of fatty streaks produced by a mass of foam cells covered by the endothelium and by a thin layer of mononucleated cells. These changes were prevented by melatonin. We conclude that long-term melatonin administration modifies the fatty acid composition of rat plasma and liver lipids and ameliorates the arterial fatty infiltration induced by cholesterol.

  19. Physiological performance of the intertidal Manila clam (Ruditapes philippinarum) to long-term daily rhythms of air exposure

    PubMed Central

    Yin, Xuwang; Chen, Peng; Chen, Hai; Jin, Wen; Yan, Xiwu

    2017-01-01

    Intertidal organisms, especially the sessile species, often experience long-term periodic air exposure during their lives. Learning the biochemical and physiological responses of intertidal organisms to long-term periodic air exposure and the relationship to duration of air exposure provides insight into adaptation to this variably stressful environment. We studied the Manila clam, Ruditapes philippinarum, an important species in world aquaculture, as a model to evaluate survival, growth, lipid composition, oxygen consumption, oxidative damage, and antioxidant enzyme activity in relation to the duration of air exposure in a long-term (60 days) laboratory study of varying durations of periodic emersion and re-immersion. Our results show: (1) clams undergoing a longer period of air exposure had lower survival and growth compared to those given a shorter exposure, (2) levels of oxidative damage and activities of antioxidant enzymes were higher in all air exposure treatments, but did not increase with duration of air exposure, and (3) the content of docosahexaenoic acid increased with duration of air exposure. Our results can largely be interpreted in the context of the energy expenditure by the clams caused by aerobic metabolism during the daily cycle of emersion and re-immersion and the roles of docosahexaenoic acid against oxidative stress. PMID:28128354

  20. Long-term variation in the ionosphere and lower thermosphere as seen in the geomagnetic solar quiet daily variation

    NASA Astrophysics Data System (ADS)

    Shinbori, A.; Koyama, Y.; Hori, T.; Nose, M.; Otsuka, Y.

    2015-12-01

    In order to investigate characteristics of the long-term variation in the ionosphere and lower thermosphere, we analyzed the amplitude of geomagnetic solar quiet (Sq) field daily variation using 1-h geomagnetic field data obtained from 69 geomagnetic stations within the period of 1947-2013. In the present data analysis, we took advantage of the Inter-university Upper atmosphere Global Observation NETwork (IUGONET) products (metadata database and analysis software) for finding and handling the long-term observation data obtained at many observatories. The Sq amplitude observed at these geomagnetic stations showed a clear solar activity dependence and tended to be enhanced during each solar maximum phase. The Sq amplitude was the smallest around the minimum of solar cycle 23/24 in 2008-2009. This significant depression implies that the solar extreme ultraviolet (EUV) radiation responsible for ionization of the upper atmosphere decreased during this solar cycle minimum. In order to examine a global distribution of the long-term trend in the Sq amplitude, we derived the residual Sq amplitude from the deviation from the fitting curve between the solar F10.7 index and Sq amplitude. As a result, a majority of the trends in the residual Sq amplitude showed negative values over a wide region. This tendency was relatively strong in Europe, India, the eastern part of Canada, and New Zealand. Moreover, we estimate the neutral wind in the lower thermosphere from the Sq amplitude and height-integrated ionospheric conductivity in order to know the physical mechanism of the long-term trend in the residual Sq amplitude. As a result, the estimated thermospheric zonal and meridional winds showed a seasonal variation with a period of one year or less, but the solar activity dependence was unclear. This result suggests that the solar cycle dependence of the Sq amplitude may be mainly attributed to the variation of the ionospheric conductivity.

  1. Daily Acclimation Handling Does Not Affect Hippocampal Long-Term Potentiation or Cause Chronic Sleep Deprivation in Mice

    PubMed Central

    Vecsey, Christopher G.; Wimmer, Mathieu E. J.; Havekes, Robbert; Park, Alan J.; Perron, Isaac J.; Meerlo, Peter; Abel, Ted

    2013-01-01

    Study Objectives: Gentle handling is commonly used to perform brief sleep deprivation in rodents. It was recently reported that daily acclimation handling, which is often used before behavioral assays, causes alterations in sleep, stress, and levels of N-methyl-D-aspartate receptor subunits prior to the actual period of sleep deprivation. It was therefore suggested that acclimation handling could mediate some of the observed effects of subsequent sleep deprivation. Here, we examine whether acclimation handling, performed as in our sleep deprivation studies, alters sleep/wake behavior, stress, or forms of hippocampal synaptic plasticity that are impaired by sleep deprivation. Design: Adult C57BL/6J mice were either handled daily for 6 days or were left undisturbed in their home cages. On the day after the 6th day of handling, long-term potentiation (LTP) was induced in hippocampal slices with spaced four-train stimulation, which we previously demonstrated to be impaired by brief sleep deprivation. Basal synaptic properties were also assessed. In three other sets of animals, activity monitoring, polysomnography, and stress hormone measurements were performed during the 6 days of handling. Results: Daily gentle handling alone does not alter LTP, rest/activity patterns, or sleep/wake architecture. Handling initially induces a minimal stress response, but by the 6th day, stress hormone levels are unaltered by handling. Conclusion: It is possible to handle mice daily to accustom them to the researcher without causing alterations in sleep, stress, or synaptic plasticity in the hippocampus. Therefore, effects of acclimation handling cannot explain the impairments in signaling mechanisms, synaptic plasticity, and memory that result from brief sleep deprivation. Citation: Vecsey CG; Wimmer MEJ; Havekes R; Park AJ; Perron IJ; Meerlo P; Abel T. Daily acclimation handling does not affect hippocampal long-term potentiation or cause chronic sleep deprivation in mice. SLEEP 2013

  2. Long-term AICAR administration and exercise prevents diabetes in ZDF rats.

    PubMed

    Pold, Rasmus; Jensen, Lasse S; Jessen, Niels; Buhl, Esben S; Schmitz, Ole; Flyvbjerg, Allan; Fujii, Nobuharu; Goodyear, Laurie J; Gotfredsen, Carsten F; Brand, Christian L; Lund, Sten

    2005-04-01

    Lifestyle interventions including exercise programs are cornerstones in the prevention of obesity-related diabetes. The AMP-activated protein kinase (AMPK) has been proposed to be responsible for many of the beneficial effects of exercise on glucose and lipid metabolism. The effects of long-term exercise training or 5-aminoimidazole-4-carboxamide-1-beta-d-riboruranoside (AICAR) treatment, both known AMPK activators, on the development of diabetes in male Zucker diabetic fatty (ZDF) rats were examined. Five-week-old, pre-diabetic ZDF rats underwent daily treadmill running or AICAR treatment over an 8-week period and were compared with an untreated group. In contrast to the untreated, both the exercised and AICAR-treated rats did not develop hyperglycemia during the intervention period. Whole-body insulin sensitivity, as assessed by a hyperinsulinemic-euglycemic clamp at the end of the intervention period, was markedly increased in the exercised and AICAR-treated animals compared with the untreated ZDF rats (P < 0.01). In addition, pancreatic beta-cell morphology was almost normal in the exercised and AICAR-treated animals, indicating that chronic AMPK activation in vivo might preserve beta-cell function. Our results suggest that activation of AMPK may represent a therapeutic approach to improve insulin action and prevent a decrease in beta-cell function associated with type 2 diabetes.

  3. Long-term administration of large doses of paracetamol impairs the reproductive competence of male rats.

    PubMed

    Ratnasooriya, W D; Jayakody, J R

    2000-12-01

    To evaluate the antireproductive effect of paracetamol in male rats. Male rats were orally administered daily with 500 mg/kg or 1000 mg/kg of paracetamol for 30 consecutive days. Their sexual behaviour and fertility were evaluated using receptive females. At 2 h after treatment, sexual behaviour was not inhibited but on day 30 both doses of paracetamol caused marked impairment of libido (assessed by % mounting, % intromission and % ejaculation), sexual vigour (number of mounts and intromissions and copulatory efficiency) or sexual performance (intercopulatory interval). In mating experiments, the fertility (in terms of quantal pregnancy, fertility index, implantation index and number of implants) was significantly reduced. All these effects were reversible. The antireproductive effect was not due to a general toxicity but due to an increase in pre-implantation losses resulting from oligozoospermia, impairments of normal and hyper-activated sperm motility, and reduction in the fertilizing potential of spermatozoa. Long-term use of high doses of paracetamol may be detrimental to male reproductive competence.

  4. Methods for long-term 17β-estradiol administration to mice.

    PubMed

    Ingberg, E; Theodorsson, A; Theodorsson, E; Strom, J O

    2012-01-01

    Rodent models constitute a cornerstone in the elucidation of the effects and biological mechanisms of 17β-estradiol. However, a thorough assessment of the methods for long-term administration of 17β-estradiol to mice is lacking. The fact that 17β-estradiol has been demonstrated to exert different effects depending on dose emphasizes the need for validated administration regimens. Therefore, 169 female C57BL/6 mice were ovariectomized and administered 17β-estradiol using one of the two commonly used subcutaneous methods; slow-release pellets (0.18 mg, 60-day release pellets; 0.72 mg, 90-day release pellets) and silastic capsules (with/without convalescence period, silastic laboratory tubing, inner/outer diameter: 1.575/3.175 mm, filled with a 14 mm column of 36 μg 17β-estradiol/mL sesame oil), or a novel peroral method (56 μg 17β-estradiol/day/kg body weight in the hazelnut cream Nutella). Forty animals were used as ovariectomized and intact controls. Serum samples were obtained weekly for five weeks and 17β-estradiol concentrations were measured using radioimmunoassay. The peroral method resulted in steady concentrations within--except on one occasion--the physiological range and the silastic capsules produced predominantly physiological concentrations, although exceeding the range by maximum a factor three during the first three weeks. The 0.18 mg pellet yielded initial concentrations an order of magnitude higher than the physiological range, which then decreased drastically, and the 0.72 mg pellet produced between 18 and 40 times higher concentrations than the physiological range during the entire experiment. The peroral method and silastic capsules described in this article constitute reliable modes of administration of 17β-estradiol, superior to the widely used commercial pellets.

  5. [Effects of steroid therapy on long-term canal prognosis and activity in the daily life of vestibular neuronitis patients].

    PubMed

    Kitahara, T; Okumura, S; Takeda, N; Nishiike, S; Uno, A; Fukushima, M; Kubo, T

    2001-11-01

    We studied 28 patients with vestibular neuronitis treated at our hospital between 1997 and 1999. To determine the effects of steroid therapy on long-term canal prognosis and daily activity, we examined caloric tests and gave questionnaires to 12 steroid-treated and 16 nonsteroid-treated patients 2 years after onset. We found that canal improvement was 50% in the nonsteroid-treated group and 75% in the steroid-treated one. In cases with severe canal paresis (CP > or = 60%), canal improvement was 33% in the nonsteroid-treated group and 67% in the steroid-treated one. Steroid therapy at the acute stage of this disease significantly reduced the duration of spontaneous nystagmus and handicap in daily life due to dizziness induced by head and body movement, decreasing mood disturbance.

  6. Long-term stability of uveitis with faint anterior chamber flare treated with once-daily topical ophthalmic betamethasone.

    PubMed

    Kawamura, Masahide; Zako, Masahiro

    2014-04-01

    The aim of our study is to investigate the long-term transitions of intraocular pressure (IOP) and aqueous flare values in uveitis patients with faint anterior chamber flare who were treated with once-daily topical ophthalmic betamethasone for more than 6 months. The study included a total of 111 eyes of 68 outpatients. The mean follow-up period was 26.8 months. The average IOP and aqueous flare value of patients divided by the 5-months follow-up period showed no significant difference. Six eyes (of four patients) were followed-up for more than 1 year after termination of the treatment. Among these patients, the average aqueous flare value was significantly higher, and the average period to reach more than 1.5 times the former aqueous flare value significantly decreased after termination than before. Once-daily topical ophthalmic betamethasone is not expected to cause steroid-induced ocular hypertension but to have prophylactic effect.

  7. Effect of the long-term care prevention project on the motor functions and daily life activities of the elderly.

    PubMed

    Wada, Yoshihiro; Sakuraba, Keisyoku; Kubota, Atsushi

    2015-01-01

    [Purpose] The purpose of this study was to verify the effects of the long-term care prevention project and develop an effective program. [Subjects] A total of 81 elderly people (age, 79 ± 5.1 years; height, 149.2 ± 9.2 cm; weight, 54.2 ± 11.4 kg). [Methods] Grip, knee extension muscular strength, 10 m walking speed, and Timed Up and Go time were measured for evaluation of motor functions, and the "Locomo 25", a 25-question risk assessment questionnaire, was used as the judgment criterion for evaluation of daily life activities, with measurements being taken at the beginning of the project and after three months. [Results] In the motor functions evaluation, significant differences were observed in 10 m walking speed, Timed Up and Go time, and knee extension strength. In the daily life activities evaluation, scores for pain, rising movement, standing movement, indoor walking, outdoor walking, and fear of falling were significantly reduced. In addition, a significant correlation was also observed between motor functions and daily life activities. [Conclusion] The result of this study indicated that the long-term care prevention project is effective in maintaining or improving muscular strength and mitigating pain in the elderly and that it is an effective program for maintaining daily life activities. We were also able to show that it would be effective to develop programs with a low exercise intensity that can be performed on a continuing by the elderly.

  8. Pharmacokinetic and pharmacodynamic properties of pergolide mesylate following long-term administration to horses with pituitary pars intermedia dysfunction.

    PubMed

    McFarlane, D; Banse, H; Knych, H K; Maxwell, L K

    2017-04-01

    The objective of this study was to gain an understanding of the pharmacokinetic and pharmacodynamic properties of pergolide in horses with PPID after of long-term oral administration. Six horses with confirmed PPID were treated with pergolide (Prascend(®) ) at 1 mg/horse po q24 h for 2 months, followed by 2 mg/horse po q24 h for 4 months. Following the last dose, plasma samples were collected for measurement of pergolide using an LC/MS/MS method and ACTH measurement using a chemiluminescent immunoassay. Noncompartmental and compartmental pharmacokinetic analyses were performed, as well as pharmacodynamic assessment of the effect of plasma pergolide concentrations on plasma ACTH concentrations. Pergolide effectively decreased plasma ACTH concentration in aged horses with PPID, with similar pharmacokinetic properties as reported in young horses, including an approximate terminal half-life of 24 h. Plasma ACTH concentration increased by 50% in 3/6 horses at 2 days and 6/6 horses 10 days after discontinuing drug administration. Pergolide was quantified in all horses at 2 days and in none at 10 days after last dose. In summary, after discontinuing pergolide treatment, plasma ACTH concentration increased while pergolide was still quantifiable in some horses. Once-daily dosing of pergolide is likely appropriate in most horses with PPID for regulating the plasma ACTH concentration. © 2016 John Wiley & Sons Ltd.

  9. Long-term variation in the upper atmosphere as seen in the geomagnetic solar quiet (Sq) daily variation

    NASA Astrophysics Data System (ADS)

    Shinbori, A.; Koyama, Y.; Yatagai, A. I.; Nose, M.; Hori, T.; Otsuka, Y.

    2012-12-01

    It has been well-known that geomagnetic solar quiet (Sq) daily variation is produced by the global ionospheric currents flowing in the E-region, which are generated by dynamo process via interaction between the neutral wind and ionospheric plasma in a region of the lower thermosphere and ionosphere. Then, to investigate the Sq amplitude is essential for understanding the long-term variations in the ionospheric conductivity and neutral wind of the lower thermosphere and ionosphere. Recently, Elias et al. [2010] reported that the Sq amplitude tends to increase by 5.4-9.9 % in the middle latitudes in a period of 1961-2001. They mentioned that the long-term variation of ionospheric conductivity associated with geomagnetic secular variation mainly determines the Sq trend, but that the rest component is due to ionospheric conductivity enhancement associated with cooling effect in the thermosphere due to increasing greenhouse gas. In the present study, we clarify the characteristics of the long-term variation in the Sq amplitude using the long-term observation data of geomagnetic field and neutral wind. In the present analysis, we used the F10.7 solar flux as a good indicator of the variation in the solar irradiance in the EUV and UV range as well as geomagnetic field data with time resolution of 1 hour observed at 184 geomagnetic stations. The definition of the Sq amplitude is the difference of the H-component between the maximum and minimum every day when the Kp index is less than 4. As a result, the long-term variation in the Sq amplitude at all the geomagnetic stations shows a strong correlation with the solar F10.7 flux which depends on 11-year solar activity. The relationship between the Sq amplitude and F10.7 flux was not linear but nonlinear. This nonlinearity could be interpreted as the decrease of production rate of electrons and ions in the ionosphere for the strong EUV and UV fluxes as already reported by Balan et al. [1993]. In order to minimize the solar

  10. Colour of muscle from 18-month-old steers given long-term daily exercise.

    PubMed

    Dunne, P G; O'Mara, F P; Monahan, F J; French, P; Moloney, A P

    2005-10-01

    Darker beef from pasture-fed compared with grain-fed cattle may result from differences in physical activity rather than differences in nutrition. The objective was to determine if steers that were exercised produced darker meat than non-exercised steers and whether any effect was muscle-related. Exercised steers were walked 4.41 km daily in a single bout, six days per week for 18 weeks at an average speed of 5.2 kmh(-1). All steers were fed grass silage on an ad libitum basis plus 6 kg concentrates. Following slaughter, muscle colour coordinates ('L' (lightness), 'a' (redness) and 'b' (yellowness) values) of M. longissimus dorsi (LD), M. semimembranosus (SM) and M. extensor carpi radialis (ECR) were recorded at 48 h postmortem and redness and yellowness were used to calculate muscle hue ('H') and colour intensity/saturation ('C'). The pH of all muscles was measured at 1.5, 3, 6, 22 and 48 h postmortem and LD samples were recovered (90 min postmortem) for glycolytic potential (GP) assessment. Exercise did not affect muscle lightness, yellowness, hue or colour intensity. However, LD was the darkest (P<0.001) and SM the most saturated (P<0.001) muscle. Exercise affected muscle redness in a muscle-dependent manner (muscle×exercise, P=0.038) whereby ECR became more red with exercise but LD and SM were unaffected. There were muscle×time (P<0.001) and time×exercise (P=0.045) interactions for muscle pH. The ECR muscle had the highest pH at all times. The exercised steers had higher (P<0.05) LD muscle pH than control steers at 3 and 6 h postmortem. Exercise did not affect myoglobin concentration, which was muscle dependent, decreasing in the order: SM (6.72 mg/g)>ECR (6.33 mg/g)>LD (5.48 mg/g), which were all different (P<0.001). Exercise had no effect on GP in LD muscle (111 vs. 99 μmol/g for control and exercised steers, respectively; SED=6.6 μmol/g). It was concluded that although application of exercise did not affect muscle lightness and thus, did not cause

  11. Long-term outcome and prediction models of activities of daily living in Alzheimer disease with cholinesterase inhibitor treatment.

    PubMed

    Wattmo, Carina; Wallin, Åsa K; Londos, Elisabet; Minthon, Lennart

    2011-01-01

    In untreated patients with Alzheimer disease (AD) the functional ability is gradually lost. What happens to the patients after continuous long-term cholinesterase inhibitor (ChEI) treatment is less investigated. The objective of this study was to describe the longitudinal functional outcome and analyze factors affecting the outcome in ChEI-treated patients. In an open, 3-year, nonrandomized, prospective, multicenter study in a routine clinical setting, 790 patients were treated with either donepezil, rivastigmine, or galantamine. At baseline and every 6 months, they were assessed with several rating scales including Instrumental Activities of Daily Living (IADL), Physical Self-Maintenance Scale (PSMS), and Mini-Mental State Examination (MMSE). A faster functional decline was associated with lower cognitive ability at baseline, older age, and the interaction of higher education and longer time in the study. The patients residing with a spouse or relative showed slower deterioration in IADL score. A higher mean dose of ChEI, regardless of drug agent, was also related to slower instrumental ADL decline. Prediction models for longitudinal functional outcome were provided. AD severity at baseline is a key factor in obtaining reliable clinical prognoses of the long-term ADL ability. The dosage of ChEI treatment could possibly lead to a different functional outcome.

  12. [Effect of the long term administration of bromantan on the reproductive function in rats].

    PubMed

    Khamidova, T V; Bugaeva, L I; Morozov, I S; Spasov, A A

    2000-01-01

    Bromantan is a new psychostimulator possessing actoprotector properties. The drug was administered to rats over two months (males) and two weeks (females) at a daily dose of 30 and 200-mg/kg, and the reproduction function parameters were monitored. Then the experimental animals were coupled and the embryonal characteristics of the breed were determined. Upon termination of the drug administration, the functional state of sperm and the morphology of gonads were studied again. It was found that bromantan (30 mg/kg) unreliably decreases the absolute amount of sperm in males. In females, the drug did not affect the ovary weight coefficient and increased the gestation index. After termination of the drug administration, the ovary weight coefficient increased. Bromantan affected neither the fertilizing capacity of male and female gametes nor the embryonal characteristics of the breed.

  13. Influence of Long-Term Zinc Administration on Spatial Learning and Exploratory Activity in Rats.

    PubMed

    Piechal, Agnieszka; Blecharz-Klin, Kamilla; Pyrzanowska, Justyna; Widy-Tyszkiewicz, Ewa

    2016-08-01

    Animal brain contains a significant amount of zinc, which is a cofactor for more than 300 enzymes. Moreover, it provides the basis for functioning of more than 2000 transcription factors, and it is necessary for memory formation and learning processes in the brain. The aim of this study was to investigate the effect of zinc supplementation on behavior in 3-month-old rats. For this purpose, the Morris water maze paradigm, hole-board, and T-maze were used. Wistar rats received a solution of ZnSO4 in drinking water at the doses of 16 mg/kg (Zn16 group) and 32 mg/kg (Zn32 group). In rats pretreated with the lower dose of zinc, the improvement of the mean escape latency was observed in comparison to the control group and Zn32 group. During memory task, both ZnSO4-supplemented groups showed an increase in crossings over the previous platform position. Furthermore, the exploratory activity in Zn16 group was improved in comparison to Zn32 and control group. In the brains of zinc-supplemented rats, we observed the higher content of zinc, both in the hippocampus and the prefrontal cortex. Hippocampal zinc level correlated positively with the mean annulus crossings of the Zn16 group during the probe trial. These findings show that the long-term administration of ZnS04 can improve learning, spatial memory, and exploratory activity in rats. Graphical Abstract Improvement of spatial learning, memory, and exploratory behavior.

  14. Evaluation of adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs.

    PubMed

    Luna, Stelio P L; Basílio, Ana C; Steagall, Paulo V M; Machado, Luciana P; Moutinho, Flávia Q; Takahira, Regina K; Brandão, Cláudia V S

    2007-03-01

    To evaluate adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs. 36 adult dogs. Values for CBC, urinalysis, serum biochemical urinalyses, and occult blood in feces were investigated before and 7, 30, 60, and 90 days after daily oral administration (n = 6 dogs/group) of lactose (1 mg/kg, control treatment), etodolac (15 mg/kg), meloxicam (0.1 mg/kg), carprofen (4 mg/kg), and ketoprofen (2 mg/kg for 4 days, followed by 1 mg/kg daily thereafter) or flunixin (1 mg/kg for 3 days, with 4-day intervals). Gastroscopy was performed before and after the end of treatment. For serum gamma-glutamyltransferase activity, values were significantly increased at day 30 in dogs treated with lactose, etodolac, and meloxicam within groups. Bleeding time was significantly increased in dogs treated with carprofen at 30 and 90 days, compared with baseline. At 7 days, bleeding time was significantly longer in dogs treated with meloxicam, ketoprofen, and flunixin, compared with control dogs. Clotting time increased significantly in all groups except those treated with etodolac. At day 90, clotting time was significantly shorter in flunixin-treated dogs, compared with lactose-treated dogs. Gastric lesions were detected in all dogs treated with etodolac, ketoprofen, and flunixin, and 1 of 6 treated with carprofen. Carprofen induced the lowest frequency of gastrointestinal adverse effects, followed by meloxicam. Monitoring for adverse effects should be considered when nonsteroidal anti-inflammatory drugs are used to treat dogs with chronic pain.

  15. An Administrator's Perspective on the Organization of Physical Activity for Older Adults in Long-Term Care Facilities.

    PubMed

    Baert, Veerle; Gorus, Ellen; Calleeuw, Koen; De Backer, Werner; Bautmans, Ivan

    2016-01-01

    level, the infrastructure of the facility (91%) and adequate and sufficient material (88%) are the main motivators. The barriers that were presented to the participants were scored as less important. The majority of the administrators (83%) are not familiar with the WHO guidelines for PA; 70% of the participants believe that the guidelines are useful, but only 40% is convinced that it is realistic to implement the guidelines in an LTCF. This study described different motivators and barriers for administrators to organize PA in LTCFs. Contrary to other studies, lack of staff, lack of adequate equipment, and lack of financial resources were rejected as potential barriers for organizing PA. Despite the fact that administrators were not familiar with the WHO guidelines for PA, they believed that the guidelines are useful. The participants reported several barriers for implementation of the guidelines. Administrators of LTCFs are motivated to implement the guidelines if PA can be integrated in daily activities and education of LTCF staff regarding PA is provided. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

  16. Recombinant human angiostatin by twice-daily subcutaneous injection in advanced cancer: a pharmacokinetic and long-term safety study.

    PubMed

    Beerepoot, Laurens V; Witteveen, Els O; Groenewegen, Gerard; Fogler, William E; Sim, B Kim Leel; Sidor, Carolyn; Zonnenberg, Bernard A; Schramel, Franz; Gebbink, Martijn F B G; Voest, Emile E

    2003-09-15

    A clinical study was performed to evaluate the pharmacokinetics (PK) and toxicity of three dose levels of the angiogenesis inhibitor recombinant human (rh) angiostatin when administered twice daily by s.c. injection. Eligible patients had cancer not amenable to standard treatments. Three groups of 8 patients received 7.5, 15, or 30 mg/m(2)/day divided in two s.c. injections for 28 consecutive days followed by a 7-day washout period. PK assessment was done at days 1 and 28. Thereafter, in absence of toxicity or a 100% increase in tumor size, treatment was continued without interruption. Median age was 53 years (range, 43-75), male:female ratio 10:14, Eastern Cooperative Oncology Group performance 0-1. At the range of doses evaluated, serum PK of all 24 of the patients showed linear relation between dose and area under the curve (0- infinity) and C(max) (reached after 2 h). Thirteen of 24 patients developed erythema at injection sites (11 patients, CTC grade 1; 2 patients, CTC grade 2) without pain or itching, spontaneously resolving within 2-3 weeks of treatment. Two patients went off study after developing hemorrhage in brain metastases, and 2 patients developed deep venous thrombosis. No other relevant treatment-related toxicities were seen, even during prolonged treatment. A panel of coagulation parameters was not influenced by rhAngiostatin treatment. Long-term (>6 months) stable disease (<25% growth of measurable uni- or bidimensional tumor size) was observed in 6 of 24 patients. Five patients received rhAngiostatin treatment for >1 year (overall median time on treatment 99 days). Long-term twice-daily s.c. treatment with rhAngiostatin is well tolerated and feasible at the selected doses, and merits additional evaluation. Systemic exposure to rhAngiostatin is within the range of drug exposure that has biological activity in preclinical models.

  17. [Long-term administration of opioids for non-tumor pain - LONTS guideline provides an orientation].

    PubMed

    Petzke, Frank

    2015-10-01

    The long-term usage of opioid analgesics (> 3 months) for chronic, non-cancer related pain is critically discussed nationally and internationally. There are indications of under- and oversupply as well as misuse of opioids in Germany, but an "opioid epidemic" such as is evident in the USA cannot be detected at present.The S3-guideline LONTS (long-term usage of opioid analgesics for non-cancer related pain)serves as an orientation to improve provision of opioids and contains statements about the available evidence, indications and contraindications of use, as well as practical recommendations for managing a long-term opioid therapy. © Georg Thieme Verlag Stuttgart · New York.

  18. Effect of long-term administration of cordycepin from Cordyceps militaris on testicular function in middle-aged rats.

    PubMed

    Sohn, Sang-Hyun; Lee, Su-Chan; Hwang, Seock-Yeon; Kim, Sung-Won; Kim, Il-Woung; Ye, Michael B; Kim, Si-Kwan

    2012-10-01

    This study was carried out to examine the potential beneficial effect of cordycepin on the decline of testicular function induced with age. A total of 30 male Sprague-Dawley rats (twenty-four 12-month-olds and six 2-month-olds) were divided into five groups. The young control (YC) and middle-aged control (MC) groups received vehicle only. Cordycepin-treated groups were administered daily doses of oral cordycepin at 5, 10, and 20 mg/kg body weight for 4 months. As a result, the MC group exhibited epididymal weight loss, decreased sperm motility, and reduced spermatogenesis compared to the young control group. Interestingly, the epididymal weights of middle-aged rats were dose-dependently increased by treatment with cordycepin. Cordycepin also improved calcium levels and decreased urea and nitrogen, uric acid, and creatinine in the blood of middle-aged rats. In addition, cordycepin significantly increased sperm motility and the progressiveness of sperm movement. All cordycepin-treated groups showed well-arranged spermatogonia, densely packed cellular material, and increased numbers of mature spermatozoa in the seminiferous lumen compared to the middle-aged control group. These results indicate that long-term administration of cordycepin can counteract the decline of testicular function in middle-aged rats.

  19. Long-term efficacy and safety of once-daily mesalazine granules for the treatment of active ulcerative colitis

    PubMed Central

    Böhm, Stephan Karl; Kruis, Wolfgang

    2014-01-01

    demonstrated that OD administration of 5-ASA is as effective as conventional dosing in mild to moderate active UC. The three 5-ASA products MMX, Salofalk®, and Pentasa® employed in those studies so far have not shown differences in efficacy between OD and conventional dosing. No differences regarding safety outcomes have been detected between OD and conventional dosing, including incidence of adverse events, serious adverse events, or withdrawal from treatment due to an adverse event. Although the majority of patients prefer OD dosing to conventional dosing, it was not possible to detect differences in adherence between OD and multiple dose regimens in the clinical trial setting. Well-designed and controlled large-scale community-based studies are necessary to further investigate and prove the point of improved long-term adherence and treatment efficacy in OD dosing. PMID:25285021

  20. Long-term variation in the upper atmosphere as seen in the amplitude of the geomagnetic solar quiet daily variation

    NASA Astrophysics Data System (ADS)

    Shinbori, A.; Koyama, Y.; Hayashi, H.; Nose, M.; Hori, T.; Otsuka, Y.; Tsuda, T.

    2011-12-01

    It has been well-known that geomagnetic solar quiet (Sq) daily variation is produced by global ionospheric currents flowing in the E-region from middle latitudes to the magnetic equator. These currents are generated by a dynamo process via interaction between the neutral wind and ionospheric plasma in a region of the thermosphere and ionosphere. From the Ohm's equation, the ionospheric currents strongly depend on the ionospheric conductivity, polarization electric field and neutral wind. Then, to investigate the Sq amplitude is essential for understanding the long-term variations in the ionospheric conductivity and neutral wind of the thermosphere and ionosphere. Elias et al. [2010] found that the Sq amplitude tends to increase by 5.4-9.9 % in the middle latitudes from 1961 to 2001. They mentioned that the long-term variation of ionospheric conductivity associated with geomagnetic secular variation mainly determines the Sq trend, but that the rest component is ionospheric conductivity enhancement associated with cooling effects in the thermosphere due to increasing the greenhouse gases. In this talk, we clarify the characteristics of the long-term variation in the Sq amplitude using the long-term observation data of geomagnetic field and neutral wind. These observation data have been provided by the IUGONET (Inter-university Upper atmosphere Global Observation NETwork) project. In the present analysis, we used the F10.7 flux as an indicator of the variation in the solar irradiance in the EUV and UV range, geomagnetic field data with time resolution of 1 hour. The definition of the Sq amplitude is the difference of the H-component between the maximum and minimum per day when the Kp index is less than 4. As a result, the Sq amplitude at all the stations strongly depends on 11-year solar activity, and tends to enhance more during the high activities (19- and 22- solar cycles) than during the low activity (20-solar cycle). The Fourier spectra of the F10.7 flux and Sq

  1. Daily acclimation handling does not affect hippocampal long-term potentiation or cause chronic sleep deprivation in mice.

    PubMed

    Vecsey, Christopher G; Wimmer, Mathieu E J; Havekes, Robbert; Park, Alan J; Perron, Isaac J; Meerlo, Peter; Abel, Ted

    2013-04-01

    Gentle handling is commonly used to perform brief sleep deprivation in rodents. It was recently reported that daily acclimation handling, which is often used before behavioral assays, causes alterations in sleep, stress, and levels of N-methyl-D-aspartate receptor subunits prior to the actual period of sleep deprivation. It was therefore suggested that acclimation handling could mediate some of the observed effects of subsequent sleep deprivation. Here, we examine whether acclimation handling, performed as in our sleep deprivation studies, alters sleep/wake behavior, stress, or forms of hippocampal synaptic plasticity that are impaired by sleep deprivation. Adult C57BL/6J mice were either handled daily for 6 days or were left undisturbed in their home cages. On the day after the 6(th) day of handling, long-term potentiation (LTP) was induced in hippocampal slices with spaced four-train stimulation, which we previously demonstrated to be impaired by brief sleep deprivation. Basal synaptic properties were also assessed. In three other sets of animals, activity monitoring, polysomnography, and stress hormone measurements were performed during the 6 days of handling. Daily gentle handling alone does not alter LTP, rest/activity patterns, or sleep/wake architecture. Handling initially induces a minimal stress response, but by the 6(th) day, stress hormone levels are unaltered by handling. It is possible to handle mice daily to accustom them to the researcher without causing alterations in sleep, stress, or synaptic plasticity in the hippocampus. Therefore, effects of acclimation handling cannot explain the impairments in signaling mechanisms, synaptic plasticity, and memory that result from brief sleep deprivation.

  2. Intrahippocampal Glutamine Administration Inhibits mTORC1 Signaling and Impairs Long-Term Memory

    ERIC Educational Resources Information Center

    Rozas, Natalia S.; Redell, John B.; Pita-Almenar, Juan D.; McKenna, James, III.; Moore, Anthony N.; Gambello, Michael J.; Dash, Pramod K.

    2015-01-01

    The mechanistic Target of Rapamycin Complex 1 (mTORC1), a key regulator of protein synthesis and cellular growth, is also required for long-term memory formation. Stimulation of mTORC1 signaling is known to be dependent on the availability of energy and growth factors, as well as the presence of amino acids. In vitro studies using serum- and amino…

  3. Intrahippocampal Glutamine Administration Inhibits mTORC1 Signaling and Impairs Long-Term Memory

    ERIC Educational Resources Information Center

    Rozas, Natalia S.; Redell, John B.; Pita-Almenar, Juan D.; McKenna, James, III.; Moore, Anthony N.; Gambello, Michael J.; Dash, Pramod K.

    2015-01-01

    The mechanistic Target of Rapamycin Complex 1 (mTORC1), a key regulator of protein synthesis and cellular growth, is also required for long-term memory formation. Stimulation of mTORC1 signaling is known to be dependent on the availability of energy and growth factors, as well as the presence of amino acids. In vitro studies using serum- and amino…

  4. Long-term variation in the upper atmosphere as seen in the geomagnetic solar quiet daily variation

    NASA Astrophysics Data System (ADS)

    Shinbori, Atsuki; Koyama, Yukinobu; Nose, Masahito; Hori, Tomoaki; Otsuka, Yuichi; Yatagai, Akiyo

    2014-12-01

    Characteristics of long-term variation in the amplitude of solar quiet (Sq) geomagnetic field daily variation have been investigated using 1-h geomagnetic field data obtained from 69 geomagnetic observation stations within the period of 1947 to 2013. The Sq amplitude observed at these geomagnetic stations showed a clear dependence on the 10- to 12-year solar activity cycle and tended to be enhanced during each solar maximum phase. The Sq amplitude was the smallest around the minimum of solar cycle 23/24 in 2008 to 2009. The relationship between the solar F10.7 index and Sq amplitude was approximately linear but about 53% of geomagnetic stations showed a weak nonlinear relation to the solar F10.7 index. In order to remove the effect of solar activity seen in the long-term variation of the Sq amplitude, we calculated a linear or second-order fitting curve between the solar F10.7 index and Sq amplitude during 1947 to 2013 and examined the residual Sq amplitude, which is defined as the deviation from the fitting curve. As a result, the majority of trends in the residual Sq amplitude that passed through a trend test showed negative values over a wide region. This tendency was relatively strong in Europe, India, the eastern part of Canada, and New Zealand. The relationship between the magnetic field intensity at 100-km altitude and residual Sq amplitude showed an anti-correlation for about 71% of the geomagnetic stations. Furthermore, the residual Sq amplitude at the equatorial station (Addis Ababa) was anti-correlated with the absolute value of the magnetic field inclination. This implies movement of the equatorial electrojet due to the secular variation of the ambient magnetic field.

  5. Long-term daily access to alcohol alters dopamine-related synthesis and signaling proteins in the rat striatum.

    PubMed

    Kashem, Mohammed Abul; Ahmed, Selina; Sarker, Ranjana; Ahmed, Eakhlas U; Hargreaves, Garth A; McGregor, Iain S

    2012-12-01

    Chronic alcohol exposure can adversely affect neuronal morphology, synaptic architecture and associated neuroplasticity. However, the effects of moderate levels of long-term alcohol intake on the brain are a matter of debate. The current study used 2-DE (two-dimensional gel electrophoresis) proteomics to examine proteomic changes in the striatum of male Wistar rats after 8 months of continuous access to a standard off-the-shelf beer in their home cages. Alcohol intake under group-housed conditions during this time was around 3-4 g/kg/day, a level below that known to induce physical dependence in rats. After 8 months of access rats were euthanased and 2-DE proteomic analysis of the striatum was conducted. A total of 28 striatal proteins were significantly altered in the beer drinking rats relative to controls. Strikingly, many of these were dopamine (DA)-related proteins, including tyrosine hydroxylase (an enzyme of DA biosynthesis), pyridoxal phosphate phosphatase (a co-enzyme in DA biosynthesis), DA and cAMP regulating phosphoprotein (a regulator of DA receptors and transporters), protein phosphatase 1 (a signaling protein) and nitric oxide synthase (which modulates DA uptake). Selected protein expression changes were verified using Western blotting. We conclude that long-term moderate alcohol consumption is associated with substantial alterations in the rat striatal proteome, particularly with regard to dopaminergic signaling pathways. This provides potentially important evidence of major neuroadaptations in dopamine systems with daily alcohol consumption at relatively modest levels. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Long-term intravenous administration of antibiotics for lumbar spinal surgery prolongs the duration of hospital stay and time to normalize body temperature after surgery.

    PubMed

    Ohtori, Seiji; Inoue, Gen; Koshi, Takana; Yamashita, Masaomi; Yamauchi, Kazuyo; Suzuki, Munetaka; Orita, Sumihisa; Eguchi, Yawara; Ochiai, Nobuyasu; Kishida, Shunji; Takaso, Masashi; Takahashi, Kazuhisa

    2008-12-15

    Comparative study of differing durations of antibiotics for spinal surgery. To compare rate of infection, duration of hospital stay, days until normal body temperature, and a panel of blood tests after surgery between long-term and short-term administration of antibiotics for spinal surgery using instrumentation. Recent studies have reported that long-term administration of intravenous antibiotics is not necessary to avoid superficial and deep infections. We therefore changed the duration of administration from 9 to 2 days in our lumbar surgery patients. We examined 135 patients (average age, 64.9 years) who underwent lumbar spinal surgery to insert a pedicle screw system to treat spinal canal stenosis. We administered 2 g of cefotiam daily to 60 patients for 9 days after surgery and to 75 patients for 2 days after surgery. Surgical time, loss of blood, rate of infection, duration of hospital stay, days until normal body temperature, and data from blood analysis (white blood cell count, and C-reactive protein [CRP] level) were statistically compared between the 2 groups. No significant differences in intraoperative measures of surgical invasion were observed between the 2 groups (surgical time, 209 vs. 220 minutes; blood loss, 530 vs. 576 mL; blood transfusion, 344 vs. 380 mL for the long-term and short-term groups, respectively). No acute infections occurred in either group. However, the duration of hospital stay (20.7 days), time until normal body temperature (5.1 days), and CRP level (2.23 mg/dL) at day 7 after surgery were significantly less in the short-term group than those in the long-term group (27.9 days, 6.8 days, and 3.13 mg/dL, respectively; P < 0.05). These results indicate that short-term intravenous administration of antibiotics did not elevate the infection rate after spinal surgery using instrumentation. However, long-term administration of antibiotics prolonged the duration of hospital stay, inhibited normalization of body temperature, and

  7. Risk-adjusted impact of administrative costs on the distribution of terminal wealth for long-term investment.

    PubMed

    Guillén, Montserrat; Jarner, Søren Fiig; Nielsen, Jens Perch; Pérez-Marín, Ana M

    2014-01-01

    The impact of administrative costs on the distribution of terminal wealth is approximated using a simple formula applicable to many investment situations. We show that the reduction in median returns attributable to administrative fees is usually at least twice the amount of the administrative costs charged for most investment funds, when considering a risk-adjustment correction over a reasonably long-term time horizon. The example we present covers a number of standard cases and can be applied to passive investments, mutual funds, and hedge funds. Our results show investors the potential losses they face in performance due to administrative costs.

  8. Risk-Adjusted Impact of Administrative Costs on the Distribution of Terminal Wealth for Long-Term Investment

    PubMed Central

    Guillén, Montserrat; Jarner, Søren Fiig; Pérez-Marín, Ana M.

    2014-01-01

    The impact of administrative costs on the distribution of terminal wealth is approximated using a simple formula applicable to many investment situations. We show that the reduction in median returns attributable to administrative fees is usually at least twice the amount of the administrative costs charged for most investment funds, when considering a risk-adjustment correction over a reasonably long-term time horizon. The example we present covers a number of standard cases and can be applied to passive investments, mutual funds, and hedge funds. Our results show investors the potential losses they face in performance due to administrative costs. PMID:25180200

  9. Direct and indirect effects of nutritional status, physical function and cognitive function on activities of daily living in Japanese older adults requiring long-term care.

    PubMed

    Kamo, Tomohiko; Nishida, Yuusuke

    2014-10-01

    To identify the direct and indirect effects of nutritional status, physical function, and cognitive function on activities of daily living in Japanese older adults requiring long-term care. In total, 179 participants aged ≥ 65 years who were eligible for long-term care insurance (mean age 85.5 ± 7.8 years) were recruited for this study. Nutritional status (Mini Nutritional Assessment, Short Form) and physical function (Short Physical Performance Battery) were examined. Activities of daily living, cognitive function and frailty were assessed using the Barthel Index, Mini-Mental State Examination and Clinical Frailty Scale, respectively. Path analysis was used to determine relationships between these factors and the activities of daily living. For Japanese older adults requiring long-term care, pathways were modeled for nutritional status, physical function and the activities of daily living. The total effect of nutritional status was 0.516 (P<0.001). The indirect effect of nutritional status through physical function on the activities of daily living was 0.458 (P<0.001). Finally, no significant direct effect of nutritional status on activities of daily living was observed (b=0.058, P=0.258). The present study identified the complex pathway from nutritional status to the activities of daily living through physical function in aged Japanese people requiring long-term care. These findings suggest that maintaining good nutritional status and nutritional support might delay physical function decline, and prolong the activities of daily living. © 2013 Japan Geriatrics Society.

  10. Effects of Chronic Vitamin D3 Hormone Administration on Anxiety-Like Behavior in Adult Female Rats after Long-Term Ovariectomy

    PubMed Central

    Fedotova, Julia; Pivina, Svetlana; Sushko, Anastasia

    2017-01-01

    The present preclinical study was created to determine the therapeutic effects of vitamin D hormone treatment as an adjunctive therapy alone or in a combination with low dose of 17β-estradiol (17β-E2) on anxiety-like behavior in female rats with long-term absence of estrogen. Accordingly, the aim of the current study was to examine the effects of chronic cholecalciferol administration (1.0, 2.5 or 5.0 mg/kg subcutaneously, SC, once daily, for 14 days) on the anxiety-like state after long-term ovariectomy in female rats. Twelve weeks postovariectomy, cholecalciferol was administered to ovariectomized (OVX) rats and OVX rats treated with 17β-E2 (0.5 µg/rat SC, once daily, for 14 days). Anxiety-like behavior was assessed in the elevated plus maze (EPM) and the light/dark test (LDT), and locomotor and grooming activities were tested in the open field test (OFT). Cholecalciferol at two doses of 1.0 and 2.5 mg/kg alone or in combination with 17β-E2 produced anxiolytic-like effects in OVX rats as evidenced in the EPM and the LDT, as well as increased grooming activity in the OFT. Our results indicate that cholecalciferol, at two doses of 1.0 and 2.5 mg/kg, has a profound anxiolytic-like effects in the experimental rat model of long-term estrogen deficiency. PMID:28054941

  11. Long-Term Oral Administration of Hop Flower Extracts Mitigates Alzheimer Phenotypes in Mice

    PubMed Central

    Sasaoka, Norio; Sakamoto, Megumi; Kanemori, Shoko; Kan, Michiru; Tsukano, Chihiro; Takemoto, Yoshiji; Kakizuka, Akira

    2014-01-01

    Coincident with the expanding population of aged people, the incidence of Alzheimer disease (AD) is rapidly increasing in most advanced countries. At present, no effective prophylactics are available. Among several pathological mechanisms proposed for AD, the “amyloid hypothesis” has been most widely accepted, in which accumulation or deposition of Aβ is considered to be the initial event. Thus, prevention of Aβ production would be an ideal strategy for the treatment or prevention of AD. Aβ is produced via the proteolytic cleavage of its precursor protein, APP (amyloid precursor protein), by two different enzymes, β and γ-secretases. Indeed, inhibitors against either or both enzymes have been developed and tested for clinical efficacy. Based on the “amyloid hypothesis”, we developed a luciferase-based screening method to monitor γ-secretase activity, screened more than 1,600 plant extracts, most of which have long been used in Chinese medicine, and observed that Hop extracts significantly inhibit Aβ production in cultured cells. A major component of the inhibitory activity was purified, and its chemical identity was determined by NMR to be Garcinielliptone HC. In vivo, oral administration of Hop extracts to AD model mice decreased Aβ depositions in the cerebral cortex of the parietal lobe, hippocampus, and artery walls (amyloid angiopathy) in the brains. In a Morris water maze test, AD model mice that had daily consumed Hop extracts in their drinking water showed significant mitigation of memory impairment at ages of 9 and 12 months. Moreover, in the open field test oral administration of Hop extracts also prevented an emotional disturbance that appeared in the AD mice at 18 months. Despite lifelong consumption of Hop extracts, no deleterious side effects were observed at any age. These results support the “amyloid hypothesis”, and indicate that Hop extract is a promising candidate for an effective prophylactic for AD. PMID:24489866

  12. Long-term oral administration of hop flower extracts mitigates Alzheimer phenotypes in mice.

    PubMed

    Sasaoka, Norio; Sakamoto, Megumi; Kanemori, Shoko; Kan, Michiru; Tsukano, Chihiro; Takemoto, Yoshiji; Kakizuka, Akira

    2014-01-01

    Coincident with the expanding population of aged people, the incidence of Alzheimer disease (AD) is rapidly increasing in most advanced countries. At present, no effective prophylactics are available. Among several pathological mechanisms proposed for AD, the "amyloid hypothesis" has been most widely accepted, in which accumulation or deposition of Aβ is considered to be the initial event. Thus, prevention of Aβ production would be an ideal strategy for the treatment or prevention of AD. Aβ is produced via the proteolytic cleavage of its precursor protein, APP (amyloid precursor protein), by two different enzymes, β and γ-secretases. Indeed, inhibitors against either or both enzymes have been developed and tested for clinical efficacy. Based on the "amyloid hypothesis", we developed a luciferase-based screening method to monitor γ-secretase activity, screened more than 1,600 plant extracts, most of which have long been used in Chinese medicine, and observed that Hop extracts significantly inhibit Aβ production in cultured cells. A major component of the inhibitory activity was purified, and its chemical identity was determined by NMR to be Garcinielliptone HC. In vivo, oral administration of Hop extracts to AD model mice decreased Aβ depositions in the cerebral cortex of the parietal lobe, hippocampus, and artery walls (amyloid angiopathy) in the brains. In a Morris water maze test, AD model mice that had daily consumed Hop extracts in their drinking water showed significant mitigation of memory impairment at ages of 9 and 12 months. Moreover, in the open field test oral administration of Hop extracts also prevented an emotional disturbance that appeared in the AD mice at 18 months. Despite lifelong consumption of Hop extracts, no deleterious side effects were observed at any age. These results support the "amyloid hypothesis", and indicate that Hop extract is a promising candidate for an effective prophylactic for AD.

  13. Long-term drug survival and clinical effectiveness of etanercept treatment in patients with ankylosing spondylitis in daily clinical practice.

    PubMed

    Arends, Suzanne; Brouwer, Elisabeth; Efde, Monique; van der Veer, Eveline; Bootsma, Hendrika; Wink, Freke; Spoorenberg, Anneke

    2017-01-01

    Randomised controlled trials and open-label extension studies have demonstrated the clinical efficacy and safety of tumour necrosis factor-alpha (TNF-α) blocking therapy in pre-selected study patients with ankylosing spondylitis (AS). Our aim was to investigate the 7-year drug survival and clinical effectiveness of etanercept treatment in AS patients in daily clinical practice. Consecutive AS patients from the prospective observational GLAS cohort who started etanercept because of active disease were included and evaluated over 7 years according to a fixed protocol. Continuation of treatment was based on BASDAI improvement and/or expert opinion. Of the 89 included AS patients, 45 (51%) were still using etanercept at 7 years of follow-up. Reasons for treatment discontinuation were adverse events (n=22), inefficacy (n=13), or other reasons although good clinical response (n=9). Etanercept treatment resulted in a rapid (after 6 weeks) and sustained improvement in disease activity (BASDAI, ASDAS, CRP, physician GDA), spinal mobility, physical function (BASFI), quality of life (ASQoL), and extra-spinal manifestations (swollen joints, tender joints and tender entheses). Furthermore, concomitant NSAID or DMARD use decreased significantly during follow-up. At 7 years, low disease activity and remission were present in 67-73% and 29-30% of the 45 patients, respectively. Of the patients who discontinued etanercept, 18 switched successfully to a second or third TNF-α blocker during follow-up. In a large cohort of AS patients treated with etanercept, approximately 50% continued this treatment for 7 years. Our broad evaluation of clinical endpoints proves the long-term effectiveness of etanercept treatment in daily clinical practice.

  14. [Role of GABA-ergic and dopaminergic mechanisms in the withdrawal syndrome after discontinuation of long-term phenazepam administration].

    PubMed

    Voronina, T A; Garibova, T L

    1980-07-01

    It has been shown that depakin, a GABA-ergic agonist, and alpha-methyl-DOPA that inhibits catecholamine synthesis are capable of removing the withdrawal syndrome (disturbed pavlovian behavior pattern and aggressiveness) occurring after discontinuance of long-term administration (30 days) of phenazepam to rats in a dose of 2 mg/kg. In contrast, bicucullin, a blocker of GABA-ergic receptors, thiosemicarbazide that inhibits GABA synthesis by the brain, disulfiram and 3,4-dioxyphenylalanine that increase dopamine and noradrenaline content in the barain aggravate the withdrawal syndrome after phenazepam is discontinued. The data obtained suggest a role of GABA-ergic and dopaminergic mechanisms in the emergence of the withdrawal syndrome after discontinuance of long-term administration of benzdiazepins.

  15. The pharmacokinetic-pharmacodynamic model of telmisartan and hydrochlorothiazide on blood pressure and plasma potassium after long-term administration in spontaneously hypertensive rats.

    PubMed

    Yu, Dan; Chen, Yuancheng; Hao, Kun

    2015-12-01

    A pharmacokinetic-pharmacodynamic model was developed to describe the time course of blood pressure and plasma potassium after long-term telmisartan and/or hydrochlorothiazide administration in spontaneously hypertensive rats. The spontaneously hypertensive rats were administered once daily for 6 weeks. The drug concentration, blood pressure and plasma potassium were monitored for several points. The time courses of blood pressure and plasma potassium were described by indirect response pharmacokinetic-pharmacodynamic model. The synergistic antihypertensive pharmacodynamic interaction between telmisartan and hydrochlorothiazide was observed, which was simulated by the inhibitory function of telmisartan and stimulatory function of hydrochlorothiazide after co-administration of the two drugs. For plasma potassium, when hydrochlorothiazide administrated alone, the plasma potassium reached to a low steady-state level at 4.64 mmol/L for 6 weeks. The plasma potassium increased to a steady-state level at 4.84 mmol/L after co-administration of telmisartan. The time courses of plasma potassium were successfully characterized by indirect response pharmacokinetic-pharmacodynamic model after long-term administration of telmisartan and/or hydrochlorothiazide. The model captured turnovers of blood pressure and plasma potassium in the different time phases and dose conditions. © 2015 Société Française de Pharmacologie et de Thérapeutique.

  16. [Long-term oxygen therapy: which form of administration can be recommended?].

    PubMed

    Tausendpfund, C; Petro, W

    1996-03-01

    A great variety of application devices for long-term-oxygen-therapy are being used. In order to find out which products can be especially recommended we conducted an inquiry among German lung specialists asking which devices they were preferring and why. Additionally, in a clinical study the efficiency of basic types of products has been compared. Data about patients' acceptance of different devices have been collected by another inquiry. As it turned out the most efficient models (e.g. oxygen catheters) are only accepted by a very small number of patients. So they can not be recommended for long-term-oxygen-therapy. Patients' acceptance concentrates on nasal oxygen cannulae having two tubes that lead into the nostrils but no foam pad. The product PARI 96.2020 is expecially favoured as it combines "tight fit", "soft material" and "easy handling", criteria most important for the patients. Similar models (PARI 96.2021 and Airlife), although following on the next two places, are only favoured by half as much patients. As obviously quite simple, functional products are preferred to very sophisticated and expensive ones, future development should also follow the demands of patients, not only theoretical considerations.

  17. Changes in renal vessels associated with long-term administration of angiotensin converting enzyme inhibitor in Zucker fatty rats

    PubMed Central

    Nakanishi, Kazushige; Nagai, Yohko; Akimoto, Tatsuo; Yamanaka, Nobuaki

    2017-01-01

    Background Recently, we showed that long-term angiotensin receptor blocker (ARB) administration induced unusual proliferative changes in smooth muscle cells (SMCs) of afferent arterioles of the kidneys of Zucker fatty rats (ZFRs). In this study, we investigated renal afferent arteriolar changes induced by the long-term administration of an angiotensin converting enzyme inhibitor (ACEI) in ZFRs. Materials and Methods Fourteen 6-week-old male ZFRs were divided into two groups (n=14): the ZFR+ACEI group (n=6) was fed a standard diet containing ACEI (Enalapril, 2 mg/kg/day), and the ZFR control group (n=8) for 12 weeks. Blood pressure and proteinuria were examined and morphological studies on kidneys were performed. Results Remarkable proliferative changes in the afferent arteriolar SMCs were frequently observed in the group given ACEI; (66.1 ± 12.9%) compared with the control group (1.77 ± 1.56%, P<0.001). Conclusions It was indicated that long-term ACEI administration induced unusual proliferative changes in SMCs in afferent arterioles of ZFRs. These changes could reduce intraglomerular pressure by narrowing the lumens of afferent arterioles, but they could cause irreversible damage to the arterioles. PMID:28260705

  18. Final Report on the Development of a Baccalaureate External Degree Program in Health Services Administration With a Major in Long Term Care Administration.

    ERIC Educational Resources Information Center

    Kleppick, Annabelle L.; And Others

    A project undertaken at the Graduate School of Public Health of the University of Pittsburgh to develop an undergraduate external degree program in health services administration with a major in long-term care administration is described. Program activities were designed to: develop a work plan, identify the parameters of knowledge and skills…

  19. Long-term trends in daily precipitation over the Yangtze River Delta region during 1960-2012, Eastern China

    NASA Astrophysics Data System (ADS)

    Hu, Chunsheng; Xu, Youpeng; Han, Longfei; Yang, Liu; Xu, Guanglai

    2016-07-01

    Based on daily precipitation data from 24 stations over the Yangtze River Delta (YRD) region, the long-term trends of daily precipitation are analyzed during the period 1960-2012 using 12 precipitation indices. The results indicate that the following. (1) For the regional average trends of precipitation, nine indices [i.e., RR, SDII, PCI(day), R25mm, R50mm, R25mmT, R50mmT, R25mmTOT, and R50mmTOT] show the increasing trends, while three indices [i.e., RX1day, RR1 and PCI(month)] display the decreasing trends. Furthermore, the annual total precipitation (RR) is correlated strongly with most of the other precipitation indices, especially indices represent the heavy precipitation which is responsible for more than 90 % of the total increase of precipitation. (2) The central and southern parts of the study area become more humid than the northern parts, although the daily precipitation undergo a consistent concentrated trend over almost all of the study area. Moreover, the frequency and contribution of the heavy precipitation also arise dramatically in almost the entire study area, and the precipitation events show the significant trend of extremeness. (3) The abrupt changes for RR, RX1day, SDII, R50mm, R50mmT, and R50mmTOT are detected in 1984, 1988, 1987, 1984, 1988, and 1988, respectively, which indicate the abrupt change of precipitation occurred consistently in the mid-1980s. Three major cycles of precipitation detected are 5-6-year cycle, 13-year cycle, and 20-year cycle, with a nonsignificant 2-year cycle coexisted. In addition, a significant change of cycles occurred in the 1980s, when the short cycle was set to overtake the long cycle, resulting in high-frequency and instability of precipitation changes over the YRD region in recent decades. (4) There are three factors (the global warming, the East Asian summer monsoon change, and the urbanization development) might potentially impact on the frequency and volume of precipitation. The variation of East Asian

  20. Effect of vitamin E deficiency on inhibition of liver regeneration by long-term administration of alcohol.

    PubMed

    Tanaka, T; Goto, Y; Imano, M; Asai, H; Yamada, T; Kawai, S; Kunitoh, S; Kondo, K; Yamashita, T; Monna, T; Nishiguchi, S; Kuroki, T; Otani, S

    1996-02-01

    The effects of vitamin E (VE) deficiency on liver regeneration suppressed by long-term administration of alcohol were studied. Male rats were divided into two groups: the alcohol group and the control group. In addition, each group was subdivided into two groups according to the presence or not of VE. Altogether, four groups were provided: a group maintained on the VE-deficient alcohol diet (group EA), a group maintained on the VE-deficient control diet (group EC), a group maintained on the ordinary alcohol diet (group A), and a group maintained on the ordinary control diet (group C). After pair-feeding for 6 weeks, partial hepatectomy was performed to determine the omithine decarboxylase (ODC) activity, polyamine levels, lipid peroxide levels, and DNA synthesis, DNA synthesis at 24 hr after partial hepatectomy was suppressed significantly in the alcohol administration group, regardless of the presence or not of VE DNA synthesis at 48 hr after partial hepatectomy tended to show low values in group EA, compared with group A. As for the hepatic ODC activity, group EA showed the lowest value at 4 hr after partial hepatectomy. Of polyamines, the putrescine level in group EA at 4 hr after partial hepatectomy was significantly low, compared with the other three groups. The levels of spermidine and spermine decreased by long-term administration of alcohol, but the effect of VE deficiency was not found. The lipid peroxide level increased significantly in the VE-deficient diet administration group, but the effect of alcohol administration was not found. These results suggested that the decrease in putrescine after ODC suppression by VE deficiency in addition to the decrease in spermidine and spermine caused by long-term alcohol administration were concerned with suppression of DNA synthesis later.

  1. Daily activity level improvement with antidepressant medications predicts long-term clinical outcomes in outpatients with major depressive disorder

    PubMed Central

    Jha, Manish K; Teer, Raymond B; Minhajuddin, Abu; Greer, Tracy L; Rush, A John; Trivedi, Madhukar H

    2017-01-01

    independently predicts long-term clinical outcomes. Brief systematic assessment of activity impairment during the course of antidepressant treatment can help inform clinical decision-making. PMID:28352180

  2. Withdrawal from Long-Term Methamphetamine Self-Administration ‘Normalizes’ Neurometabolites in Rhesus Monkeys: A 1H MR Spectroscopy Study

    PubMed Central

    Yang, Shaolin; Belcher, Annabelle M.; Chefer, Svetlana; Vaupel, D.Bruce; Schindler, Charles W.; Stein, Elliot A.; Yang, Yihong

    2013-01-01

    1H magnetic resonance spectroscopy has demonstrated alterations in several neurometabolites in methamphetamine (METH)-dependent individuals in brain regions implicated in addiction. Yet it is unclear whether these neurochemicals return to homeostatic levels after an individual abstains from drug use, a difficult question to address due to high recidivism and poor study retention in human subjects. We thus utilized a nonhuman primate model of addiction to explore the effects of long-term drug exposure and withdrawal on brain neurochemistry. Ten rhesus macaque monkeys on an active METH self-administration protocol (average use 4.6±0.8 years, average daily intake between 0.4-1.2 mg/kg) and 10 age- and sex-matched drug-naïve controls (CONT) served as subjects. Concentrations of several neurochemicals were evaluated at several time points following withdrawal from drug availability (10 monkeys at 1 week and 1 and 3 months, and 6 monkeys at 6 and 12 months; CONT examined at one time point). At one week following METH withdrawal, we found increases in myo-inositol in anterior cingulate cortex in the METH group relative to CONT. These alterations showed a linear pattern of decreased levels (‘normalization’) by one year of abstinence. We also found decreases in glutamine and Glx (composed mainly of glutamate and glutamine) in the caudate-putamen of the same animals at early withdrawal that showed a similar linear pattern of increasing concentration by one year. These results demonstrate that despite protracted, long-term use, neurochemical changes seen following long term drug administration do not persist following prolonged abstinence, suggesting therapeutic effects of long-term withdrawal from drug use. PMID:23910722

  3. Effect of long-term administration of zinc after scrotal heating on mice spermatozoa and subsequent offspring quality.

    PubMed

    Ghasemi, N; Babaei, H; Azizallahi, S; Kheradmand, A

    2009-08-01

    This study was set to investigate whether the adverse effects of heat on spermatozoa and subsequent foetuses could be prevented by long-term zinc administration. The scrotums of animals were immersed in water at either 43 degrees C (heat group) or 23 degrees C (control group). Half of the heat and control mice were given 10 mg kg(-1) zinc every other day for 60 days and the others received sterile saline instead of zinc. Heat stress significantly reduced sperm motility, concentration, hypoosmotic swelling-water test (HOS-WT) positive and chromomycin A(3) (CMA(3)) negative spermatozoa at the first 15 days, and the greatest decrease occurred at 30 days (P < 0.05). Sperm motility, concentration and HOS-WT positive spermatozoa were also reduced initially in the zinc administered group, but we did not observe any further decrease in the above mentioned parameters on day 30 (P < 0.05). The weight of foetuses obtained from the females mated with paternal heat treatment males was significantly lower than that of the control group (P < 0.05) and long-term zinc therapy caused a partial recovery (P > 0.05). This study demonstrates that the adverse effects of hyperthermia on semen parameters may be prevented by zinc therapy. Likewise, long-term administration of zinc could improve quality of litter obtained from the females mated with scrotal heat treatment males.

  4. 41 CFR 301-11.15 - What expenses may be considered part of the daily lodging cost when I rent on a long-term basis?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 41 Public Contracts and Property Management 4 2012-07-01 2012-07-01 false What expenses may be considered part of the daily lodging cost when I rent on a long-term basis? 301-11.15 Section 301-11.15...., stove, refrigerator, chairs, tables, bed, sofa, television, or vacuum cleaner); (b) Cost of...

  5. Long-term globular adiponectin administration improves adipose tissue dysmetabolism in high-fat diet-fed Wistar rats.

    PubMed

    Matafome, P; Rodrigues, T; Pereira, A; Letra, L; Azevedo, H; Paixão, A; Silvério, M; Almeida, A; Sena, C; Seiça, R

    2014-10-01

    Adiponectin administration to obese or type 2 diabetic patients is still far off, due to its expensive costs and absence of studies demonstrating the effectiveness of its chronic administration. We performed long-term globular adiponectin administration, testing its usefulness in improving adipose tissue metabolism. Adiponectin (98 υg/day) was administered through a subcutaneous minipump with continued release (28 days) to Wistar rats fed a high-fat diet. Adiponectin decreased body weight and adipocyte size, while decreasing circulating leptin levels. More, adiponectin was able to increase IkappaBalpha and PPARgamma levels and to prevent high-fat diet-induced impairment of insulin signalling, especially in epididymal adipose tissue. This resulted in improved glucose profile. High-fat diet caused an impairment of lipolysis in epididymal adipose tissue, which was partially restored by adiponectin treatment. Long-term globular adiponectin administration was able to improve pathways of insulin signalling and lipid storage in adipose tissue of high-fat diet-fed rats, contributing to a better metabolic profile.

  6. Long-term changes of information environments and computer anxiety of nurse administrators in Japan.

    PubMed

    Majima, Yukie; Izumi, Takako

    2013-01-01

    In Japan, medical information systems, including electronic medical records, are being introduced increasingly at medical and nursing fields. Nurse administrators, who are involved in the introduction of medical information systems and who must make proper judgment, are particularly required to have at least minimal knowledge of computers and networks and the ability to think about easy-to-use medical information systems. However, few of the current generation of nurse administrators studied information science subjects in their basic education curriculum. It can be said that information education for nurse administrators has become a pressing issue. Consequently, in this study, we conducted a survey of participants taking the first level program of the education course for Japanese certified nurse administrators to ascertain the actual conditions, such as the information environments that nurse administrators are in, their anxiety attitude to computers. Comparisons over the seven years since 2004 revealed that although introduction of electronic medical records in hospitals was progressing, little change in attributes of participants taking the course was observed, such as computer anxiety.

  7. Using Department of Veterans Affairs Administrative databases to examine long-term care utilization for men and women veterans.

    PubMed

    Guihan, M; Weaver, F M; Cowper, D C; Nydam, T; Miskevics, S

    1999-06-01

    We examined long-term care (LTC) utilization by male and female veterans using administrative databases maintained by VA. Research questions included: (1) Which LTC services are utilized? (2) Do utilization patterns of older veterans differ from those of elderly persons in the general U.S. population? (3) Do LTC needs of veterans vary by gender? We were unable to track LTC utilization of individuals across administrative databases. Some databases could only provide information at the national level, or alternatively, were available only at local facilities, or only at the patient or program-level data--making it impossible to get a clear picture of all the services received by an individual. Those planning to use administrative databases to conduct research must: (1) take more time than expected; (2) be flexible/willing to compromise, (3) "ferret out" information, and (4) recognize that because of dynamism inherent in information systems, results may change over time.

  8. Long-Term Tolerability and Effectiveness of Once-Daily Mixed Amphetamine Salts (Adderall XR) in Children with ADHD

    ERIC Educational Resources Information Center

    McGough, James J.; Biederman, Joseph; Wigal, Sharon B.; Lopez, Frank A.; McCracken, James T.; Spencer, Thomas; Zhang, Yuxin; Tulloch, Simon J.

    2005-01-01

    Objective: To evaluate the long-term tolerability and effectiveness of extended-release mixed amphetamine salts (MAS XR; Adderall XR[R]) in children with attention-deficit/hyperactivity disorder (ADHD). Method: This was a 24-month, multicenter, open-label extension of TWO placebo-controlled studies of MAS XR in children with ADHD aged 6 to 12…

  9. Long-Term Tolerability and Effectiveness of Once-Daily Mixed Amphetamine Salts (Adderall XR) in Children with ADHD

    ERIC Educational Resources Information Center

    McGough, James J.; Biederman, Joseph; Wigal, Sharon B.; Lopez, Frank A.; McCracken, James T.; Spencer, Thomas; Zhang, Yuxin; Tulloch, Simon J.

    2005-01-01

    Objective: To evaluate the long-term tolerability and effectiveness of extended-release mixed amphetamine salts (MAS XR; Adderall XR[R]) in children with attention-deficit/hyperactivity disorder (ADHD). Method: This was a 24-month, multicenter, open-label extension of TWO placebo-controlled studies of MAS XR in children with ADHD aged 6 to 12…

  10. Detection of pivaloylcarnitine in pediatric patients with hypocarnitinemia after long-term administration of pivalate-containing antibiotics.

    PubMed

    Nakajima, Yoko; Ito, Tetsuya; Maeda, Yasuhiro; Ichiki, Sayaka; Sugiyama, Naruji; Mizuno, Mihoko; Makino, Yasuko; Sugiura, Tokio; Kurono, Yukihisa; Togari, Hajime

    2010-08-01

    Some oral antibiotics contain a pivalate ester, because molecules with a pivalate entity show enhanced absorption in the intestine. Upon absorption, such a "prodrug" is broken down into the active form of a given antibiotic and a pivalate molecule, the latter of which is converted to pivaloylcarnitine through pivaloyl-CoA and is excreted in the urine. Long-term administration of drugs containing pivalate decreases blood carnitine level and causes defects in fatty acid oxidation. Here, we used liquid chromatography tandem mass spectrometry to measure carnitine and pivaloylcarnitine levels in two patients (Patient 1: 16-month-old boy and Patient 2: 18-month-old boy) with secondary carnitine deficiency and hypoglycemic convulsions caused by pivalate-containing antibiotics. Both patients were administered excessive doses of pivalate for the long-term treatment of recurrent infection, and consequently, the serum free carnitine levels were very low (Patient 1: 1.0 micromol/L and Patient 2: 0.4 micromol/L), compared to normal range of 33.3-43.0 micromol/l, while the serum pivaloylcarnitine levels were elevated from normally undetectable level (Patient 1: 3.7 micromol/L and Patient 2: 1.6 micromol/L). Patient 1 recovered immediately after the glucose infusion, whereas Patient 2 remained symptomatic even after blood glucose level was normalized and fully recovered after carnitine supplementation. The urine pivaloylcarnitine level in Patient 2 was increased during carnitine supplementation (from 821.4 to 12,200 micromol/g creatinine) even after discontinuing the antibiotics, indicating that a considerable amount of pivalate was accumulated in the tissues. In conclusion, long-term administration of pivalate-containing antibiotics should be avoided particularly in children.

