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Sample records for administering zoledronic acid

  1. Zoledronic Acid Injection

    Science.gov (United States)

    ... experience a reaction during the first few days after you receive a dose of zoledronic acid injection. Symptoms ... symptoms may begin during the first 3 days after you receive a dose of zoledronic acid injection and ...

  2. Preventive Effects of Zoledronic Acid on Bone Metastasis in Mice Injected with Human Breast Cancer Cells

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    Jeong, Joon; Lee, Kyung Sun; Choi, Yang-Kyu; Oh, Young Ju; Lee, Hy-De

    2011-01-01

    Bisphosphonates are used routinely to reduce bone-related events in breast cancer patients with bone metastasis. We evaluated the effects of zoledronic acid, a third generation, nitrogen-containing bisphosphonate, to prevent bone metastasis in breast cancer. Zoledronic acid or vehicle alone was administered to nude mice either simultaneously or after intracardiac injection of human breast cancer MDA-MB-231 cells. Nude mice treated with zoledronic acid at early time points showed a lower incid...

  3. Zoledronic acid and clinical fractures and mortality after hip fracture

    DEFF Research Database (Denmark)

    Lyles, Kenneth W; Colón-Emeric, Cathleen S; Magaziner, Jay S;

    2007-01-01

    BACKGROUND: Mortality is increased after a hip fracture, and strategies that improve outcomes are needed. METHODS: In this randomized, double-blind, placebo-controlled trial, 1065 patients were assigned to receive yearly intravenous zoledronic acid (at a dose of 5 mg), and 1062 patients were...... assigned to receive placebo. The infusions were first administered within 90 days after surgical repair of a hip fracture. All patients (mean age, 74.5 years) received supplemental vitamin D and calcium. The median follow-up was 1.9 years. The primary end point was a new clinical fracture. RESULTS: The...... rates of any new clinical fracture were 8.6% in the zoledronic acid group and 13.9% in the placebo group, a 35% risk reduction with zoledronic acid (P=0.001); the respective rates of a new clinical vertebral fracture were 1.7% and 3.8% (P=0.02), and the respective rates of new nonvertebral fractures...

  4. Life-threatening hyperkalemia following zoledronic acid infusion for Paget's disease: a case report

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    Naysmith Morag

    2011-08-01

    Full Text Available Abstract Introduction Zoledronic acid is a highly effective treatment in Paget's disease for persistent bone pain and prevention of further progression of the disease. The commonest electrolyte abnormality is hypocalcemia. To the best of our knowledge this is the first case of hyperkalemia secondary to zoledronic acid to be published in the world literature. The commonest arrhythmia related to zoledronic acid is atrial fibrillation. Case presentation We describe the case of an 80-year-old Caucasian man, with a history of ischemic heart disease, who had an in-hospital cardiac arrest related to hyperkalemia. Increasing potassium levels were noted following his first zoledronic acid infusion for symptomatic control of bone pain secondary to Paget's disease. Our patient suffered a cardiac arrest 10 days following the zoledronic acid infusion. Our patient's biochemistry and electrocardiogram output were monitored until his death 26 days after his cardiac arrest. Our patient developed paroxysmal atrial fibrillation in the post-resuscitation period and there was persistent hyperkalemia that required prolonged treatment with calcium resonium. All other possible causes of hyperkalemia were excluded. Conclusion In our patient's case persistent hyperkalemia and life-threatening arrhythmias were associated with use of zoledronic acid. These side effects have not been reported before and the causative mechanism is far from clear as there are no obvious systemic effects of zoledronic acid. The combination of zoledronic acid with predisposing factors such as structural heart disease might account for the clinical picture we witnessed. As a result, electrolyte monitoring should be adopted early in zoledronic acid use. Further studies are required to elucidate the underlying mechanism of hyperkalemia and identify the target group of patients where zoledronic acid can be safely administered. Great caution is advised in patients with underlying heart conditions.

  5. Fracture risk and zoledronic acid therapy in men with osteoporosis

    DEFF Research Database (Denmark)

    Boonen, Steven; Reginster, Jean-Yves; Kaufman, Jean-Marc;

    2012-01-01

    Fractures in men are a major health issue, and data on the antifracture efficacy of therapies for osteoporosis in men are limited. We studied the effect of zoledronic acid on fracture risk among men with osteoporosis.......Fractures in men are a major health issue, and data on the antifracture efficacy of therapies for osteoporosis in men are limited. We studied the effect of zoledronic acid on fracture risk among men with osteoporosis....

  6. Zoledronic acid and clinical fractures and mortality after hip fracture

    DEFF Research Database (Denmark)

    Lyles, Kenneth W; Colón-Emeric, Cathleen S; Magaziner, Jay S;

    2007-01-01

    were 7.6% and 10.7% (P=0.03). In the safety analysis, 101 of 1054 patients in the zoledronic acid group (9.6%) and 141 of 1057 patients in the placebo group (13.3%) died, a reduction of 28% in deaths from any cause in the zoledronic acid group (P=0.01). The most frequent adverse events in patients...

  7. Zoledronic acid in the management of metastatic bone disease

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    Thomas J Polascik

    2008-03-01

    Full Text Available Thomas J Polascik, Vladimir MouravievDuke Prostate Center and Division of Urologic Surgery, Duke University Medical Center, Durham, NC, USAAbstract: Many patients with advanced cancer experience decreased bone strength due to metastatic foci, underlying osteoporosis and/or cancer treatment induced bone loss. The clinical consequences of metastatic disease involving the skeleton are widespread. This review focuses on the efficacy, pharmacology, and safety when using intravenous biphosphonate such a zoledronic acid for cancer bone metastases. Zoledronic acid is the gold standard for the medical management of metastatic bone disease. The indications for treatment include prevention of skeletal relevant events (SRE, osteoporotic complications, and palliation of bone pain, among others. Zoledronic acid is the only bisphosphonate effective in decreasing SREs associated with bone metastases from advanced renal cell carcinoma and prostate cancer. Regarding prostate cancer, zoledronic acid effectively prevents both bone loss in patients with locally advanced disease receiving androgen deprivation therapy and SREs in men with hormone-refractory or hormonesensitive metastatic disease. Zoledronic acid has an acceptable safety profile and tolerability, and has been effective at significantly decreasing the incidence, delaying the onset, and reducing the overall risk of experiencing an SRE compared to placebo. It is the only bisphosphonate currently approved for the prevention and treatment of skeletal complications in patients with bone metastases due to all solid tumors.Keywords: zoledronic acid, metastatic bone disease, osteoporosis, skeletal relevant events, advanced prostate cancer

  8. Correlation between zoledronic acid infusion and repeat vertebroplasty surgery in osteoporotic patients.

    Science.gov (United States)

    Lin, Tung-Yi; Yang, Shih-Chieh; Tsai, Tsung-Ting; Lai, Po-Liang; Fu, Tsai-Sheng; Niu, Chi-Chien; Chen, Lih-Huei; Chen, Wen-Jer

    2016-05-01

    Objective The incidence of bone fractures rapidly increases as people age, mostly due to bone loss resulting from osteoporosis. The purpose of this study is to compare the rates of repeat vertebroplasty in osteoporotic patients treated with or without zoledronic acid (ZOL) infusion following initial vertebroplasty. Research design and methods We conducted a retrospective chart review of osteoporotic patients who underwent vertebroplasty from June 2009 to June 2012. Patients with existing vertebral fracture(s) were retrospectively divided into two groups according to whether or not they received zoledronic acid infusion after initial vertebroplasty. Zoledronic acid infusion was intravenously administered once a year for three consecutive years, as a single 5 mg dose in 100 mL solution infused over at least 15 minutes. The primary efficacy variable was the number of patients requiring repeat vertebroplasty procedures after the initial surgery due to subsequent vertebral fractures. The Cox proportional hazards model was used to compare the risk ratios of repeat vertebroplasty between these two groups. Results A total of 1646 patients, including 456 males and 1190 females (age range: 65-89 years), were enrolled. Compared to the 1595 patients who did not receive osteoporosis medication, the 51 patients treated with zoledronic acid infusion demonstrated a significantly lower rate of repeat vertebroplasty. In the ZOL-treated group, only 4% of the patients (2/51) required a second vertebroplasty, compared to 13% (206/1595) in the non-ZOL-treated group (p = 0.032). Conclusions The results indicate that osteoporotic patients who undergo vertebroplasty are significantly less likely to require reoperation if treated with zoledronic acid infusion. However, since the number of male patients in the ZOL-treated group was limited, and since Taiwan's National Health System program does not cover the cost of receiving zoledronic acid infusions for male patients, the

  9. Inhibition of osteoblast activity by zoledronic acid

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    Fernanda Gonçalves Basso

    2013-10-01

    Full Text Available INTRODUCTION: Patients treated with nitrogen-containing bisphosphonates, such as zoledronic acid (ZA, have frequently shown oral bone exposure areas, termed osteonecrosis. In addition, these patients may also present low repair and regeneration potential, mainly after tooth extractions. These side-effects caused by bisphosphonates may be due to their inhibitory effects on oral mucosa and local bone cells. OBJECTIVE: To evaluate the effects of ZA on the mineralization capacity of cultured osteoblasts. MATERIALS AND METHODS: Human immortalized osteoblasts (SaOs-2 were grown in plain culture medium (Dulbecco's Modified Eagle Medium [DMEM] + 10% fetal bovine serum [FBS] in wells of 24-well plates. After 48-hour incubation, the plain DMEM was replaced by a solution with ZA at 5 µM which was maintained in contact with cells for seven, 14 or 21 days. After these periods, cells were evaluated regarding alkaline phosphatase (ALP activity and mineral nodule formation (alizarin red. Data were statistically analyzed by Mann-Whitney test, at 5% of significance level. RESULTS: ZA caused significant reduction on ALP activity and mineral nodules formation by cultured osteoblasts in all evaluated periods (p < 0.05. CONCLUSION: These data indicate that ZA causes inhibition on the osteogenic phenotype of cultured human osteoblasts, which, in turn, may reduce bone repair in patients subjected to ZA therapy.

  10. Combined use of zoledronic acid and 153Sm-EDTMP in hormone-refractory prostate cancer patients with bone metastases

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    Lam, Marnix G.E.H.; Rijk, Peter P. van [University Medical Center Utrecht, Department of Nuclear Medicine, P.O. Box 85500, Utrecht (Netherlands); Dahmane, Amel; Stevens, Wil H.M. [CIS bio International, Saclay (France); Klerk, John M.H. de [Meander Medical Center, Department of Nuclear Medicine, Amersfoort (Netherlands); Zonnenberg, Bernard A. [UMC Utrecht, Department of Internal Medicine, Utrecht (Netherlands)

    2008-04-15

    {sup 153}Sm-ethylenediaminetetramethylenephosphonic acid (EDTMP; Quadramet {sup registered}) is indicated for the treatment of painful bone metastases, whereas zoledronic acid (Zometa {sup registered}) is indicated for the prevention of skeletal complications. Because of the different therapeutic effects, combining the treatments may be beneficial. Both, however, accumulate in areas with increased osteoblastic activity. Possible drug interactions were investigated. Patients with hormone-refractory prostate cancer were treated with 18.5 MBq/kg {sup 153}Sm-EDTMP in weeks 1 and 3 and with 37 MBq/kg in week 15. Treatment with 4 mg zoledronic acid began in week 3 and continued every 4 weeks through week 23. In weeks 3 and 15, zoledronic acid was administered 2 days before {sup 153}Sm-EDTMP treatment. Urine was collected 48 h after injection of {sup 153}Sm-EDTMP, and whole-body images were obtained 6, 24 and 48 h post-injection. The effect of zoledronic acid on total bone uptake of {sup 153}Sm-EDTMP was measured indirectly by the cumulative activity excreted in the urine in weeks 1, 3 and 15. Biodistribution, safety, tolerability and effect on prostate-specific antigen level were also studied. The urinary excretion in week 3 divided by the urinary excretion in week 1 (baseline) times 100% was mean 98.4 {+-} 11.6% (median 96.2%). From week 1 to 15, after four zoledronic acid treatments, the mean ratio was 101.9 {+-} 10.7% (median 101.8%). Bioequivalence could be concluded by using a two-sample t test for both per-protocol (n = 13) and full-analysis sets (n = 18). Toxicity was comparable to of monotherapy with {sup 153}Sm-EDTMP. Zoledronic acid treatment does not influence {sup 153}Sm-EDTMP skeletal uptake. Combined treatment is feasible and safe. (orig.)

  11. Combined use of zoledronic acid and 153Sm-EDTMP in hormone-refractory prostate cancer patients with bone metastases

    International Nuclear Information System (INIS)

    153Sm-ethylenediaminetetramethylenephosphonic acid (EDTMP; Quadramet registered) is indicated for the treatment of painful bone metastases, whereas zoledronic acid (Zometa registered) is indicated for the prevention of skeletal complications. Because of the different therapeutic effects, combining the treatments may be beneficial. Both, however, accumulate in areas with increased osteoblastic activity. Possible drug interactions were investigated. Patients with hormone-refractory prostate cancer were treated with 18.5 MBq/kg 153Sm-EDTMP in weeks 1 and 3 and with 37 MBq/kg in week 15. Treatment with 4 mg zoledronic acid began in week 3 and continued every 4 weeks through week 23. In weeks 3 and 15, zoledronic acid was administered 2 days before 153Sm-EDTMP treatment. Urine was collected 48 h after injection of 153Sm-EDTMP, and whole-body images were obtained 6, 24 and 48 h post-injection. The effect of zoledronic acid on total bone uptake of 153Sm-EDTMP was measured indirectly by the cumulative activity excreted in the urine in weeks 1, 3 and 15. Biodistribution, safety, tolerability and effect on prostate-specific antigen level were also studied. The urinary excretion in week 3 divided by the urinary excretion in week 1 (baseline) times 100% was mean 98.4 ± 11.6% (median 96.2%). From week 1 to 15, after four zoledronic acid treatments, the mean ratio was 101.9 ± 10.7% (median 101.8%). Bioequivalence could be concluded by using a two-sample t test for both per-protocol (n = 13) and full-analysis sets (n = 18). Toxicity was comparable to of monotherapy with 153Sm-EDTMP. Zoledronic acid treatment does not influence 153Sm-EDTMP skeletal uptake. Combined treatment is feasible and safe. (orig.)