  11. Hepatitis B Surface Antigen Reduction by Switching from Long-term Nucleoside/nucleotide Analog Administration to Pegylated Interferon.

    PubMed

    Tamaki, Nobuharu; Kurosaki, Masayuki; Kusakabe, Atsunori; Orito, Etsuro; Joko, Kouji; Kojima, Yuji; Kimura, Hiroyuki; Uchida, Yasushi; Hasebe, Chitomi; Asahina, Yasuhiro; Izumi, Namiki

    2017-02-15

    Hepatitis B surface antigen (HBsAg) reduction during nucleoside/nucleotide analog (NA) therapy is slow and an alternative strategy for patients receiving ongoing NA to facilitate HBsAg reduction is required. We investigated whether switching to pegylated interferon (PEG-IFN) after long-term NA administration enhances HBsAg reduction. Forty-nine patients who switched from long-term NA to 48 weeks of PEG-IFN alfa-2a were studied. The mean duration of previous NA was 48 months (sequential group). A total of 147 patients who continued NA and matched for baseline characteristics were analyzed for comparison (NA continuation group). The treatment response was defined as HBsAg reduction ≥1.0 logIU/ml at the end of PEG-IFN. HBsAg reduction at week 48 was 0.81 ± 1.1 logIU/ml in the sequential group, which was significantly higher than that in the NA continuation group (0.11 ± 0.3 logIU/ml, p <0.001). The treatment response was achieved in 29% and 2% of the sequential group and NA continuation group (p <0.001), and the odds ratio of sequential therapy for treatment response was 19 compared with NA continuation (p <0.001). In patients positive for hepatitis B e antigen (HBeAg), HBeAg seroconversion was higher in the sequential group (44% vs. 8%, p <0.001). In HBeAg negative patients, only patients in the sequential group achieved HBsAg loss. No patient needed to resume NA administration because of HBV DNA increase accompanied by alanine aminotransferase flares. In summary, sequential therapy with PEG-IFN after long-term NA enhances the reduction of HBsAg and may represent a treatment option to promote HBsAg loss. This article is protected by copyright. All rights reserved.

  12. Projection of China's near- and long-term climate in a new high-resolution daily downscaled dataset NEX-GDDP

    NASA Astrophysics Data System (ADS)

    Bao, Yun; Wen, Xinyu

    2017-02-01

    The projection of China's near- and long-term future climate is revisited with a new-generation statistically downscaled dataset, NEX-GDDP (NASA Earth Exchange Global Daily Downscaled Projections). This dataset presents a high-resolution seamless climate projection from 1950 to 2100 by combining observations and GCM results, and remarkably improves CMIP5 hindcasts and projections from large scale to regional-to-local scales with an unchanged long-term trend. Three aspects are significantly improved: (1) the climatology in the past as compared against the observations; (2) more reliable near- and long-term projections, with a modified range of absolute value and reduced inter-model spread as compared to CMIP5 GCMs; and (3) much added value at regional-to-local scales compared to GCM outputs. NEX-GDDP has great potential to become a widely-used high-resolution dataset and a benchmark of modern climate change for diverse earth science communities.

  13. Long-term ascorbic acid administration causes anticonvulsant activity during moderate and long-duration swimming exercise in experimental epilepsy.

    PubMed

    Tutkun, Erkut; Arslan, Gokhan; Soslu, Recep; Ayyildiz, Mustafa; Agar, Erdal

    2015-01-01

    The benefits of regular exercise on brain health are undeniable. Long-term exercise increases the production of reactive oxygen species in brain. Therefore, athletes often consume antioxidant supplements to remedy exercise-related damage and fatigue during exercise. The aim of this study is to evaluate the role of ascorbic acid in the effects of different intensities of swimming exercise on the brain susceptibility to experimental epilepsy in rats. Ascorbic acid was administered intraperitoneally (ip) during three different swimming exercise programme for 90 days (15 min, 30 min, 90 min/day). The anticonvulsant activity regarding the frequency of epileptiform activity appeared in the 80 min after 500 units intracortical penicillin injection in 30 min and 90 min/day exercise groups. The administration of ascorbic acid (100 mg/kg, ip) did not alter the anticonvulsant properties seen in the in short-duration (15 min/day) swimming exercise group. The amplitude of epileptiform activity also became significant in the 110 and 120 min after penicillin injection in the moderate (30 min/day) and long duration (60 min/day) groups, respectively. The results of the present study provide electrophysiologic evidence that long-term administration of ascorbic acid causes anticonvulsant activities in the moderate and long-duration swimming exercise. Antioxidant supplementation such as ascorbic acid might be suggested for moderate and long-duration swimming exercise in epilepsy.

  14. Effects of long-term salicylate administration on synaptic ultrastructure and metabolic activity in the rat CNS

    PubMed Central

    Yi, Bin; Hu, Shousen; Zuo, Chuantao; Jiao, Fangyang; Lv, Jingrong; Chen, Dongye; Ma, Yufei; Chen, Jianyong; Mei, Ling; Wang, Xueling; Huang, Zhiwu; Wu, Hao

    2016-01-01

    Tinnitus is associated with neural hyperactivity in the central nervous system (CNS). Salicylate is a well-known ototoxic drug, and we induced tinnitus in rats using a model of long-term salicylate administration. The gap pre-pulse inhibition of acoustic startle test was used to infer tinnitus perception, and only rats in the chronic salicylate-treatment (14 days) group showed evidence of experiencing tinnitus. After small animal positron emission tomography scans were performed, we found that the metabolic activity of the inferior colliculus (IC), the auditory cortex (AC), and the hippocampus (HP) were significantly higher in the chronic treatment group compared with saline group (treated for 14 days), which was further supported by ultrastructural changes at the synapses. The alterations all returned to baseline 14 days after the cessation of salicylate-treatment (wash-out group), indicating that these changes were reversible. These findings indicate that long-term salicylate administration induces tinnitus, enhanced neural activity and synaptic ultrastructural changes in the IC, AC, and HP of rats due to neuroplasticity. Thus, an increased metabolic rate and synaptic transmission in specific areas of the CNS may contribute to the development of tinnitus. PMID:27068004

  15. Subcortical gray matter changes in transgender subjects after long-term cross-sex hormone administration.

    PubMed

    Seiger, Rene; Hahn, Andreas; Hummer, Allan; Kranz, Georg S; Ganger, Sebastian; Woletz, Michael; Kraus, Christoph; Sladky, Ronald; Kautzky, Alexander; Kasper, Siegfried; Windischberger, Christian; Lanzenberger, Rupert

    2016-12-01

    Sex-steroid hormones are primarily involved in sexual differentiation and development and are thought to underlie processes related to cognition and emotion. However, divergent results have been reported concerning the effects of hormone administration on brain structure including side effects like brain atrophy and dementia. Cross-sex hormone therapy in transgender subjects offers a unique model for studying the effects of sex hormones on the living human brain. In this study, 25 Female-to-Male (FtM) and 14 Male-to-Female (MtF) subjects underwent MRI examinations at baseline and after a period of at least 4-months of continuous cross-sex hormone administration. While MtFs received estradiol and anti-androgens, FtM subjects underwent high-dose testosterone treatment. The longitudinal processing stream of the FreeSurfer software suite was used for the automated assessment and delineation of brain volumes to assess the structural changes over the treatment period of cross-sex hormone administration. Most prominent results were found for MtFs receiving estradiol and anti-androgens in the form of significant decreases in the hippocampal region. Further analysis revealed that these decreases were reflected by increases in the ventricles. Additionally, changes in progesterone levels correlated with changes in gray matter structures in MtF subjects. In line with prior studies, our results indicate hormonal influences on subcortical structures related to memory and emotional processing. Additionally, this study adds valuable knowledge that progesterone may play an important role in this process.

  16. Efficacy of Long-Term Daily Dosage of Alfuzosin 10 mg upon Sexual Function of Benign Prostatic Hypertrophy Patients: Two-Year Prospective Observational Study.

    PubMed

    Yoon, Sol; Choi, Jae Hwi; Lee, Seung Hyun; Choi, See Min; Jeh, Seong Uk; Kam, Sung Chul; Hwa, Jeong Seok; Chung, Ky Hyun; Hyun, Jae Seog

    2014-12-01

    To identify sexual function improvement associated with alfuzosin (10 mg daily for 2 years). We enrolled 30 men with lower urinary tract symptom (LUTS) who visited Gyeongsang National University Hospital between 2010 and 2012. At first visit, urinalysis, prostate specific antigen, transrectal ultrasound, and uroflowmetry were performed. The nternational Prostate Symptom Score (IPSS), quality of life (QoL), International Index of Erectile Function (IIEF), and Male Sexual Health Questionnaire Ejaculation Function Domain (MSHQ-EjFD) questionnaires were administered, and the subjects answered the same questionnaires at 1 month, 6 months, 1 year, and 2 years of follow-up. Twelve men completed of the entire study. After administration of alfuzosin, the median IPSS at first visit, 1 month, 6 months, 1 year, and 2 years was 18.00 (interquatile range [IQR]: 14.00~29.75), 20.00 (IQR: 11.50~30.00), 15.50 (IQR: 8.50~25.25), 14.50 (IQR: 9.25~19.50), and 11.50 (IQR: 5.00~17.75), respectively, which showed an improvement. The median QoL at the same times was 4.50 (IQR: 4.00~5.00), 4.50 (IQR: 4.00~5.00), 3.00 (IQR: 2.00~4.00), 3.50 (IQR: 2.25~4.00), and 3.00 (IQR: 1.00~3.00), respectively, and also showed improvement. Likewise, the median IIEF was 36.50 (IQR: 24.50~46.75), 37.50 (IQR: 26.75~47.25), 45.50 (IQR: 35.00~59.75), 48.50 (IQR: 34.75~62.75), and 47.50 (IQR: 43.25~61.00), while the median MSHQ-EjFD was 19.00 (IQR: 12.0~24.75), 19.50 (IQR: 13.50~27.75), 23.00 (IQR: 19.25~32.25), 26.50 (IQR: 18.25~34.50), 27.00 (IQR: 21.50~32.50), respectively, with both showing improvement. After administration of alfuzosin (10 mg daily for 2 years), the IPSS, QoL, IIEF, and MSHQ-EjFD all improved significantly. This means long-term administration of 10 mg of alfuzosin daily would be effective not only for LUTS but also erectile function and ejaculation.

  17. Long-term L-carnitine administration reduces erythropoietin resistance in chronic hemodialysis patients with thalassemia minor.

    PubMed

    Di Iorio, Biagio R; Guastaferro, Pasquale; Cillo, Nicola; Cucciniello, Emanuele; Bellizzi, Vincenzo

    2007-01-01

    Both thalassemia and carnitine deficiency represent independent causes of erythropoietin resistance, and thus anemia, in uremic patients. We evaluated the unknown long-term effects of L-carnitine administration in β-thalassemic on chronic hemodialysis. We studied twelve subjects (M = 8; F = 4) affected by β-thalassemia minor (β-thal; HbA2 level = 6.6 ± 0.6%) and forty non-thalassemic subjects (M = 24; F = 16) as controls (C), on chronic hemodialysis treatment. Patients and controls were at target hemoglobin levels (11-12g/dl) prior to the study and underwent to i.v. L-carnitine administration for a one year period-time. Groups were comparable for age, gender, serum levels of hemoglobin (Hb), iron, ferritine, PTH and aluminum, transferrin saturation, and dialysis modalities. During the study both groups showed significant Hb increase and erythropoietin (EPO) decrease; as a difference, such changes emerged at the 3rd month in C but at the 8th month in β-thal. At start, during the dialysis session the erythrocyte MCV reduced in C but not in β-thal (65.3 ± 3.2 to 65.5 ± 3.2 fl; NS); along carnitine administration period, however, MCV during dialysis decreased also in β-thal, starting since the 9th month of treatment. This study provides evidence of the lowering of EPO resistance in β-thalassemia patients on hemodialysis due to long-term carnitine administration. Thus, prolonged carnitine supplementation should be suggested to patients on dialysis affected by β-thalassemia with poorly responsive anemia, or requiring large doses of erythropoietin.

  18. The effect of acute stress and long-term corticosteroid administration on plasma metabolites in an urban and desert songbird.

    PubMed

    Davies, Scott; Rodriguez, Natalie S; Sweazea, Karen L; Deviche, Pierre

    2013-01-01

    In response to stressful stimuli, animals activate the hypothalamic-pituitary-adrenal axis, which can result in transition to the "emergency life history stage." A key adaptive characteristic of this life history stage is the mobilization of energy stores. However, few data are available on the metabolic response to acute stress in wild-caught, free-ranging birds. We quantified the effect of acute capture and restraint stress on plasma glucose, free fatty acid, and uric acid in free-ranging Abert's towhees Melozone aberti. Furthermore, birds were caught from urban and desert localities of Phoenix, Arizona, to investigate potential effects of urban versus desert habitats on the corticosterone (CORT) and metabolic response to acute stress. Complementing work on free-ranging birds, captive towhees received CORT-filled Silastic capsules to investigate the response of urban and desert conspecifics to long-term CORT administration. We quantified the effect of CORT administration on baseline plasma glucose and uric acid, liver and pectoralis muscle glycogen stores, kidney phosphoenolpyruvate carboxykinase (PEPCK-C, a key gluconeogenic enzyme), and body mass. Acute stress increased plasma CORT and glucose and decreased plasma uric acid but had no effect on plasma free fatty acid. There was no difference between urban and desert localities in body mass, fat scores, and the response to acute stress. CORT administration decreased body mass but had no effect on glucose and uric acid, pectoral muscle glycogen, or kidney PEPCK-C. However, liver glycogen of CORT-treated urban birds increased compared with corresponding controls, whereas glycogen decreased in CORT-treated desert birds. This study suggests that Abert's towhees principally mobilize glucose during acute stress but urban and desert towhees do not differ in their CORT and metabolic response to acute stress or long-term CORT administration.

  19. Long-term clopidogrel administration following severe coronary injury reduces proliferation and inflammation via inhibition of nuclear factor-kappaB and activator protein 1 activation in pigs.

    PubMed

    Pels, K; Schwimmbeck, P L; Rosenthal, P; Loddenkemper, C; Dang-Heine, C; Rauch, U; Martens, H; Schultheiss, H-P; Dechend, R; Deiner, C

    2009-03-01

    The optimal duration of clopidogrel treatment following percutaneous coronary intervention (PCI) and the patient population that would benefit most are still unknown. In a porcine coronary injury model, we tested two different durations of clopidogrel treatment on severely or moderately injured arteries and examined the arterial response to injury. To understand the molecular mechanism, we also investigated the effects on transcription factors nuclear factor-kappaB (NF-kappaB) and activator protein 1 (AP-1). In 24 cross-bred pigs, one coronary artery was only moderately injured by percutaneous transluminal coronary angioplasty (PTCA) and one coronary artery was severely injured by PTCA and subsequent beta-irradiation (Brachy group). Animals received 325 mg aspirin daily for 3 months and 75 mg clopidogrel daily for either 28 days [short-term (ST) clopidogrel group] or 3 months [long-term (LT) clopidogrel group]. After 3 months, the number of proliferating cells per cross-section differed significantly between ST and LT in both injury groups (PTCA(ST) 90.2 +/- 10.3 vs. PTCA(LT )19.2 +/- 4.7, P < 0.05; Brachy(ST) 35.8 +/- 8.4 vs. Brachy(LT) 7.5 +/- 2.0, P < 0.05). Similar results were seen for inflammatory cells (CD3(+) cells): PTCA(ST) 23.5 +/- 3.55 vs. PTCA(LT )4.67 +/- 0.92, P < 0.05; Brachy(ST) 83.17 +/- 11.17 vs. Brachy(LT) 20 +/- 4.82, P < 0.05). Long-term administration also reduced the activity of NF-kappaB and AP-1 by 62-64% and 42-58%, respectively. However, the effects of different durations of clopidogrel administration on artery dimensions were not statistically significant. Regarding inflammation and transcription factor activity at the PCI site, long-term clopidogrel administration is superior to short-term administration, especially in severely injured arteries. Transferring our results to the human situation, patients with more severely diseased arteries may benefit from a prolonged clopidogrel medication after PCI.

  20. Effects of long term administration of testosterone and estradiol on spatial memory in rats

    PubMed Central

    Mohammadi-Farani, Ahmad; Haghighi, Arash; Ghazvineh, Milad

    2015-01-01

    There are many discrepancies around the effect of sex hormones on spatial learning and memory in rodents. The aim of the present study was to investigate the effects of chronic administration of estradiol (ES) and testosterone (TES) on spatial memory in adult castrated male rats. Cholinesterase activity of the hippocampus in treated animals was also measured to seek if hormonal treatment can change the acetylcholinesterase (AChE) activity in this region. Six groups of castrated male rats received different doses of ES valerate (1, 4, 10 mg/kg, by subcutaneous, sc) and TES enanthate (10, 20, 40 mg/kg, sc) in weekly injection intervals for 6 weeks. Morris water maze (MWM) was used to assess the spatial reference memory of the rats. The specific activity of AChE in the hippocampus was also measured. The treatment duration and the dose quantity of ES had significant (P<0.001 and P=0.048, respectively) effect on the learning ability in the rats. For TES treated rats, treatment duration showed a significant effect (P<0.001) on learning performance of the rats. The activity of AChE compared to the control group was significantly increased in ES treated rats in a dose dependent manner and it was decreased in the group that received the highest dose of TES. Our results showed that chronic high dose of ES decreased the learning ability of male castrated rats in a reference memory version of MWM test. This can be explained by the decreased AChE activity in the hippocampus. PMID:26752989

  1. The Effect of Long-term Antiglaucomatous Drug Administration on Central Corneal Thickness.

    PubMed

    Schrems, Wolfgang A; Schrems-Hoesl, Laura M; Mardin, Christian Y; Horn, Folkert K; Juenemann, Anselm G M; Kruse, Friedrich E; Braun, Joachim M; Laemmer, Robert

    2016-03-01

    To evaluate rates of changes per year of central corneal thickness after antiglaucomatous drug administration with β-blockers, prostaglandin analogs, and carbonic anhydrase inhibitors monotherapy and combined topical antiglaucomatous therapy, in a cohort of patients with ocular hypertension, glaucoma suspects, and patients with perimetric glaucoma as compared with normal controls. This retrospective single-center study included 130 eyes as healthy controls, 121 eyes of ocular hypertensive patients, 105 eyes of glaucoma suspects, and 49 eyes of perimetric glaucoma patients. All patients underwent standard automated perimetry, 24-hour intraocular pressure profile, optic disc photography, and optical coherence pachymetry (OCP; Heidelberg Engineering). The cohort was divided into 8 groups on the basis of topical antiglaucomatous medication. Linear regression analysis was conducted to analyze the relationship between central corneal thickness and exposure to antiglaucomatous medication during the follow-up. Central corneal thickness did not change during the follow-up for investigated diagnostic subgroups. There was a statistically significant decrease in central corneal thickness for eyes treated with prostaglandin monotherapy (-3.1 μm/y for left eye), and a combined therapy with prostaglandins, carbonic anhydrase inhibitors, and β-blockers (-5.8 and -3.8 μm/y for right and left eye, respectively). We recommend regular measurements before and during therapy with prostaglandin monotherapy and a combined therapy with prostaglandins, carbonic anhydrase inhibitors, and β-blockers. Follow-up intraocular pressure measurements may be underestimated for eyes treated with the aforementioned treatment regimens if central corneal thickness is not measured on a regular basis.

  2. No Untoward Effect of Long-Term Ketoconazole Administration on Electrocardiographic QT Interval in Patients with Cushing's Disease.

    PubMed

    De Martin, Martina; Toja, Paola Maria; Goulene, Karine; Radaelli, Piero; Cavagnini, Francesco; Stramba-Badiale, Marco; Pecori Giraldi, Francesca

    2016-04-01

    Ketoconazole is listed among drugs that prolong QT interval and may increase the risk of torsade de pointes, a severe ventricular arrhythmia. This compound has recently been approved for treatment of Cushing's syndrome, a severe endocrine disorder. These patients harbour several risk factors for prolonged QT interval, for example hypokalaemia and left ventricular hypertrophy, but no study has evaluated whether administration of ketoconazole affects their QT interval. The aim of this study was to assess the QT interval in patients with Cushing's disease during long-term administration of ketoconazole. Electrocardiograms from 15 patients with Cushing's disease (12 women, 3 men, age: 37.8 ± 2.66 years) on ketoconazole treatment (100 mg-800 mg qd) for 1 month to 12 years were reviewed retrospectively. QT interval was measured and corrected for heart rate (QTc). Measurements before and during ketoconazole treatment were compared and any abnormal QTc value recorded. Concurrent medical therapies were also documented. On average, QTc was superimposable before and during ketoconazole treatment (393.2 ± 7.17 versus 403.3 ± 6.05 msec. in women; 424.3 ± 23.54 versus 398.0 ± 14.93 msec. in men, N.S.). QTc normalized on ketoconazole in one man with prolonged QTc prior to treatment; no abnormal QTc was observed in any other patient during the entire observation period, even during concurrent treatment with other QT-prolonging drugs. In conclusion, long-term ketoconazole administration does not appear to be associated with significant prolongation of QT interval in patients with Cushing's disease. ECG monitoring can follow recommendations drawn for other low-risk QT-prolonging drugs with attention to specific risk factors, for example hypokalaemia and drug interactions.

  3. Long-term mTOR inhibitors administration evokes altered calcium homeostasis and platelet dysfunction in kidney transplant patients

    PubMed Central

    López, Esther; Berna-Erro, Alejandro; Bermejo, Nuria; Brull, José María; Martinez, Rocío; Garcia Pino, Guadalupe; Alvarado, Raul; Salido, Ginés María; Rosado, Juan Antonio; Cubero, Juan José; Redondo, Pedro Cosme

    2013-01-01

    The use of the mammal target of rapamycin (mTOR) inhibitors has been consolidated as the therapy of election for preventing graft rejection in kidney transplant patients, despite their immunosuppressive activity is less strong than anti-calcineurin agents like tacrolimus and cyclosporine A. Furthermore, as mTOR is widely expressed, rapamycin (a macrolide antibiotic produced by Streptomyces hygroscopicus) is recommended in patients presenting neoplasia due to its antiproliferative actions. Hence, we have investigated whether rapamycin presents side effects in the physiology of other cell types different from leucocytes, such as platelets. Blood samples were drawn from healthy volunteers and kidney transplant patients long-term medicated with rapamycin: sirolimus and everolimus. Platelets were either loaded with fura-2 or directly stimulated, and immunoassayed or fixed with Laemmli's buffer to perform the subsequent analysis of platelet physiology. Our results indicate that rapamycin evokes a biphasic time-dependent alteration in calcium homeostasis and function in platelets from kidney transplant patients under rapamycin regime, as demonstrated by the reduction in granule secretion observed and subsequent impairment of platelet aggregation in these patients compared with healthy volunteers. Platelet count was also reduced in these patients, thus 41% of patients presented thrombocytopenia. All together our results show that long-term administration of rapamycin to kidney transplant patients evokes alteration in platelet function. PMID:23577651

  4. Anxiolytic effects of short- and long-term administration of cacao mass on rat elevated T-maze test.

    PubMed

    Yamada, Takashi; Yamada, Yasushi; Okano, Yasuyo; Terashima, Takehiko; Yokogoshi, Hidehiko

    2009-12-01

    We demonstrated the effects of short- and long-term administration of cacao mass on anxiety in the elevated T-maze test, which is an animal model of anxiety. In the first study, we administered cacao mass (100 mg/100 g body weight) per os and immediately performed the elevated T-maze test. Short-term cacao mass significantly abolished delayed avoidance latency compared with the control but did not change escape latency. This result suggested that cacao mass administration reduced conditional fear-relating behavior. Short-term cacao mass administration did not affect the concentration of brain monoamines, emotion-related neurotransmitters such as norepinephrine, serotonin and dopamine, in the rat brain. In the next study, we fed a cacao mass-containing diet to rats for 2 weeks and performed the elevated T-maze test. Contrary to short-term administration, chronic consumption of cacao mass tended to increase avoidance latency and did not change escape latency. Brain serotonin concentration and its turnover were enhanced by chronic consumption of cacao mass. These results suggested that chronic consumption of cacao did not affect fear-related behavior but was involved in brain monoamine metabolism. In conclusion, we suggest that short-term cacao mass consumption showed an anxiolytic effect but chronic consumption did not.

  5. Does Long-Term Administration of a Beta-Blocker (Timolol) Induce Fibril-Based Cataract Formation In-vivo?

    PubMed Central

    Nikbakht, Mohammad Reza; Ashrafi-Kooshk, Mohammad Reza; Jaafari, Morteza; Ghasemi, Moosa; Khodarahmi, Reza

    2014-01-01

    Timolol is a non-selective beta-adrenergic receptor antagonist administered for treating glaucoma, heart attacks and hypertension. In the present study, we set out to determine whether or not timolol can provoke cataract formation, thus the influence of timolol on the amyloid-type aggregation of crystallin was investigated. We then provided experimental evidence of crystallin aggregation and its induction by timolol using different spectroscopic measurements. Turbidimetric measurements as well as ThT fluorescence data indicated that timolol induce extent of crystallin amyloid formation. The kinetic of protein aggregation was also changed in presence of increasing concentrations of the drug suggesting that long-term drug administration may contribute to the development of cataract. Since the consequence of timolol-crystallin interaction has yet to be identified, additional data on it may help us to postpone amyloid cataract formation. PMID:25237356

  6. Benzodiazepine self-administration in humans and laboratory animals--implications for problems of long-term use and abuse.

    PubMed

    Griffiths, R R; Weerts, E M

    1997-11-01

    Drug reinforcement may represent the primary behavioral-pharmacological mechanism underlying two types of problematic use of benzodiazepines--recreational abuse by polydrug abusers and inappropriate chronic use by patients. High dose polydrug abuse for the purpose of getting high is readily recognized as a significant social problem. Inappropriate chronic benzodiazepine use is more subtle but relatively common: for anxiolytics, 36% of past-year users (3% of the adult population in the US) report using these drugs for 4 consecutive months or longer. The risks of such long-term use are much better documented than the benefits. This paper provides a current review of various problems that have been identified with the long-term use and the recreational abuse of benzodiazepines, including memory impairment, risk of accidents, falls and hip fractures in the elderly, a withdrawal syndrome, brain damage, overuse in the elderly, overuse by chronic pain patients, overuse by alcoholics and recreational abuse among alcoholics and polydrug abusers. A comprehensive review of the literature on benzodiazepine reinforcing effects in humans and laboratory animals is also provided. Drug self-administration studies in humans and laboratory animals provide models of both types of problematic benzodiazepine use. Recreational abuse of benzodiazepines has been modeled in human research with polydrug abusers and in laboratory animal studies, which show that the reinforcing effect of benzodiazepines is intermediate relative to other sedative compounds and is increased in subjects with histories of previous sedative drug self-administration. The problem of inappropriate long-term use of benzodiazepines by people without histories of drug abuse has been partially modeled in human studies showing that benzodiazepines function as reinforcers in subjects with anxiety, insomnia, and histories of moderate alcohol consumption, and in preclinical studies showing stable, low-rate benzodiazepine self

  7. Maternal administration of melatonin exerts short- and long-term neuroprotective effects on the offspring from lipopolysaccharide-treated mice.

    PubMed

    Domínguez Rubio, Ana Paula; Correa, Fernando; Aisemberg, Julieta; Dorfman, Damián; Bariani, María Victoria; Rosenstein, Ruth Estela; Zorrilla Zubilete, María; Franchi, Ana María

    2017-08-04

    Preterm birth is a major contributor to early and delayed physical and cognitive impairment. Epidemiological and experimental data indicate that maternal infections are a significant and preventable cause of preterm birth. Recently, melatonin has been suggested to exert neuroprotective effects in several models of brain injury. Here, we sought to investigate whether the administration of melatonin is able to prevent lipopolysaccharide (LPS)-induced fetal brain damage in a model of LPS-induced preterm labor. For this purpose, 15-day pregnant BALB/c mice received intraperitoneally 2 doses of LPS or vehicle: the first one at 10:00 hours (0.26 mg/kg) and the second at 13:00 hours (0.52 mg/kg). On day 14 of pregnancy, a group of mice was subcutaneously implanted with a pellet of 25 mg melatonin. This experimental protocol resulted in 100% of preterm birth and pup death in the LPS group and a 50% of term birth and pup survival in the melatonin + LPS group. In the absence of melatonin, fetuses from LPS-treated mothers showed histological signs of brain damage, microglial/macrophage activation, and higher levels of IL-1β, inducible nitric oxide synthase (NOS), and neuronal NOS mRNAs as well as increased histone acetyltransferase activity and histone H3 hyperacetylation. In contrast, antenatal administration of melatonin prevented LPS-induced fetal brain damage. Moreover, when behavioral traits were analyzed in the offspring from control, melatonin, and melatonin + LPS, no significant differences were found, suggesting that melatonin prevented LPS-induced long-term neurodevelopmental impairments. Collectively, our results suggest that melatonin could be a new therapeutic tool to prevent fetal brain damage and its long-term consequences induced by maternal inflammation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Acute and long-term administration of citalopram desensitizes alpha2-adrenoceptors in the rat vas deferens.

    PubMed

    Grandoso, Laura; García, Laura; Pineda, Joseba; Ugedo, Luisa

    2006-03-01

    The aim of this study was to investigate the effect of citalopram, a selective serotonin reuptake inhibitor, on the sensitivity of rat vas deferens alpha2-adrenoceptors and to compare it with the effects of serotonin and the dual noradrenaline-serotonin uptake inhibitor duloxetine. To this end, we studied the inhibitory effect of the alpha2-adrenoceptor agonist bromoxidine on the electrically induced contraction of the vas deferens. Citalopram (1, 3 x 10(3) and 3 x 10(4) nM) applied in-vitro significantly attenuated the concentration-response inhibition induced by activation of alpha2-adrenoceptors on the electrically evoked contraction of the vas deferens (concentration of the agonist required to promote 50% of the maximal effect, EC50, for bromoxidine increased by 232%, 421% and 818%, respectively). Similarly, serotonin also attenuated the concentration-response inhibition mediated by presynaptic alpha2-adrenoceptors (96% increase in EC50). Acute and long-term systemic administration of citalopram and duloxetine also produced a loss in the sensitivity of alpha2-adrenoceptors to bromoxidine (EC50 for bromoxidine increased by 97% and 144%, respectively, after citalopram, and by 214% and 167% after duloxetine). In addition, we observed that an increased fraction of receptors was required to be occupied to yield 50% of the inhibitory effect of bromoxidine after long-term administration of citalopram and duloxetine (KE increased by 142% and 83%). These results are indicative of early-onset and persistent down-regulation of peripheral alpha2-adrenoceptors by citalopram, which may account for some of its side effects.

  9. Long-term daily intake estimates of polychlorinated dibenzo-p-dioxins and furans, polychlorinated biphenyls and polybrominated diphenylethers from food in Finnish children: risk assessment implications.

    PubMed

    Karjalainen, Anna K; Hirvonen, Tero; Kiviranta, Hannu; Sinkko, Harri; Kronberg-Kippilä, Carina; Virtanen, Suvi M; Hallikainen, Anja; Leino, Olli; Knip, Mikael; Veijola, Riitta; Simell, Olli; Tuomisto, Jouni T

    2012-01-01

    Food is contaminated by polychlorinated dibenzo-p-dioxins and furans (PCDD/F), polychlorinated biphenyls (PCB) and polybrominated diphenylethers (PBDE) worldwide. Previous data show elevated intakes in children. We determined intakes of POPs in Finnish children. Because no children-specific safe limit values exist, we used tolerable daily intakes (TDIs) set for adults by international expert bodies to examine the proportion of the study population that exceed those limits. We utilised dietary monitoring data with food consumption of Finnish boys and girls aged 1-6 years, measured the contaminant concentrations in all the main food items and calculated age-specific contaminant sum and congener-specific long-term daily intake levels. Our food intake and contaminant data correspond to years 2002-2005. The long-term upper-bound dioxin intakes ranged between 0.1 and 12.8 pg WHO(PCDD/F-PCB)-TEQ/kg bw/d (min and max). An immediate TDI for WHO(PCDD/F-PCB)-TEQs of 4.0 pg/kg bw/d were exceeded by 2.5%-7.5% of the children. PBDE long-term upper-bound intake was between 0.1 and 5.8 ng/kg bw/d (min and max). Congener-specific analyses indicated a typical Finnish adult exposure pattern of the children to PCDD/Fs, PCBs and PBDEs. The highest POP intakes were observed in children aged 3 years. Long-term daily PCDD/F, PCB and PBDE intakes among Finnish children varied greatly between individuals and ages. In each age group of the study population, there was a proportion of children with their WHO(PCDD/F-PCB)-TEQ intake exceeding considered safe limits set for adults. Based on the exposure profile reported herein, children should be clearly considered as a specific sub-population in food-mediated contaminant risk assessment.

  10. Long-term methamphetamine administration in the vervet monkey models aspects of a human exposure: brain neurotoxicity and behavioral profiles.

    PubMed

    Melega, William P; Jorgensen, Matthew J; Laćan, Goran; Way, Baldwin M; Pham, Jamie; Morton, Grenvill; Cho, Arthur K; Fairbanks, Lynn A

    2008-05-01

    Methamphetamine (METH)-associated alterations in the human striatal dopamine (DA) system have been identified with positron emission tomography (PET) imaging and post-mortem studies but have not been well correlated with behavioral changes or cumulative METH intake. Animal studies that model some aspects of human long-term METH abuse can establish dose-dependency profiles of both behavioral changes and potential brain neurotoxicities for identifying consequences of particular cumulative exposures. Based on parameters from human and our monkey pharmacokinetic studies, we modeled a prevalent human METH exposure of daily multiple doses in socially housed vervet monkeys. METH doses were escalated over 33 weeks, with final dosages resulting in estimated peak plasma METH concentrations of 1-3 microM, a range measured in human abusers. With larger METH doses, progressive increases in abnormal behavior and decreases in social behavior were observed on 'injection' days. Anxiety increased on 'no injection' days while aggression decreased throughout the study. Thereafter, during 3 weeks abstinence, differences in baseline vs post-METH behaviors were not observed. Post-mortem analysis of METH brains showed 20% lower striatal DA content while autoradiography studies of precommissural striatum showed 35% lower [3H]WIN35428 binding to the DA transporter. No statistically significant changes were detected for [3H]dihydrotetrabenazine binding to the vesicular monoamine transporter (METH-lower by 10%) or for [3H]SCH 23390 and [3H]raclopride binding to DA D1 and D2 receptors, respectively. Collectively, this long-term, escalating dose METH exposure modeling a human abuse pattern, not associated with high-dose binges, resulted in dose-dependent behavioral effects and caused persistent changes in presynaptic striatal DA system integrity.

  11. Effects of long-term administration of omeprazole on bone mineral density and the mechanical properties of the bone☆

    PubMed Central

    Yanagihara, Gabriela Rezende; de Paiva, Aline Goulart; Neto, Maurílio Pacheco; Torres, Larissa Helena; Shimano, Antônio Carlos; Louzada, Mário Jefferson Quirino; Annoni, Raquel; de Oliveira Penoni, Álvaro César

    2015-01-01

    Objectives Epidemiological studies have shown a relationship between long-term use of proton pump inhibitors and bone metabolism. However, this relationship has not yet become established. The aim of the present study was to analyze the mechanical properties and bone mineral density (BMD) of rats that were subjected to long-term omeprazole use. Methods Fifty Wistar rats weighing between 200 and 240 g were divided equally into five groups: OMP300 (omeprazole intake at a dose of 300 μmoL/kg/day); OMP200 (200 μmoL/kg/day); OMP40 (40 μmoL/kg/day); OMP10 (10 μmoL/kg/day); and Cont (control group; intake of dilution vehicle). The solutions were administered for 90 consecutive days. After the rats had been sacrificed, their BMD, the mechanical properties of the dissected femurs and their serum Ca++ levels were analyzed. Results The BMD of the OMP300 group was lower than that of the controls (p = 0.006). There was no difference on comparing the OMP200, OMP40 and OMP10 groups with the controls. The maximum strength and rigidity of the femur did not differ in the experimental groups in comparison with the controls. The OMP300 group had a statistically lower serum Ca++ concentration than that of the controls (p = 0.049), but the other groups did not show any difference in relation to the controls. Conclusion Daily intake of 300 μmoL/kg/day of omeprazole decreased the BMD of the femur, but without changes to the rigidity and strength of the femur in adult rats. PMID:26229922

  12. Effect of long term-administration with Gymnema sylvestre R. BR on plasma and liver lipid in rats.

    PubMed

    Shigematsu, N; Asano, R; Shimosaka, M; Okazaki, M

    2001-06-01

    Extract of Gymnema sylvestre leaves was administered to rats receiving either a high fat diet or normal fat diet for 10 weeks to investigate its influence on plasma and liver lipids and on visceral fat accumulation. In addition, its effect was compared with those of chitosan and the influence of combined use of these two substances was also evaluated. Within the high fat diet groups, the extract suppressed body weight gain and accumulation of liver lipids to the same extent as chitosan and the combined use. In addition, intraperitoneal fat and fat drop vacuoles on the epithelium of renal tubules, noted in the high fat diet group, were scattered by administration of the extract with the same results as for chitosan and combined use. Within the normal fat diet groups, plasma triglyceride levels decreased by administration of the extract, with similar results as chitosan and combined use. Concerning plasma total cholesterol, there was no decreasing effects with the extract, as found with chitosan and combined use. However, the effect of chitosan on plasma total cholesterol tended to be enhanced when used in combination with the extract. In addition, long-term administration of the extract did not show any influence on hematological and blood chemical parameters.

  13. Surface temperature patterns in complex terrain: Daily variations and long-term change in the central Sierra Nevada, California

    USGS Publications Warehouse

    Lundquist, J.D.; Cayan, D.R.

    2007-01-01

    A realistic description of how temperatures vary with elevation is crucial for ecosystem studies and for models of basin-scale snowmelt and spring streamflow. This paper explores surface temperature variability using temperature data from an array of 37 sensors, called the Yosemite network, which traverses both slopes of the Sierra Nevada in the vicinity of Yosemite National Park, California. These data indicate that a simple lapse rate is often a poor description of the spatial temperature structure. Rather, the spatial pattern of temperature over the Yosemite network varies considerably with synoptic conditions. Empirical orthogonal functions (EOFs) were used to identify the dominant spatial temperature patterns and how they vary in time. Temporal variations of these surface temperature patterns were correlated with large-scale weather conditions, as described by National Centers for Environmental Prediction-National Center for Atmospheric Research Reanalysis data. Regression equations were used to downscale larger-scale weather parameters, such as Reanalysis winds and pressure, to the surface temperature structure over the Yosemite network. These relationships demonstrate that strong westerly winds are associated with relatively warmer temperatures on the east slope and cooler temperatures on the west slope of the Sierra, and weaker westerly winds are associated with the opposite pattern. Reanalysis data from 1948 to 2005 indicate weakening westerlies over this time period, a trend leading to relatively cooler temperatures on the east slope over decadal timescale's. This trend also appears in long-term observations and demonstrates the need to consider topographic effects when examining long-term changes in mountain regions. Copyright 2007 by the American Geophysical Union.

  14. Uptake, distribution and elimination of monosodium methanearsonate following long term oral administration of the herbicide to sheep and goats.

    PubMed

    Shariatpanahi, M; Anderson, A C

    1984-08-01

    The rate and extent of accumulation and washout of arsenic, during daily oral administration of the herbicide monosodium methanearsonate (MSMA) were evaluated in Iranian dairy sheep and goats. Subjects received a dose of 10 mg of MSMA as arsenic per kg of body weight daily for 28 consecutive days. The total arsenic concentration in blood and milk was measured during and after the period of MSMA administration while arsenic in urine and feces was measured for 10 days following administration of last dosage of MSMA. Arsenic was accumulated slowly during 28 days of MSMA administration and steady states were essentially complete in sheep after 20 days and in goats following 25 days of MSMA administration. Blood arsenic concentration decreased rapidly after termination of MSMA administration. In both test animals, the half-lives of washout were smaller than accumulation. The concentration of arsenic in the urine and feces of both species did not increase significantly over controls and animals were free of arsenic relatively shortly after administration stopped. These data indicate that arsenic from MSMA is mainly absorbed from gastrointestinal tract and is not significantly accumulated in the body. Arsenic is eliminated from body by way of urine and feces with urinary excretion being the most important route.

  15. Long-term oral melatonin administration reduces ethanol-induced increases in duodenal mucosal permeability and motility in rats.

    PubMed

    Sommansson, A; Yamskova, O; Schiöth, H B; Nylander, O; Sjöblom, M

    2014-10-01

    Increased intestinal epithelial permeability is associated with intestinal inflammation and dysfunction. The aim of the present study was to investigate the role of long-term oral melatonin administration on ethanol-induced increases in duodenal mucosal permeability and hypermotility. Male Sprague-Dawley rats were administered melatonin in their tap water (0.1 mg mL(-1) or 0.5 mg mL(-1) ) for 2 or 4 weeks. After the treatment period, the rats were anaesthetized with Inactin(®) , and a 30-mm duodenal segment was perfused in situ. The effects on duodenal mucosal paracellular permeability, bicarbonate secretion, fluid flux and motor activity were studied. The expression levels of the tight junction components, zona occludens (ZO)-1, ZO-2, and ZO-3, claudin-2, claudin-3, claudin-4, occludin, and myosin light chain kinase and of the melatonin receptors MT1 and MT2 were assessed using qRT-PCR. Melatonin administration for 2 weeks significantly reduced the basal paracellular permeability, an effect that was absent after 4 weeks. Perfusing the duodenal segment with 15% ethanol induced marked increases in duodenal paracellular permeability, bicarbonate secretion and motor activity. Melatonin for 2 weeks dose-dependently reduced ethanol-induced increases in permeability and motor activity. Four weeks of melatonin administration reduced the ethanol-induced increases in duodenal motility and bicarbonate secretion but had no effect on the increases in permeability. Two weeks of melatonin administration upregulated the expression of MT1 and MT2 , although both were downregulated after 4 weeks. Melatonin downregulated the expression of ZO-3 and upregulated the expression of claudin-2, even as all other mRNA-levels investigated were unaffected. Although further studies are needed, our data demonstrate that melatonin administration markedly improves duodenal barrier functions, suggesting its utility in clinical applications when intestinal barrier functions are compromised.

  16. Long-term, open-label, safety study of once-daily ropinirole extended/prolonged release in early and advanced Parkinson's disease.

    PubMed

    Makumi, Clare W; Asgharian, Afsaneh; Ellis, Jeffrey; Shaikh, Soraya; Jimenez, Teri; VanMeter, Susan

    2016-01-01

    Long-term safety of once-daily ropinirole extended/prolonged release (ropinirole XL/PR) was evaluated in subjects with early and advanced Parkinson's disease (PD) in this study, 101468/248. Subjects (n = 419) who completed one of three prior studies evaluating ropinirole XL/PR for the treatment of PD were enrolled in this open-label, multicenter, extension study, and were to be followed for up to 73 months. Ropinirole XL/PR was titrated/continued, and adjusted as appropriate during the maintenance phase (maximum 24 mg/d). Levodopa (L-dopa) and other nondopamine agonist PD medications were permitted. Safety outcomes that were investigated included frequency of adverse events (AEs). Subjects' preference regarding once daily versus three times daily study medication regimens was also investigated in a subset of the study population. The median duration of ropinirole XL/PR exposure was 1275 d. Most subjects (87%) reported at least one AE, with the most common (≥ 10%) AEs being, back pain (14%), hallucinations (13%), somnolence (11%) and peripheral edema (11%). Twenty-five percent of subjects discontinued the study prematurely due to an AE during the treatment period. Long-term treatment with ropinirole XL/PR was not associated with any new or unexpected safety concerns in patients with early and advanced PD, and a majority of subjects preferred the once-daily dosing regimen.

  17. Influence of the sampling period and time resolution on the PM source apportionment: Study based on the high time-resolution data and long-term daily data

    NASA Astrophysics Data System (ADS)

    Tian, Yingze; Xiao, Zhimei; Wang, Haiting; Peng, Xing; Guan, Liao; Huangfu, Yanqi; Shi, Guoliang; Chen, Kui; Bi, Xiaohui; Feng, Yinchang

    2017-09-01

    When planning short-term and long-term measurement campaigns of particulate matter (PM), parameters such as sampling period, time resolution, sampling number, etc. are vital. To study their influence and to provide suggestion for the sampling plan of PM source apportionment (SA), ambient and synthetic speciated datasets (including a high time-resolution dataset and a long-term daily dataset) were studied. First, aiming at studying the sampling period required to generate representative and reliable results for SA, high time-resolution ambient samples were collected by online instruments in a megacity in China. Datasets with different sampling periods (four months, two months, one month, two weeks and one week) were modeled by the Positive Matrix Factorization (PMF). Compared with four month results, AAEs (percent absolute errors between true and estimated contributions) ranged from 11.2 to 27.2% (two months), 19.8-44.5% (one month), 21.0-45.9% (two weeks) and 23.9-44.6% (one week), indicating that divergence increased with decreasing sampling periods. To systematically evaluate this problem and investigate if the increasing time resolutions in a short period could enhance the modeling performance, synthetic datasets were constructed. Results revealed that a sufficient sampling period is required to ensure stable results; without sufficient sampling period, the contributions cannot be reliably estimated, even if the number of samples is large. Then, to explore the influence of variability absences, long-term daily datasets with various variability absences were apportioned and compared. The summed AAEs were 102.2% (no winter), 73.6% (no weekend), 138.7% (no weekday) and 165.6% (no autumn, winter or weekends). This general increase of AAEs can indicate that uncertainty enhanced with the increase in variability absences. When planning short-term measurement campaigns, except for number of samples, sampling period that involves sufficient source cycles has significant

  18. A Case of an Insufficiency Fracture of the Medial Proximal Tibia Secondary to Osteomalacia Associated with Long-Term Saccharated Ferric Oxide Administration.

    PubMed

    Ishimaru, Daichi; Sumi, Hiroshi

    2017-01-01

    This article presents a case of insufficiency fracture of medial proximal tibia caused by long-term administration of saccharated ferric oxide (SFO) in a 77-year-old female. In this case, 2-year administration of SFO for iron deficit anemia induced hypophosphatemic osteomalacia and finally resulted in an insufficiency fracture of medial proximal tibia. Hypophosphatemia and pain due to the insufficiency fracture were recovered promptly by withdrawing SFO administration and rest. This case represented varus deformity of the knee associated with osteoarthritis, which may also cause the insufficiency fracture of medial proximal tibia in addition to osteomalacia due to long-term administration of SFO. Long-term SFO administration should be avoided because of a definitive risk of osteomalacia and fragile fracture.

  19. [Let us not underestimate the importance of good long-term programming and competent administration of health care].

    PubMed

    Holcík, J

    2009-01-01

    The origin of Social Medicine is in the theories on the health services in the 18th and 19th centuries. The first step was establishing so-called State Medicine. Socio-medical thinking, the beginnings of which were determined by the process of the industrial revolution and the increasing social differences, led at the beginning of 20th century to the first attempts to establish Social Medicine as a separate medical discipline. In the history of Social Medicine in the Czech Republic the important personalities were mainly professors Frantisek Procházka, Frantisek Hamza, Hynek Pelc, and Adolf Zácek. The main motivation of qualitative changes of Social Medicine in Czechoslovakia after 1989 were great political, economic and social changes, documents of the World Health Organization and the European health policy. Present health care reform brings new opportunities, challenges, and problems. As a tool of its implementation a long-term programming based on human values should be used in a larger scale. The adequate professional skills in health care administration are indispensable. Article presents concise information on the work of the Society of Social Medicine and Health Care Administration of the Czech Medical Society of J. E. Purkynje.

  20. Long-term effect of morphine administration in young rats on the analgesic opioid response in adult life.

    PubMed

    Rozisky, Joanna Ripoll; Dantas, Giovana; Adachi, Lauren Spezia; Alves, Viviane Soares; Ferreira, Maria Beatriz Cardoso; Sarkis, João José Freitas; Torres, Iraci Lucena Da Silva

    2008-10-01

    Neonates, infants and children are often exposed to pain from invasive procedures during intensive care and during the post-operative period. Opioid anesthesia and post-operative opioid analgesia have been used in infants and result in clinical benefits. The objectives of this study were to verify the effect of repeated 5 microg morphine administration (subcutaneous), once a day for 7 days in 8-day-old rats, at P8 until P14. To verify the long-term effect of morphine, the animals were submitted to a second exposure of 5mg/kg (intraperitoneal) of morphine at P80 until P86. Animals that received morphine for 7 days, at P14 did not develop tolerance, however at P80, rats demonstrated greater morphine analgesia. At P86, after 7 days of morphine administration, animals showed classical tolerance. These findings may have important implications for the human neonate, suggesting a possible explanation for the differences in the requirements of morphine observed in the youngest patients.

  1. Long-term risk of repeat occupational injury or illness incidents among veterans health administration nursing employees.

    PubMed

    Welch, Charles E

    2010-08-01

    This retrospective population-based study assessed the long-term risk of repeat reported occupational injury or illness incidents among Veterans Health Administration (VHA) nursing employees. Using fiscal year (FY) 2002 as the start date for the longitudinal surveillance of incidents, descriptive analyses included all VHA nursing employees (N = 25,697) who reported an initial (index) incident that occurred between FY 2002 and FY 2005. Adjusted for total administrative loss rates (e.g., attrition, disability, retirements), approximately half of the "surviving" index cases reported repeat incidents during an ensuing 3-year period. This total increased to approximately two thirds during a 6-year period. Compared to their nurse counterparts, practical nurses and nursing assistants had higher cumulative probabilities of multiple reported repeat occupational injury or illness incidents. Study findings suggest that reported levels of repeat occupational injury or illness incidents represent a complex interplay between environmental factors (e.g., location) and nursing staff demographics (e.g., level of education).

  2. Short and long-term motor and behavioral effects of diazoxide and dimethyl sulfoxide administration in the mouse after traumatic brain injury.

    PubMed

    Budinich, Craig S; Tucker, Laura B; Lowe, Dennell; Rosenberger, John G; McCabe, Joseph T

    2013-07-01

    Traumatic brain injury (TBI) is a worldwide phenomenon that affects all ages and socioeconomic classes and results in varying degrees of immediate and delayed motor, cognitive, and emotional deficiencies. A plethora of pharmacologic interventions that target recognized initiators and propagators of pathology are being investigated in an attempt to ameliorate secondary injury processes that follow primary injury. Diazoxide (DZ), a K(ATP) channel activator, has been shown to provide short- and long-term protective effects in a variety of in vitro and in vivo cerebral ischemia models. However, the effects of DZ on behavioral outcome following TBI have not been investigated. TBI was induced in male C57BL/6J mice by controlled cortical impact (CCI) and followed by intraperitoneal administration of either normal saline, dimethyl sulfoxide (DMSO), or 2.5 mg/kg DZ in DMSO, 30 min post-injury and daily for three days. Open field and beam walk performances were used to assess motor and behavioral function 1, 7, and 14 days following injury. Spatial learning and memory were assessed three weeks following injury using the Morris water maze. Injured mice were significantly impaired on the beam-walk and Morris water maze tasks, and were hyperactive and anxious in an open field environment. On post-injury days 1 and 14, mice treated with DMSO exhibited an increase in the amount of time required to perform the beam walk task. In addition, animals exposed to DMSO or DZ+DMSO exhibited slower swimming speed in the Morris water maze on the final day of testing. There was no therapeutic effect, however, of the treatment or vehicle on open field behavior or learning and memory function in the Morris water maze. In summary, CCI produced significant long-term impairment of motor, memory, and behavioral performance measures, and DZ administration, under the conditions used, provided no functional benefits following injury.

  3. Adolescents and adults differ in the immediate and long-term impact of nicotine administration and withdrawal on cardiac norepinephrine.

    PubMed

    Slotkin, Theodore A; Stadler, Ashley; Skavicus, Samantha; Seidler, Frederic J

    2016-04-01

    Cardiovascular responses to smoking cessation may differ in adolescents compared to adults. We administered nicotine by osmotic minipump infusion for 17 days to adolescent and adult rats (30 and 90 days of age, respectively) and examined cardiac norepinephrine levels during treatment, after withdrawal, and for months after cessation. In adults, nicotine evoked a significant elevation of cardiac norepinephrine and a distinct spike upon withdrawal, after which the levels returned to normal; the effect was specific to males. In contrast, adolescents did not show significant changes during nicotine treatment or in the immediate post-withdrawal period. However, beginning in young adulthood, males exposed to adolescent nicotine showed sustained elevations of cardiac norepinephrine, followed by later-emerging deficits that persisted through six months of age. We then conducted adolescent exposure using twice-daily injections, a regimen that augments stress associated with inter-dose withdrawal episodes. With the injection route, adolescents showed an enhanced cardiac norepinephrine response, reinforcing the relationship between withdrawal stress and a surge in cardiac norepinephrine levels. The relative resistance of adolescents to the acute nicotine withdrawal response is likely to make episodic nicotine exposure less stressful or aversive than in adults. Equally important, the long-term changes after adolescent nicotine exposure resemble those known to be associated with risk of hypertension in young adulthood (elevated norepinephrine) or subsequent congestive heart disease (norepinephrine deficits). Our findings reinforce the unique responses and consequences of nicotine exposure in adolescence, the period in which most smokers commence tobacco use.

  4. Adolescents and Adults Differ in the Immediate and Long-Term Impact of Nicotine Administration and Withdrawal on Cardiac Norepinephrine

    PubMed Central

    Slotkin, Theodore A.; Stadler, Ashley; Skavicus, Samantha; Seidler, Frederic J.

    2016-01-01

    Cardiovascular responses to smoking cessation may differ in adolescents compared to adults. We administered nicotine by osmotic minipump infusion for 17 days to adolescent and adult rats (30 and 90 days of age, respectively) and examined cardiac norepinephrine levels during treatment, after withdrawal, and for months after cessation. In adults, nicotine evoked a significant elevation of cardiac norepinephrine and a distinct spike upon withdrawal, after which the levels returned to normal; the effect was specific to males. In contrast, adolescents did not show significant changes during nicotine treatment or in the immediate post-withdrawal period. However, beginning in young adulthood, males exposed to adolescent nicotine showed sustained elevations of cardiac norepinephrine, followed by later-emerging deficits that persisted through six months of age. We then conducted adolescent exposure using twice-daily injections, a regimen that augments stress associated with inter-dose withdrawal episodes. With the injection route, adolescents showed an enhanced cardiac norepinephrine response, reinforcing the relationship between withdrawal stress and a surge in cardiac norepinephrine levels. The relative resistance of adolescents to the acute nicotine withdrawal response is likely to make episodic nicotine exposure less stressful or aversive than in adults. Equally important, the long-term changes after adolescent nicotine exposure resemble those known to be associated with risk of hypertension in young adulthood (elevated norepinephrine) or subsequent congestive heart disease (norepinephrine deficits). Our findings reinforce the unique responses and consequences of nicotine exposure in adolescence, the period in which most smokers commence tobacco use. PMID:26993795

  5. ADHD Treatment with Once-Daily OROS Methylphenidate: Final Results from a Long-term Open-Label Study

    ERIC Educational Resources Information Center

    Wilens, Timothy; McBurnett, Keith; Stein, Mark; Lerner, Marc; Spencer, Thomas; Wolraich, Mark

    2005-01-01

    Objective: Few studies have assessed effectiveness and tolerability of stimulants when used for prolonged periods in children with attention-deficit/hyperactivity disorder (ADHD). This article presents final results from an open-label, multisite study of a once-daily formulation of methylphenidate (MPH), OROS[R] MPH. Method: Subjects received OROS…

  6. Long-Term Chinese Herbs Decoction Administration for Management of Hot Flashes Associated with Endocrine Therapy in Breast Cancer Patients

    PubMed Central

    Xue, Dong; Sun, Hong; Li, Ping-ping

    2011-01-01

    Objective To evaluate the effect of Chinese herbs decoction Shu-Gan-Liang-Xue on endocrine therapy- associated hot flashes symptom in breast cancer patients. Methods Sixty-six patients with breast cancer receiving adjuvant endocrine therapy were categorized to two groups, the control group received endocrine therapy alone, the other group is administered with Chinese herbs decoction Shu-Gan-Liang-Xue besides the endocrine therapy: Shu-Gan-Liang-Xue decoction was administered above 6 months per year for more than 2 years. Frequency of hot flashes per day was recorded, and the effect of Shu-Gan-Liang-Xue decoction on hot flashes symptom being assessed with Kupperman Scoring Index. Results Sixty cases were analyzed, 32 cases in endocrine therapy combining Chinese herbs decoction group, 28 cases in mere endocrine therapy group. For hot flashes symptom, in Chinese herbs decoction administration group, 7 cases (21.9%) reported symptom disappeared, 22 cases (68.7%) reported symptom alleviated, 3 cases (9.4%) reported symptom not changed; in endocrine therapy alone group, 5 cases (17.9%) reported symptom disappeared, 13 cases (46.4%) reported symptom alleviated, 10 cases (10/28, 35.7%) reported symptom not changed. The difference between two groups was statistically significant (P=0.013). For sleeping disorder, in Chinese herbs decoction administration group, 27 cases (84.4%) reported symptom improved, 5 cases (15.6%) reported no change; in endocrine therapy alone group, 16 cases (57.1%) symptom improved, 12 cases (42.9%) reported no change in sleeping disorder (P=0.019), the difference was also of significance statistically. Conclusion Long-term Chinese herbs decoction administration remarkably improved hot flashes symptom and sleeping disorder associated with endocrine therapy, meanwhile without definite toxicity and influence on the risk of recurrence of tumor. PMID:23467638

  7. Large artery biomechanical, geometrical, and structural remodeling elicited by long-term propranolol administration in an animal model.

    PubMed

    Lampropoulos, Konstantinos M; Sokolis, Dimitrios P

    2016-11-09

    Limited attention has been paid to the role of beta-adrenergic blocking agents on large artery function/structure, despite being clinically useful for treating many forms of cardiovascular disease. To assess long-term consequences of beta-blocker administration on the biomechanical properties, geometry, and histological structure of two major elastic arteries. Healthy male rats received water with their food, while beta-blockade was produced in rats by adding propranolol in their drinking water. The thoracic aorta and carotid artery were resected after three months for biomechanical (failure and inflation-extension) testing along with geometrical and histological evaluation. The thoracic aorta presented increased strength longitudinally in propranolol-treated than untreated rats, resulting from increased adventitial collagen content. The distensibility of carotid artery increased in propranolol-treated rats at low-to-physiologic pressures, resulting from decreased medial collagen content. Structural remodeling was characterized by reduced lumen diameter, wall mass, and thickness-to-radius ratio. The latter, together with the greater resorption of the media than adventitia, related with the measured opening angle decrease in propranolol-treated rats. The geometrical/biomechanical remodeling was mediated by the hemodynamic effects of propranolol treatment, namely the reduced blood flow, and served to normalize in vivo hoop stresses as well as vessel compliance.

  8. Proliferative response of different exocrine pancreatic cell types to hormonal stimuli. I. Effects of long-term cerulein administration.

    PubMed

    Gasslander, T; Smeds, S; Blomqvist, L; Ihse, I

    1990-11-01

    The trophic effect on the exocrine pancreas of the cholecystokinin analogue cerulein was studied in a long-term experiment (20 or 160 micrograms/kg/24 h for 14 days) in mice by measuring changes in pancreatic weight and protein, amylase, and DNA content. Further, the selective cell growth stimulation exerted by various doses of cerulein (4, 20, 54, 160 micrograms/kg/24 h) on different exocrine pancreatic cell types was studied by continuous administration of 3H-thymidine. In the first experiment animals given 20 micrograms/kg/24 h of cerulein had increased pancreatic weight and amylase and protein content, whereas the animals given the higher dose had unchanged weight and a less pronounced increase in amylase and protein content. The pancreatic DNA content was unaffected in the 20-micrograms group but was clearly decreased by the higher dose. In the second experiment a statistically significant increase over controls was found in the fraction of labeled ductal cells when 20, 54, and 160 micrograms of cerulein was administered. However, in the acinar cell population an increase was measured only in the 160-micrograms group. A tendency to nadir in cell labeling was observed in both acinar and ductal cell groups at less stimulation. Labeling of centroacinar cells increased in all cerulein-treated groups. The results show that all cell types of the exocrine pancreas can be forced into proliferation by the cholecystokinin analogue used and that there is preferential cell growth stimulation in the ductal and centroacinar cell populations.

  9. Long-term Administration of Nuclear Bile Acid Receptor FXR Agonist Prevents Spontaneous Hepatocarcinogenesis in Abcb4(-/-) Mice.

    PubMed

    Cariello, Marica; Peres, Claudia; Zerlotin, Roberta; Porru, Emanuele; Sabbà, Carlo; Roda, Aldo; Moschetta, Antonio

    2017-09-11

    Altered bile acid (BA) signaling is associated with hepatotoxicity. The farnesoid X receptor (FXR) is a nuclear receptor that transcriptionally regulates BA homeostasis. Mice with FXR ablation present hepatocarcinoma (HCC) due to high toxic BA levels. Mice with Abcb4 ablation accumulate toxic BA within the bile ducts and present HCC. We have previously shown that intestinal specific activation of FXR by transgenic VP16-FXR chimera is able to reduce BA pool size and prevent HCC. Here we tested chemical FXR activation by administering for 15 months the dual FXR/ membrane G protein-coupled receptor (TGR5) agonist INT-767 (6α-ethyl-3α,7α,23-trihydroxy-24-nor-5β-cholan-23-sulphate) to Fxr(-/-) and Abcb4(-/-) mice. HCC number and size were significantly reduced by INT-767 administration. In contrast, no changes in HCC tumor number and size were observed in Fxr(-/-) mice fed with or without INT-767. Notably, INT-767 preserved the hepatic parenchyma, improved hepatic function and down-regulated pro-inflammatory cytokines. Moreover, in Abcb4(-/-) mice INT-767 prevented fibrosis by reducing collagen expression and deposition. Thus, long term activation of FXR is able to reduce BA pool, reprogram BA metabolism and prevent HCC. These data provide the impetus to address the bona fide therapeutic potential of FXR activation in disease with BA-associated development of HCC.

  10. Prospective evaluation of long-term safety of dual-release hydrocortisone replacement administered once daily in patients with adrenal insufficiency

    PubMed Central

    Nilsson, A G; Marelli, C; Fitts, D; Bergthorsdottir, R; Burman, P; Dahlqvist, P; Ekman, B; Edén Engström, B; Olsson, T; Ragnarsson, O; Ryberg, M; Wahlberg, J; Lennernäs, H; Skrtic, S; Johannsson, G

    2014-01-01

    Objective The objective was to assess the long-term safety profile of dual-release hydrocortisone (DR-HC) in patients with adrenal insufficiency (AI). Design Randomised, open-label, crossover trial of DR-HC or thrice-daily hydrocortisone for 3 months each (stage 1) followed by two consecutive, prospective, open-label studies of DR-HC for 6 months (stage 2) and 18 months (stage 3) at five university clinics in Sweden. Methods Sixty-four adults with primary AI started stage 1, and an additional 16 entered stage 3. Patients received DR-HC 20–40 mg once daily and hydrocortisone 20–40 mg divided into three daily doses (stage 1 only). Main outcome measures were adverse events (AEs) and intercurrent illness (self-reported hydrocortisone use during illness). Results In stage 1, patients had a median 1.5 (range, 1–9) intercurrent illness events with DR-HC and 1.0 (1–8) with thrice-daily hydrocortisone. AEs during stage 1 were not related to the cortisol exposure-time profile. The percentage of patients with one or more AEs during stage 1 (73.4% with DR-HC; 65.6% with thrice-daily hydrocortisone) decreased during stage 2, when all patients received DR-HC (51% in the first 3 months; 54% in the second 3 months). In stages 1–3 combined, 19 patients experienced 27 serious AEs, equating to 18.6 serious AEs/100 patient-years of DR-HC exposure. Conclusions This long-term prospective trial is the first to document the safety of DR-HC in patients with primary AI and demonstrates that such treatment is well tolerated during 24 consecutive months of therapy. PMID:24944332

  11. How patients with long-term experience of living with irritable bowel syndrome manage illness in daily life: a qualitative study.

    PubMed

    Jakobsson Ung, Eva; Ringstrom, Gisela; Sjövall, Henrik; Simrén, Magnus

    2013-12-01

    Irritable bowel syndrome (IBS) is a chronic, disabling and functional gastrointestinal disorder. Effective treatments are lacking. Self-care and coping with symptoms are considered important but little is known about what patients with IBS actually do to manage their illness. The aim of this study was to explore how patients with long-term experience of living with IBS perceive their situation and manage illness in daily life. The study adopted a qualitative approach - an interpretative phenomenological analysis. Twenty patients with IBS (16 women) with a mean age of 46 (27-74) years were interviewed. The mean IBS duration was 24 (7-65) years. Two themes emerged from the analysis: Healed but not cured and Take control of daily life. Healed but not cured is about mastering IBS. Even though the patients feel there has been an improvement, their abdomen is constantly present. The patients live with intermittent interaction between well-being and illness and construct explanations for the cause of the IBS symptoms. Taking control of daily life is about the activities the patients perform to master IBS symptoms: self-centredness, disciplined self-care, control over daily routines and finding social support. These results suggest that the negative impact of IBS on daily life can be reduced. Over time, the patients had found effective strategies for symptom improvement, although this is a long-term learning process. The healthcare system could be more effective in supporting patients to find solutions to problems caused by IBS that are consistent with person-centred care and could be adopted as part of different supportive/educational interventions.

  12. Method to Estimate Long-term Change of Heat and Electric Power Daily Load Curves in Japan

    NASA Astrophysics Data System (ADS)

    Oda, Takuya; Akisawa, Atushi; Kashiwagi, Takao

    The rapid spread of CHP systems will put pressure on the regional power system to requiring an examination of the power and heat output of CHP systems. When considering the country-wide potential of the CHP system one should examine such system in coordination with the grid power system. It is essential to calculate the heat and power demand at end-use level. In the paper, annual heat and power demands of end-use sectors are forecast to the year 2025 based on 20 year data. Regression analysis is used. Estimated annual demands are divided into the seasonal hourly demands considering demand characteristics. Daily load curves of heat and power demands are determined for the Japanese end-use sectors, and the annual changes of such demands are shown by duration curves of heat to power ratios. Moreover, the grid power daily load curves are computed numerically from the estimated heat and power demands at manufacturing, residential and commercial sectors. Such load curves also consider self-generated power at manufacturing industry and own consumption of the grid power. Estimating heat and power demands allow for a joint analysis between the power system and the future phasing in of CHP systems.

  13. Lactation traits associated with short- and long-term once-daily milking performance in New Zealand crossbred dairy cattle.

    PubMed

    Davis, S R; Turner, S-A; Obolonkin, V; Tiplady, K; Spelman, R J; Phyn, C V C

    2015-09-01

    The main objectives of this study were to establish the relative value of milk yields under twice-daily milking (TDM) as a predictor of yield and yield loss under once-daily milking (ODM), and to understand the role of residual milk and udder storage capacity-related traits in regulating yield and yield loss during ODM. A Holstein-Friesian × Jersey crossbred herd was established over 2 seasons (years), as 2 individual cohorts on the same farm, managed on a pasture-based system over 4 lactations. Short-term (1-wk) ODM studies, with a starting total of 690 cows, were undertaken in mid- and late-lactation in lactation 2 and in mid-lactation in lactation 3 for each cohort. A 10-wk study of ODM performance began in mid-lactation in lactation 3, whereas lactation 4 was a full-lactation assessment of ODM. In the short-term studies, milk yield under ODM was well predicted (R(2)=0.7 to 0.8 in 5 of 6 studies) by the daily yield under TDM in the week before ODM. Yield loss (kg/d) increased with increasing milk yield and with increasing somatic cell count (SCC), although predictions were relatively poor (R(2)=0.09 to 0.30). Yield loss (%) decreased with increasing TDM yield in 3 of the 6 studies and was positively correlated with SCC during ODM. Nevertheless, ODM yield loss, in absolute or percentage terms, was a poorly repeatable trait in grazing cows. Part of the variation in yield loss percentage (30%) was positively associated with residual milk (%), measured pretrial, during measurement of functional udder capacity in lactation 3. Total production (kg of milk) over the full-lactation ODM study in lactation 4 was correlated with total production in the 10-wk trial in lactation 3 (r=0.72 and 0.63 for cohorts 1 and 2, respectively). Identifying the highest- and lowest-producing 10% of animals during the full lactation of ODM indicated that poor production was associated with high yields of residual milk (measured in lactation 3) and, conversely, high production was

  14. Investigating short- and long-term transfer effects of a Taiji beginner course in participants' daily life.

    PubMed

    Schitter, Agnes Maria; Ausfeld-Hafter, Brigitte; Nedeljkovic, Marko

    2013-09-01

    In recent years research investigating various health benefits of Taiji practice has markedly increased. Despite this growing scientific interest, essential questions such as to what extent a Taiji course may exert noticeable effects in participants' everyday life, what these effects are, and how and where potential transfer effects occur, have hardly been considered. The aim of our study was to explore transfer effects from a Taiji course into participants' daily lives. We conducted a longitudinal observational study in 45 healthy participants at the end of their three-month Taiji beginner course (tp1) and at two months (tp2) as well as one year after course completion (tp3). Participants were asked to report their Taiji practice behavior at all time points, as well as to rate and describe perceived transfer effects of Taiji course contents on their daily life at tp1 and tp3. Transfer effects were reported by 91.1% of all respondents after course completion (tp1) and persisted in 73.3% at the one-year follow-up assessment (tp3), counting "increase of self-efficacy", "improvement of stress management", and "increase of body awareness" as the most frequently mentioned effects. Transfer effects predominantly occurred in participants' work and social environments, as well as during everyday activities in public areas. While self-reliant Taiji practice frequency significantly decreased from 82.2% at tp1 to 55.6% at tp3 (P < 0.001), the magnitude of self-reported transfer effects did not (P = 0.35). As explorative analyses revealed, regular Taiji course attendance was highly correlated with stronger transfer effects at tp1 (r = 0.51; P < 0.001) and tp3 (r = 0.35; P = 0.020). Participants reporting high self-reliant Taiji practice frequency at tp2 were likely to maintain a regular practice routine at tp3 (r = 0.42; P < 0.004), whereas self-reliant practice frequency and transfer effects at tp1 were positively correlated with self-reliant practice frequency at tp3 on a

  15. Case of femoral diaphyseal stress fracture after long-term risedronate administration diagnosed by iliac bone biopsy

    PubMed Central

    Nagai, Takashi; Sakamoto, Keizo; Ishikawa, Koji; Saito, Emi; Kuroda, Takuma; Inagaki, Katsunori

    2013-01-01

    Bisphosphonate excessively inhibits bone resorption and results in pathological fracture of the femur or ilium. The subject of this study was administered risedronate for 7 years; we suspected an easy fracture of the femoral diaphysis. In this study, we report the results of this patient’s bone biopsy and bone morphometric analysis. A 76-year-old female patient presented with right femoral pain. Bone mineral density of the anteroposterior surface of the 2nd to 4th lumbar vertebrae (L2–L4) was decreased and levels of bone turnover markers were high. Therefore, we initiated treatment with risedronate. As she continued the medication, urinary levels of cross-linked N-terminal telopeptides of type I collagen and alkaline phosphatase (bone-type isozyme) were found to be within the normal ranges. After 7 years of administration, the patient experienced pain when she put weight on the right femur and right femoral pain while walking. Plain radiographic examination revealed polypoid stress fracture-like lesions on the right femoral diaphysis and on the slightly distal-lateral cortical bone. Similar lesions were observed on magnetic resonance imaging and bone scintigraphy. We suspected severely suppressed bone turnover. Bone biopsy was obtained after labeling with tetracycline, and bone morphometric analysis was performed. On microscopic examination, slight double tetracycline labeling was observed. The trabeculae were narrow, and the numbers of osteoblasts and osteoclasts were decreased. Further, rates of bone calcification and bone formation were slow. Hence, we diagnosed fracture as a result of low turnover osteopathy. Risedronate was withdrawn, and Vitamin D3 was administered to improve the bone turnover. At 6 months, abnormal signals on magnetic resonance imaging had decreased and her pain while walking or undergoing the stress test disappeared as well. Thus, long-term administration of bisphosphonates may lead to easy fracture, although bone turnover markers were

  16. Case of femoral diaphyseal stress fracture after long-term risedronate administration diagnosed by iliac bone biopsy.

    PubMed

    Nagai, Takashi; Sakamoto, Keizo; Ishikawa, Koji; Saito, Emi; Kuroda, Takuma; Inagaki, Katsunori

    2013-01-01

    Bisphosphonate excessively inhibits bone resorption and results in pathological fracture of the femur or ilium. The subject of this study was administered risedronate for 7 years; we suspected an easy fracture of the femoral diaphysis. In this study, we report the results of this patient's bone biopsy and bone morphometric analysis. A 76-year-old female patient presented with right femoral pain. Bone mineral density of the anteroposterior surface of the 2nd to 4th lumbar vertebrae (L2-L4) was decreased and levels of bone turnover markers were high. Therefore, we initiated treatment with risedronate. As she continued the medication, urinary levels of cross-linked N-terminal telopeptides of type I collagen and alkaline phosphatase (bone-type isozyme) were found to be within the normal ranges. After 7 years of administration, the patient experienced pain when she put weight on the right femur and right femoral pain while walking. Plain radiographic examination revealed polypoid stress fracture-like lesions on the right femoral diaphysis and on the slightly distal-lateral cortical bone. Similar lesions were observed on magnetic resonance imaging and bone scintigraphy. We suspected severely suppressed bone turnover. Bone biopsy was obtained after labeling with tetracycline, and bone morphometric analysis was performed. On microscopic examination, slight double tetracycline labeling was observed. The trabeculae were narrow, and the numbers of osteoblasts and osteoclasts were decreased. Further, rates of bone calcification and bone formation were slow. Hence, we diagnosed fracture as a result of low turnover osteopathy. Risedronate was withdrawn, and Vitamin D3 was administered to improve the bone turnover. At 6 months, abnormal signals on magnetic resonance imaging had decreased and her pain while walking or undergoing the stress test disappeared as well. Thus, long-term administration of bisphosphonates may lead to easy fracture, although bone turnover markers were

  17. Effects of long-term administration of recombinant bovine tumor necrosis factor-alpha on glucose metabolism and growth hormone secretion in steers.

    PubMed

    Kushibiki, S; Hodate, K; Shingu, H; Ueda, Y; Mori, Y; Itoh, T; Yokomizo, Y

    2001-05-01

    To investigate the effects of long-term administration of recombinant bovine tumor necrosis factor-alpha (rbTNF) on plasma glucose and growth hormone concentrations, and to determine whether treatment with rbTNF causes insulin resistance in steers. 5 steers treated with rbTNF and 5 steers treated with saline (0.9% NaCl) solution (control). In experiment 1, rbTNF (5.0 microg/kg of body weight) or saline solution (5 ml) was administered SC daily for 12 days. Blood samples were obtained before treatment, and plasma was harvested for determination of glucose, insulin, and growth hormone (GH) concentrations. In experiment 2, insulin, glucose, or growth hormone-releasing hormone (GHRH) was administered IV on days 7, 9, and 11, respectively, after initiation of rbTNF or saline treatment in experiment 1. Plasma glucose and insulin concentrations were measured before and at various times for 4 hours after insulin or glucose administration. Plasma GH concentrations were measured at various times for 3 hours after GHRH administration. In experiment 1, administration of rbTNF resulted in hyperinsulinemia without hypoglycemia and decreased plasma GH concentrations. In experiment 2, plasma glucose concentrations were higher in steers treated with rbTNF and insulin than in controls. Plasma GH concentrations were lower in steers treated with rbTNF and GHRH than in controls. Prolonged treatment with rbTNF induced insulin resistance and inhibited GHRH-stimulated release of GH in steers. Results indicate that rbTNF is a proximal mediator of insulin resistance and inhibits release of GH during periods of endotoxemia or infection.

  18. Antihypertensive Properties of a Pea Protein Hydrolysate during Short- and Long-Term Oral Administration to Spontaneously Hypertensive Rats.

    PubMed

    Girgih, Abraham T; Nwachukwu, Ifeanyi D; Onuh, John O; Malomo, Sunday A; Aluko, Rotimi E

    2016-05-01

    This study investigated short-term (24 h) and long-term (5 wk) systolic blood pressure (SBP)-lowering effects in spontaneously hypertensive rats (SHR) of a 5 kDa membrane pea protein hydrolysate permeate (PPH-5) produced through thermoase hydrolysis of pea protein isolate (PPI). Amino acid analysis showed that the PPH-5 had lower contents of sulfur-containing amino acids than the PPI. Size-exclusion chromatography indicated mainly low molecular weight (<10 kDa) peptides in PPH-5 but not in the PPI. The PPH-5 had renin and angiotensin converting enzyme inhibition IC50 values of 0.57 and 0.10 mg/mL (P < 0.05), respectively, and consisted mainly of peptides with 2 to 6 amino acids. Mass spectrometry analysis revealed mainly hydrophilic tetrapeptide sequences. After a single oral administration (100 mg/kg body weight) to SHR, the unheated PPI showed weakest (P < 0.05) SBP-lowering effect with a -4 mm Hg maximum when compared to -25 mm Hg for heat-treated PPI and -36 mm Hg for PPH-5. Incorporation of the PPH-5 as 0.5% or 1% (w/w) casein substitute in the SHR diet produced maximum SBP reductions of -22 or -26 mm Hg (P < 0.05), respectively after 3 wk. In comparison, the unhydrolyzed PPI produced a maximum SBP reduction of -17 mm Hg also after 3 wk. Potency of the pea products decreased in the 4th and 5th wk, though SBP values of the treated rats were still lower than the untreated control. We conclude that the antihypertensive potency of PPH-5 may have been due to the presence of easily absorbed hydrophilic peptides. © 2016 Institute of Food Technologists®

  19. Long-term administration of BAY 41-2272 prevents bladder dysfunction in nitric oxide-deficient rats.

    PubMed

    Mónica, Fabíola Z; Reges, Ricardo; Cohen, David; Silva, Fabio H; De Nucci, Gilberto; D'Ancona, Carlos A L; Antunes, Edson

    2011-03-01

    Chronic blockade of nitric oxide (NO) synthesis leads to detrusor smooth muscle overactivity. This study aimed to evaluate the protective effects of BAY 41-2272, a soluble guanlylate cyclase activator, on changes in cystometric parameters in NO-deficient rats. Rats were divided into the following groups: (a) control, (b) DMSO, (c) N(ω)-nitro-L-arginine methyl ester hydrochrolide (L-NAME), (d) BAY 41-2272 alone, and (e) L-NAME + BAY 41-2272. The NO synthase blocker L-NAME (20 mg/rat/day) was giving in the drinking water concomitantly or not with BAY 41-2272 (10 mg/kg/day, given by gavage). Chronic L-NAME treatment markedly increased the mean arterial blood pressure (MABP), and co-treatment with BAY 41-2272 nearly reversed L-NAME-induced rise on MABP. Non-void contractions were significantly increased in L-NAME group (0.90 ± 0.1 number/min) compared with either DMSO or control group (0.49 ± 0.1 number/min), which were prevented by co-treatment with BAY 41-2271 (0.56 ± 025 number/min; P < 0.05). The threshold pressure and peak pressure increased by 70% and 44% after chronic L-NAME treatment, while co-treatment with BAY 41-2272 largely attenuated both of these effects (27% and 22% increase, respectively). The frequency of micturition cycles decreased by about of 50% in L-NAME-treated rats compared with control animals, and co-treatment with BAY 41-2272 normalized this parameter. Our data show that long-term oral administration of BAY 41-2272 counteracts the bladder dysfunction seen in NO-deficient rats, indicating that restoration of the NO-cGMP pathway by this compound may be of beneficial value to treat bladder symptoms. Copyright © 2010 Wiley-Liss, Inc.

  20. Effect of long-term GHRH and somatostatin administration on GH release and body weight in prepubertal female rats.

    PubMed

    Pérez-Romero, A; Rol de Lama, M A; Ariznavarreta, C; Tresguerres, J A

    1999-12-01

    In order to find a chronic GHRH administration capable of stimulating growth rate without depleting pituitary GH content, prepubertal female rats were subcutaneously (sc) treated with GHRH (1-29)-NH2 and somatostatin (SS). In experiment 1, the rats received sc injections of GHRH and cyclic natural SS for 19 days. In the second study, female rats were continuously treated during 21 days with GHRH, using a slow release pellet, alone or combined with one daily injection of long acting SS (octreotide). In experiment 1, body weight was significantly increased when GHRH was administered at the highest daily dosage (1200 microg/day), accompanied by an slight increment in pituitary GH content. Hypothalamic SS concentrations decreased when GHRH or SS were administered alone whereas the combined treatment with both peptides did not modify this parameter, which suggests the existence of a balance between the chronic actions of both peptides on hypothalamus. In experiment 2, the continuous infusion of GHRH increased plasma GH levels and tended to enhance pituitary GH content. Nevertheless, GHRH effect was not effective enough to increase body weight. By adding one daily injection of SS both GHRH effects on the pituitary gland were abolished. Our study indicates that female rats retain responsiveness to chronic GHRH and SS treatments at both pituitary and hypothalamic levels.

  1. Chronic cocaine administration induces long-term impairment in the drive to obtain natural reinforcers in high- but not low-demanding tasks.

    PubMed

    Barnea-Ygael, Noam; Gal, Ram; Zangen, Abraham

    2016-03-01

    Repeated drug exposure induces short- and long-term neuroadaptations in brain reward circuitries that are normally involved in the regulation of motivation. Hence, repeated drug exposure has been suggested to also affect the drive to acquire natural reinforcers. Here, we tested how chronic exposure of rats to cocaine, as well as a subsequent withdrawal period, affects acquisition of natural reinforcers in high- and low-demanding tasks (HD and LD tasks, respectively). We chronically administered cocaine (i.p., 15 mg/kg once daily, or saline in control) for 30 days, followed by a 30-day withdrawal period. We tested the effect of this treatment on the acquisition of two natural appetitive reinforcers, namely self-administering a 10% sucrose solution and mounting a receptive female, under LD and HD conditions. During the cocaine exposure period, behavioral testing took place 18 hours after cocaine injection, namely after the acute pharmacologic effect of the drug dissipated. We show that chronic i.p. cocaine exposure decreased procurement of both reinforcers in HD but not in LD tasks. The effect was observed throughout the administration period with partial recovery after withdrawal. Taken together, we present empirical evidence that chronic exposure to a constant dose of cocaine is sufficient to reduce natural reinforcement, and that this decrease can outlast drug exposure. Importantly, such effects are observed only when high demands are opposing the consumption of the natural reinforcer. © 2014 Society for the Study of Addiction.

  2. Relationship between activity of daily living and asteatosis in the lower legs among elderly residents in long-term care institutions: a cross-sectional study.

    PubMed

    Nakagami, Gojiro; Kimura, Nao; Takehara, Kimie; Nakamura, Tetsuro; Kawashima, Makoto; Tsunemi, Yuichiro; Sanada, Hiromi

    2015-10-01

    This cross-sectional observational study investigated the relationship between the level of activities of daily living (ADL) and asteatosis in the lower legs among elderly residents. We enrolled 173 residents from a long-term care health facility and two special nursing homes for elderly persons in the Tokyo metropolitan area and Oshima Island, Japan. The level of ADL was measured by the Barthel Index. The relationship between the Barthel Index total score and the presence of asteatosis in the lower legs diagnosed by a dermatologist was analysed by multivariate logistic regression analysis. Among the residents, 79·2% had asteatosis in their lower legs. An increase of 1 point in the Barthel Index total score was significantly associated with a decreased probability of lower leg asteatosis after adjusting for age, sex and the type of institution (adjusted odds ratio = 0·982; 95% confidence interval: 0·966-0·998). A higher level of ADL is associated with a lower probability of having asteatosis in the lower legs among residents in long-term care institutions. Nurses should pay specific attention to residents with limited ADL for initiating preventive care for asteatosis.

  3. Dolutegravir 50 mg thrice weekly plus atazanavir 400 mg daily in a long-term virologically suppressed HIV-infected patient.

    PubMed

    Lanzafame, Massimiliano; Lattuada, Emanuela; Nicolè, Stefano; Rigo, Fabio; Cucchetto, Giulia; Concia, Ercole; Vento, Sandro

    2017-06-01

    Highly active antiretroviral therapy (HAART) has changed the natural course of HIV infection. However, the toxicities associated with long-term use of nucleoside reverse transcriptase inhibitors (NRTIs) have led to the assessment of dual-therapy approaches with less toxicity. Atazanavir and dolutegravir have antiviral potency, tolerability and favourable metabolic profile. In suppressed HIV-infected patients, with NRTIs-related toxicity effects, the association of atazanavir and dolutegravir, favoured by their positive pharmacokinetics interaction, could be used as 'maintenance' antiretroviral therapy. We report a case report about one HIV-infected patient, on HAART and with a persistent suppression of HIV RNA, switched to dolutegravir 50 mg three times weekly plus atazanavir 400 mg once daily, as 'maintenance antiretroviral therapy', with persistence of viral suppression.

  4. The PANGAEA study design - a prospective, multicenter, non-interventional, long-term study on fingolimod for the treatment of multiple sclerosis in daily practice.

    PubMed

    Ziemssen, Tjalf; Kern, Raimar; Cornelissen, Christian

    2015-06-18

    Fingolimod (Gilenya) is an oral medication for patients with highly active relapsing-remitting Multiple Sclerosis (RRMS). Clinical trials and post-marketing experience on more than 114,000 patients have established a detailed safety profile. Total patient exposure now exceeds 195,000 patient-years as stated in the last financial report (Dec 2014) of the Novartis Pharma AG, Basel, Switzerland. However, less is known about the safety of long-term fingolimod use in daily practice. Here, we describe the study design of PANGAEA (Post-Authorization Non-interventional German sAfety of GilEnyA in RRMS patients), a prospective, multicenter, non-interventional, long-term study to collect safety, efficacy, and pharmacoeconomic data on RRMS patients treated with fingolimod (0.5 mg/daily) under real-world conditions in Germany. PANGAEA is striving to assess a real-world safety and efficacy profile of fingolimod, based on data from 4,000 RRMS patients, obtained during a 60-month observational phase. A pharmacoeconomic sub-study of 800 RRMS patients further collects patient-reported outcome measures of disability, quality of life, compliance, treatment satisfaction, and usage of resources during a 24-month observational phase. Descriptive statistical analyses of the safety set as well as of stratified subgroups such as patients with concomitant diabetes mellitus and pretreated patients (e.g., natalizumab) will be conducted. PANGAEA seeks to confirm the current safety profile of fingolimod obtained in phase I-III clinical trials. The study design presented here will additionally provide guidance on the therapeutic use of fingolimod in clinical practice and possibly assists physicians in making evidence-based decisions.

  5. Short- and Long-term Outcomes of De Novo Liver Transplant Patients Treated With Once-Daily Prolonged-Release Tacrolimus.

    PubMed

    Okumura, Yuichiro; Noda, Takehiro; Eguchi, Hidetoshi; Iwagami, Yoshifumi; Yamada, Daisaku; Asaoka, Tadafumi; Wada, Hiroshi; Kawamoto, Koichi; Gotoh, Kunihito; Takeda, Yutaka; Tanemura, Masahiro; Marubashi, Shigeru; Umeshita, Koji; Doki, Yuichiro; Mori, Masaki

    2017-09-01

    Tacrolimus is the key immunosuppressive drug for liver transplantation. Once-daily prolonged-release tacrolimus (TAC-PR) exhibits good drug adherence but has difficulty controlling the trough level in the early phase of liver transplantation. The aim of this study was to compare the feasibility and efficacy of immediately starting oral TAC-PR versus traditional twice-daily tacrolimus (TAC-BID) in de novo liver transplantation recipients. The study included 28 patients treated with conventional TAC-BID and 60 patients treated with TAC-PR (median follow-up 70.5 months). Short-term and long-term outcomes were compared. Patient characteristics were similar except for the incidence of hepatocellular carcinoma and type of graft. Dose adjustment was more frequently required for TAC-PR than TAC-BID (73.3% vs 42.9%, P = 0.006), but trough levels of TAC during the first 3 months after liver transplantation were controlled well in both groups. The rate of acute cellular rejection and long-term renal function were similar in both groups. In both groups, renal function worsened during the first 6 months after transplantation and remained stable until the end of the follow-up period. The 1-year, 3-year, and 5-year survival rates were 96.4%, 85.7%, and 85.7% for TAC-BID and 96.7%, 94.8%, and 94.8% for TAC-PR, respectively. The overall survival curve for TAC-PR was not inferior to that of TAC-BID. The TAC-PR protocol was feasible and effective with strict adjustment.

  6. Determining the Long-term Effect of Antibiotic Administration on the Human Normal Intestinal Microbiota Using Culture and Pyrosequencing Methods.

    PubMed

    Rashid, Mamun-Ur; Zaura, Egijia; Buijs, Mark J; Keijser, Bart J F; Crielaard, Wim; Nord, Carl Erik; Weintraub, Andrej

    2015-05-15

    The purpose of the study was to assess the effect of ciprofloxacin (500 mg twice daily for 10 days) or clindamycin (150 mg 4 times daily for 10 days) on the fecal microbiota of healthy humans for a period of 1 year as compared to placebo. Two different methods, culture and microbiome analysis, were used. Fecal samples were collected for analyses at 6 time-points. The interval needed for the normal microbiota to be normalized after ciprofloxacin or clindamycin treatment differed for various bacterial species. It took 1-12 months to normalize the human microbiota after antibiotic administration, with the most pronounced effect on day 11. Exposure to ciprofloxacin or clindamycin had a strong effect on the diversity of the microbiome, and changes in microbial composition were observed until the 12th month, with the most pronounced microbial shift at month 1. No Clostridium difficile colonization or C. difficile infections were reported. Based on the pyrosequencing results, it appears that clindamycin has more impact than ciprofloxacin on the intestinal microbiota. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. Effects by daily long term provision of ghrelin to unselected weight-losing cancer patients: a randomized double-blind study.

    PubMed

    Lundholm, Kent; Gunnebo, Lena; Körner, Ulla; Iresjö, Britt-Marie; Engström, Cecilia; Hyltander, Anders; Smedh, Ulrika; Bosaeus, Ingvar

    2010-04-15

    The short-term provision of ghrelin to patients with cancer indicates that there may be benefits from long-term provision of ghrelin for the palliative treatment of weight-losing cancer patients. This hypothesis was evaluated in a randomized, double-blind, phase 2 study. Weight-losing cancer patients with solid gastrointestinal tumors were randomized to receive either high-dose ghrelin treatment (13 microg/kg daily; n = 17 patients) or low-dose ghrelin treatment (0.7 microg/kg daily; n = 14 patients) for 8 weeks as a once-daily, subcutaneous injections. Appetite was scored on a visual analog scale; and food intake, resting energy expenditure, and body composition (dual x-ray absorpitometry) were measured before the start of treatment and during follow-up. Serum levels of ghrelin, insulin, insulin-like growth factor 1, growth hormone (GH), triglycerides, free fatty acids, and glucose were measured. Health-related quality of life, anxiety, and depression were assessed by using standardized methods (the 36-item Short Form Health Survey and the Hospital Anxiety and Depression Scale). Physical activity, rest, and sleep were measured by using a multisensor body monitor. Treatment groups were comparable at inclusion. Appetite scores were increased significantly by high-dose ghrelin analyzed both on an intent-to-treat basis and according to the protocol. High-dose ghrelin reduced the loss of whole body fat (P < .04) and serum GH (P < .05). There was a trend for high-dose ghrelin to improve energy balance (P < .07; per protocol). Otherwise, no statistically significant differences in outcome variables were observed between the high-dose and low-dose groups. Adverse effects were not observed by high-dose ghrelin, such as serum levels of tumor markers (cancer antigen 125 [CA 125], carcinoembryonic antigen, and CA 19-9). The current results suggested that daily, long-term provision of ghrelin to weight-losing cancer patients with solid tumors supports host metabolism, improves

  8. Improvement of glucose metabolism in patients with impaired glucose tolerance or diabetes by long-term administration of a palatinose-based liquid formula as a part of breakfast.

    PubMed

    Sakuma, Masae; Arai, Hidekazu; Mizuno, Akira; Fukaya, Makiko; Matsuura, Motoi; Sasaki, Hajime; Yamanaka-Okumura, Hisami; Yamamoto, Hironori; Taketani, Yutaka; Doi, Toshio; Takeda, Eiji

    2009-09-01

    A palatinose-based liquid formula (palatinose-formula), suppresses postprandial plasma glucose and insulin levels in healthy men. The objective of this study was to investigate the effects of long-term palatinose-formula ingestion on glucose metabolism in patients with impaired glucose tolerance (IGT) or type 2 diabetes. Two patients with IGT and 7 patients with type 2 diabetes participated in the palatinose-formula and dextrin-based liquid formula (dextrin-formula) loading test and long-term palatinose-formula administration study. After a 3-month control period, palatinose-formula (1046 kJ) was ingested daily by patients as a part of breakfast for 5 months. In the loading test, palatinose-formula suppressed postprandial plasma glucose and insulin levels and areas under the curve compared with those after dextrin-formula ingestion. In the long-term study, glycated hemoglobin levels (after 3 months and 5 months of treatment) and serum 8-hydroxydeoxyguanosine levels (after 5 months of treatment) were markedly decreased comparing with those at baseline. Intake of 1046 kJ palatinose-formula as a part of breakfast over a long-term period may be effective for improvement of glucose metabolism in patients with IGT or type 2 diabetes.

  9. Effects of long-term administration of aspartame on biochemical indices, lipid profile and redox status of cellular system of male rats.

    PubMed

    Adaramoye, Oluwatosin A; Akanni, Olubukola O

    2016-01-01

    Aspartame (N-L-α-aspartyl-L-phenylalanine-1-methyl ester) (ASP) is a synthetic sweetener used in foods and its safety remains controversial. The study was designed to investigate the effects of long-term administration of aspartame on redox status, lipid profile and biochemical indices in tissues of male Wistar rats. Rats were assigned into four groups and given distilled water (control), aspartame at doses of 15 mg/kg (ASP 1), 35 mg/kg (ASP 2) and 70 mg/kg (ASP 3) daily by oral gavage for consecutive 9 weeks. Administration of ASP 2 and ASP 3 significantly increased the weight of liver and brain, and relative weight of liver of rats. Lipid peroxidation products significantly increased in the kidney, liver and brain of rats at all doses of ASP with concomitant depletion of antioxidant parameters, viz. glutathione-s-transferase, glutathione peroxidase, superoxide dismutase, catalase and reduced glutathione. Furthermore, ASP 2 and ASP 3 significantly increased the levels of gamma glutamyl transferase by 70% and 85%; alanine aminotransferase by 66% and 117%; aspartate aminotransferase by 21% and 48%; urea by 72% and 58% and conjugated bilirubin by 63% and 64%, respectively. Also, ASP 2 and ASP 3 significantly increased the levels of total cholesterol, triglycerides and low-density lipoprotein cholesterol in the rats. Histological findings showed that ASP 2 and ASP 3 caused cyto-architectural changes such as degeneration, monocytes infiltration and necrotic lesions in brain, kidney and liver of rats. Aspartame may induce redox and lipid imbalance in rats via mechanism that involves oxidative stress and depletion of glutathione-dependent system.

  10. Effects of 50 mg vildagliptin twice daily vs. 50 mg sitagliptin once daily on blood glucose fluctuations evaluated by long-term self-monitoring of blood glucose.

    PubMed

    Nomoto, Hiroshi; Kimachi, Kimihiko; Miyoshi, Hideaki; Kameda, Hiraku; Cho, Kyu Yong; Nakamura, Akinobu; Nagai, So; Kondo, Takuma; Atsumi, Tatsuya

    2017-03-03

    To date, several clinical trials have compared differences in glucose fluctuation observed with dipeptidyl peptidase-4 inhibitor treatment in patients with type 2 diabetes mellitus. However, most patients were assessed for limited periods or during hospitalization. The aim of the present study was to evaluate the effects of switching from sitagliptin to vildagliptin, or vice versa, on 12-week glucose fluctuations using self-monitoring of blood glucose in the standard care setting. We conducted a multicenter, prospective, open-label controlled trial in Japanese patients with type 2 diabetes. Thirty-two patients were treated with vildagliptin (50 mg) twice daily or sitagliptin (50 mg) once daily and were allocated to one of two groups: vildagliptin treatment for 12 weeks before switching to sitagliptin for 12 weeks, or vice versa. Daily profiles of blood glucose were assessed several times during each treatment period, and the mean amplitude of glycemic excursions and M-value were calculated. Metabolic biomarkers such as hemoglobin A1c (HbA1c), glycated albumin, and 1,5-anhydroglucitol were also assessed. With vildagliptin treatment, mean amplitude of glycemic excursions was significantly improved compared with sitagliptin treatment (57.9 ± 22.2 vs. 68.9 ± 33.0 mg/dL; p=0.0045). M-value (p=0.019) and mean blood glucose (p=0.0021) were also lower with vildagliptin, as were HbA1c, glycated albumin, and 1,5-anhydroglucitol. There were no significant differences in other metabolic parameters evaluated. Reduction of daily blood glucose profile fluctuations by vildagliptin was superior to that of sitagliptin in Japanese patients with type 2 diabetes.

  11. Comparison of Dental Caries Experience in Children Suffering From Epilepsy with and without Administration of Long Term Liquid Oral Medication

    PubMed Central

    Bhadravathi, Manjunath Chaluvaiah; Kumar, Adarsh; Narang, Ridhi; Gupta, Ambika; Singh, Harneet

    2016-01-01

    Introduction Sucrose is added as sweetening agent in liquid oral medication (LOM) to mask the acrid taste of medicines which may be potentially cariogenic. Many children under long term LOM therapy for treatment of epilepsy may be susceptible to dental caries. Aim To assess and compare dental caries experience in children under long term liquid oral medication with those not under such medication among 2-12 years old children suffering from epilepsy. Materials and Methods A cross-sectional study was undertaken on a total of 84 children aged 2–12 years, who were suffering from epilepsy receiving liquid oral medication for more than 3 months were selected (study group) and for comparison 106 children of similar age group and disease but on other forms of medication were included as control group. Dental caries was assessed using DMFT/DMFS (Decayed, Missing, Fillled Teeth / Surfaces), dmft/dft and dmfs/dfs indices. One-way ANOVA and t-test were used with p-value fixed at 0.05. Univariate logistic regression was applied. Results Children on LOM were at increased risk of dental caries than those with other forms of medications (OR: 2.55, 95% CI (2.37-4.15) p=0.000, HS). Caries prevalence was high in the study group (76.1%) when compared to control group (55.6%). Conclusion Long term use of liquid medicines containing sucrose is a risk factor for dental caries among children with epilepsy. PMID:27504416

  12. Comparison of Dental Caries Experience in Children Suffering From Epilepsy with and without Administration of Long Term Liquid Oral Medication.

    PubMed

    Goyal, Ankita; Bhadravathi, Manjunath Chaluvaiah; Kumar, Adarsh; Narang, Ridhi; Gupta, Ambika; Singh, Harneet

    2016-06-01

    Sucrose is added as sweetening agent in liquid oral medication (LOM) to mask the acrid taste of medicines which may be potentially cariogenic. Many children under long term LOM therapy for treatment of epilepsy may be susceptible to dental caries. To assess and compare dental caries experience in children under long term liquid oral medication with those not under such medication among 2-12 years old children suffering from epilepsy. A cross-sectional study was undertaken on a total of 84 children aged 2-12 years, who were suffering from epilepsy receiving liquid oral medication for more than 3 months were selected (study group) and for comparison 106 children of similar age group and disease but on other forms of medication were included as control group. Dental caries was assessed using DMFT/DMFS (Decayed, Missing, Fillled Teeth / Surfaces), dmft/dft and dmfs/dfs indices. One-way ANOVA and t-test were used with p-value fixed at 0.05. Univariate logistic regression was applied. Children on LOM were at increased risk of dental caries than those with other forms of medications (OR: 2.55, 95% CI (2.37-4.15) p=0.000, HS). Caries prevalence was high in the study group (76.1%) when compared to control group (55.6%). Long term use of liquid medicines containing sucrose is a risk factor for dental caries among children with epilepsy.

  13. Acute and long-term effects of intracerebroventricular administration of α-ketoisocaproic acid on oxidative stress parameters and cognitive and noncognitive behaviors.

    PubMed

    Taschetto, Luciane; Scaini, Giselli; Zapelini, Hugo G; Ramos, Ândrea C; Strapazzon, Giulia; Andrade, Vanessa M; Réus, Gislaine Z; Michels, Monique; Dal-Pizzol, Felipe; Quevedo, João; Schuck, Patrícia F; Ferreira, Gustavo C; Streck, Emilio L

    2017-05-27

    Maple Syrup Urine Disease (MSUD) is biochemically characterized by elevated levels of leucine, isoleucine and valine, as well as their corresponding transaminated branched-chain α-keto acids in tissue and biological fluids. Neurological symptoms and cerebral abnormalities, whose mechanisms are still unknown, are typical of this metabolic disorder. In the present study, we evaluated the early effects (1 h after injection) and long-term effects (15 days after injection) of a single intracerebroventricular administration of α-ketoisocaproic acid (KIC) on oxidative stress parameters and cognitive and noncognitive behaviors. Our results showed that KIC induced early and long-term effects; we found an increase in TBARS levels, protein carbonyl content and DNA damage in the hippocampus, striatum and cerebral cortex both one hour and 15 days after KIC administration. Moreover, SOD activity increased in the hippocampus and striatum one hour after injection, whereas after 15 days, SOD activity decreased only in the striatum. On the other hand, KIC significantly decreased CAT activity in the striatum one hour after injection, but 15 days after KIC administration, we found a decrease in CAT activity in the hippocampus and striatum. Finally, we showed that long-term cognitive deficits follow the oxidative damage; KIC induced impaired habituation memory and long-term memory impairment. From the biochemical and behavioral findings, it we presume that KIC provokes oxidative damage, and the persistence of brain oxidative stress is associated with long-term memory impairment and prepulse inhibition.

  14. Long-term patterns of air temperatures, daily temperature range, precipitation, grass-reference evapotranspiration and aridity index in the USA great plains: Part II. Temporal trends

    NASA Astrophysics Data System (ADS)

    Kukal, M.; Irmak, S.

    2016-11-01

    Detection of long-term changes in climate variables over large spatial scales is a very important prerequisite to the development of effective mitigation and adaptation measures for the future potential climate change and for developing strategies for future hydrologic balance analyses under changing climate. Moreover, there is a need for effective approaches of providing information about these changes to decision makers, water managers and stakeholders to aid in efficient implementation of the developed strategies. This study involves computation, mapping and analyses of long-term (1968-2013) county-specific trends in annual, growing-season (1st May-30th September) and monthly air temperatures [(maximum (Tmax), minimum (Tmin) and average (Tavg)], daily temperature range (DTR), precipitation, grass reference evapotranspiration (ETo) and aridity index (AI) over the USA Great Plains region using datasets from over 800 weather station sites. Positive trends in annual Tavg, Tmax and Tmin, DTR, precipitation, ETo and AI were observed in 71%, 89%, 85%, 31%, 61%, 38% and 66% of the counties in the region, respectively, whereas these proportions were 48%, 89%, 62%, 20%, 57%, 28%, and 63%, respectively, for the growing-season averages of the same variables. On a regional average basis, the positive trends in growing-season Tavg, Tmax and Tmin, DTR, precipitation, ETo and AI were 0.18 °C decade-1, 0.19 °C decade-1, 0.17 °C decade-1, 0.09 °C decade-1, 1.12 mm yr-1, 0.4 mm yr-1 and 0.02 decade-1, respectively, and the negative trends were 0.21 °C decade-1, 0.06 °C decade-1, 0.09 °C decade-1, 0.22 °C decade-1, 1.16 mm yr-1, 0.76 mm yr-1 and 0.02 decade-1, respectively. The temporal trends were highly variable in space and were appropriately represented using monthly, annual and growing-season maps developed using Geographic Information System (GIS) techniques. The long-term and spatial and temporal information and data for a large region provided in this study can be

  15. Long-term safety of once-daily, dual-release hydrocortisone in patients with adrenal insufficiency: a phase 3b, open-label, extension study.

    PubMed

    Nilsson, Anna G; Bergthorsdottir, Ragnhildur; Burman, Pia; Dahlqvist, Per; Ekman, Bertil; Engström, Britt Edén; Ragnarsson, Oskar; Skrtic, Stanko; Wahlberg, Jeanette; Achenbach, Heinrich; Uddin, Sharif; Marelli, Claudio; Johannsson, Gudmundur

    2017-06-01

    To investigate the long-term safety and tolerability of a once-daily, dual-release hydrocortisone (DR-HC) tablet as oral glucocorticoid replacement therapy in patients with primary adrenal insufficiency (AI). Prospective, open-label, multicenter, 5-year extension study of DR-HC conducted at five university clinics in Sweden. Seventy-one adult patients diagnosed with primary AI who were receiving stable glucocorticoid replacement therapy were recruited. Safety and tolerability outcomes included adverse events (AEs), intercurrent illness episodes, laboratory parameters and vital signs. Quality of life (QoL) was evaluated using generic questionnaires. Total DR-HC exposure was 328 patient-treatment years. Seventy patients reported 1060 AEs (323 per 100 patient-years); 85% were considered unrelated to DR-HC by the investigator. The most common AEs were nasopharyngitis (70%), fatigue (52%) and gastroenteritis (48%). Of 65 serious AEs reported by 32 patients (20 per 100 patient-years), four were considered to be possibly related to DR-HC: acute AI (n = 2), gastritis (n = 1) and syncope (n = 1). Two deaths were reported (fall from height and subarachnoid hemorrhage), both considered to be unrelated to DR-HC. From baseline to 5 years, intercurrent illness episodes remained relatively stable (mean 2.6-5.4 episodes per patient per year), fasting plasma glucose (0.7 mmol/L; P < 0.0001) and HDL cholesterol (0.2 mmol/L; P < 0.0001) increased and patient-/investigator-assessed tolerability improved. QoL total scores were unchanged but worsening physical functioning was recorded (P = 0.008). In the first prospective study evaluating the long-term safety of glucocorticoid replacement therapy in patients with primary AI, DR-HC was well tolerated with no safety concerns observed during 5-year treatment. © 2017 The authors.

  16. Fatigue as a long-term risk factor for limitations in instrumental activities of daily living and/or mobility performance in older adults after 10 years

    PubMed Central

    Mueller-Schotte, Sigrid; Bleijenberg, Nienke; van der Schouw, Yvonne T; Schuurmans, Marieke J

    2016-01-01

    Objectives Decline in the performance of instrumental activities of daily living (IADL) and mobility may be preceded by symptoms the patient experiences, such as fatigue. The aim of this study is to investigate whether self-reported non-task-specific fatigue is a long-term risk factor for IADL-limitations and/or mobility performance in older adults after 10 years. Methods A prospective study from two previously conducted cross-sectional studies with 10-year follow-up was conducted among 285 males and 249 females aged 40–79 years at baseline. Fatigue was measured by asking “Did you feel tired within the past 4 weeks?” (males) and “Do you feel tired?” (females). Self-reported IADLs were assessed at baseline and follow-up. Mobility was assessed by the 6-minute walk test. Gender-specific associations between fatigue and IADL-limitations and mobility were estimated by multivariable logistic and linear regression models. Results A total of 18.6% of males and 28.1% of females were fatigued. After adjustment, the odds ratio for fatigued versus non-fatigued males affected by IADL-limitations was 3.3 (P=0.023). In females, the association was weaker and not statistically significant, with odds ratio being 1.7 (P=0.154). Fatigued males walked 39.1 m shorter distance than those non-fatigued (P=0.048). For fatigued females, the distance was 17.5 m shorter compared to those non-fatigued (P=0.479). Conclusion Our data suggest that self-reported fatigue may be a long-term risk factor for IADL-limitations and mobility performance in middle-aged and elderly males but possibly not in females. PMID:27877027

  17. Dysphagia Assessed by the 10-Item Eating Assessment Tool Is Associated with Nutritional Status and Activities of Daily Living in Elderly Individuals Requiring Long-Term Care.

    PubMed

    Wakabayashi, H; Matsushima, M

    2016-01-01

    The 10-item Eating Assessment Tool (EAT-10) is a self-administered questionnaire for dysphagia screening, with each item scored from 0 to 4. We assessed the associations among the EAT-10 score, nutritional status and activities of daily living (ADL) in elderly individuals requiring long-term care. Cross-sectional study. Geriatric health services facilities, acute hospitals, and the community. Elderly individuals ≥65 years of age with dysphagia or possible dysphagia (N=237). The EAT-10, the Mini Nutritional Assessment Short Form (MNA-SF) and the Barthel Index. There were 90 males and 147 females. Mean age was 82 ± 8 years. Eighty-nine were in geriatric health services facilities, 28 were in acute hospitals, and 120 were community-dwelling. The median Barthel Index score was 55 (interquartile range: 25, 80). The median EAT-10 score was 1 (interquartile range: 0, 9), and 101 respondents a score > 3, indicating the presence of dysphagia. The MNA-SF revealed that 81 were malnourished, 117 were at risk of malnutrition, and 39 had a normal nutritional status. The Barthel Index score and MNA-SF score were significantly lower in those with an EAT-10 score between 3 and 40, compared to those with an EAT-10 score between 0 and 2. The EAT-10 has an independent effect on the Barthel Index and the MNA-SF by adjusting for covariates such as age, gender, and setting in multiple regression analysis. Dysphagia assessed by the EAT-10 is associated with nutritional status and ADL in elderly individuals requiring long-term care.

  18. Patient-reported convenience of once-daily versus three-times-daily dosing during long-term studies of pramipexole in early and advanced Parkinson's disease.

    PubMed

    Schapira, A H V; Barone, P; Hauser, R A; Mizuno, Y; Rascol, O; Busse, M; Debieuvre, C; Fraessdorf, M; Poewe, W

    2013-01-01

      In chronic diseases including Parkinson's disease (PD), complex pharmacotherapy dosing schedules are reported to reduce adherence, perhaps leading to less-effective symptom control and, in PD, more erratic stimulation of dopamine receptors. However, blinded clinical-trial designs preclude direct comparisons of adherence to various schedules.   In two double-blind (DB) studies of early PD and one of advanced PD, subjects received three-times-daily (t.i.d.) pramipexole or placebo. In open-label (OL) extensions, subjects took extended-release, once-daily (q.d.) pramipexole. At 24 or 32 OL weeks, q.d. versus t.i.d. dosing preference was surveyed by questionnaire.   Of 590 DB-trial completers with early PD, 511 entered the OL extension. Of 374 survey respondents, 94.4% preferred q.d. dosing (72.2% of them found it 'very much more convenient' and 27.8%'more convenient'), 2.7% preferred t.i.d., and 2.9% chose 'no difference'. Of 465 DB-trial completers with advanced PD, 391 entered its OL extension. Of 334 survey respondents, 88.9% preferred q.d. dosing (59.9% of them found it 'very much more convenient' and 40.1%'more convenient'), 5.7% preferred t.i.d., and 5.4% chose 'no difference'. Results excluding DB-placebo recipients were highly similar.   In this first direct comparison of patient preference for q.d. versus t.i.d. dopamine-agonist dosing, patients with early or advanced PD had a strong preference for q.d. rather than t.i.d. pramipexole. The high proportion of advanced-PD patients declaring this preference indicates that it does not depend on whether a patient is taking concomitant PD medications dosed more frequently than q.d. © 2012 The Author(s). European Journal of Neurology © 2012 EFNS.

  19. Long-term AICAR administration reduces metabolic disturbances and lowers blood pressure in rats displaying features of the insulin resistance syndrome.

    PubMed

    Buhl, Esben S; Jessen, Niels; Pold, Rasmus; Ledet, Thomas; Flyvbjerg, Allan; Pedersen, Steen B; Pedersen, Oluf; Schmitz, Ole; Lund, Sten

    2002-07-01

    data provide strong evidence that long-term administration of AICAR improves glucose tolerance, improves the lipid profile, and reduces systolic blood pressure in an insulin-resistant animal model. The present study gives additional support to the hypothesis that AMPK activation might be a potential future pharmacological strategy for treating the insulin resistance syndrome.

  20. Long-term effects of an acute and systemic administration of LPS on adult neurogenesis and spatial memory.

    PubMed

    Valero, Jorge; Mastrella, Giorgia; Neiva, Ismael; Sánchez, Silvia; Malva, João O

    2014-01-01

    The cognitive reserve is the capacity of the brain to maintain normal performance while exposed to insults or ageing. Increasing evidences point to a role for the interaction between inflammatory conditions and cognitive reserve status during Alzheimer's disease (AD) progression. The production of new neurons along adult life can be considered as one of the components of the cognitive reserve. Interestingly, adult neurogenesis is decreased in mouse models of AD and following inflammatory processes. The aim of this work is to reveal the long-term impact of a systemic inflammatory event on memory and adult neurogenesis in wild type (WT) and triple transgenic mouse model of AD (3xTg-AD). Four month-old mice were intraperitoneally injected once with saline or lipopolysaccharide (LPS) and their performance on spatial memory analyzed with the Morris water maze (MWM) test 7 weeks later. Our data showed that a single intraperitoneal injection with LPS has a long-term impact in the production of hippocampal neurons. Consistently, LPS-treated WT mice showed less doublecortin-positive neurons, less synaptic contacts in newborn neurons, and decreased dendritic volume and complexity. These surprising observations were accompanied with memory deficits. 3xTg-AD mice showed a decrease in new neurons in the dentate gyrus compatible with, although exacerbated, the pattern observed in WT LPS-treated mice. In 3xTg-AD mice, LPS injection did not significantly affected the production of new neurons but reduced their number of synaptic puncta and impaired memory performance, when compared to the observations made in saline-treated 3xTg-AD mice. These data indicate that LPS treatment induces a long-term impairment on hippocampal neurogenesis and memory. Our results show that acute neuroinflammatory events influence the production of new hippocampal neurons, affecting the cognitive reserve and leading to the development of memory deficits associated to AD pathology.

  1. Raloxifene Administration in Women Treated with Long Term Gonadotropin-releasing Hormone Agonist for Severe Endometriosis: Effects on Bone Mineral Density

    PubMed Central

    Cho, Young Hwa; Um, Mi Jung; Kim, Suk Jin; Kim, Soo Ah

    2016-01-01

    Objectives To evaluate the efficacy of raloxifene in preventing bone loss associated with long term gonadotropin-releasing hormone agonist (GnRH-a) administration. Methods Twenty-two premenopausal women with severe endometriosis were treated with leuprolide acetate depot at a dosage of 3.75 mg/4 weeks, for 48 weeks. Bone mineral density (BMD) was evaluated at admission, and after 12 treatment cycles. Results At cycle 12 of GnRH-a plus raloxifene treatment, lumbar spine, trochanter femoral neck, and Ward's BMD differed from before the treatment. A year after treatment, the lumbar spine and trochanter decreased slightly, but were not significantly different. Conclusions Our study shows that the administration of GnRH-a plus raloxifene in pre-menopausal women with severe endometriosis, is an effective long-term treatment to prevent bone loss. PMID:28119898

  2. Effect of long-term caffeine administration on depressive-like behavior in rats exposed to chronic unpredictable stress.

    PubMed

    Pechlivanova, Daniela M; Tchekalarova, Jana D; Alova, Liana H; Petkov, Vesselin V; Nikolov, Rumen P; Yakimova, Krassimira S

    2012-08-01

    Chronic unpredictable stress (CUS) was used to study the effects of a long-term treatment with either caffeine (8 mg/kg, orally) or desipramine (DMI) (10 mg/kg, intraperitoneally) in Wistar rats. The CUS procedure was applied for 6 weeks. Animals underwent a 2-week drug-free CUS procedure. Drugs were administered for 4 weeks alongside the stress and both drug and stress were continued throughout the behavioral testing period. CUS-exposed rats showed depressive-like behavior with reduced weight gain, reduced consumption of sucrose solution, increased immobility in the forced swimming test, and hypolocomotion in an open field. For the open field and elevated plus maze, calculation of an anxiety index confirmed that CUS increased anxiety, which was accompanied by an increase in the core temperature. DMI counteracted these physical and behavioral changes. Caffeine caused similar effects to DMI on weight gain, motor activity, anxiety level, and core temperature. In CUS-exposed rats, caffeine showed antidepressant and anxiolytic activity, accompanied by increased hippocampal dopamine and serotonin levels. However, no significant change in weight gain or core temperature was observed after caffeine treatment in CUS-exposed rats. These results suggest that, similar to the antidepressant DMI, long-term caffeine exposure exerts an antidepressant and anxiolytic effect in the CUS model. The involvement of the dopaminergic and serotonergic systems is discussed.

  3. Evaluation of the long-term energy analysis program used for the 1978 EIA Administrator's Report to Congress

    SciTech Connect

    Peelle, R. W.; Weisbin, C. R.; Alsmiller, Jr., R. G.

    1981-10-01

    An evaluation of the Long-Term Energy Analysis Program (LEAP), a computer model of the energy portion of the US economy that was used for the 1995-2020 projections in its 1978 Annual Report to Congress, is presented. An overview of the 1978 version, LEAP Model 22C, is followed by an analysis of the important results needed by its users. The model is then evaluated on the basis of: (1) the adequacy of its documentation; (2) the local experience in operating the model; (3) the adequacy of the numerical techniques used; (4) the soundness of the economic and technical foundations of the model equations; and (5) the degree to which the computer program has been verified. To show which parameters strongly influence the results and to approach the question of whether the model can project important results with sufficient accuracy to support qualitative conclusions, the numerical sensitivities of some important results to model input parameters are described. The input data are categorized and discussed, and uncertainties are given for some parameters as examples. From this background and from the relation of LEAP to other available approaches for long-term energy modeling, an overall evaluation is given of the model's suitability for use by the EIA.

  4. Histopathological studies of cardiac lesions after long term administration of methamphetamine in high dosage--Part II.

    PubMed

    Islam, Mohammed Nasimul; Jesmine, Khan; Kong Sn Molh, Arthur; Hasnan, Jaafar

    2009-04-01

    A small amount of Methamphetamine (MA) can produce behavioural changes such as euphoria, increased alertness, paranoia, decreased appetite and increased physical activity. In cardiovascular system, it can produce chest pain and hypertension which can result in cardiovascular collapse. In addition, MA causes accelerated heartbeat, elevated blood pressure. It can also cause irreversible damage to blood vessels in the brain. A number of sympathomimetic amines are capable of causing myocardial damage, but the cardio-toxic action of MA has been of particular interest since standardized dosage consistently produces myocardial lesions. As this drug is a choice of many teenagers and young adults, the damage to their health, as well as their future aspects could be greatly affected, therefore more evidence must be sought to convince them the negative root and show them the optimism of recovery and salvation. To clarify the effect of Methamphetamine (MA) on myocardium, 56 male Wister rats aged four weeks were divided equally into MA, Methamphetamine withdrawal (MW), Placebo (P) and Control (C) group were examined following daily intra-peritoneal administration of MA at a dose of 5 mg/kg body weight for 2, 4, 8 and 12 weeks. Normal saline was similarly injected in P group. Light microscopic changes was seen in the myocardium of MA treated group including eosinophilic degeneration, atrophy, hypertrophy, disarray, edema, cellular infiltration, myolysis, granulation tissue, fibrosis and vacuolization. On the other hand, the withdrawal group showed evidence of gradual recovery of those myocardial changes. Optimism is therefore generated about possibility of returning towards normal by withdrawing of this drug by the addicts.

  5. Homogenised daily lake surface water temperature data generated from multiple satellite sensors: A long-term case study of a large sub-Alpine lake

    PubMed Central

    Pareeth, Sajid; Salmaso, Nico; Adrian, Rita; Neteler, Markus

    2016-01-01

    Availability of remotely sensed multi-spectral images since the 1980’s, which cover three decades of voluminous data could help researchers to study the changing dynamics of bio-physical characteristics of land and water. In this study, we introduce a new methodology to develop homogenised Lake Surface Water Temperature (LSWT) from multiple polar orbiting satellites. Precisely, we developed homogenised 1 km daily LSWT maps covering the last 30 years (1986 to 2015) combining data from 13 satellites. We used a split-window technique to derive LSWT from brightness temperatures and a modified diurnal temperature cycle model to homogenise data which were acquired between 8:00 to 17:00 UTC. Gaps in the temporal LSWT data due to the presence of clouds were filled by applying Harmonic ANalysis of Time Series (HANTS). The satellite derived LSWT maps were validated based on long-term monthly in-situ bulk temperature measurements in Lake Garda, the largest lake in Italy. We found the satellite derived homogenised LSWT being significantly correlated to in-situ data. The new LSWT time series showed a significant annual rate of increase of 0.020 °C yr−1 (*P < 0.05), and of 0.036 °C yr−1 (***P < 0.001) during summer. PMID:27502177

  6. Comparisons of social interaction and activities of daily living between long-term care facility and community-dwelling stroke patients

    PubMed Central

    Yoon, Jeong-Ae; Park, Se-Gwan; Roh, Hyo-Lyun

    2015-01-01

    [Purpose] This study was conducted to compare the correlation between social interaction and activities of daily living (ADL) between community-dwelling and long-term care facility stroke patients. [Subjects and Methods] The Subjects were 65 chronic stroke patients (32 facility-residing, 33 community-dwelling). The Evaluation Social Interaction (ESI) tool was used to evaluate social interaction and the Assessment of Motor and Process Skills (AMPS) measure was used to evaluate ADL. [Results] Both social interaction and ADL were higher in community-dwelling than facility-residing stroke patients. There was a correlation between ESI and ADL for both motor and process skills among facility-residing patients, while only ADL process skills and ESI correlated among community-dwelling patients. In a partial correlation analysis using ADL motor and process skills as control variables, only process skills correlated with ESI. [Conclusion] For rehabilitation of stroke patients, an extended treatment process that combines ADL and social activities is likely to be required. Furthermore, treatment programs and institutional systems that can improve social interaction and promote health maintenance for community-dwelling and facility-residing chronic stroke patients are needed throughout the rehabilitation process. PMID:26644659

  7. Comparisons of social interaction and activities of daily living between long-term care facility and community-dwelling stroke patients.

    PubMed

    Yoon, Jeong-Ae; Park, Se-Gwan; Roh, Hyo-Lyun

    2015-10-01

    [Purpose] This study was conducted to compare the correlation between social interaction and activities of daily living (ADL) between community-dwelling and long-term care facility stroke patients. [Subjects and Methods] The Subjects were 65 chronic stroke patients (32 facility-residing, 33 community-dwelling). The Evaluation Social Interaction (ESI) tool was used to evaluate social interaction and the Assessment of Motor and Process Skills (AMPS) measure was used to evaluate ADL. [Results] Both social interaction and ADL were higher in community-dwelling than facility-residing stroke patients. There was a correlation between ESI and ADL for both motor and process skills among facility-residing patients, while only ADL process skills and ESI correlated among community-dwelling patients. In a partial correlation analysis using ADL motor and process skills as control variables, only process skills correlated with ESI. [Conclusion] For rehabilitation of stroke patients, an extended treatment process that combines ADL and social activities is likely to be required. Furthermore, treatment programs and institutional systems that can improve social interaction and promote health maintenance for community-dwelling and facility-residing chronic stroke patients are needed throughout the rehabilitation process.

  8. Homogenised daily lake surface water temperature data generated from multiple satellite sensors: A long-term case study of a large sub-Alpine lake

    NASA Astrophysics Data System (ADS)

    Pareeth, Sajid; Salmaso, Nico; Adrian, Rita; Neteler, Markus

    2016-08-01

    Availability of remotely sensed multi-spectral images since the 1980’s, which cover three decades of voluminous data could help researchers to study the changing dynamics of bio-physical characteristics of land and water. In this study, we introduce a new methodology to develop homogenised Lake Surface Water Temperature (LSWT) from multiple polar orbiting satellites. Precisely, we developed homogenised 1 km daily LSWT maps covering the last 30 years (1986 to 2015) combining data from 13 satellites. We used a split-window technique to derive LSWT from brightness temperatures and a modified diurnal temperature cycle model to homogenise data which were acquired between 8:00 to 17:00 UTC. Gaps in the temporal LSWT data due to the presence of clouds were filled by applying Harmonic ANalysis of Time Series (HANTS). The satellite derived LSWT maps were validated based on long-term monthly in-situ bulk temperature measurements in Lake Garda, the largest lake in Italy. We found the satellite derived homogenised LSWT being significantly correlated to in-situ data. The new LSWT time series showed a significant annual rate of increase of 0.020 °C yr‑1 (*P < 0.05), and of 0.036 °C yr‑1 (***P < 0.001) during summer.

  9. Homogenised daily lake surface water temperature data generated from multiple satellite sensors: A long-term case study of a large sub-Alpine lake.

    PubMed

    Pareeth, Sajid; Salmaso, Nico; Adrian, Rita; Neteler, Markus

    2016-08-09

    Availability of remotely sensed multi-spectral images since the 1980's, which cover three decades of voluminous data could help researchers to study the changing dynamics of bio-physical characteristics of land and water. In this study, we introduce a new methodology to develop homogenised Lake Surface Water Temperature (LSWT) from multiple polar orbiting satellites. Precisely, we developed homogenised 1 km daily LSWT maps covering the last 30 years (1986 to 2015) combining data from 13 satellites. We used a split-window technique to derive LSWT from brightness temperatures and a modified diurnal temperature cycle model to homogenise data which were acquired between 8:00 to 17:00 UTC. Gaps in the temporal LSWT data due to the presence of clouds were filled by applying Harmonic ANalysis of Time Series (HANTS). The satellite derived LSWT maps were validated based on long-term monthly in-situ bulk temperature measurements in Lake Garda, the largest lake in Italy. We found the satellite derived homogenised LSWT being significantly correlated to in-situ data. The new LSWT time series showed a significant annual rate of increase of 0.020 °C yr(-1) (*P < 0.05), and of 0.036 °C yr(-1) (***P < 0.001) during summer.

  10. Modulation of 5-HT release in the guinea-pig brain following long-term administration of antidepressant drugs.

    PubMed Central

    Blier, P; Bouchard, C

    1994-01-01

    1. The aims of the present study were to determine whether long-term 5-hydroxytryptamine (5-HT) reuptake blockade and inhibition of type-A monoamine oxidase (MAO-A) lead to an enhancement of the electrically evoked release of tritum from guinea-pig brain slices preloaded with [3H]-5-HT, and to assess the sensitivity of the terminal 5-HT1D autoreceptor, the alpha 2-adrenoceptor also located on 5-HT terminals, and the 5-HT3 receptor that modulates 5-HT release following these two types of antidepressant treatments. 2. The electrically evoked release of tritium was significantly enhanced following a 21-day treatment with the 5-HT reuptake blocker, paroxetine and the reversible MAO-A inhibitor, befloxatone, in preloaded slices of the hypothalamus, hippocampus and frontal cortex 48 h after removal of the osmotic minipumps used to deliver the drugs. 3. The inhibitory effect of the terminal 5-HT autoreceptor agonist, 5-methoxytryptamine, on the evoked release of tritium was attenuated in slices of the hypothalamus, hippocampus, but not frontal cortex, following the paroxetine treatment. In the befloxatone group, the effectiveness of 5-methoxytryptamine was unaltered in the same brain structures. 4. The sensitivity of the alpha 2-adrenoceptor on 5-HT terminals, assessed using UK 14.304, was attenuated in hypothalamus, hippocampus, but not frontal cortex slices prepared from befloxatone-treated guinea-pigs and preloaded with [3H]-5-HT. The paroxetine treatment did not alter the sensitivity of this alpha 2-adrenoceptor in the hypothalamus. 5. The sensitivity of the alpha 2-adrenoceptor on noradrenaline terminals, also assessed using UK 14.304, was not altered in hippocampus and hypothalamus slices preloaded with [3H]-noradrenaline following the long-term befloxatone treatment. 6. In frontal cortex slices, [3H]-5-HT uptake was no longer significantly attenuated after a 21-day treatment with paroxetine, whereas it was still markedly inhibited in hypothalamus slices. The

  11. Pharmacogenetics may Influence Tacrolimus Daily Dose, but not Urinary Tubular Damage Markers in the Long-Term Period after Renal Transplantation

    PubMed Central

    Stefanović, Nikola Z.; Cvetković, Tatjana P.; Veličković-Radovanović, Radmila M.; Jevtović-Stoimenov, Tatjana M.; Vlahović, Predrag M.; Stojanović, Ivana R.; Pavlović, Dušica D.

    2015-01-01

    Summary Background The primary goal of this study was to evaluate the influence of cytochrome P450 (CYP) 3A5 (6986A>G) and ABCB1 (3435C>T) polymorphisms on tacrolimus (TAC) dosage regimen and exposure. Second, we evaluated the influence of TAC dosage regimen and the tested polymorphisms on renal oxidative injury, as well as the urinary activities of tubular ectoenzymes in a long-term period after transplantation. Also, we aimed to determine the association between renal oxidative stress and tubular damage markers in the renal transplant patients. Methods The study included 72 patients who were on TAC based immunosuppression. Allele-specific PCR was used for polymorphism determination. We measured the urinary thiobarbituric acid reactive substances (TBARS) and reactive carbonyl derivates (RCD) in order to evaluate oxidative injury, as well as the urinary activities of ectoenzymes (N-acetyl-β-D-glucosaminidase, aminopeptidase N and dipeptidyl peptidase IV) to evaluate tubular damage. Results The carriers of CYP 3A5*1 allele required statistically higher daily doses of TAC than CYP *3/*3 carriers, as well as the carriers of C allele of ABCB1 gene compared to those with TT genotype. Also, there were no differences in TBARS, RCD and the activities of ectoenzymes between the patients’ genotypes. Our results showed significant correlations between urinary TBARS and RCD and the ectoenzymes’ activities. Conclusions Our findings suggest that CYP 3A5 and ABCB1 3435 polymorphism may affect TAC daily doses, but not the drug’s tubular toxicity. Furthermore, tubular damage may be associated with increased renal oxidative stress. PMID:28356851

  12. Long-term outcome of a phase 2 trial with nilotinib 400 mg twice daily in first-line treatment of chronic myeloid leukemia

    PubMed Central

    Gugliotta, Gabriele; Castagnetti, Fausto; Breccia, Massimo; Levato, Luciano; D’Adda, Mariella; Stagno, Fabio; Tiribelli, Mario; Salvucci, Marzia; Fava, Carmen; Martino, Bruno; Cedrone, Michele; Bocchia, Monica; Trabacchi, Elena; Cavazzini, Francesco; Usala, Emilio; Rossi, Antonella Russo; Bochicchio, Maria Teresa; Soverini, Simona; Alimena, Giuliana; Cavo, Michele; Pane, Fabrizio; Martinelli, Giovanni; Saglio, Giuseppe; Baccarani, Michele; Rosti, Gianantonio

    2015-01-01

    Nilotinib is a second-generation tyrosine kinase inhibitor that has been approved for the first-line treatment of chronic-phase chronic myeloid leukemia, based on the results of a prospective randomized study of nilotinib versus imatinib (ENESTnd). Apart from this registration study, very few data are currently available on first-line nilotinib treatment. We report here the long-term, 6-year results of the first investigator-sponsored, GIMEMA multicenter phase 2, single-arm trial with nilotinib 400 mg twice daily as first-line treatment in 73 patients with chronic-phase chronic myeloid leukemia. Six-year overall survival and progression-free survival rates were 96%, with one death after progression to blast phase. At 6 years, 75% of the patients were still on nilotinib. The cumulative incidence of major molecular response was 98%; only one patient had a confirmed loss of major molecular response. The cumulative incidence of deep molecular response (MR 4.0) was 76%. Deep molecular response was stable (≥2 years) in 34% of these patients. Cardiovascular adverse events, mainly due to arterial thrombosis, occurred in 11/73 patients (15%), after 24 to 76 months of therapy. They were more frequent in elderly patients, and in those with baseline cardiovascular risk factors. None was fatal, although there was a relevant morbidity. This is the study with the longest follow-up of a high dose of nilotinib (400 mg twice daily): it highlights the high efficacy and the cardiovascular toxicity of the drug (CTG.NCT.00481052). PMID:26113419

  13. Alteration in plasma corticosterone levels following long term oral administration of lead produces depression like symptoms in rats.

    PubMed

    Haider, Saida; Saleem, Sadia; Tabassum, Saiqa; Khaliq, Saima; Shamim, Saima; Batool, Zehra; Parveen, Tahira; Inam, Qurat-ul-ain; Haleem, Darakhshan J

    2013-03-01

    Lead toxicity is known to induce a broad range of physiological, biochemical and behavioral dysfunctions that may result in adverse effects on several organs, including the central nervous system. Long-term exposure to low levels of lead (Pb(2+)) has been shown to produce behavioral deficits in rodents and humans by affecting hypothalamic-pituitary-adrenal (HPA) axis. These deficits are thought to be associated with altered brain monoamine neurotransmission and due to changes in glucocorticoids levels. This study was designed to investigate the effects of Pb(2+)exposure on growth rate, locomotor activity, anxiety, depression, plasma corticosterone and brain serotonin (5-HT) levels in rats. Rats were exposed to lead in drinking water (500 ppm; lead acetate) for 5 weeks. The assessment of depression was done using the forced swimming test (FST). Estimation of brain 5-HT was determined by high-performance liquid chromatography with electrochemical detection. Plasma corticosterone was determined by spectrofluorimetric method. The present study showed that long term exposure to Pb(2+) significantly decreased the food intake followed by the decrease in growth rate in Pb(2+)exposed rats as compared to control group. No significant changes in open field activity were observed following Pb(2+)exposure while significant increase in anxiogenic effect was observed. Increased plasma corticosterone and decreased 5-HT levels were exhibited by Pb(2+)exposed rats as compared to controls. A significant increase in depressive like symptoms was exhibited by Pb(2+)exposed rats as compared to control rats. The results are discussed in the context of Pb(2+) inducing a stress-like response in rats leading to changes in plasma corticosterone and brain 5-HT levels via altering tryptophan pyrrolase activity.

  14. Benzodiazepine long-term administration is associated with impaired attention/working memory in schizophrenia: results from the national multicentre FACE-SZ data set.

    PubMed

    Fond, Guillaume; Berna, F; Boyer, L; Godin, O; Brunel, L; Andrianarisoa, M; Aouizerate, B; Capdevielle, D; Chereau, I; Danion, J M; Dubertret, C; Dubreucq, J; Faget, C; Gabayet, F; Le Gloahec, T; Llorca, P M; Mallet, J; Misdrahi, D; Rey, R; Richieri, R; Passerieux, C; Portalier, C; Roux, P; Vehier, A; Yazbek, H; Schürhoff, F; Bulzacka, E

    2017-03-27

    The effect of benzodiazepine long-term administration (BLTA) in cognitive functioning of subjects with schizophrenia (SZ) has been partially explored to date. The objective was to assess BLTA-associated cognitive impairment with a comprehensive cognitive battery in a non-selected multicentric/national community-dwelling sample of stabilized SZ subjects. 407 community-dwelling stabilized SZ subjects were consecutively included in the FondaMental Academic Centers of Expertise for Schizophrenia Cohort (FACE-SZ). Patients taking daily benzodiazepine were defined as BLTA+ as all patients examined by the Expert Center were clinically stabilized and under stable dose of treatment for at least 3 months. Each patient has been administered a 1-day long comprehensive cognitive battery (including The National Adult Reading Test, the Wechsler Adult Intelligence Scale, the Trail Making Test, the California Verbal Learning Test, the Doors test, and The Continuous Performance Test-Identical Pairs). In the multivariate analyses, results showed that BLTA was associated with impaired attention/working memory (OR 0.60, 95% confidence interval 0.42-0.86; p = 0.005) independently of socio-demographic variables and illness characteristics. Verbal and performance current IQ-[respectively, OR 0.98, 95% CI (0.96;0.99), p = 0.016 and 0.98, 95% CI(0.97;0.99), p = 0.034] but not premorbid IQ-(p > 0.05) have been associated with BLTA in a multivariate model including the same confounding variables. BLTA is associated with impaired attention/working memory in schizophrenia. The BLTA benefit/risk ratio should be regularly reevaluated. Alternative pharmacological and non-pharmacological strategies for comorbid anxiety disorders and sleep disorders should be preferred when possible. It seems reasonable to withdraw BLTA before the start of cognitive remediation therapy, as soon as possible, to improve the effectiveness of this therapy. Limits: the delay between the last benzodiazepine

  15. Long-term patterns of air temperatures, daily temperature range, precipitation, grass-reference evapotranspiration and aridity index in the USA Great Plains: Part I. Spatial trends

    NASA Astrophysics Data System (ADS)

    Kukal, M.; Irmak, S.

    2016-11-01

    Due to their substantial spatio-temporal behavior, long-term quantification and analyses of important hydrological variables are essential for practical applications in water resources planning, evaluating the water use of agricultural crop production and quantifying crop evapotranspiration patterns and irrigation management vs. hydrologic balance relationships. Observed data at over 800 sites across the Great Plains of USA, comprising of 9 states and 2,307,410 km2 of surface area, which is about 30% of the terrestrial area of the USA, were used to quantify and map large-scale and long-term (1968-2013) spatial trends of air temperatures, daily temperature range (DTR), precipitation, grass-reference evapotranspiration (ETo) and aridity index (AI) at monthly, growing season and annual time steps. Air temperatures had a strong north to south increasing trend, with annual average varying from -1 to 24 °C, and growing season average temperature varying from 8 to 30 °C. DTR gradually decreased from western to eastern parts of the region, with a regional annual and growing season averages of 14.25 °C and 14.79 °C, respectively. Precipitation had a gradual shift towards higher magnitudes from west to east, with the average annual and growing season (May-September) precipitation ranging from 163 to 1486 mm and from 98 to 746 mm, respectively. ETo had a southwest-northeast decreasing trend, with regional annual and growing season averages of 1297 mm and 823 mm, respectively. AI increased from west to east, indicating higher humidity (less arid) towards the east, with regional annual and growing season averages of 0.49 and 0.44, respectively. The spatial datasets and maps for these important climate variables can serve as valuable background for climate change and hydrologic studies in the Great Plains region. Through identification of priority areas from the developed maps, efforts of the concerned personnel and agencies and resources can be diverted towards development

  16. Drug-Containing Gelatin Treats as an Alternative to Gavage for Long-Term Oral Administration in Rhesus Monkeys (Macaca mulatta)

    PubMed Central

    Zhang, Shuang; Ye, Bin; Zeng, Li; Chen, Younan; He, Sirong; Wang, Chengshi; Li, Xinli; Zhao, Jiuming; Shi, Meimei; Wang, Li; Li, Hongxia; Cheng, Jingqiu; Wang, Wei; Lu, Yanrong

    2012-01-01

    Long-term oral administration of immunosuppressive agents to transplanted rhesus monkeys (Macaca mulatta) is one of the major challenges in such studies. To avoid the drawbacks of gavage, we tested an alternative method for oral dosing of sirolimus in rhesus monkeys by adding sirolimus, a commonly used immunosuppressant, to gelatin to create drug-containing gelatin ‘treats’ that our macaques would accept voluntarily. We evaluated the oral bioequivalence of the oral solution and drug-containing gelatin and assayed the whole-blood levels of sirolimus after long-term drug delivery. We found that time to peak concentration but not peak concentration itself or the area under the time–concentration curve differed between the 2 groups. Although the maximal concentration data did not fit the condition of bioequivalence, those for the time–concentration curves from 0 to 24 h and from 0 h to infinity did; therefore the extent of sirolimus absorption did not differ significantly between the 2 formulations. The sirolimus levels for long-term drug delivery were equivalent at 2.97 ± 1.91 ng/mL in the gelatin group and 3.13 ± 2.03 ng/mL in the solution group. The gelatin dosing technique we describe here is convenient and effective for oral administration of sirolimus in rhesus monkeys and likely can be adapted for other drugs. PMID:23294893

  17. Day/night variation of 5-hydroxyindole acetic acid concentration in rat cerebrospinal fluid after acute and long-term administration of a selective serotonin reuptake inhibitor, fluvoxamine.

    PubMed

    Egashira, T; Takayama, F; Yamanaka, Y; Takada, K; Takeda, H; Matsumiya, T

    2000-08-01

    When 30 mg/kg, p.o. of fluvoxamine, a selective serotonin reuptake inhibitor, was administered, significant increases of 3-methoxy-4-hydroxyphenylglycol (MHPG) and 5-hydroxy indole-3-acetic acid (5-HIAA) contents in rat cerebrospinal fluid (CSF) were observed from two days after administration of fluvoxamine in both the light and dark periods and in the dark period of the light/dark cycle, respectively. In long-term treatment with 15 mg/kg, p.o. of fluvoxamine, the level of MHPG in CSF exhibited no difference, whereas the levels of 5-HIAA showed a significant increase during the light periods. These results suggest that fluvoxamine enhances the 5-HT system, but only with long-term treatment.