  12. Codelivery of zoledronic acid and double-stranded RNA from core-shell nanoparticles

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    Yan W

    2013-01-01

    Full Text Available Li Chen,1 Yunfei Ding,2 Yongzhong Wang,3 Xingrong Liu,2 RJ Babu,1 WR Ravis,1 Weili Yan21Department of Pharmaceutical Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL, USA; 2Department of Pharmaceutical Sciences, College of Life Sciences and Engineering, Southwest Jiaotong University, Chengdu, China; 3School of Life Sciences, Anhui University, Hefei, ChinaBackground: Zoledronic acid, an inhibitor of osteoclast-mediated bone resorption, has been shown to have both direct and indirect antitumor activity. However, its use in extraskeletal malignancy is limited due to rapid uptake and accumulation within bone. Polyinosinic acid-polycytidylic acid [poly (I:C] is a synthetic double-stranded RNA with direct antitumor cytotoxicity if it can be delivered to tumor cells intracellularly.Methods: Cationic lipid-coated calcium phosphate nanoparticles (LCP were developed to enable intracellular codelivery of zoledronic acid and poly (I:C. LCP codelivering zoledronic acid and poly (I:C were prepared using an ethanol injection method. Briefly, the ethanol solution of lipids was rapidly injected into newly formed calcium phosphate crystals containing poly (I:C and zoledronic acid, and the mixture was then sonicated briefly to form LCP. The LCP were fully characterized for mean diameter size and zeta potential, efficiency in loading zoledronic acid, cytotoxic effect in a B16BL6 melanoma cell line in vitro, and antitumor effect in B16BL6 melanoma-bearing mice.Results: LCP with a mean diameter around 200 nm and a narrow size distribution (polydispersity index 0.17 and high zoledronic acid encapsulation efficiency (94% were achieved. LCP loaded with zoledronic acid and poly (I:C had significantly greater antitumor activity than the free drugs in the B16BL6 melanoma cell line (P < 0.05. Furthermore, codelivery of zoledronic acid and poly (I:C by LCP had higher cytotoxicity than delivering poly (I:C alone by LCP (P < 0.05, indicating a synergism

  13. Once-yearly zoledronic acid in hip fracture prevention

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    Oddom Demontiero

    2009-03-01

    Full Text Available Oddom Demontiero, Gustavo DuqueAging Bone Research Program, Nepean Clinical School, University of Sydney, Penrith, NSW, Australia; Department of Geriatric Medicine, Nepean Hospital, Penrith, NSW, AustraliaAbstract: Osteoporosis is an escalating global problem. Hip fractures, the most catastrophic complication of osteoporosis, continue to cause significant mortality and morbidity despite increasing availability of effective preventative agents. Among these agents, oral bisphosphonates have been the first choice for the treatment and prevention of osteoporotic fractures. However, the use of oral bisphosphonates, especially in the older population, has been limited by their side effects and method of administration thus compromising their persistent use. The resultant low adherence by patients has undermined their full potential and has been associated with an increase in the incidence of fragility fractures. Recently, annual intravenous zoledronic acid (ZOL has been approved for osteoporosis. Randomized controlled trials have demonstrated ZOL to be safe, have good tolerability and produce significant effect on bone mass and microarchitecture. Adherence has also been shown to be better with ZOL. Furthermore two large trials firmly demonstrated significant anti-osteoporotic effect (-59% relative risk reduction of hip fractures and mortality benefit (28% reduction in mortality of ZOL in older persons with recent hip fractures. In this review, we report the current evidence on the use of ZOL for the prevention of hip fractures in the elderly. We also report the pharmacological characteristics and the advantages and disadvantages of ZOL in this particular group.Keywords: osteoporosis, zoledronic acid, hip fracture, elderly

  14. Data from extension trials: denosumab and zoledronic acid.

    Science.gov (United States)

    Dore, Robin K

    2012-03-01

    Osteoporosis and fractures that occur as a result of this condition pose a huge public health problem to society and result in morbidity and mortality to individuals. Because osteoporosis is often a result of aging, many people are not aware that therapies exist to reduce the risk of fracture. Until recently, the most common therapies used to treat osteoporosis, the oral bisphosphonates, had an inconvenient and cumbersome mode of administration. Within the last 4 years, two new parenteral antiresorptive drugs to treat osteoporosis were approved by the US Food and Drug Administration. As treatment of osteoporosis may extend for many years, the collection of long-term efficacy and safety data is warranted. This paper discusses data from the extension trials of denosumab and zoledronic acid. PMID:22086442

  15. Zoledronic acid in metastatic chondrosarcoma and advanced sacrum chordoma: two case reports

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    Capasso Elena

    2009-01-01

    Full Text Available Abstract Introduction Chondrosarcomas and chordomas are usually chemoresistant bone tumors and may have a poor prognosis when advanced. They are usually associated with worsening pain difficult to control. Patients and Methods Zoledronic acid was used in a 63-year-old man with metastatic chondrosarcoma and in a 66-year-old woman with a diagnosis of sacrum chordoma both reporting severe pain related to tumor. Results In the first case, zoledronic acid was able to maintain pain control despite disease progression following chemotherapy, in the other case, zoledronic acid only produced significant clinical benefit. Conclusion Control of pain associated with bone tumors such as chondrosarcoma and chondroma may significantly improve from use of zoledronic acid, independently from tumor response to other treatments. Evaluation on larger series are needed to confirm the clinical effect of this bisphosphonate on such tumors.

  16. Zoledronic Acid in Reducing Clinical Fracture and Mortality after Hip Fracture

    DEFF Research Database (Denmark)

    Lyles, Kenneth W; Colón-Emeric, Cathleen S; Magaziner, Jay S; Adachi, Jonathan D; Pieper, Carl F; Mautalen, Carlos; Hyldstrup, Lars; Recknor, Chris; Nordsletten, Lars; Moore, Kathy A; Lavecchia, Catherine; Zhang, Jie; Mesenbrink, Peter; Hodgson, Patricia K; Abrams, Ken; Orloff, John J; Horowitz, Zebulun; Eriksen, Erik Fink; Boonen, Steven; NN, NN

    2007-01-01

    fracture were 8.6% in the zoledronic acid group and 13.9% in the placebo group, a 35% risk reduction (P = 0.001); the respective rates of a new clinical vertebral fracture were 1.7% and 3.8% (P = 0.02), and the respective rates of new nonvertebral fractures were 7.6% and 10.7% (P = 0.03). In the safety......BACKGROUND: Mortality is increased after a hip fracture, and strategies that improve outcomes are needed. METHODS: In this randomized, double-blind, placebo-controlled trial, 1065 patients were assigned to receive yearly intravenous zoledronic acid (at a dose of 5 mg), and 1062 patients were...... assigned to receive placebo. The infusions were first administered within 90 days after surgical repair of a hip fracture. All patients received supplemental vitamin D and calcium. The median follow-up was 1.9 years. The primary end point was a new clinical fracture. RESULTS: The rates of any new clinical...

  17. Detecting Early Biomechanical Effects of Zoledronic Acid on Femurs of Osteoporotic Female Rats

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    Evandro Pereira Palacio

    2012-01-01

    Full Text Available Aim. To investigate the biomechanical effects of zoledronic acid (ZA on femurs of female osteoporotic rats after follow-up periods of 9 and 12 months. Methods. Eighty female Wistar rats were prospectively assessed. At 60 days of age, the animals were randomly divided into two groups: bilateral oophorectomy (O (n=40 and sham surgery (S (n=40. At 90 days of age, groups O and S were randomly subdivided into four groups, according to whether 0.1 mg/kg of ZA or distilled water (DW was intraperitoneally administered: OZA (n=20, ODW (n=20, SZA (n=20, and SDW (n=20. The animals were sacrificed at 9 and 12 months after the administration of the substances, and then their right femurs were removed and analyzed biomechanically. Axial compression tests that focused on determining the maximum load (N, yield point (N, and stiffness coefficient (N/mm of the proximal femur were performed in the biomechanical study. Results. ZA significantly increased the maximum load and yield point, reducing the stiffness coefficient concerning the oophorectomy status and follow-up period. Conclusion. Zoledronic acid, at a dose of 0.1 mg/kg, significantly increased the maximum loads and yield points and reduced the stiffness coefficients in the femurs of female rats with osteoporosis caused by bilateral oophorectomy.

  18. Antifracture efficacy and reduction of mortality in relation to timing of the first dose of zoledronic acid after hip fracture

    DEFF Research Database (Denmark)

    Eriksen, Erik Fink; Lyles, Kenneth W; Colón-Emeric, Cathleen S;

    2009-01-01

    undergone surgical repair of hip fracture. In this analysis, we examined whether timing of the first infusion of zoledronic acid study drug after hip fracture repair influenced the antifracture efficacy and mortality benefit observed in the study. A total of 2127 patients (1065 on active treatment and 1062...... on placebo; mean age, 75 yr; 76% women and 24% men) were administered zoledronic acid or placebo within 90 days after surgical repair of an osteoporotic hip fracture and annually thereafter, with a median follow-up time of 1.9 yr. Median time to first dose after the incident hip fracture surgery was...... approximately 6 wk. Posthoc analyses were performed by dividing the study population into 2-wk intervals (calculated from time of first infusion in relation to surgical repair) to examine effects on BMD, fracture, and mortality. Analysis by 2-wk intervals showed a significant total hip BMD response and a...

  19. EFFICACY OF ZOLEDRONIC ACID IN THE PREVENTION OF BONE METASTASES IN PATIENTS WITH LOCALLY ADVANCED PROSTATE CANCER

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    T. N. Musaev

    2014-07-01

    Full Text Available The analysis of the performed study has established that zoledronic acid is an effective agent in multimodality therapy for locally advanced prostate cancer (PC and allows long-term stabilization of bone tissue. In addition, there is evidence for the efficacy of zoledronic acid in preventing bone metastases (BM and increasing the time to the first BM. The currently accumulated experience with zoledronic acid used in PC permits one to consider its use as standard concomitant therapy.

  20. Zoledronic acid inhibits macrophage/microglia-assisted breast cancer cell invasion

    NARCIS (Netherlands)

    Rietkoetter, Eva; Menck, Kerstin; Bleckmann, Annalen; Farhat, Katja; Schaffrinski, Meike; Schulz, Matthias; Hanisch, Uwe-Karsten; Binder, Claudia; Pukrop, Tobias

    2013-01-01

    The bisphosphonate zoledronic acid (ZA) significantly reduces complications of bone metastasis by inhibiting resident macrophages, the osteoclasts. Recent clinical trials indicate additional anti-metastatic effects of ZA outside the bone. However, which step of metastasis is influenced and whether t

  1. Management of osteoporosis in the aging male: Focus on zoledronic acid

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    Paul K Piper Jr

    2009-06-01

    Full Text Available Paul K Piper Jr1, Ugis Gruntmanis1,21Division of Endocrinology and Metabolism, University of Texas Southwestern Medical Center, Dallas, TX USA; 2North Texas Veterans Affairs Medical Center, Dallas, TX USAAbstract: Osteoporosis in the aging male remains an important yet under-recognized and undertreated disease. Current US estimates indicate that over 14 million men have osteoporosis or low bone mass, and men suffer approximately 500,000 osteoporotic fractures each year. Men experience fewer osteoporotic fractures than women but have higher mortality after fracture. Bisphosphonates are potent antiresorptive agents that inhibit osteoclast activity, suppress in vivo markers of bone turnover, increase bone mineral density, decrease fractures, and improve survival in men with osteoporosis. Intravenous zoledronic acid may be a preferable alternative to oral bisphosphonate therapy in patients with cognitive dysfunction, the inability to sit upright, or significant gastrointestinal pathology. Zoledronic acid (Reclast is approved in the US as an annual 5 mg intravenous infusion to treat osteoporosis in men. The zoledronic acid (Zometa 4 mg intravenous dose has been studied in the prevention of bone loss associated with androgen deprivation therapy.Keywords: male osteoporosis, bisphosphonates, zoledronic acid

  2. Ab initio investigation of the adsorption of zoledronic acid molecule on hydroxyapatite (001) surface: an atomistic insight of bone protection

    Science.gov (United States)

    Ri, Mun-Hyok; Yu, Chol-Jun; Jang, Yong-Man; Kim, Song-Un

    2016-03-01

    We report a computational study of the adsorption of zoledronic acid molecule on hydroxyapatite (001) surface within ab initio density functional theory. The systematic study has been performed, from hydroxyapatite bulk and surface, and zoledronic acid molecule to the adsorption of the molecule on the surface. The optimized bond lengths and bond angles were obtained and analyzed, giving an evidence of structural similarity between subjects under study. The formation energies of hydroxyapatite (001) surfaces with two kinds of terminations were computed as about 1.2 and 1.5 J/m^2 with detailed atomistic structural information. We determined the adsorption energies of zoledronic acid molecule on the surfaces, which are -260 kJ/mol at 0.25 ML and -400 kJ/mol at 0.5 ML. An atomistic insight of strong binding affinity of zoledronic acid to the hydroxyapatite surface was given and discussed.

  3. The rabbit biodistribution of a therapeutic dose of zoledronic acid labeled with Tc-99m

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    Asikoglu, Makbule [Ege University, Faculty of Pharmacy, Department of Radiopharmacy, Bornova 35100, Izmir (Turkey)], E-mail: makbule.asikoglu@ege.edu.tr; Gamze Durak, Funda [Ege University, Faculty of Pharmacy, Department of Radiopharmacy, Bornova 35100, Izmir (Turkey)

    2009-09-15

    The aim of the present study was to label a therapeutic dose of zoledronic acid (ZOL) with Tc-99m, evaluate its in vitro stability and compare its biodistribution to {sup 99m}Tc-methylene biphosphonate ({sup 99m}Tc-MDP) in normal rabbits. Preparation of 0.50 mg of {sup 99m}Tc-ZOL was carried out by the reduction of {sup 99m}Tc-pertechnetate in the presence of stannous chloride. The radiolabeling efficiency was found to be greater than 99%. The labeled complex was stable at least up to 6 h at room temperature determined by paper chromatography. {sup 99m}Tc-ZOL and {sup 99m}Tc-MDP were administered intravenously to the rabbits for scintigraphic studies. Between {sup 99m}Tc-ZOL and {sup 99m}Tc-MDP, there were no significant differences in the ratios of femur/BG and lumbar vertebrae/BG, whereas epiphysis/BG and the kidney/BG ratios of {sup 99m}Tc-MDP were higher than {sup 99m}Tc-ZOL at the static studies.