  18. Canakinumab efficacy and long-term tocilizumab administration in tumor necrosis factor receptor-associated periodic syndrome (TRAPS).

    PubMed

    La Torre, Francesco; Muratore, Maurizio; Vitale, Antonio; Moramarco, Fulvio; Quarta, Laura; Cantarini, Luca

    2015-11-01

    Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is an autosomal dominantly inherited autoinflammatory disease caused by mutations in the TNFRSF1A gene. Treatment is aimed at preventing acute disease attacks, improving quality of life, and preventing long-term complications such as systemic reactive amyloidosis. Biologic agents have significantly improved TRAPS management. In particular, interleukin 1 (IL-1) inhibition either with the recombinant IL-1 receptor antagonist anakinra or with the human IgG1 anti-IL-1β monoclonal antibody canakinumab has recently shown to induce a prompt and stable disease remission. Conversely, the successful experience with IL-6 inhibition is nowadays limited to a single patient. Anyway, introduction of new treatment options for patients requiring a lifelong therapy is desirable. We describe two TRAPS patients (son and father) successfully treated with canakinumab and tocilizumab, respectively. In particular, we highlight the clinical and laboratory efficacy as well as the good safety profile of tocilizumab during a 42-month follow-up period.

  19. Long-Term Care

    MedlinePlus

    ... this page please turn Javascript on. Long-Term Care What Is Long-Term Care? Long-term care involves a variety of services ... the Escape (Esc) button on your keyboard.) Most Care Provided at Home Long-term care is provided ...

  20. Changes in monoamine metabolites concentrations in rat cerebrospinal fluid after acute and long-term administration of a selective serotonin reuptake inhibitor, trazodone.

    PubMed

    Egashira, T; Takayama, F; Yamanaka, Y

    1999-12-01

    In order to clarify the mechanism of the antidepressive effects of trazodone, a selective serotonin reuptake inhibitor, we investigated the dynamics of monoamine metabolites in cerebrospinal fluid (CSF) of free-moving conscious rats by acute and long-term treatment with trazodone. When 100 mg kg-1 p.o. of trazodone were administered, a significant increase of 3-methoxy-4-hydroxyphenylglycol (MHPG) concentration was soon observed in the light period of the light/dark cycle, and a significant decrease of dihydroxy phenyl acetic acid (DOPAC) concentration was observed during the 2 days after administration of trazodone; in contrast, the homovanilic acid (HVA) level was increased. However, we detected no significant changes in the 5-hydroxy indole-3-acetic acid (5-HIAA) concentration during the 3 days. In the case of long-term treatment with 50 mg kg-1, p.o. of trazodone, the levels of MHPG, DOPAC and HVA exhibited no difference when compared with values obtained during saline treatment in either the light or dark period, whereas the levels of 5-HIAA showed a significant increase during the light period. These findings suggest that a long-term treatment with trazodone enhances the serotonergic neurons.

  1. Long-Term Administration of Neuropeptide Y in the Subcutaneous Infusion Results in Cardiac Dysfunction and Hypertrophy in Rats.

    PubMed

    Zhang, Rong; Niu, Huifang; Kang, Xiaohui; Ban, Tao; Hong, Hong; Ai, Jing

    2015-01-01

    The purpose of the present study was to clarify whether chronically elevated plasma neuropeptide Y (NPY) might affect heart function and cardiac remodeling in rats. Male Wistar rats were administered NPY (85 μg for 30 days) by mini-osmotic pump subcutaneously implanted between the scapulae. Associated indices for heart function, cardiac remodeling and hypertrophy were evaluated. Compared to the sham group, the baseline systolic blood pressure (SBP) in rats administered NPY was significantly increased; cardiac function was significantly decreased, as indicated by reduced ejection fraction (EF), left ventricular end-systolic pressure (LVESP), maximum change velocity of left ventricular pressure in the isovolumic contraction or relaxation period (± dp/dtmax) and increased left ventricular end-diastolic pressure (LVEDP); hematoxylin-eosin (H&E) staining detection displayed enlarged cell areas and a consistent increase in heart-to-body weight ratios (HW/BW) was observed; quantitative real time PCR (qRT-PCR) and Western blot analysis showed markedly increased expressions of β-myosin heavy chain (β-MHC), calcineurin (CaN) and phosphorylated p38 proteins, while no changes were found in the expressions of p38 total protein and the phosphorylations of JNK and ERK. This study reported for the first time that long-term elevated plasma concentration of NPY could induce cardiac dysfunction and cardiac hypertrophy and this phenomenon could, in part, be mediated by the Ca2+/CaM-dependent CaN pathway and p38 mitogen-activated protein kinase (MAPK) signal pathway in rats. © 2015 S. Karger AG, Basel.

  2. Differences in impact of long term caregiving for mentally ill older adults on the daily life of informal caregivers: a qualitative study.

    PubMed

    Zegwaard, Marian I; Aartsen, Marja J; Grypdonck, Mieke Hf; Cuijpers, Pim

    2013-03-27

    Owing to the policy of extramuralization of care in most Western countries older people with severe mental illness have to rely more and more on informal caregivers for daily care. Caregivers themselves are often aged, and although caregiving implies an impact on daily life that exceeds the boundaries of usual informal care, the impact differs across caregivers. Some caregivers seem to suffer more than others, and the differences cannot be fully understood by factors currently known to exacerbate the burden of caregiving. In order to help caregivers reduce the impact of caregiving it is important to gain a deeper understanding of factors influencing the burden and its impact on the caregiver's life. With this in mind, the aim of the study is to explore and understand differences in the impact of long-term caregiving on the quality of life of caregivers who look after older adults with severe mental illness. A qualitative, associative, inductive strategy and continuous simultaneous coding were used to interpret the data of 19 semi-structured interviews. We identified an underlying psychological factor "perceived freedom of choice" which explains the gross differences in impact, leading to a definition of two main types of caregivers. Depending on how people perceive freedom of choice to provide care, the consequences of caregiving can be characterized as a process of gain (type 1) or loss (type 2). Four influential factors deepen the impact of caregiving for the type 2 caregivers, and two subtypes are identified for this category. Consequences of caregiving are most readily seen in a deteriorating quality of the relationship with the care recipient and in the psychosocial well-being of the caregiver. The concept of freedom of choice adds to our understanding of the differences and explains the variation in impact on the caregivers' life. The type 1 caregiver generally experiences gain whereas type 2 generally experiences loss, which puts the latter group typically

  3. Differences in impact of long term caregiving for mentally ill older adults on the daily life of informal caregivers: a qualitative study

    PubMed Central

    2013-01-01

    Background Owing to the policy of extramuralization of care in most Western countries older people with severe mental illness have to rely more and more on informal caregivers for daily care. Caregivers themselves are often aged, and although caregiving implies an impact on daily life that exceeds the boundaries of usual informal care, the impact differs across caregivers. Some caregivers seem to suffer more than others, and the differences cannot be fully understood by factors currently known to exacerbate the burden of caregiving. In order to help caregivers reduce the impact of caregiving it is important to gain a deeper understanding of factors influencing the burden and its impact on the caregiver’s life. With this in mind, the aim of the study is to explore and understand differences in the impact of long-term caregiving on the quality of life of caregivers who look after older adults with severe mental illness. Methods A qualitative, associative, inductive strategy and continuous simultaneous coding were used to interpret the data of 19 semi-structured interviews. Results We identified an underlying psychological factor “perceived freedom of choice” which explains the gross differences in impact, leading to a definition of two main types of caregivers. Depending on how people perceive freedom of choice to provide care, the consequences of caregiving can be characterized as a process of gain (type 1) or loss (type 2). Four influential factors deepen the impact of caregiving for the type 2 caregivers, and two subtypes are identified for this category. Consequences of caregiving are most readily seen in a deteriorating quality of the relationship with the care recipient and in the psychosocial well-being of the caregiver. Conclusions The concept of freedom of choice adds to our understanding of the differences and explains the variation in impact on the caregivers’ life. The type 1 caregiver generally experiences gain whereas type 2 generally

  4. Long-term administration of Delta9-tetrahydrocannabinol desensitizes CB1-, adenosine A1-, and GABAB-mediated inhibition of adenylyl cyclase in mouse cerebellum.

    PubMed

    Selley, Dana E; Cassidy, Michael P; Martin, Billy R; Sim-Selley, Laura J

    2004-11-01

    Cannabinoid CB(1) receptors in the cerebellum mediate the inhibitory effects of Delta(9)-tetrahydrocannabinol (THC) on motor coordination. Intracellular effects of CB(1) receptors include inhibition of adenylyl cyclase via activation of G(i/o) proteins. There is evidence for the convergence of other neuronal receptors, such as adenosine A(1) and GABA(B), with the cannabinoid system on this signaling pathway to influence motor function. Previous studies have shown that brain CB(1) receptors are desensitized and down-regulated by long-term THC treatment, but few studies have examined the effects of long-term THC treatment on downstream effector activity in brain. Therefore, these studies examined the relationship between CB(1), adenosine A(1), and GABA(B) receptors in cerebella of mice undergoing prolonged treatment with vehicle or THC at the level of G protein activation and adenylyl cyclase inhibition. In control cerebella, CB(1) receptors produced less than additive inhibition of adenylyl cyclase with GABA(B) and A(1) receptors, indicating that these receptors are localized on overlapping populations of cells. Long-term THC treatment produced CB(1) receptor down-regulation and desensitization of both cannabinoid agonist-stimulated G protein activation and inhibition of forskolin-stimulated adenylyl cyclase. However, G protein activation by GABA(B) or A(1) receptors was unaffected. It is noteworthy that heterologous attenuation of GABA(B) and A(1) receptor-mediated inhibition of adenylyl cyclase was observed, even though absolute levels of basal and forskolin- or G(s)-stimulated activity were unchanged. These results indicate that long-term THC administration produces a disruption of inhibitory receptor control of cerebellar adenylyl cyclase and suggest a potential mechanism of cross-tolerance to the motor incoordinating effects of cannabinoid, GABA(B), and A(1) agonists.

  5. Long-term administration of a small molecular weight catalytic metalloporphyrin antioxidant, AEOL 10150, protects lungs from radiation-induced injury

    SciTech Connect

    Rabbani, Zahid N.; Batinic-Haberle, Ines; Anscher, Mitchell S.; Huang Jie; Day, Brian J.; Alexander, Elaine; Dewhirst, Mark W.; Vujaskovic, Zeljko . E-mail: vujas@radonc.duke.edu

    2007-02-01

    Purpose: To determine whether administration of a catalytic antioxidant, Mn(III) tetrakis(N,N'-diethylimidazolium-2-yl) porphyrin, AEOL 10150, with superoxide dismutase (SOD) mimetic properties, reduces the severity of radiation-induced injury to the lung from single-dose irradiation (RT) of 28 Gy. Methods and Materials: Rats were randomly divided into four different dose groups (0, 1, 10, and 30 mg/kg/day of AEOL 10150), receiving either short-term (1 week) or long-term (10 weeks) drug administration via osmotic pumps. Rats received single-dose irradiation (RT) of 28 Gy to the right hemithorax. Breathing rates, body weights, blood samples, histopathology, and immunohistochemistry were used to assess lung damage. Results: There was no significant difference in any of the study endpoints between the irradiated controls and the three groups receiving RT and short-term administration of AEOL 10150. For the long-term administration, functional determinants of lung damage 20 weeks postradiation were significantly worse for RT + phosphate-buffered saline (PBS) and RT + 1 mg/kg/day of AEOL 10150 as compared with the irradiated groups treated with higher doses of AEOL 10150 (10 or 30 mg/kg/day). Lung histology at 20 weeks revealed a significant decrease in structural damage and collagen deposition in rats receiving 10 or 30 mg/kg/day after radiation in comparison to the RT + PBS and 1 mg/kg/day groups. Immunohistochemistry demonstrated a significant reduction in macrophage accumulation, oxidative stress, and hypoxia in rats receiving AEOL 10150 (10 or 30 mg/kg/day) after lung irradiation compared with the RT + PBS and 1 mg/kg/day groups. Conclusions: The chronic administration of a novel catalytic antioxidant, AEOL 10150, demonstrates a significant protective effect from radiation-induced lung injury. AEOL 10150 has its primary impact on the cascade of events after irradiation, and adding the drug before irradiation and its short-term administration have no significant

  6. Long-term statin administration to dams on high-fat diet protects not only them but also their offspring from cardiovascular risk.

    PubMed

    Elahi, M M; Cagampang, F R; Ohri, S K; Hanson, M A

    2013-01-01

    We aimed to study the effects of long-term statin administration to high fat (HF)-fed female mice from the time they were weaned through to pregnancy and lactation on cardiovascular and metabolic risk factors in their HF-fed offspring. Female C57 mice on HF (45% kcal fat) were given pravastatin in their drinking water from the time they were weaned, during pregnancy and lactation. Weaned offspring were then fed an HF diet until adulthood generating the dam/offspring dietary groups HF/HF and HF plus pravastatin from the time dams were weaned, during pregnancy and lactation/HF (HF+S/HF). These groups were compared with offspring from mothers fed standard chow (control) which were then fed a control diet up to adulthood (control/control; C/C). HF+S dams showed significantly reduced total cholesterol concentrations and systolic blood pressure (SBP) versus HF dams. The reduction in total cholesterol and SBP in the HF+S dams did not restore values to those observed in the C group. Both male and female HF+S/HF offspring were significantly lighter in weight, and had lower SBP and serum cholesterol concentrations versus HF/HF. HF/HF offspring had elevated C-reactive protein levels but HF+S/HF animals of both sexes had reduced levels similar to those found in the C/C group. Long-term pravastatin administration to dams not only protects them from the deleterious effects of an HF diet, but this long-term maternal statin protection also has an equal and permanent effect in both male and female offspring up to their adult life, which is a novel finding.

  7. Disappearance of a uterine arteriovenous malformation following long-term administration of oral norgestrel/ethinyl estradiol.

    PubMed

    Oride, Aki; Kanasaki, Haruhiko; Miyazaki, Kohji

    2014-06-01

    Uterine arteriovenous malformation (AVM) can cause sudden massive hemorrhage. We report a case of uterine AVM following curettage in a patient treated conservatively with an intermediate-dose pill. An 18-year-old gravida 2 para 0 underwent curettage at 12 weeks of gestation and was examined for massive genital hemorrhage that occurred in postoperative month 4. Abundant blood flow in a mass within the uterine lumen was observed on color Doppler ultrasonography, and the patient was diagnosed with AVM. Six days after starting oral norgestrel/ethinyl estradiol, the hemorrhage ceased, and computed tomography on day 37 of administration showed disappearance of the abnormal vasculature. After 12 months, the patient's course remains favorable without relapse. Transarterial embolization for AVM can cause ovarian failure and subsequent placental malpositioning. Administration of oral norgestrel/ethinyl estradiol may be an alternative conservative treatment option for patients who wish to maintain fertility.

  8. Long-term Stability of a Compounded Suspension of Torsemide (5 mg/mL) for Oral Administration.

    PubMed

    Adin, D; Johnson, P R; Kim, C H; Nguyenba, T; Rosen, S

    2017-09-15

    Torsemide use for congestive heart failure (CHF) has been reported, but prescription frequency is unknown. Commercially available tablet sizes in North America limit dosing precision, indicating a need to evaluate its strength and stability in suspension. To determine the frequency of torsemide prescriptions and to determine a beyond use date (BUD) of a compounded suspension of torsemide for oral administration stored under 2 temperature conditions for 90 days. No animals used. Pharmacy records were retrospectively reviewed for torsemide and furosemide prescriptions from 2008 to 2015 at 2 veterinary referral centers. After preliminary strength testing, compounded torsemide suspension (5 mg/mL) for oral administration was prepared using torsemide tablets suspended in OraPlus:OraSweet 1:1, buffered to a pH of 8.3 and stored at refrigeration (2-8°C) and room temperature (20-25°C) in 2 oz amber plastic bottles. Samples were analyzed by reverse phase high-performance liquid chromatography (RP-HPLC) on days 0, 14, 30, 60, and 90. Prescriptions for torsemide increased from 2008 to 2015. Analysis of the torsemide 5 mg/mL suspension for oral administration at each time point met United States Pharmacopeia (USP) requirements for torsemide content of 90-110% of label claim. The average strength at 90 days decreased to 92 ± 3% at 2-8°C and 95 ± 2% at 20-25°C. Stability testing did not detect unknown impurities. Increasing torsemide use warrants availability of a validated and stable compounded formulation. Our results support the assignment of a 90-day BUD for torsemide 5 mg/mL suspension for oral administration compounded in OraPlus:Sweet 1:1 buffered to a pH of 8.3. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  9. Restoration of serotonin neuronal firing following long-term administration of bupropion but not paroxetine in olfactory bulbectomized rats.

    PubMed

    El Mansari, Mostafa; Manta, Stella; Oosterhof, Chris; El Iskandrani, Kareem S; Chenu, Franck; Shim, Stacey; Blier, Pierre

    2014-10-31

    Olfactory bulbectomized rats generally manifest many of the neurochemical, physiological, and behavioral features of major depressive disorder in humans. Another interesting feature of this model is that it responds to chronic but not acute antidepressant treatments, including selective serotonin reuptake inhibitors. The purpose of the present study was first to characterize the firing activity of dorsal raphe serotonin neurons in olfactory bulbectomized rats and then examine the effects of 2 antidepressants, bupropion and paroxetine. Olfactory bulbectomy was performed by aspirating olfactory bulbs in anesthetized rats. Vehicle and drugs were delivered for 2 and 14 days via subcutaneously implanted minipumps. In vivo electrophysiological recordings were carried out in male anesthetized Sprague-Dawley rats. Following ablation of olfactory bulbs, the firing rate of serotonin neurons was decreased by 36%, leaving those of norepinephrine and dopamine neurons unchanged. In olfactory bulbectomized rats, bupropion (30 mg/kg/d) restored the firing rate of serotonin neurons to the control level following 2- and 14-day administration and also induced an increase in the tonic activation of serotonin(1A) receptors; paroxetine (10 mg/kg/d) did not result in a return to normal of the attenuated firing of serotonin neurons in olfactory bulbectomized rats. In the hippocampus, although at a higher dose of WAY 100635 than that required in bupropion-treated animals, paroxetine administration also resulted in an increase in the tonic activation of serotonin(1A) receptors. The present results indicate that unlike paroxetine, bupropion administration normalized serotonin neuronal activity and increased tonic activation of the serotonin(1A) receptors in hippocampus. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  10. Restoration of Serotonin Neuronal Firing Following Long-Term Administration of Bupropion but Not Paroxetine in Olfactory Bulbectomized Rats

    PubMed Central

    Manta, Stella; Oosterhof, Chris; El Iskandrani, Kareem S.; Chenu, Franck; Shim, Stacey; Blier, Pierre

    2015-01-01

    Background: Olfactory bulbectomized rats generally manifest many of the neurochemical, physiological, and behavioral features of major depressive disorder in humans. Another interesting feature of this model is that it responds to chronic but not acute antidepressant treatments, including selective serotonin reuptake inhibitors. The purpose of the present study was first to characterize the firing activity of dorsal raphe serotonin neurons in olfactory bulbectomized rats and then examine the effects of 2 antidepressants, bupropion and paroxetine. Methods: Olfactory bulbectomy was performed by aspirating olfactory bulbs in anesthetized rats. Vehicle and drugs were delivered for 2 and 14 days via subcutaneously implanted minipumps. In vivo electrophysiological recordings were carried out in male anesthetized Sprague-Dawley rats. Results: Following ablation of olfactory bulbs, the firing rate of serotonin neurons was decreased by 36%, leaving those of norepinephrine and dopamine neurons unchanged. In olfactory bulbectomized rats, bupropion (30mg/kg/d) restored the firing rate of serotonin neurons to the control level following 2- and 14-day administration and also induced an increase in the tonic activation of serotonin1A receptors; paroxetine (10mg/kg/d) did not result in a return to normal of the attenuated firing of serotonin neurons in olfactory bulbectomized rats. In the hippocampus, although at a higher dose of WAY 100635 than that required in bupropion-treated animals, paroxetine administration also resulted in an increase in the tonic activation of serotonin1A receptors. Conclusions: The present results indicate that unlike paroxetine, bupropion administration normalized serotonin neuronal activity and increased tonic activation of the serotonin1A receptors in hippocampus. PMID:25522394

  11. Effect of long-term administration of melatonin on adrenal histomorphology of the Indian desert gerbil Meriones hurrianae Jerdon.

    PubMed

    Joshi, B N; Sujathakumari, M

    1995-11-01

    Melatonin treatment for 8 weeks resulted in a significant increase (P < 0.01) in weights of the adrenal glands, in both male and female, M. hurrianae. The weight increase was not related to the time of administration of melatonin. Histology of adrenal glands in melatonin treated gerbils revealed a stimulatory response. In treated gerbils, adrenal cortex exhibited significant hypertrophy with enlarged nuclei and degranulated cytoplasm. Signs of hypertrophy were also evident in the adrenal medulla. The physiological significance of this response is not yet clear. It remains to be clarified if the hypertrophy indicates enhanced synthesis of corticosteroids.

  12. Long-term vascular access ports as a means of sedative administration in a rodent fMRI survival model.

    PubMed

    Hettinger, Patrick C; Li, Rupeng; Yan, Ji-Geng; Matloub, Hani S; Cho, Younghoon R; Pawela, Christopher P; Rowe, Daniel B; Hyde, James S

    2011-09-15

    The purpose of this study is to develop a rodent functional magnetic resonance imaging (fMRI) survival model with the use of heparin-coated vascular access devices. Such a model would ease the administration of sedative agents, reduce the number of animals required in survival experiments and eliminate animal-to-animal variability seen in previous designs. Seven male Sprague-Dawley rats underwent surgical placement of an MRI-compatible vascular access port, followed by implantable electrode placement on the right median nerve. Functional MRI during nerve stimulation and resting-state functional connectivity MRI (fcMRI) were performed at times 0, 2, 4, 8 and 12 weeks postoperatively using a 9.4T scanner. Anesthesia was maintained using intravenous dexmedetomidine and reversed using atipamezole. There were no fatalities or infectious complications during this study. All vascular access ports remained patent. Blood oxygen level dependent (BOLD) activation by electrical stimulation of the median nerve using implanted electrodes was seen within the forelimb sensory region (S1FL) for all animals at all time points. The number of activated voxels decreased at time points 4 and 8 weeks, returning to a normal level at 12 weeks, which is attributed to scar tissue formation and resolution around the embedded electrode. The applications of this experiment extend far beyond the scope of peripheral nerve experimentation. These vascular access ports can be applied to any survival MRI study requiring repeated medication administration, intravenous contrast, or blood sampling.

  13. Effect of long-term propranolol administration on specific binding of /sup 3/H-WB-4101 with rat mesenteric vascular membranes

    SciTech Connect

    Ismailov, S.I.; Rozhanets, V.V.; Val'dman, A.V.

    1985-12-01

    The aim of this investigation was, first, to study the affinity of certain beta-adrenoblockers for specific binding sites of /sup 3/H-WB-4101 (identifiable as alpha-adrenoreceptors) of brain membranes and, second, to study the characteristics of these same receptors in membranes of mesenteric vessels of rats during long-term administration of propranolol. Isotherms of specific binding, because of the limited quantity of vascular membranes, were determined by the use of three concentrations of /sup 3/H-WB-4101: 0.1, 0.5, and 1.0 nM. It is shown that some beta-adrenoblockers have weak affinity for alpha-adrenoreceptors of brain synaptic membranes exhibited only when these compounds are present in relatively high concentrations. It is also shown that administration of propranolol for 15 days led to a significant decrease in affinity of the alpha-adrenorecptors for their specific antagonist WB-4101.

  14. Effects of long-term administration of a cocoa polyphenolic extract (Acticoa powder) on cognitive performances in aged rats.

    PubMed

    Bisson, Jean-François; Nejdi, Amine; Rozan, Pascale; Hidalgo, Sophie; Lalonde, Robert; Messaoudi, Michaël

    2008-07-01

    Numerous studies have indicated that increased vulnerability to oxidative stress may be the main factor involved in functional declines during normal and pathological ageing, and that antioxidant agents, such as polyphenols, may improve or prevent these deficits. We examined whether 1-year administration of a cocoa polyphenolic extract (Acticoa powder), orally delivered at the dose of 24 mg/kg per d between 15 and 27 months of age, affects the onset of age-related cognitive deficits, urinary free dopamine levels and lifespan in old Wistar-Unilever rats. Acticoa powder improved cognitive performances in light extinction and water maze paradigms, increased lifespan and preserved high urinary free dopamine levels. These results suggest that Acticoa powder may be beneficial in retarding age-related brain impairments, including cognitive deficits in normal ageing and perhaps neurodegenerative diseases. Further studies are required to elucidate the mechanisms of cocoa polyphenols in neuroprotection and to explore their effects in man.

  15. Long-term administration of the dopamine D3/2 receptor agonist pramipexole increases dopamine and serotonin neurotransmission in the male rat forebrain

    PubMed Central

    Chernoloz, Olga; El Mansari, Mostafa; Blier, Pierre

    2012-01-01

    Background Long-term administration of the dopamine (DA) D2-like (D3/2) receptor agonist pramipexole (PPX) has been previously found to desensitize D2 autoreceptors, thereby allowing a normalization of the firing of DA neurons and serotonin (5-HT)1A autoreceptors, permitting an enhancement of the spontaneous firing of 5-HT neurons. We hypothesized that PPX would increase overall DA and 5-HT neurotransmission in the forebrain as a result of these changes at the presynaptic level. Methods Osmotic minipumps were implanted subcutaneously in male Sprague-Dawley rats, delivering PPX at a dose of 1 mg/kg/d for 14 days. The in vivo electrophysiologic microiontophoretic experiments were carried out in anesthetized rats. Results The sensitivity of postsynaptic D2 receptors in the prefrontal cortex (PFC) remained unaltered following PPX administration, as indicated by the unchanged responsiveness to the microiontophoretic application of DA. Their tonic activation was, however, significantly increased by 104% compared with the control level. The sensitivity of postsynaptic 5-HT1A receptors was not altered, as indicated by the unchanged responsiveness to the microiontophoretic application of 5-HT. Similar to other antidepressant treatments, long-term PPX administration enhanced the tonic activation of 5-HT1A receptors on CA3 pyramidal neurons by 142% compared with the control level. Limitations The assessment of DA and 5-HT neuronal tone was restricted to the PFC and the hippocampus, respectively. Conclusion Chronic PPX administration led to a net enhancement in DA and 5-HT neurotransmission, as indicated by the increased tonic activation of postsynaptic D2 and 5-HT1A receptors in forebrain structures. PMID:22023785

  16. Long-term effect of prazosin administration on blood pressure, heart and structure of coronary artery of young spontaneously hypertensive rats.

    PubMed

    Kristek, F; Koprdova, R

    2011-06-01

    The sympathetic nervous system belongs to the essential systems participating in blood pressure (BP) regulation. Inhibitory intervention into the key point of its operation (alfa 1 adrenoceptors) in the prehypertensive period of spontaneously hypertensive rats (SHR) might affect the development of the hypertension in later ontogenic periods. We studied the long-term effect of prazosin administration on the cardiovascular system of young Wistar rats and SHR. Four-week-old animals were used: Wistar rats, SHR, and Wistar rats and SHR receiving prazosin (10 mg/kg/day in tap water) by gavage. Blood pressure (BP) was measured weekly by the plethysmographic method. After six weeks under anaesthesia, the carotid artery was cannulated for BP registration, and the jugular vein was cannulated for administration of drugs. Afterwards, the animals were perfused with a glutaraldehyde fixative at a pressure of 120 mmHg. The septal branch of the left descending coronary artery was processed using electron microscopy. The prazosin administration evoked the following results in both groups: a decrease of BP and heart/body weight ratio, enhancement of hypotensive responses to acetylcholine (0.1 μg, 1 μg, and 10 μg), and an increase in the inner diameter of the coronary artery without changes in wall thickness, cross sectional area (CSA) (tunica intima+media), CSA of smooth muscle cells, and extracellular matrix. In the SHR group, a reduction was observed in BP increase after noradrenaline (1 μg) application. CSA of endothelial cells which was decreased in the SHR (compared to the control Wistar rats) was increased after prazosin treatment (up to control value). Long-term prazosin administration from early ontogeny partially prevented some pathological alterations in the cardiovascular system of SHR.

  17. Long-term suppression of experimental arthritis following intramuscular administration of a pseudotyped AAV2/1-TNFR:Fc Vector.

    PubMed

    Sandalon, Ziv; Bruckheimer, Elizabeth M; Lustig, Kurt H; Burstein, Haim

    2007-02-01

    We previously reported that administration of an adeno-associated virus 2 (AAV2) vector encoding a rat tumor necrosis factor (TNF) receptor-immunoglobulin Fc (TNFR:Fc) fusion gene to rats with streptococcal cell wall-induced arthritis resulted in suppression of joint inflammation and cartilage and bone destruction, as well as expression of joint proinflammatory cytokines. In this study, we used an alternate rat model of arthritis to compare the serum levels and duration of TNFR:Fc protein expression following intramuscular administration of pseudotyped AAV-TNFR:Fc vectors based on serotypes 1, 2, and 5. All three pseudotyped AAV-TNFR:Fc vectors led to sustained expression of serum TNFR:Fc protein for at least one year. Serum TNFR:Fc protein levels in rats administered intramuscularly with AAV2/1-TNFR:Fc vector were up to 100- and 10-fold higher than in rats administered the AAV2-TNFR:Fc or AAV2/5-TNFR:Fc vectors, respectively. A single intramuscular administration of AAV2/1-TNFR:Fc vector at vector doses ranging from 10(10) to 10(12) DNase-resistant particles (DRP) per animal, resulted in complete and long-term suppression of recurrent joint inflammation for at least 150 days. Our results establish a proof of concept for administration of an AAV2/1-TNFR:Fc vector to the muscle to achieve long-term, sustained and therapeutically relevant levels of TNFR:Fc protein to treat chronic systemic inflammatory joint diseases.

  18. Age-specific administration of chemotherapy and long-term quality of life in stage II and III colorectal cancer patients: a population-based prospective cohort.

    PubMed

    Jansen, Lina; Hoffmeister, Michael; Chang-Claude, Jenny; Koch, Moritz; Brenner, Hermann; Arndt, Volker

    2011-01-01

    To investigate the age-specific pattern of administration of chemotherapy and its association with long-term survival and quality of life (QoL) in stage II and III colorectal cancer patients. Chemotherapy allocation according to disease and patient characteristics was investigated in a population-based cohort of 562 stage II and III colorectal cancer patients. Five years after diagnosis, survival was determined and QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 Items and a tumor specific module. The association among chemotherapy, survival, and QoL was examined while controlling for potential confounders. Chemotherapy was administered in 71% of patients aged <60 years and in only 20% of patients aged ≥80 years. A significant association between chemotherapy and longer survival time was found for stage III cancer only. Chemotherapy was associated with higher symptom levels for trouble with taste, anxiety, and hair loss. In age-specific analyses, younger survivors (<70 years at time of follow-up) with a history of chemotherapy reported significantly lower physical, role, and cognitive functioning and higher pain, appetite loss, hair loss, and trouble with taste symptom levels. In contrast, for older survivors (≥70 years), only two (hair loss and dry mouth) out of 38 QoL scores were significantly associated with chemotherapy. Chemotherapy is associated with lower long-term QoL, especially in younger survivors. In cases of uncertain survival benefits of chemotherapy, consideration of its long-term effects on QoL should be incorporated into final decisions on treatment.

  19. Effect of zinc or S-adenosyl-l-methionine on long term administration of low doses of lead to rats.

    PubMed

    Muñoz, J J; Roca, C; Santos, J L; Arroyo, M; de Salamanca, R E

    1993-10-01

    Two alternatives for the treatment of lead intoxication, administration of zinc or a thiol donor, S-adenosyl-L-methionine (SAM), were analysed. Rats were exposed to lead (Pb)-acetate (60 mg/l) in drinking water during 90 days; one group also received SO4Zn in water (40 mg/l), while another received both Pb and SAM (5 mg/24 hr intraperitoneally. Erythrocytic delta-aminolaevulinic dehydratase (ALA-D) activity was significantly reduced (P < 0.001) both in rats receiving Pb alone and in rats receiving Pb and each of the other two treatments. The high erythrocytic uroporphyrinogen synthetase (URO-S) activity noticed in Pb administered rats, was significantly (P < 0.001) reduced in animals treated either with zinc or with SAM. Hepatic ALA-D activity tended to decrease while renal enzyme activity was not modified by the low level Pb exposure used in this work. Interestingly, SAM treated rats in both tissues exhibited significantly (P < 0.01) higher activities of the enzyme. It is argued that SAM treatment causes a surplus of thiols that allows the full expression of ALA-D catalytic activity.

  20. Effects of long-term light, darkness and oral administration of melatonin on serum levels of melatonin.

    PubMed

    Farhadi, Naser; Gharghani, Majid; Farhadi, Zahra

    2016-02-01

    Continuous light or darkness has various effects on different systems. In the present research work, the effects of constant light and darkness exposure of male rats and oral administration of exogenous melatonin on the serum levels of melatonin have been studied. Thirty adult male Wistar rats were divided into six groups of: (1) Control, (2) melatonin, (3) light, (4) light and melatonin, (5) darkness, and (6) darkness and melatonin. All groups were placed according to light conditions for 10 days. Melatonin was administered orally after a period of 10 days to Groups 2, 4, and 6 (10 mg/kg of body weight). Serum levels of melatonin were measured using ELISA. The results showed the significant difference on serum melatonin in darkness, no light, and control groups. Although serum levels of melatonin were different in melatonin groups, the difference is not significant. We concluded that being exposed to continuous darkness leads to an increase in serum melatonin. Copyright © 2016 Chang Gung University. Published by Elsevier B.V. All rights reserved.

  1. Effects of long-term administration of the antiepileptic drug--sodium valproate upon the ultrastructure of hepatocytes in rats.

    PubMed

    Sobaniec-Lotowska, M E

    1997-08-01

    Chronic intragastric application (1, 3, 6, 9 and 12 months) of the antiepileptic drug--sodium valproate (VPA; Vupral "Polfa") to rats in the effective dose of 200 mg/kg b.w./day exerts hepatotoxic effect after 9 and 12 months of the experiment. The first ultrastructural changes in hepatocytes were observed after 3 months of the drug administration. These became more intense in the subsequent stages of the experiment, to be most pronounced after 12 months. The most striking changes were in the mitochondria (significant swelling, an increase in their number, degeneration of matrix and cristae, disruption of the outer mitochondrial membrane) and in peroxisomes (proliferation, enlargement and the presence of distinct nucleoids). Further alterations in hepatocytes manifested themselves in: microvesicular fatty change with cholesterolosis (cholesterol clefts), damage to the cellular membrane of the sinusoidal pole with dilation of the perisinusoidal space of Disse, presence of cystern-like cytoplasmic vacuoles in the sinusoidal region, filled with plasma-like material and focal cytoplasmic necrosis. The changes in hepatocytes coexisted with the swelling and activation of sinusoidal cells, endothelial cells and Kupffer cells. The author suggests that mitochondria and peroxisomes considerably contribute to the morphogenesis of hepatocyte damage by VPA in the chronic experimental model.

  2. Enhanced motor activity and brain dopamine turnover in mice during long-term nicotine administration in the drinking water.

    PubMed

    Gäddnäs, H; Pietilä, K; Piepponen, T P; Ahtee, L

    2001-12-01

    Nicotine was administered chronically to NMRI mice in their drinking water in gradually increasing concentrations to measure gross motor activity and brain nicotine concentrations over 24 h on the 50th day of nicotine administration. Also, the striatal postmortem tissue concentrations and accumbal extracellular concentrations of dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured to study the role of dopaminergic systems in nicotine-induced hyperactivity in mice. The cerebral nicotine concentration was at its highest at the end of the dark period. The activity of nicotine-treated mice and their striatal DA metabolism were parallelly increased at 2 to 3 h after midnight and in the forenoon. Microdialysis experiments carried out in the forenoon showed that the extracellular levels of DA and DOPAC were elevated in the nucleus accumbens of these mice. Nicotine did not alter the circadian rhythmicity of activity in the mice. Rather, our findings suggest that the mice consume more nicotine when active and this might lead to enhanced release and metabolism of DA and further, to enhanced motor behavior. These findings support the suggestions that nicotine's effects on limbic and striatal DA are critical for its stimulating effects.

  3. A mathematical model for long-term effect of diethylcarbamazine-albendazole mass drug administration on lymphatic filariasis

    NASA Astrophysics Data System (ADS)

    Tasman, H.; Supali, T.; Supriatna, A. K.; Nuraini, N.; Soewono, E.

    2015-03-01

    In this paper we discuss a mathematical model for the transmission of lymphatic filariasis disease. The human population is divided into susceptible, latent, acute and chronic subpopulations. Treatment is carried out within the scheme of mass drug administration (MDA) by giving the diethylcarbamazine (DEC) and albendazole (ALB) to all individuals. In the model, we assume that the treatments have direct killing effect to microfilariae, increase of immune-mediated effect. The treated individuals are assumed to remain susceptible to the disease. This is due to the fact that the treatment is only partially effective against macrofilaria. Simulations of the model reveals that DEC-ALB treatment does give significant reduction of acute and chronic compartments at the end of the treatment period and slow down the growth after the treatment before eventually tend to the endemic state. It showed that repeated treatment during MDA is effective to decrease the transmission. This suggests that terminating MDA program after a long period of its application may still effective in controlling the disease.

  4. Withdrawal symptoms in critically ill children after long-term administration of sedatives and/or analgesics: a first evaluation.

    PubMed

    Ista, Erwin; van Dijk, Monique; Gamel, Claudia; Tibboel, Dick; de Hoog, Matthijs

    2008-08-01

    To establish frequencies of benzodiazepine and opioid withdrawal symptoms, and correlations with total doses and duration of administration. A prospective, repeated-measures design. Two pediatric intensive care units in a university children's hospital. Seventy-nine children, aged 0 days to 16 yrs, who received intravenous midazolam and/or opioids for >5 days. None. Pediatric intensive care unit nurses assessed withdrawal symptoms using the Sophia Benzodiazepine and Opioid Withdrawal Checklist, which includes all withdrawal symptoms (n = 24) described in the pediatric literature. Over 6 months, 2188 observations in 79 children were recorded. Forty-two percent of observations were performed within 24 hrs after tapering off or discontinuation of medication. Symptoms representing overstimulation of the central nervous system, such as anxiety, agitation, grimacing, sleep disturbance, increased muscle tension, and movement disorder, were observed in >10% of observations. Of symptoms reflecting gastrointestinal dysfunction, diarrhea and gastric retention were most frequently observed. Tachypnea, fever, sweating, and hypertension as manifestations of autonomic dysfunction were observed in >13% of observations. The Spearman's rank-correlation coefficient between total doses of midazolam and maximum sum score (of the Sophia Benzodiazepine and Opioid Withdrawal Checklist) was .51 (p < 0.001). The correlation between total doses of opioids and the maximum sum score was .39 (p < 0.01). A significant correlation (.52; p < 0.001) was also found between duration of use and maximum sum score. This is the first study to report frequencies of all 24 withdrawal symptoms observed in children after decrease or discontinuation of benzodiazepines and/or opioids. Agitation, anxiety, muscle tension, sleeping <1 hr, diarrhea, fever, sweating, and tachypnea were observed most frequently. Longer duration of use and high dosing are risk factors for development of withdrawal symptoms in

  5. Metabolic and Testicular Effects of the Long-Term Administration of Different High-Fat Diets in Adult Rats

    PubMed Central

    Campos-Silva, Pamella; Furriel, Angelica; Costa, Waldemar S.; Sampaio, Francisco J. B.; Gregório, Bianca M.

    2015-01-01

    ABSTRACT Purpose: To evaluate the effects of different high-fat diets on body mass, carbohydrate metabolism and testicular morphology in rats seven months old. Materials and Methods: Male Wistar rats were divided into four groups: SC (standard chow), HF-S (high fat diet rich in saturated fatty acids), HF-P (high fat diet rich in polyunsaturated fatty acids), HF-SP (high fat diet rich in saturated and polyunsaturated fatty acids). The rats were fed for 16 weeks. Blood samples, testes and genital fat deposits were collected for analysis. Data were analyzed by one-way ANOVA and Bonferroni post hoc test, considering p<0.05 as statistically significant. Results: Different high-fat diets promoted an increase in the body mass (p<0.0001). The genital fat deposits were higher in the high-fat groups (HF-S, HF-P, HF-SP) (p=0.0004). Regarding serum parameters, the animals in the HF-S and HF-SP groups presented hyperglycemia (p=0.0060), hyperinsulinemia (p=0.0030) and hypercholesterolemia (p=0.0021). All of the hyperlipidemic groups showed hyperleptinemia (p=0.0019). Concerning the testis, the HF-S group showed a reduction on the seminiferous epithelium height (p=0.0003) and cell proliferation (p=0.0450). Seminiferous tubule diameter was lower in the HF-SP than in the SC group (p=0.0010). Conclusions: The high fat diet administration, independent of the lipid quality, promotes overweight. Diet rich in saturated fatty acids (lard) alters the carbohydrate metabolism and the testicular morphology with reductions of seminiferous epithelium height, seminiferous tubule diameter and cell proliferation which could be related to a disturbance of spermatogenesis. PMID:26200553

  6. Myocardial fibrosis is unaltered by long-term administration of L-arginine in dystrophin deficient mdx mice: a histomorphometric analysis.

    PubMed

    Marques, Maria Julia; Barbin, Isabel Cristina Chagas; Taniguti, Ana Paula Tiemi; Oggian, Daniela Silva; Ferretti, R; Santo Neto, H

    2010-06-01

    Cardiac failure secondary to myocardial fibrosis (MF) significantly contributes to death in Duchenne muscular dystrophy (DMD), a fatal form of muscle disease. In aging, the mdx mice, an animal model of DMD, MF is similar to that observed in humans. Nitric oxide-based therapy has been proposed to retard MF in DMD and a candidate is L-arginine (L-arg). In this study we evaluated the effects of long-term therapy with L-arg in the MF of mdx mice. mdx mice (6 months old) were treated with L-arg in drinking water. Control mdx mice received water only. After 15 months of treatment, hearts were stained with Masson's trichrome for analysis of MF and with hematoxilyn and eosin for analysis of inflammation and cardiomyocyte damage. We observed that MF was not affected (29.5 +/- 2.5% of MF area for control vs 31.4 +/- 2% for L-arginine-treated animals; P > 0.05). The density of inflammatory cells was reduced (169 +/- 12 cells/mm 2 in control vs 102 +/- 9 cells/mm 2 in L-arg-treated; P < 0.05). The present study shows that long-term administration of L-arg is not effective in retarding MF in mdx dystrophinopathy.

  7. Improvement in Long-Term Memory following Chronic Administration of Eryngium planum Root Extract in Scopolamine Model: Behavioral and Molecular Study

    PubMed Central

    Ozarowski, Marcin; Thiem, Barbara; Mikolajczak, Przemyslaw L.; Piasecka, Anna; Kachlicki, Piotr; Szulc, Michal; Kaminska, Ewa; Bogacz, Anna; Kujawski, Radoslaw; Bartkowiak-Wieczorek, Joanna; Kujawska, Malgorzata; Jodynis-Liebert, Jadwiga; Budzianowski, Jaromir; Kędziora, Izabela; Seremak-Mrozikiewicz, Agnieszka; Czerny, Boguslaw; Bobkiewicz-Kozłowska, Teresa

    2015-01-01

    Eryngium planum L. (EP) is as a rare medicinal plant with a lot of potentials as pharmaceutical crops. The aim of our study was to assess the effect of subchronic (28-fold) administration of a 70% ethanol extract of EP roots (200 mg/kg, p.o.) on behavioral and cognitive responses in Wistar rats linked with acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and beta-secretase (BACE-1) mRNA levels and AChE and BuChE activities in the hippocampus and frontal cortex. On the last day of experiment, 30 min after the last dose of EP or Huperzine A (HU), scopolamine (SC) was given at a dose of 0.5 mg/kg b.w. intraperitoneally. The results of a passive avoidance test showed an improvement in long-term memory produced by the EP extract in both scopolamine-induced rats and control group. EP caused an insignificant inhibition of AChE and BuChE activities in the frontal cortex and the hippocampus. EP decreased mRNA AChE, BuChE, and BACE-1 levels, especially in the cortex. Our results suggest that the EP extract led to the improvement of the long-term memory in rats coupled with total saponin content. The mechanism of EP action is probably complicated, since HPLC-MS analysis showed 64 chemical compounds (phenolics, saponins) in the extract of EP roots. PMID:26483842

  8. Long-term effect of three different strategies for mass diethylcarbamazine administration in bancroftian filariasis: follow-up at 10 years after treatment.

    PubMed

    Meyrowitsch, Dan W; Simonsen, Paul E; Magesa, Stephen M

    2004-11-01

    The long-term effect of three different strategies for mass diethylcarbamazine (DEC) administration in bancroftian filariasis was assessed 10 years after start of treatment in three endemic communities in Tanzania. The strategies were the standard 12 day treatment (strategy I); a semi-annual single-dose treatment (strategy II); and a monthly low-dose treatment (strategy III). Treatment was given only during the first year. Following reductions immediately after treatment, overall community microfilaraemia levels were approaching pre-treatment levels in all three communities, 10 years later. In individuals who were microfilaria-positive and treated at baseline, the treatment had a long-term effect on microfilarial intensities, with geometric mean intensities being only 11%, 13% and 2% of pre-treatment levels 10 years later for strategies I, II and III, respectively. This suppressive effect was most pronounced for strategy III, which also cleared microfilaraemia and circulating filarial antigenaemia in a larger proportion of treated individuals than the other strategies. Most of the follow-up individuals who developed microfilaraemia between 2 and 10 years after start of treatment had also been microfilaraemic before treatment, suggesting that reappearance of microfilaraemia may be due to surviving female worms and/or that previously microfilaraemic individuals have a higher chance of reinfection than previously amicrofilaraemic individuals.

  9. Long-term retention on treatment with lumiracoxib 100 mg once or twice daily compared with celecoxib 200 mg once daily: A randomised controlled trial in patients with osteoarthritis

    PubMed Central

    Fleischmann, Roy; Tannenbaum, Hyman; Patel, Neha P; Notter, Marianne; Sallstig, Peter; Reginster, Jean-Yves

    2008-01-01

    Background The efficacy, safety and tolerability of lumiracoxib, a novel selective cyclooxygenase-2 (COX-2) inhibitor, has been demonstrated in previous studies of patients with osteoarthritis (OA). As it is important to establish the long-term safety and efficacy of treatments for a chronic disease such as OA, the present study compared the effects of lumiracoxib at doses of 100 mg once daily (o.d.) and 100 mg twice daily (b.i.d.) with those of celecoxib 200 mg o.d. on retention on treatment over 1 year. Methods In this 52-week, multicentre, randomised, double-blind, parallel-group study, male and female patients (aged at least 40 years) with symptomatic primary OA of the hip, knee, hand or spine were randomised (1:2:1) to lumiracoxib 100 mg o.d. (n = 755), lumiracoxib 100 mg b.i.d. (n = 1,519) or celecoxib 200 mg o.d. (n = 758). The primary objective of the study was to demonstrate non-inferiority of lumiracoxib at either dose compared with celecoxib 200 mg o.d. with respect to the 1-year retention on treatment rate. Secondary outcome variables included OA pain in the target joint, patient's and physician's global assessments of disease activity, Short Arthritis assessment Scale (SAS) total score, rescue medication use, and safety and tolerability. Results Retention rates at 1 year were similar for the lumiracoxib 100 mg o.d., lumiracoxib 100 mg b.i.d. and celecoxib 200 mg o.d. groups (46.9% vs 47.5% vs 45.3%, respectively). It was demonstrated that retention on treatment with lumiracoxib at either dose was non-inferior to celecoxib 200 mg o.d. Similarly, Kaplan-Meier curves for the probability of premature discontinuation from the study for any reason were similar across the treatment groups. All three treatments generally yielded comparable results for the secondary efficacy variables and all treatments were well tolerated. Conclusion Long-term treatment with lumiracoxib 100 mg o.d., the recommended dose for OA, was as effective and well tolerated as celecoxib

  10. The effects of prolonged administration of norepinephrine reuptake inhibitors on long-term potentiation in dentate gyrus, and on tests of spatial and object recognition memory in rats.

    PubMed

    Walling, Susan G; Milway, J Stephen; Ingram, Matthew; Lau, Catherine; Morrison, Gillian; Martin, Gerard M

    2016-02-01

    Phasic norepinephrine (NE) release events are involved in arousal, novelty detection and in plasticity processes underlying learning and memory in mammalian systems. Although the effects of phasic NE release events on plasticity and memory are prevalently documented, it is less understood what effects chronic NE reuptake inhibition and sustained increases in noradrenergic tone, might have on plasticity and cognitive processes in rodent models of learning and memory. This study investigates the effects of chronic NE reuptake inhibition on hippocampal plasticity and memory in rats. Rats were administered NE reuptake inhibitors (NRIs) desipramine (DMI; 0, 3, or 7.5mg/kg/day) or nortriptyline (NTP; 0, 10 or 20mg/kg/day) in drinking water. Long-term potentiation (LTP; 200 Hz) of the perforant path-dentate gyrus evoked potential was examined in urethane anesthetized rats after 30-32 days of DMI treatment. Short- (4-h) and long-term (24-h) spatial memory was tested in separate rats administered 0 or 7.5mg/kg/day DMI (25-30 days) using a two-trial spatial memory test. Additionally, the effects of chronically administered DMI and NTP were tested in rats using a two-trial, Object Recognition Test (ORT) at 2- and 24-h after 45 and 60 days of drug administration. Rats administered 3 or 7.5mg/kg/day DMI had attenuated LTP of the EPSP slope but not the population spike at the perforant path-dentate gyrus synapse. Short- and long-term memory for objects is differentially disrupted in rats after prolonged administration of DMI and NTP. Rats that were administered 7.5mg/kg/day DMI showed decreased memory for a two-trial spatial task when tested at 4-h. In the novel ORT, rats receiving 0 or 7.5mg/kg/day DMI showed a preference for the arm containing a Novel object when tested at both 2- and 24-h demonstrating both short- and long-term memory retention of the Familiar object. Rats that received either dose of NTP or 3mg/kg/day DMI showed impaired memory at 2-h, however this

  11. Long-term effect of prazosin and losartan administration on blood pressure, heart, carotid artery, and acetylcholine induced dilation of cardiovascular system of young Wistar rats and SHR.

    PubMed

    Kristek, Frantisek; Malekova, Magdalena; Cacanyiova, Sona

    2013-06-01

    The long-term effects of prazosin and losartan administration on blood pressure, trophicity of the heart and carotid arteries, and responses of the cardiovascular system to acetylcholine, were studied in Wistar rats and spontaneously hypertensive rats (SHRs). Four-week-old rats were treated with prazosin (10 mg/kg b.w./day in tap water) or losartan (20 mg/kg b.w./day in tap water) for 5-6 weeks. BP was measured by plethysmographic method. Ten animals of each group were subjected to in vivo studies and subsequent to morphological investigations. The right jugular vein was cannulated for administration of acetylcholine (0.1, 1, and 10 µg). After perfusion with a glutaraldehyde fixative (120 mmHg), the carotid arteries were embedded in Durcupan ACM, and the inner diameter (ID), wall thickness (WT) (tunica intima and media), cross sectional area (CSA) (tunica intima and media), and WT/ID ratio were calculated. In Wistar rats and SHRs, prazosin and losartan administration produced a decrease in the blood pressure and trophicity of the heart. In Wistar rats, both drugs decreased the WT, CSA, and the WT/ID ratio. In addition, these drugs increased the circumferential stress of the artery without affecting the ID. In contrast, in the SHRs, only losartan administration produced these effects. Importantly, both the drugs improved the responses to acetylcholine in SHRs.

  12. Different effects of long-term haloperidol administration on GABA/sub A/ and benzodiazepine receptors in various parts of the brain

    SciTech Connect

    Vasar, Oe.Oe.; Nurk, A.M.; Maimets, M.O.; Soosaar, A.H.; Allikmets, L.H.

    1986-09-01

    The data described in this paper are evidence that long-term administration of haloperidol has an opposite effect on the density of GABA/sub A/ and benzodiazepine receptors in the fore- and hindbrain. These changes are reflected at the molecular level as reversal of behavioral effect of the GABA/sub A/ agonist muscimol and the benzodiazepine agonist Ro15-1788. By means of parallel behavioral tests, binding of /sup 3/H-muscimol in the fore- and hindbrain of rats was investigated in experiments in vitro. /sup 3/H-flunitrazepam binding experiments were carried out in vivo on mice. Parallel with reversal of the behavioral effects of muscimol and Ro15-1788, the number of binding sites both for /sup 3/H-muscimol and for /sup 3/H-flunitrazepam in the forebrain was reduced; in the hindbrain the opposite process took place.

  13. Successful Long-term Management with a Single Administration of Tri-weekly Nab-paclitaxel in a Patient with Advanced Gastric Cancer with Peritoneal Dissemination.

    PubMed

    Matano, Daisuke; Moriwaki, Toshikazu; Tange, Yoshitaka; Niisato, Yusuke; Yamaura, Masamichi; Nagase, Masaomi; Suganuma, Daisuke; Takagi Taketa, Kaoruko; Iwai, Kentaro; Enami, Chiaki; Yamamoto, Yoshiyuki; Hyodo, Ichinosuke

    2017-01-01

    Nanoparticle albumin-bound (nab)-paclitaxel has shown promising activity in advanced gastric cancer treatment. We herein report a case of advanced gastric cancer involving long-term management with a single administration of nab-paclitaxel. A 71-year-old man diagnosed with advanced gastric cancer with malignant ascites was treated with nab-paclitaxel as a second-line chemotherapy. He refused treatment continuation because of various severe toxicities in the first treatment cycle; he was therefore followed-up without any further treatments. Despite this, no disease progression was observed over 9 months. After progression, he received dose-dense paclitaxel, but he did not respond to this treatment and eventually died.

  14. [Long-term administration of a low-protein diet with keto-analogs of essential amino acids and the metabolic status of patients with chronic kidney failure].

    PubMed

    Teplan, V; Schück, O; Nádvorníková, H; Růzicková, J; Grafnetter, D; Kaslík, J

    1989-01-06

    To 12 patients with chronic renal failure (CHRI) for 12-22 months a diet containing 20 g high quality protein supplemented by keto analogues of essential amino acids (KA)--4.8 g/day--was administered. During the investigation period no significant change of the albumin, prealbumin or transferrin level was recorded, nor of Whitehead's quotient, immunoglobulin levels and haemoglobin concentration, serum iron and its binding capacity. However, there was decline of the C3 complement component (p less than 0.01). The investigated parameters of carbohydrate metabolism (fasting blood sugar, immunoreactive insulin, oral glucose tolerance test) did not change, similarly as total cholesterol and triglyceride levels. The originally reduced HDL-cholesterol level increased (p less than 0.05). The achieved results suggest that the long-term administration of a diet with 20 g protein supplemented by the minimal necessary dose of KA does not produce undesirable changes of the investigated metabolic parameters.

  15. Long-term maintenance combination chemotherapy with OPEC/MPEC (vincristine or methotrexate, prednisolone, etoposide and cyclophosphamide) or with daily oral etoposide and prednisolone can improve survival and quality of life in adult T-cell leukemia/lymphoma.

    PubMed

    Matsushita, K; Matsumoto, T; Ohtsubo, H; Fujiwara, H; Imamura, N; Hidaka, S; Kukita, T; Tei, C; Matsumoto, M; Arima, N

    1999-12-01

    Acute leukemia and lymphoma varieties of adult T-cell leukemia/lymphoma (ATL) usually carry a poor prognosis. While etoposide is generally useful for treating ATL, especially as a daily oral maintenance regimen, etoposide has not proven effective in severe types of ATL efficient in some patients. Of 87 ATL patients whom we have treated, 51 had acute leukemia, 22 lymphoma and 14 progressive chronic leukemia. Seventy-nine patients were treated with a long term maintenance combination protocol, OPEC/MPEC (weekly doses of vincristine, 0.7 mg/m2 or methotrexate, 14 mg/m2; prednisolone, 20 mg/m2; etoposide, 70 mg/m2 and cyclophosphamide, 200 mg/m2). The other 8 patients, 3 with acute leukemia, 2 with lymphoma and 3 with progressive chronic leukemia, were treated with daily oral administration of 25 mg of etoposide and 10 mg of prednisolone (DOEP). The dose administered was modified in individual cases to maintain the granulocyte count and reduce the number of ATL cells. Considering both protocols, a complete response and a partial response were achieved in 31.0% and 58.6% patients, respectively. Median survival times (MST) of all patients and, acute leukemia, lymphoma and progressive chronic leukemia types were 7.5, 6.7, 9.6 and 12.4 months, respectively. Respective MST of patients treated with OPEC/MPEC or DOEP protocols were 7.1 and 18.0 months. Relatively normal WBC counts, lower lactate dehydrogenase concentration and normal calcium concentration, limited numbers of anatomic sites involved, good performance status and good response to chemotherapy were significantly associated with long survival time. Drug toxicity was not apparent, and about half of patients were treated in an outpatient setting.

  16. Administration of anabolic steroid during adolescence induces long-term cardiac hypertrophy and increases susceptibility to ischemia/reperfusion injury in adult Wistar rats.

    PubMed

    Seara, Fernando de Azevedo Cruz; Barbosa, Raiana Andrade Quintanilha; de Oliveira, Dahienne Ferreira; Gran da Silva, Diorney Luiz Souza; Carvalho, Adriana Bastos; Freitas Ferreira, Andrea Claudia; Matheus Nascimento, José Hamilton; Olivares, Emerson Lopes

    2017-07-01

    Chronic administration of anabolic androgenic steroids (AAS) in adult rats results in cardiac hypertrophy and increased susceptibility to myocardial ischemia/reperfusion (IR) injury. Molecular analyses demonstrated that hyperactivation of type 1 angiotensin II (AT1) receptor mediates cardiac hypertrophy induced by AAS and also induces down-regulation of myocardial ATP-sensitive potassium channel (KATP), resulting in loss of exercise-induced cardioprotection. Exposure to AAS during adolescence promoted long-term cardiovascular dysfunctions, such as dysautonomia. We tested the hypothesis that chronic AAS exposure in the pre/pubertal phase increases the susceptibility to myocardial ischemia/reperfusion (IR) injury in adult rats. Male Wistar rats (26day old) were treated with vehicle (Control, n=12) or testosterone propionate (TP) (AAS, 5mgkg(-1) n=12) 5 times/week during 5 weeks. At the end of AAS exposure, rats underwent 23days of washout period and were submitted to euthanasia. Langendorff-perfused hearts were submitted to IR injury and evaluated for mechanical dysfunctions and infarct size. Molecular analysis was performed by mRNA levels of α-myosin heavy chain (MHC), βMHC and brain-derived natriuretic peptide (BNP), ryanodine receptor (RyR2) and sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) by quantitative RT-PCR (qRT-PCR). The expression of AT1 receptor and KATP channel subunits (Kir6.1 and SURa) was analyzed by qRT-PCR and Western Blot. NADPH oxidase (Nox)-related reactive oxygen species generation was assessed by spectrofluorimetry. The expression of antioxidant enzymes was measured by qRT-PCR in order to address a potential role of redox unbalance. AAS exposure promoted long-term cardiac hypertrophy characterized by increased expression of βMHC and βMHC/αMHC ratio. Baseline derivative of pressure (dP/dt) was impaired by AAS exposure. Postischemic recovery of mechanical properties was impaired (decreased left ventricle [LV] developed pressure and

  17. Vaccination with liposomal leishmanial antigens adjuvanted with monophosphoryl lipid-trehalose dicorynomycolate (MPL-TDM) confers long-term protection against visceral leishmaniasis through a human administrable route.

    PubMed

    Ravindran, Rajesh; Maji, Mithun; Ali, Nahid

    2012-01-01

    The development of a long-term protective subunit vaccine against visceral leishmaniasis depends on antigens and adjuvants that can induce an appropriate immune response. The immunization of leishmanial antigens alone shows limited efficacy in the absence of an appropriate adjuvant. Earlier we demonstrated sustained protection against Leishmania donovani with leishmanial antigens entrapped in cationic liposomes through an intraperitoneal route. However, this route is not applicable for human administration. Herein, we therefore evaluated the immune response and protection induced by liposomal soluble leishmanial antigen (SLA) formulated with monophosphoryl lipid-trehalose dicorynomycolate (MPL-TDM) through a subcutaneous route. Subcutaneous immunization of BALB/c mice with SLA entrapped in liposomes or with MPL-TDM elicited partial protection against experimental visceral leishmaniasis. In contrast, liposomal SLA adjuvanted with MPL-TDM induced significantly higher levels of protection in liver and spleen in BALB/c mice challenged 10 days post-vaccination. Protection conferred by this formulation was sustained up to 12 weeks of immunization, and infection was controlled for at least 4 months of the challenge, similar to liposomal SLA immunization administered intraperitoneally. An analysis of cellular immune responses of liposomal SLA + MPL-TDM immunized mice demonstrated the induction of IFN-γ and IgG2a antibody production not only 10 days or 12 weeks post-vaccination but also 4 months after the challenge infection and a down regulation of IL-4 production after infection. Moreover, long-term immunity elicited by this formulation was associated with IFN-γ production also by CD8⁺ T cells. Taken together, our results suggest that liposomal SLA + MPL-TDM represent a good vaccine formulation for the induction of durable protection against L. donovani through a human administrable route.

  18. Performance of a Predictive Model for Long-Term Hemoglobin Response to Darbepoetin and Iron Administration in a Large Cohort of Hemodialysis Patients.

    PubMed

    Barbieri, Carlo; Bolzoni, Elena; Mari, Flavio; Cattinelli, Isabella; Bellocchio, Francesco; Martin, José D; Amato, Claudia; Stopper, Andrea; Gatti, Emanuele; Macdougall, Iain C; Stuard, Stefano; Canaud, Bernard

    2016-01-01

    Anemia management, based on erythropoiesis stimulating agents (ESA) and iron supplementation, has become an increasingly challenging problem in hemodialysis patients. Maintaining hemodialysis patients within narrow hemoglobin targets, preventing cycling outside target, and reducing ESA dosing to prevent adverse outcomes requires considerable attention from caregivers. Anticipation of the long-term response (i.e. at 3 months) to the ESA/iron therapy would be of fundamental importance for planning a successful treatment strategy. To this end, we developed a predictive model designed to support decision-making regarding anemia management in hemodialysis (HD) patients treated in center. An Artificial Neural Network (ANN) algorithm for predicting hemoglobin concentrations three months into the future was developed and evaluated in a retrospective study on a sample population of 1558 HD patients treated with intravenous (IV) darbepoetin alfa, and IV iron (sucrose or gluconate). Model inputs were the last 90 days of patients' medical history and the subsequent 90 days of darbepoetin/iron prescription. Our model was able to predict individual variation of hemoglobin concentration 3 months in the future with a Mean Absolute Error (MAE) of 0.75 g/dL. Error analysis showed a narrow Gaussian distribution centered in 0 g/dL; a root cause analysis identified intercurrent and/or unpredictable events associated with hospitalization, blood transfusion, and laboratory error or misreported hemoglobin values as the main reasons for large discrepancy between predicted versus observed hemoglobin values. Our ANN predictive model offers a simple and reliable tool applicable in daily clinical practice for predicting the long-term response to ESA/iron therapy of HD patients.

  19. Co-Administration of a Plasmid DNA Encoding IL-15 Improves Long-Term Protection of a Genetic Vaccine against Trypanosoma cruzi

    PubMed Central

    Sullivan, Nicole L.; Blazevic, Azra; Bruna-Romero, Oscar; Rodrigues, Mauricio M.; Hoft, Daniel F.

    2011-01-01

    Background Immunization of mice with the Trypanosoma cruzi trans-sialidase (TS) gene using plasmid DNA, adenoviral vector, and CpG-adjuvanted protein delivery has proven highly immunogenic and provides protection against acute lethal challenge. However, long-term protection induced by TS DNA vaccines has not been reported. The goal of the present work was to test whether the co-administration of a plasmid encoding IL-15 (pIL-15) could improve the duration of protection achieved through genetic vaccination with plasmid encoding TS (pTS) alone. Methodology We immunized BALB/c mice with pTS in the presence or absence of pIL-15 and studied immune responses [with TS-specific IFN-γ ELISPOT, serum IgG ELISAs, intracellular cytokine staining (IFN-γ, TNF-α, and IL-2), tetramer staining, and CFSE dilution assays] and protection against lethal systemic challenge at 1 to 6 months post vaccination. Mice receiving pTS alone developed robust TS-specific IFN-γ responses and survived a lethal challenge given within the first 3 months following immunization. The addition of pIL-15 to pTS vaccination did not significantly alter T cell responses or protection during this early post-vaccination period. However, mice vaccinated with both pTS and pIL-15 challenged 6 months post-vaccination were significantly more protected against lethal T. cruzi challenges than mice vaccinated with pTS alone (P<0.05). Improved protection correlated with significantly higher numbers of TS-specific IFN-γ producing total and CD8+ T cells detected>6 months post immunization. Also, these TS-specific T cells were better able to expand after in vitro re-stimulation. Conclusion Addition of pIL-15 during genetic vaccination greatly improved long-term T cell survival, memory T cell expansion, and long-term protection against the important human parasite, T. cruzi. PMID:21408124

  20. Short communication: Modulation of the small intestinal microbial community composition over short-term or long-term administration with Lactobacillus plantarum ZDY2013.

    PubMed

    Xie, Qiong; Pan, Mingfang; Huang, Renhui; Tian, Ximei; Tao, Xueying; Shah, Nagendra P; Wei, Hua; Wan, Cuixiang

    2016-09-01

    The small intestinal (SI) microbiota has an essential role in the maintenance of human health. However, data about the indigenous bacteria in SI as affected by probiotics are limited. In our study, the short-term and long-term effects of a probiotic candidate, Lactobacillus plantarum ZDY2013, on the SI microbiota of C57BL/6J mice were investigated by the Illumina HiSeq (Novogene Bioinformatics Technology Co., Ltd., Tianjin, China) platform targeting the V4 region of the 16S rDNA. A total of 858,011 sequences in 15 samples were read. The α diversity analysis revealed that oral administration with L. plantarum ZDY2013 for 3 wk led to a significant increase in the richness and diversity of the SI bacterial community. Principal coordinate analysis and unweighted pair-group method with arithmetic means analysis showed a clear alteration in the SI microbiota composition after 3 wk of L. plantarum ZDY2013 treatment, although these changes were not found 6 wk after ceasing L. plantarum ZDY2013 administration. Species annotation showed that the dominant phyla in SI microbiota were Firmicutes, Bacteroidetes, Proteobacteria, and Verrucomicrobia. Interestingly, operational taxonomic unit cluster analysis showed that administration with L. plantarum ZDY2013 for 3 wk significantly increased the abundance of Proteobacteria, but decreased that of Bacteroidetes. Linear discriminant analysis coupled with effect size identified 18 bacterial taxa (e.g., Ruminococcus spp. and Clostridium spp.) that overgrew in the SI microbiota of the mice administered with L. plantarum ZDY2013 for 3 wk, and most of them belonged to the phyla Bacteroidetes and Proteobacteria. However, only one bacterial taxon (e.g., Nocardioides spp.) was over-represented in the SI microbiota of mice 6 wk after L. plantarum ZDY2013 administration. Overall, this study shows that oral administration with probiotic results in an important but transient alteration in the microbiota of SI.

  1. Effects of preoperative administration of hypertonic saline or pentastarch solution on hematologic variables and long-term survival of surgically managed horses with colic.

    PubMed

    Dugdale, Alexandra H A; Barron, Kirsty E; Miller, Andrew J; Proudman, Christopher J

    2015-05-15

    To compare the effects of preoperatively administered pentastarch (10% concentration in isotonic saline [0.9% NaCl] solution) and hypertonic saline (7.2% NaCl) solutions on PCV and circulating total protein (TP) concentration in horses with colic undergoing emergency exploratory laparotomy and to assess survival rates of horses that received each treatment. Prospective, randomized study. 100 horses with signs of abdominal pain and PCV ≥ 0.46 L/L. Procedures-Horses received a 4 mL/kg (1.8 mL/lb) dose of pentastarch solution (n = 50) or hypertonic saline solution (50) over a 10- to 20-minute period before anesthetic induction. Blood samples were collected at the time of evaluation and ≤ 5 minutes after fluid resuscitation; changes in PCV and TP concentration were compared. Survival was evaluated by Kaplan-Meier and Cox proportional hazards analyses. Age, weight, sex, PCV, and heart rate on initial examination were similar between treatment groups. Hypertonic saline solution treatment resulted in a significantly greater reduction in PCV (median change, -0.14 L/L) than did pentastarch treatment (median change, -0.07 L/L). Reduction in TP concentration was also significantly greater after hypertonic saline solution treatment (median change, -16 g/L) than after pentastarch treatment (median change, -2 g/L). Long-term survival was not significantly different between groups. Despite a greater reduction in preanesthetic hemoconcentration following administration of hypertonic saline solution (4 mL/kg infusion, once), no difference in overall long-term survival was found between horses that received this treatment and those that received an equal volume of pentastarch solution. Findings suggested that, in a clinical setting, either of these fluids would be appropriate for preoperative fluid resuscitation in horses with colic.