  4. Zoledronic acid inhibits macrophage/microglia-assisted breast cancer cell invasion

    OpenAIRE

    Rietkötter, Eva; Menck, Kerstin; Bleckmann, Annalen; Farhat, Katja; Schaffrinski, Meike; Schulz, Matthias; Hanisch, Uwe-Karsten; Binder, Claudia; Pukrop, Tobias

    2013-01-01

    The bisphosphonate zoledronic acid (ZA) significantly reduces complications of bone metastasis by inhibiting resident macrophages, the osteoclasts. Recent clinical trials indicate additional anti-metastatic effects of ZA outside the bone. However, which step of metastasis is influenced and whether this is due to direct toxicity on cancer cells or inhibition of the tumor promoting microenvironment, is unknown. In particular, tumor-associated and resident macrophages support each step of organ ...

  5. Jaw osteonecrosis management around a dental implant inserted 2 years before starting treatment with zoledronic acid

    OpenAIRE

    Marín Fernández, A.B.; García Medina, Blas; Aguilar Salvatierra, Antonio; Jiménez Burkhardt, Alberto; Gómez Moreno, Gerardo

    2015-01-01

    Bisphosphonates (BP) are a type of drug known to inhibit bone resorption through complex interventions. Their primary mechanism of action is aimed at the cellular level, inhibiting osteoclast activity and so bone resorption. BPs are widely used, with many patients receiving continuous treatment for years. But it is well known that these drugs can produce osteonecrosis of the jaw (ONJ). Zoledronic acid (ZA) is an intravenous BP used in the treatment and prophylaxis of bone disease in patients ...

  6. Effect of acetaminophen and fluvastatin on post-dose symptoms following infusion of zoledronic acid

    OpenAIRE

    Silverman, S. L.; Kriegman, A.; Goncalves, J.; Kianifard, F; Carlson, T.; Leary, E.

    2010-01-01

    Summary A randomized, double-blind, placebo-controlled study assessed the efficacy of acetaminophen or fluvastatin in preventing post-dose symptoms (increases in body temperature or use of rescue medication) following a single infusion of the intravenous (IV) bisphosphonate zoledronic acid (ZOL). Acetaminophen, but not fluvastatin, significantly reduced the incidence and severity of post-dose symptoms. Introduction Transient symptoms including myalgia and pyrexia have been reported post-infus...

  7. Reactive oxygen species and autophagy associated apoptosis and limitation of clonogenic survival induced by zoledronic acid in salivary adenoid cystic carcinoma cell line SACC-83.

    Directory of Open Access Journals (Sweden)

    Xi-Yuan Ge

    Full Text Available Salivary adenoid cystic carcinoma is an epithelial tumor in the head and neck region. Despite its slow growth, patients with salivary adenoid cystic carcinoma exhibit poor long term survival because of a high rate of distant metastasis. Lung and bone are common distant metastasis sites. Zoledronic acid, a third generation bisphosphonate, has been used for tumor-induced osteolysis due to bone metastasis and has direct antitumor activity in several human neoplasms. Here, we observed that zoledronic acid inhibited salivary adenoid cystic carcinoma cell line SACC-83 xenograft tumor growth in nude mice. In vitro, zoledronic acid induced apoptosis and reduced clonogenic survival in SACC-83. Flow cytometry and western blotting indicated that the cell cycle was arrested at G0/G1. Zoledronic acid treatment upregulated reactive oxygen species as well as the autophagy marker protein LC-3B. Reactive oxygen species scavenger N-acetylcysteine and autophagy antagonist 3-methyladenine decreased zoledronic acid-induced apoptosis and increased clonogenic survival. Silencing of the autophagy related gene Beclin-1 also decreased zoledronic acid-induced apoptosis and inhibition of clonogenic formation. In addition, isobolographic analysis revealed synergistic effects on apoptosis when zoledronic acid and paclitaxel/cisplatin were combined. Taken together, our results suggest that zoledronic acid induced apoptosis and reduced clonogenic survival via upregulation of reactive oxygen species and autophagy in the SACC-83 cell line. Thus, zoledronic acid should be considered a promising drug for the treatment of salivary adenoid cystic carcinoma.

  8. Symptomatic Hypocalcemia Associated with Zoledronic Acid Treatment for Osteoporosis: A Case Report

    Directory of Open Access Journals (Sweden)

    Abdulmohsen H. Al Elq

    2013-03-01

    Full Text Available Intravenous bisphosphonates are widely used in the management of solid tumors, metastatic bone disease, metabolic bone diseases and hypercalcemia of malignancies. Recently, yearly intravenous injections of zoledronic acid, one of the potent nitrogen-containing bisphosphonates, have also been approved for the prevention and treatment of osteoporosis. Although infrequently observed, asymptomatic hypocalcemia mainly due to intravenous bisphosphonates has been documented. Here we report a female patient who exhibited profound symptomatic hypocalcemia after receiving intravenous zoledronic acid as treatment of postmenopausal osteoporosis. The patient was not assessed for calcium status prior to the intravenous bisphosphonate therapy, and she was later found to have severe vitamin D deficiency. To our knowledge, this is the first patient with symptomatic hypocalcemia to be reported after zoledronic acid was approved for the management of osteoporosis. We highlight the importance of evaluating calcium and vitamin D levels before initiating intravenous bisphosphonate treatment, particularly in the presence of widespread vitamin D deficiency and the likelihood of future increases in the prescription of intravenous bisphosphonates.

  9. Efficacy of intravenous zoledronic acid in the prevention and treatment of osteoporosis:A meta-analysis

    Institute of Scientific and Technical Information of China (English)

    Jun Zhang; Ran Wang; Yi-Lei Zhao; Xiao-Hui Sun; Hong-Xing Zhao; Tan Lu; De-Cai Chen; Hai-Bin Xu

    2012-01-01

    Objective:To compare the effect of zoledronic acid in treatment and prevention of osteoporosis with placebo.Methods:Random control trials regarding zoledronic acid in treatment of osteoporosis were retrieved by selectingMedline,EMbase andPubmed databases tillApril2012. TheRevMan software was used for all of the statistical analysis.Results:A total of9 trials were included in this meta-analysis.The pooled effect showed that zoledronic acid could increase the bone mineral density by2.98 times compared with placebo, and reduce the rate of fracture in patients by32%.The results should the zoledronic acid intervention had significantly less serious adverse events than controls, and the odds ratio was0.81(0.76-0.87).The longer term intervention, more than12 months intervention, could gain a better prevention effect for osteoporosis(OR,95%CI forBMD was3.35,2.77-3.92; for fracture was0.67,0.54-0.82).Conclusions:This present study shows that zoledronic acid could be effective approach in the prevention of osteoporosis, and could increase the bone mineral density and reduce the risk of facture.

  10. Sandwich Structure-like Meshes Fabricated via Electrospinning for Controllable Release of Zoledronic Acid

    Institute of Scientific and Technical Information of China (English)

    LU Jian; LIU Jian-guo; SONG Xiao-feng; CHEN Xue-si; WU Xiao-dong

    2011-01-01

    Novel sandwich structure-like nanofiber multilayered meshes were fabricated via electrospinning. The purpose of the present work was to control zoledronic acid release via the novel structure of sandwich structure-like meshes. The in vitro release experiments reveal that the drug release speed and initial burst release were controllable by adjusting the thicknesses of electrospun barrier mesh and drug-loaded mesh. Compared with those of other drug delivery systems, the main advantages of the sandwich structure-like fiber meshes are facile preparation conditions and the generality for hydrophobic and hydrophilic pharmaceuticals.

  11. Data in support of the bone analysis of NOD–SCID mice treated with zoledronic acid and prednisolone

    Science.gov (United States)

    Hori, Naoko; Abe, Takahiro; Sato, Tsuyoshi; Kokabu, Shoichiro; Shimamura, Yumiko; Sato, Tomoya; Yoda, Tetsuya

    2016-01-01

    This paper reports data on the bone, specifically the tibia and mandible, of nonobese diabetic mice with severe combined immunodeficiency disease (NOD–SCID mice) treated with zoledronic acid (ZA) and prednisolone (PSL). The data described here are related to the research article titled “Zoledronic acid basically increases circulating soluble RANKL level in mice, and in glucocorticoid-administrated mice, more increases lymphocytes derived sRANKL by bacterial endotoxic stimuli” [1]. The present data and the NOD–SCID mice experiments described contain insights into the role of bone-remodeling factors induced by ZA treatment. PMID:27182545

  12. Bones, breasts, and bisphosphonates: rationale for the use of zoledronic acid in advanced and early breast cancer

    Directory of Open Access Journals (Sweden)

    Allan Lipton

    2011-03-01

    Full Text Available Allan LiptonMilton S. Hershey Medical Center, Pennsylvania State University, Hershey, PA, USAAbstract: Bisphosphonates inhibit osteoclast-mediated bone resorption, thereby inhibiting the release of growth factors necessary to promote cancer cell growth, differentiation, and tumor formation in bone. These agents have demonstrated efficacy for delaying the onset and reducing the incidence of skeletal-related events in the advanced breast cancer setting, and have been shown to prevent cancer therapy-induced bone loss in the early breast cancer setting. Emerging clinical data indicate that the role of bisphosphonates in advanced and early breast cancer is evolving. Retrospective analyses and recent clinical trial data show that zoledronic acid may improve outcomes in some patients with breast cancer. Data from ABCSG-12 and ZO-FAST suggest that zoledronic acid may improve disease-free survival in the adjuvant breast cancer setting in postmenopausal women or women with endocrine therapy-induced menopause, and recent data from a predefined subset of the AZURE trial added to the anticancer story. However, the overall negative AZURE trial also raises questions about the role of bisphosphonates as an anticancer agent in patients with breast cancer. Overall, these data suggest that the addition of zoledronic acid to established anticancer regimens may have potential anticancer benefits in specific patient populations, although more studies are required to define its role.Keywords: anticancer, adjuvant therapy, bone metastasis, skeletal, zoledronic acid

  13. Complexes of low energy beta emitters {sup 47}Sc and {sup 177}Lu with zoledronic acid for bone pain therapy

    Energy Technology Data Exchange (ETDEWEB)

    Majkowska, Agnieszka [Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw (Poland)], E-mail: a.majkowska@ichtj.waw.pl; Neves, Maria; Antunes, Ines [Instituto Tecnologico e Nuclear, Estrada Nacional 10, 2686-953 Sacavem (Portugal); Bilewicz, Aleksander [Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw (Poland)

    2009-01-15

    Targeted radiopharmaceuticals have been mostly developed to visualize and/or treat oncologic diseases. In targeted radiotherapy radionuclide selection is a key issue, because the radionuclide should provide the appropriate radiation absorbed dose, matching the desirable biologic effect, but at the same time it should preclude irradiation of surrounding healthy tissues. Among the last generation of bisphosphonates with cyclic side chains, zoledronic acid is the most potent bisphosphonate, described till now, which inhibits bone resorption. In this paper, we describe the synthesis, properties and hydroxyapatite binding of zoledronic acid labeled with two low energy beta emitters, {sup 47}Sc and {sup 177}Lu. Radiochemicals labeled with low energy electron emitters are preferred, because they deliver both a therapeutic dose to the bone and spare the bone marrow. Hydroxyapatite adsorption experiments have shown that the binding values obtained with complexes of zoledronic acid labeled with {sup 46}Sc and {sup 177}Lu are much higher than those of bisphosphonates labeled with {sup 153}Sm and {sup 166}Ho. Hence, complexes of zoledronic acid with either {sup 46}Sc or {sup 177}Lu seems to be a promising radiopharmaceutical for bone pain therapy.

  14. Safety and tolerability of zoledronic acid and other bisphosphonates in osteoporosis management

    Directory of Open Access Journals (Sweden)

    Luca Dalle Carbonare

    2010-08-01

    Full Text Available Luca Dalle Carbonare, Mirko Zanatta, Adriano Gasparetto, Maria Teresa ValentiClinic of Internal Medicine D, Department of Medicine, University of Verona, ItalyAbstract: Bisphosphonates (BPs are widely used in the treatment of postmenopausal ­osteoporosis and other metabolic bone diseases. They bind strongly to bone matrix and reduce bone loss through inhibition of osteoclast activity. They are classified as nitrogen- and non-nitrogen-containing bisphosphonates (NBPs and NNBPs, respectively. The former inhibit farnesyl diphosphate synthase while the latter induce the production of toxic analogs of adenosine triphosphate. These mechanisms of action are associated with different antifracture efficacy, and NBPs show the most powerful action. Moreover, recent evidence indicates that NBPs can also stimulate osteoblast activity and differentiation. Several randomized control trials have demonstrated that NBPs significantly improve bone mineral density, suppress bone turnover, and reduce the incidence of both vertebral and nonvertebral fragility fractures. Although they are generally considered safe, some side effects are reported (esophagitis, acute phase reaction, hypocalcemia, uveitis, and compliance with therapy is often inadequate. In particular, gastrointestinal discomfort is frequent with the older daily oral administrations and is responsible for a high proportion of discontinuation. The most recent weekly and monthly formulations, and in particular the yearly infusion of zoledronate, significantly improve persistence with treatment, and optimize clinical, densitometric, and antifracture outcomes.Keywords: bisphosphonates, osteoporosis, safety, tolerability, zoledronic acid

  15. Long-term leukopenia in a lung transplanted patient with cystic fibrosis treated with zoledronic acid

    DEFF Research Database (Denmark)

    Karahasanovic, A; Thorsteinsson, A-L; Bjarnason, N H;

    2016-01-01

    Cystic fibrosis (CF) is a serious autosomal recessive genetic disorder associated with chronic lung disease, malabsorption, malnutrition, pancreatic insufficiency and premature respiratory failure. Recent advances in medical science and technology have increased the lifespan of patients with CF......, albeit with long-term consequences of the disease, such as osteoporosis, becoming of increasing significance. The medical treatment of osteoporosis in patients with CF or after organ transplantation is still being explored, and no clear guidelines regarding the best choice of bisphosphonate exist. We...... report a case of a young woman with CF, lung transplantation and low bone mass developing long-term leukopenia after treatment with zoledronic acid. The leukopenia, with a strong affection of the neutrocytes, lasted for 4 months and the condition only went into remission after granulocyte...

  16. Association between timing of zoledronic acid infusion and hip fracture healing

    DEFF Research Database (Denmark)

    Colón-Emeric, C; Nordsletten, L; Olson, S;

    2010-01-01

    evident effect on fracture healing, even when the drug is infused in the immediate postoperative period. INTRODUCTION: Intravenous zoledronic acid 5 mg (ZOL) given after a hip fracture reduces secondary fracture rates and mortality. It has been postulated that bisphosphonates may affect healing if given...... soon after a fracture. We sought to determine whether the timing of ZOL infusion affected the risk of delayed hip fracture healing. METHODS: In the HORIZON Recurrent Fracture Trial, patients were randomized within 90 days of a low-trauma hip fracture to receive either once-yearly ZOL (n¿=¿1......¿=¿0.44). There was no interaction by timing of infusion, and nonunion rates were similar even when ZOL was given within 2 weeks of hip fracture repair. NSAID use was significantly associated with delayed fracture healing (OR, 2.55; 95% CI, 1.49-4.39; p¿

  17. Protection of bone in premenopausal women with breast cancer: focus on zoledronic acid

    Directory of Open Access Journals (Sweden)

    Aft R

    2012-10-01

    Full Text Available Rebecca AftDepartment of Surgery, Washington University School of Medicine, St Louis, MO, USAAbstract: Maintaining bone health is important for patients with breast cancer (BC, the most commonly diagnosed cancer in American women. Indeed, bone loss is common throughout the BC disease continuum. In the metastatic BC setting, patients are likely to develop bone metastases, a painful complication that can lead to potentially debilitating skeletal-related events. Bone health is equally important for patients with early BC. During adjuvant therapy for early BC, the largest challenge to bone health is from accelerated bone mineral density (BMD loss. Although decreased BMD is well recognized in older, postmenopausal women, it may be underestimated in younger, premenopausal women undergoing endocrine therapy for BC. The rate and extent of cancer therapy-induced bone loss (from chemotherapy or endocrine therapy are substantially greater than normal decreases in BMD during menopause. Bisphosphonates such as zoledronic acid (ZOL are antiresorptive agents indicated for the treatment of bone metastases from BC. Clinical trials over the past few years suggest that, although not yet approved for this indication, ZOL can prevent cancer therapy-induced bone loss and improve BMD in premenopausal women receiving adjuvant (endocrine or chemo- therapy for BC. Furthermore, the benefits of ZOL therapy may go beyond maintaining bone health and include potential anticancer benefits together with favorable tolerability and cost/benefit profiles. This review will focus specifically on the role of ZOL in preserving the bone health of premenopausal women with BC.Keywords: breast cancer, premenopausal, zoledronic acid

  18. Long-term leukopenia in a lung transplanted patient with cystic fibrosis treated with zoledronic acid: a case report.

    Science.gov (United States)

    Karahasanovic, A; Thorsteinsson, A-L; Bjarnason, N H; Eiken, P

    2016-08-01

    Cystic fibrosis (CF) is a serious autosomal recessive genetic disorder associated with chronic lung disease, malabsorption, malnutrition, pancreatic insufficiency and premature respiratory failure. Recent advances in medical science and technology have increased the lifespan of patients with CF, albeit with long-term consequences of the disease, such as osteoporosis, becoming of increasing significance. The medical treatment of osteoporosis in patients with CF or after organ transplantation is still being explored, and no clear guidelines regarding the best choice of bisphosphonate exist. We report a case of a young woman with CF, lung transplantation and low bone mass developing long-term leukopenia after treatment with zoledronic acid. The leukopenia, with a strong affection of the neutrocytes, lasted for 4 months and the condition only went into remission after granulocyte-colony stimulating factor (G-CSF) treatment. It is important to be aware of symptomatic leukopenia in immunosuppressive patients after treatment with zoledronic acid. PMID:27080707

  19. Time associated with intravenous zoledronic acid administration in patients with breast or prostate cancer and bone metastasis

    OpenAIRE

    Richhariya A; Qian Y; Zhao Y.; Chung K

    2012-01-01

    Akshara Richhariya1, Yi Qian2, Yufan Zhao2, Karen Chung11Amgen Inc, Global Health Economics, Thousand Oaks, CA, USA; 2Amgen Inc, Global Biostatistical Sciences, Thousand Oaks, CA, USAPurpose: Intravenous (IV) zoledronic acid (ZA) is commonly used to delay skeletal complications secondary to bone metastases. However, the time associated with ZA administration may represent a significant burden to healthcare providers and patients. This study assessed the time associated with IV ZA infusion in ...

  20. OPG-Fc but Not Zoledronic Acid Discontinuation Reverses Osteonecrosis of the Jaws (ONJ) in Mice

    Science.gov (United States)

    de Molon, Rafael Scaf; Shimamoto, Hiroaki; Bezouglaia, Olga; Pirih, Flavia Q; Dry, Sarah M; Kostenuik, Paul; Boyce, Rogely W; Dwyer, Denise; Aghaloo, Tara L; Tetradis, Sotirios

    2016-01-01

    Osteonecrosis of the jaws (ONJ) is a significant complication of antiresorptive medications, such as bisphosphonates and denosumab. Antiresorptive discontinuation to promote healing of ONJ lesions remains highly controversial and understudied. Here, we investigated whether antiresorptive discontinuation alters ONJ features in mice, employing the potent bisphosphonate zoledronic acid (ZA) or the receptor activator of NF-κB ligand (RANKL) inhibitor OPG-Fc, utilizing previously published ONJ animal models. Mice were treated with vehicle (veh), ZA, or OPG-Fc for 11 weeks to induce ONJ, and antiresorptives were discontinued for 6 or 10 weeks. Maxillae and mandibles were examined by µCT imaging and histologically. ONJ features in ZA and OPG-Fc groups included periosteal bone deposition, empty osteocyte lacunae, osteonecrotic areas, and bone exposure, each of which substantially resolved 10 weeks after discontinuing OPG-Fc but not ZA. Full recovery of tartrate-resistant acid phosphatase-positive (TRAP+) osteoclast numbers occurred after discontinuing OPG-Fc but not ZA. Our data provide the first experimental evidence demonstrating that discontinuation of a RANKL inhibitor, but not a bisphosphonate, reverses features of osteonecrosis in mice. It remains unclear whether antiresorptive discontinuation increases the risk of skeletal-related events in patients with bone metastases or fracture risk in osteoporosis patients, but these preclinical data may nonetheless help to inform discussions on the rationale for a “drug holiday” in managing the ONJ patient. PMID:25727550

  1. Association between timing of zoledronic acid infusion and hip fracture healing

    DEFF Research Database (Denmark)

    Colón-Emeric, C; Nordsletten, L; Olson, S; Major, N; Boonen, S; Haentjens, P; Mesenbrink, P; Magaziner, J; Adachi, J; Lyles, K W; Hyldstrup, L; Bucci-Rechtweg, C; Recknor, C; NN, NN

    2011-01-01

    evident effect on fracture healing, even when the drug is infused in the immediate postoperative period. INTRODUCTION: Intravenous zoledronic acid 5 mg (ZOL) given after a hip fracture reduces secondary fracture rates and mortality. It has been postulated that bisphosphonates may affect healing if given...... soon after a fracture. We sought to determine whether the timing of ZOL infusion affected the risk of delayed hip fracture healing. METHODS: In the HORIZON Recurrent Fracture Trial, patients were randomized within 90 days of a low-trauma hip fracture to receive either once-yearly ZOL (n = 1,065) or...... = 0.44). There was no interaction by timing of infusion, and nonunion rates were similar even when ZOL was given within 2 weeks of hip fracture repair. NSAID use was significantly associated with delayed fracture healing (OR, 2.55; 95% CI, 1.49-4.39; p < 0.001). CONCLUSIONS: ZOL has no clinically...

  2. Probe into medication timing of acetaminophen for prevention of zoledronic acid adverse reaction%对乙酰氨基酚预防唑来膦酸不良反应用药时机的探讨1)

    Institute of Scientific and Technical Information of China (English)

    陈楚娴; 彭松林; 赵坚

    2014-01-01

    [目的]探讨对乙酰氨基酚预防唑来膦酸注射液(密固达)不良反应最佳用药时机。[方法]将60例绝经后骨质疏松症病人随机分入观察组和对照组,每组30例。观察组静脉输注唑来膦酸注射液前1 h,对照组在静脉输注后1h给予口服对乙酰氨基酚缓释片,两组间隔6h 后和次日再分别给药1次。用副反应量表(TESS)评定不良反应。[结果]在使用唑来膦酸注射液后4h、8 h和第2日3个评分时段,观察组TESS评分低于对照组(t=-7.087,-4.777和-5.087,P均<0.01)。[结论]在静脉输注唑来膦酸注射液前使用对乙酰氨基酚,能有效预防唑来膦酸不良反应,效果优于静脉输注后给药。%Obj ective:To probe into the best medication timing of acetamino-phen for prevention of zoledronic acid adverse reaction.Methods:A total of 60 cases of patients with postmenopausal osteoporosis were randomly divided into observation group and control group,30 cases in each.At 1 h before intrave-nous infusion of zoledronic acid inj ection in observation group and at 1 h after intravenous infusion in control group,the patients were given oral acetamino-phen sustained release tablets,oral acetaminophen were administered once a-gain respectively after interval 6 h and the next day in two groups.The adverse reactions were evaluated with TESS (TESS).Results:three ratings periods in-cluding 4 h,8h and the 2nd day after the use of zoledronic acid injection,the TESS score in observation group was lower than that in control group (t= -7.087,-4.777 and -5.087,P<0.01).Conclusion:acetaminophen used before intravenous infusion of zoledronic acid inj ection using can effectively prevent adverse effects of zoledronic acid,and its effect is better than that after intrave-nous administration.

  3. Zoledronic acid suppresses transforming growth factor-β-induced fibrogenesis by human gingival fibroblasts

    Science.gov (United States)

    KOMATSU, YUKO; IBI, MIHO; CHOSA, NAOYUKI; KYAKUMOTO, SEIKO; KAMO, MASAHARU; SHIBATA, TOSHIYUKI; SUGIYAMA, YOSHIKI; ISHISAKI, AKIRA

    2016-01-01

    Bisphosphonates (BPs) are analogues of pyro-phosphate that are known to prevent bone resorption by inhibiting osteoclast activity. Nitrogen-containing BPs, such as zoledronic acid (ZA), are widely used in the treatment of osteoporosis and bone metastasis. However, despite having benefits, ZA has been reported to induce BP-related osteonecrosis of the jaw (BRONJ) in cancer patients. The molecular pathological mechanisms responsible for the development of BRONJ, including necrotic bone exposure after tooth extraction, remain to be elucidated. In this study, we examined the effects of ZA on the transforming growth factor-β (TGF-β)-induced myofibroblast (MF) differentiation of human gingival fibroblasts (hGFs) and the migratory activity of hGFs, which are important for wound closure by fibrous tissue formation. The ZA maximum concentration in serum (Cmax) was found to be approximately 1.47 µM, which clinically, is found after the intravenous administration of 4 mg ZA, and ZA at this dose is considered appropriate for the treatment of cancer bone metastasis or bone diseases, such as Erdheim-Chester disease. At Cmax, ZA significantly suppressed i) the TGF-β-induced promotion of cell viability, ii) the TGF-β-induced expression of MF markers such as α-smooth muscle actin (α-SMA) and type I collagen, iii) the TGF-β-induced migratory activity of hGFs and iv) the expression level of TGF-β type I receptor on the surfaces of hGFs, as well as the TGF-β-induced phosphorylation of Smad2/3. Thus, ZA suppresses TGF-β-induced fibrous tissue formation by hGFs, possibly through the inhibition of Smad-dependent signal transduction. Our findings partly elucidate the molecular mechanisms underlying BRONJ and may prove to be beneficial to the identification of drug targets for the treatment of this symptom at the molecular level. PMID:27176567

  4. Osteoclasts but not osteoblasts are affected by a calcified surface treated with zoledronic acid in vitro

    International Nuclear Information System (INIS)

    Bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption. Recent interest has centered on the effects of bisphosphonates on osteoblasts. Chronic dosing of osteoblasts with solubilized bisphosphonates has been reported to enhance osteogenesis and mineralization in vitro. However, this methodology poorly reflects the in vivo situation, where free bisphosphonate becomes rapidly bound to mineralized bone surfaces. To establish a more clinically relevant cell culture model, we cultured bone cells on calcium phosphate coated quartz discs pre-treated with the potent nitrogen-containing bisphosphonate, zoledronic acid (ZA). Binding studies utilizing [14C]-labeled ZA confirmed that the bisphosphonate bound in a concentration-dependent manner over the 1-50 μM dose range. When grown on ZA-treated discs, the viability of bone-marrow derived osteoclasts was greatly reduced, while the viability and mineralization of the osteoblastic MC3T3-E1 cell line were largely unaffected. This suggests that only bone resorbing cells are affected by bound bisphosphonate. However, this system does not account for transient exposure to unbound bisphosphonate in the hours following a clinical dosing. To model this event, we transiently treated osteoblasts with ZA in the absence of a calcified surface. Osteoblasts proved highly resistant to all transitory treatment regimes, even when utilizing ZA concentrations that prevented mineralization and/or induced cell death when dosed chronically. This study represents a pharmacologically more relevant approach to modeling bisphosphonate treatment on cultured bone cells and implies that bisphosphonate therapies may not directly affect osteoblasts at bone surfaces

  5. Enhanced antimelanoma activity of methotrexate and zoledronic acid within polymeric sandwiches.

    Science.gov (United States)

    Schilrreff, Priscila; Cervini, Gabriela; Romero, Eder Lilia; Morilla, Maria Jose

    2014-10-01

    New therapies are urgently needed against melanoma, one of the most aggressive tumors. Melanoma cells are resistant to the antifolate methotrexate (MTX), since MTX is taken up by the folate receptor-α (FRα), sequestered in melanosomes and exported out of the cell. The bisphosphonate zoledronic acid (ZOL) is active in several non-skeletal tumors; however, its antitumoral activity is hampered by its long-term accumulation in bones and low cellular permeability. Recently, we showed that core-shell tecto-dendrimers made of amine-terminated polyamidoamine generation 5 dendrimer (G5) as core and carboxyl-terminated G2.5 dendrimer as shell (G5G2.5) had selective cytotoxicity to melanoma cells. We hypothesized here that the activity of MTX and ZOL on melanoma cells could be enhanced when loaded within G5G2.5. MTX and ZOL were loaded within G5 cores, which were coated by a covalently bound shell of G2.5 dendrimers (drug-sandwiches). 12nm mean diameter and -12mV Z potential drug-sandwiches incorporating 6 and 31 molecules of MTX and ZOL, respectively, per G5G2.5, showed higher cytotoxicity (by MTT and apoptosis/necrosis assays) to melanoma (Sk-Mel-28) cells than free drugs and G5G2.5. Only MTX-sandwich was cytotoxic to Sk-Mel-28 cells and harmless to keratinocytes (HaCaT cells). The intracellular pathway of G5G2.5 was followed using chemical inhibitors of endocytosis. The increased cytotoxicity of MTX-sandwich could be due to its uptake by macropinocytosis instead of by FRα, avoiding MTX exocytosis. The increased cytotoxicity of ZOL-sandwich could be due to an increased intracellular accumulation of ZOL, owed by its endocytic uptake instead of diffusing as free drug. PMID:25016541

  6. Zoledronic acid results in better health-related quality of life following hip fracture: the HORIZON-Recurrent Fracture Trial

    DEFF Research Database (Denmark)

    Adachi, J D; Lyles, K W; Colón-Emeric, C S; Boonen, S; Pieper, C F; Mautalen, C; Hyldstrup, L; Recknor, C; Nordsletten, L; Moore, K A; Bucci-Rechtweg, C; Su, G; Eriksen, E F; Magaziner, J S

    2011-01-01

    placebo group. At the end of the study, mean change from baseline in EQ-5D VAS was greater for ZOL vs. placebo in all patients (7.67¿±¿0.56 vs. 5.42¿±¿0.56), and in subgroups of patients experiencing clinical vertebral fractures (8.86¿±¿4.91 vs. -1.69¿±¿3.42), non-vertebral fractures (5.03¿±¿2.48 vs. -1...... evaluate the benefits of zoledronic acid (ZOL) versus placebo on health-related quality of life (HRQoL) among patients from The Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly Recurrent Fracture Trial (HORIZON-RFT). METHODS: In this randomized, double-blind, placebo-controlled trial......, 2,127 patients were randomized to receive annual infusion of ZOL 5 mg (n¿=¿1,065) or placebo (n¿=¿1,062) within 90 days after surgical repair of low-trauma hip fracture. HRQoL was measured using EQ-5D Visual Analogue Scale (VAS) and utility scores (EuroQol instrument) at months 6, 12, 24, 36, and...