  2. Safety and efficacy of long-term esomeprazole 20 mg in Japanese patients with a history of peptic ulcer receiving daily non-steroidal anti-inflammatory drugs

    PubMed Central

    2013-01-01

    Background Non-steroidal anti-inflammatory drugs (NSAIDs) are an effective and common treatment for chronic pain disorders, but long-term use is associated with risk of potentially life-threatening gastrointestinal adverse events (AEs). The proton pump inhibitor esomeprazole has been found to be effective for gastroprotection in NSAID users, but few long-term studies have been conducted in Japan. Methods This was an open-label, multicentre, single-arm, prospective 1-year study of treatment with esomeprazole (20 mg once daily) in Japanese patients (aged ≥20 years) with endoscopic evidence of previous peptic ulcer and receiving daily oral NSAID therapy (at a stable dose) for a chronic condition. Eligibility was not dictated by type of oral NSAID. The primary objective was to determine long-term safety and tolerability of esomeprazole. Efficacy for prevention of peptic ulcers was also determined (Kaplan-Meier method). All statistical analyses were descriptive. Results A total of 130 patients (73.1% women, mean age 62.1 years, 43.8% Helicobacter pylori-positive) received treatment with esomeprazole in addition to long-term NSAID therapy (most commonly for rheumatoid arthritis [n=42] and osteoarthritis [n=34]). Loxoprofen, meloxicam and diclofenac were the most commonly used NSAIDs; cyclo-oxygenase (COX)-2 selective agents were used by 16.2% of patients (n=21). Long-term compliance with esomeprazole (capsule counts) was >75% for the majority of patients. Although 16.9% of patients (n=22) experienced AEs judged to be possibly related to treatment with esomeprazole, they were mostly mild and transient. The most commonly reported possibly treatment-related AEs were abnormal hepatic function, headache, increased γ-glutamyltransferase levels and muscle spasms (2 patients each). Overall, 95.9% (95% confidence interval: 92.3, 99.4) of patients remained ulcer free at 1 year. Conclusion Long-term treatment with esomeprazole (20 mg once daily) is well tolerated and

  3. Failure to Recognize Novelty after Extended Methamphetamine Self-Administration Results from Loss of Long-Term Depression in the Perirhinal Cortex.

    PubMed

    Scofield, Michael D; Trantham-Davidson, Heather; Schwendt, Marek; Leong, Kah-Chung; Peters, Jamie; See, Ronald E; Reichel, Carmela M

    2015-10-01

    Exposure to methamphetamine (meth) can produce lasting memory impairments in humans and rodents. We recently demonstrated that extended access meth self-administration results in novel object recognition (NOR) memory deficits in rats. Recognition of novelty depends upon intact perirhinal (pRh) cortex function, which is compromised by meth-induced downregulation of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors. NMDA receptors containing this subunit have a critical role in pRh long-term depression (LTD), one of the primary physiological processes thought to underlie object recognition memory. We hypothesized that meth-induced downregulation of GluN2B receptors would compromise pRh LTD, leading to loss of NOR memory. We found that meth self-administration resulted in an inability to induce pRh LTD following 1 Hz stimulation, an effect that was reversed with bath application of the NMDA receptor partial agonist D-cycloserine (DCS). In addition, pRh microinfusion of DCS restored meth-induced memory deficits. Furthermore, blockade of GluN2B-containing NMDA receptors with Ro 25-6981 prevented DCS restoration of pRh LTD in meth subjects. Thus, targeting pRh LTD may be a promising strategy to treat meth-induced cognitive impairment.

  4. Long-term administration of advanced glycation end-product stimulates the activation of NLRP3 inflammasome and sparking the development of renal injury.

    PubMed

    Yeh, Wan-Ju; Yang, Hsin-Yi; Pai, Man-Hui; Wu, Chi-Hao; Chen, Jiun-Rong

    2017-01-01

    The accumulation of advanced glycation end-products (AGEs) and the enhanced interaction of AGE with their cellular receptor (RAGE) have been implicated in the progression of chronic kidney disease. The purpose of this study was to examine whether the AGE/RAGE-induced nephrotoxic effects are associated with inflammasome activation and endothelial dysfunction. Chronic renal injury was examined in BALB/c mice by the long-term administration of carbonyl-AGE for 16 weeks. Endothelial dysfunction was detected by measuring the number of circulating endothelial progenitor cells (EPCs) and the levels of nitric oxide synthase (eNOS) and nitric oxide (NO) in kidneys. Results showed that administration of methylglyoxal-bovine serum albumin (MG-BSA) AGE accelerated renal MG, carboxyethyl lysine, carboxymethyl lysine and malondialdehyde formation and, in parallel, the levels of serum creatinine and blood urea nitrogen (BUN) were significantly increased. Expression of RAGE and NLRP3 inflammasome-related proteins (TXNIP, NLRP3, procaspase-1 and caspase-1) and IL (interleukin)-1β secretion were upregulated, whereas the levels of EPCs, eNOS and NO were lower in MG-BSA-treated mice. This induction by MG-BSA was significantly inhibited by RAGE antagonist. Our results firstly reveal a possible mechanism of AGE-mediated renal dysfunction upon NLRP3 inflammasome activation. Therapeutic blockade of RAGE may ameliorate renal and endothelial functions in subjects under high AGE burden.

  5. Failure to Recognize Novelty after Extended Methamphetamine Self-Administration Results from Loss of Long-Term Depression in the Perirhinal Cortex

    PubMed Central

    Scofield, Michael D; Trantham-Davidson, Heather; Schwendt, Marek; Leong, Kah-Chung; Peters, Jamie; See, Ronald E; Reichel, Carmela M

    2015-01-01

    Exposure to methamphetamine (meth) can produce lasting memory impairments in humans and rodents. We recently demonstrated that extended access meth self-administration results in novel object recognition (NOR) memory deficits in rats. Recognition of novelty depends upon intact perirhinal (pRh) cortex function, which is compromised by meth-induced downregulation of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors. NMDA receptors containing this subunit have a critical role in pRh long-term depression (LTD), one of the primary physiological processes thought to underlie object recognition memory. We hypothesized that meth-induced downregulation of GluN2B receptors would compromise pRh LTD, leading to loss of NOR memory. We found that meth self-administration resulted in an inability to induce pRh LTD following 1 Hz stimulation, an effect that was reversed with bath application of the NMDA receptor partial agonist D-cycloserine (DCS). In addition, pRh microinfusion of DCS restored meth-induced memory deficits. Furthermore, blockade of GluN2B-containing NMDA receptors with Ro 25-6981 prevented DCS restoration of pRh LTD in meth subjects. Thus, targeting pRh LTD may be a promising strategy to treat meth-induced cognitive impairment. PMID:25865928

  6. Long-term inhibition of ethanol intake by the administration of an aldehyde dehydrogenase-2 (ALDH2)-coding lentiviral vector into the ventral tegmental area of rats.

    PubMed

    Karahanian, Eduardo; Rivera-Meza, Mario; Tampier, Lutske; Quintanilla, María Elena; Herrera-Marschitz, Mario; Israel, Yedy

    2015-03-01

    Previous studies suggest that acetaldehyde generated from ethanol in the brain is reinforcing. The present studies tested the feasibility of achieving a long-term reduction of chronic and post-deprivation binge ethanol drinking by a single administration into the brain ventral tegmental area (VTA) of a lentiviral vector that codes for aldehyde dehydrogenase-2 (ALDH2), which degrades acetaldehyde. The ALDH2 gene coding vector or a control lentiviral vector were microinjected into the VTA of rats bred for their alcohol preference. In the chronic alcohol administration model, naïve animals administered the control vector and subsequently offered 10% ethanol and water ingested 8-9 g ethanol/kg body weight/day. The single administration of the ALDH2-coding vector prior to allowing ethanol availability reduced ethanol drinking by 85-90% (P < 0.001) for the 45 days tested. In the post-deprivation binge-drinking model, animals that had previously consumed ethanol chronically for 81 days were administered the lentiviral vector and were thereafter deprived of ethanol for three 7-day periods, each interrupted by a single 60-minute ethanol re-access after the last day of each deprivation period. Upon ethanol re-access, control vector-treated animals consumed intoxicating 'binge' amounts of ethanol, reaching intakes of 2.7 g ethanol/kg body weight in 60 minutes. The administration of the ALDH2-coding vector reduced re-access binge drinking by 75-80% (P < 0.001). This study shows that endowing the ventral tegmental with an increased ability to degrade acetaldehyde greatly reduces chronic alcohol consumption and post-deprivation binge drinking for prolonged periods and supports the hypothesis that brain-generated acetaldehyde promotes alcohol drinking. © 2014 Society for the Study of Addiction.

  7. Neoadjuvant administration of Semliki Forest virus expressing interleukin-12 combined with attenuated Salmonella eradicates breast cancer metastasis and achieves long-term survival in immunocompetent mice.

    PubMed

    Kramer, M Gabriela; Masner, Martín; Casales, Erkuden; Moreno, María; Smerdou, Cristian; Chabalgoity, José A

    2015-09-07

    Metastatic breast cancer is a major cause of death among women worldwide; therefore efficient therapeutic strategies are extremely needed. In this work we have developed a gene therapy- and bacteria-based combined neoadjuvant approach and evaluated its antitumor effect in a clinically relevant animal model of metastatic breast cancer. 2×10(8) particles of a Semliki Forest virus vector expressing interleukin-12 (SFV-IL-12) and/or 2×10(7) units of an aroC (-) Samonella Typhimurium strain (LVR01) were injected into 4T1 tumor nodules orthotopically implanted in mice. Tumors were surgically resected and long-term survival was determined. IL-12 and interferon-γ were quantified by Enzyme-Linked ImmunoSorbent Assay, bacteria was visualized by inmunohistochemistry and the number of lung metastasis was calculated with a clonogenic assay. SFV-IL-12 and LVR01 timely inoculated and followed by surgical resection of tumors succeeded in complete inhibition of lethal lung metastasis and long-term survival in 90% of treated mice. The combined therapy was markedly synergistic compared to each treatment alone, since SFV-IL-12 monotherapy showed a potent antiangiogenic effect, being able to inhibit tumor growth and extend survival, but could not prevent establishment of distant metastasis and death of tumor-excised animals. On the other hand, LVR01 alone also showed a significant, although limited, antitumor potential, despite its ability to invade breast cancer cells and induce granulocyte recruitment. The efficacy of the combined therapy depended on the order in which both factors were administered; inasmuch the therapeutic effect was only observed when SFV-IL-12 was administered previous to LVR01, whereas administration of LVR01 before SFV-IL-12 had negligible antitumor activity. Moreover, pre-treatment with LVR01 seemed to suppress SFV-IL-12 antiangiogenic effects associated to lower IL-12 expression in this group. Re-challenged mice were unable to reject a second 4T1 tumor

  8. Long Term Prognosis

    MedlinePlus

    ... TERM PROGNOSIS The long-term outlook of pediatric cardiomyopathy continues to be unpredictable because it occurs with ... a child also depends on the type of cardiomyopathy and the stage the disease is first diagnosed. ...

  9. The effects of long-term daily folic acid and vitamin B12 supplementation on genome-wide DNA methylation in elderly subjects.

    PubMed

    Kok, Dieuwertje E G; Dhonukshe-Rutten, Rosalie A M; Lute, Carolien; Heil, Sandra G; Uitterlinden, André G; van der Velde, Nathalie; van Meurs, Joyce B J; van Schoor, Natasja M; Hooiveld, Guido J E J; de Groot, Lisette C P G M; Kampman, Ellen; Steegenga, Wilma T

    2015-01-01

    Folate and its synthetic form folic acid function as donor of one-carbon units and have been, together with other B-vitamins, implicated in programming of epigenetic processes such as DNA methylation during early development. To what extent regulation of DNA methylation can be altered via B-vitamins later in life, and how this relates to health and disease, is not exactly known. The aim of this study was to identify effects of long-term supplementation with folic acid and vitamin B12 on genome-wide DNA methylation in elderly subjects. This project was part of a randomized, placebo-controlled trial on effects of supplemental intake of folic acid and vitamin B12 on bone fracture incidence (B-vitamins for the PRevention Of Osteoporotic Fractures (B-PROOF) study). Participants with mildly elevated homocysteine levels, aged 65-75 years, were randomly assigned to take 400 μg folic acid and 500 μg vitamin B12 per day or a placebo during an intervention period of 2 years. DNA was isolated from buffy coats, collected before and after intervention, and genome-wide DNA methylation was determined in 87 participants (n = 44 folic acid/vitamin B12, n = 43 placebo) using the Infinium HumanMethylation450 BeadChip. After intervention with folic acid and vitamin B12, 162 (versus 14 in the placebo group) of the 431,312 positions were differentially methylated as compared to baseline. Comparisons of the DNA methylation changes in the participants receiving folic acid and vitamin B12 versus placebo revealed one single differentially methylated position (cg19380919) with a borderline statistical significance. However, based on the analyses of differentially methylated regions (DMRs) consisting of multiple positions, we identified 6 regions that differed statistically significantly between the intervention and placebo group. Pronounced changes were found for regions in the DIRAS3, ARMC8, and NODAL genes, implicated in carcinogenesis and early embryonic development

  10. Long term efficacy of a pen injector.

    PubMed

    Dinneen, S F; Cronin, C C; O'Sullivan, D J

    1991-09-01

    We assessed the long term efficacy of Novopen as a form of insulin administration. Records were obtained on 48 patients who were treated with Novopen between January '86 and October '88. Six patients were excluded due to insufficient data. The study group of 42 patients comprised 22 females and 20 males of average age 33 years (range 17-66). Mean Hb.A1 rose from 10.6% to 12.1% after Novopen therapy, a rise of 14.1%. This rise is both clinically and statistically significant (p less than 0.001; 99% confidence limits 0.59-2.78). Increases in weight and insulin dose were also noted, but did not reach statistical significance. The majority of patients felt Novopen was superior to twice daily insulin in terms of ease of administration (81%) and flexibility of lifestyle (95%), and all who were using Novopen wished to continue with it. More than 50% of patients admitted to altering their dietary habits while using Novopen. Despite continuing patient satisfaction with this form of insulin administration, its long-term use may be associated with sub-optimal metabolic control.

  11. scAAVIL-1ra dosing trial in a large animal model and validation of long-term expression with repeat administration for osteoarthritis therapy

    PubMed Central

    Goodrich, LR; Grieger, JC; Phillips, JN; Khan, N; Gray, SJ; McIlwraith, CW; Samulski, RJ

    2017-01-01

    A gene therapeutic approach to treat osteoarthritis (OA) appears to be on the horizon for millions of people who suffer from this disease. Previously we described optimization of a scAAVIL-1ra gene therapeutic vector and initially tested this in an equine model verifying long-term intrasynovial IL-1ra protein at therapeutic levels. Using this vector, we carried out a dosing trial in six horses to verify protein levels and establish a dose that would express relevant levels of therapeutic protein for extended periods of time (8 months). A novel arthroscopic procedure used to detect green fluorescence protein (GFP) fluorescence intrasynovially confirmed successful transduction of the scAAVGFP vector in both the synovial and cartilage tissues. No evidence of intra-articular toxicity was detected. Immune responses to vector revealed development of neutralizing antibodies (Nabs) within 2 weeks of administration, which persisted for the duration of the study but did not lower protein expression intra-articularly. Re-dosing with a different serotype to attain therapeutic levels of protein confirmed establishment of successful transduction. This is the first study in an equine model to establish a dosing/redosing protocol, as well as examine the Nab response to capsid and supports further clinical investigation to determine the clinical efficacy of scAAVIL-1ra to treat OA. PMID:25902762

  12. The long-term administration of Orai 1 antagonist possesses antitussive, bronchodilatory and anti-inflammatory effects in experimental asthma model.

    PubMed

    Sutovská, Martina; Kocmálová, Michaela; Adamkov, Marian; Výbohová, Desanka; Mikolka, Pavol; Mokrá, Daniela; Hatok, Jozef; Antošová, Martina; Fraňová, Soňa

    2013-06-01

    The best-studied store-operated Ca2+ channels (SOCs), Ca2+ release activated Ca2+ (CRAC) channels, are activated by depleting endoplasmic reticulum Ca2+ pool and mediate Ca2+ influx vitally important for Ca2+ restoration and many cellular function. CRAC channels were identified on immune and airway smooth muscle (ASM) cells. Emerging evidence points to its involvement in allergic airways diseases. This article evaluated therapeutic potency of CRAC antagonist in experimental animal model of allergic asthma. Allergic asthma, induced by repetitive exposure of guinea pigs to ovalbumine, was followed by 14 days therapy by CRAC antagonist (3-fluoropyridine-4-carboxylic acid, FPCA). In vivo changes of specific airways resistance (sRaw) evaluated bronchodilatory effect of FPCA and salbutamol. The method of citric acid-induced cough reflex assessed antitussive activity of FPCA and codeine. The measurement of exhaled NO (ENO), expression of inducible NO-synthase (iNOS) by RT-PCR and immunohistochemical staining of airways tissue verified anti-inflammatory effect of FPCA. Long-term administration of FPCA resulted in significant cough suppression and bronchodilation, both comparable to the effect of control drugs. FPCA significantly decreased ENO and iNOS expression, which together with immunohistochemical analysis validated its anti-inflammatory effect. Presented data confirmed CRAC channels as a promising target for treatment of respiratory diseases associated with allergic inflammation.

  13. Long-term follow-up of oral administration of flavonoids, Centella asiatica and Melilotus, for diabetic cystoid macular edema without macular thickening.

    PubMed

    Forte, Raimondo; Cennamo, Gilda; Bonavolontà, Paola; Pascotto, Arduino; de Crecchio, Giuseppe; Cennamo, Giovanni

    2013-10-01

    To evaluate long-term follow-up of the orally administered combination of flavonoids with Centella asiatica and Melilotus for treatment of diabetic cystoid macular edema (CME) without macular thickening. Seventy consecutive patients with type 2 diabetes and CME without macular thickening at optical coherence tomography (OCT) were prospectively and randomly enrolled in two groups of 35 subjects each (treatment and control groups). Patients in the treatment group were treated with an oral combination of diosmin (300 mg/day), with C. asiatica (15 mg/day) and Melilotus (160 mg/day). All patients underwent a complete ophthalmologic examination, OCT (Spectralis HRA-OCT), and central microperimetry (SD-SLO/OCT) at baseline, month 3, month 6, month 12, month 24, and month 36. No differences in HbAc1 percentage, blood pressure, microalbuminuria, visual acuity, mean central retinal thickness, and stability of fixation were present between the two groups during follow up (p>0.05). Retinal sensitivity reduced in the control group only from month 6 until month 36 (p<0.001). In the treatment group, a greater retinal sensitivity was present at month 12, month 24, and month 36 (p=0.001). No side effects of treatment were observed. Oral administration of flavonoids, C. asiatica and Melilotus, in patients with CME without macular thickening provided preservation of retinal sensitivity during 36 months of follow up when compared with untreated patients.

  14. Rescue administration of a helper-dependent adenovirus vector with long-term efficacy in dogs with glycogen storage disease type Ia.

    PubMed

    Crane, B; Luo, X; Demaster, A; Williams, K D; Kozink, D M; Zhang, P; Brown, T T; Pinto, C R; Oka, K; Sun, F; Jackson, M W; Chan, L; Koeberl, D D

    2012-04-01

    Glycogen storage disease type Ia (GSD-Ia) stems from glucose-6-phosphatase (G6Pase) deficiency and causes hypoglycemia, hepatomegaly, hypercholesterolemia and lactic acidemia. Three dogs with GSD-Ia were initially treated with a helper-dependent adenovirus encoding a human G6Pase transgene (HDAd-cG6Pase serotype 5) on postnatal day 3. Unlike untreated dogs with GSD-Ia, all three dogs initially maintained normal blood glucose levels. After 6-22 months, vector-treated dogs developed hypoglycemia, anorexia and lethargy, suggesting that the HDAd-cG6Pase serotype 5 vector had lost efficacy. Liver biopsies collected at this time revealed significantly elevated hepatic G6Pase activity and reduced glycogen content, when compared with affected dogs treated only by frequent feeding. Subsequently, the HDAd-cG6Pase serotype 2 vector was administered to two dogs, and hypoglycemia was reversed; however, renal dysfunction and recurrent hypoglycemia complicated their management. Administration of a serotype 2 HDAd vector prolonged survival in one GSD-Ia dog to 12 months of age and 36 months of age in the other, but the persistence of long-term complications limited HDAd vectors in the canine model for GSD-Ia.

  15. A multicenter, open-label, long-term study of three-year infliximab administration in Japanese patients with ankylosing spondylitis.

    PubMed

    Kobayashi, Shigeto; Yoshinari, Toru

    2017-01-01

    To investigate the efficacy, safety, and pharmacokinetics of infliximab (IFX) in Japanese patients with active ankylosing spondylitis (AS). In this multicenter open-label study, IFX was infused at 5 mg/kg to 33 Japanese patients with active AS using or intolerable to non-steroidal anti-inflammatory drugs (NSAIDs) at Weeks 0, 2, and 6, and then every six weeks for approximately three years (mean: 149.5 weeks). Assessment in Ankylosing Spondylitis (ASAS) 20 response at Week 24 (primary endpoint) was 97.0% (32/33) and was thereafter maintained at approximately 90% over the three-year study period. Improvements in range of motion, physical function, inflammatory parameters, and quality of life (QOL) were all maintained throughout the three-year study period. A serum IFX level of ≥5 μg/mL was maintained with six-week infusion intervals, and only two patients (6.1%) developed antibodies to IFX. Specific adverse events in AS patients were not observed. These findings suggest that a 5 mg/kg administration of IFX at six-week intervals to Japanese patients with active AS is safe, effective and provides long-term therapeutic benefits.

  16. Long-term estradiol-17β administration reduces population of neurons in the sympathetic chain ganglia supplying the ovary in adult gilts.

    PubMed

    Koszykowska, Marlena; Całka, Jarosław; Gańko, Marta; Jana, Barbara

    2011-08-01

    Elevated levels of endogenous estrogens occurring in the course of pathological states of ovaries (follicular cysts, tumors) as well as xenoestrogens may result in hyperestrogenism. In rat, a close relationship between estrogens and sympathetic and sensory neurons supplying the genito-urinary system was reported. Recently, we have shown that long-term estradiol-17β (E(2)) administration affected morphological and immunochemical organization of the sympathetic ovarian neurons in the caudal mesenteric ganglion of adult gilts. In this study, the influence of E(2) overdose on the number and distribution of neurons in the sympathetic chain ganglia (SChG) projecting to the ovary of adult pigs was investigated. The numbers of ovarian dopamine-β-hydroxylase (DβH-), neuropeptide Y (NPY-), somatostatin (SOM-), galanin (GAL-) and estrogen receptors (ERs-) immunoreactive perikarya as well as the density of the intraganglionic nerve fibers containing DβH and/or NPY, SOM, GAL were also determined. On day 3 of the estrous cycle the ovaries of both the control and experimental gilts were injected with retrograde neuronal tracer Fast Blue, to identify the neurons innervating gonads. From day 4 of the estrous cycle to the expected day 20 of the second studied cycle, the experimental gilts were injected with E(2), while the control gilts were receiving oil. After the last E(2)/oil injection, the SChG Th16-S2 were collected and processed for double-labeling immunofluorescence. Injections of E(2): (1) increased the E(2) level in the peripheral blood ~4-5 fold, (2) reduced the total number of Fast Blue-positive postganglionic neurons in the ganglia under investigation, (3) decreased the number of perikarya in the L2-L4 ganglia, (4) reduced the number of perikarya in the ventral, dorsal and central regions of the SChG, (5) decreased the numbers of DβH(+)/NPY(+) and DβH(+)/GAL(+) perikarya and the numbers of DβH(+) but NPY(-), SOM(-) and GAL(-) perikarya in the SChG, (6) decreased

  17. Post-training administration of a synthetic peptide ligand of the neural cell adhesion molecule, C3d, attenuates long-term expression of contextual fear conditioning.

    PubMed

    Cambon, K; Venero, C; Berezin, V; Bock, E; Sandi, C

    2003-01-01

    The neural cell adhesion molecule (NCAM) plays a key role in synaptic plasticity and memory formation. We have recently developed a synthetic peptide, termed C3d, which, through the binding to the first, N-terminal immunoglobulin-like (Ig) module in the extracellular portion of NCAM, has been shown to promote neurite outgrowth and synapse formation in vitro, and to interfere with passive avoidance memory in rats in vivo. In this study, we investigated whether the i.c.v. administration of C3d, either 5.5 h after or 2 days before training, could be effective to modulate the strength at which emotional memory for aversive situations is established into a long-term memory. The effects of the peptide were evaluated in adult male Wistar rats trained in the contextual fear conditioning task. The results indicated that C3d significantly reduced the subsequent long-term retention of the conditioned fear response when administered 5.5 h post-training, as indicated by retention tests performed 2-3 and 7 days post-training. However, this treatment failed to influence conditioning for this task when injected 2 days pre-training. Additional experiments showed that C3d did not influence the emotional or locomotor behaviour of the animals, when tested in the open field task. Furthermore, hippocampal levels of microtubule-associated protein 2 (MAP2), Synaptophysin and NCAM were found unchanged when evaluated by enzyme-linked immunosorbent assay in crude synaptosomal preparations 2 days after peptide i.c.v. injection. Therefore, post-training injection of this synthetic peptide was efficient to attenuate the strength at which memory for contextual fear conditioning was enduringly stored, whilst it did not affect the acquisition of new memories. In addition to further support the view that NCAM is critically involved in memory consolidation, the current findings suggest that the NCAM IgI module is a potential target for the development of therapeutic drugs capable to reduce the

  18. Effects of acute and long-term administration of escitalopram and citalopram on serotonin neurotransmission: an in vivo electrophysiological study in rat brain.

    PubMed

    El Mansari, Mostafa; Sánchez, Connie; Chouvet, Guy; Renaud, Bernard; Haddjeri, Nasser

    2005-07-01

    The present study was undertaken to compare the acute and long-term effects of escitalopram and citalopram on rat brain 5-HT neurotransmission, using electrophysiological techniques. In hippocampus, after 2 weeks of treatment with escitalopram (10 mg/kg/day, s.c.) or citalopram (20 mg/kg/day, s.c.), the administration of the selective 5-HT(1A) receptor antagonist WAY-100,635 (20-100 microg/kg, i.v.) dose-dependently induced a similar increase in the firing activity of dorsal hippocampus CA(3) pyramidal neurons, thus revealing direct functional evidence of an enhanced tonic activation of postsynaptic 5-HT(1A) receptors. In dorsal raphe nucleus, escitalopram was four times more potent than citalopram in suppressing the firing activity of presumed 5-HT neurons (ED(50)=58 and 254 mug/kg, i.v., respectively). Interestingly, the suppressant effect of escitalopram (100 microg/kg, i.v.) was significantly prevented, but not reversed by R-citalopram (250 microg/kg, i.v.). Sustained administration of escitalopram and citalopram significantly decreased the spontaneous firing activity of presumed 5-HT neurons. This firing activity returned to control rate after 2 weeks in rats treated with escitalopram, but only after 3 weeks using citalopram, and was associated with a desensitization of somatodendritic 5-HT(1A) autoreceptors. These results suggest that the time course of the gradual return of presumed 5-HT neuronal firing activity, which was reported to account for the delayed effect of SSRI on 5-HT transmission, is congruent with the earlier onset of action of escitalopram vs citalopram in validated animal models of depression and anxiety.

  19. Long-Term Blockade of Cocaine Self-Administration and Locomotor Activation in Rats by an Adenoviral Vector-Delivered Cocaine Hydrolase.

    PubMed

    Smethells, John R; Swalve, Natashia; Brimijoin, Stephen; Gao, Yang; Parks, Robin J; Greer, Adam; Carroll, Marilyn E

    2016-05-01

    A promising approach in treating cocaine abuse is to metabolize cocaine in the blood using a mutated butyrylcholinesterase (BChE) that functions as a cocaine hydrolase (CocH). In rats, a helper-dependent adenoviral (hdAD) vector-mediated delivery of CocH abolished ongoing cocaine use and cocaine-primed reinstatement of drug-seeking for several months. This enzyme also metabolizes ghrelin, an effect that may be beneficial in maintaining healthy weights. The effect of a single hdAD-CocH vector injection was examined in rats on measures of anxiety, body weight, cocaine self-administration, and cocaine-induced locomotor activity. To examine anxiety, periadolescent rats were tested in an elevated-plus maze. Weight gain was then examined under four rodent diets. Ten months after CocH-injection, adult rats were trained to self-administer cocaine intravenously and, subsequently, cocaine-induced locomotion was tested. Viral gene transfer produced sustained plasma levels of CocH for over 13 months of testing. CocH-treated rats did not differ from controls in measures of anxiety, and only showed a transient reduction in weight gain during the first 3 weeks postinjection. However, CocH-treated rats were insensitive to cocaine. At 10 months postinjection, none of the CocH-treated rats initiated cocaine self-administration, unlike 90% of the control rats. At 13 months postinjection, CocH-treated rats showed no cocaine-induced locomotion, whereas control rats showed a dose-dependent enhancement of locomotion. CocH vector produced a long-term blockade of the rewarding and behavioral effects of cocaine in rats, emphasizing its role as a promising therapeutic intervention in cocaine abuse.

  20. Long-term melatonin administration reduces hyperinsulinemia and improves the altered fatty-acid compositions in type 2 diabetic rats via the restoration of Delta-5 desaturase activity.

    PubMed

    Nishida, Shigeru; Segawa, Toshiko; Murai, Ichiro; Nakagawa, Shigeki

    2002-01-01

    The objective of this study was to investigate the effect of long-term melatonin administration on plasma levels of triglycerides, insulin and leptin, and on the fatty-acid metabolism of plasma and hepatic lipids in type 2 diabetic rats. Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes mellitus, were divided into two groups: one untreated (n=6), and one implanted with time-releasing melatonin pellets (1.1 mg/day for 30 wk) under the abdominal skin (n=6). Age-matched Long-Evans Tokushima Otsuka (LETO) rats (n=6) were used as healthy controls. The untreated diabetic rats had the increased plasma levels of triglycerides, cholesterol, insulin and leptin at 35 wk, as compared with the healthy control rats (n=6). The diabetic rats also had augmented ratios of 20:3n-6/20:4n-6 fatty acids, owing to diminished activity of Delta-5 desaturase, an insulin-permissive enzyme, in the liver. Melatonin administration to OLETF rats reduced the hypertriglyceridemia (-39%, P < 0.05), hyperinsulinemia (-33%, P < 0.01) and hyperleptinemia (-43%, P < 0.01), and restored hepatic Delta-5 desaturase activity (148%, P < 0.005). This resulted in a return to normal ratios of 20:3n-6/20:4n-6 fatty acids in plasma and hepatic lipids. There was a significant correlation (r=0.64, P < 0.005) between plasma levels of insulin and the ratios of 20:3n-6/20:4n-6 in plasma phospholipids of all rats in the three groups. Thus, subcutaneous implantation of a melatonin-releasing pellet thus resulted in improved lipid metabolism in diabetic rats, probably through restored insulin resistance.

  1. Prophylactic Subacute Administration of Zinc Increases CCL2, CCR2, FGF2, and IGF-1 Expression and Prevents the Long-Term Memory Loss in a Rat Model of Cerebral Hypoxia-Ischemia.

    PubMed

    Blanco-Alvarez, Victor Manuel; Soto-Rodriguez, Guadalupe; Gonzalez-Barrios, Juan Antonio; Martinez-Fong, Daniel; Brambila, Eduardo; Torres-Soto, Maricela; Aguilar-Peralta, Ana Karina; Gonzalez-Vazquez, Alejandro; Tomás-Sanchez, Constantino; Limón, I Daniel; Eguibar, Jose R; Ugarte, Araceli; Hernandez-Castillo, Jeanett; Leon-Chavez, Bertha Alicia

    2015-01-01

    Prophylactic subacute administration of zinc decreases lipoperoxidation and cell death following a transient cerebral hypoxia-ischemia, thus suggesting neuroprotective and preconditioning effects. Chemokines and growth factors are also involved in the neuroprotective effect in hypoxia-ischemia. We explored whether zinc prevents the cerebral cortex-hippocampus injury through regulation of CCL2, CCR2, FGF2, and IGF-1 expression following a 10 min of common carotid artery occlusion (CCAO). Male rats were grouped as follows: (1) Zn96h, rats injected with ZnCl2 (one dose every 24 h during four days); (2) Zn96h + CCAO, rats treated with ZnCl2 before CCAO; (3) CCAO, rats with CCAO only; (4) Sham group, rats with mock CCAO; and (5) untreated rats. The cerebral cortex-hippocampus was dissected at different times before and after CCAO. CCL2/CCR2, FGF2, and IGF-1 expression was assessed by RT-PCR and ELISA. Learning in Morris Water Maze was achieved by daily training during 5 days. Long-term memory was evaluated on day 7 after learning. Subacute administration of zinc increased expression of CCL2, CCR2, FGF2, and IGF-1 in the early and late phases of postreperfusion and prevented the CCAO-induced memory loss in the rat. These results might be explained by the induction of neural plasticity because of the expression of CCL2 and growth factors.

  2. Prophylactic Subacute Administration of Zinc Increases CCL2, CCR2, FGF2, and IGF-1 Expression and Prevents the Long-Term Memory Loss in a Rat Model of Cerebral Hypoxia-Ischemia

    PubMed Central

    Blanco-Alvarez, Victor Manuel; Soto-Rodriguez, Guadalupe; Gonzalez-Barrios, Juan Antonio; Martinez-Fong, Daniel; Brambila, Eduardo; Torres-Soto, Maricela; Aguilar-Peralta, Ana Karina; Gonzalez-Vazquez, Alejandro; Tomás-Sanchez, Constantino; Limón, I. Daniel; Eguibar, Jose R.; Ugarte, Araceli; Hernandez-Castillo, Jeanett; Leon-Chavez, Bertha Alicia

    2015-01-01

    Prophylactic subacute administration of zinc decreases lipoperoxidation and cell death following a transient cerebral hypoxia-ischemia, thus suggesting neuroprotective and preconditioning effects. Chemokines and growth factors are also involved in the neuroprotective effect in hypoxia-ischemia. We explored whether zinc prevents the cerebral cortex-hippocampus injury through regulation of CCL2, CCR2, FGF2, and IGF-1 expression following a 10 min of common carotid artery occlusion (CCAO). Male rats were grouped as follows: (1) Zn96h, rats injected with ZnCl2 (one dose every 24 h during four days); (2) Zn96h + CCAO, rats treated with ZnCl2 before CCAO; (3) CCAO, rats with CCAO only; (4) Sham group, rats with mock CCAO; and (5) untreated rats. The cerebral cortex-hippocampus was dissected at different times before and after CCAO. CCL2/CCR2, FGF2, and IGF-1 expression was assessed by RT-PCR and ELISA. Learning in Morris Water Maze was achieved by daily training during 5 days. Long-term memory was evaluated on day 7 after learning. Subacute administration of zinc increased expression of CCL2, CCR2, FGF2, and IGF-1 in the early and late phases of postreperfusion and prevented the CCAO-induced memory loss in the rat. These results might be explained by the induction of neural plasticity because of the expression of CCL2 and growth factors. PMID:26355725

  3. Daily self-monitoring of body weight, step count, fruit/vegetable intake, and water consumption: a feasible and effective long-term weight loss maintenance approach.

    PubMed

    Akers, Jeremy D; Cornett, Rachel A; Savla, Jyoti S; Davy, Kevin P; Davy, Brenda M

    2012-05-01

    Maintenance of weight loss remains a challenge for most individuals. Thus, practical and effective weight-loss maintenance (WTLM) strategies are needed. A two-group 12-month WTLM intervention trial was conducted from June 2007 to February 2010 to determine the feasibility and effectiveness of a WTLM intervention for older adults using daily self-monitoring of body weight, step count, fruit/vegetable (F/V) intake, and water consumption. Forty weight-reduced individuals (mean weight lost=6.7±0.6 kg; body mass index [calculated as kg/m²] 29.2±1.1), age 63±1 years, who had previously participated in a 12-week randomized controlled weight-loss intervention trial, were instructed to record daily body weight, step count, and F/V intake (WEV [defined as weight, exercise, and F/V]). Experimental group (WEV+) participants were also instructed to consume 16 fl oz of water before each main meal (ie, three times daily), and to record daily water intake. Outcome measures included weight change, diet/physical activity behaviors, theoretical constructs related to health behaviors, and other clinical measures. Statistical analyses included growth curve analyses and repeated measures analysis of variance. Over 12 months, there was a linear decrease in weight (β=-0.32, P<0.001) and a quadratic trend (β=0.02, P<0.01) over time, but no group difference (β=-0.23, P=0.08). Analysis of the 365 days of self-reported body weight for each participant determined that weight loss was greater over the study period in the WEV+ group than in the WEV group, corresponding to weight changes of -0.67 kg and 1.00 kg, respectively, and an 87% greater weight loss (β=-0.01, P<0.01). Overall compliance to daily tracking was 76%±5%. Daily self-monitoring of weight, physical activity, and F/V consumption is a feasible and effective approach for maintaining weight loss for 12 months, and daily self-monitoring of increased water consumption may provide additional WTLM benefits.

  4. Daily Self-Monitoring of Body Weight, Step Count, Fruit/Vegetable Intake and Water Consumption: A Feasible and Effective Long-Term Weight Loss Maintenance Approach

    PubMed Central

    Akers, Jeremy D.; Cornett, Rachel A.; Savla, Jyoti S.; Davy, Kevin P.; Davy, Brenda M.

    2012-01-01

    Maintenance of weight loss remains a challenge for most individuals, thus practical and effective weight loss maintenance (WTLM) strategies are needed. A two-group (WEV versus WEV+) 12-month WTLM intervention trial was conducted (June 2007–February 2010) to determine the feasibility and effectiveness of weight loss maintenance intervention for older adults using daily self-monitoring of body weight, step count, fruit/vegetable intake and water consumption. Forty weight-reduced (mean weight lost = 6.7 ± 0.6 kg; BMI 29.2 ± 1.1 kg/m2) individuals aged 63 ± 1 yrs, who had previously participated in a 12-week randomized controlled weight loss intervention trial, were instructed to record daily body weight (Weight), step count (Exercise), and fruit/vegetable intake (Vegetable). Experimental group (WEV+) participants were also instructed to consume 16 floz of water before each main meal (i.e., three times daily), and to record daily water intake. Outcome measures included weight change, diet/physical activity behaviors, theoretical constructs related to health behaviors, and other clinical measures. Statistical analyses included growth curve analyses and repeated measures ANOVA. Over 12 months, there was a linear decline in weight (β = −0.32, P < 0.001) and a quadratic trend (β = 0.02, P < 0.01) over time, but no group difference (β = −0.23, P = 0.08). Analysis of the 365 days of self-reported body weight for each participant determined that weight loss was greater over the study period in WEV+ than WEV, corresponding to weight changes of −0.67 kg and 1.00 kg respectively, and an 87% greater weight loss (β = −0.01, P < 0.01). Overall compliance to daily tracking was 76 ± 5%. Daily self-monitoring of weight, physical activity, and fruit/vegetable consumption is a feasible and effective approach for maintaining weight loss for 12 months, and daily self-monitoring of increased water consumption may provide additional WTLM benefits. PMID:22709772

  5. Dose-dependent effect of donepezil administration on long-term enhancement of visually evoked potentials and cholinergic receptor overexpression in rat visual cortex.

    PubMed

    Chamoun, Mira; Groleau, Marianne; Bhat, Menakshi; Vaucher, Elvire

    2016-09-01

    Stimulation of the cholinergic system tightly coupled with periods of visual stimulation boosts the processing of specific visual stimuli via muscarinic and nicotinic receptors in terms of intensity, priority and long-term effect. However, it is not known whether more diffuse pharmacological stimulation with donepezil, a cholinesterase inhibitor, is an efficient tool for enhancing visual processing and perception. The goal of the present study was to potentiate cholinergic transmission with donepezil treatment (0.5 and 1mg/kg) during a 2-week visual training to examine the effect on visually evoked potentials and to profile the expression of cholinergic receptor subtypes. The visual training was performed daily, 10min a day, for 2weeks. One week after the last training session, visual evoked potentials were recorded, or the mRNA expression level of muscarinic (M1-5) and nicotinic (α/β) receptors subunits was determined by quantitative RT-PCR. The visual stimulation coupled with any of the two doses of donepezil produced significant amplitude enhancement of cortical evoked potentials compared to pre-training values. The enhancement induced by the 1mg/kg dose of donepezil was spread to neighboring spatial frequencies, suggesting a better sensitivity near the visual detection threshold. The M3, M4, M5 and α7 receptors mRNA were upregulated in the visual cortex for the higher dose of donepezil but not the lower one, and the receptors expression was stable in the somatosensory (non-visual control) cortex. Therefore, higher levels of acetylcholine within the cortex sustain the increased intensity of the cortical response and trigger the upregulation of cholinergic receptors.

  6. Long-term safety and efficacy of once-daily topical brimonidine tartrate gel 0.5% for the treatment of moderate to severe facial erythema of rosacea: results of a 1-year open-label study.

    PubMed

    Moore, Angela; Kempers, Steven; Murakawa, George; Weiss, Jonathan; Tauscher, Amanda; Swinyer, Leonard; Liu, Hong; Leoni, Matthew

    2014-01-01

    Once-daily topical brimonidine tartrate (BT) gel 0.5% was shown to be efficacious and safe for the treatment of erythema of rosacea in previous studies including a 4-week treatment phase. In the present 1-year study, we aimed to assess the long-term safety and efficacy of the treatment. Subjects with moderate to severe erythema of rosacea were instructed to apply topical BT gel 0.5% once daily for 12 months. Severity of erythema and adverse events (AEs) were evaluated. Approximately 345 subject years of exposure to BT gel 0.5% was achieved in the study. The incidence of AEs and AEs judged to be related to the study drug was higher at the beginning and decreased over the course of the study. Similar safety profiles were observed between the subjects who had received or not received concomitant therapies for the inflammatory lesions of rosacea. Effect of topical BT gel 0.5% on erythema severity was observed after the first application and the durability of the effect was maintained until the end of the study at month 12, with no tachyphylaxis observed. In conclusion, once-daily topical BT gel 0.5% is safe and consistently effective for the long-term treatment of moderate to severe erythema of rosacea, even in the presence of concomitant therapies for the inflammatory lesions of rosacea.

  7. Developmental associations between short-term variability and long-term changes: Intraindividual correlation of positive and negative affect in daily life and cognitive aging.

    PubMed

    Hülür, Gizem; Hoppmann, Christiane A; Ram, Nilam; Gerstorf, Denis

    2015-07-01

    Conceptual notions and empirical evidence suggest that the intraindividual correlation (iCorr) of positive affect (PA) and negative affect (NA) is a meaningful characteristic of affective functioning. PA and NA are typically negatively correlated within-person. Previous research has found that the iCorr of PA and NA is relatively stable over time within individuals, that it differs across individuals, and that a less negative iCorr is associated with better resilience and less vulnerability. However, little is known about how the iCorr of PA and NA relates to cognitive aging. This project examined how the association between PA and NA in everyday life is associated with long-term cognitive aging trajectories. To do so, we linked microlongitudinal data on PA and NA obtained on up to 33 occasions over 6 consecutive days with macrolongitudinal data on fluid and crystallized cognitive abilities obtained over 15 years from a subsample of Berlin Aging Study participants (N = 81, mean age at the microlongitudinal study = 81 years, range 73-98; 41% women). Over and above age, gender, education, overall levels of PA and NA, and number of health conditions, a less negative iCorr of PA and NA was associated with lower levels of cognitive ability and steeper cognitive declines, particularly for fluency and knowledge abilities. We discuss possible mechanisms for this finding and argue that a less negative iCorr of PA and NA may be indicative of deficits in emotional integration that are tied to changes in crystallized aspects of cognitive abilities. (c) 2015 APA, all rights reserved).

  8. Long-term follow-up of patients undergoing adipose-derived adult stem cell administration to treat complex perianal fistulas.

    PubMed

    Guadalajara, Hector; Herreros, Dolores; De-La-Quintana, Paloma; Trebol, Jacobo; Garcia-Arranz, Mariano; Garcia-Olmo, Damian

    2012-05-01

    In patients with perianal fistulas, administration of adult stem cells (ASCs) derived from liposuction samples has proved a promising technique in a preceding phase II trial. We aimed to extend follow-up of these patients with this retrospective study. Patients who had received at least one dose of treatment (ASCs plus fibrin glue or fibrin glue alone) were included. Adverse events notified since the end of the phase II study were recorded. Clinical and magnetic resonance imaging (MRI) criteria were used to determine whether recurrence of the healed fistula had occurred. Data were available for 21 out of 24 patients treated with ASCs plus fibrin glue and 13 out of 25 patients treated with fibrin glue in the phase II study. Follow-up lasted a mean of 38.0 and 42.6 months, respectively. Two adverse events unrelated to the original treatment were reported, one in each group. There were no reports of anal incontinence associated with the procedure. Of the 12 patients treated with ASCs plus fibrin glue who were included in the retrospective follow-up in the complete closure group, only 7 remained free of recurrence. MRI was done in 31 patients. No relationship was detected between MRI results and the clinical fistula status, independent of the treatment received. Long-term follow-up reaffirmed the very good safety profile of the treatment. Nevertheless, a low proportion of the stem cell-treated patients with closure after the procedure remained free of recurrence after more than 3 years of follow-up.

  9. Bone health in long-term gastric cancer survivors: A prospective study of high-dose vitamin D supplementation using an easy administration scheme.

    PubMed

    Climent, Marta; Pera, Manuel; Aymar, Isabel; Ramón, José M; Grande, Luis; Nogués, Xavier

    2017-08-01

    Bone disease in long-term survivors after gastric cancer resection has received little research attention. This study aimed to investigate bone health after curative resection of gastric cancer and the consequences of high-dose vitamin D supplementation in patients with low levels of 25-(OH)-vitamin D. Disease-free patients at least 24 months after gastric cancer resection represented the study cohort. Serum markers of bone metabolism were assessed at baseline and at 3 and 12 months. Bone mineral density and presence of fractures were assessed by X-ray at baseline. Patients with 25-(OH)-vitamin D ≤30 ng/mL at baseline received 16,000 IU of vitamin D3 every 10 days during the 1-year follow-up. Forty patients were included in the study. Mean time from surgery was 48.9 (24-109) months. Vitamin D insufficiency and secondary hyperparathyroidism were observed in 38 and 20 patients, respectively. Densitometry showed osteoporosis in 14 women and seven men and prevalent fractures in 12 women and six men at baseline. After 3 months of vitamin D supplementation, 35 patients reached values of 25-(OH)-vitamin D over 30 ng/mL. After 12 months, 38 patients were in the normal range of 25-(OH)-vitamin D. At the same time, iPTH levels and markers of bone turnover (C-terminal cross-linked telopeptide of type-I collagen, serum concentrations of bone-specific alkaline phosphatase and osteocalcin) significantly decreased after vitamin D intervention. Oral administration of high doses of vitamin D is easily implemented and restored 25-(OH)-vitamin D and iPTH values, which are frequently disturbed after gastric cancer resection.

  10. Epigenetic alterations in the brains of Fisher 344 rats induced by long-term administration of folate/methyl-deficient diet.

    PubMed

    Pogribny, Igor P; Karpf, Adam R; James, Smitha R; Melnyk, Stepan; Han, Tao; Tryndyak, Volodymyr P

    2008-10-27

    The maintenance of the cellular epigenomic landscape, which depends on the status of the one-carbon metabolic pathway, is essential for normal central nervous system development and function. In the present study, we examined the epigenetic alterations in the brains of Fisher 344 rats induced by the long-term administration of a diet lacking of essential one-carbon nutrients, methionine, choline, and folic acid. The results demonstrated that feeding a folate/methyl-deficient diet causes global DNA hypermethylation as indicated by an increase of genomic 5-methyl-2'-deoxycytidine (5mdC) content and more importantly, by an increase of methylation within unmethylated CpG-rich DNA domains. Interestingly, these epigenetic changes were opposite to those observed in the livers of the same folate/methyl-deficient rats. The hypermethylation changes were associated with an increased protein expression of de novo DNA methyltransferase DNMT3a and methyl-CpG-binding protein 2. Additionally, the gene expression profiling identified 33 significantly up- or down-regulated genes (fold change > or =1.5 and p< or =0.05) in the brains of rats fed a folate/methyl-deficient diet for 36 weeks. Interestingly, we detected an up-regulation of regulatory factor X, 3 (Rfx3) gene, a sequence-specific DNA-binding protein, that mediates the transcriptional activation of silenced by methylation genes, which may be an adaptive protective brain response to hypermethylation. Together, these data suggest that the proper maintenance of the epigenomic landscape in normal brain depends on the adequate supply of essential nutrients involved in the metabolism of methyl groups.

  11. Impact of AP@LZ in the daily life of three persons with Alzheimer's disease: long-term use and further exploration of its effectiveness.

    PubMed

    Imbeault, Hélène; Gagnon, Lise; Pigot, Hélène; Giroux, Sylvain; Marcotte, Nicolas; Cribier-Delande, Perrine; Duval, Julie; Bocti, Christian; Lacombe, Guy; Fülöp, Tamás; Bier, Nathalie

    2016-04-28

    AP@LZ is an electronic organiser that was designed to support the day-to-day activities of persons with Alzheimer's disease. To assess the potential of this technology, three participants (NI, JB, RD) were approached to take part in the study. They benefited from a structured cognitive intervention to learn how to operate AP@LZ; the intervention included the following learning stages: Acquisition, Application and Adaptation. Pre- and post-intervention measures were collected. NI, for whom a longitudinal study was conducted, still continued to use AP@LZ 24 months post-intervention. JB and RD also showed a gradual improvement in their performance throughout the intervention phase (sessions 1 to 19 for JB: performance increased from 50 to 100%; sessions 1 to 25 for RD: from 56 to 89%). The results of the use of AP@LZ in activities of daily living suggest that the application was beneficial for three persons with Alzheimer's disease whose profiles differed notably (age, cognitive and social profiles). Thus, results indicate that they were all able to learn how to operate AP@LZ's functions and to use them in their activities of daily living. Cognitive intervention appears to play an important role for the promotion of learning and adoption of such technology.

  12. Attenuation of cadmium-induced decline in spatial, habituation and recognition memory by long-term administration of almond and walnut supplementation: Role of cholinergic function.

    PubMed

    Batool, Zehra; Agha, Faiza; Ahmad, Saara; Liaquat, Laraib; Tabassum, Saiqa; Khaliq, Saima; Anis, Lubna; Sajid, Irfan; Emad, Shaista; Perveen, Tahira; Haider, Saida

    2017-01-01

    Excessive exposure of cadmium which is regarded as a neurotoxin can stimulate aging process by inducing abnormality in neuronal function. It has been reported that supplementation of almond and walnut attenuate age-related memory loss. Present study was designed to investigate the weekly administration of cadmium for one month on learning and memory function with relation to cholinergic activity. Cadmium was administered at the dose of 50 mg/kg/week. Whereas, almond and walnut was supplemented at the dose of 400 mg/kg/day along with cadmium administration to separate set of rats. At the end of experiment, memory function was assessed by Morris water maze, open field test and novel object recognition test. Results of the present study showed that cadmium administration significantly reduced memory retention. Reduced acetylcholine levels and elevated acetyl cholinesterase activity were also observed in frontal cortex and hippocampus of cadmium treated rats. Malondialdehyde levels were also significantly increased following the administration of cadmium. Daily supplementation of almond and walnut for 28 days significantly attenuated cadmium-induced memory impairment in rats. Results of the present study are discussed in term of cholinergic activity in cadmium-induced memory loss and its attenuation by nuts supplementation in rats.

  13. Long term effectiveness of once-daily unboosted atazanavir plus abacavir/lamivudine as a switch strategy in subjects with virological suppression.

    PubMed

    Llibre, Josep M; Cozzi-Lepri, Alessandro; La Rosa, Jorge Antonio Valencia; Pedersen, Court; Ristola, Matti; Losso, Marcelo; Mocroft, Amanda; Mitsura, Victor M; Ormaasen, Vidar; Maltez, Fernando; Beniowski, Marek; Paredes, Roger

    2014-01-01

    used in the previous regimen. A switch to ATV400+ABC/3TC in selected subjects with HIV-RNA below 50 c/mL is associated with relatively low rates of VF and discontinuation due to adverse events. Use might be considered in those with long-term suppression and without prior PI failure. Larger cohorts are required to further define the appropriate selection criteria.

  14. Using long-term daily satellite based rainfall data (1983-2015) to analyze spatio-temporal changes in the sahelian rainfall regime

    NASA Astrophysics Data System (ADS)

    Zhang, Wenmin; Brandt, Martin; Guichard, Francoise; Tian, Qingjiu; Fensholt, Rasmus

    2017-07-01

    The sahelian rainfall regime is characterized by a strong spatial as well as intra- and inter-annual variability. The satellite based African Rainfall Climatology Version 2 (ARC2) daily gridded rainfall estimates with a 0.1° × 0.1° spatial resolution provides the possibility for in-depth studies of seasonal changes over a 33-year period (1983-2015). Here we analyze rainfall regime variables that require daily observations: onset, cessation, and length of the wet season; seasonal rainfall amount; number of rainy days; intensity and frequency of rainfall events; number, length, and cumulative duration of dry spells. Rain gauge stations and MSWEP (Multi-Source Weighted-Ensemble Precipitation) data were used to evaluate the agreement of rainfall variables in both space and time, and trends were analyzed. Overall, ARC2 rainfall variables reliably show the spatio-temporal dynamics of seasonal rainfall over 33 years when compared to gauge and MSWEP data. However, a higher frequency of low rainfall events (<10 mm day-1) is found for satellite estimates as compared to gauge data, which also causes disagreements between satellite and gauge based variables due to sensitivity to the number of days with observations (frequency, intensity, and dry spell characteristics). Most rainfall variables (both ARC2 and gauge data) show negative anomalies (except for onset of rainy season) from 1983 until the end of the 1990s, from which anomalies become mostly positive and inter-annual variability is higher. ARC2 data show a strong increase in seasonal rainfall, wet season length (caused by both earlier onset and a late end), number of rainy days, and high rainfall events (>20 mm day-1) for the western/central Sahel over the period of analysis, whereas the opposite trend characterizes the eastern part of the Sahel.

  15. Calcipotriol/betamethasone dipropionate ointment in mild-to-moderate paediatric psoriasis: long-term daily clinical practice data in a prospective cohort.

    PubMed

    van Geel, M J; Mul, K; Oostveen, A M; van de Kerkhof, P C M; de Jong, E M G J; Seyger, M M B

    2014-08-01

    Psoriasis in children has a significant negative impact on the quality of life (QoL) and effective treatment can improve this. The two-compound ointment calcipotriol 50 μg g(-1) and betamethasone dipropionate 0·5 mg g(-1) is an effective treatment option for moderate-to-severe psoriasis in adults. To study prospectively the effectiveness and safety of calcipotriol/betamethasone dipropionate ointment in paediatric patients with mild-to-moderate plaque psoriasis in daily clinical practice and to investigate the influence on QoL. Data were obtained from a prospective, longitudinal paediatric psoriasis registry, called Child-CAPTURE. Severity was assessed using the Psoriasis Area and Severity Index (PASI) and body surface area (BSA). The Children's Dermatology Life Quality Index (CDLQI) was used to assess QoL and visual analogue scores (VAS) for pain and itch were collected. For safety data the number of (serious) adverse events was recorded. Seventy-three patients (mean age 10·8 years, range 3-18) were treated for a median time of 35·0 weeks (range 1·0-176·0). At week 12, mean PASI decreased 15·4% (from 5·2 to 4·4), BSA barely changed, and median CDLQI decreased significantly from 5·5 to 4·0. VAS scores for pain and itch declined. At week 24, mean PASI decreased to 4·3 (17·3%). No related serious adverse events were observed. In this daily clinical practice study in paediatric psoriasis, calcipotriol/betamethasone dipropionate ointment initially improved mild-to-moderate psoriasis and then maintained its effect. In addition, it improved QoL, with few adverse events. © 2014 British Association of Dermatologists.

  16. Mindfulness Meditation-Based Intervention Is Feasible, Acceptable, and Safe for Chronic Low Back Pain Requiring Long-Term Daily Opioid Therapy

    PubMed Central

    Burzinski, Cindy A.; Cox, Jennifer; Kloke, John; Singles, Janice; Mirgain, Shilagh; Stegner, Aaron; Cook, Dane B.; Bačkonja, Miroslav

    2016-01-01

    Abstract Objective: Although mindfulness meditation (MM) is increasingly used for chronic pain treatment, limited evidence supports its clinical application for opioid-treated chronic low back pain (CLBP). The goal of this study was to determine feasibility, acceptability, and safety of an MM-based intervention in patients with CLBP requiring daily opioid therapy. Design: 26-week pilot randomized controlled trial comparing MM-based intervention, combined with usual care, to usual care alone. Setting: Outpatient. Patients: Adults with CLBP treated with ≥30 mg of morphine-equivalent dose (MED) per day for 3 months or longer. Interventions: Targeted MM-based intervention consisted of eight weekly 2-hour group sessions and home practice (30 minutes/d, 6 days/wk) during the study. “Usual care” for opioid-treated CLBP was provided to participants by their regular clinicians. Outcome measures: Feasibility and acceptability of the MM intervention were assessed by adherence to intervention protocol and treatment satisfaction among experimental participants. Safety was evaluated by inquiry about side effects/adverse events and opioid dose among all study participants. Results: Thirty-five participants enrolled during the 10-week recruitment period. The mean age (±standard deviation) was 51.8 ± 9.7 years; the patients were predominantly female, with substantial CLBP-related pain and disability, and treated with 148.3 ± 129.2 mg of MED per day. All participants completed baseline assessments; none missed both follow-up assessments or withdrew. Among experimental participants (n = 21), 19 attended 1 or more intervention sessions and 14 attended 4 or more. They reported, on average, 164.0 ± 122.1 minutes of formal practice per week during the 26-week study and 103.5 ± 111.5 minutes of brief, informal practice per week. Seventeen patients evaluated the intervention, indicating satisfaction; their qualitative responses described the course as

  17. Long term statistics (1845-2014) of daily runoff maxima, monthly rainfall and runoff in the Adda basin (Italian Alps) under natural and anthropogenic changes.

    NASA Astrophysics Data System (ADS)

    Ranzi, Roberto; Goatelli, Federica; Castioni, Camilla; Tomirotti, Massimo; Crespi, Alice; Mattea, Enrico; Brunetti, Michele; Maugeri, Maurizio

    2017-04-01

    A new time series of daily runoff reconstructed at the inflow in the Como Lake in the Italian Alps is presented. The time series covers a 170 years time period and includes the two largest floods ever recorded for the region: the 1868 and 1987 ones. Statistics of annual maxima show a decrease which is not statistically significant and a decrease of annual runoff which is statistically significant, instead. To investigate the possible reasons of such changes monthly temperature and precipitation are analysed. Decrease of runoff peaks can be justified by the increase of reservoir storage volumes. Evapotranspiration indexes based on monthly temperature indicate an increase of evapotranspiration losses as a possible cause of runoff decrease. Secular precipitation series for the Adda basin are then computed by a methodology projecting observational data onto a high-resolution grid (30-arc-second, DEM GTOPO30). It is based on the assumption that the spatio-temporal behaviour of a meteorological variable over a given area can be described by superimposing two fields: the climatological normals over a reference period, i.e. the climatologies, and the departure from them, i.e. the anomalies. The two fields can be reconstructed independently and are based on different datasets. To compute the precipitation climatologies all the available stations within the Adda basin are considered while, for the anomalies, only the longest and the most homogeneous records are selected. To this aim, a great effort was made to extend these series to the past as much as possible, also by digitising the historical records available from the hardcopy archives. The climatological values at each DEM cell of the Adda basin are obtained by a local weighted linear regression of precipitation versus elevation (LWLR) taking into account the closest stations with similar geographical characteristics to those of the cell itself. The anomaly field is obtained by a weighted average of the anomalies of

  18. [Tolerance and metabolic results of long-term administration of a mixture of saturated triglycerides by recto-colic route in rabbits].

    PubMed

    Dorier, A; Perret, J P; Bacques, C

    1976-01-01

    Rabbit's and Dog's colonic absorption of triglycerides is shown in previous works. Further, we are studying the possibility to use the rectal route for nutritive substances. This way remains now poorly used and an exceptional therapeutic. However, bringing triglycerides in adequate state would be an energetic, supply, all the more as it is very difficult to provide potent caloric source in parenteral nutrition. This is why we investigate, on the Rabbit, the issues of chronic administration of glycerides by rectal route, on caloric balance and on a biochemical view to seek for in lipid composition of tissues the print of lipids administrated by transanal way. The animals are individually housed in metabolism units feeding a standard diet and drinking ad libitum. The treated subjects are given by transanal way, twice a day, for eight weeds, a sum of 1 g/kg of medium chain triglycerides. The metabolic balance-sheet is daily drawn. The clinic balance-sheet is set on the end, by biological controls to explore the hepatic and renal function (prothrombine ratio, transaminases (SGOT, SGPT), ornithine, carbamyl transferase (OCT), urea, total proteins ratio and electrolyte imbalance. We measure also the concentration of total lipids plasma and tissue (liver, kidney, heart, lungs, perirenal adipose tissue). The triglyceride composition and fatty acid composition of different lipids fractions of control and treated subjects are analyzed by gas-liquid chromatography. The animals support perfectly, without damage, a chronic and massive (1 g/kg/each day) administration of medium chain triglycerides by rectal route. The growth of treated subjects is normal. On the opposite, they adjust their alimentary consumption with the caloric charge of the diet, this is the reason why the reduction is about 12p. 100 with respect to the control animals. The coli-rectal administration of saturated glycerides produces at middle end only qualitative variations of lipids extracts. They essentially

  19. Acute and long-term effects of once-daily oral bromocriptine and a new long-acting non-ergot dopamine agonist, quinagolide, in the treatment of hyperprolactinemia: a double-blind study.

    PubMed

    Verhelst, J A; Froud, A L; Touzel, R; Wass, J A; Besser, G M; Grossman, A B

    1991-10-01

    Quinagolide (CV 205-502, Sandoz), an octahydrobenzo (g) quinoline, is a new non-ergot dopamine agonist which has specific D2 receptor activity and a long half-life, making it suitable for once-daily treatment. Recent uncontrolled reports have suggested that quinagolide may be successfully used for the clinical management of hyperprolactinemia with fewer adverse reactions than bromocriptine. This study is the first to compare quinagolide in a double-blind manner with bromocriptine, given only once-daily instead of the usual multidose regimen. In the first phase we compared, in 7 hyperprolactinemic patients, the effects over 24 h of a single oral dose of 0.05 mg quinagolide with 2.5 mg bromocriptine. Compared with placebo, both bromocriptine and quinagolide showed potent PRL-inhibiting and GH-releasing effects, with comparable effects at 24 h; no significant changes were observed in TSH, LH, FSH or cortisol. Twelve hyperprolactinemic patients were then randomized to receive either once-daily bromocriptine or quinagolide in incremental doses for a period of six months. Both drugs were found to be equally effective, and no differences were seen either in adverse reactions or PRL levels during repeated diurnal sampling. We therefore conclude that quinagolide and bromocriptine are therapeutically equivalent in long-term use, and both are equally effective when given once a day. However, some patients intolerant of bromocriptine may respond better to quinagolide, and vice versa.

  20. Long-term sustained-released in situ gels of a water-insoluble drug amphotericin B for mycotic arthritis intra-articular administration: preparation, in vitro and in vivo evaluation.

    PubMed

    Shan-Bin, Guo; Yue, Tian; Ling-Yan, Jian

    2015-04-01

    Amphotericin B (AMB) was often used in intra-articular injection administration for fungal arthritis, because it could often bring a satisfactory therapeutic efficacy and a minimum systemic toxic side effect. However, because of the multiple operations and the frequent injections, the compliance of the patients was bad. Therefore, to develop a long-term sustained-released preparation of AMB for mycotic arthritis intra-articular administration is of great significance. The purpose of present study was to develop a long-term sustained-released in situ gel of a water-insoluble drug AMB for mycotic arthritis intra-articular administration. Based on the evaluations of the in vitro properties of the formulations, the formulation containing 10% (w/w) ethanol, 15% (w/w) PG, 0.75% (w/w) HA, 5% (w/w) purified soybean oil, 0.03% (w/w) α-tocopherol, 15% (w/w) water and 55% (w/w) glyceryl monooleate was selected as a suitable intra-articular injectable in situ gel drug delivery system for water-insoluble drug AMB. Furthermore, the results of the in vivo study on rabbits showed that the selected formulation was a safe and effective long-term sustained-released intra-articular injectable AMB preparation. Therefore, the presented in situ AMB gel could reduce the frequency of the administration in the AMB treatment of fungal arthritis, and then would get a good patient compliance.

  1. Protection against cognitive deficits and markers of neurodegeneration by long-term oral administration of melatonin in a transgenic model of Alzheimer disease.

    PubMed

    Olcese, James M; Cao, Chuanhai; Mori, Takashi; Mamcarz, Malgorzata B; Maxwell, Anne; Runfeldt, Melissa J; Wang, Li; Zhang, Chi; Lin, Xiaoyang; Zhang, Guixin; Arendash, Gary W

    2009-08-01

    The neurohormone melatonin has been reported to exert anti-beta-amyloid aggregation, antioxidant, and anti-inflammatory actions in various in vitro and animal models. To comprehensively determine the potential for long-term melatonin treatment to protect Alzheimer's transgenic mice against cognitive impairment and development of beta-amyloid (Abeta) neuropathology, we administered melatonin (100 mg/L drinking water) to APP + PS1 double transgenic (Tg) mice from 2-2.5 months of age to their killing at age 7.5 months. A comprehensive behavioral battery administered during the final 6 weeks of treatment revealed that Tg mice given melatonin were protected from cognitive impairment in a variety of tasks of working memory, spatial reference learning/memory, and basic mnemonic function; Tg control mice remained impaired in all of these cognitive tasks/domains. Immunoreactive Abeta deposition was significantly reduced in hippocampus (43%) and entorhinal cortex (37%) of melatonin-treated Tg mice. Although soluble and oligomeric forms of Abeta1-40 and 1-42 were unchanged in the hippocampus and cortex of the same melatonin-treated Tg mice, their plasma Abeta levels were elevated. These Abeta results, together with our concurrent demonstration that melatonin suppresses Abeta aggregation in brain homogenates, are consistent with a melatonin-facilitated removal of Abeta from the brain. Inflammatory cytokines such as tumor necrosis factor (TNF)-alpha were decreased in hippocampus (but not plasma) of Tg+ melatonin mice. Finally, the cortical mRNA expression of three antioxidant enzymes (SOD-1, glutathione peroxidase, and catalase) was significantly reduced to non-Tg levels by long-term melatonin treatment in Tg mice. Thus, melatonin's cognitive benefits could involve its anti-Abeta aggregation, anti-inflammatory, and/or antioxidant properties. Our findings provide support for long-term melatonin therapy as a primary or complementary strategy for abating the progression of

  2. Induction of testicular damage by daily methamphetamine administration in rats.

    PubMed

    Lin, Ji-Fan; Lin, Yi-Hsuan; Liao, Po-Cheng; Lin, Yi-Chia; Tsai, Te-Fu; Chou, Kuang-Yu; Chen, Hung-En; Tsai, Shiow-Chwen; Hwang, Thomas I-Sheng

    2014-02-28

    Methamphetamine (METH)-induced brain damage and apoptosis within the central nervous system are well documented. This study was conducted to investigate the toxic effects of daily METH administration on the testes in a rat model. Male Sprague-Dawley rats (5 weeks old, ~100 g, n = 64) were divided into two groups and treated with vehicle (saline, control) or METH (10 mg/kg) for 15, 30, 60 and 90 days. The results showed that daily administration of METH decreased the body, testicular and epididymis weights as well as the serum levels of total testosterone. The increased apoptotic index (Bad/Bcl2 expression ratio) and levels of cleaved caspase-3 indicated that apoptosis had occurred in the testes of the METH-treated rats. The oxidative stress levels increased as the reduced and oxidized glutathione (GSH/GSSG) ratio decreased. The overall sperm counts decreased at 15 and 90 days, where- as morphologically abnormal sperm counts increased at 30, 60 and 90 days in the METH-treated rats. This study demonstrates that daily exposure to METH significantly reduced the number and quality of sperm in rats. The underlying pathophysiological mechanisms likely include the reduction of serum testosterone levels and the increase of oxidative stress and apoptosis in the rat testes.

  3. Long-term oral administration of glucosamine or chondroitin sulfate reduces destruction of cartilage and up-regulation of MMP-3 mRNA in a model of spontaneous osteoarthritis in Hartley guinea pigs.

    PubMed

    Taniguchi, Shin; Ryu, Junnosuke; Seki, Masayuki; Sumino, Takanobu; Tokuhashi, Yasuaki; Esumi, Mariko

    2012-05-01

    Histological and molecular changes were examined to investigate the effects of long-term administration of glucosamine (GlcN) and chondroitin sulfate (CS) in a model of spontaneous osteoarthritis (OA) in Hartley guinea pigs. Three groups of female 3-week-old Hartley guinea pigs received GlcN, CS, and neither agent, respectively. Five animals in each group were sacrificed at 8, 12, and 18 months of age. At 8 months of age, Hartley guinea pigs had severe degeneration of knee joint cartilage, chondrocyte apoptosis, marked reduction of tissue total RNA, decreases of aggrecan and collagen type 2 mRNAs, and increases in MMP-3 and MMP-8 mRNAs. Long-term administration of GlcN and CS reduced cartilage degeneration at 8 months of age. The marked loss of total RNA and the increase in MMP-3 mRNA were also inhibited by GlcN and CS. Thus, long-term oral administration of GlcN or CS inhibits OA progression, maintains total RNA and down-regulates MMP-3 mRNA in a spontaneous OA model in Hartley guinea pigs.

  4. Characteristics of long-term variation in the amlitude of the geomagnetic solar quiet (Sq) daily variation using the Inter-university Upper atmosphere Gobal Observation NETwork (IUGONET) data analysis system

    NASA Astrophysics Data System (ADS)

    Shinbori, A.; Koyama, Y.; Nose, M.; Hori, T.; Otsuka, Y.; Yatagai, A. I.