  7. Zoledronic acid improves bone mineral density, reduces bone turnover and improves skeletal architecture over 2 years of treatment in children with secondary osteoporosis

    DEFF Research Database (Denmark)

    Simm, Peter J; Johannesen, Jesper; Briody, Julie;

    2011-01-01

    There are limited data on the use of bisphosphonate therapy for secondary osteoporoses in childhood, and no previous reports of the use of zoledronic acid in this group. We report 20 children with a variety of underlying primary diagnoses with associated secondary osteoporosis, who were treated...

  8. Randomized Controlled Trial of Zoledronic Acid plus Chemotherapy versus Chemotherapy Alone as Neoadjuvant Treatment of HER2-Negative Primary Breast Cancer (JONIE Study.

    Directory of Open Access Journals (Sweden)

    Yoshie Hasegawa

    Full Text Available Zoledronic acid (ZOL is a nitrogen-containing bisphosphonate that induces osteoclast apoptosis and inhibits bone resorption by inhibiting the mevalonate pathway. Its benefit for the prevention of skeletal complications due to bone metastases has been established. However, the antitumor efficacy of ZOL, although suggested by multiple preclinical and clinical studies, has not yet been clinically proven. We performed the present randomized Phase 2 trial to investigate the antitumor effect of ZOL with chemotherapy (CT.Asian patients with HER2-negative invasive breast cancer were randomly assigned to either the CT or CT+ZOL (CTZ group. One hundred and eighty-eight patients were randomized to either the CT group (n = 95 or the CTZ group (n = 93 from March 2010 to April 2012, and 180 patients were assessed. All patients received four cycles of FEC100 (fluorouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 500 mg/m2, followed by 12 cycles of paclitaxel at 80 mg/m2 weekly. ZOL (4 mg was administered three to four times weekly for 7 weeks to the patients in the CTZ group. The primary endpoint was the pathological complete response (pCR rate, which was defined as no invasive cancer in the breast tissue specimen. Safety was assessed in all patients who received at least one dose of the study drug.This randomized controlled trial indicated that the rates of pCR in CTZ group (14.8% was doubled to CT group (7.7%, respectively (one-sided chi-square test, p = 0.068, though the additional efficacy of zoledronic acid was not demonstrated statistically. The pCR rate in postmenopausal patients was 18.4% and 5.1% in the CTZ and CT groups, respectively (one-sided Fisher's exact test, p = 0.071, and that in patients with triple-negative breast cancer was 35.3% and 11.8% in the CTZ and CT groups, respectively (one-sided Fisher's exact test, p = 0.112. Thus the addition of ZOL to neoadjuvant CT has potential anticancer benefits in postmenopausal patients and

  9. Time associated with intravenous zoledronic acid administration in patients with breast or prostate cancer and bone metastasis

    Directory of Open Access Journals (Sweden)

    Richhariya A

    2012-02-01

    Full Text Available Akshara Richhariya1, Yi Qian2, Yufan Zhao2, Karen Chung11Amgen Inc, Global Health Economics, Thousand Oaks, CA, USA; 2Amgen Inc, Global Biostatistical Sciences, Thousand Oaks, CA, USAPurpose: Intravenous (IV zoledronic acid (ZA is commonly used to delay skeletal complications secondary to bone metastases. However, the time associated with ZA administration may represent a significant burden to healthcare providers and patients. This study assessed the time associated with IV ZA infusion in patients with bone metastases secondary to breast or prostate cancer (BC or PC in the clinic setting.Methods: Eligible BC or PC patients with bone metastases scheduled to receive IV ZA were observed at seven US-based oncology clinics. Trained observers recorded the time for preinfusion tasks, ZA drug preparation, intravenous infusion, and follow-up activities.Results: Data are reported for 39 patients (BC: 24; PC: 15. Mean administration time was 69 (standard deviation [SD] 42 minutes for all patients combined, 72 (SD 47 minutes for BC, and 65 (SD 33 minutes for PC. Activity times were comparable between tumor types. Mean time for preinfusion tasks (eg, assessment of vital signs, blood draw and ZA preparation were 12 (SD 20 minutes and 2 (SD 1 minutes, respectively. Mean time required for intravenous infusion (ZA infusion and hydration, when provided and follow-up activities were 54 (SD 31 minutes and 2 (SD 1 minutes, respectively.Conclusion: Infusion time was the greatest time commitment associated with IV ZA administration, representing 78% of the total time on average. Time for preinfusion activities varied substantially. Overall, the mean time for ZA administration represents a notable time burden for healthcare providers and patients.Keywords: time and motion, bisphosphonates, zoledronic acid, intravenous administration

  10. Influence of zoledronic acid on disseminated tumor cells in bone marrow and survival: results of a prospective clinical trial

    International Nuclear Information System (INIS)

    The presence of disseminated tumor cells (DTC) in bone marrow (BM) of breast cancer patients is associated with reduced clinical outcome. Bisphosphonate treatment was shown to eradicate DTC from BM in several studies. This controlled randomized open-label multi-center study aimed to investigate the influence of zoledronic acid (ZOL) on DTC and survival of breast cancer patients (Clinical Trial Registration Number: NCT00172068). Patients with primary breast cancer and DTC-positive bone marrow were randomized to treatment with ZOL plus adjuvant systemic therapy (n = 40) or adjuvant systemic therapy alone (n = 46) between 03/2002 and 12/2004. DTC were identified by immunocytochemistry using the pancytokeratin antibody A45B/B3 and by cytomorphology. The change in DTC numbers at 12 months and 24 months versus baseline, as well as patient outcomes were evaluated. 86 patients could be included into survival analysis (median follow-up: 88 months, range: 8–108 mths). Patients in the control group were more likely to die during follow-up than those in the ZOL-group (11% vs. 2%, p = 0.106). 15% of patients in the control group presented with relapse whereas only 8% of ZOL group patients developed metastatic or recurrent disease during follow-up (p = 0.205). At 24 months, 16% of patients from the control group were still DTC positive, whereas all patients treated with ZOL became DTC negative (p = 0.032). Patients presenting with persistent DTC 12 months after diagnosis had significantly shorter overall survival (p = 0.011). Bisphosphonate therapy contributes to eradication of disseminated tumor cells. The positive influence of bisphosphonates on survival in the adjuvant setting may be due to their effects on DTC. ClinicalTrials.gov Identifier: http://clinicaltrials.gov/show/NCT00172068 [Zoledronic Acid in the Treatment of Breast Cancer With Minimal Residual Disease in the Bone Marrow (MRD-1)

  11. Local treatment of a bone graft by soaking in zoledronic acid inhibits bone resorption and bone formation. A bone chamber study in rats

    Directory of Open Access Journals (Sweden)

    Belfrage Ola

    2012-12-01

    Full Text Available Abstract Background Bone grafts are frequently used in orthopaedic surgery. Graft remodelling is advantageous but can occur too quickly, and premature bone resorption might lead to decreased mechanical integrity of the graft. Bisphosphonates delay osteoclastic bone resorption but may also impair formation of new bone. We hypothesize that these effects are dose dependent. In the present study we evaluate different ways of applying bisphosphonates locally to the graft in a bone chamber model, and compare that with systemic treatment. Methods Cancellous bone grafts were placed in titanium chambers and implanted in the tibia of 50 male rats, randomly divided into five groups. The first group served as negative control and the grafts were rinsed in saline before implantation. In the second and third groups, the grafts were soaked in a zoledronic acid solution (0.5 mg/ml for 5 seconds and 10 minutes respectively before being rinsed in saline. In the fourth group, 8 μL of zoledronic acid solution (0.5 mg/ml was pipetted onto the freeze-dried grafts without rinsing. The fifth group served as positive control and the rats were given zoledronic acid (0.1 mg/kg systemically as a single injection two weeks after surgery. The grafts were harvested at 6 weeks and analysed with histomorphometry, evaluating the ingrowth distance of new bone into the graft as an equivalent to the anabolic osteoblast effect and the amount (bone volume/total volume; BV/TV of remaining bone in the remodelled graft as equivalent to the catabolic osteoclast effect. Results In all chambers, almost the entire graft had been revascularized but only partly remodelled at harvest. The ingrowth distance of new bone into the graft was lower in grafts soaked in zoledronic acid for 10 minutes compared to control (p = 0.007. In all groups receiving zoledronic acid, the BV/TV was higher compared to control. Conclusions This study found a strong inhibitory effect on bone resorption by

  12. 密固达在老年骨质疏松治疗中的安全观察%The safety observation of zoledronic acid in the treatment of senile osteoporosis

    Institute of Scientific and Technical Information of China (English)

    郭冰凌; 李法琦

    2014-01-01

    目的:本研究通过与口服阿仑膦酸钠( alendronate sodium)的对比,旨在评价老年人使用唑来膦酸注射液( zoledronic acid)的疗效、应用、安全性、依从性。方法回顾性分析2012年8月至2013年9月,重庆医科大学附属第一医院的116例原发性骨质疏松患者的医疗记录。两组药物组各包含58例,选取绝经后妇女、60岁以上原发性骨质疏松患者且首次使用阿仑膦酸钠/唑来膦酸注射液患者入组。通过对比两组用药前后腰椎和(或)髋部骨密度改变、依从性、不良反应和新发骨折率,比较两种药物的疗效。结果两组入组患者性别、年龄、骨密度相似。唑来膦酸注射液组的骨密度增加量比阿仑膦酸钠组有显著差异,其中腰椎骨密度(P=0.007)、髋部骨密度(P=0.006)。唑来膦酸注射液组有更多的不良反应(n=50);新发骨折数较阿仑膦酸钠组少( n=12)。两组患者中,疼痛为主的主观症状以视觉模拟标度尺( visual analogue scale,VAS)表示,唑来膦酸注射液组中疼痛症状明显缓解( P<0.01)。两组中治疗前后血钙( blood calcium,BC)和碱性磷酸酶( alkaline phosphatase,AP)均无明显差异。结论唑来膦酸注射液治疗老年性骨质疏松更优于阿仑膦酸钠。在提高腰椎及髋部骨密度方面疗效相似。虽然在治疗前3天有更多的不良反应,但减少了新发骨折率,缓解症状更显著。两组药物对血生化的影响均无明显差异。%Objective To assess real-life effectiveness, health care resource utilization, safety, and compliance to the treatment with zoledronic acid in comparison with orally administered alendronate sodium in senile patients with osteoporosis.Methods The medical records of 116 patients with primary osteoporosis, who were treated in the First Affiliated Hospital of Chongqing Medical University from August 2012 to

  13. Biostimulatory effects of low-level laser therapy on epithelial cells and gingival fibroblasts treated with zoledronic acid

    Science.gov (United States)

    Basso, F. G.; Pansani, T. N.; Turrioni, A. P. S.; Kurachi, C.; Bagnato, V. S.; Hebling, J.; de Souza Costa, C. A.

    2013-05-01

    Low-level laser therapy (LLLT) has been considered as an adjuvant treatment for bisphosphonate-related osteonecrosis, presenting positive clinical outcomes. However, there are no data regarding the effect of LLLT on oral tissue cells exposed to bisphosphonates. This study aimed to evaluate the effects of LLLT on epithelial cells and gingival fibroblasts exposed to a nitrogen-containing bisphosphonate—zoledronic acid (ZA). Cells were seeded in wells of 24-well plates, incubated for 48 h and then exposed to ZA at 5 μM for an additional 48 h. LLLT was performed with a diode laser prototype—LaserTABLE (InGaAsP—780 nm ± 3 nm, 25 mW), at selected energy doses of 0.5, 1.5, 3, 5, and 7 J cm-2 in three irradiation sessions, every 24 h. Cell metabolism, total protein production, gene expression of vascular endothelial growth factor (VEGF) and collagen type I (Col-I), and cell morphology were evaluated 24 h after the last irradiation. Data were statistically analyzed by Kruskal-Wallis and Mann-Whitney tests at 5% significance. Selected LLLT parameters increased the functions of epithelial cells and gingival fibroblasts treated with ZA. Gene expression of VEGF and Col-I was also increased. Specific parameters of LLLT biostimulated fibroblasts and epithelial cells treated with ZA. Analysis of these in vitro data may explain the positive in vivo effects of LLLT applied to osteonecrosis lesions.

  14. Is retention of zoledronic acid onto bone different in multiple myeloma and breast cancer patients with bone metastasis?

    DEFF Research Database (Denmark)

    Søe, Kent; Plesner, Torben; Jakobsen, Erik H;

    2013-01-01

    Zoledronic acid (Zol) is used to treat bone disease in both multiple myeloma (MM) and breast cancer patients with bone metastasis (BC). However, bones of MM and BC patients show a difference in retention of the bisphosphonate used for bone scintigraphy. Therefore, we hypothesized that disease......-specific factors may differently influence Zol retention in MM and BC patients. We tested this hypothesis in an investigator initiated phase II clinical trial in which we compared the whole-body retention (WBrt) of Zol in a cohort of 30 multiple myeloma (MM) and 30 breast cancer (BC) (20 Zol naive and 40 with six...... of Zol correlated with bone-specific alkaline phosphatase (bALP) levels in BC (p = 0.001), and with CTX/bALP in Zol naive MM patients (p = 0.012). Especially in BC patients, WBrt correlated with age (p = 0.014) independently of kidney function. In MM patients WBrt was found to primarily correlate...