    2014-12-01

    Characteristics of long-term variation in the amplitude of solar quiet geomagnetic field daily variation (Sq) have been investigated using 1-hour geomagnetic field data obtained from 69 geomagnetic stations in a period of 1947-2013. In the present data analysis, we took advantage of the IUGONET data analysis system. The Sq amplitude clearly showed a 10-12 year solar activity dependence and it tended to enhance during each solar maximum. During the minimum of solar cycle 23/24 in 2008-2009, the Sq amplitude became the smallest in the investigated period. The relationship between the solar F10.7 index and Sq amplitude is approximately linear but 64 percent of geomagnetic stations show a weak nonlinear dependence on the solar F10.7 index. In order to remove the effect of solar activity seen in the long-term variation of the Sq amplitude, we calculated a linear or second order fitting curve between the solar F10.7 index and Sq amplitude during 1947-2013, and examined the residual Sq amplitude, which is defined as the deviation from the fitting curve. As a result, a majority of the trends in the residual Sq amplitude that passed through a trend test showed a negative value in a wide region. This tendency was relatively strong in Europe, India, the eastern part of Canada, and New Zealand. The relationship between the magnetic field intensity and residual Sq amplitude showed an anti-correlation for about 71 percent of geomagnetic stations. On the other hand, the residual Sq amplitude in the equatorial station (Addis Ababa) was anti-correlated with the absolute value of the magnetic field inclination. This implies the movement of the equatorial electrojet due to the secular variation of the ambient magnetic field.

  5. Long-Term Once-Daily Tiotropium Respimat® Is Well Tolerated and Maintains Efficacy over 52 Weeks in Patients with Symptomatic Asthma in Japan: A Randomised, Placebo-Controlled Study

    PubMed Central

    Ohta, Ken; Ichinose, Masakazu; Tohda, Yuji; Engel, Michael; Moroni-Zentgraf, Petra; Kunimitsu, Satoko; Sakamoto, Wataru; Adachi, Mitsuru

    2015-01-01

    Background This study assessed the long-term safety and efficacy of tiotropium Respimat, a long-acting inhaled anticholinergic bronchodilator, in asthma, added on to inhaled corticosteroids (ICS) with or without long-acting β2-agonist (LABA). Methods 285 patients with symptomatic asthma, despite treatment with ICS±LABA, were randomised 2:2:1 to once-daily tiotropium 5 μg, tiotropium 2.5 μg or placebo for 52 weeks (via the Respimat SoftMist inhaler) added on to ICS±LABA, in a double-blind, placebo-controlled, parallel-group study (NCT01340209). Primary objective: to describe the long-term safety profile of tiotropium. Secondary end points included: trough forced expiratory volume in 1 second (FEV1) response; peak expiratory flow rate (PEFR) response; seven-question Asthma Control Questionnaire (ACQ-7) score. Results At Week 52, adverse-event (AE) rates with tiotropium 5 μg, 2.5 μg and placebo were 88.6%, 86.8% and 89.5%, respectively. Commonly reported AEs with tiotropium 5 μg, 2.5 μg and placebo were nasopharyngitis (48.2%, 44.7%, 42.1%), asthma (28.9%, 29.8%, 38.6%), decreased PEFR (15.8%, 7.9%, 21.1%), bronchitis (9.6%, 13.2%, 7.0%), pharyngitis (7.9%, 13.2%, 3.5%) and gastroenteritis (10.5%, 3.5%, 5.3%). In the tiotropium 5 μg, 2.5 μg and placebo groups, 8.8%, 5.3% and 5.3% of patients reported drug-related AEs; 3.5%, 3.5% and 15.8% reported serious AEs. Asthma worsening was the only serious AE reported in more than one patient. At Week 52, adjusted mean trough FEV1 and trough PEFR responses were significantly higher with tiotropium 5 μg (but not 2.5 μg) versus placebo. ACQ-7 responder rates were higher with tiotropium 5 μg and 2.5 μg versus placebo at Week 24. Conclusions The long-term tiotropium Respimat safety profile was comparable with that of placebo Respimat, and associated with mild to moderate, non-serious AEs in patients with symptomatic asthma despite ICS±LABA therapy. Compared with placebo, tiotropium 5 μg, but not 2.5

  6. Effects of long-term testosterone administration on cognition in older men with low or low-to-normal testosterone concentrations: a prespecified secondary analysis of data from the randomised, double-blind, placebo-controlled TEAAM trial.

    PubMed

    Huang, Grace; Wharton, Whitney; Bhasin, Shalender; Harman, S Mitchell; Pencina, Karol M; Tsitouras, Panayiotis; Li, Zhuoying; Hally, Kathleen A; Asthana, Sanjay; Storer, Thomas W; Basaria, Shehzad

    2016-08-01

    The effects of testosterone on cognitive function in older men are incompletely understood. We aimed to establish the effects of long-term testosterone administration on multiple domains of cognitive function in older men with low or low-to-normal testosterone concentrations. We did the randomised, double-blind, placebo-controlled, parallel-group TEAAM trial at three medical centres in Boston, Phoenix, and Los Angeles, USA. Men aged 60 years and older with low or low-to-normal testosterone concentrations (3·47-13·9 nmol/L, or free testosterone <173 pmol/L) were randomly assigned (1:1), via computer-generated randomisation, to receive either 7·5 g of 1% testosterone gel or placebo gel daily for 3 years. Randomisation was stratified by age (60-75 years vs >75 years) and study site. The testosterone dose was adjusted to achieve concentrations of 17·3-31·2 nmol/L. Participants and all study personnel were masked to treatment allocation. Multiple domains of cognitive function were assessed as prespecified secondary outcomes by use of standardised tests at baseline and months 6, 18, and 36. We did analyses by intention to treat (in men who had baseline assessments of cognitive function) and per protocol (restricted to participants who completed the study drug and had both baseline and 36 month assessments of cognitive function). The TEAAM trial is registered with ClinicalTrials.gov, number NCT00287586. Between Sept 1, 2004, and Feb 12, 2009, we randomly assigned 308 participants to receive either testosterone (n=156) or placebo (n=152). 280 men had baseline cognitive assessments (n=140 per group). Mean follow-up time was 29·0 months (SD 11·5) in the testosterone group and 31·1 months (9·5) in the placebo group. The last participant completed the study on May 11, 2012. In the testosterone group, mean concentrations of serum total testosterone increased from 10·6 nmol/L (SD 2·2) to 19·7 nmol/L (9·2) and free testosterone concentrations increased from 222 pmol

  7. Long-term fixed income market structure

    NASA Astrophysics Data System (ADS)

    Grilli, Luca

    2004-02-01

    Long-term fixed income market securities present a strong positive correlation in daily returns. By using a metrical approach and considering “modified” time series, I show how it is possible to show a more complex structure which depends strictly on the maturity date.

  8. Long-term testing

    SciTech Connect

    Ferber, M.; Graves, G.A. Jr.

    1994-12-31

    Land-based gas turbines are significantly different from automotive gas turbines in that they are designed to operate for 50,000 h or greater (compared to 5,000--10,000 h). The primary goal of this research is to determine the long-term survivability of ceramic materials for industrial gas turbine applications. Research activities in this program focus on the evaluation of the static tensile creep and stress rupture (SR) behavior of three commercially available structural ceramics which have been identified by the gas turbine manufacturers as leading candidates for use in industrial gas turbines. For each material investigated, a minimum of three temperatures and four stresses will be used to establish the stress and temperature sensitivities of the creep and SR behavior. Because existing data for many candidate structural ceramics are limited to testing times less than 2,000 h, this program will focus on extending these data to times on the order of 10,000 h, which represents the lower limit of operating time anticipated for ceramic blades and vanes in gas turbine engines. A secondary goal of the program will be to investigate the possibility of enhancing life prediction estimates by combining interrupted tensile SR tests and tensile dynamic fatigue tests in which tensile strength is measured as a function of stressing rate. The third goal of this program will be to investigate the effects of water vapor upon the SR behavior of the three structural ceramics chosen for the static tensile studies by measuring the flexural strength as a function of stressing rate at three temperatures.

  9. Long Term Outcomes after Pediatric Liver Transplantation

    PubMed Central

    2013-01-01

    Long term outcomes after liver transplantation are major determinants of quality of life and of the value of this heroic treatment. As short term outcomes are excellent, our community is turning to take a harder look at long term outcomes. The purpose of this paper is to review these outcomes, and highlight proposed treatments, as well as pressing topics needing to be studied. A systemic review of the English literature was carried in PubMed, covering all papers addressing long term outcomes in pediatric liver transplant from 2000-2013. Late outcomes after pediatric liver transplant affect the liver graft in the form of chronic liver dysfunction. The causes include rejection particularly humoral rejection, but also de novo autoimmune hepatitis, and recurrent disease. The metabolic syndrome is a major factor in long term cardiovascular complication risk. Secondary infections, kidney dysfunction and malignancy remain a reality of those patients. There is growing evidence of late cognitive and executive function delays affecting daily life productivity as well as likely adherence. Finally, despite a good health status, quality of life measures are comparable to those of children with chronic diseases. Long term outcomes are the new frontier in pediatric liver transplantation. Much is needed to improve graft survival, but also to avoid systemic morbidities from long term immunosuppression. Quality of life is a new inclusive measure that will require interventions and innovative approaches respectful not only on the patients but also of their social circle. PMID:24511516

  10. Nonresected Non-Small-Cell Lung Cancer in Stages I Through IIIB: Accelerated, Twice-Daily, High-Dose Radiotherapy-A Prospective Phase I/II Trial With Long-Term Follow-Up

    SciTech Connect

    Wurstbauer, Karl; Deutschmann, Heinz; Kopp, Peter; Kranzinger, Manfred; Merz, Florian; Nairz, Olaf; Studnicka, Michael; Sedlmayer, Felix

    2010-08-01

    Purpose: Our purpose was to investigate the tolerability of accelerated, twice-daily, high-dose radiotherapy. The secondary endpoints were survival and locoregional tumor control. Methods and Materials: Thirty consecutive patients with histologically/cytologically proven non-small-cell lung cancer were enrolled. Tumor Stage I, II, IIIA, and IIIB was found in 7, 3, 12, and 8 patients, respectively. We applied a median of 84.6 Gy (range, 75.6-90.0 Gy) to the primary tumors, 63.0 Gy (range, 59.4-72.0 Gy) to lymph nodes, and 45 Gy to nodes electively (within a region of about 6 cm cranial to macroscopically involved sites). Fractional doses of 1.8 Gy twice daily, with an interval of 11 hours, were given, resulting in a median treatment time of 35 days. In the majority of patients the conformal target-splitting technique was used. In 19 patients (63%) two cycles of induction chemotherapy were given. The median follow-up time of survivors is 72 months (range, 62-74 months). Results: We found Grade 1, 2 and 3 acute esophageal toxicity in 11 patients (37%), 2 patients (7%), and 2 patients (7%), respectively. Grade 2 acute pneumonitis was seen in 2 patients (7%). No late toxicity greater than Grade 1 was observed. The actual overall survival rates at 2 and 5 years are 63% and 23%, respectively; the median overall survival, 27.7 months. In 9 patients a local failure occurred, 7 of them presenting initially with an atelectasis without availability of 18-fluorodeoxyglucose-positron emission tomography staging at that time. In 4 patients recurrence occurred regionally. Conclusions: This Phase I/II trial with long-term follow-up shows low toxicity with promising results for survival and locoregional tumor control.

  11. Long-term administration of cocaine or serotonin reuptake inhibitors results in anatomical and neurochemical changes in noradrenergic, dopaminergic, and serotonin pathways.

    PubMed

    Horne, Malcolm K; Lee, Joohyung; Chen, Feng; Lanning, Katherine; Tomas, Doris; Lawrence, Andrew J

    2008-08-01

    The catechol and indole pathways are important components underlying plasticity in the frontal cortex and basal ganglia. This study demonstrates that administering rats either cocaine or a selective serotonin (or 5-hydroxytryptamine; 5-HT) reuptake inhibitor (SSRI) for 16 weeks results in reduced density of dopaminergic and noradrenergic terminals in the striatum and olfactory bulb, respectively, reflecting pruning of the terminal arbor of ventral midbrain dopaminergic and locus coeruleus noradrenergic neurones. In the striatum of cocaine-treated animals, basal dopamine levels, as well as cocaine-induced dopamine release, is diminished compared with controls. In contrast, serotonergic fibers, projecting from the raphe, sprout and have increased terminal density in the lateral septal nucleus and frontal cortex, following long-term cocaine or SSRI treatment. This is associated with elevated basal 5-HT and enhanced cocaine-induced 5-HT release in the frontal cortex. The anatomical and neurochemical changes in serotonergic fibers following cocaine or SSRI treatment may be explained by attenuated 5-HT(1A) autoreceptor function in the raphe. This study demonstrates extensive plasticity in the morphology and neurochemistry of the catechol and indole pathways that contribute to drug-induced plasticity of the corticostriatal (and other) projections. Moreover, our data suggest that drug-induced plastic adaptation is anatomically widespread and consequently, likely to have multiple and complex consequences.

  12. Circulating fetuin-A levels are not affected by short and long-term energy deprivation and/or by leptin administration.

    PubMed

    Hwang, Janice J; Thakkar, Bindiya; Chamberland, John P; Mantzoros, Christos S

    2014-06-01

    Fetuin-A may mediate cross-talk between the liver and adipose tissue. We studied the physiologic regulation of fetuin-A and explored its potential regulation by leptin. Fetuin-A levels were measured in three interventional studies as well as in in vitro experiments. Study 1: 15 lean subjects received placebo or physiologic replacement-dose recombinant human leptin (metreleptin) following short term complete caloric deprivation to induce severe hypoleptinemia; Study 2: 7 women with relative leptin deficiency due to strenuous exercise or low weight received 3 months of metreleptin; Study 3: 17 women with relative leptin deficiency were randomized to receive metreleptin or placebo over 9 months. In study 4 human hepatoma Hep G2 cells were treated with leptin. Fetuin-A mRNA expression and secretion were measured. Complete caloric deprivation significantly decreased leptin but had no effect on fetuin-A levels. Normalizing leptin levels with metreleptin in hypoleptinemic subjects had no effect on circulating fetuin-A levels. Leptin treatment had no effect on fetuin-A mRNA expression and secretion in vitro. Circulating fetuin-A levels are not affected by short and long-term energy deprivation. Furthermore, both in vivo and in vitro experiments confirm that fetuin-A is not regulated by leptin. Published by Elsevier Inc.

  13. Safety and comfort of long-term continuous combined transdermal estrogen and intrauterine levonorgestrel administration for postmenopausal hormone substitution - a review.

    PubMed

    Wildemeersch, D

    2016-08-01

    To review the endometrial safety and patient acceptability of long-term use of continuous transdermal estrogen substitution combined with intrauterine release of levonorgestrel (LNG) in postmenopausal women. One-hundred and fifty-three women who utilized the regimen for 2 IUD cycles were followed-up for a period of 10 years. Histology of the endometrium was evaluated at the end of this period to assess endometrial safety and the acceptability of the method was assessed based on the replacement rate of the LNG-IUS and continuation of ET. The regimen, administered over a 10-year period, was very well tolerated and the IUD was retained well and no expulsions occurred. The dominant endometrial histologic picture was that of inactive endometrium characterized by glandular atrophy and stroma decidualization (Kurman classification 5b). No cases of endometrial hyperplasia were found. The low systemic absorption of LNG could be desirable, thus allowing for maximization of the beneficial effects of ET on organ tissues (e.g. cardiovascular tissues and breast). Repeat LNG-IUS is associated with high patient satisfaction. If started before the age of 60, this regimen could be advised for lifelong prevention of cardiovascular disease and other prevention measures. The LNG-IUS was shown to effectively oppose the secondary effects of systemic estrogen on the endometrium tissue resulting in strong suppression during the entire period of EPT.

  14. Short- and long-term distribution and toxicity of gold nanoparticles in the rat after a single-dose intravenous administration.

    PubMed

    Fraga, Sónia; Brandão, Ana; Soares, Maria Elisa; Morais, Tiago; Duarte, José Alberto; Pereira, Laura; Soares, Leonor; Neves, Cristina; Pereira, Eulália; Bastos, Maria de Lourdes; Carmo, Helena

    2014-11-01

    Surface chemistry plays an important role in gold nanoparticles (AuNPs) stability and biocompatibility, which are crucial for their implementation into the clinical setting. We evaluated short- (30 min) and long-term (28 days) biodistribution and toxicity of ~20 nm citrate- and pentapeptide CALNN-coated AuNPs after a single intravenous injection in rats. The pattern of AuNPs distribution in Cit- and CALNN-AuNPs-injected rats was very similar in the assessed time-points. Both AuNPs were quickly removed from the bloodstream and preferentially accumulated in the liver. At 28 days liver remained the main accumulation site but at significantly lower levels compared to those found at 30 min. Spleen atrophy and hematological findings compatible with mild anemia were observed in CALNN-AuNPs-administered rats. Under our experimental conditions, surface coating had more impact on toxicity rather than on biodistribution of the AuNPs. Improvements in the design of capping peptides need to be done to increase biomedical applicability of peptide-coated AuNPs. The biodistribution and toxicity of ~ 20 nm citrate- and pentapeptide CALNN-coated gold nanoparticles was investigated after a single intravenous injection in rats. Rapid clearance and hepatic accumulation was found at 30-minutes, whereas mild anemia and spleen atrophy was seen 28 days post injection. The authors also concluded that the toxicity was related to the capping proteins as opposed to the biodistribution of the particles, providing important suggestion for future design of gold nanoparticles. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Therapeutic administration of IL-15 superagonist complex ALT-803 leads to long-term survival and durable antitumor immune response in a murine glioblastoma model.

    PubMed

    Mathios, Dimitrios; Park, Chul-Kee; Marcus, Warren D; Alter, Sarah; Rhode, Peter R; Jeng, Emily K; Wong, Hing C; Pardoll, Drew M; Lim, Michael

    2016-01-01

    Glioblastoma is the most aggressive primary central nervous system malignancy with a poor prognosis in patients. Despite the need for better treatments against glioblastoma, very little progress has been made in discovering new therapies that exhibit superior survival benefit than the standard of care. Immunotherapy has been shown to be a promising treatment modality that could help improve clinical outcomes of glioblastoma patients by assisting the immune system to overcome the immunosuppressive tumor environment. Interleukin-15 (IL-15), a cytokine shown to activate several effector components of the immune system, may serve as an excellent immunotherapeutic candidate for the treatment of glioblastoma. Thus, we evaluated the efficacy of an IL-15 superagonist complex (IL-15N72D:IL-15RαSu-Fc; also known as ALT-803) in a murine GL261-luc glioblastoma model. We show that ALT-803, as a single treatment as well as in combination with anti-PD-1 antibody or stereotactic radiosurgery, exhibits a robust antitumor immune response resulting in a prolonged survival including complete remission in tumor bearing mice. In addition, ALT-803 treatment results in long-term immune memory against glioblastoma tumor rechallenge. Flow cytometric analysis of tumor infiltrating immune cells shows that ALT-803 leads to increased percentage of CD8+-cell infiltration, but not the NK cells, and IFN-γ production into the tumor microenvironment. Cell depletion studies, in accordance with the flow cytometric results, show that the ALT-803 therapeutic effect is dependent on CD4+ and CD8+ cells. These results provide a rationale for evaluating the therapeutic activity of ALT-803 against glioblastoma in the clinical setting.

  16. Identifying and overcoming implementation challenges: Experience of 59 noninstitutional long-term services and support pilot programs in the Veterans Health Administration.

    PubMed

    Sullivan, Jennifer L; Adjognon, Omonyêlé L; Engle, Ryann L; Shin, Marlena H; Afable, Melissa K; Rudin, Whitney; White, Bert; Shay, Kenneth; Lukas, Carol VanDeusen

    2017-01-25

    From 2010 to 2013, the Department of Veterans Affairs (VA) funded a large pilot initiative to implement noninstitutional long-term services and supports (LTSS) programs to support aging Veterans. Our team evaluated implementation of 59 VA noninstitutional LTSS programs. The specific objectives of this study are to (a) examine the challenges influencing program implementation comparing active sites that remained open and inactive sites that closed during the funding period and (b) identify ways that active sites overcame the challenges they experienced. Key informant semistructured interviews occurred between 2011 and 2013. We conducted 217 telephone interviews over four time points. Content analysis was used to identify emergent themes. The study team met regularly to define each challenge, review all codes, and discuss discrepancies. For each follow-up interview with the sites, the list of established challenges was used as a priori themes. Emergent data were also coded. The challenges affecting implementation included human resources and staffing issues, infrastructure, resources allocation and geography, referrals and marketing, leadership support, and team dynamics and processes. Programs were able to overcome challenges by communicating with team members and other areas in the organization, utilizing information technology solutions, creative use of staff and flexible schedules, and obtaining additional resources. This study highlights several common challenges programs can address during the program implementation. The most often mentioned strategy was effective communication. Strategies also targeted several components of the organization including organizational functions and processes (e.g., importance of coordination within a team and across disciplines to provide good care), infrastructure (e.g., information technology and human resources), and program fit with priorities in the organization (e.g., leadership support). Anticipating potential pitfalls of

  17. Co-administration of walnut (Juglans regia) prevents systemic hypertension induced by long-term use of dexamethasone: a promising strategy for steroid consumers.

    PubMed

    Joukar, Siyavash; Ebrahimi, Sahar; Khazaei, Majid; Bashiri, Alireza; Shakibi, Mohammad Reza; Naderi, Vida; Shahouzehi, Beydolah; Alasvand, Masoud

    2017-12-01

    The long-term consumption of glucocorticoids (GCs) may induce serious adverse effects such as hypertension. There is sufficient evidence related to the benefit of walnuts on the cardiovascular system. This study assesses the effect of methanol extract of walnut [Juglans regia L. (Juglandaceae)] on dexamethasone-induced hypertension and the possible mechanisms in Wistar rats. Animals were randomized into control, kernel extract (100 and 200 mg/kg/d, orally), dexamethasone (0.03 mg/kg/d, subcutaneously), dexamethasone + kernel (100 and 200 mg/kg/d, separately), and dexamethasone + captopril (25 mg/kg/d, orally) groups. Animals were treated with water, kernel extract or captopril by gavage 4 d before and during 11 d of saline or dexamethasone treatment. On the 16th day, blood pressure (BP) was recorded and blood samples were collected to measure nitric oxide (NO). Animal hearts were frozen for measurement of malondialdehyde (MDA) and glutathione peroxidase (GPX). Dexamethasone increased the diastolic BP and MDA/GPX ratio in comparison with control group (128 ± 7 vs. 105 ± 3 mmHg, p < 0.05 and 0.2 ± 0.046 vs. 0.08 ± 0.02, p < 0.05). Combination of dexamethasone and walnut (200 mg/kg) prevented the dexamethasone-induced diastolic hypertension (109 ± 3 vs. 128 ± 7 mmHg; p < 0.05), increased the GPX level (14.8 ± 1.46 vs. 5.1 ± 0.64 unit/mg, p < 0.05), reduced the MDA/GPX ratio (0.16 ± 0.015 vs. 0.2 ± 0.046) and improved serum NO level. Similar to captopril, walnut extract normalized dexamethasone-induced hypertension. A part of this beneficial effect apparently involves maintaining balance of the redox system and NO production.

  18. Long-Term, Open-Label, Safety Study of Edivoxetine 12 to 18 mg Once Daily as Adjunctive Treatment for Patients With Major Depressive Disorder Who Are Partial Responders to Selective Serotonin Reuptake Inhibitor Treatment.

    PubMed

    Ball, Susan G; Atkinson, Sarah; Sparks, JonDavid; Bangs, Mark; Goldberger, Celine; Dubé, Sanjay

    2015-06-01

    Long-term safety, tolerability, and efficacy of adjunctive edivoxetine hydrochloride (hereafter edivoxetine), a highly selective and potent norepinephrine reuptake inhibitor, was assessed in patients with major depressive disorder (MDD) experiencing partial response to selective serotonin reuptake inhibitor treatment. Data are from a multicenter, 54-week, open-label trial of adjunctive edivoxetine 12 to 18 mg once daily in patients with MDD who had experienced partial response by history to 6 or more weeks of current selective serotonin reuptake inhibitor therapy and who had a 17-item GRID Hamilton Rating Scale for Depression total score 16 or higher at study entry. Safety measures included discontinuation rate, treatment-emergent adverse events, serious adverse events, and vital signs. Efficacy measures included the Montgomery-Åsberg Depression Rating Scale. Of 608 patients, 328 (54%) completed the open-label adjunctive treatment. Study discontinuation due to adverse events occurred in 17.0%, and there were 13 serious adverse events (1 death). Treatment-emergent adverse events 5% or higher were nausea, hyperhidrosis, constipation, headache, dry mouth, dizziness, vomiting, insomnia, and upper respiratory tract infection. Mean increases were observed in systolic blood pressure (range, 0.0-2.3 mm Hg), diastolic blood pressure (range, 1.9-3.3 mm Hg), and pulse (range, 5.9-8.4 beats per minute). Mean improvements on the Montgomery-Åsberg Depression Rating Scale (-17.0) were observed from baseline to week 54. The safety profile from this study provides an overview of outcomes associated with edivoxetine and norepinephrine reuptake inhibition as an adjunctive treatment in patients with MDD who were treated up to 1 year.

  19. Long-term environmental stewardship.

    SciTech Connect

    Nagy, Michael David

    2010-08-01

    The purpose of this Supplemental Information Source Document is to effectively describe Long-Term Environmental Stewardship (LTES) at Sandia National Laboratories/New Mexico (SNL/NM). More specifically, this document describes the LTES and Long-Term Stewardship (LTS) Programs, distinguishes between the LTES and LTS Programs, and summarizes the current status of the Environmental Restoration (ER) Project.

  20. Long-term urethral catheterisation.

    PubMed

    Turner, Bruce; Dickens, Nicola

    This article discusses long-term urethral catheterisation, focusing on the relevant anatomy and physiology, indications for the procedure, catheter selection and catheter care. It is important that nurses have a good working knowledge of long-term catheterisation as the need for this intervention will increase with the rise in chronic health conditions and the ageing population.

  1. Long-term efficacy and safety of once-daily enoxaparin plus warfarin for the outpatient ambulatory treatment of lower-limb deep vein thrombosis in the TROMBOTEK trial.

    PubMed

    Kurtoglu, Mehmet; Koksoy, Cuneyt; Hasan, Ekim; Akcalı, Yigit; Karabay, Ozalp; Filizcan, Ugur

    2010-11-01

    The present study was designed to evaluate the long-term efficacy and safety of once-daily enoxaparin plus warfarin for the outpatient ambulatory treatment of lower-limb deep venous thrombosis (DVT). A total of 246 patients, comprising 128 men (mean age, 54.28±16.48 years) and 118 women (mean age, 50.11±16.47 years) with symptomatic lower extremity DVT, were included in this open-label, single-arm, multicenter, phase IV clinical trial conducted at 14 centers in Turkey. All patients were administered subcutaneous enoxaparin (1.5 mg/kg, once-daily) until international normalized ratio (INR) levels reached to 2 to 3, followed by oral warfarin (5 mg/d) for at least 3 months and elastic compression stockings (30-40 mm Hg). Clinical signs (leg circumference), symptoms (edema, pain, tenderness), recanalization rates upon duplex ultrasound examination, laboratory findings (D-dimer and INR levels), and postthrombotic syndrome status with CEAP classification were the efficacy parameters evaluated every 3 months during 18 months of follow-up. Safety end points included minor and major bleeding as well as serious adverse events. Ambulatory treatment with enoxaparin plus warfarin significantly reduced physical symptoms, including tenderness, edema, pain (P<.001), and the circumference of the affected leg (P<.001). The leg circumference difference in almost all patients was <1.5 cm at the end of 18 months (P<.001). Recanalization rates for occluded iliofemoral vein were 76.1% at 3 months and 86.5% at 18 months (P<.001). An early and significant decrease obtained in D-dimer levels on day 10 continued to decline significantly until month 6 and remained unchanged afterwards (P<.001). Of four patients diagnosed with major bleeding during oral anticoagulant use, three recovered with conservative treatment (reduction in hemoglobin levels in 2 developed at visit 2 [day 10] and intracranial bleeding in 1 developed at visit 3 [day 30]), and one patient required a hysterectomy after

  2. Presynaptic long-term plasticity

    PubMed Central

    Yang, Ying; Calakos, Nicole

    2013-01-01

    Long-term synaptic plasticity is a major cellular substrate for learning, memory, and behavioral adaptation. Although early examples of long-term synaptic plasticity described a mechanism by which postsynaptic signal transduction was potentiated, it is now apparent that there is a vast array of mechanisms for long-term synaptic plasticity that involve modifications to either or both the presynaptic terminal and postsynaptic site. In this article, we discuss current and evolving approaches to identify presynaptic mechanisms as well as discuss their limitations. We next provide examples of the diverse circuits in which presynaptic forms of long-term synaptic plasticity have been described and discuss the potential contribution this form of plasticity might add to circuit function. Finally, we examine the present evidence for the molecular pathways and cellular events underlying presynaptic long-term synaptic plasticity. PMID:24146648

  3. Long-term cilostazol administration ameliorates memory decline in senescence-accelerated mouse prone 8 (SAMP8) through a dual effect on cAMP and blood-brain barrier.

    PubMed

    Yanai, Shuichi; Toyohara, Jun; Ishiwata, Kiichi; Ito, Hideki; Endo, Shogo

    2017-04-01

    Phosphodiesterases (PDEs), which hydrolyze and inactivate 3', 5'-cyclic adenosine monophosphate (cAMP) and 3', 5'-cyclic guanosine monophosphate (cGMP), play an important role in synaptic plasticity that underlies memory. Recently, several PDE inhibitors were assessed for their possible therapeutic efficacy in treating cognitive disorders. Here, we examined how cilostazol, a selective PDE3 inhibitor, affects brain functions in senescence-accelerated mouse prone 8 (SAMP8), an animal model of age-related cognitive impairment. Long-term administration of cilostazol restored the impaired context-dependent conditioned fear memory of SAMP8 to match that in normal aging control substrain SAMR1. Cilostazol also increased the number of cells containing phosphorylated cAMP-responsive element binding protein (CREB), a downstream component of the cAMP pathway. Finally, cilostazol improves blood-brain barrier (BBB) integrity, demonstrated by reduced extravasation of 2-deoxy-2-(18)F-fluoro-d-glucose and Evans Blue dye in the brains of SAMP8. This improvement in BBB integrity was associated with an increased amount of zona occludens protein 1 (ZO-1) and occludin proteins, components of tight junctions integral to the BBB. The results suggest that long-term administration of cilostazol exerts its beneficial effects on age-related cognitive impairment through a dual mechanism: by enhancing the cAMP system in the brain and by maintaining or improving BBB integrity.

  4. Administration of memantine during ethanol withdrawal in neonatal rats: effects on long-term ethanol-induced motor incoordination and cerebellar Purkinje cell loss.

    PubMed

    Idrus, Nirelia M; McGough, Nancy N H; Riley, Edward P; Thomas, Jennifer D

    2011-02-01

    Alcohol consumption during pregnancy can damage the developing fetus, illustrated by central nervous system dysfunction and deficits in motor and cognitive abilities. Binge drinking has been associated with an increased risk of fetal alcohol spectrum disorders, likely due to increased episodes of ethanol withdrawal. We hypothesized that overactivity of the N-methyl-D-aspartate (NMDA) receptor during ethanol withdrawal leads to excitotoxic cell death in the developing brain. Consistent with this, administration of NMDA receptor antagonists (e.g., MK-801) during withdrawal can attenuate ethanol's teratogenic effects. The aim of this study was to determine whether administration of memantine, an NMDA receptor antagonist, during ethanol withdrawal could effectively attenuate ethanol-related deficits, without the adverse side effects associated with other NMDA receptor antagonists. Sprague-Dawley pups were exposed to 6.0 g/kg ethanol or isocaloric maltose solution via intubation on postnatal day 6, a period of brain development equivalent to a portion of the 3rd trimester. Twenty-four and 36 hours after ethanol, subjects were injected with 0, 10, or 15 mg/kg memantine, totaling doses of 0, 20, or 30 mg/kg. Motor coordination was tested on a parallel bar task and the total number of cerebellar Purkinje cells was estimated using unbiased stereology. Alcohol exposure induced significant parallel bar motor incoordination and reduced Purkinje cell number. Memantine administration significantly attenuated both ethanol-associated motor deficits and cerebellar cell loss in a dose-dependent manner. Memantine was neuroprotective when administered during ethanol withdrawal. These data provide further support that ethanol withdrawal contributes to fetal alcohol spectrum disorders. Copyright © 2010 by the Research Society on Alcoholism.

  5. Effect of long-term administration of arsenic (III) and bromine with and without selenium and iodine supplementation on the element level in the thyroid of rat.

    PubMed

    Kotyzová, Dana; Eybl, Vladislav; Mihaljevic, Martin; Glattre, Eystein

    2005-12-01

    The aim of this study was to evaluate the influence of arsenic and bromine exposure with or without iodine and selenium supplementation on the element level in the thyroid of rats. Four major groups of Wistar female rats were fed with respective diets: group A - standard diet, group B - iodine rich diet (10 mg I/kg food), group C - selenium rich diet (1 mg Se/kg) and group D - iodine and selenium rich diet (as in group B and C). Each group was divided into four subgroups per 7 animals each receiving either NaAsO(2) ip (6.5 mg.kg(-1) twice a week for two weeks and 3.25 mg.kg(-1) for six weeks) or KBr in drinking water (58.8 mg.l(-1)) for 8 weeks or combined administration of both substances. Remaining subgroup served as controls. After 8 weeks thyroid glands were analyzed by ICP-MS for As, Br, Se, and I content. The exposition of rat to arsenic or bromine causes the accumulation of these elements in the thyroid gland ( approximately 18 ppm of As, approximately 90 ppm of Br) and significantly affects iodine and selenium concentration in the thyroid. In iodine and/or selenium supplemented rats the bromine intake into the thyroid was lowered to approximately 50% of the level in unsupplemented animals. Also selenium thyroid level elevated due to KBr administration was lowered by iodine supplementation in the diet. The accumulation of arsenic in the thyroid was not influenced by selenium or iodine supplementation; however, As(III) administration increased iodine thyroid level and suppressed selenium thyroid level in selenium or iodine supplemented group of animals.

  6. Effects of pantoprazole 20 mg in mildgastroesophageal reflux disease: Once-daily treatment in the acute phase, and comparison of on-demand versus continuous treatment in the long term

    PubMed Central

    Janssen, Werner; Meier, Eberhard; Gatz, Gudrun; Pfaffenberger, Bernd

    2005-01-01

    Background: Gastroesophageal reflux disease (GERD) is a chronic disorder,and although effective short-term treatment strategies are known, the rate of relapse within 1 year is as high as 90% despite successful acute treatment. Consequently, most patients with GERD require an effective long-term management strategy to achieve adequate symptom control and maintain mucosal healing. Objective: The present study was undertaken to compare the control ofGERD symptoms during long-term (24-week) treatment with pantoprazole 20 mg used on-demand or continuously in patients with mild GERD after complete relief of acute GERD symptoms. Methods: Patients with endoscopically confirmed Savary/Miller grade 0(normal mucosa) or I (patchy red lesions without white coating or with central white coating) GERD were enrolled in this multinational, multicenter study comprising 2 phases. In the first phase, which was open label, patients were treated with pantoprazole 20 mg QD for 4 weeks. The presence and intensity of the symptoms of heartburn, acid regurgitation, and pain on swallowing were assessed. In the second phase, which was an open-label, 24-week, randomized design, only patients completely free of GERD symptoms after acute treatment were included. During this phase, on-demand treatment with pantoprazole 20 mg was directly compared with continuous treatment. The rate of failure to control GERD symptoms after 24 weeks of treatment was estimated using the Kaplan-Meier method. Subsequently, the difference between treatments (on-demand minus continuous) and its 95% CI were calculated, and the on-demand treatment was tested for noninferiority using a predefined noninferiority margin of 20%. The mean daily symptom loads were compared between the treatment groups using the 1-sided Wilcoxon rank sum test on a 5% α level. The point estimate of the difference was determined using the Hodges-Lehman estimator and the 1-sided 95% CI according to Moses. The number of patients unwilling to

  7. The Effects of Long-Term Chaetomellic Acid A Administration on Renal Function and Oxidative Stress in a Rat Model of Renal Mass Reduction

    PubMed Central

    Nogueira, António; Oliveira, Maria Manuel; Pires, Carlos André; Colaço, Bruno

    2017-01-01

    Purpose. This study aimed to evaluate the effect of chronic treatment with chaetomellic acid A (CAA) on oxidative stress and renal function in a model of renal mass reduction. Methods. Male Wistar rats were subjected to 5/6 nephrectomy (RMR) or sham-operated (SO). One week after surgery, rats have been divided into four experimental groups: RMR: RMR rats without treatment (n = 14); RMR + CAA: RMR rats treated with CAA (n = 13); SO: SO rats without treatment (n = 13); and SO + CAA: SO rats treated with CAA (n = 13). CAA was intraperitoneally administered in a dose of 0.23 µg/Kg three times a week for six months. Results. RMR was accompanied by a significant reduction in catalase and glutathione reductase (GR) activity (p < 0.05) and a decrease in reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio. CAA administration significantly increased catalase and GR activity (p < 0.05) and increased GSH/GSSG ratio, but no significant difference between the treated and nontreated groups was found in this ratio. No significant differences were found between the RMR groups in any of the parameters of renal function. However, CAA administration slightly improves some parameters of renal function. Conclusions. These data suggest that CAA could attenuate 5/6 RMR-induced oxidative stress. PMID:28326323

  8. [The dynamics of behavioral and neuroreceptor effects after acute and long-term noopept administration in C57BL/6 and BALB/c mice].

    PubMed

    Kovalev, G I; Kondrakhin, E A; Salimov, R M; Neznamov, G G

    2014-01-01

    The effect of acute, 7-fold and 14-fold noopept (1 mg/kg/day) administration on the dynamics of anxiolitic and nootropic behavioral effects in cross-maze, as well as their correlations with NMDA- and BDZ-receptor density was studied in inbred mice strains, differing in exploratory and emotional status--C57BL/6 and BALB/c. The dipeptide failed to affect the anxiety and exploration activity in C57BL/6 mice at each of 3 steps of experimental session. In this strain the B(max) values of [3H]-MK-801 and [3H]-Flunitrazepam binding changed only after single administration. In respect to BALB/c mice noopept induced both the anxiolitic and nootropic effects reaching their maximum on 7th day. In BALB/c strain the dynamics of hippocampal NMDA-receptor binding corresponds to the dynamics of exploratory efficacy whereas the dynamics of BDZ-receptors in prefrontal cortex was reciprocally to dynamics of anxiety level.

  9. Long-term administration of PACAP receptor antagonist, PACAP(6-27), impairs glucose tolerance and insulin sensitivity in obese diabetic ob/ob mice.

    PubMed

    Green, Brian D; Irwin, Nigel; Cassidy, Roslyn S; Gault, Victor A; Flatt, Peter R

    2006-09-01

    Pituitary adenylate cyclase-activating peptide (PACAP) is a ubiquitous peptide of the glucagon superfamily that is involved in glucose homeostasis and regulation of insulin secretion. This study employed the PACAP receptor antagonist, PACAP(6-27) to evaluate the role of endogenous PACAP in genetic obesity-related diabetes and related metabolic abnormalities using ob/ob mice. Acute in vivo antagonistic potency of PACAP(6-27) was confirmed in ob/ob mice by blockade of the insulin-releasing action but not hyperglycaemia. In longer-term studies, ob/ob mice were given once daily injections of PACAP(6-27) or vehicle for 14 days. Feeding activity, body weight, basal plasma glucose and plasma insulin concentrations were not significantly affected by chronic PACAP(6-27) treatment. However, PACAP(6-27) treatment impaired glucose tolerance, insulin sensitivity and the glycaemic response to feeding. Plasma glucagon and lipids were unchanged. These observations indicate a role of endogenous PACAP for normal glucose homeostasis, but indicate a minor involvement in the regulation of insulin secretion in ob/ob mice.

  10. 47 CFR 54.303 - Long term support.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... base-level of Long Term Support for 1998, the Administrator shall calculate the difference between the.... (2) To calculate Long Term Support for calendar year 1998, the Administrator shall adjust the base...; and (4) The line port costs in excess of basic analog service pursuant to § 69.130 of this...

  11. 47 CFR 54.303 - Long term support.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... base-level of Long Term Support for 1998, the Administrator shall calculate the difference between the.... (2) To calculate Long Term Support for calendar year 1998, the Administrator shall adjust the base...; and (4) The line port costs in excess of basic analog service pursuant to § 69.130 of this...

  12. [Effect of long-term monosodium glutamate administration on structure and functional state of the stomach and body weight in rats].

    PubMed

    Falalieieva, T M; Kukhars'kyĭ, V M; Berehova, T V

    2010-01-01

    The influence of prolonged administration of monosodium glutamate (MSG) on basal gastric acid secretion, body weight and gastric mucosa in rats was studied. We found that 10-, 20-, 30-days feeding by MSG in doses 15 to 30 mg/kg (equivalent to I and 2 g/person) leads to erosive and ulcerative lesions of the gastric mucosa and an increased secretion of hydrochloric acid and an increased body weight. It is concluded that the stimulating effect of MSG on the basal secretion of hydrochloric acid in the stomach may be implicated in the pathogenesis of a number of acid-dependent diseases. An excessive consumption of MSG can cause a "Chinese Restaurant Syndrome" and gastritis, gastric and duodenal ulcers. Therefore, the maximum dose of MSG should be reconsidered taking into account its influence on the secretory capacity of the stomach. We also conclude that prolonged, excessive and systemic consumption of MSG causes obesity.

  13. Long-term continuous administration of a hydro-ethanolic extract of Synedrella nodiflora (L) Gaertn in male Sprague-Dawley rats: biochemical, haematological and histopathological changes.

    PubMed

    Amoateng, Patrick; Adjei, Samuel; Osei-Safo, Dorcas; Ahedor, Believe; Mahmood, Seidu A; N'guessan, Benoit B; Asiedu-Gyekye, Isaac J; Nyarko, Alexander K

    2016-09-01

    Conflicting reports about the toxicity of Synedrella nodiflora (L) Gaertn (family Asteraceae), a plant traditionally used in Ghana for the management of epilepsy, abound in literature. The present study evaluates the effect of a 90-day continuous oral administration of a hydro-ethanolic whole plant extract of Synedrella nodiflora (SNE) in male Sprague-Dawley rats. The toxicological evaluation of the extract (100, 300 and 1000 mgkg(-1)) was focused on haematological, serum biochemical parameters and histopathological changes of some isolated organs. The extract produced no mortality in the rats treated during the study period. Only SNE 100 mgkg(-1) produced significant decrease in white blood cell and neutrophil counts and an increase in albumin, globulin, total bilirubin, total protein and potassium levels. The higher doses (SNE 300 and 1000 mgkg(-1)) had no significant effect on all the haematological and biochemical parameters measured. Histopathological assessment of the liver, kidney and heart revealed no abnormalities in rats treated with the extracts. Only the SNE 1000 mgkg(-1) produced distortions of the branching arrangements of the myocardial fibres and a congested vessel which indicates a healed infarction. The findings suggest hydro-ethanolic extract of Synedrella nodiflora (L) Gaertn generally has a low toxicity profile following a 90-day continuous oral administration in male Sprague-Dawley rats under the present laboratory conditions. However patients with renal or cardiac problems should use the plant with caution. Jointly supported by the International Foundation for Science, Stockholm, Sweden, through a grant (# F/5191-1) to Dr. Patrick Amoateng and the Office of Research, Innovation and Development (ORID), University of Ghana, Accra, Ghana, grant awarded to Dr. Patrick Amoateng (reference number: URF/6/ILG-002/2012-2013).

  14. Repeated amphetamine administration and long-term effects on 50-kHz ultrasonic vocalizations: possible relevance to the motivational and dopamine-stimulating properties of the drug.

    PubMed

    Simola, Nicola; Morelli, Micaela

    2015-03-01

    Ultrasonic vocalizations (USVs) of 50kHz are thought to indicate positive affective states in rats, and are increasingly being used to investigate the motivational properties of drugs of abuse. However, previous studies have observed that only dopaminergic psychostimulants of abuse, but not other addictive drugs, stimulate 50-kHz USVs immediately after their administration. This would suggest that 50-kHz USVs induced by addictive dopaminergic psychostimulants might reflect rewarding dopaminergic effect, rather than motivational effect. To elucidate this issue, our study compared the effects of the psychostimulant of abuse amphetamine and the dopamine receptor agonist apomorphine on 50-kHz USVs. Rats that received five drug administrations on alternate days in a novel test-cage were first re-exposed to the test-cage 7 days after treatment discontinuation to assess drug-conditioning, and then received a drug challenge. USVs were recorded throughout the experiments together with locomotor activity. To further clarify how amphetamine and apomorphine influenced 50-kHz USVs, rats were subdivided into "low" and "high" vocalizers, and time-dependence of drug effects was assessed. Amphetamine and apomorphine stimulated both 50-kHz USVs and locomotor activity, though they elicited dissimilar changes in these behaviors, depending on drug dose, rats׳ individual predisposition to vocalize, and time. Moreover, only amphetamine-treated rats displayed both sensitized 50-kHz USVs emission and conditioned vocalizations on test-cage re-exposure. These results indicate that the effects of amphetamine on 50-kHz USVs are not mimicked by a dopaminergic agonist with a low abuse potential, and may further support the usefulness of 50-kHz USVs in the study of the motivational properties of psychoactive drugs. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  15. Long-term ethanol self-administration induces ΔFosB in male and female adolescent, but not in adult, Wistar rats.

    PubMed

    Wille-Bille, Aranza; de Olmos, Soledad; Marengo, Leonardo; Chiner, Florencia; Pautassi, Ricardo Marcos

    2017-03-06

    Early-onset ethanol consumption predicts later development of alcohol use disorders. Age-related differences in reactivity to ethanol's effects may underlie this effect. Adolescent rats are more sensitive and less sensitive than adults to the appetitive and aversive behavioral effects of ethanol, respectively, and more sensitive to the neurotoxic effects of experimenter-administered binge doses of ethanol. However, less is known about age-related differences in the neural consequences of self-administered ethanol. ΔFosB is a transcription factor that accumulates after chronic drug exposure and serves as a molecular marker of neural plasticity associated with the transition to addiction. We analyzed the impact of chronic (18 two-bottle choice intake sessions spread across 42days, session length: 18h) ethanol [or only vehicle (control group)] self-administration during adolescence or adulthood on the induction of ΔFosB in several brain areas, anxiety-like behavior, and ethanol-induced locomotor activity and conditioned place preference (CPP) in Wistar rats. Adolescent rats exhibited a progressive escalation of ethanol intake and preference, whereas adult rats exhibited a stable pattern of ingestion. Few behavioral differences in the open field or light-dark test were observed after the intake test. Furthermore, ethanol self-administration did not promote the expression of ethanol-induced CPP. There were, however, large age-related differences in the neural consequences of ethanol drinking: a significantly greater number of ethanol-induced ΔFosB-positive cells was found in adolescents vs. adults in the prelimbic cortex, dorsolateral striatum, nucleus accumbens core and shell, and central amygdala nucleus capsular and basolateral amygdala, with sex-related differences found at central amygdala. This greater ethanol-induced ΔFosB induction may represent yet another age-related difference in the sensitivity to ethanol that may put adolescents at higher risk for

  16. Tolerance to Ethanol or Nicotine Results in Increased Ethanol Self-Administration and Long-Term Depression in the Dorsolateral Striatum.

    PubMed

    Abburi, Chandrika; Wolfman, Shannon L; Metz, Ryan A E; Kamber, Rinya; McGehee, Daniel S; McDaid, John

    2016-01-01

    Ethanol (EtOH) and nicotine are the most widely coabused drugs. Tolerance to EtOH intoxication, including motor impairment, results in greater EtOH consumption and may result in a greater likelihood of addiction. Previous studies suggest that cross-tolerance between EtOH and nicotine may contribute to the abuse potential of these drugs. Here we demonstrate that repeated intermittent administration of either EtOH or nicotine in adult male Sprague Dawley rats results in tolerance to EtOH-induced motor impairment and increased EtOH self-administration. These findings suggest that nicotine and EtOH cross-tolerance results in decreased aversive and enhanced rewarding effects of EtOH. Endocannabinoid signaling in the dorsolateral striatum (DLS) has been implicated in both EtOH tolerance and reward, so we investigated whether nicotine or EtOH pretreatment might modulate endocannabinoid signaling in this region. Using similar EtOH and nicotine pretreatment methods resulted in increased paired-pulse ratios of evoked EPSCs in enkephalin-positive medium spiny neurons in DLS slices. Thus, EtOH and nicotine pretreatment may modulate glutamatergic synapses in the DLS presynaptically. Bath application of the CB1 receptor agonist Win 55,2-212 increased the paired-pulse ratio of evoked EPSCs in control slices, while Win 55,2-212 had no effect on paired-pulse ratio in slices from either EtOH- or nicotine-pretreated rats. Consistent with these effects, nicotine pretreatment occluded LTD induction by high-frequency stimulation of the corticostriatal inputs to the dorsolateral striatum. These results suggest that nicotine and EtOH pretreatment modulates striatal synapses to induce tolerance to the motor-impairing effects of EtOH, which may contribute to nicotine and EtOH coabuse.

  17. Tolerance to Ethanol or Nicotine Results in Increased Ethanol Self-Administration and Long-Term Depression in the Dorsolateral Striatum

    PubMed Central

    Abburi, Chandrika; Wolfman, Shannon L.; Metz, Ryan A. E.; Kamber, Rinya

    2016-01-01

    Abstract Ethanol (EtOH) and nicotine are the most widely coabused drugs. Tolerance to EtOH intoxication, including motor impairment, results in greater EtOH consumption and may result in a greater likelihood of addiction. Previous studies suggest that cross-tolerance between EtOH and nicotine may contribute to the abuse potential of these drugs. Here we demonstrate that repeated intermittent administration of either EtOH or nicotine in adult male Sprague Dawley rats results in tolerance to EtOH-induced motor impairment and increased EtOH self-administration. These findings suggest that nicotine and EtOH cross-tolerance results in decreased aversive and enhanced rewarding effects of EtOH. Endocannabinoid signaling in the dorsolateral striatum (DLS) has been implicated in both EtOH tolerance and reward, so we investigated whether nicotine or EtOH pretreatment might modulate endocannabinoid signaling in this region. Using similar EtOH and nicotine pretreatment methods resulted in increased paired-pulse ratios of evoked EPSCs in enkephalin-positive medium spiny neurons in DLS slices. Thus, EtOH and nicotine pretreatment may modulate glutamatergic synapses in the DLS presynaptically. Bath application of the CB1 receptor agonist Win 55,2-212 increased the paired-pulse ratio of evoked EPSCs in control slices, while Win 55,2-212 had no effect on paired-pulse ratio in slices from either EtOH- or nicotine-pretreated rats. Consistent with these effects, nicotine pretreatment occluded LTD induction by high-frequency stimulation of the corticostriatal inputs to the dorsolateral striatum. These results suggest that nicotine and EtOH pretreatment modulates striatal synapses to induce tolerance to the motor-impairing effects of EtOH, which may contribute to nicotine and EtOH coabuse. PMID:27517088

  18. The long-term effects of FSH and triiodothyronine administration during the pubertal period on Connexin 43 expression and spermatogenesis efficiency in adult rats.

    PubMed

    Marchlewska, Katarzyna; Slowikowska-Hilczer, Jolanta; Walczak-Jedrzejowska, Renata; Oszukowska, Elzbieta; Filipiak, Eliza; Kula, Krzysztof

    2015-04-01

    Follicle-stimulating hormone (FSH) and triiodothyronine (T3) are known regulatory factors of spermatogenesis initiation. Hyperstimulation of both hormones evokes regressional changes in connexin 43 expression and the seminiferous epithelium in young rats during testicular maturation. However, separate treatments with T3 reduce Sertoli cell number, which seems to be closely connected with the maturation of connexin 43 gap junctions. FSH elevates Sertoli cell number and function, but this effect may take place regardless of the presence of connexin 43-dependent intercellular communication. The aim of the study was to evaluate the later effects of such treatments. Newborn, male Wistar rats were divided randomly into experimental groups receiving daily subcutaneous injections of either 7.5 IU/animal FSH, or 100 mg/kg b.w. T3, or both substances or the same volume of vehicle (control group) until day 15 of life. The animals were sacrificed on day 50. Morphometric analysis and immunohistochemical reactions were performed using antibodies against Vimentin, Proliferating Cell Nuclear Antigen and Connexin 43 in the testis. Sertoli cell count, efficiency of spermatogenesis, and hormonal pattern were examined. Disturbances in the connexin 43 expression reduced the number of Sertoli cells, the efficiency of spermatogenesis and impaired endocrine function of testes in adult rats treated with FSH and T3 during puberty. Stimulation with FSH alone increased Sertoli cell number, but was associated with a negative effect on cell-to-cell connexin 43-dependent communication, with a consequential reduction of spermatogenesis efficiency. J. Exp. Zool. 323A: 256-265, 2015. © 2015 Wiley Periodicals, Inc.

  19. Withdrawal symptoms in children after long-term administration of sedatives and/or analgesics: a literature review. "Assessment remains troublesome".

    PubMed

    Ista, Erwin; van Dijk, Monique; Gamel, Claudia; Tibboel, Dick; de Hoog, Matthijs

    2007-08-01

    Prolonged administration of benzodiazepines and/or opioids to children in a pediatric intensive care unit (PICU) may induce physiological dependence and withdrawal symptoms. We reviewed the literature for relevant contributions on the nature of these withdrawal symptoms and on availability of valid scoring systems to assess the extent of symptoms. The databases PubMed, CINAHL, and Psychinfo (1980-June 2006) were searched using relevant key terms. Symptoms of benzodiazepine and opioid withdrawal can be classified in two groups: central nervous system effects and autonomic dysfunction. However, symptoms of the two types show a large overlap for benzodiazepine and opioid withdrawal. Symptoms of gastrointestinal dysfunction in the PICU population have been described for opioid withdrawal only. Six assessment tools for withdrawal symptoms are used in children. Four of these have been validated for neonates only. Two instruments are available to specifically determine withdrawal symptoms in the PICU: the Sedation Withdrawal Score (SWS) and the Opioid Benzodiazepine Withdrawal Scale (OBWS). The OBWS is the only available assessment tool with prospective validation; however, the sensitivity is low. Withdrawal symptoms for benzodiazepines and opioids largely overlap. A sufficiently sensitive instrument for assessing withdrawal symptoms in PICU patients needs to be developed.

  20. Association of anemia with worsened activities of daily living and health-related quality of life scores derived from the Minimum Data Set in long-term care residents.

    PubMed

    Bailey, Robert A; Reardon, Gregory; Wasserman, Michael R; McKenzie, R Scott; Hord, R Steve

    2012-10-19

    Among long-term care (LTC) residents, we explored the association between anemia status and hemoglobin (Hb) level with Activities of Daily Living (ADL) functioning and health-related quality of life (HRQOL). Data were derived from the AnalytiCare database, containing laboratory and Minimum Data Set (MDS) reports for 27 LTC facilities in Colorado. Study timeframe was 1/1/07-9/15/08. Patients were selected based on: residence in LTC >90 days, Hb and serum creatinine value within 90 days of the earliest non-admission (index) MDS. From the index MDS, the method of 1) Carpenter et al. [BMC Geriatrics 6:7(2006)] was used to derive a summary measure of ADL performance (the MDS-ADL score) and 2) Wodchis et al. [IJTAHC 19:3(2003)] was used to assign HRQOL scores (MDS items were mapped to the Health Utilities Index Mark 2 (HUI2) scoring function to create the MDS-HSI score). Anemia was defined as Hb <12 g/dL females and <13 g/dL males. Adjusted linear regression was used to evaluate the independent association of anemia and hemoglobin level on MDS-ADL and MDS-HSI scores. 838 residents met all inclusion criteria; 46% of residents were anemic. Mean (SD) MDS-ADL score was 14.9 (7.5) [0-28 scale, where higher score indicates worse functioning]. In the adjusted model, anemia was associated with a significantly worse MDS-ADL score (+1.62 points, P=.001). Residents with Hb levels 10 to <11 g/dL had significantly worse ADL score (+2.06 points, P=.005) than the >13 g/dL reference. The mean MDS-HSI score was 0.431 (0.169) [range, where 0=dead to 1=perfect health]. Compared with non-anemic residents, in this adjusted model, residents with anemia had significantly worse MDS-HSI scores (-0.034 points, P=.005). Residents with hemoglobin levels <10 g/dL had significantly worse MDS-HSI scores (-0.058 points, P=.016) than the >13 g/dL reference. After adjusting for several covariates, LTC residents with anemia, and many of those with moderate to severe declines in Hb level, had significantly

  1. Association of anemia with worsened activities of daily living and health-related quality of life scores derived from the Minimum Data Set in long-term care residents

    PubMed Central

    2012-01-01

    Background Among long-term care (LTC) residents, we explored the association between anemia status and hemoglobin (Hb) level with Activities of Daily Living (ADL) functioning and health-related quality of life (HRQOL). Methods Data were derived from the AnalytiCare database, containing laboratory and Minimum Data Set (MDS) reports for 27 LTC facilities in Colorado. Study timeframe was 1/1/07-9/15/08. Patients were selected based on: residence in LTC >90 days, Hb and serum creatinine value within 90 days of the earliest non-admission (index) MDS. From the index MDS, the method of 1) Carpenter et al. [BMC Geriatrics 6:7(2006)] was used to derive a summary measure of ADL performance (the MDS-ADL score) and 2) Wodchis et al. [IJTAHC 19:3(2003)] was used to assign HRQOL scores (MDS items were mapped to the Health Utilities Index Mark 2 (HUI2) scoring function to create the MDS-HSI score). Anemia was defined as Hb <12 g/dL females and <13 g/dL males. Adjusted linear regression was used to evaluate the independent association of anemia and hemoglobin level on MDS-ADL and MDS-HSI scores. Results 838 residents met all inclusion criteria; 46% of residents were anemic. Mean (SD) MDS-ADL score was 14.9 (7.5) [0–28 scale, where higher score indicates worse functioning]. In the adjusted model, anemia was associated with a significantly worse MDS-ADL score (+1.62 points, P=.001). Residents with Hb levels 10 to <11 g/dL had significantly worse ADL score (+2.06 points, P=.005) than the >13 g/dL reference. The mean MDS-HSI score was 0.431 (0.169) [range, where 0=dead to 1=perfect health]. Compared with non-anemic residents, in this adjusted model, residents with anemia had significantly worse MDS-HSI scores (−0.034 points, P=.005). Residents with hemoglobin levels <10 g/dL had significantly worse MDS-HSI scores (−0.058 points, P=.016) than the >13 g/dL reference. Conclusions After adjusting for several covariates, LTC residents with anemia, and many of those with moderate to

  2. Evaluation of Short- and Long-Term Efficacy of Combined Intracoronary Administration of High-Dose Adenosine and Tirofiban during Primary Percutaneous Coronary Intervention

    PubMed Central

    Li, Yanbing; Li, Qiang; Li, Feiou; Zong, Min; Miao, Guobin; Yang, Xinchun; Tong, Zichuan; Zhang, Jianjun

    2016-01-01

    Background To assess the influence of combined intracoronary application of high-dose adenosine and tirofiban in primary percutaneous coronary intervention (PCI) on clinical events and cardiac function. Methods Our study evaluated consecutive patients with acute ST-segment elevation myocardial infarction undergoing primary PCI, who were randomly divided into adenosine group (n = 130) and control group (n = 128). Combined with thrombus aspiration and then intracoronary tirofiban, the adenosine group received intracoronary adenosine (2 mg) through the aspiration catheter 2 times. After thrombus aspiration and stenting of the infarct- related artery, the control group received placebo. The primary endpoint of our investigation was major adverse cardiac events (MACE) at the 1-year and 3-year marks. The secondary endpoint comprised left ventricular remodeling (LVR) at 6 months, myocardial blush grade (MBG), thrombolysis in myocardial infarction (TIMI) flow grade and corrected TIMI frame count (CTFC) after PCI. Results Our study found that TIMI flow grade post-PCI did not differ significantly between the 2 groups, while CTFC favored the adenosine-treated patients (21.6 ± 6.5 vs. 25.1 ± 7.8, p = 0.001). Although the adenosine group achieved a higher rate of MBG 3 (45.1% vs. 32.0%, p = 0.035) and MBG 2-3 (76.2% vs. 62.3%, p = 0.018) than the control group, the incidences of MACE at 1 year (20.0% vs. 25.0%, p = 0.373) and 3 years (26.9% vs. 32.0%, p = 0.413) were comparable. LVR occurred in 23.1% (27/117) of adenosine-treated patients and in 29.8% (43/114) of the controls (p = 0.296). Conclusions Intracoronary administration of high-dose adenosine combined with intracoronary tirofiban and thrombus aspiration may further improve myocardial perfusion after primary PCI. PMID:27899850

  3. Concurrent administration of adjuvant chemotherapy and radiotherapy after breast-conserving surgery enhances late toxicities: Long-term results of the ARCOSEIN multicenter randomized study

    SciTech Connect

    Toledano, Alain . E-mail: alain.toledano@gmail.com; Garaud, Pascal; Serin, Daniel; Fourquet, Alain; Bosset, Jean-Francois; Breteau, Noel; Body, Gilles; Azria, David; Le Floch, Olivier; Calais, Gilles

    2006-06-01

    Purpose: In 1996, a multicenter randomized study was initiated that compared sequential vs. concurrent adjuvant chemotherapy (CT) with radiation therapy (RT) after breast-conserving surgery (ARCOSEIN study). After a median follow-up of 6.7 years (range, 4.3-9 years), we decided to prospectively evaluate the late effects of these 2 strategies. Methods and Materials: A total of 297 patients from the 5 larger participating institutions were asked to report for a follow-up examination. Seventy-two percent (214 patients) were eligible for evaluation of late toxicity. After breast-conserving surgery, patients were treated either with sequential treatment with CT first followed by RT (Arm A) or CT administered concurrently with RT (Arm B). In all patients, CT regimen consisted of mitoxantrone (12 mg/m{sup 2}), 5-FU (500 mg/m{sup 2}), and cyclophosphamide (500 mg/m{sup 2}), 6 cycles (Day 1 to Day 21). Conventional RT was delivered to the whole breast by administration of a 2 Gy per fraction protocol to a total dose of 50 Gy ({+-} boost to the primary tumor bed). The assessment of toxicity was blinded to treatment and was graded by the radiation oncologist, according to the LENT/SOMA scale. Skin pigmentation was also evaluated according to a personal 5-points scoring system (excellent, good, moderate, poor, very poor). Results: Among the 214 evaluable patients, 107 were treated in each arm. The 2 populations were homogeneous for patient, tumor, and treatment characteristics. Subcutaneous fibrosis (SF), telangectasia (T), skin pigmentation (SP), and breast atrophy (BA) were significantly increased in Arm B. No statistical difference was observed between the 2 arms of the study concerning Grade 2 or higher pain, breast edema, or lymphedema. No deaths were caused by late toxicity. Conclusion: After breast-conserving surgery, the concurrent use of CT with RT is significantly associated with an increase incidence of Grade 2 or greater late side effects.

  4. Long-Term Impact of Implementation of a Stroke Protocol on Door-to-Needle Time in the Administration of Intravenous Tissue Plasminogen Activator.

    PubMed

    Hillen, Machteld E; He, Wenzhuan; Al-Qudah, Zaid; Wang, Weizhen; Hidalgo, Andrea; Walia, Jessy

    2017-07-01

    This study aims to evaluate the effectiveness of implementing a stroke protocol (SP) in improving door-to-needle time (DTNT) and door-to-computed tomography (DTCT) time from 2010 to 2014. Published data from the Get With The Guidelines-Stroke (GWTGS) participating hospitals showed that median DTNT = 75 minutes with 26.6% of the patients achieving the recommended DTNT of 60 minutes or less. Implementation of an SP, which specifies the role of nurses, physicians, and technicians during acute stroke evaluation, can improve DTNT. This longitudinal quality assurance study was designed to compare the DTNT and the DTCT time pre- and post implementation of an SP in our hospital. Patients' data before (2009-2010) and after (2010-2014) the implementation of an SP were collected each year during the same 6-month period and compared using statistical software SPSS 20.0 for Windows (SPSS Inc., Chicago, IL). Although our DTNT did not significantly improve over the years, the median DTNT (59 minutes) was much less than the reported 75 minutes of GWTGS hospitals. Our DTCT time diminished from 20.6 minutes in 2009 to 15.9 minutes in 2014. The percentage of patients with a DTNT of 1 hour or less did not differ among all years (P = .296) and was 55.8%. Our study suggests that our performance in evaluating acute ischemic stroke patients within the American Heart Association/American Stroke Association suggested time window is reachable for prolonged periods of time. Continuous monitoring and education of all players involved are crucial to ensure best possible outcomes in the timely administration of intravenous tissue plasminogen activator. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  5. Long-term administration of ranolazine attenuates diastolic dysfunction and adverse myocardial remodeling in a model of heart failure with preserved ejection fraction.

    PubMed

    De Angelis, Antonella; Cappetta, Donato; Piegari, Elena; Rinaldi, Barbara; Ciuffreda, Loreta Pia; Esposito, Grazia; Ferraiolo, Fiorella Angelica Valeria; Rivellino, Alessia; Russo, Rosa; Donniacuo, Maria; Rossi, Francesco; Urbanek, Konrad; Berrino, Liberato

    2016-08-15

    To investigate the effects of chronic administration of ranolazine (RAN) on experimental model of heart failure with preserved ejection fraction. Seven-weeks old Dahl salt-sensitive rats were fed a high salt diet for 5weeks to induce hypertension. Afterwards, rats continued with a high salt diet and were administered either with vehicle or RAN (20mg/kg/die, ip) for the following 8weeks. Control rats were maintained on a low salt diet. While systolic parameters were not altered, diastolic parameters were changed in high salt animals. Hemodynamic analysis showed a decreased dP/dt min, increased LVEDP, longer time constant and steeper slope of the end-diastolic pressure-volume relationship. Treatment with RAN attenuated these alterations and determined a reduction in mortality. Additionally, the magnitude of myocardial hypertrophy and activation of PI3K/Akt pathway were reduced. Alteration in diastolic compliance as a consequence of elevated myocardial stiffness was confirmed by an increase of collagen deposition and activation of pro-fibrotic TGF-β/SMAD3/CTGF signaling. These effects were counteracted by RAN. High salt rats had a decrease in SERCA2 and an increase in Na(+)/Ca(2+) exchanger (NCX). Treatment with RAN reduced NCX expression and determined an increment of SERCA2. Moreover, the levels of nitrotyrosine and oxidized dyhydroethidium were higher in high salt rats. RAN induced a decrement of oxidative stress, supporting the concept that reduction in ROS may mediate beneficial effects. Our findings support the possibility that diastolic dysfunction can be attenuated by RAN, indicating its ability to affect active relaxation and passive diastolic compliance. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Long-term use of ceftriaxone sodium induced changes in gut microbiota and immune system

    PubMed Central

    Guo, Yanjie; Yang, Xuefei; Qi, Yane; Wen, Shu; Liu, Yinhui; Tang, Shaoying; Huang, Rongsheng; Tang, Li

    2017-01-01

    Antibiotic administration, while facilitating clearance of targeted infections, also perturbs commensal microbial communities. Previous studies have all focused on the effects of short term use of antibiotics. Here, we focus on the effects of long term use of antibiotic on gut microbiota and immunity. BALB/c mice received saline or different doses of ceftriaxone sodium (100, 200 and 400 mg/mL) via daily gavage for 150 days. Alterations of fecal microbiota, small intestine histopathology, body weight, spleen index, serum IgG, mucus SIgA, IFN-γ/IL-4 ratio, CD4/CD8 ratio and CD4+CD25+ cells were evaluated. Long term ceftriaxone sodium administration resulted in gut microbiota dysbiosis, intestine histological lesions, growth inhibition, spleen index reducing. The immune defense ability reduced as serum IgG and mucus SIgA decreased significantly. Not only the immune defense, long term ceftriaxone administration also affected immune regulation. The IFN-γ/IL-4 and CD4/CD8 ratios increased, the CD4+CD25+ cells reduced on days 30 and 60 after ceftriaxone administration. However, after 90 days of ceftriaxone administration, the IFN-γ/IL-4, CD4/CD8 ratios and CD4+CD25+ cells restored, which indicated a new balance of immune regulation had been formed. Overall, these findings contribute to our understanding of long term antibiotic administration influencing gut microbiota and immunity. PMID:28220870

  7. Long-term use of ceftriaxone sodium induced changes in gut microbiota and immune system.

    PubMed

    Guo, Yanjie; Yang, Xuefei; Qi, Yane; Wen, Shu; Liu, Yinhui; Tang, Shaoying; Huang, Rongsheng; Tang, Li

    2017-02-21

    Antibiotic administration, while facilitating clearance of targeted infections, also perturbs commensal microbial communities. Previous studies have all focused on the effects of short term use of antibiotics. Here, we focus on the effects of long term use of antibiotic on gut microbiota and immunity. BALB/c mice received saline or different doses of ceftriaxone sodium (100, 200 and 400 mg/mL) via daily gavage for 150 days. Alterations of fecal microbiota, small intestine histopathology, body weight, spleen index, serum IgG, mucus SIgA, IFN-γ/IL-4 ratio, CD4/CD8 ratio and CD4(+)CD25(+) cells were evaluated. Long term ceftriaxone sodium administration resulted in gut microbiota dysbiosis, intestine histological lesions, growth inhibition, spleen index reducing. The immune defense ability reduced as serum IgG and mucus SIgA decreased significantly. Not only the immune defense, long term ceftriaxone administration also affected immune regulation. The IFN-γ/IL-4 and CD4/CD8 ratios increased, the CD4(+)CD25(+) cells reduced on days 30 and 60 after ceftriaxone administration. However, after 90 days of ceftriaxone administration, the IFN-γ/IL-4, CD4/CD8 ratios and CD4(+)CD25(+) cells restored, which indicated a new balance of immune regulation had been formed. Overall, these findings contribute to our understanding of long term antibiotic administration influencing gut microbiota and immunity.

  8. The long-term effects of neonatal morphine administration on the pentylenetetrazol seizure model in rats: the role of hippocampal cholinergic receptors in adulthood.

    PubMed

    Saboory, Ehsan; Gholami, Morteza; Zare, Samad; Roshan-Milani, Shiva

    2014-04-01

    Early life exposure to opiates may affect neuropathological conditions, such as epilepsy, during adulthood. We investigated whether neonatal morphine exposure affects pentylenetetrazol (PTZ)-induced seizures in adulthood. Male rats were subcutaneously injected with morphine or saline on postnatal days 8-14. During adulthood, each rat was assigned to 1 of the following 10 sub-groups: saline, nicotine (0.1, 0.5, or 1 μg), atropine (0.25 or 1 μg), oxotremorine M (0.1 or 1 μg), or mecamylamine (2 or 8 μg). An intrahippocampal infusion of the indicated compound was administered 30 min before seizure induction (80 mg/kg PTZ). Compared with the saline/oxotremorine (1 μg), saline/saline, and morphine/saline groups, the morphine/oxotremorine (1 μg) group showed a significantly increased latency to the first epileptic behavior. The duration of tonic-clonic seizures was significantly lower in the morphine/oxotremorine (1 μg) group compared to the saline/saline and morphine/saline groups. The severity of seizure was significantly decreased in the morphine/atropine (1 μg) group than in the saline/atropine (1 μg). Seizure severity was also decreased in the morphine/mecamylamine (2 μg) group than in the saline/mecamylamine (2 μg) group. Latency for death was significantly lower in the morphine/mecamylamine (2 μg) group compared with the saline/mecamylamine (2 μg) group. Mortality rates in the morphine/atropine (1 μg) and morphine/mecamylamine (2 μg) groups were significantly lower than those in the saline/atropine (1 μg) and saline/mecamylamine (2 μg) groups, respectively. Chronic neonatal morphine administration attenuated PTZ-induced seizures, reduced the mortality rate, and decreased the impact of the hippocampal cholinergic system on seizures and mortality rate in adult rats. Neonatal morphine exposure induces changes to μ-receptors that may lead to activation of GABAergic neurons in the hippocampus. This pathway may explain the anti-convulsant effects of

  9. Long-Term Durability of Tenofovir-Based Antiretroviral Therapy in Relation to the Co-Administration of Other Drug Classes in Routine Clinical Practice

    PubMed Central

    Bonora, Stefano; Madeddu, Giordano; Maggiolo, Franco; Antinori, Andrea; Galli, Massimo; Di Perri, Giovanni; Viale, Pierluigi; d’Arminio Monforte, Antonella; Gori, Andrea

    2016-01-01

    Background In clinical trials, toxicity leading to tenofovir disoproxil fumarate (TDF) discontinuation is rare (3% by 2 years); however in clinical practice it seems to be higher, particularly when TDF is co-administered with ritonavir-boosted protease inhibitors (PI/r). Aims of this study were to assess the rate of TDF discontinuations in clinical practice and to identify factors associated with the risk of stopping TDF. Methods All antiretroviral treatment (ART)-naive patients initiating a TDF-based regimen were selected from the ICONA Foundation Study cohort. The primary outcome was TDF discontinuation regardless of the reason; secondary outcome measures were TDF discontinuation due to toxicity and selective TDF discontinuation (that is, TDF discontinuation or substitution, maintaining unchanged the remaining antiretroviral treatment). Results 3,618 ART-naïve patients were included: 54% started a PI/r-based and 46% a NNRTI-based based regimen. Two-hundred-seventy-seven patients discontinued TDF and reintroduced ART within 30 days without TDF. The probability of TDF discontinuation regardless of the reason was of 7.4% (95%CI:6.4–8.5) by 2 years and 14.1% (95%CI:12.2–16.1) by 5 years. The 5-year KM estimates in the PI/r vs. NNRTI group were 20.4% vs. 7.6%, respectively (log-rank p = 0.0001), for the outcome of stopping regardless of the reason, and 10.7% vs. 4.7% (p = 0.0001) for discontinuation due to toxicity. PI/r use and lower eGFR were associated with an increased risk of discontinuing TDF. Conclusion In our cohort, the frequency of TDF discontinuations was higher than that observed in clinical trials. Co-administration of TDF with PI/r was associated with an increased rate of TDF discontinuations. Further studies are needed to clarify the mechanisms that might have led to this outcome. PMID:27716843

  10. Long-term administration of the mitochondria-targeted antioxidant mitoquinone mesylate fails to attenuate age-related oxidative damage or rescue the loss of muscle mass and function associated with aging of skeletal muscle.

    PubMed

    Sakellariou, Giorgos K; Pearson, Timothy; Lightfoot, Adam P; Nye, Gareth A; Wells, Nicola; Giakoumaki, Ifigeneia I; Griffiths, Richard D; McArdle, Anne; Jackson, Malcolm J

    2016-11-01

    Age-related skeletal muscle dysfunction is the underlying cause of morbidity that affects up to half the population aged 80 and over. Considerable evidence indicates that oxidative damage and mitochondrial dysfunction contribute to the sarcopenic phenotype that occurs with aging. To examine this, we administered the mitochondria-targeted antioxidant mitoquinone mesylate {[10-(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4-cyclohexadien-1-yl)decyl] triphenylphosphonium; 100 μM} to wild-type C57BL/6 mice for 15 wk (from 24 to 28 mo of age) and investigated the effects on age-related loss of muscle mass and function, changes in redox homeostasis, and mitochondrial organelle integrity and function. We found that mitoquinone mesylate treatment failed to prevent age-dependent loss of skeletal muscle mass associated with myofiber atrophy or alter a variety of in situ and ex vivo muscle function analyses, including maximum isometric tetanic force, decline in force after a tetanic fatiguing protocol, and single-fiber-specific force. We also found evidence that long-term mitoquinone mesylate administration did not reduce mitochondrial reactive oxygen species or induce significant changes in muscle redox homeostasis, as assessed by changes in 4-hydroxynonenal protein adducts, protein carbonyl content, protein nitration, and DNA damage determined by the content of 8-hydroxydeoxyguanosine. Mitochondrial membrane potential, abundance, and respiration assessed in permeabilized myofibers were not significantly altered in response to mitoquinone mesylate treatment. Collectively, these findings demonstrate that long-term mitochondria-targeted mitoquinone mesylate administration failed to attenuate age-related oxidative damage in skeletal muscle of old mice or provide any protective effect in the context of muscle aging.-Sakellariou, G. K., Pearson, T., Lightfoot, A. P., Nye, G. A., Wells, N., Giakoumaki, I. I., Griffiths, R. D., McArdle, A., Jackson, M. J. Long-term administration of the

  11. Long-term administration of the mitochondria-targeted antioxidant mitoquinone mesylate fails to attenuate age-related oxidative damage or rescue the loss of muscle mass and function associated with aging of skeletal muscle

    PubMed Central

    Sakellariou, Giorgos K.; Pearson, Timothy; Lightfoot, Adam P.; Nye, Gareth A.; Wells, Nicola; Giakoumaki, Ifigeneia I.; Griffiths, Richard D.; McArdle, Anne; Jackson, Malcolm J.

    2016-01-01

    Age-related skeletal muscle dysfunction is the underlying cause of morbidity that affects up to half the population aged 80 and over. Considerable evidence indicates that oxidative damage and mitochondrial dysfunction contribute to the sarcopenic phenotype that occurs with aging. To examine this, we administered the mitochondria-targeted antioxidant mitoquinone mesylate {[10-(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4-cyclohexadien-1-yl)decyl] triphenylphosphonium; 100 μM} to wild-type C57BL/6 mice for 15 wk (from 24 to 28 mo of age) and investigated the effects on age-related loss of muscle mass and function, changes in redox homeostasis, and mitochondrial organelle integrity and function. We found that mitoquinone mesylate treatment failed to prevent age-dependent loss of skeletal muscle mass associated with myofiber atrophy or alter a variety of in situ and ex vivo muscle function analyses, including maximum isometric tetanic force, decline in force after a tetanic fatiguing protocol, and single-fiber-specific force. We also found evidence that long-term mitoquinone mesylate administration did not reduce mitochondrial reactive oxygen species or induce significant changes in muscle redox homeostasis, as assessed by changes in 4-hydroxynonenal protein adducts, protein carbonyl content, protein nitration, and DNA damage determined by the content of 8-hydroxydeoxyguanosine. Mitochondrial membrane potential, abundance, and respiration assessed in permeabilized myofibers were not significantly altered in response to mitoquinone mesylate treatment. Collectively, these findings demonstrate that long-term mitochondria-targeted mitoquinone mesylate administration failed to attenuate age-related oxidative damage in skeletal muscle of old mice or provide any protective effect in the context of muscle aging.—Sakellariou, G. K., Pearson, T., Lightfoot, A. P., Nye, G. A., Wells, N., Giakoumaki, I. I., Griffiths, R. D., McArdle, A., Jackson, M. J. Long-term administration of the

  12. Long-term intravenous administration of carboxylated single-walled carbon nanotubes induces persistent accumulation in the lungs and pulmonary fibrosis via the nuclear factor-kappa B pathway

    PubMed Central

    Qin, Yue; Li, Suning; Zhao, Gan; Fu, Xuanhao; Xie, Xueping; Huang, Yiyi; Cheng, Xiaojing; Wei, Jinbin; Liu, Huagang; Lai, Zefeng

    2017-01-01

    Numerous studies have demonstrated promising application of single-walled carbon nanotubes (SWNTs) in drug delivery, diagnosis, and targeted therapy. However, the adverse health effects resulting from intravenous injection of SWNTs are not completely understood. Studies have shown that levels of “pristine” or carboxylated carbon nanotubes are very high in mouse lungs after intravenous injection. We hypothesized that long-term and repeated intravenous administration of carboxylated SWNTs (c-SWNTs) can result in persistent accumulation and induce histopathologic changes in rat lungs. Here, c-SWNTs were administered repeatedly to rats via tail-vein injection for 90 days. Long-term intravenous injection of c-SWNTs caused sustained embolization in lung capillaries and granuloma formation. It also induced a persistent inflammatory response that was regulated by the nuclear factor-kappa B signaling pathway, and which resulted in pulmonary fibrogenesis. c-SWNTs trapped within lung capillaries traversed capillary walls and injured alveolar epithelial cells, thereby stimulating production of pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-1 beta) and pro-fibrotic growth factors (transforming growth factor-beta 1). Protein levels of type-I and type-III collagens, matrix metalloproteinase-2, and the tissue inhibitor of metalloproteinase-2 were upregulated after intravenous exposure to c-SWNTs as determined by immunohistochemical assays and Western blotting, which suggested collagen deposition and remodeling of the extracellular matrix. These data suggest that chronic and cumulative toxicity of nanomaterials to organs with abundant capillaries should be assessed if such nanomaterials are applied via intravenous administration. PMID:28115845

  13. Long-term intravenous administration of carboxylated single-walled carbon nanotubes induces persistent accumulation in the lungs and pulmonary fibrosis via the nuclear factor-kappa B pathway.

    PubMed

    Qin, Yue; Li, Suning; Zhao, Gan; Fu, Xuanhao; Xie, Xueping; Huang, Yiyi; Cheng, Xiaojing; Wei, Jinbin; Liu, Huagang; Lai, Zefeng

    2017-01-01

    Numerous studies have demonstrated promising application of single-walled carbon nanotubes (SWNTs) in drug delivery, diagnosis, and targeted therapy. However, the adverse health effects resulting from intravenous injection of SWNTs are not completely understood. Studies have shown that levels of "pristine" or carboxylated carbon nanotubes are very high in mouse lungs after intravenous injection. We hypothesized that long-term and repeated intravenous administration of carboxylated SWNTs (c-SWNTs) can result in persistent accumulation and induce histopathologic changes in rat lungs. Here, c-SWNTs were administered repeatedly to rats via tail-vein injection for 90 days. Long-term intravenous injection of c-SWNTs caused sustained embolization in lung capillaries and granuloma formation. It also induced a persistent inflammatory response that was regulated by the nuclear factor-kappa B signaling pathway, and which resulted in pulmonary fibrogenesis. c-SWNTs trapped within lung capillaries traversed capillary walls and injured alveolar epithelial cells, thereby stimulating production of pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-1 beta) and pro-fibrotic growth factors (transforming growth factor-beta 1). Protein levels of type-I and type-III collagens, matrix metalloproteinase-2, and the tissue inhibitor of metalloproteinase-2 were upregulated after intravenous exposure to c-SWNTs as determined by immunohistochemical assays and Western blotting, which suggested collagen deposition and remodeling of the extracellular matrix. These data suggest that chronic and cumulative toxicity of nanomaterials to organs with abundant capillaries should be assessed if such nanomaterials are applied via intravenous administration.

  14. Long-Term Orientation and Educational Performance. Working Paper 174

    ERIC Educational Resources Information Center

    Figlio, David; Giuliano, Paola; Özek, Umut; Sapienza, Paola

    2017-01-01

    We use remarkable population-level administrative education and birth records from Florida to study the role of Long-Term Orientation on the educational attainment of immigrant students living in the US. Controlling for the quality of schools and individual characteristics, students from countries with long-term oriented attitudes perform better…

  15. Long-term benefit of early pre-reperfusion metoprolol administration in patients with acute myocardial infarction: results from the METOCARD-CNIC trial (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction).

    PubMed

    Pizarro, Gonzalo; Fernández-Friera, Leticia; Fuster, Valentin; Fernández-Jiménez, Rodrigo; García-Ruiz, José M; García-Álvarez, Ana; Mateos, Alonso; Barreiro, María V; Escalera, Noemí; Rodriguez, Maite D; de Miguel, Antonio; García-Lunar, Inés; Parra-Fuertes, Juan J; Sánchez-González, Javier; Pardillos, Luis; Nieto, Beatriz; Jiménez, Adriana; Abejón, Raquel; Bastante, Teresa; Martínez de Vega, Vicente; Cabrera, José A; López-Melgar, Beatriz; Guzman, Gabriela; García-Prieto, Jaime; Mirelis, Jesús G; Zamorano, José Luis; Albarrán, Agustín; Goicolea, Javier; Escaned, Javier; Pocock, Stuart; Iñiguez, Andrés; Fernández-Ortiz, Antonio; Sánchez-Brunete, Vicente; Macaya, Carlos; Ibanez, Borja

    2014-06-10

    The goal of this trial was to study the long-term effects of intravenous (IV) metoprolol administration before reperfusion on left ventricular (LV) function and clinical events. Early IV metoprolol during ST-segment elevation myocardial infarction (STEMI) has been shown to reduce infarct size when used in conjunction with primary percutaneous coronary intervention (pPCI). The METOCARD-CNIC (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction) trial recruited 270 patients with Killip class ≤II anterior STEMI presenting early after symptom onset (<6 h) and randomized them to pre-reperfusion IV metoprolol or control group. Long-term magnetic resonance imaging (MRI) was performed on 202 patients (101 per group) 6 months after STEMI. Patients had a minimal 12-month clinical follow-up. Left ventricular ejection fraction (LVEF) at the 6 months MRI was higher after IV metoprolol (48.7 ± 9.9% vs. 45.0 ± 11.7% in control subjects; adjusted treatment effect 3.49%; 95% confidence interval [CI]: 0.44% to 6.55%; p = 0.025). The occurrence of severely depressed LVEF (≤35%) at 6 months was significantly lower in patients treated with IV metoprolol (11% vs. 27%, p = 0.006). The proportion of patients fulfilling Class I indications for an implantable cardioverter-defibrillator (ICD) was significantly lower in the IV metoprolol group (7% vs. 20%, p = 0.012). At a median follow-up of 2 years, occurrence of the pre-specified composite of death, heart failure admission, reinfarction, and malignant arrhythmias was 10.8% in the IV metoprolol group versus 18.3% in the control group, adjusted hazard ratio (HR): 0.55; 95% CI: 0.26 to 1.04; p = 0.065. Heart failure admission was significantly lower in the IV metoprolol group (HR: 0.32; 95% CI: 0.015 to 0.95; p = 0.046). In patients with anterior Killip class ≤II STEMI undergoing pPCI, early IV metoprolol before reperfusion resulted in higher long-term LVEF, reduced incidence of severe LV systolic dysfunction

  16. Effects of daily morphine administration and deprivation on choice and demand for remifentanil and cocaine in rhesus monkeys.

    PubMed

    Wade-Galuska, Tammy; Galuska, Chad M; Winger, Gail

    2011-01-01

    Choice procedures have indicated that the relative reinforcing effectiveness of opioid drugs increases during opioid withdrawal. The demand curve, an absolute measure of reinforcer value, has not been applied to this question. The present study assessed whether mild morphine withdrawal would increase demand for or choice of remifentanil or cocaine. Four rhesus monkeys chose between remifentanil and cocaine during daily sessions. Demand curves for both drugs were subsequently obtained. The effects of daily injections of 3.2 mg/kg morphine on both choice and demand for these drugs was assayed 3 and 20.5 hr after each morphine injection, and then during a postmorphine period. Three hours following morphine injections, choice of remifentanil over cocaine decreased and demand for remifentanil--but not cocaine--became more elastic. During morphine withdrawal (20.5 hr postinjection), choice of remifentanil increased and remifentanil demand became more inelastic in 3 of 4 monkeys. Cocaine demand also became more inelastic during this period. Four to five weeks following the morphine regimen, demand for both drugs was more inelastic relative to the initial determination. The results suggest that both the relative and absolute reinforcing effectiveness of remifentanil decreased following morphine administration and increased during morphine withdrawal. The absolute reinforcing effectiveness of cocaine also increased during morphine withdrawal. In addition, extended exposure to drug self-administration and/or exposure to the morphine regimen produced long-term increases in demand for both drugs.

  17. Effects of Daily Morphine Administration and Deprivation on Choice and Demand for Remifentanil and Cocaine in Rhesus Monkeys

    PubMed Central

    Wade-Galuska, Tammy; Galuska, Chad M; Winger, Gail

    2011-01-01

    Choice procedures have indicated that the relative reinforcing effectiveness of opioid drugs increases during opioid withdrawal. The demand curve, an absolute measure of reinforcer value, has not been applied to this question. The present study assessed whether mild morphine withdrawal would increase demand for or choice of remifentanil or cocaine. Four rhesus monkeys chose between remifentanil and cocaine during daily sessions. Demand curves for both drugs were subsequently obtained. The effects of daily injections of 3.2 mg/kg morphine on both choice and demand for these drugs was assayed 3 and 20.5 hr after each morphine injection, and then during a postmorphine period. Three hours following morphine injections, choice of remifentanil over cocaine decreased and demand for remifentanil—but not cocaine—became more elastic. During morphine withdrawal (20.5 hr postinjection), choice of remifentanil increased and remifentanil demand became more inelastic in 3 of 4 monkeys. Cocaine demand also became more inelastic during this period. Four to five weeks following the morphine regimen, demand for both drugs was more inelastic relative to the initial determination. The results suggest that both the relative and absolute reinforcing effectiveness of remifentanil decreased following morphine administration and increased during morphine withdrawal. The absolute reinforcing effectiveness of cocaine also increased during morphine withdrawal. In addition, extended exposure to drug self-administration and/or exposure to the morphine regimen produced long-term increases in demand for both drugs. PMID:21541117

  18. Long-term parenteral nutrition

    PubMed Central

    Ladefoged, Karin; Jarnum, Stig

    1978-01-01

    Nineteen patients (11 women and eight men) aged 20-68 received long-term parenteral nutrition, mostly at home, for six to 63 months (mean 19 months). Indications for LTPN were extensive, active Crohn's disease in three patients, intestinocutaneous fistulas in three, and short-bowel syndrome in the remaining 13 patients. Subclavian or intra-atrial (Broviac) catheters were most commonly used, for which the average life was four and seven months respectively. Complications of long-term parenteral nutrition included pneumothorax in four out of 48 subclavian vein punctures. Catheter-induced thrombosis of central veins was shown by phlebography 17 times in nine patients, and eight episodes of total occlusion occurred. Two of these patients had pulmonary infarction. Nineteen episodes of catheter sepsis occurred in 11 patients, but only one was fatal. Complications related to intestinal disease included intra-abdominal abscesses and intestinal fistulas, and disturbances of liver function. Five patients died, though in only two was death related to long-term parenteral nutrition. One of these patients died from catheter sepsis, the other had subdural haematoma possibly caused by anticoagulant treatment. Eight of the 14 surviving patients still needed parenteral nutrition. All received a disability pension, but six had an acceptable quality of life with almost normal social activities. Despite problems such as difficulties in maintaining standardised infusion programmes, it was concluded that long-term parenteral nutrition at home is practicable and consistent with an acceptable quality of life. ImagesFIG 2 PMID:98199

  19. Long-term CD4(+) and CD8(+) T-cell responses induced in HIV-uninfected volunteers following intradermal or intramuscular administration of an HIV-lipopeptide vaccine (ANRS VAC16).

    PubMed

    Launay, Odile; Surenaud, Mathieu; Desaint, Corinne; Ben Hamouda, Nadine; Pialoux, Gilles; Bonnet, Bénédicte; Poizot-Martin, Isabelle; Gonzales, Gustavo; Cuzin, Lise; Bourgault-Villada, Isabelle; Lévy, Yves; Choppin, Jeannine; Durier, Christine

    2013-09-13

    We have shown that the intradermal (ID) administration of an HIV-1 lipopeptide candidate vaccine (LIPO-4) is well tolerated in healthy volunteers, with one fifth the IM dose delivered by this route inducing HIV-1-specific CD8(+) T-cell responses of a magnitude and quality similar to those achieved by IM administration. In this long-term follow-up, we aimed to investigate the sustainability and epitopic breadth of the immune responses induced. In a prospective multicentre trial, 68 healthy volunteers were randomised to receive, at weeks 0, 4 and 12, either a 0.5 ml IM (500 μg of each lipopeptide; 35 volunteers) dose or a 0.1 ml ID (100 μg of each lipopeptide; 33 volunteers) dose of the LIPO-4 vaccine, in the deltoid region of the non-dominant arm. All 68 volunteers received the first two vaccinations, and 44 volunteers in the ID group and 22 in the IM group received the third. We describe here the long-term CD8(+) and CD4(+) T-cell immune responses, up to 48 weeks after the first immunisation. Response frequency was highest at week 14 for CD4(+) T cells, at 85% (28/33) for the IM group and 61% (20/33) for the ID group (p=0.027), and at week 48 for CD8(+) T cells, at 36% (12/33) for the ID group and 31% (11/35) for the IM group (p=0.67). Response rates tended to be lower for volunteers receiving the third vaccination boost, whether IM or ID. Finally, we also observed a striking change in the specificity of the CD8(+) T-cell responses induced shortly (2 weeks) or several months (48 weeks) after LIPO-4 vaccination. Lipopeptide vaccines elicited sustainable CD4(+) and CD8(+) T-cell responses, following IM or ID administration. CD8(+) T-cell responses had shifted and expanded to different epitopes after one year of follow-up. These results should facilitate the design of the next generation of prime-boost trials with repeated doses of lipopeptide vaccines. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Successful Re-administration of Low-dose of Methimazole (MMI) in Graves' Disease Patients Who Experienced Allergic Cutaneous Reactions to MMI at Initial Treatment and Had Received Long-term Propylthiouracil (PTU)

    PubMed Central

    Kubota, Sumihisa

    2016-01-01

    Objective When patients with Graves' disease show severe allergic cutaneous reactions, physicians often suggest that they undergo radioiodine therapy instead of receiving propylthiouracil (PTU), another antithyroid drug, because anti-neutrophil cytoplasmic antibody (ANCA)-related vasculitis can occur with PTU, especially with long-term use. However, some patients refuse radioiodine therapy and chose PTU. Sometimes PTU treatment may be prolonged. Since the frequency of adverse effects of methimazole (MMI) is dose-related, there is a possibility that we can re-administer a low dose without adverse effects to patients well-controlled with PTU who once experienced an allergic reaction to MMI. Methods I prospectively re-administered a low dose of MMI to patients who previously experienced an allergic reaction to MMI at initial treatment. The dose of re-administered MMI ranged from 5 mg twice a week to 5 mg daily. Patients Nine patients with Graves' disease who developed urticaria at initial treatment with MMI and had been treated with PTU for 6 to 21 years were recruited. Results Eight of the 9 patients were successfully controlled with MMI without allergic cutaneous reactions. Only one patient felt itchiness 2 days after switching to MMI. However, skin change was not observed. Conclusion If the patients show allergic cutaneous reactions as a side effect of MMI at the initial treatment for Graves' disease, then there is a strong possibility that such patients can tolerate a low dose of MMI without adverse effects after the disease activity has subsided. PMID:27853063

  1. Long-term data archiving

    SciTech Connect

    Moore, David Steven

    2009-01-01

    Long term data archiving has much value for chemists, not only to retain access to research and product development records, but also to enable new developments and new discoveries. There are some recent regulatory requirements (e.g., FDA 21 CFR Part 11), but good science and good business both benefit regardless. A particular example of the benefits of and need for long term data archiving is the management of data from spectroscopic laboratory instruments. The sheer amount of spectroscopic data is increasing at a scary rate, and the pressures to archive come from the expense to create the data (or recreate it if it is lost) as well as its high information content. The goal of long-term data archiving is to save and organize instrument data files as well as any needed meta data (such as sample ID, LIMS information, operator, date, time, instrument conditions, sample type, excitation details, environmental parameters, etc.). This editorial explores the issues involved in long-term data archiving using the example of Raman spectral databases. There are at present several such databases, including common data format libraries and proprietary libraries. However, such databases and libraries should ultimately satisfy stringent criteria for long term data archiving, including readability for long times into the future, robustness to changes in computer hardware and operating systems, and use of public domain data formats. The latter criterion implies the data format should be platform independent and the tools to create the data format should be easily and publicly obtainable or developable. Several examples of attempts at spectral libraries exist, such as the ASTM ANDI format, and the JCAMP-DX format. On the other hand, proprietary library spectra can be exchanged and manipulated using proprietary tools. As the above examples have deficiencies according to the three long term data archiving criteria, Extensible Markup Language (XML; a product of the World Wide Web

  2. LONG-TERM MANAGEMENT OF PATIENTS AFTER ADRENALECTOMY

    PubMed Central

    Simkin, Benjamin

    1957-01-01

    Experience with the long-term medical management of 17 patients previously subjected to surgical adrenalectomy was reviewed. Maintenance adrenal cortical replacement requirements consisted of oral cortisone, 37.5 to 50 mg. daily in all patients; desoxycorticosterone acetate (DOCA), 2 mg. daily, sublingually in all patients; and supplemental sodium chloride, 1 to 4 grams daily, in seven patients. This provides steroids with glucocorticoid and mineralocorticoid activity and an adequate salt intake. The subjective well-being of the patient was the best indicator of adequate replacement therapy. Under stable conditions, established dosage schedules required surprisingly little adjustment over long periods of time. The primary need of patients without adrenal glands when they are subjected to such stresses as infections, trauma or surgical operation, is for more glucocorticoids. Ordinarily, more DOCA and extra sodium chloride is not required. Mild infections can be dealt with by temporarily increasing the daily oral cortisone requirement, the patient remaining ambulatory. Severe infections with pronounced systemic manifestations require hospitalization and parenteral administration of glucocorticoids. Knowing how long it takes for the various glucocorticoid preparations to take effect and how long they continue to act is important in the management of patients who have had adrenalectomy, particularly in dealing with extraordinary stresses or emergencies. PMID:13489497

  3. Effects of twice-daily icodextrin administration on blood pressure and left ventricular mass in patients on continuous ambulatory peritoneal dialysis.

    PubMed

    Sav, Tansu; Oymak, Oktay; Inanc, Mehmet Tugrul; Dogan, Ali; Tokgoz, Bulent; Utas, Cengiz

    2009-01-01

    Hypervolemia is a risk factor for left ventricular hypertrophy and hypertension in peritoneal dialysis patients. Icodextrin improves volume control by increasing ultrafiltration in peritoneal dialysis patients. To examine the effects of twice-daily icodextrin administration on blood pressure and left ventricular hypertrophy in peritoneal dialysis patients with hypervolemia and ultrafiltration failure. Administration of icodextrin twice daily resulted in a significant reduction in the left ventricular mass index (LVMI) of patients by the end of the third month (p < 0.05). The reduction in LVMI was also significant for the once-daily icodextrin group (p < 0.05). Mean blood pressure of patients receiving icodextrin twice daily was significantly reduced (p < 0.05). By the end of the third month no significant changes were observed in mean blood pressure of the patients using once-daily icodextrin (p > 0.05). No statistically significant changes were observed in weekly total creatinine clearances or Kt/V of patients in either group at the end of 3 months (NS). Twice-daily icodextrin administration was clinically beneficial as shown by reduced blood pressure and prevention of the progress of left ventricular hypertrophy without causing any decrease in dialysis adequacy or any side effects. The icodextrin metabolite results did not suggest any further increase in their values when comparing once- to twice-daily administration of icodextrin. Although prescription of icodextrin once daily may yield good clinical results in the long term, this study showed that it may be more efficient to use twice-daily icodextrin for at least a specific period for the purpose of obtaining quicker results in patients with ultrafiltration failure, serious hypervolemia, or hard-to-control blood pressure conditions.

  4. Modulation of axonal sprouting along rostro-caudal axis of dorsal hippocampus and no neuronal survival in parahippocampal cortices by long-term post-lesion melatonin administration in lithium-pilocarpine model of temporal lobe epilepsy

    PubMed Central

    Ganjkhani, Mahin; Ali, Rostami; Iraj, Jafari Anarkooli

    2016-01-01

    Feature outcome of hippocampus and extra-hippocampal cortices was evaluated in melatonin treated lithium-pilocarpine epileptic rats during early and chronic phases of temporal lobe epilepsy (TLE). After status epilepticus (SE) induction, 5 and 20 mg/kg melatonin were administered for 14 days or 60 days. All animals were killed 60 days post SE induction and the histological features of the rosrto-caudal axis of the dorsal hippocampus, piriform and entorhinal cortices were evaluated utilizing Nissl, Timm, and synapsin I immunoflorescent staining. Melatonin (20 mg/kg) effect on CA1 and CA3 neurons showed a region-specific pattern along the rostro-caudal axis of the dorsal hippocampus. The number of counted granular cells by melatonin (20 mg/kg) treatment increased along the rostro-caudal axis of the dorsal hippocampus in comparison to the untreated epileptic group. The density of Timm granules in the inner molecular layer of the dentate gyrus decreased significantly in all melatonin treated groups in comparison to the untreated epileptic animals. The increased density of synapsin I immunoreactivity in the outer molecular layer of the dentate gyrus of untreated epileptic rats showed a profound decrease following melatonin treatment. There was no neuronal protection in the piriform and entorhinal cortices whatever the melatonin treatment. Long-term melatonin administration as a co-adjuvant probably could reduce the post-lesion histological consequences of TLE in a region-specific pattern along the rostro-caudal axis of the dorsal hippocampus. PMID:27051565

  5. Long-term ginsenoside administration prevents memory loss in aged female C57BL/6J mice by modulating the redox status and up-regulating the plasticity-related proteins in hippocampus.

    PubMed

    Zhao, H F; Li, Q; Li, Y

    2011-06-02

    the hippocampus. These results demonstrated that long-term ginsenoside administration may prevent memory loss in aged C57BL/6J mice by modulating the redox status and up-regulating the plasticity-related proteins in hippocampus. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. Changes at cholecystokinin receptors induced by long-term treatment with diazepam and haloperidol.

    PubMed

    Vasar, E; Soosaar, A; Harro, J; Lang, A

    1992-12-01

    Fourteen days administration of haloperidol (1 mg/kg daily) prevented the motor depressant effect of caerulein (an agonist at cholecystokinin receptors, 15 micrograms/kg) and the antagonistic effect of caerulein (100 micrograms/kg) against (+)-amphetamine (5 mg/kg) induced hyperlocomotion in mice. The antiaggressive effect of caerulein (40 micrograms/kg) in saline-treated mice was replaced by increased aggressiveness after long-term haloperidol and diazepam (5 mg/kg daily) treatment. The anticonvulsant effect of caerulein (125 micrograms/kg) against picrotoxin (10 mg/kg) induced seizures was abolished after 14 days diazepam, but not after haloperidol, treatment. The above described changes in the mouse behaviour are probably related to the development of subsensitivity at CCKA receptors, whereas the CCKB receptor subtype becomes more sensitized to the action of caerulein after long-term haloperidol and diazepam treatment.

  7. Safety, Efficacy, and Persistence of Long-Term Mirabegron Treatment for Overactive Bladder in the Daily Clinical Setting: Interim (1-Year) Report from a Japanese Post-Marketing Surveillance Study.

    PubMed

    Kato, Daisuke; Tabuchi, Hiromi; Uno, Satoshi

    2017-08-01

    To report interim 1-year results from a 3-year surveillance study evaluating safety, efficacy, and persistence of long-term mirabegron for overactive bladder (OAB). Patients starting treatment with mirabegron for urinary urgency, daytime frequency, and urgency incontinence associated with OAB were registered and followed up for 3 years. Data were collected on adverse drug reactions (ADR), changes in OAB symptoms, changes in Overactive Bladder Symptom Score (OABSS), and treatment discontinuations. Treatment persistence rates were calculated by Kaplan-Meier analysis. Eighty-one ADR were observed in 72/1139 patients (6.3%) through 1 year of mirabegron treatment, with the incidence highest during the first month. No significant change in residual urine volume was observed at any observation point up to 1 year of mirabegron treatment. Mirabegron was deemed "effective" in 883/1091 patients (80.9%) at 1 year/discontinuation. Total OABSS was decreased with statistical significance at 3 months, 6 months, and 1 year, or at discontinuation (P < 0.001 at each time point). Kaplan-Meier treatment persistence rates were 84.8% at 3 months, 77.6% at 6 months, and 66.0% at 1 year. Treatment persistence rates were similar for male and female patients but significantly higher for patients aged ≥65 years (67.3%; n = 908) compared with those aged <65 years (59.8%; n = 231; log-rank test: P = 0.032). Long-term OAB treatment with mirabegron was well-tolerated, with effectiveness maintained through 1 year. Mirabegron treatment persistence was higher than has been previously reported, and was greater in patients aged ≥65 years compared with those aged <65 years. © 2017 John Wiley & Sons Australia, Ltd.

  8. RHEUMATOID ARTHRITIS—An Evaluation of Long-Term Treatment with Cortisone

    PubMed Central

    Engleman, Ephraim P.; Krupp, Marcus A.; Saunders, William W.; Wilson, Lloyd E.; Fredell, Erling W.

    1954-01-01

    Fifty-six patients with rheumatoid arthritis were treated continuously with cortisone for periods ranging between 4 and 38 months, in daily doses of 15 to 100 mg. Concomitant therapy included periods of rest, physical therapy, and salicylates. The incidence of subjective improvement exceeded that of objective improvement. The incidence of objective improvement was higher in females; also, in those patients whose disease was in an early stage and of short duration at the time therapy was begun, and who required relatively smaller maintenance doses of cortisone. Therapeutic results were not affected by the age of the patient or by the presence of spondylitis. Despite precautions, the long-term administration of cortisone was, in some patients, productive of serious undesirable side-effects. Although cortisone usually suppressed the symptoms and signs of rheumatoid arthritis, progression of the disease was frequently noted during its long-term administration. ImagesFigure 1 PMID:13150213

  9. The protective effects of long-term oral administration of marine collagen hydrolysate from chum salmon on collagen matrix homeostasis in the chronological aged skin of Sprague-Dawley male rats.

    PubMed

    Liang, Jiang; Pei, Xinrong; Zhang, Zhaofeng; Wang, Nan; Wang, Junbo; Li, Yong

    2010-10-01

    To investigate the long-term effects of marine collagen hydrolysate (MCH) from Chum Salmon skin on the aberrant collagen matrix homeostasis in chronological aged skin, Sprague-Dawley male rats of 4-wk-old were orally administrated with MCH at the diet concentrations of 2.25% and 4.5% for 24 mo. Histological and biochemical analysis revealed that MCH had the potential to inhibit the collagen loss and collagen fragmentation in chronological aged skin. Based on immunohistochemistry and western blot analysis, collagen type I and III protein expression levels in MCH-treated groups significantly increased as compared with the aged control group. Furthermore, quantitative real-time polymerase chain reaction and western blot analysis showed MCH was able to increase the expressions of procollagen type I and III mRNA (COL1A2 and COL3A1) through activating Smad signaling pathway with up-regulated TGF-βRII (TβRII) expression level. Meanwhile, MCH was shown to inhibit the age-related increased collagen degradation through attenuating MMP-1 expression and increasing tissue inhibitor of metalloproteinases-1 expression in a dose-dependent manner. Moreover, MCH could alleviate the oxidative stress in chronological aged skin, which was revealed from the data of superoxide dismutase activity and the thiobarbituric acid reactive substances level in skin homogenates. Therefore, MCH was demonstrated to have the protective effects on chronological skin aging due to the influence on collagen matrix homeostasis. And the antioxidative property of MCH might play an important role in the process.

  10. Peripheral administration of the soluble TNF inhibitor XPro1595 modifies brain immune cell profiles, decreases beta-amyloid plaque load, and rescues impaired long-term potentiation in 5xFAD mice.

    PubMed

    MacPherson, Kathryn P; Sompol, Pradoldej; Kannarkat, George T; Chang, Jianjun; Sniffen, Lindsey; Wildner, Mary E; Norris, Christopher M; Tansey, Malú G

    2017-06-01

    Clinical and animal model studies have implicated inflammation and peripheral immune cell responses in the pathophysiology of Alzheimer's disease (AD). Peripheral immune cells including T cells circulate in the cerebrospinal fluid (CSF) of healthy adults and are found in the brains of AD patients and AD rodent models. Blocking entry of peripheral macrophages into the CNS was reported to increase amyloid burden in an AD mouse model. To assess inflammation in the 5xFAD (Tg) mouse model, we first quantified central and immune cell profiles in the deep cervical lymph nodes and spleen. In the brains of Tg mice, activated (MHCII(+), CD45(high), and Ly6C(high)) myeloid-derived CD11b(+) immune cells are decreased while CD3(+) T cells are increased as a function of age relative to non-Tg mice. These immunological changes along with evidence of increased mRNA levels for several cytokines suggest that immune regulation and trafficking patterns are altered in Tg mice. Levels of soluble Tumor Necrosis Factor (sTNF) modulate blood-brain barrier (BBB) permeability and are increased in CSF and brain parenchyma post-mortem in AD subjects and Tg mice. We report here that in vivo peripheral administration of XPro1595, a novel biologic that sequesters sTNF into inactive heterotrimers, reduced the age-dependent increase in activated immune cells in Tg mice, while decreasing the overall number of CD4(+) T cells. In addition, XPro1595 treatment in vivo rescued impaired long-term potentiation (LTP) measured in brain slices in association with decreased Aβ plaques in the subiculum. Selective targeting of sTNF may modulate brain immune cell infiltration, and prevent or delay neuronal dysfunction in AD.

  11. The effect of banana (Musa acuminata) peels hot-water extract on the immunity and resistance of giant freshwater prawn, Macrobrachium rosenbergii via dietary administration for a long term: Activity and gene transcription.

    PubMed

    Rattanavichai, Wutti; Chen, Ying-Nan; Chang, Chin-Chyuan; Cheng, Winton

    2015-10-01

    The non-specific immune parameters, disease resistance and immune genes expressions in Macrobrachium rosenbergii were evaluated at 120 days of post feeding the diets containing the extracts of banana, Musa acuminate, fruit's peel (banana peels extract, BPE) at 0, 1.0, 3.0 and 6.0 g kg(-1). Results showed that prawns fed with a diet containing BPE at the level of 1.0, 3.0 and 6.0 g kg(-1) for 120 days had a significantly higher survival rate (30.0%, 40.0% and 56.7%, respectively) than those fed with the control diet after challenge with Lactococcus garvieae for 144 h, and the respective relative survival percentages were 22.2%, 33.3%, and 51.9%, respectively. Dietary BPE supplementation at 3.0 and/or 6.0 g kg(-1) for 120 days showed a significant increase total haemocyte count (THC), granular cell (GC), superoxide dismutase (SOD) activity, phenoloxidase (PO) activity, transglutaminase (TG) activity, and phagocytic activity and clearance efficiency to L. garvieae infection, and meanwhile, the significant decrease in haemolymph clotting times and respiratory bursts (RBs) per haemocyte of prawns were revealed. Furthermore, the mRNA expressions of prophenoloxidase (proPO), lipopolysaccharide and β-1,3-glucan binding protein (LGBP), peroxinectin (PE), transglutaminase (TG), and crustin (CT) were significantly increased. We therefore recommend that BPE can be used as an immunomodulator for prawns through dietary administration at 6.0 g kg(-1) for a long term (over 120 days) to modify immune responses and genes expression following the enhanced resistance against pathogens. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Medical care evaluation studies in long-term care facilities.

    PubMed

    Zimmer, J G

    1979-02-01

    This report describes the selection, design, conduct, analysis, and application of medical care evaluation studies in long-term care facilities (skilled nursing homes) in a regional program in the Rochester region of upstate New York. Eight examples are presented to highlight methodologic approaches and problems. They are classified under four general headings: Administration Audits, Diagnosis-specific Studies, Care Modality-specific Studies, and General Outcome Indicators. The implementation of results and recommendations from the studies is discussed and an application of "tracer" methodology for assessing the components of care activities in long-term facilities is described. Problems and challenges in long-term quality care are outlined.

  13. Long-term experience with indapamide.

    PubMed

    Beling, S; Vukovich, R A; Neiss, E S; Zisblatt, M; Webb, E; Losi, M

    1983-07-01

    Indapamide, 2.5 mg administered once daily for periods up to 36 months, was found to be safe and effective for the long-term control of mild to moderate hypertension. The effects of hydrochlorothiazide, 50 mg, and indapamide, 2.5 mg, were studied in two randomized, double-blind, multicenter trials. Data from the two multicenter trials (20 study sites) were pooled for purposes of comparison. Significant reductions in systolic and diastolic blood pressure, with patients in both supine and standing positions, occurred in both groups within the first 8 weeks of treatment. This effect was maintained throughout the active treatment period. Success, as determined by the therapeutic success rate (percentage of patients with decreases of standing phase V diastolic blood pressure of at least 10 mm Hg or to below 90 mm Hg), occurred in 53% of the patients given hydrochlorothiazide and in 56% of the indapamide-treated patients. During the study period, the nature, frequency, and severity of adverse reactions were similar for both groups. There was no clinically significant difference between the treatment groups for the laboratory assessments. Patients who completed the multicenter trials were eligible for participation in an ongoing long-term extension study of the safety of indapamide. Data are available for periods up to 36 months and demonstrate neither augmentation of clinical or laboratory adverse effects nor any potentially harmful indicators that could be attributed to prolonged treatment.

  14. Long term effects of Escherichia coli mastitis.

    PubMed

    Blum, Shlomo E; Heller, Elimelech D; Leitner, Gabriel

    2014-07-01

    Escherichia coli is one of the most frequently diagnosed causes of bovine mastitis, and is typically associated with acute, clinical mastitis. The objective of the present study was to evaluate the long term effects of intramammary infections by E. coli on milk yield and quality, especially milk coagulation. Twenty-four Israeli Holstein cows diagnosed with clinical mastitis due to intramammary infection by E. coli were used in this study. Mean lactation number, days in milk (DIM) and daily milk yield (DMY) at the time of infection was 3.3 ± 1.3, 131.7 days ± 78.6 and 45.7 L ± 8.4, respectively. DMY, milk constituents, somatic cells count (SCC), differential leukocytes count and coagulation parameters were subsequently assessed. Two patterns of inflammation were identified: 'short inflammation', characterized by <15% decrease in DMY and <30 days until return to normal (n = 5), and 'long inflammation', characterized by >15% decrease in DMY and >30 days to reach a new maximum DMY (n = 19). The estimated mean loss of marketable milk during the study was 200 L/cow for 'short inflammation' cases, and 1,500 L/cow for 'long inflammation' ones. Significant differences between 'short' and 'long inflammation' effects were found in almost all parameters studied. Long-term detrimental effects on milk quality were found regardless of clinical or bacteriological cure of affected glands.

  15. Long-term oxygen therapy.

    PubMed

    Christopher, Kent L; Porte, Phillip

    2011-02-01

    This article provides an overview of the status of long-term oxygen therapy (LTOT). In the United States, payment cutbacks are occurring as a result of congressionally mandated competitive bidding and capped rental programs. These Medicare programs are discussed. These legislative and regulatory changes may result in reduced patient access to appropriate oxygen-delivery systems that meet medical needs, including optimal ambulation. Prescribing LTOT is addressed in this article, as is the need for adequate patient education. The importance of appropriate monitoring and reassessment is presented. The use of an LTOT collaborative care model is discussed. Although the new intermittent flow oxygen-delivery systems have potential benefits, there is consensus that each patient should be tested on the specific device because of variability in delivery and patient response. Feasible locations for patient education and monitoring are identified.

  16. Long-Term Outcomes after Treatment with Clofarabine ± Fludarabine with Once-Daily Intravenous Busulfan as Pretransplant Conditioning Therapy for Advanced Myeloid Leukemia and Myelodysplastic Syndrome.

    PubMed

    Alatrash, Gheath; Thall, Peter F; Valdez, Benigno C; Fox, Patricia S; Ning, Jing; Garber, Haven R; Janbey, Selma; Worth, Laura L; Popat, Uday; Hosing, Chitra; Alousi, Amin M; Kebriaei, Partow; Shpall, Elizabeth J; Jones, Roy B; de Lima, Marcos; Rondon, Gabriela; Chen, Julianne; Champlin, Richard E; Andersson, Borje S

    2016-10-01

    Pretransplant conditioning regimens critically determine outcomes in the setting of allogeneic stem cell transplantation (allo-SCT). The use of nucleoside analogs such as fludarabine (Flu) in combination with i.v. busulfan (Bu) has been shown to be highly effective as a pretransplant conditioning regimen in acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and myelodysplastic syndrome (MDS). Because leukemia relapse remains the leading cause of death after allo-SCT, we studied whether clofarabine (Clo), a nucleoside analog with potent antileukemia activity, can be used to complement Flu. In a preliminary report, we previously showed the safety and efficacy of Clo ± Flu with i.v. Bu in 51 patients with high-risk AML, CML, and MDS. The study has now been completed, and we present long-term follow-up data on the entire 70-patient population, which included 49 (70%), 8 (11%), and 13 (19%) patients with AML, MDS, and CML, respectively. Thirteen patients (19%) were in complete remission, and 41 patients (59%) received matched unrelated donor grafts. Engraftment was achieved in all patients. Sixty-three patients (90%) achieved complete remission. There were no deaths reported at day +30, and the 100-day nonrelapse mortality rate was 4% (n = 3). Thirty-one percent of patients (n = 22) developed grades II to IV acute graft-versus-host disease, and the median overall survival and progression-free survival times were 2.4 years and .9 years, respectively. Our results confirm the safety and overall and progression-free survival advantage of the arms with higher Clo doses and lower Flu doses, which was most prominent in the AML/MDS group.

  17. Long term care facilities: the benefits of having a dietitian.

    PubMed

    Gardner, J

    1983-01-01

    This article describes the improvements made by a dietitian in two long term care facilities. Neither facility had previously employed a dietitian. Nutritional status of residents was improved by menu revisions that included more dairy products. Accurate serving of calculated diets was instigated. Administrative tools such as policy and procedure manuals and standardized recipes were introduced. It is to be hoped that the positive experiences of these long term care facilities in employing dietitians will encourage other facilities to follow suit.

  18. Withdrawal from long-term benzodiazepine treatment.

    PubMed Central

    Petursson, H; Lader, M H

    1981-01-01

    Long-term, normal-dose benzodiazepine treatment was discontinued in 16 patients who were suspected of being dependent on their medication. The withdrawal was gradual, placebo-controlled, and double-blind. All the patients experienced some form of withdrawal reaction, which ranged from anxiety and dysphoria to moderate affective and perceptual changes. Symptom ratings rose as the drugs were discontinued, but usually subsided to prewithdrawal levels over the next two to four weeks. Other features of the withdrawal included disturbance of sleep and appetite and noticeable weight loss. Electroencephalography showed appreciable reduction in fast-wave activity as the drugs were withdrawn, and an improvement in psychological performance was recorded by the Digit Symbol Substitution Test. Because of the risk of dependence on benzodiazepines these agents should probably not be given as regular daily treatment for chronic anxiety. PMID:6114776

  19. Asthma Medicines: Long-Term Control

    MedlinePlus

    ... Size Email Print Share Asthma Medicines: Long-term Control Page Content Article Body Corticosteroids Synthetic versions of ... form, they are used exclusively for long-term control; they are not very effective for acute symptoms. ...

  20. Consumer Direction in Long-Term Care.

    ERIC Educational Resources Information Center

    Generations, 2000

    2000-01-01

    Issue includes 17 theme articles on long-term care, covering legal issues, federal role, state programs, demonstration programs, family caregivers, home health care, home care workers, culturally appropriate long-term care, financial support, and cognitive impairments. (SK)

  1. Long Term Surface Salinity Measurements

    NASA Technical Reports Server (NTRS)

    Schmitt, Raymond W.; Brown, Neil L.

    2005-01-01

    Our long-term goal is to establish a reliable system for monitoring surface salinity around the global ocean. Salinity is a strong indicator of the freshwater cycle and has a great influence on upper ocean stratification. Global salinity measurements have potential to improve climate forecasts if an observation system can be developed. This project is developing a new internal field conductivity cell that can be protected from biological fouling for two years. Combined with a temperature sensor, this foul-proof cell can be deployed widely on surface drifters. A reliable in-situ network of surface salinity sensors will be an important adjunct to the salinity sensing satellite AQUARIUS to be deployed by NASA in 2009. A new internal-field conductivity cell has been developed by N Brown, along with new electronics. This sensor system has been combined with a temperature sensor to make a conductivity - temperature (UT) sensor suitable for deployment on drifters. The basic sensor concepts have been proven on a high resolution CTD. A simpler (lower cost) circuit has been built for this application. A protection mechanism for the conductivity cell that includes antifouling protection has also been designed and built. Mr. A.Walsh of our commercial partner E-Paint has designed and delivered time-release formulations of antifoulants for our application. Mr. G. Williams of partner Clearwater Instrumentation advised on power and communication issues and supplied surface drifters for testing.

  2. AB055. Long term NIV

    PubMed Central

    Siopi, Dimitra

    2016-01-01

    During the last decades, non-invasive mechanical ventilation has evolved into one of the most evidence-based areas of respiratory medicine, with many indications in acute or chronic respiratory failure. From the first application of negative pressure models during poliomyelitis epidemics to the new sophisticated positive pressure models, and the development of the “intelligent ventilators”, there has been a long time course. Undoubtedly the spur was given by better understanding of respiratory physiology during sleep and the shift of healthcare towards a chronic base. Novel randomized controlled trials (RCTs) established the use of NIV in acute respiratory failure due to exacerbations of COPD, as well as acute pulmonary edema and weaning from invasive mechanical ventilation. Long-term NIV has been used in neuromuscular diseases for many decades, first in Duchenne muscular dystrophy, and then spreading to other disorders of this category, increasing survival in inherited neuromuscular diseases. NIV should be initiated early in the course of the disease, when symptomatic nocturnal hypoventilation is detected. Combined with cough augmentation (physiotherapy, insufflation-exsufflation devices) and percutaneous gastrostomy feeding, it can delay tracheostomy and invasive ventilation. In ALS patients NIV improves the quality of life and increases survival, especially when there is no bulbar involvement. The right time to initiate ventilation in this group of patients is not well established since it is difficult to detect signs and symptom of respiratory impairment. Patients seem to benefit from an early application of NIV, and their personal decisions should always be considered before any intervention. In patients with chest wall disorders NIV—despite the fact that RCTs are lacking—has proved its value in many uncontrolled trials and numerous reports. It seems to improve the work of breathing, sleep architecture, nocturnal and daytime arterial blood gases. The

  3. Stapedectomy - long-term report.

    PubMed

    Shea, J J

    1982-01-01

    The long-term results with large fenestra stapedectomy with vein graft and Teflon piston are compared with results with the small fenestra stapedectomy with teflon piston directly into the vestibule. There were 1,943 operations in the former group and 2,155 in the latter when compared in 1970. One hundred consecutive patients from the beginning of each group with follow-up to present were compared. Results were generally the same with no great change in 15 and 20 years as compared to those at 5 years. The complication of perilymph fistula was caused by creating an opening in the footplate much larger than the prosthesis and was eliminated by interposing a living oval window seal if the opening was much larger than the prosthesis and a flap of lining membrane from the promontory when it was not. Other factors that influence a good result are discussed, including the type and the diameter of the piston used, the type of living oval window seal and the method of attachment to the incus. The small fenestra operation was found to be superior to the large, not only for the hearing gain achieved, but the case of performance and the freedom from complications due to migration of the prosthesis and/or the oval window seal. At present we have done about all that can be done for the conductive components. What remains is the sensorineural component which our studies indicate may be due to an autoimmune response.

  4. Long-term corrosion studies

    SciTech Connect

    Gdowski, G.

    1998-05-29

    The scope of this activity is to assess the long-term corrosion properties of metallic materials under consideration for fabricating waste package containers. Three classes of metals are to be assessed: corrosion resistant, intermediate corrosion resistant, and corrosion allowance. Corrosion properties to be evaluated are general, pitting and crevice corrosion, stress-corrosion cracking, and galvanic corrosion. The performance of these materials will be investigated under conditions that are considered relevant to the potential emplacement site. Testing in four aqueous solutions, and vapor phases above them, and at two temperatures are planned for this activity. (The environmental conditions, test metals, and matrix are described in detail in Section 3.0.) The purpose and objective of this activity is to obtain the kinetic and mechanistic information on degradation of metallic alloys currently being considered for waste package containers. This information will be used to provide assistance to (1) waste package design (metal barrier selection) (E-20-90 to E-20-92), (2) waste package performance assessment activities (SIP-PA-2), (3) model development (E-20-75 to E-20-89). and (4) repository license application.

  5. Long-Term Planning in Higher Education.

    ERIC Educational Resources Information Center

    United Nations Educational, Scientific and Cultural Organization, Bangkok (Thailand). Principal Regional Office for Asia and the Pacific.

    This report presents the concepts and issues discussed at a Regional Symposium on Long-term Planning in Higher Education held in Dhaka, Bangladesh, September 21-30, 1986. Chapter 1 explores some fundamental issues about the rationale for the objectives of long-term planning. It defines long-term planning in higher education, considers its…

  6. Long Term TOA - M Data and Information

    Atmospheric Science Data Center

    2015-06-30

    A Long-Term TOA and Constrained Surface Radiation Budget Project A Long-Term TOA and Constrained Surface Readiation Budget Dataset Using Merged CERES, ... and apply the knowledge to existing data to develop long-term (nearly 30 years) consistent and calibrated data product (TOA irradiances ...

  7. Long-Term Administration of Dehydroepiandrosterone Accelerates Glucose Catabolism via Activation of PI3K/Akt-PFK-2 Signaling Pathway in Rats Fed a High-Fat Diet

    PubMed Central

    Kang, Jian; Ge, Chongyang; Yu, Lei; Li, Longlong; Ma, Haitian

    2016-01-01

    Dehydroepiandrosterone (DHEA) has a fat-reducing effect, while little information is available on whether DHEA regulates glucose metabolism, which would in turn affect fat deposition. To investigate the effects of DHEA on glucose metabolism, rats were administered a high-fat diet containing either 0 (HCG), 25 (HLG), 50 (HMG), or 100 (HHG) mg·kg-1 DHEA per day via gavage for 8 weeks. Results showed that long-term administration of DHEA inhibited body weight gain in rats on a high-fat diet. No statistical differences in serum glucose levels were observed, whereas hepatic glycogen content in HMG and HHG groups and muscle glycogen content in HLG and HMG groups were higher than those in HCG group. Glucokinase, malate dehydrogenase and phosphofructokinase-2 activities in HMG and HHG groups, pyruvate kinase and succinate dehydrogenase activities in HMG group, and pyruvate dehydrogenase activity in all DHEA treatment groups were increased compared with those in HCG group. Phosphoenolpyruvate carboxykinase and glycogen phosphorylase mRNA levels were decreased in HMG and HHG groups, whereas glycogen synthase-2 mRNA level was increased in HMG group compared with those in HCG. The abundance of Glut2 mRNA in HMG and HHG groups and Glut4 mRNA in HMG group was higher than that in HCG group. DHEA treatment increased serum leptin content in HMG and HHG groups compared with that in HCG group. Serum insulin content and insulin receptor mRNA level in HMG group and insulin receptor substrate-2 mRNA level in HMG and HHG group were increased compared with those in HCG group. Furthermore, Pi3k mRNA level in HMG and Akt mRNA level in HMG and HHG groups were significantly increased than those in HCG group. These data showed that DHEA treatment could enhance glycogen storage and accelerate glucose catabolism in rats fed a high-fat diet, and this effect may be associated with the activation of PI3K/Akt-PFK-2 signaling pathway. PMID:27410429

  8. Long-term U. S. energy outlook

    SciTech Connect

    Friesen, G.

    1984-01-01

    Each year Chase Econometrics offers its clients a brief summary of the assumptions underlying the long-term energy forecast for the U.S. To illustrate the uncertainty involved in forecasting for the period to the year 2000, they choose to compare forecasts with some recent projections prepared by the Department of Energy's Office of Policy, Planning and Analysis for the annual National Energy Policy Plan supplement. Particular emphasis is placed on Scenario B, which is the mid-range reference case. As the introduction to the supplement emphasizes, the NEPP projections should not be considered a statement of the policy goals of the Reagan Administration. They represent an analysis of the possible evolution of U.S. energy markets, given current information and existing policies. The purpose of providing Scenario B as a reference case as well as Scenarios A and C as alternate cases is to show the sensitivity of oil price projections to small swings in energy demand.

  9. Elders' Use of Informal Long-Term Care Assistance.

    ERIC Educational Resources Information Center

    Branch, Laurence G.; Jette, Alan M.

    1983-01-01

    Over 80 percent of a sample of community-living elderly were self-sufficient in performing basic activities of daily living (ADL); only 18 percent were self-sufficient in performing instrumental ADL. Most elders who use long-term care assistance relied solely on the informal support network in both instrumental (86 percent) and basic (50 percent)…

  10. Risk factors for hypernatremia in patients with short- and long-term tolvaptan treatment.

    PubMed

    Hirai, Keita; Shimomura, Tatsuki; Moriwaki, Hideaki; Ishii, Hidetoshi; Shimoshikiryo, Takayuki; Tsuji, Daiki; Inoue, Kazuyuki; Kadoiri, Toshihiko; Itoh, Kunihiko

    2016-10-01

    The long-term efficacy of tolvaptan, a vasopressin V2 receptor antagonist, has been reported. However, the safety of long-term treatment remains to be fully elucidated. We assessed the safety profile of tolvaptan with respect to hypernatremia. This retrospective study included 371 patients treated with tolvaptan. Risk factors for hypernatremia (serum sodium concentration ≥147 mEq/L) were determined. Hypernatremia occurred in 95 patients (25.6 %), of whom 71 (19.1 %) developed hypernatremia within 7 days of tolvaptan treatment (early onset). Stepwise logistic regression analysis demonstrated that baseline serum sodium ≥140 mEq/L, an initial tolvaptan dosage >7.5 mg, and a BUN/serum creatinine ratio ≥20 were independent risk factors for early onset of hypernatremia. Tolvaptan was prescribed for more than 7 days to 233 patients, of whom 123 were administrated tolvaptan for more than 1 month. Hypernatremia occurred in 24 of these patients (10.3 %) (late onset). Predictive factors for late onset of hypernatremia were an average daily dosage of tolvaptan >7.5 mg and age ≥75 years. A daily dosage of 7.5 mg or less was recommended to prevent hypernatremia in short- as well as long-term tolvaptan treatment, and mainly elderly patients were at risk for hypernatremia.

  11. Prolonged Administration of Twice-Daily Bolus Intravenous Tacrolimus in the Early Phase After Lung Transplantation.

    PubMed

    Hirano, Yutaka; Sugimoto, Seiichiro; Mano, Toshifumi; Kurosaki, Takeshi; Miyoshi, Kentaroh; Otani, Shinji; Yamane, Masaomi; Kobayashi, Motomu; Miyoshi, Shinichiro; Oto, Takahiro

    2017-08-11

    BACKGROUND Although administration of tacrolimus, whether by the enteric, sublingual, or continuous intravenous routes, has some limitations, twice-daily bolus intravenous tacrolimus administration has been shown to be beneficial in optimizing efficacy and safety after lung transplantation. However, at present, the duration of bolus intravenous tacrolimus administration is limited, and the effects of prolonged bolus intravenous tacrolimus administration remain unknown. Our study was aimed at assessing the safety and efficacy of prolonged twice-daily bolus intravenous tacrolimus administration in the early phase after lung transplantation. MATERIAL AND METHODS We retrospectively investigated the data of 62 recipients of lung transplantation who had received twice-daily bolus intravenous administration of tacrolimus, followed by oral tacrolimus, after lung transplantation at our institution between January 2011 and October 2015. RESULTS The median duration of bolus intravenous tacrolimus administration was 19 days (4-72 days). The target trough level was achieved in 89% of the patients by day 3. Acute kidney injury occurred in 27% of the patients during bolus intravenous tacrolimus. Two patients (3%) had neurotoxicity, necessitating discontinuation of tacrolimus. Suspected acute rejection requiring steroid pulse therapy occurred in 21% of patients during the follow-up period. Eight patients (13%) developed chronic lung allograft dysfunction during the follow-up period. The 1-year and 5-year survival rates after lung transplantation were 95% and 76%, respectively. CONCLUSIONS These results suggest that prolonged bolus intravenous tacrolimus administration in the early phase after lung transplantation is a safe and effective alternative to enteric, sublingual, or continuous intravenous administration.

  12. Effects of daily delta-9-tetrahydrocannabinol treatment on heroin self-administration in rhesus monkeys

    PubMed Central

    Maguire, David R.; France, Charles P.

    2015-01-01

    Opioid abuse remains a significant public health problem; together with the greater availability of marijuana in some regions there is an increasing likelihood that opioids and marijuana will be used together. Poly-drug abuse is associated with increased toxicity and poorer treatment outcome; thus, a better understanding of the consequences of repeated co-administration of these drugs will facilitate the development of better prevention and treatment strategies. This study examined the effects of daily treatment with the cannabinoid receptor agonist delta-9-tetrahydrocannabinol (Δ9-THC) and its discontinuation on self-administration of heroin in rhesus monkeys (n=4) lever-pressing under a fixed-ratio 30 schedule. Heroin self-administration (0.32–32 μg/kg/infusion, i.v.) generated an inverted U-shaped dose–effect curve. Administered acutely, Δ9-THC (0.01–0.32 mg/kg, s.c.) dose dependently decreased responding for heroin and flattened the self-administration dose-effect curve. Daily treatment with Δ9-THC (0.01–0.1 mg/kg/12hr, s.c.) either had no effect on or decreased responding for heroin. In addition, daily treatment did not significantly impact extinction of heroin self-administration or resumption of responding for heroin after extinction. Discontinuation of daily Δ9-THC treatment did not systematically impact rates of heroin self-administration. These data suggest that repeated administration of a cannabinoid receptor agonist likely does not increase, and possibly decreases, the positive reinforcing effects of a mu opioid receptor agonist. PMID:26397756

  13. Long-term solar-terrestrial observations

    NASA Technical Reports Server (NTRS)

    1988-01-01

    The results of an 18-month study of the requirements for long-term monitoring and archiving of solar-terrestrial data is presented. The value of long-term solar-terrestrial observations is discussed together with parameters, associated measurements, and observational problem areas in each of the solar-terrestrial links (the sun, the interplanetary medium, the magnetosphere, and the thermosphere-ionosphere). Some recommendations are offered for coordinated planning for long-term solar-terrestrial observations.

  14. Caffeine and diphenyl diselenide improve long-term memory impaired in middle-aged rats.

    PubMed

    Leite, Marlon R; Marcondes Sari, Marcel Henrique; de Freitas, Mayara L; Oliveira, Lia P; Dalmolin, Laíza; Brandão, Ricardo; Zeni, Gilson

    2014-05-01

    The aim of the present study was to evaluate the effects of diphenyl diselenide (PhSe)2 supplemented diet (10ppm) associated to the administration of caffeine (15mg/kg; i.g.) for 30days on the novel object recognition memory in middle-aged rats. The present findings showed that (PhSe)2-supplemented diet enhanced short-term memory, but not long-term memory, of middle-aged rats in the novel object recognition task. The (PhSe)2 supplemented diet associated with caffeine administration improved long-term memory, but did not alter short-term memory, impaired in middle-aged rats. Daily caffeine administration to middle-aged rats had no effect on the memory tasks. Diet supplemented with (PhSe)2 plus caffeine administration increased the number of crossings and rearings reduced in middle-aged rats. Caffeine administration plus (PhSe)2 diets were effective in increasing the number of rearings and crossings, respectively, in middle-aged rats, [(3)H] glutamate uptake was reduced in hippocampal slices of rats from (PhSe)2 and caffeine plus (PhSe)2 groups. In addition, animals supplemented with (PhSe)2 showed an increase in the pCREB/CREB ratio whereas pAkt/Akt ratio was not modified. These results suggest that the effects of (PhSe)2 on the short-term memory may be related to its ability to decrease the uptake of glutamate, influencing the increase of CREB phosphorylation. (PhSe)2-supplemented diet associated to the administration of caffeine improved long-term memory impaired in middle-aged rats, an effect independent of CREB and Akt phosphorylation. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. [Perspectives in long-term care insurance].

    PubMed

    Pick, P

    2007-03-01

    Twelve years after its introduction, long-term care insurance is back on the agenda and up for political reform. This paper shows why long-term care insurance needs to be reformed. The two central aspects on which reform projects focus are addressed: firstly, the structural improvement of nursing care and long-term care insurance and, secondly, the creation of a sustained financing. The principal conclusion is that, while there is a broad consensus about the structural improvement of long-term care insurance, opinions differ widely in the matter of its sustained financing. As a consequence, a coherent financing concept has yet to emerge.

  16. The nature of long-term care nursing work.

    PubMed

    Leppa, Carol J

    2004-03-01

    Data from a pilot study on the nature of nursing work in long-term care (LTC) facilities are compared with data on nursing work in intensive care units (ICUs). The comparison suggests that the LTC nursing work environment is a complex, demanding, and interesting one that is different from, not less than, nursing work in acute care environments. The data also suggests that nursing educators and researchers should reconsider LTC nursing work environments. Long-term care nursing offers an ideal, relatively controlled environment for research on what nursing work is and how nursing interventions affect patient outcomes. Long-term care nurses, whose daily work has always involved working with a variety of professional and unlicensed staff members, can serve as models for delegation and interpersonal skills. Finally, the LTC setting offers the ideal environment for clinical sites in connection with the proposed curriculum changes in end-of-life care for patients and their families.

  17. Effects of daily delta-9-tetrahydrocannabinol treatment on heroin self-administration in rhesus monkeys.

    PubMed

    Maguire, David R; France, Charles P

    2016-04-01

    Opioid abuse remains a significant public health problem; together with the greater availability of marijuana in some regions there is an increasing likelihood that opioids and marijuana will be used together. Polydrug abuse is associated with increased toxicity and poorer treatment outcome; thus, a better understanding of the consequences of repeated coadministration of these drugs will facilitate the development of better prevention and treatment strategies. This study examined the effects of daily treatment with the cannabinoid receptor agonist delta-9-tetrahydrocannabinol (Δ-THC) and its discontinuation on self-administration of heroin in rhesus monkeys (n=4) lever-pressing under a fixed-ratio 30 schedule. Heroin self-administration (0.32-32 μg/kg/infusion, intravenously) generated an inverted U-shaped dose-effect curve. Administered acutely, Δ-THC (0.01-0.32 mg/kg, subcutaneously) dose dependently decreased responding for heroin and flattened the self-administration dose-effect curve. Daily treatment with Δ-THC (0.01-0.1 mg/kg/12 h, subcutaneously) either had no effect on or decreased responding for heroin. In addition, daily treatment did not significantly impact extinction of heroin self-administration or resumption of responding for heroin after extinction. Discontinuation of daily Δ-THC treatment did not systematically impact rates of heroin self-administration. These data suggest that repeated administration of a cannabinoid receptor agonist likely does not increase, and possibly decreases, the positive reinforcing effects of a mu opioid receptor agonist.

  18. Appearance of anaphylactic shock after long-term intravenous itraconazole treatment.

    PubMed

    Chen, Jie; Song, Xianmin; Yang, Peng; Wang, Jianmin

    2009-03-01

    To report a rare but severe adverse effect of intravenous itraconazole, anaphylactic shock with hypotension and hypoxemia, in a female patient with acute lymphoblastic leukemia (ALL). A 36-year-old woman with ALL received antifungal therapy for pulmonary fungal infections. On day 17 of itraconazole treatment, she developed hypotension and hypoxemia shock after intravenous administration of itraconazole 200 mg, which was eventually reversed by steroid treatment. On days 18 and 19, the patient developed the same type of shock 2 more times in the course of itraconazole administration. These 2 episodes of shock occurred more quickly after intravenous itraconazole administration (100 mg on day 18, 40 mg on day 19), and were reversed by stopping itraconazole and applying steroid treatment. In the modified antifungal therapy, intravenous administration of itraconazole was replaced by oral administration of voriconazole 200 mg twice daily. Shock did not recur after discontinuation of itraconazole treatment. The Naranjo probability scale showed a probable relationship between itraconazole treatment and shock occurrence. Itraconazole is a widely used antifungal drugs and is well tolerated. However, long-term itraconazole treatment might lead to serious and even life-threatening adverse effects such as anaphylactic shock, as seen in our patient. T cell reduction caused by immunosuppression and itraconazole accumulation in patients with ALL are considered to be important causal factors for this delayed-type hypersensitivity reaction. Anaphylactic shock represents a previously undocumented severe adverse effect associated with long-term itraconazole treatment; patients receiving this therapy and should be monitored closely.

  19. Long-term in vivo pineal microdialysis.

    PubMed

    Sun, Xing; Liu, Tiecheng; Deng, Jie; Borjigin, Jimo

    2003-09-01

    This study describes the development of a new technique for long-term measurement of daily 5-hydroxytryptamine (5-HT) and melatonin contents in the pineal gland of freely moving rats. The technique features a number of novel improvements over previous protocols. It allows visualization of the pineal gland for accurate targeting of the guide cannula, which minimizes bleeding; incurs no direct injury to the surrounding brain tissues; and causes no interference with the sympathetic innervation from the superior cervical ganglia. Robust releases of melatonin and indole precursors were continuously monitored quantitatively and reproducibly for more than 2 wk in the same animal. In addition, effects of pharmacological agents on in vivo pineal circadian rhythms can be studied reproducibly over time, and gene expression profiles can be correlated with physiological consequences in single animals. Using these approaches, it is found that beta-adrenergic activation leads to decreased release of 5-HT, and that increased cAMP signaling in vivo results in activation of N-acetyltransferase gene induction and melatonin production. These studies will enhance the understanding of signaling pathways that regulate pineal 5-HT and melatonin synthesis and secretion.