  15. Generalized skin rash due to zoledronic acid%唑来膦酸致全身皮疹

    Institute of Scientific and Technical Information of China (English)

    刘剑锋; 冯巧飞

    2012-01-01

    1例57岁女性患者因重度骨质疏松症给予碳酸钙和骨化三醇口服,1周后,给予唑来膦酸5 mg溶于0 9%氯化钠注射液100 ml静脉滴注.第2天,患者出现发热、全身皮疹,头晕、乏力、关节疼痛及双下肢肌肉酸痛.立即给予地塞米松、氯雷他定.第7天,患者头晕、乏力、关节疼痛及双下肢肌肉酸痛等症状消失,体温降至正常.第10天皮疹完全消退.%A 57-year- old woman received oral calcium carbonate and calcitriol for severe osteoporosis. One week later, an IV infusion of zoledronic acid 5 mg dissolved in 0. 9% sodium chloride solution 100 ml was given. On day 2, she developed fever, generalized skin rash, dizziness, asthenia, as well as joint pain and muscle aches in her lower limbs. She was given dexamethasone and loratadine immediately. On day 7, her clinical symptoms such as dizziness, asthenia, as well as joint pain and muscle aches in her lower limbs disappeared, and her body temperature returned to normal. On day 10, her skin rash completely disappeared.

  16. Biostimulatory effects of low-level laser therapy on epithelial cells and gingival fibroblasts treated with zoledronic acid

    International Nuclear Information System (INIS)

    Low-level laser therapy (LLLT) has been considered as an adjuvant treatment for bisphosphonate-related osteonecrosis, presenting positive clinical outcomes. However, there are no data regarding the effect of LLLT on oral tissue cells exposed to bisphosphonates. This study aimed to evaluate the effects of LLLT on epithelial cells and gingival fibroblasts exposed to a nitrogen-containing bisphosphonate—zoledronic acid (ZA). Cells were seeded in wells of 24-well plates, incubated for 48 h and then exposed to ZA at 5 μM for an additional 48 h. LLLT was performed with a diode laser prototype—LaserTABLE (InGaAsP—780 nm ± 3 nm, 25 mW), at selected energy doses of 0.5, 1.5, 3, 5, and 7 J cm−2 in three irradiation sessions, every 24 h. Cell metabolism, total protein production, gene expression of vascular endothelial growth factor (VEGF) and collagen type I (Col-I), and cell morphology were evaluated 24 h after the last irradiation. Data were statistically analyzed by Kruskal–Wallis and Mann–Whitney tests at 5% significance. Selected LLLT parameters increased the functions of epithelial cells and gingival fibroblasts treated with ZA. Gene expression of VEGF and Col-I was also increased. Specific parameters of LLLT biostimulated fibroblasts and epithelial cells treated with ZA. Analysis of these in vitro data may explain the positive in vivo effects of LLLT applied to osteonecrosis lesions. (paper)

  17. A Biphasic Calcium Sulphate/Hydroxyapatite Carrier Containing Bone Morphogenic Protein-2 and Zoledronic Acid Generates Bone

    Science.gov (United States)

    Raina, Deepak Bushan; Isaksson, Hanna; Hettwer, Werner; Kumar, Ashok; Lidgren, Lars; Tägil, Magnus

    2016-01-01

    In orthopedic surgery, large amount of diseased or injured bone routinely needs to be replaced. Autografts are mainly used but their availability is limited. Commercially available bone substitutes allow bone ingrowth but lack the capacity to induce bone formation. Thus, off-the-shelf osteoinductive bone substitutes that can replace bone grafts are required. We tested the carrier properties of a biphasic, calcium sulphate and hydroxyapatite ceramic material, containing a combination of recombinant human bone morphogenic protein-2 (rhBMP-2) to induce bone, and zoledronic acid (ZA) to delay early resorption. In-vitro, the biphasic material released 90% of rhBMP-2 and 10% of ZA in the first week. No major changes were found in the surface structure using scanning electron microscopy (SEM) or in the mechanical properties after adding rhBMP-2 or ZA. In-vivo bone formation was studied in an abdominal muscle pouch model in rats (n = 6/group). The mineralized volume was significantly higher when the biphasic material was combined with both rhBMP-2 and ZA (21.4 ± 5.5 mm3) as compared to rhBMP-2 alone (10.9 ± 2.1 mm3) when analyzed using micro computed tomography (μ-CT) (p < 0.01). In the clinical setting, the biphasic material combined with both rhBMP-2 and ZA can potentially regenerate large volumes of bone. PMID:27189411

  18. L-MTP-PE and zoledronic acid combination in osteosarcoma: preclinical evidence of positive therapeutic combination for clinical transfer

    Science.gov (United States)

    Biteau, Kevin; Guiho, Romain; Chatelais, Mathias; Taurelle, Julien; Chesneau, Julie; Corradini, Nadège; Heymann, Dominique; Redini, Françoise

    2016-01-01

    Osteosarcoma, the most frequent malignant primary bone tumor in pediatric patients is characterized by osteolysis promoting tumor growth. Lung metastasis is the major bad prognosis factor of this disease. Zoledronic Acid (ZA), a potent inhibitor of bone resorption is currently evaluated in phase III randomized studies in Europe for the treatment of osteosarcoma and Ewing sarcoma. The beneficial effect of the liposomal form of Muramyl-TriPeptide-Phosphatidyl Ethanolamine (L-mifamurtide, MEPACT®), an activator of macrophage populations has been demonstrated to eradicate lung metastatic foci in osteosarcoma. The objective of this study was to evaluate the potential therapeutic benefit and the safety of the ZA and L-mifamurtide combination in preclinical models of osteosarcoma, as a prerequisite before translation to patients. The effects of ZA (100 μg/kg) and L-mifamurtide (1 mg/kg) were investigated in vivo in xenogeneic and syngeneic mice models of osteosarcoma, at clinical (tumor proliferation, spontaneous lung metastases development), radiological (bone microarchitecture by microCT analysis), biological and histological levels. No interference between the two drugs could be observed on ZA-induced bone protection and on L-mifamurtide-induced inhibition of lung metastasis development. Unexpectedly, ZA and L-mifamurtide association induced an additional and in some cases synergistic inhibition of primary tumor progression. L-mifamurtide has no effect on tumor proliferation in vitro or in vivo, and macrophage population was not affected at the tumor site whatever the treatment. This study evidenced for the first time a significant inhibition of primary osteosarcoma progression when both drugs are combined. This result constitutes a first proof-of-principle for clinical application in osteosarcoma patients.

  19. L-MTP-PE and zoledronic acid combination in osteosarcoma: preclinical evidence of positive therapeutic combination for clinical transfer.

    Science.gov (United States)

    Biteau, Kevin; Guiho, Romain; Chatelais, Mathias; Taurelle, Julien; Chesneau, Julie; Corradini, Nadège; Heymann, Dominique; Redini, Françoise

    2016-01-01

    Osteosarcoma, the most frequent malignant primary bone tumor in pediatric patients is characterized by osteolysis promoting tumor growth. Lung metastasis is the major bad prognosis factor of this disease. Zoledronic Acid (ZA), a potent inhibitor of bone resorption is currently evaluated in phase III randomized studies in Europe for the treatment of osteosarcoma and Ewing sarcoma. The beneficial effect of the liposomal form of Muramyl-TriPeptide-Phosphatidyl Ethanolamine (L-mifamurtide, MEPACT®), an activator of macrophage populations has been demonstrated to eradicate lung metastatic foci in osteosarcoma. The objective of this study was to evaluate the potential therapeutic benefit and the safety of the ZA and L-mifamurtide combination in preclinical models of osteosarcoma, as a prerequisite before translation to patients. The effects of ZA (100 μg/kg) and L-mifamurtide (1 mg/kg) were investigated in vivo in xenogeneic and syngeneic mice models of osteosarcoma, at clinical (tumor proliferation, spontaneous lung metastases development), radiological (bone microarchitecture by microCT analysis), biological and histological levels. No interference between the two drugs could be observed on ZA-induced bone protection and on L-mifamurtide-induced inhibition of lung metastasis development. Unexpectedly, ZA and L-mifamurtide association induced an additional and in some cases synergistic inhibition of primary tumor progression. L-mifamurtide has no effect on tumor proliferation in vitro or in vivo, and macrophage population was not affected at the tumor site whatever the treatment. This study evidenced for the first time a significant inhibition of primary osteosarcoma progression when both drugs are combined. This result constitutes a first proof-of-principle for clinical application in osteosarcoma patients. PMID:27152244

  20. Solvent effect on molecular structure, IR spectra, thermodynamic properties and chemical stability of zoledronic acid: DFT study.

    Science.gov (United States)

    Liu, Qingzhu; Qiu, Ling; Wang, Yang; Lv, Gaochao; Liu, Guiqing; Wang, Shanshan; Lin, Jianguo

    2016-04-01

    Zoledronic acid (ZL) has been used widely for treating skeletal diseases because of its high potency in inhibiting bone resorption. A detailed understanding of its physicochemical characteristics may be of great significance in both medicinal chemistry and structural biology for the design of novel bisphosphonates with higher activity. In the present work, the monoclinic (IM) and triclinic (IT) polymorphs of ZL in the gas phase and the aqueous phase were studied by density functional theory (DFT) method at the B3LYP/6-311++G** level. The polarizable continuum model (PCM) was employed to study the solvent effect on structures and properties. The optimized IM and IT conformations in both phases are in reasonable agreement with the experimental structures with the overall mean absolute percent deviation (MAPD%) less than 3.1 %. The presence of intramolecular hydrogen bond within both conformations was identified in the solvent. The IR spectra were simulated and assigned in detail, which agreed well with the experimental data. The intramolecular hydrogen bonding interactions resulted in the shift of vibrational frequencies of hydroxyl to the low band by 12-22 cm(-1) and 24-26 cm(-1) for IM and IT conformations, respectively. Their thermodynamic properties were also calculated based on the harmonic vibrational analysis, including standard heat capacity (C(°)p,m), entropy (S(°)m), and enthalpy (H(°)m). The molecular stability, hydrogen bonding interaction and other electronic properties have been further analyzed by the natural bond orbital (NBO), atoms in molecules (AIM), molecular electrostatic potential (MEP) and frontier molecular orbital (FMO) analysis. PMID:26994018

  1. Zoledronic acid increases the circulating soluble RANKL level in mice, with a further increase in lymphocyte-derived soluble RANKL in zoledronic acid- and glucocorticoid-treated mice stimulated with bacterial lipopolysaccharide.

    Science.gov (United States)

    Abe, Takahiro; Sato, Tsuyoshi; Kokabu, Shoichiro; Hori, Naoko; Shimamura, Yumiko; Sato, Tomoya; Yoda, Tetsuya

    2016-07-01

    The nitrogen-containing bisphosphonate (BP) zoledronic acid (ZA) is a potent antiresorptive drug used in conjunction with standard cancer therapy to treat osteolysis or hypercalcemia due to malignancy. However, it is unclear how ZA influences the circulating levels of bone remodeling factors. The aim of this study was to evaluate the effects of ZA on the serum levels of soluble receptor activator of NF-kB ligand (sRANKL) and osteoprotegerin (OPG). The following four groups of C57BL/6 mice were used (five mice per group): (1) the placebo+phosphate-buffered saline (PBS) group, in which placebo-treated mice were injected once weekly with PBS for 4weeks; (2) the placebo+ZA group, in which placebo-treated mice were injected once weekly with ZA for 4weeks; (3) the prednisolone (PSL)+PBS group, in which PSL-treated mice were injected once weekly with PBS for 4weeks; and (4) the PSL+ZA group, in which PSL-treated mice were injected once weekly with ZA for 4weeks. At the 3-week time point, all mice were subjected to oral inflammatory stimulation with bacterial lipopolysaccharide (LPS). The sera of these mice were obtained every week and the levels of sRANKL and OPG were measured using enzyme-linked immunosorbent assay. At the time of sacrifice, femurs were prepared for micro-computed tomography (micro-CT), histological, and histomorphometric analyses. Our data indicated that ZA administration remarkably reduced bone turnover and significantly increased the basal level of sRANKL. Interestingly, the PSL+ZA group showed a dramatically elevated sRANKL level after LPS stimulation. In contrast, the PSL+ZA group in nonobese diabetic mice with severe combined immunodeficiency disease (NOD-SCID mice), which are characterized by the absence of functional T- and B-lymphocytes, showed no increase in the sRANKL level. Our data suggest that, particularly with combination treatment of ZA and glucocorticoids, surviving lymphocytes might be the source of inflammation-induced sRANKL. Thus

  2. Oral Osteonecrosis Associated with the Use of Zoledronic Acid: First Case of a Patient with Advanced Pancreatic Cancer and Bone Metastases

    Directory of Open Access Journals (Sweden)

    Alla Smith

    2009-03-01

    Full Text Available Dear Sir: while traditionally associated with radiation therapy for head and neck cancer, osteonecrosis of the jaw has recently been described mainly in breast cancer and multiple myeloma patients undergoing long-term intravenous bisphosphonate treatment [1, 2, 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15]. Bisphosphonates are used to treat bone metastases, as they decrease bone resorption, primarily through their apoptotic effects on osteoclasts [16]. Studies indicate that zoledronic acid is the most potent bisphosphonate [17]. While there has been some variation in the reported frequency of osteonecrosis of the jaw development in patients treated with i.v. bisphosphonate, a recent large retrospective analysis by Hoff et al. reported that 0.72% of these patients ultimately developed osteonecrosis of the jaw [18]. This study also identified several risk factors associated with the development of osteonecrosis of the jaw, including high cumulative doses of bisphosphonates, poor oral health and dental extractions [18]. The high incidence of osteonecrosis of the jaw in patients with breast cancer and multiple myeloma was explained by the significantly higher cumulative dose and significantly longer duration of treatment that these patients receive, compared to patients with other malignancies [18]. A separate smaller analysis of osteonecrosis of the jaw in multiple myeloma patients identified the number of zoledronic acid infusions as the most important risk factor [19].