  20. Suicidal Behavior in Long-Term Care Facilities.

    ERIC Educational Resources Information Center

    Osgood, Nancy J.; Brant, Barbara A.

    1990-01-01

    Surveyed administrators of 463 long-term care facilities concerning overt suicides and intentional life-threatening behaviors. Data revealed that White males were highest risk group. Refusal to eat, drink, or take medications were most common suicidal behaviors. Depression, loneliness, feelings of family rejection, and loss were significant…

  1. 78 FR 36449 - State Long-Term Care Ombudsman Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-18

    ... HUMAN SERVICES Administration on Aging 45 CFR Parts 1321 and 1327 RIN 0985-AA08 State Long-Term Care...) within the Department of Health and Human Services (HHS) is issuing a Notice of Proposed Rulemaking, with... Aging, US Department of Health and Human Services, Attention: Becky Kurtz, Washington, DC 20201. Please...

  2. Virtual Models of Long-Term Care

    ERIC Educational Resources Information Center

    Phenice, Lillian A.; Griffore, Robert J.

    2012-01-01

    Nursing homes, assisted living facilities and home-care organizations, use web sites to describe their services to potential consumers. This virtual ethnographic study developed models representing how potential consumers may understand this information using data from web sites of 69 long-term-care providers. The content of long-term-care web…

  3. Virtual Models of Long-Term Care

    ERIC Educational Resources Information Center

    Phenice, Lillian A.; Griffore, Robert J.

    2012-01-01

    Nursing homes, assisted living facilities and home-care organizations, use web sites to describe their services to potential consumers. This virtual ethnographic study developed models representing how potential consumers may understand this information using data from web sites of 69 long-term-care providers. The content of long-term-care web…

  4. Long Term Preservation of Digital Information.

    ERIC Educational Resources Information Center

    Lorie, Raymond A.

    The preservation of digital data for the long term presents a variety of challenges from technical to social and organizational. The technical challenge is to ensure that the information, generated today, can survive long term changes in storage media, devices, and data formats. This paper presents a novel approach to the problem. It distinguishes…

  5. Long-Term Nutrition: A Clinician's Guide to Successful Long-Term Enteral Access in Adults.

    PubMed

    Bechtold, Matthew L; Mir, Fazia A; Boumitri, Christine; Palmer, Lena B; Evans, David C; Kiraly, Laszlo N; Nguyen, Douglas L

    2016-09-22

    Long-term nutrition support requires long-term enteral access. To ensure the success of long-term enteral access, many factors need to be taken into consideration. This article represents a guide to placing and maintaining access in patients requiring long-term nutrition and addresses many of the common questions regarding long-term enteral access, such as indications, types of access, feeding after access placed, and recognition and treatment of potential complications. This guide will help the clinician establish and maintain access to maximize nutrition in patients requiring long-term nutrition.

  6. Long term and transitional intermittent smokers: a longitudinal study

    PubMed Central

    Lindstrom, M; Isacsson, S

    2002-01-01

    Objective: To investigate differences in snuff consumption, sociodemographic and psychosocial characteristics between baseline intermittent smokers that had become daily smokers, stopped smoking or remained intermittent smokers at the one year follow up. Design/setting/participants/measurements: A population of 12 507 individuals interviewed at baseline in 1992-94 and at a one year follow up, aged 45–69 years, was investigated in a longitudinal study. The three groups of baseline intermittent smokers were compared to the reference population (all others) according to sociodemographic, psychosocial, and snuff consumption characteristics. A multivariate logistic regression model was used to assess differences in psychosocial conditions, adjusting for age, sex, country of origin, marital status, education, and snuff consumption. Results: 60% of all baseline intermittent smokers had remained intermittent smokers, 16% had become daily smokers, and 24% had stopped smoking at the one year follow up. The long term intermittent smokers and those who had stopped smoking were young, unmarried, highly educated, and snuff consumers to a higher extent than the reference population. They also had more psychosocial resources than the reference population, while the psychosocial resources of those who had become daily smokers were poorer. Conclusions: The majority of intermittent smokers are long term intermittent smokers. The results suggest that long term intermittent smokers have other psychosocial characteristics than daily smokers. PMID:11891370

  7. Paying for long-term care.

    PubMed Central

    Estes, C L; Bodenheimer, T

    1994-01-01

    Everyone agrees that insurance for long-term care is inadequate in the United States. Disagreement exists, however, on whether such insurance should be provided through the private or public sector. Private insurance generally uses the experience-rating principle that persons with higher risk of illness are charged higher premiums. For private insurance for long-term care, this principle creates a dilemma. Most policies will be purchased by the elderly; yet, because the elderly have a high risk of needing long-term care, only about 20% of them can afford the cost of premiums. A public-private partnership by which the government partially subsidizes private long-term-care insurance is unlikely to resolve this dilemma. Only a social insurance program for long-term care can provide universal, affordable, and equitable coverage. PMID:8128712

  8. Cytokine profiles in long-term smokers of opium (Taryak).

    PubMed

    Ghazavi, Ali; Solhi, Hassan; Moazzeni, Seyed Mohammad; Rafiei, Mohammad; Mosayebi, Ghasem

    2013-01-01

    There are few studies with conflicting results on the effects of in vivo administration of opioids on immune function. The aim of this study was to evaluate the serum levels of interferon (IFN)-γ, interleukin (IL)-4, IL-10, IL-17, and hs-C-reactive protein (hs-CRP) in opium smokers. The study was conducted between 44 male opium addicts and 44 controls aged 20 to 40 years. The control group was healthy individuals with no lifetime history of substance abuse. All the opium abusers were selected from those who had a history of use of opium, as a regular habit, at least for 1 year, with a daily opium dosage of not less than 2 g. Addicts known to abuse alcohol or other drugs were excluded. Serum samples were collected from all participants and tested for the cytokine and hs-CRP levels by ELISA (enzyme-linked immunosorbent assay) method. Statistical analysis was performed using the Student t test. The mean serum levels of IFN-γ, IL-10, and IL-17 in the opium addicts were significantly higher than those observed in the control group. The mean concentration of serum IL-4 in opium addicts did not differ from that in the control group. Systemic IL-10 levels correlated positively and significantly with CRP in opium addicts. Long-term, daily use of opium is associated with higher Th1 (IFN-γ), Tr1 (IL-10), and Th17 (IL-17) cytokines concentration in serum. Interferon-γ and IL-17 are involved in inducing and mediating proinflammatory responses. Our data suggest that an immunoregulatory response is occurring with the upregulation of IL-10.

  9. Mitigating effects of vaccination on influenza outbreaks given constraints in stockpile size and daily administration capacity

    PubMed Central

    2011-01-01

    Background Influenza viruses are a major cause of morbidity and mortality worldwide. Vaccination remains a powerful tool for preventing or mitigating influenza outbreaks. Yet, vaccine supplies and daily administration capacities are limited, even in developed countries. Understanding how such constraints can alter the mitigating effects of vaccination is a crucial part of influenza preparedness plans. Mathematical models provide tools for government and medical officials to assess the impact of different vaccination strategies and plan accordingly. However, many existing models of vaccination employ several questionable assumptions, including a rate of vaccination proportional to the population at each point in time. Methods We present a SIR-like model that explicitly takes into account vaccine supply and the number of vaccines administered per day and places data-informed limits on these parameters. We refer to this as the non-proportional model of vaccination and compare it to the proportional scheme typically found in the literature. Results The proportional and non-proportional models behave similarly for a few different vaccination scenarios. However, there are parameter regimes involving the vaccination campaign duration and daily supply limit for which the non-proportional model predicts smaller epidemics that peak later, but may last longer, than those of the proportional model. We also use the non-proportional model to predict the mitigating effects of variably timed vaccination campaigns for different levels of vaccination coverage, using specific constraints on daily administration capacity. Conclusions The non-proportional model of vaccination is a theoretical improvement that provides more accurate predictions of the mitigating effects of vaccination on influenza outbreaks than the proportional model. In addition, parameters such as vaccine supply and daily administration limit can be easily adjusted to simulate conditions in developed and developing

  10. Mitigating effects of vaccination on influenza outbreaks given constraints in stockpile size and daily administration capacity.

    PubMed

    Cruz-Aponte, Maytee; McKiernan, Erin C; Herrera-Valdez, Marco A

    2011-08-01

    Influenza viruses are a major cause of morbidity and mortality worldwide. Vaccination remains a powerful tool for preventing or mitigating influenza outbreaks. Yet, vaccine supplies and daily administration capacities are limited, even in developed countries. Understanding how such constraints can alter the mitigating effects of vaccination is a crucial part of influenza preparedness plans. Mathematical models provide tools for government and medical officials to assess the impact of different vaccination strategies and plan accordingly. However, many existing models of vaccination employ several questionable assumptions, including a rate of vaccination proportional to the population at each point in time. We present a SIR-like model that explicitly takes into account vaccine supply and the number of vaccines administered per day and places data-informed limits on these parameters. We refer to this as the non-proportional model of vaccination and compare it to the proportional scheme typically found in the literature. The proportional and non-proportional models behave similarly for a few different vaccination scenarios. However, there are parameter regimes involving the vaccination campaign duration and daily supply limit for which the non-proportional model predicts smaller epidemics that peak later, but may last longer, than those of the proportional model. We also use the non-proportional model to predict the mitigating effects of variably timed vaccination campaigns for different levels of vaccination coverage, using specific constraints on daily administration capacity. The non-proportional model of vaccination is a theoretical improvement that provides more accurate predictions of the mitigating effects of vaccination on influenza outbreaks than the proportional model. In addition, parameters such as vaccine supply and daily administration limit can be easily adjusted to simulate conditions in developed and developing nations with a wide variety of financial

  11. [Renal side effects of long-term lithium therapy].

    PubMed

    Ibbeken, C; Becker, J U; Baumgärtel, M W

    2012-01-01

    Lithium is widely used in the treatment of bipolar disorders. Long-term administration of lithium often leads to side effects concerning the subjects: nephrology, endocrinology and surgery. This review emphasizes nephrotoxicity.Lithium treatment may disturb responsiveness to antidiuretic hormone (ADH), causing a nephrogenic diabetes insipidus. Furthermore long-term lithium therapy may trigger hyperparathyreoidism with hypercalcemia and chronic interstitial nephritis with development of microcysts. Long-term patients have an increased risk to develop impaired renal function. Lithium-induced endstage renal disease is rare. Termination of lithium treatment may decrease the risk of progression.To ensure security of lithium treatment regular controls of urine osmolarity, lithium-, creatinine- , thyroid stimulating hormone- and calcium-levels are essential. Patients with decreased renal function should be referred to a specialist early.

  12. Issues in the Development of Long Term Care Gerontology Centers: The Centers Concept. Selected Topics in Long Term Care. Volume 6.

    ERIC Educational Resources Information Center

    Mortenson, Lee E.; Berdes, Celia M.

    This document, one in a series developed to provide technical assistance to 22 Long-Term Care Gerontology Centers, describes the current administrative and structural phenomenon of these centers. Precedents useful in assessing both the current climate and actual prospects for development of long term care centers are cited. The first section…

  13. Long-term melatonin administration attenuates low-LET γ-radiation-induced lymphatic tissue injury during the reproductively active and inactive phases of Indian palm squirrels (Funambulus pennanti)

    PubMed Central

    Sharma, S; Haldar, C; Chaube, S K; Laxmi, T; Singh, S S

    2010-01-01

    A comparative analysis of low linear energy transfer (LET) γ-radiation-induced damage in the lymphatic tissue of a tropical seasonal breeder, Indian palm squirrel (Funambulus pennanti), during its reproductively active phase (RAP) and inactive phase (RIP) was performed with simultaneous investigation of the effects of long-term melatonin pre-treatment (100 μg/100 g body weight). A total of 120 squirrels (60 during RAP and 60 during RIP) were divided into 12 groups and sacrificed at 4, 24, 48, 72 and 168 h following 5 Gy γ-radiation exposure; control groups were excluded from exposure. Total leukocyte count and absolute lymphocyte count (ALC) and melatonin only of peripheral blood, stimulation index, thiobarbituric-acid-reactive substances (TBARS) level, superoxide dismutase (SOD) activity, and the apoptotic index of spleen as analysed by terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end labelling (TUNEL) noted at observed time-points were significantly reduced in melatonin pre-treated groups during RAP and RIP. Long-term melatonin pre-treatment mitigated radiation-induced alterations more prominently during RIP, as assessed by ALC, TBARS, SOD, TUNEL and caspase-3 activity, at some time-points. Our results demonstrate an inhibitory role of melatonin on caspase-3 activity in splenocytes during RAP and RIP following γ-radiation-induced caspase-mediated apoptosis. Hence, we propose that melatonin might preserve the viability of immune cells of a seasonal breeder against background radiation, which is constantly present in the environment. PMID:20139262

  14. The long-term costs of career interruptions.

    PubMed

    Ketsche, Patricia G; Branscomb, Lisette

    2003-01-01

    This article is based on a study that analyzed the long-term salary implications of career choices made by healthcare administrators. The study used a cohort of graduates from a single health administration program; these individuals had comparable levels of human capital at the outset of their careers. We estimated the effect of periods of part-time employment and job interruptions--voluntary and involuntary--on long-term salary progression. We also estimated the impact of other career choices, such as membership in a professional organization or the decision to relocate. After controlling for these choices, we estimated the residual effect of gender on salary. We found that voluntary interruptions had a greater effect on long-term salary growth than did involuntary interruptions of the same length or periods of part-time employment. Individuals evaluating options for balancing career and family constraints should understand the long-term cost of choosing a career interruption rather than part-time employment during periods of heightened responsibilities outside the workplace. Healthcare administrators should also be educated about the positive association between professional memberships and career advancement to make informed decisions about participation in such organizations. Surprisingly, after controlling for all choice variables, gender had no measurable effect on long-term salary growth. Half of those who indicated a voluntary interruption for dependent care reasons preferred part-time or flexible-hour work if it had been available. These results suggest that a pool of healthcare administrators might compete for positions if more part-time opportunities were available.

  15. Hospital diversification into long-term care.

    PubMed

    Shah, A; Fennell, M; Mor, V

    2001-01-01

    In the 1990s, acute care hospitals in the United States encountered an unstable operating environment created by a series of transformations in the health care delivery system and long-term-care market. Confronted with an array of economic pressures and demographic changes, hospitals were motivated to engage in long-term-care diversification, such as establishing a long-term-care unit or providing home health services, as a means of entering new markets and ensuring financial stability. This article examines the organizational, market, and community factors associated with this strategic activity among a national sample of urban and rural hospitals.

  16. Predicting long-term outcome following traumatic brain injury (TBI).

    PubMed

    Rassovsky, Yuri; Levi, Yifat; Agranov, Eugenia; Sela-Kaufman, Michal; Sverdlik, Anna; Vakil, Eli

    2015-01-01

    Traumatic brain injury (TBI) is the most common cause of brain damage, resulting in long-term disability. The ever increasing life expectancies among TBI patients necessitate a critical examination of the factors that influence long-term outcome. Our objective was to evaluate the contribution of premorbid factors (which were identified in our previous work) and acute injury indices to long-term functioning following TBI. Eighty-nine participants with moderate-to-severe TBI were evaluated at an average of 14.2 years postinjury (range: 1-53 years) with neuropsychological battery, medical examination, clinical interviews, and questionnaires. TBI severity predicted cognitive, social, and daily functioning outcomes. After controlling for injury severity, preinjury intellectual functioning predicted cognitive status, as well as occupational, social, emotional, and daily functioning. Preinjury leisure activity also predicted cognitive, emotional, and daily functioning, whereas socioeconomic status failed to predict any of these variables. Findings offer further support for the cognitive reserve construct in explaining significant variance in TBI outcome, over and above the variance explained by injury severity.

  17. Randomized clinical trial to comparing efficacy of daily, weekly and monthly administration of vitamin D3.

    PubMed

    Takács, István; Tóth, Béla E; Szekeres, László; Szabó, Boglárka; Bakos, Bence; Lakatos, Péter

    2017-01-01

    The comparative efficacy and safety profiles of selected daily 1000 IU, weekly 7000 IU and monthly 30,000 IU vitamin D 3-not previously investigated-will be evaluated. Here, a prospective, randomized clinical trial, comparing efficacy and safety of a daily single dose of 1000 IU (group A) to a once-weekly 7000 IU dose (group B), or monthly 30,000 IU dose (group C) of vitamin D3. The present study is a controlled, randomized, open-label, multicenter clinical trial, 3  months in duration. Sixty-four adult subjects with vitamin D deficiency (25OHD<20 ng/ml), were included according to the inclusion and exclusion criteria. Dose-responses for increases in serum vitamin 25OHD were statistically equivalent for each of the three groups: A, B and C. Outcomes were 13.0 ± 1.5; 12.6 ± 1.1 and 12.9 ± 0.9 ng/ml increases in serum 25OHD per 1000 IU, daily, weekly and monthly, respectively. The treatment of subjects with selected doses restored 25OHD values to levels above 20 ng/ml in all groups. Treatment with distinct administration frequency of vitamin D3 did not exhibit any differences in safety parameters. The daily, weekly and monthly administrations of daily equivalent of 1000 IU of vitamin D3 provide equal efficacy and safety profiles.

  18. Long Term Effects of Food Poisoning

    MedlinePlus

    ... develop chronic arthritis. Brain and nerve damage A Listeria infection can lead to meningitis, an inflammation of ... brain. If a newborn infant is infected with Listeria , long-term consequences may include mental retardation, seizures, ...

  19. Mental Health in Long Term Care Settings.

    ERIC Educational Resources Information Center

    Shore, Herbert

    1978-01-01

    There are many ways in which long-term care facilities attempt to cope with the mental health problems of the elderly. The author reviews five factors crucial to effective care for the aged in these facilities. (Author/RK)

  20. Roadmap to Long-Term Monitoring Optimization

    EPA Pesticide Factsheets

    This roadmap focuses on optimization of established long-term monitoring programs for groundwater. Tools and techniques discussed concentrate on methods for optimizing the monitoring frequency and spatial (three-dimensional) distribution of wells ...

  1. Long-term-care legal update.

    PubMed

    Fiesta, J

    1998-04-01

    As more nurses move from the acute care setting to long-term-care and home health care, different practice issues arise. To maximize liability protection, nurses must understand the legal issues unique to each delivery system.

  2. 75 FR 15495 - Agency Information Collection (Application for Furnishing Long-Term Care Services to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-29

    ... Veterans Health Administration, Department of Veterans Affairs, will submit the collection of information... AFFAIRS Agency Information Collection (Application for Furnishing Long- Term Care Services to...: Veterans Health Administration, Department of Veterans Affairs. ACTION: Notice. SUMMARY: In compliance with...

  3. Comparison of long-term care in an acute care institution and in a long-term care institution.

    PubMed

    Friedman, R; Kalant, N

    1998-11-03

    Acute care hospitals in Quebec are required to reserve 10% of their beds for patients receiving long-term care while awaiting transfer to a long-term care facility. It is widely believed that this is inefficient because it is more costly to provide long-term care in an acute care hospital than in one dedicated to long-term care. The purpose of this study was to compare the quality and cost of long-term care in an acute care hospital and in a long-term care facility. A concurrent cross-sectional study was conducted of 101 patients at the acute care hospital and 102 patients at the long-term care hospital. The 2 groups were closely matched in terms of age, sex, nursing care requirements and major diagnoses. Several indicators were used to assess the quality of care: the number of medical specialist consultations, drugs, biochemical tests and radiographic examinations; the number of adverse events (reportable incidents, nosocomial infections and pressure ulcers); and anthropometric and biochemical indicators of nutritional status. Costs were determined for nursing personnel, drugs and biochemical tests. A longitudinal study was conducted of 45 patients who had been receiving long-term care at the acute care hospital for at least 5 months and were then transferred to the long-term care facility where they remained for at least 6 months. For each patient, the number of adverse events, the number of medical specialist consultations and the changes in activities of daily living status were assessed at the 2 institutions. In the concurrent study, no differences in the number of adverse events were observed; however, patients at the acute care hospital received more drugs (5.9 v. 4.7 for each patient, p < 0.01) and underwent more tests (299 v. 79 laboratory units/year for each patient, p < 0.001) and radiographic examinations (64 v. 46 per 1000 patient-weeks, p < 0.05). At both institutions, 36% of the patients showed anthropometric and biochemical evidence of protein

  4. Comparison of long-term care in an acute care institution and in a long-term care institution

    PubMed Central

    Friedman, R; Kalant, N

    1998-01-01

    BACKGROUND: Acute care hospitals in Quebec are required to reserve 10% of their beds for patients receiving long-term care while awaiting transfer to a long-term care facility. It is widely believed that this is inefficient because it is more costly to provide long-term care in an acute care hospital than in one dedicated to long-term care. The purpose of this study was to compare the quality and cost of long-term care in an acute care hospital and in a long-term care facility. METHODS: A concurrent cross-sectional study was conducted of 101 patients at the acute care hospital and 102 patients at the long-term care hospital. The 2 groups were closely matched in terms of age, sex, nursing care requirements and major diagnoses. Several indicators were used to assess the quality of care: the number of medical specialist consultations, drugs, biochemical tests and radiographic examinations; the number of adverse events (reportable incidents, nosocomial infections and pressure ulcers); and anthropometric and biochemical indicators of nutritional status. Costs were determined for nursing personnel, drugs and biochemical tests. A longitudinal study was conducted of 45 patients who had been receiving long-term care at the acute care hospital for at least 5 months and were then transferred to the long-term care facility where they remained for at least 6 months. For each patient, the number of adverse events, the number of medical specialist consultations and the changes in activities of daily living status were assessed at the 2 institutions. RESULTS: In the concurrent study, no differences in the number of adverse events were observed; however, patients at the acute care hospital received more drugs (5.9 v. 4.7 for each patient, p < 0.01) and underwent more tests (299 v. 79 laboratory units/year for each patient, p < 0.001) and radiographic examinations (64 v. 46 per 1000 patient-weeks, p < 0.05). At both institutions, 36% of the patients showed anthropometric and

  5. Effects of daily chlorpromazine administration on behavioural and physiological parameters in the rat.

    PubMed

    Nsimba, S E D

    2009-01-01

    Chlorpromazine is a classical neuroleptic drug which produces both therapeutic effects as well as unwanted side effects in human such as sedation, autonomic, endocrine and neurological effects. It is thought that blockade of dopamine D-2 receptors caused by chlorpromazine induces these untoward side effects. Pre-clinical studies on catalepsy has been proposed as an animal model for neuroleptic induced extrapyramidal side effects. The drug also blocks certain stereotypic behaviours in animals induced by dopamine agonists such as apomorphine and amphetamine. These stereotypic behaviours are circling, chewing, rearing, grooming and hyperactivity. Daily administration of chlorpromazine (1, 3 and 10 mg/kg, i.p) to rats for 21 days induced catalepsy, tolerance to catalepsy and locomotor sensitization following PCP (10 mg/kg, i.p) challenge. These results suggest that daily chlorpromazine treatment induced DA/NMDA-receptor sensitization to total locomotor activity following PCP challenge. Furthermore, there were no changes in other behavioural parameters assessed. Surprisingly daily chlorpromazine administration in rats also produced no changes in other physiological parameters assessed (body weight, food and water intake).

  6. Evidence-based long term care design.

    PubMed

    Calkins, Margaret P

    2009-01-01

    Research on the impact of the built environment in long-term care settings continues to grow. This article focuses on work conducted and published since 2000, when an earlier review on research on dementia and design was published. The vast majority of research that addressed neurological conditions in residents in long-term care settings (assisted living and nursing homes) relates to Alzheimer's disease and related dementias.

  7. Pulmonary complications after long term amiodarone treatment.

    PubMed Central

    Roca, J; Heras, M; Rodriguez-Roisin, R; Magriñà, J; Xaubet, A; Sanz, G

    1992-01-01

    BACKGROUND: Amiodarone hydrochloride is an antiarrhythmic agent useful in arrhythmias refractory to standard therapy. Although interstitial pneumonitis is known to be its most serious side effect, several aspects of amiodarone lung toxicity are still controversial. METHODS: Pulmonary side effects were examined in a sample of 61 symptomless patients (mean (SD) age 55 (7) years) who had had long term treatment with amiodarone (daily maintenance dose 400 mg), selected from 482 men attending the University of Barcelona myocardial infarction project. To allow for the confounding effects of coronary artery disease and tobacco history on lung function, 46 patients who had taken amiodarone for more than one year were matched with a control group from the same population. Subjects underwent measurement of lung volumes, arterial blood gas analysis and an incremental bicycle exercise test. RESULTS: Most lung function values were close to predicted values, though there was a small increase in resting alveolar-arterial oxygen tension difference (A-aDO2) at rest (4.8 (1.4) kPa in both groups). There were no differences in the results of forced spirometry or static lung volumes between the two groups, or in the fall in A-aDO2 from rest to exercise. There was a small difference between the amiodarone and the control group in transfer factor for carbon monoxide corrected for lung volume (KCO 1.67 (0.3) and 1.83 (0.3) mmol min-1 kPa-1 l-1 respectively) and in exercise capacity (140 (25) and 120 (30)w). Only three patients showed lung function impairment consistent with pneumonitis. No relation between lung function measures and cumulative doses of amiodarone or desethylamiodarone was found. CONCLUSIONS: The prevalence of clinically evident pulmonary side effects was 4.9%, which is lower than that reported in studies in which higher daily maintenance doses of amiodarone were given. The slightly lower KCO values and lower work load achieved by the patients taking amiodarone suggest a

  8. Long-term administration of valacyclovir reduces the number of Epstein-Barr virus (EBV)-infected B cells but not the number of EBV DNA copies per B cell in healthy volunteers.

    PubMed

    Hoshino, Yo; Katano, Harutaka; Zou, Ping; Hohman, Patricia; Marques, Adriana; Tyring, Stephen K; Follmann, Dean; Cohen, Jeffrey I

    2009-11-01

    Epstein-Barr virus (EBV) establishes a latent infection in B cells in the blood, and the latent EBV load in healthy individuals is generally stable over time, maintaining a "set point." It is unknown if the EBV load changes after long-term antiviral therapy in healthy individuals. We treated volunteers with either valacyclovir (valaciclovir) or no antiviral therapy for 1 year and measured the amount of EBV DNA in B cells every 3 months with a novel, highly sensitive assay. The number of EBV-infected B cells decreased in subjects receiving valacyclovir (half-life of 11 months; P = 0.02) but not in controls (half-life of 31 years; P = 0.86). The difference in the slopes of the lines for the number of EBV-infected B cells over time for the valacyclovir group versus the control group approached significance (P = 0.054). In contrast, the number of EBV DNA copies per B cell remained unchanged in both groups (P = 0.62 and P = 0.92 for the control and valacyclovir groups, respectively). Valacyclovir reduces the frequency of EBV-infected B cells when administered over a long period and, in theory, might allow eradication of EBV from the body if reinfection does not occur.

  9. Extracellular-signal regulated kinase 1-dependent metabotropic glutamate receptor 5-induced long-term depression in the bed nucleus of the stria terminalis is disrupted by cocaine administration.

    PubMed

    Grueter, Brad A; Gosnell, Heather B; Olsen, Christopher M; Schramm-Sapyta, Nicole L; Nekrasova, Tanya; Landreth, Gary E; Winder, Danny G

    2006-03-22

    The bed nucleus of the stria terminalis (BNST) is a key component of the CNS stress and reward circuit. Synaptic plasticity in this region could in part underlie the persistent behavioral alterations in generalized anxiety and addiction. Group I metabotropic glutamate receptors (mGluRs) have been implicated in stress, addiction, and synaptic plasticity, but their roles in the BNST are unknown. We find that activation of group I mGluRs in the dorsal BNST induces depression of excitatory synaptic transmission through two distinct mechanisms. First, a combined activation of group I mGluRs (mGluR1 and mGluR5) induces a transient depression that is cannabinoid 1 receptor dependent. Second, as with endocannabinoid-independent group I mGluR long-term depression (LTD) in the adult hippocampus, we find that activation of mGluR5 induces an extracellular signal-regulated kinase (ERK)-dependent LTD. Surprisingly, our data demonstrate that this LTD requires the ERK1 rather than ERK2 isoform, establishing a key role for this isoform in the CNS. Finally, we find that this LTD is dramatically reduced after multiple exposures but not a single exposure to cocaine, suggesting a role for this form of plasticity in the actions of psychostimulants on anxiety and reward circuitries and their emergent control of animal behavior.

  10. LONG-TERM BEHAVIORAL EFFECTS IN A RAT MODEL OF PROLONGED POSTNATAL MORPHINE EXPOSURE

    PubMed Central

    Craig, Michael M.; Bajic, Dusica

    2015-01-01

    Prolonged morphine treatment in neonatal pediatric populations is associated with a high incidence of opioid tolerance and dependence. Despite the clinical relevance of this problem, our knowledge of the long-term consequences is sparse. The main objective of this study was to investigate whether prolonged morphine administration in a neonatal rat is associated with long-term behavioral changes in adulthood. Newborn animals received either morphine (10mg/kg) or equal volume of saline subcutaneously twice daily for the first 2 weeks of life. Morphine treated animals underwent 10 days of morphine weaning to reduce the potential for observable physical signs of withdrawal. Animals were subjected to non-stressful testing (locomotor activity recording and a Novel-Object Recognition test) at a young age (PD27-31) or later in adulthood (PD55-56), as well as stressful testing (calibrated forceps test, Hot Plate test, and Forced Swim test) only in adulthood. Analysis revealed that prolonged neonatal morphine exposure resulted in decreased thermal, but not mechanical threshold. Importantly, no differences were found for total locomotor activity (proxy of drug reward/reinforcement behavior), individual Forced Swim test behaviors (proxy of affective processing), or Novel-Object Recognition test. Performance on the Novel-Object Recognition test was compromised in the morphine treated group at the young age, however the effect disappeared in adulthood. These novel results provide insight into the long-term consequences of opioid treatment during an early developmental period and suggest long-term neuroplastic differences in sensory processing related to thermal stimuli. PMID:26214209

  11. Daily propranolol administration reduces persistent injury-associated anemia after severe trauma and chronic stress.

    PubMed

    Alamo, Ines G; Kannan, Kolenkode B; Bible, Letitia E; Loftus, Tyler J; Ramos, Harry; Efron, Philip A; Mohr, Alicia M

    2017-04-01

    After severe trauma, patients develop a norepinephrine-mediated persistent, injury-associated anemia. This anemia is associated with suppression of bone marrow (BM) erythroid colony growth, along with decreased iron levels, and elevated erythropoietin (EPO) levels, which are insufficient to promote effective erythropoiesis. The impact of norepinephrine on iron regulators, such as ferroportin, transferrin, and transferrin receptor-1 (TFR-1), is unknown. Using a clinically relevant rodent model of lung contusion (LC), hemorrhagic shock (HS), and chronic stress (CS), we hypothesize that daily propranolol (BB), a nonselective β blocker, restores BM function and improves iron homeostasis. Male Sprague-Dawley rats were subjected to LCHS ± BB and LCHS/CS ± BB. BB was achieved with propranolol (10 mg/kg) daily until the day of sacrifice. Hemoglobin, plasma EPO, plasma hepcidin, BM cellularity and BM erythroid colony growth were assessed. RNA was isolated to measure transferrin, TFR-1 and ferroportin expression. Data are presented as mean ± SD; *p < 0.05 versus untreated counterpart by t test. The addition of CS to LCHS leads to persistent anemia on posttrauma day 7, while the addition of BB improved hemoglobin levels (LCHS/CS: 10.6 ± 0.8 vs. LCHS/CS + BB: 13.9 ± 0.4* g/dL). Daily BB use after LCHS/CS improved BM cellularity, colony-forming units granulocyte, erythrocyte, monocyte megakaryocyte, burst-forming unit erythroid and colony-forming unit erythroid cell colony growth. LCHS/CS + BB significantly reduced plasma EPO levels and increased plasma hepcidin levels on day 7. The addition of CS to LCHS resulted in decreased liver ferroportin expression as well as decreased BM transferrin and TFR-1 expression, thus, blocking iron supply to erythroid cells. However, daily BB after LCHS/CS improved expression of all iron regulators. Daily propranolol administration after LCHS/CS restored BM function and improved anemia after severe trauma. In addition, iron regulators are

  12. Long-Term Outcome of Administration of c-kit(POS) Cardiac Progenitor Cells After Acute Myocardial Infarction: Transplanted Cells Do not Become Cardiomyocytes, but Structural and Functional Improvement and Proliferation of Endogenous Cells Persist for at Least One Year.

    PubMed

    Tang, Xian-Liang; Li, Qianhong; Rokosh, Gregg; Sanganalmath, Santosh K; Chen, Ning; Ou, Qinghui; Stowers, Heather; Hunt, Greg; Bolli, Roberto

    2016-04-01

    Cardiac progenitor cells (CPCs) improve left ventricular remodeling and function after acute or chronic myocardial infarction. However, the long-term (>5 weeks) effects, potential tumorigenicity, and fate of transplanted CPCs are unknown. To assess the outcome of CPC therapy at 1 year. Female rats underwent a 90-minute coronary occlusion; 4 hours after reperfusion, they received intracoronarily vehicle or 1 million male, syngeneic CPCs. One year later, CPC-treated rats exhibited smaller scars and more viable myocardium in the risk region, along with improved left ventricular remodeling and regional and global left ventricular function. No tumors were observed. Some transplanted (Y-chromosome(POS)) CPCs (or their progeny) persisted and continued to proliferate, but they failed to acquire a mature cardiomyocyte phenotype and were too few (4-8% of nuclei) to account for the benefits of CPC therapy. Surprisingly, CPC transplantation triggered a prolonged proliferative response of endogenous cells, resulting in increased formation of endothelial cells and Y-chromosome(NEG) CPCs for 12 months and increased formation, for at least 7 months, of small cells that expressed cardiomyocytic proteins (α-sarcomeric actin) but did not have a mature cardiomyocyte phenotype. The beneficial effects of CPCs on left ventricular remodeling and dysfunction are sustained for at least 1 year and thus are likely to be permanent. Because transplanted CPCs do not differentiate into mature myocytes, their major mechanism of action must involve paracrine actions. These paracrine mechanisms could be very prolonged because some CPCs engraft, proliferate, and persist at 1 year. This is the first report that transplantation of any cell type in the heart induces a proliferative response that lasts at least 1 year. The results strongly support the safety and clinical utility of CPC therapy. © 2016 American Heart Association, Inc.

  13. Chronic cocaine causes long-term alterations in circadian period and photic entrainment in the mouse.

    PubMed

    Stowie, A C; Amicarelli, M J; Prosser, R A; Glass, J D

    2015-01-22

    The disruptive effects of cocaine on physiological, behavioral and genetic processes are well established. However, few studies have focused on the actions of cocaine on the adult circadian timekeeping system, and none have explored the circadian implications of long-term (weeks to months) cocaine exposure. The present study was undertaken to explore the actions of such long-term cocaine administration on core circadian parameters in mice, including rhythm period, length of the nocturnal activity period and photic entrainment. For cocaine dosing over extended periods, cocaine was provided in drinking water using continuous and scheduled regimens. The impact of chronic cocaine on circadian regulation was evidenced by disruptions of the period of circadian entrainment and intrinsic free-running circadian period. Specifically, mice under a skeleton photoperiod (1-min pulse of dim light delivered daily) receiving continuous ad libitum cocaine entrained rapidly to the light pulse at activity onset. Conversely, water controls entrained more slowly at activity offset through a process of phase-delays, which resulted in their activity rhythms being entrained 147° out of phase with the cocaine group. This pattern persisted after cocaine withdrawal. Next, mice exposed to scheduled daily cocaine presentations exhibited free-running periods under constant darkness that were significantly longer than water controls and which also persisted after cocaine withdrawal. These cocaine-induced perturbations of clock timing could produce chronic psychological and physiological stress, contributing to increased cocaine use and dependence. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. Long-term symptom relief after septoplasty.

    PubMed

    Sundh, Carolina; Sunnergren, Ola

    2015-10-01

    The results for long-term symptom relief after septoplasty are contradictory in reviewed publications but the findings suggest that results are unsatisfactory. In this study, we analyzed and compared short- and long-term symptom relief after septoplasty and factors possibly associated with symptom relief. 111 patients that underwent septoplasty between 2008 and 2010 were included in the study. Medical charts were reviewed for preoperative characteristics and assessments. Data on short-term symptom relief (6 months) were retrieved from the Swedish National Quality Registry for Septoplasty; data on long-term symptom relief (34-70 months) were collected through a questionnaire. Upon the 34-70 month follow-up, 53% of the patients reported that symptoms either remained or had worsened and 83% reported nasal obstruction. Degree of symptom relief was significantly higher among patients not reporting nasal obstruction than among patients reporting nasal obstruction at long-term follow-up. The proportion of patients that reported "my symptoms are gone" declined from 53% after 6 months to 18% after 34-70 months. None of the factors taken into consideration, age at surgery, gender, follow-up time, primary operation/reoperation, history of nasal trauma, self-reported allergy, rhinometric obstruction, or same sided rhinometric, clinical and subjective nasal obstruction were associated with symptom relief. The long-term results after septoplasty are unsatisfactory. A majority of patients report that their symptoms remain after septoplasty.

  15. Long-term outcomes of autoimmune pancreatitis

    PubMed Central

    Ikeura, Tsukasa; Miyoshi, Hideaki; Shimatani, Masaaki; Uchida, Kazushige; Takaoka, Makoto; Okazaki, Kazuichi

    2016-01-01

    Autoimmune pancreatitis (AIP) has been considered a favorable-prognosis disease; however, currently, there is limited information on natural course of AIP during long-term follow-up. Recently published studies regarding the long-term outcomes of AIP has demonstrated the developments of pancreatic stone formation, exocrine insufficiency, and endocrine insufficiency are observed in 5%-41%, 34%-82%, and 38%-57% of patients having the disease. Furthermore, the incidence rate of developing pancreatic cancer ranges from 0% to 4.8% during the long-term follow-up. The event of death from AIP-related complications other than accompanying cancer is likely to be rare. During follow-up of AIP patients, careful surveillance for not only relapse of the disease but also development of complications at regular intervals is needed. PMID:27678359

  16. Impacts of Wildfires on Long-term Land Surface Phenology

    NASA Astrophysics Data System (ADS)

    Wang, J.; Zhang, X.

    2016-12-01

    Land surface phenology (LSP) detected from satellite data characterizes seasonal dynamics of vegetation communities within a moderate or coarse resolution pixel. Its long-term variation has been widely used to indicate the biological responses to climate changes. However, few studies have focused on the influence of land disturbance on LSP variations. The wildfire is one of the most important drivers of land disturbances across the world, which shows an increasing trend during past decades. To explore the wildfire impacts on LSP, we analyzed post-fire and pre-fire LSP in two forest fire events that are Hayman Fire occurred in 2002 and Mason Fire occurred in 2005 in Colorado. Specifically, we first generated a two band enhanced vegetation index (EVI2) from MODIS daily surface reflectance product (MOD09GQ) at a spatial resolution of 250 m from 2001-2014. The time series of daily EVI2 was then used to detect the start of growing season (SOS) by applying the LSP detection algorithm based on a hybrid piecewise logistic model (HPLM-LSPD). The SOS was further separated for four levels of burn severity obtained from Monitoring Trends in Burn Severity (MTBS) maps for each fire event. The long-term SOS in the burn scars was finally deviated from surrounding areas based on land cover types. Results show that forests were mainly converted to shrubs in both fire events with some grasslands in Hayman. On average, SOS in Hayman burn scar area was advanced 11 days relative to surrounding region while it was delayed 9 days in Mason fire. The deviation also varied with the burn severity spatially. Moreover, the long-term SOS trend in the local area from 2001-2014 was significantly different with and without considerations of the fire influences. This study demonstrates that the long-term LSP SOS trend is significantly influenced by land disturbances in a local and regional scales.

  17. Long-term cardiac safety and tolerability of fingolimod in multiple sclerosis: A postmarketing study.

    PubMed

    Paolicelli, Damiano; Manni, Alessia; Direnzo, Vita; D'Onghia, Mariangela; Tortorella, Carla; Zoccolella, Stefano; Trojano, Maria

    2015-10-01

    Fingolimod is the first oral disease-modifying therapy approved for multiple sclerosis (MS). The risks associated with the use of fingolimod include cardiovascular adverse events (AEs). First-dose observation (FDO) is required for all patients for at least 6 hours. We describe FDO data and long-term cardiac tolerability in a cohort of fingolimod-treated relapsing MS patients. Two hundred and twelve patients started fingolimod 0.5 mg once daily. Before the first administration, all subjects had an electrocardiogram (ECG) with cardiologist interpretation. Following administration they were monitored for 6 hours and underwent a cardiac monitoring every 3 months. In this cohort, there was a heart rate reduction at the VI hour of 9.6 ± 8 beats per minute (P < .001). Fifty-four individuals (25.5%) presented an abnormal ECG during the 6 hours. We experienced 1 case (0.22%) of symptomatic second-degree atrioventricular block. The mean follow-up period was 1.5 ± 0.7 years. During this period, 1 patient showed atrial fibrillation that needed to be treated. We also observed 5 cases of persistent increase in blood pressure. This postmarketing study shows that fingolimod is well tolerated and tha tcardiologic AEs are generally self-limited in the long term.

  18. Overexpression of the steroidogenic enzyme cytochrome P450 side chain cleavage in the ventral tegmental area increases 3α,5α-THP and reduces long-term operant ethanol self-administration.

    PubMed

    Cook, Jason B; Werner, David F; Maldonado-Devincci, Antoniette M; Leonard, Maggie N; Fisher, Kristen R; O'Buckley, Todd K; Porcu, Patrizia; McCown, Thomas J; Besheer, Joyce; Hodge, Clyde W; Morrow, A Leslie

    2014-04-23

    Neuroactive steroids are endogenous neuromodulators capable of altering neuronal activity and behavior. In rodents, systemic administration of endogenous or synthetic neuroactive steroids reduces ethanol self-administration. We hypothesized this effect arises from actions within mesolimbic brain regions that we targeted by viral gene delivery. Cytochrome P450 side chain cleavage (P450scc) converts cholesterol to pregnenolone, the rate-limiting enzymatic reaction in neurosteroidogenesis. Therefore, we constructed a recombinant adeno-associated serotype 2 viral vector (rAAV2), which drives P450scc expression and neuroactive steroid synthesis. The P450scc-expressing vector (rAAV2-P450scc) or control GFP-expressing vector (rAAV2-GFP) were injected bilaterally into the ventral tegmental area (VTA) or nucleus accumbens (NAc) of alcohol preferring (P) rats trained to self-administer ethanol. P450scc overexpression in the VTA significantly reduced ethanol self-administration by 20% over the 3 week test period. P450scc overexpression in the NAc, however, did not alter ethanol self-administration. Locomotor activity was unaltered by vector administration to either region. P450scc overexpression produced a 36% increase in (3α,5α)-3-hydroxypregnan-20-one (3α,5α-THP, allopregnanolone)-positive cells in the VTA, but did not increase 3α,5α-THP immunoreactivity in NAc. These results suggest that P450scc overexpression and the resultant increase of 3α,5α-THP-positive cells in the VTA reduces ethanol reinforcement. 3α,5α-THP is localized to neurons in the VTA, including tyrosine hydroxylase neurons, but not astrocytes. Overall, the results demonstrate that using gene delivery to modulate neuroactive steroids shows promise for examining the neuronal mechanisms of moderate ethanol drinking, which could be extended to other behavioral paradigms and neuropsychiatric pathology.

  19. Overexpression of the Steroidogenic Enzyme Cytochrome P450 Side Chain Cleavage in the Ventral Tegmental Area Increases 3α,5α-THP and Reduces Long-Term Operant Ethanol Self-Administration

    PubMed Central

    Cook, Jason B.; Werner, David F.; Maldonado-Devincci, Antoniette M.; Leonard, Maggie N.; Fisher, Kristen R.; O'Buckley, Todd K.; Porcu, Patrizia; McCown, Thomas J.; Besheer, Joyce; Hodge, Clyde W.

    2014-01-01

    Neuroactive steroids are endogenous neuromodulators capable of altering neuronal activity and behavior. In rodents, systemic administration of endogenous or synthetic neuroactive steroids reduces ethanol self-administration. We hypothesized this effect arises from actions within mesolimbic brain regions that we targeted by viral gene delivery. Cytochrome P450 side chain cleavage (P450scc) converts cholesterol to pregnenolone, the rate-limiting enzymatic reaction in neurosteroidogenesis. Therefore, we constructed a recombinant adeno-associated serotype 2 viral vector (rAAV2), which drives P450scc expression and neuroactive steroid synthesis. The P450scc-expressing vector (rAAV2-P450scc) or control GFP-expressing vector (rAAV2-GFP) were injected bilaterally into the ventral tegmental area (VTA) or nucleus accumbens (NAc) of alcohol preferring (P) rats trained to self-administer ethanol. P450scc overexpression in the VTA significantly reduced ethanol self-administration by 20% over the 3 week test period. P450scc overexpression in the NAc, however, did not alter ethanol self-administration. Locomotor activity was unaltered by vector administration to either region. P450scc overexpression produced a 36% increase in (3α,5α)-3-hydroxypregnan-20-one (3α,5α-THP, allopregnanolone)-positive cells in the VTA, but did not increase 3α,5α-THP immunoreactivity in NAc. These results suggest that P450scc overexpression and the resultant increase of 3α,5α-THP-positive cells in the VTA reduces ethanol reinforcement. 3α,5α-THP is localized to neurons in the VTA, including tyrosine hydroxylase neurons, but not astrocytes. Overall, the results demonstrate that using gene delivery to modulate neuroactive steroids shows promise for examining the neuronal mechanisms of moderate ethanol drinking, which could be extended to other behavioral paradigms and neuropsychiatric pathology. PMID:24760842

  20. Valuing a long-term care facility.

    PubMed

    Mellen, C M

    1992-10-01

    The business valuation industry generally uses at least one of three basic approaches to value a long-term care facility: the cost approach, sales comparison approach, or income approach. The approach that is chosen and the resulting weight that is applied to it depend largely on the circumstances involved. Because a long-term care facility is a business enterprise, more weight usually is given to the income approach which factors into the estimate of value both the tangible and intangible assets of the facility.

  1. Keratoprosthesis: a long-term review.

    PubMed Central

    Barnham, J. J.; Roper-Hall, M. J.

    1983-01-01

    A keratoprosthesis (KP), is an artificial cornea which is inserted into an opacified cornea in an attempt to restore useful vision or, less commonly, to make the eye comfortable in painful keratopathy. Results o a retrospective study of 35 patients, with 55 KP insertions, are reviewed with regard to visual acuity, length of time vision is maintained, retention time, and complication. Overall there were a number of long-term real successes, eith retention of the KP and maintenance of improved vision in eyes not amenable to conventional treatment. Careful long-term follow-up was needed, with further surgical procedures often being necessary. Images PMID:6860613

  2. Long-term Outcomes after Severe Shock

    PubMed Central

    Pratt, Cristina M.; Hirshberg, Eliotte L.; Jones, Jason P.; Kuttler, Kathryn G.; Lanspa, Michael J.; Wilson, Emily L.; Hopkins, Ramona O.; Brown, Samuel M.

    2014-01-01

    Background Severe shock is a life-threatening condition with very high short-term mortality. Whether the long-term outcomes among survivors of severe shock are similar to long-term outcomes of other critical illness survivors is unknown. We therefore sought to assess long-term survival and functional outcomes among 90-day survivors of severe shock and determine whether clinical predictors were associated with outcomes. Methods Seventy-six patients who were alive 90 days after severe shock (received ≥1 mcg/kg/min of norepinephrine equivalent) were eligible for the study. We measured three-year survival and long-term functional outcomes using the Medical Outcomes Study 36-Item Short-Form Health Survey, the EuroQOL 5-D-3L, the Hospital Anxiety and Depression Scale, the Impact of Event Scale-Revised and an employment instrument. We also assessed the relationship between in-hospital predictors and long-term outcomes. Results The mean long-term survival was 5.1 years: 82% (62/76) of patients survived, of whom 49 were eligible for follow-up. Patients who died were older than patients who survived. Thirty-six patients completed a telephone interview a mean of five years after hospital admission. The patients’ Physical Functioning scores were below US population norms (p<0.001), whereas mental health scores were similar to population norms. Nineteen percent of the patients had symptoms of depression, 39% had symptoms of anxiety and 8% had symptoms of posttraumatic stress disorder. Thirty-six percent were disabled, and 17% were working full time. Conclusions Early survivors of severe shock had a high three-year survival rate. Patients’ long term physical and psychological outcomes were similar to those reported for cohorts of less severely ill ICU survivors. Anxiety and depression were relatively common, but only a few patients had symptoms of posttraumatic stress disorder. This study supports the observation that acute illness severity does not determine long-term

  3. [Fetal pain: immediate and long term consequences].

    PubMed

    Houfflin Debarge, Véronique; Dutriez, Isabelle; Pusniak, Benoit; Delarue, Eléonore; Storme, Laurent

    2010-06-01

    Several situations are potentially painful for fetuses, such as malformations and invasive procedures. Nociceptive pathways are known to be functional at 26 weeks. Even if it is not possible to evaluate the fetal experience of pain, it is essential to examine its immediate and long-term consequences. As early as the beginning of the second trimester, hemodynamic and hormonal responses are observed following fetal nociceptive stimulation, In experimental studies, long-term changes have been noted in the corticotrop axis, subsequent responses to pain, and behavior after perinatal nociceptive stimulation.

  4. Long-term outcomes after severe shock.

    PubMed

    Pratt, Cristina M; Hirshberg, Eliotte L; Jones, Jason P; Kuttler, Kathryn G; Lanspa, Michael J; Wilson, Emily L; Hopkins, Ramona O; Brown, Samuel M

    2015-02-01

    Severe shock is a life-threatening condition with very high short-term mortality. Whether the long-term outcomes among survivors of severe shock are similar to long-term outcomes of other critical illness survivors is unknown. We therefore sought to assess long-term survival and functional outcomes among 90-day survivors of severe shock and determine whether clinical predictors were associated with outcomes. Seventy-six patients who were alive 90 days after severe shock (received ≥1 μg/kg per minute of norepinephrine equivalent) were eligible for the study. We measured 3-year survival and long-term functional outcomes using the Medical Outcomes Study 36-Item Short-Form Health Survey, the EuroQOL 5-D-3L, the Hospital Anxiety and Depression Scale, the Impact of Event Scale-Revised, and an employment instrument. We also assessed the relationship between in-hospital predictors and long-term outcomes. The mean long-term survival was 5.1 years; 82% (62 of 76) of patients survived, of whom 49 were eligible for follow-up. Patients who died were older than patients who survived. Thirty-six patients completed a telephone interview a mean of 5 years after hospital admission. The patients' Physical Functioning scores were below U.S. population norms (P < 0.001), whereas mental health scores were similar to population norms. Nineteen percent of the patients had symptoms of depression, 39% had symptoms of anxiety, and 8% had symptoms of posttraumatic stress disorder. Thirty-six percent were disabled, and 17% were working full-time. Early survivors of severe shock had a high 3-year survival rate. Patients' long-term physical and psychological outcomes were similar to those reported for cohorts of less severely ill intensive care unit survivors. Anxiety and depression were relatively common, but only a few patients had symptoms of posttraumatic stress disorder. This study supports the observation that acute illness severity does not determine long-term outcomes. Even extremely

  5. Naltrexone Maintenance Decreases Cannabis Self-Administration and Subjective Effects in Daily Cannabis Smokers.

    PubMed

    Haney, Margaret; Ramesh, Divya; Glass, Andrew; Pavlicova, Martina; Bedi, Gillinder; Cooper, Ziva D

    2015-10-01

    Given that cannabis use is increasing in the United States, pharmacological treatment options to treat cannabis use disorder are needed. Opioid antagonists modulate cannabinoid effects and may offer a potential approach to reducing cannabis use. In this double-blind, placebo-controlled human laboratory study, we assessed the effects of naltrexone maintenance on the reinforcing, subjective, psychomotor, and cardiovascular effects of active and inactive cannabis. Nontreatment-seeking, daily cannabis smokers were randomized to receive naltrexone (50 mg: n=18 M and 5 F) or placebo (0 mg; n=26 M and 2 F) capsules for 16 days. Before, during, and after medication maintenance, participants completed 10 laboratory sessions over 4-6 weeks, assessing cannabis' behavioral and cardiovascular effects. Medication compliance was verified by observed capsule administration, plasma naltrexone, and urinary riboflavin. Relative to placebo, maintenance on naltrexone significantly reduced both active cannabis self-administration and its positive subjective effects ('good effect'). Participants in the placebo group had 7.6 times (95% CI: 1.1-51.8) the odds of self-administering active cannabis compared with the naltrexone group. This attenuation of reinforcing and positive subjective effects also influenced cannabis use in the natural ecology. Naltrexone had intrinsic effects: decreasing ratings of friendliness, food intake, and systolic blood pressure, and increasing spontaneous reports of stomach upset and headache, yet dropout rates were comparable between groups. In summary, we show for the first time that maintenance on naltrexone decreased cannabis self-administration and ratings of 'good effect' in nontreatment-seeking daily cannabis smokers. Clinical studies in patients motivated to reduce their cannabis use are warranted to evaluate naltrexone's efficacy as a treatment for cannabis use disorder.

  6. Naltrexone Maintenance Decreases Cannabis Self-Administration and Subjective Effects in Daily Cannabis Smokers

    PubMed Central

    Haney, Margaret; Ramesh, Divya; Glass, Andrew; Pavlicova, Martina; Bedi, Gillinder; Cooper, Ziva D

    2015-01-01

    Given that cannabis use is increasing in the United States, pharmacological treatment options to treat cannabis use disorder are needed. Opioid antagonists modulate cannabinoid effects and may offer a potential approach to reducing cannabis use. In this double-blind, placebo-controlled human laboratory study, we assessed the effects of naltrexone maintenance on the reinforcing, subjective, psychomotor, and cardiovascular effects of active and inactive cannabis. Nontreatment-seeking, daily cannabis smokers were randomized to receive naltrexone (50 mg: n=18 M and 5 F) or placebo (0 mg; n=26 M and 2 F) capsules for 16 days. Before, during, and after medication maintenance, participants completed 10 laboratory sessions over 4–6 weeks, assessing cannabis' behavioral and cardiovascular effects. Medication compliance was verified by observed capsule administration, plasma naltrexone, and urinary riboflavin. Relative to placebo, maintenance on naltrexone significantly reduced both active cannabis self-administration and its positive subjective effects (‘good effect'). Participants in the placebo group had 7.6 times (95% CI: 1.1–51.8) the odds of self-administering active cannabis compared with the naltrexone group. This attenuation of reinforcing and positive subjective effects also influenced cannabis use in the natural ecology. Naltrexone had intrinsic effects: decreasing ratings of friendliness, food intake, and systolic blood pressure, and increasing spontaneous reports of stomach upset and headache, yet dropout rates were comparable between groups. In summary, we show for the first time that maintenance on naltrexone decreased cannabis self-administration and ratings of ‘good effect' in nontreatment-seeking daily cannabis smokers. Clinical studies in patients motivated to reduce their cannabis use are warranted to evaluate naltrexone's efficacy as a treatment for cannabis use disorder. PMID:25881117

  7. Fostering Humane Care of Dying Persons in Long-Term Care. Guidebook for Staff Development Instructors.

    ERIC Educational Resources Information Center

    Wilson, Sarah A.; Daley, Barbara

    This guide is intended for staff development instructors responsible for inservice education on the topic of fostering humane care for dying persons in long-term care. The introduction discusses the guide's development based on input from administrators, staff, and families of residents in long-term care facilities and focus group interviews in…

  8. Rifaximin is safe and well tolerated for long-term maintenance of remission from overt hepatic encephalopathy.

    PubMed

    Mullen, Kevin D; Sanyal, Arun J; Bass, Nathan M; Poordad, Fred F; Sheikh, Muhammad Y; Frederick, R Todd; Bortey, Enoch; Forbes, William P

    2014-08-01

    Rifaximin is a gut-selective, oral antimicrobial agent shown to reduce the recurrence of overt hepatic encephalopathy (HE) and HE-related hospitalizations in a 6-month, randomized, controlled trial (RCT). We performed a phase 3, open-label maintenance study to assess the safety and rate of hospitalization with long-term rifaximin use. We conducted a 24-month, open-label maintenance study of rifaximin (550 mg, twice daily) in patients with HE who participated in the previous RCT of rifaximin or new patients enrolled from March 2007 to December 2010. Safety was assessed (adverse events, clinical laboratory parameters) for the integrated population of all patients, who were given rifaximin 550 mg twice daily (all-rifaximin population, N = 392). Safety and hospitalization data were compared between the group given placebo in the original RCT (n = 159) and those given rifaximin (n = 140). In the all-rifaximin population, the median exposure to rifaximin was 427.0 days (range, 2-1427 d), with 510.5 person-years of exposure. The profile and rate of adverse events with long-term rifaximin treatment were similar to those of the original RCT. There was no increase in the rate of infections, including with Clostridium difficile, or development of bacterial antibiotic resistance. Rates of hospitalizations with long-term rifaximin administration remained low: the HE-related hospitalization rate, normalized for exposure (0.21; all-rifaximin population), was similar to that of the rifaximin group in the original RCT (0.30), and lower than that for the placebo group (0.72). Long-term treatment (≥24 mo) with rifaximin (550 mg, twice daily) appears to provide a continued reduction in the rate of HE-related and all-cause hospitalization, without an increased rate of adverse events. ClinicalTrials.gov number: NCT00686920. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  9. Globalization, women's migration, and the long-term-care workforce.

    PubMed

    Browne, Colette V; Braun, Kathryn L

    2008-02-01

    With the aging of the world's population comes the rising need for qualified direct long-term-care (DLTC) workers (i.e., those who provide personal care to frail and disabled older adults). Developed nations are increasingly turning to immigrant women to fill these needs. In this article, we examine the impact of three global trends-population aging, globalization, and women's migration-on the supply and demand for DLTC workers in the United States. Following an overview of these trends, we identify three areas with embedded social justice issues that are shaping the DLTC workforce in the United States, with a specific focus on immigrant workers in these settings. These include world poverty and economic inequalities, the feminization and colorization of labor (especially in long-term care), and empowerment and women's rights. We conclude with a discussion of the contradictory effects that both population aging and globalization have on immigrant women, source countries, and the long-term-care workforce in the United States. We raise a number of policy, practice, and research implications and questions. For policy makers and long-term-care administrators in receiver nations such as the United States, the meeting of DLTC worker needs with immigrants may result in greater access to needed employees but also in the continued devaluation of eldercare as a profession. Source (supply) nations must balance the real and potential economic benefits of remittances from women who migrate for labor with the negative consequences of disrupting family care traditions and draining the long-term-care workforce of those countries.

  10. Long-term care and hospital collaboration. To survive in a reformed healthcare system, long-term care facilities can initiate hospital-based SNFs.

    PubMed

    Hume, S K

    1993-06-01

    Establishing relationships with hospitals may be critical for long-term care facilities facing financial pressures and uncertain futures. One option is to initiate collaborative efforts to develop hospital-based skilled nursing facilities (SNFs). Hospitals, under pressure to move patients to less intensive settings and to diversify, are naturally drawn to long-term care as a related business where they can make limited personnel and financial commitments and extend their continuum of care. Before approaching hospitals to initiate collaborative efforts, long-term care providers should understand how they think and what their strengths and weaknesses are. Long-term and acute care providers have many options for collaboration, including management contracts and joint ventures. In a traditional management contract, the long-term care provider furnishes the administrator and a few key staff in exchange for direct reimbursement for those staff plus a management fee. Another option is for the long-term care facility to provide all the staff for a fee or percentage of revenue. Joint venture options are to form a subsidiary corporation to renovate a floor of the hospital or to have the hospital buy a large percentage of the long-term care facility and share the profits. All these options have potential pitfalls, including differing financial expectations and the threat of unionization at the SNF. Nevertheless, for long-term care facilities struggling under reimbursement cutbacks and other pressures, the benefits may outweigh the risks.

  11. Long-Term Memory and Learning

    ERIC Educational Resources Information Center

    Crossland, John

    2011-01-01

    The English National Curriculum Programmes of Study emphasise the importance of knowledge, understanding and skills, and teachers are well versed in structuring learning in those terms. Research outcomes into how long-term memory is stored and retrieved provide support for structuring learning in this way. Four further messages are added to the…

  12. Long-Term Memory and Learning

    ERIC Educational Resources Information Center

    Crossland, John

    2011-01-01

    The English National Curriculum Programmes of Study emphasise the importance of knowledge, understanding and skills, and teachers are well versed in structuring learning in those terms. Research outcomes into how long-term memory is stored and retrieved provide support for structuring learning in this way. Four further messages are added to the…

  13. Professionalism in Long-Term Care Settings

    ERIC Educational Resources Information Center

    Lubinski, Rosemary

    2006-01-01

    Speech-language pathologists who serve elders in a variety of long-term care settings have a variety of professional skills and responsibilities. Fundamental to quality service is knowledge of aging and communication changes and disorders associated with this process, institutional alternatives, and the changing nature of today's elders in…

  14. Long-Term Impacts of Educational Interventions

    ERIC Educational Resources Information Center

    Deming, David James

    2010-01-01

    The school accountability movement has led to a marked increase in the use of standardized test scores to measure school and teacher productivity, yet little is known about the correlation between test score gains and improvements in long-term outcomes. In the first chapter of my dissertation, I study the impact of a school choice policy in…

  15. Long-term studies of dopamine agonists.

    PubMed

    Hubble, Jean P

    2002-02-26

    Dopamine agonists have long been used as adjunctive therapy for the treatment of Parkinson's disease (PD). In more recent years these drugs have also been proved safe and effective as initial therapy in lieu of levodopa in the treatment of PD. Long-term levodopa therapy is associated with motor complications, including fluctuating response patterns and dyskinesia. By initially introducing a dopamine agonist as symptomatic drug therapy, it may be possible to postpone the use of levodopa and delay or prevent the development of motor complications. Recently, four clinical trials have explored this hypothesis by comparing the long-term response and side effects of levodopa with dopamine agonist therapy. The drugs studied have included ropinirole, pramipexole, cabergoline, and pergolide. In each of these projects, the occurrence of motor complications, such as wearing off and dyskinesia, was significantly less in the subjects assigned to initiation of therapy with a dopamine agonist. The addition of levodopa could be postponed by many months or even several years. Therefore, these long-term studies of dopamine agonists support the initiation of a dopamine agonist instead of levodopa in an effort to postpone levodopa-related motor complications. This therapeutic approach may be particularly appropriate in PD patients with a long treatment horizon on the basis of age and general good health. The extension phase of the long-term study comparing pramipexole with levodopa is ongoing, and follow-up information may help to establish the value of this treatment strategy.

  16. Long Term Care Aide. Course Outline.

    ERIC Educational Resources Information Center

    Wilbee, Judy

    This course outline is intended to assist the instructor in the development of a curriculum for a long-term care aide program by specifying one component of the curriculum--the objectives. These objectives, or competencies expected as outcomes for student performance on completion of the program, describe the capabilities an individual must…

  17. Long-term lysimeter data on evapotranspiration

    USDA-ARS?s Scientific Manuscript database

    Long term crop evapotranspiration (ET) data measured using large weighing lysimeters have only been gathered in a few places in the world, yet are of great importance for ground truthing of many models of plant water use, mesoscale climate, remote sensing estimation of ET, climate change and climate...

  18. Who Recommends Long-Term Care Matters

    ERIC Educational Resources Information Center

    Kane, Robert L.; Bershadsky, Boris; Bershadsky, Julie

    2006-01-01

    Purpose: Making good consumer decisions requires having good information. This study compared long-term-care recommendations among various types of health professionals. Design and Methods: We gave randomly varied scenarios to a convenience national sample of 211 professionals from varying disciplines and work locations. For each scenario, we…

  19. Professionalism in Long-Term Care Settings

    ERIC Educational Resources Information Center

    Lubinski, Rosemary

    2006-01-01

    Speech-language pathologists who serve elders in a variety of long-term care settings have a variety of professional skills and responsibilities. Fundamental to quality service is knowledge of aging and communication changes and disorders associated with this process, institutional alternatives, and the changing nature of today's elders in…

  20. Evaluating Long-Term Disability Insurance Plans.

    ERIC Educational Resources Information Center

    Powell, Jan

    1992-01-01

    This report analyzes the factors involved in reviewing benefits and services of employer-sponsored group long-term disability plans for higher education institutions. Opening sections describe the evolution of disability insurance and its shape today. Further sections looks at the complex nature of "value" within a plan, relationship…

  1. LONG TERM HYDROLOGICAL IMPACT ASSESSMENT (LTHIA)

    EPA Science Inventory

    LTHIA is a universal Urban Sprawl analysis tool that is available to all at no charge through the Internet. It estimates impacts on runoff, recharge and nonpoint source pollution resulting from past or proposed land use changes. It gives long-term average annual runoff for a lan...

  2. Long-Term Stability of Tutor Performance.

    ERIC Educational Resources Information Center

    Dolmans, Diana H. J. M.; And Others

    1996-01-01

    Examined the extent to which tutor ratings remained stable in the long term by evaluating 291 ratings of 140 tutors at Maastricht University in the Netherlands between 1992 and 1995. The results indicated that, if the aggregated score and overall judgement are used to interpret the precision of individual scores, four and two occasions,…

  3. Urethroplasty for hypospadias: long-term results.

    PubMed

    Glassman, C N; Machlus, B J; Kelalis, P P

    1980-06-01

    A retrospective study of patients who had undergone multi-staged hypospadias repair at the Mayo Clinic was undertaken to identify long-term problems associated with this surgery. Patients were queried concerning their satisfaction with quality of urinary stream; penile erection and ejaculation; sexual function and fertility; and cosmetic appearance.

  4. LONG TERM HYDROLOGICAL IMPACT ASSESSMENT (LTHIA)

    EPA Science Inventory

    LTHIA is a universal Urban Sprawl analysis tool that is available to all at no charge through the Internet. It estimates impacts on runoff, recharge and nonpoint source pollution resulting from past or proposed land use changes. It gives long-term average annual runoff for a lan...

  5. Very Long Term Memory for Tacit Knowledge.

    ERIC Educational Resources Information Center

    Allen, Rhianon; Reber, Arthur S.

    1980-01-01

    Very long-term memory for abstract materials was examined for subjects who had served in a synthetic grammar learning experiment two years earlier. Knowledge of these grammars was retained. The form and structure of knowledge and the manner in which it is put to use remained similar to the original. (Author/RD)

  6. Long-term opioid therapy reconsidered.

    PubMed

    Von Korff, Michael; Kolodny, Andrew; Deyo, Richard A; Chou, Roger

    2011-09-06

    In the past 20 years, primary care physicians have greatly increased prescribing of long-term opioid therapy. However, the rise in opioid prescribing has outpaced the evidence regarding this practice. Increased opioid availability has been accompanied by an epidemic of opioid abuse and overdose. The rate of opioid addiction among patients receiving long-term opioid therapy remains unclear, but research suggests that opioid misuse is not rare. Recent studies report increased risks for serious adverse events, including fractures, cardiovascular events, and bowel obstruction, although further research on medical risks is needed. New data indicate that opioid-related risks may increase with dose. From a societal perspective, higher-dose regimens account for the majority of opioids dispensed, so cautious dosing may reduce both diversion potential and patient risks for adverse effects. Limiting long-term opioid therapy to patients for whom it provides decisive benefits could also reduce risks. Given the warning signs and knowledge gaps, greater caution and selectivity are needed in prescribing long-term opioid therapy. Until stronger evidence becomes available, clinicians should err on the side of caution when considering this treatment.

  7. Long-term function after restorative proctocolectomy.

    PubMed

    Wheeler, J M D; Banerjee, A; Ahuja, N; Jewell, D P; Mortensen, N J McC

    2005-05-01

    Early functional outcome after restorative proctocolectomy and formation of an ileoanal pouch is known to be good, but there are minimal data on the long-term function of the pouch. The aim of this study was to look at the long-term functional outcome in patients who had undergone restorative proctocolectomy and formation of an ileoanal pouch. A total of 151 consecutive patients (96 males, 55 females) who underwent ileoanal pouch surgery between April 1983 and May 1993 were identified. Functional outcomes from the previous 12 months were appraised by a standardized questionnaire. The median age at surgery was 31 years (range, 6-63 years), with a median follow-up of 142 months (range, 100-221 months). Eighteen patients have had their pouches excised, with another patient being defunctioned. Therefore 19 patients (13 percent) had suffered pouch failure. Altogether, 115 patients were available for follow-up, and 98 patients (85 percent) returned questionnaires. The median pouch-emptying frequency was five times (range, 1-17) during the day and one time (range, 0-6) at night. A total of 74 percent of patients had perfect continence during the day. Most of the patients had no life-style restrictions related to the pouch, and 98 percent of patients would recommend a pouch to others. Long-term functional outcome after ileoanal pouch surgery is good in most patients. For patients requiring proctocolectomy, ileoanal pouch surgery can now be recommended as an excellent long-term option.

  8. Long-Term Impacts of Educational Interventions

    ERIC Educational Resources Information Center

    Deming, David James

    2010-01-01

    The school accountability movement has led to a marked increase in the use of standardized test scores to measure school and teacher productivity, yet little is known about the correlation between test score gains and improvements in long-term outcomes. In the first chapter of my dissertation, I study the impact of a school choice policy in…

  9. Long-Term Stability of Tutor Performance.

    ERIC Educational Resources Information Center

    Dolmans, Diana H. J. M.; And Others

    1996-01-01

    Examined the extent to which tutor ratings remained stable in the long term by evaluating 291 ratings of 140 tutors at Maastricht University in the Netherlands between 1992 and 1995. The results indicated that, if the aggregated score and overall judgement are used to interpret the precision of individual scores, four and two occasions,…

  10. Who Recommends Long-Term Care Matters

    ERIC Educational Resources Information Center

    Kane, Robert L.; Bershadsky, Boris; Bershadsky, Julie

    2006-01-01

    Purpose: Making good consumer decisions requires having good information. This study compared long-term-care recommendations among various types of health professionals. Design and Methods: We gave randomly varied scenarios to a convenience national sample of 211 professionals from varying disciplines and work locations. For each scenario, we…

  11. Long-term disability in anxiety disorders.