  3. Revisión de las implicaciones clínicas del ácido zoledrónico en el tratamiento del dolor Clinical implications of zoledronic acid for the treatment of pain

    Directory of Open Access Journals (Sweden)

    M. A. Vidal

    2006-11-01

    bone metastasis in multiple myeloma , prostate, breast, lung cancer and other types of solid tumours. It is also approved for the treatment of tumour-induced hypercalcemia. The European Commission has authorized the use of zoledronic acid for the treatment of Paget disease. Effectiveness: Several studies demonstrate the effectiveness of zoledronic acid for the treatment of diverse conditions. In vitro studies showing the antitumour activity of zoledronic acid have been carried out. It has also been shown that it can have an additive or synergistic affect with other antitumour agents. Multiple in vivo studies demostrate that zoledronic acid can inhibit the formation or progression of bone metastasis and reduce the growth of bone tumour. Adverse effects: Biphosphonates can cause renal adverse effects, related to dose and rate of infusion when administered intravenously. In vitro studies demonstrate a better tolerance of zoledronic acid when compared to pamidronate. Clinical trials have shown an acceptable security profile in patients with bone metastasis and hypercalcemia of tumour origin. Reported adverse events were flu-like symptoms, gastrointestinal reactions, anemia, weakness, cough, dyspnea and edema. Cost-effectiveness: The economic cost of cancer-related skeletal complications is very high, also due to the cost of radiotherapy and hospital stay. The great variability of cost in patients with advanced cancer makes the analysis difficult. Discussion: Considering the existing evidence of the antitumour activity of zoledronic acid, it is necessary to elucidate the mechanisms involved and to determine the most effective dose, in order to maximize this potential effect. The objectives that must be considered when bone metastasis are diagnosed should be focused in the most suitable moment to start the treatment with zoledronic acid, as well as its duration depending on the therapeutic answer.

  4. Effect of zoledronate acid treatment on osseointegration and fixation of implants in autologous iliac bone grafts in ovariectomized rabbits.

    Science.gov (United States)

    Qi, Mengchun; Hu, Jing; Li, Jianping; Li, Jinyuan; Dong, Wei; Feng, Xiaojie; Yu, Jing

    2012-01-01

    One main problem associated with alveolar bone augmentation in implant dentistry is resorption of grafted bone, which may be further compromised by systemic skeletal disorders such as osteoporosis. Zoledronate acid (ZOL) is the most potent bisphosphonate to treat osteoporosis and therefore it is hypothesized to be able to invert the negative effect of osteoporosis on osseointegration and fixation of dental implants in autologous bone grafts. In this study, 56 rabbits received bilateral ovariectomy (OVX) (40 rabbits) or sham operation (16 rabbits). Three months later, 8 animals from each group were sacrificed for bone mineral density (BMD) examination. Then the remaining animals underwent bilateral autologous iliac bone grafting with simultaneous implantation of titanium implants in tibiae and were divided into 5 groups (n=8): Sham, OVX, Loc-ZOL (local treatment), Sys-ZOL (systemic treatment) and Loc+Sys-ZOL (local plus systemic) group. At 3 months after implantation, all animals were sacrificed and specimens were harvested for examinations. Both BMD and histological examinations of femurs showed osteoporotic changes after ovariectomy, while systemic treatment with ZOL restored mineralized bone. Micro-CT examination demonstrated that OVX group showed significant decrease of mineralized bone and implant-bone contact when compared with sham control, whereas both systemic and local treatments of ZOL significantly increased mineralized bone and implant-bone contact in ovariectomized animals. However, the best effects were observed in Loc+Sys-ZOL group (combined use of ZOL) and most of bone indices were similar to (IBCR, p>0.05) or higher than (BV/TV, Conn.D and Tb.N) (peffects were also confirmed by histomorphometric analysis of bone indices on implant-bone contact and mineralized bone. In addition, biomechanical testing further supported the beneficial effect of ZOL treatment and maximal removal torque of titanium implants was observed in Loc+Sys-ZOL group. In

  5. A randomised controlled trial of intravenous zoledronic acid in malignant pleural disease: a proof of principle pilot study.

    Directory of Open Access Journals (Sweden)

    Amelia O Clive

    Full Text Available Animal studies have shown Zoledronic Acid (ZA may diminish pleural fluid accumulation and tumour bulk in malignant pleural disease (MPD. We performed a pilot study to evaluate its effects in humans.We undertook a single centre, double-blind, placebo-controlled trial in adults with MPD. Patients were randomised (1:1 to receive 2 doses of intravenous ZA or placebo, 3 weeks apart and were followed-up for 6 weeks. The co-primary outcomes were change in Visual Analogue Scale (VAS score measured breathlessness during trial follow-up and change in the initial area under the curve (iAUC on thoracic Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI from randomisation to week 5. Multiple secondary endpoints were also evaluated.Between January 2010 and May 2013, 30 patients were enrolled, 24 randomised and 4 withdrew after randomisation (1 withdrew consent; 3 had a clinical decline. At baseline, the ZA group were more breathless, had more advanced disease on radiology and worse quality of life than the placebo group. There was no significant difference between the groups with regards change in breathlessness (Adjusted mean difference (AMD 4.16 (95%CI -4.7 to 13.0 or change in DCE-MRI iAUC (AMD -15.4 (95%CI -58.1 to 27.3. Two of nine (22% in the ZA arm had a >10% improvement by modified RECIST (vs 0/11 who received placebo. There was no significant difference in quality of life measured by the QLQ-C30 score (global QOL: AMD -4.1 (-13.0 to 4.9, side effects or serious adverse event rates.This is the first human study to evaluate ZA in MPD. The study is limited by small numbers and imbalanced baseline characteristics. Although no convincing treatment effect was identified, potential benefits for specific subgroups of patients cannot be excluded. This study provides important information regarding the feasibility of future trials to evaluate the effects of ZA further.UK Clinical Research Network ID 8877 ISRCTN17030426 www.isrctn.com.

  6. 希罗达联合唑来膦酸治疗乳腺癌多发骨转移疗效观察%Therapeutic effect of xeloda combined with zoledronic acid on breast cancer with multiple bone metastases

    Institute of Scientific and Technical Information of China (English)

    车建华; 杨保庆; 杨玲玲; 潘海波

    2012-01-01

    Objective To investigate the efficacy and safety of xeloda combined with zoledronic acid in the treatment for breast cancer with multiple bone metastases. Methods Fifty-six patients with breast cancer combined with multiple bone metastases were randomly assigned to trial group (n = 28) and control group (n = 28). Patients in trial group was administered with xeloda plus zoledronic acid and patients in control group was administered with xeloda alone. The efficacy of the two groups was analyzed and compared. Results The overall response and the clinical benefit rates of the trial group were 57.1% and 75.0% , and those of the control group were 46.4% and 60.7%. The curative efficacy, improvement in quality of life, and toxic side effects between the two groups showed no significant difference (P > 0.05). Relief rate of bone pain and the effect on bone metastases were 82.1% and 75% in trial group, which were significantly higher than those in control group (42.8% and 46.4%) (P < 0.05). Conclusions Xeloda combined with zoledronic acid in the treatment for breast cancer with bone metastases has synergistic and favorable therapeutic effects on bone metastases and relief of bone pain.%目的:观察评价希罗达(卡培他滨)联合唑来膦酸治疗乳腺癌多发骨转移的效果及安全性.方法:采用随机对照研究,56例乳腺癌多发骨转移分为治疗组与对照组,治疗组28例给予希罗达片口服化疗联合唑来膦酸治疗.对照组28例单纯给予希罗达治疗.对两组进行治疗并比较和分析治疗结果.结果:两组治疗的有效率、临床获益率分别为57.1%、75.0%和46.4%、60.7%;两组近期疗效、生存质量改善及毒副反应比较,无统计学差异(P > 0.05).治疗组骨痛缓解率及骨转移灶修率分别是82.1%和75.0%,高于对照组(42.8%和46.4%),差异有统计学意义(P < 0.05).结论:希罗达联合唑来膦酸治疗乳腺癌多发骨转移具有协同效应,较单用希罗达近期疗效好,骨

  7. Zoledronic Acid Injection

    Science.gov (United States)

    (zoe' le dron ik) ... supplements, and herbal products you are taking or plan to take. Be sure to mention any of ... disease.tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. You ...

  8. Dosing related effects of zoledronic acid on bone markers and creatinine clearance in patients with multiple myeloma and metastatic breast cancer

    DEFF Research Database (Denmark)

    Søe, Kent; Delaissé, Jean-Marie; Jakobsen, Erik H;

    2014-01-01

    Zoledronic acid (Zol) is frequently used for the treatment of bone disease in patients with multiple myeloma and breast cancer with metastasis to bone. Therefore, there is also an interest in finding the optimal dosing regimen to optimize effects, minimize side effects and reduce costs. In our...... phase II clinical trial we investigated the effect of Zol treatment on the serum levels of the bone markers collagen type 1 cross-linked C-telopeptide (CTX) and bone specific alkaline phosphatase (bALP) as well as on creatinine clearance (kidney function) in response to dosing and duration of treatment...... for each individual patient. Methods. We enrolled 30 multiple myeloma (MM) and 30 breast cancer (BC) patients whereof 10 of each had never received bisphosphonate and 20 had received at least six prior Zol treatments. Results. We found that Zol treatment strongly reduced CTX (Spearman's correlation...

  9. The effect of 6 versus 9 years of zoledronic acid treatment in osteoporosis: a randomized second extension to the HORIZON-Pivotal Fracture Trial (PFT).

    Science.gov (United States)

    Black, Dennis M; Reid, Ian R; Cauley, Jane A; Cosman, Felicia; Leung, Ping Chung; Lakatos, Peter; Lippuner, Kurt; Cummings, Steven R; Hue, Trisha F; Mukhopadhyay, Amitava; Tan, Monique; Aftring, R Paul; Eastell, Richard

    2015-05-01

    While bisphosphonates reduce fracture risk over 3 to 5 years, the optimal duration of treatment is uncertain. In a randomized extension study (E1) of the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT), zoledronic acid (ZOL) 5 mg annually for 6 years showed maintenance of bone mineral density (BMD), decrease in morphometric vertebral fractures, and a modest reduction in bone turnover markers (BTMs) compared with discontinuation after 3 years. To investigate the longer-term efficacy and safety of ZOL, a second extension (E2) was conducted to 9 years in which women on ZOL for 6 years in E1 were randomized to either ZOL (Z9) or placebo (Z6P3) for 3 additional years. In this multicenter, randomized, double-blind study, 190 women were randomized to Z9 (n = 95) and Z6P3 (n = 95). The primary endpoint was change in total hip BMD at year 9 vs. year 6 in Z9 compared with Z6P3. Other secondary endpoints included fractures, BTMs, and safety. From year 6 to 9, the mean change in total hip BMD was -0.54% in Z9 vs. -1.31% in Z6P3 (difference 0.78%; 95% confidence interval [CI]: -0.37%, 1.93%; p = 0.183). BTMs showed small, non-significant increases in those who discontinued after 6 years compared with those who continued for 9 years. The number of fractures was low and did not significantly differ by treatment. While generally safe, there was a small increase in cardiac arrhythmias (combined serious and non-serious) in the Z9 group but no significant imbalance in other safety parameters. The results suggest almost all patients who have received six annual ZOL infusions can stop medication for up to 3 years with apparent maintenance of benefits. PMID:25545380

  10. Effect of Nd:YAG laser light on post-extractive socket healing in rats treated with zoledronic acid and dexamethasone

    Science.gov (United States)

    Mergoni, Giovanni; Merigo, Elisabetta; Passerini, Pietro; Corradi, Domenico; Maestri, Roberta; Bussolati, Ovidio; Bianchi, Massimiliano; Sala, Roberto; Govoni, Paolo; Namour, Samir; Vescovi, Paolo

    2016-03-01

    Introduction The effect of low level laser therapy (LLLT) on the healing process could be useful for the prevention of post-extractive Bisphosphonate-related Osteonecrosis of the Jaws (BRONJ). The aim of the study was to investigate the effect of LLLT on the post-extractive socket healing in rats treated with zoledronic acid and dexamethasone. Material and Methods Thirty male Sprague-Dawley rats were divided in 4 groups: control group (C, n = 5), laser group (L, n = 5), treatment group (T, n = 10) and treatment plus laser group (T+L, n = 10). Rats of group T and T+L received zoledronate 0,1 mg/Kg and dexamethasone 1 mg/Kg every 2 days for 10 weeks. Rats of group C and L were infused with vehicle. After 9 weeks the first maxillary molars were extracted in all rats. Rats of groups L and T+L received laser therapy (Nd:YAG, 1064 nm, 1.25W, 15Hz, 5 min, 14.37 J/cm2) in the socket area at days 0, 2, 4 and 6 after surgery. At 8 days from extraction, the sockets were clinically assessed with a grading score and the wound area was measured with a dedicate software. Histomorphometric evaluation and western blot analysis of osteopontin and osteocalcin expression were performed. Results Group T+L showed a trend toward a better clinical grading score compared to group T (grade I 22% Vs 28 % - grade II 56% Vs 28% - grade III 22% Vs 44%, respectively). The average wound area was similar among the groups. Inhibition of osteoclastic alveolar bone resorption was found in groups T and T+L (Plaser irradiation. Conclusion Our findings suggest that laser irradiation after tooth extraction can promote osteoblast differentiation, as demonstrated by the higher expression of osteocalcin. Thus, laser irradiation could be considered a way to improve socket healing in conditions at risk for MRONJ development.

  11. USE OF ZOLEDRONIC ACID AND A RАNK LIGAND INHIBITOR IN THE PALLIATIVE TREATMENT OF CANCERS OF THE PROSTATE WITH BONE METASTASES

    Directory of Open Access Journals (Sweden)

    S. V. Mushigin

    2014-07-01

    Full Text Available In the metastatic patterns of the cancer, the tumor foci are located more frequently in the tubular bones and vertebral column, just less frequently in the bones of the pelvis, and even more rarely in those of the shoulder and skull. Bone pain is usually related to the involvement of the periosteum that has an extensive network of nociceptors. Auxiliary exposures that directly affect the intensity of pain syndrome and the strength of bone structures are used in addition to basic therapy options for cancer of the prostate. Among these agents there are bisphosphonates. Once ingested, bisphosphonates are transported by blood to the areas of active bone tissue rearrangement where they are tightly bound to the mineral matrix. Their administration causes a considerable reduction in pain syndrome, a decrease in the frequency of complications of bone metastases, and an increase in time before a first bone complication. Antiresorptive therapy including particularly zoledronic acid (resorba or denosumab is a necessary treatment option in the above category of patients with bone metastases.

  12. Zoledronic acid negatively affects the expansion of in vitro activated human NK cells and their cytolytic interactions with Ewing sarcoma cells.

    Science.gov (United States)

    Mueller, Sarah-Kristin; Altvater, Bianca; Chen, Christiane; Kailayangiri, Sareetha; Ahlmann, Martina; Dirksen, Uta; Juergens, Heribert; Rossig, Claudia

    2013-06-01

    Disseminated Ewing sarcoma remains a fatal disease despite advanced multimodal treatment regimens. Immunotherapies as well as novel drugs and biologicals are currently being explored to eliminate minimal residual disease after conventional therapy thereby rescuing patients at a high risk for relapse. Insights into the interactions between novel therapies provide the basis for the development of effective combination strategies. We investigated the effects of the aminobisphosphonate zoledronic acid (ZA) on the in vitro expansion of human natural killer (NK) cells and their cytolytic activity against Ewing sarcoma cells. ZA significantly impaired the in vitro expansion of activated NK cells from both healthy donors and Ewing sarcoma patients in a dose-dependent manner. Expression of differentiation markers and activating receptors was unaffected by the drug. Activated NK cells from both healthy donors and patients had potent degranulation responses to Ewing sarcoma cells. In the presence of ZA at concentrations reflecting pharmaceutical serum levels, the in vitro antitumor activity of NK cells from Ewing sarcoma patients was significantly impaired. We conclude that ZA can impede in vitro NK cell expansion and cytolytic NK cell responses to Ewing sarcoma. These observations raise caution against the combination of adoptive NK cell transfer with ZA maintenance therapy in Ewing sarcoma. Future studies aim to identify potentiating interactions of novel drugs with cellular therapies. PMID:23525469

  13. Annexin A1 is involved in the acquisition and maintenance of a stem cell-like/aggressive phenotype in prostate cancer cells with acquired resistance to zoledronic acid.

    Science.gov (United States)

    Bizzarro, Valentina; Belvedere, Raffaella; Milone, Maria Rita; Pucci, Biagio; Lombardi, Rita; Bruzzese, Francesca; Popolo, Ada; Parente, Luca; Budillon, Alfredo; Petrella, Antonello

    2015-09-22

    In this study, we have characterized the role of annexin A1 (ANXA1) in the acquisition and maintenance of stem-like/aggressive features in prostate cancer (PCa) cells comparing zoledronic acid (ZA)-resistant DU145R80 with their parental DU145 cells. ANXA1 is over-expressed in DU145R80 cells and its down-regulation abolishes their resistance to ZA. Moreover, ANXA1 induces DU145 and DU145R80 invasiveness acting through formyl peptide receptors (FPRs). Also, ANXA1 knockdown is able to inhibit epithelial to mesenchymal transition (EMT) and to reduce focal adhesion kinase (FAK) and metalloproteases (MMP)-2/9 expression in PCa cells. DU145R80 show a cancer stem cell (CSC)-like signature with a high expression of CSC markers including CD44, CD133, NANOG, Snail, Oct4 and ALDH7A1 and CSC-related genes as STAT3. Interestingly, ANXA1 knockdown induces these cells to revert from a putative prostate CSC to a more differentiated phenotype resembling DU145 PCa cell signature. Similar results are obtained concerning some drug resistance-related genes such as ATP Binding Cassette G2 (ABCG2) and Lung Resistant Protein (LRP). Our study provides new insights on the role of ANXA1 protein in PCa onset and progression. PMID:26312765

  14. Structural simulation of adenosine phosphate via plumbagin and zoledronic acid competitively targets JNK/Erk to synergistically attenuate osteoclastogenesis in a breast cancer model.

    Science.gov (United States)

    Qiao, H; Wang, T-y; Yu, Z-f; Han, X-g; Liu, X-q; Wang, Y-g; Fan, Q-m; Qin, A; Tang, T-t

    2016-01-01

    The treatment of breast cancer-induced osteolysis remains a challenge in clinical settings. Here, we explored the effect and mechanism of combined treatment with zoledronic acid (ZA) and plumbagin (PL), a widely investigated component derived from Plumbago zeylanica, against breast cancer-induced osteoclastogenesis. We found that the combined treatment with PL and ZA suppressed cell viability of precursor osteoclasts and synergistically inhibited MDA-MB-231-induced osteoclast formation (combination index=0.28) with the abrogation of recombinant mouse receptor activator of nuclear factor-κB ligand (RANKL)-induced activation of NF-κB/MAPK (nuclear factor-κB/mitogen-activated protein kinase) pathways. Molecular docking suggested a putative binding area within c-Jun N-terminal kinase/extracellular signal-regulated kinase (JNK/Erk) protease active sites through the structural mimicking of adenosine phosphate (ANP) by the spatial combination of PL with ZA. A homogeneous time-resolved fluorescence assay further illustrated the direct competitiveness of the dual drugs against ANP docking to phosphorylated JNK/Erk, contributing to the inhibited downstream expression of c-Jun/c-Fos/NFATc-1 (nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 1). Then, in vivo testing demonstrated that the combined administration of PL and ZA attenuated breast cancer growth in the bone microenvironment. Additionally, these molecules prevented the destruction of proximal tibia, with significant reduction of tartrate-resistant acid phosphatase (TRAcP)-positive osteoclast cells and potentiation of apoptotic cancer cells, to a greater extent when combined than when the drugs were applied independently. Altogether, the combination treatment with PL and ZA could significantly and synergistically suppress osteoclastogenesis and inhibit tumorigenesis both in vitro and in vivo by simulating the spatial structure of ANP to inhibit competitively phosphorylation of c-Jun N

  15. Doses effects of zoledronic acid on mineral apatite and collagen quality of newly-formed bone in the rat's calvaria defect.

    Science.gov (United States)

    Olejnik, Cécile; Falgayrac, Guillaume; During, Alexandrine; Cortet, Bernard; Penel, Guillaume

    2016-08-01

    Due to their inhibitory effects on resorption, bisphosphonates are widely used in the treatment of diseases associated to an extensive bone loss. Yet, little is known about bisphosphonates effects on newly-formed bone quality. In the present study, adult male Sprague-Dawley rats (n=80) with a bone defect calvaria area were used and short-term effects of zoledronic acid (ZA) were studied on the healing bone area. Three ZA treatments were tested by using either: 1°) a low single dose (120μgZA/kg, n=10; equivalent to human osteoporosis treatment), 2°) a low fractionated doses (20μgZA/kg daily for 6days either a total of 120μg/kg, n=15), and 3°) a high fractionated doses, (100μgZA/kg weekly for 6weeks, n=15; equivalent to 6months of human bone metastasis treatment). For each treatment, a control "vehicle" treatment was performed (with an identical number of rats). After ZA administration, the intrinsic bone material properties were evaluated by quantitative backscattered electron imaging (qBEI) and Raman microspectroscopy. Neither single nor fractionated low ZA doses modify the intrinsic bone material properties of the newly-formed bone compared to their respective control animals. On the opposite, the high ZA treatment resulted in a significant decrease of the crystallinity (-25%, Porganization. In addition, we report here for the first time that high ZA doses decreased the hydroxyproline-to-proline ratio suggesting that ZA may affect the early collagen organization during the bone healing. PMID:27168397

  16. Panobinostat synergizes with zoledronic acid in prostate cancer and multiple myeloma models by increasing ROS and modulating mevalonate and p38-MAPK pathways

    Science.gov (United States)

    Bruzzese, F; Pucci, B; Milone, M R; Ciardiello, C; Franco, R; Chianese, M I; Rocco, M; Di Gennaro, E; Leone, A; Luciano, A; Arra, C; Santini, D; Caraglia, M; Budillon, A

    2013-01-01

    Patients with advanced prostate cancer (PCa) and multiple myeloma (MM) have limited long-term responses to available therapies. The histone deacetylase inhibitor panobinostat has shown significant preclinical and clinical anticancer activity in both hematological and solid malignancies and is currently in phase III trials for relapsed MM. Bisphosphonates (BPs), such as zoledronic acid (ZOL), inhibit osteoclast-mediated bone resorption and are indicated for the treatment of bone metastasis. BPs, including ZOL, have also shown anticancer activity in several preclinical and clinical studies. In the present report, we found a potent synergistic antiproliferative effect of panobinostat/ZOL treatment in three PCa and three MM cell lines as well as in a PCa ZOL-resistant subline, independently of p53/KRAS status, androgen dependency, or the schedule of administration. The synergistic effect was also observed in an anchorage-independent agar assay in both ZOL-sensitive and ZOL-resistant cells and was confirmed in vivo in a PCa xenograft model. The co-administration of the antioxidant N-acetyl-L-cysteine blocked the increased reactive oxygen species generation and apoptosis observed in the combination setting compared with control or single-agent treatments, suggesting that oxidative injury plays a functional role in the synergism. Proapoptotic synergy was also partially antagonized by the addition of geranyl-geraniol, which bypasses the inhibition of farnesylpyrophosphate synthase by ZOL in the mevalonate pathway, supporting the involvement of this pathway in the synergy. Finally, at the molecular level, the inhibition of basal and ZOL-induced activation of p38-MAPK by panobinostat in sensitive and ZOL-resistant cells and in tumor xenografts could explain, at least in part, the observed synergism. PMID:24157872

  17. Preparation and in vivo biological investigations on a novel radioligand for bone scanning: technetium-99m-labeled zoledronic acid derivative

    Energy Technology Data Exchange (ETDEWEB)

    Lin Jianguo; Qiu Ling, E-mail: qiulingwx@gmail.com; Cheng Wen; Luo Shineng; Ye Wanzhong

    2011-07-15

    Introduction: To enable imaging at an earlier time after injection, a radiopharmaceutical with higher affinity for bone, larger ratio of bone-to-soft tissue uptake and more rapid clearance from blood is required. The nature of diphosphonic acid is a key factor to determine the advantages of the radiopharmaceuticals. The purpose of this study is to optimize the linker chain between the imidazolyl and geminal diphosphonate group in the zoledronic acid (ZL) to develop novel single photon emission computed tomography (SPECT) bone imaging agent. Methods: A novel ZL derivative, 1-hydroxy-3-(1H-imidazol-1-yl)propane-1,1-diyldiphosphonic acid (IPrDP), was successfully prepared and labeled with {sup 99m}Tc in a high labeling yield. Biodistribution of {sup 99m}Tc-IPrDP and {sup 99m}Tc-ZL in normal mice were studied and compared. SPECT bone scanning was performed on the rabbit and a series of dynamic and static images were recorded by Philips SKY Light emission computed tomography. Results: In the biodistribution studies, {sup 99m}Tc-IPrDP exhibits significant advantages on the bone resorption and the clearance from soft tissues compared with {sup 99m}Tc-ZL. Kinetics of blood clearance in mice showed that T{sub 1/2{alpha}} and T{sub 1/2{beta}} of {sup 99m}Tc-IPrDP were 1.47 min and 46.47 min, while those of {sup 99m}Tc-ZL were 2.28 and 52.63 min respectively. Excellent images of the rabbit skeleton can be quickly obtained for {sup 99m}Tc-IPrDP, which was faster than {sup 99m}Tc-ZL and the clinically widely used bone imaging agent {sup 99m}Tc-MDP (technetium-99m labeled with methylenediphosphonate). Conclusions: {sup 99m}Tc-IPrDP possesses excellent characteristics for the potential application as a novel bone scanning agent.

  18. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial

    Science.gov (United States)

    James, Nicholas D; Sydes, Matthew R; Clarke, Noel W; Mason, Malcolm D; Dearnaley, David P; Spears, Melissa R; Ritchie, Alastair W S; Parker, Christopher C; Russell, J Martin; Attard, Gerhardt; de Bono, Johann; Cross, William; Jones, Rob J; Thalmann, George; Amos, Claire; Matheson, David; Millman, Robin; Alzouebi, Mymoona; Beesley, Sharon; Birtle, Alison J; Brock, Susannah; Cathomas, Richard; Chakraborti, Prabir; Chowdhury, Simon; Cook, Audrey; Elliott, Tony; Gale, Joanna; Gibbs, Stephanie; Graham, John D; Hetherington, John; Hughes, Robert; Laing, Robert; McKinna, Fiona; McLaren, Duncan B; O'Sullivan, Joe M; Parikh, Omi; Peedell, Clive; Protheroe, Andrew; Robinson, Angus J; Srihari, Narayanan; Srinivasan, Rajaguru; Staffurth, John; Sundar, Santhanam; Tolan, Shaun; Tsang, David; Wagstaff, John; Parmar, Mahesh K B

    2016-01-01

    Summary Background Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone. Methods Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m2) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544). Findings 2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60–71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6

  19. One case of influenza-like adverse reaction induced by zoledronic acid injection%唑来膦酸注射液致流感样不良反应1例

    Institute of Scientific and Technical Information of China (English)

    李铮

    2011-01-01

    1 例老年女性患者应用唑来膦酸注射液治疗骨质疏松症,出现了恶心、呕吐、心悸等流感样症状及白细胞的异常升高,未见其他感染,4 d 后体温逐步恢复正常水平.%An old female patient experienced an abnormal increase in WBC and influenza-like symptoms,including nausea, vomiting and cardiopalmus, after administration of zoledronic acid injection for osteoporosis treatment. No infections were found, and the body temperature gradually recovered to normal level 4 days later.

  20. 唑来膦酸对髋关节置换后假体柄周围骨丢失的预防效果%Preventive effect of zoledronic acid on bone loss around the prosthesis stem after hip replacement

    Institute of Scientific and Technical Information of China (English)

    刘国青; 苑振峰; 刘鹏; 庞同涛; 张先巍

    2015-01-01

    to prevent fractures surrounding the prosthesis. OBJECTIVE:To observe the preventive effect of zoledronic acid on bone loss surrounding the prosthesis stem after hip replacement. METHODS:A total of 80 patients after total hip replacement in the People’s Hospital of Shenxian from February 2011 to September 2014 were enrol ed in this study. They were divided into two groups (n=40). At 4 days after replacement, patients in the observation group received treatment with zoledronic acid, but those in the control group did not give zoledronic acid. The rest medication was identical between the two groups. Bone mineral density in the hip was measured before replacement and at 1 year after replacement in both groups. Serum calcium and phosphorus levels and alkaline phosphatase activities were observed before replacement, 3 days and 1 year after medication in the two groups. Adverse reaction during medication was recorded in the observation group. RESULTS AND CONCLUSION:The average bone mineral density was significantly decreased in both groups at 1 year after replacement, and significant differences were found as compared with before replacement (P replacement (P0.05). Alkaline phosphatase activities were low in the observation group at 1 year after medication, and significant difference was detected as compared with the control group and that before replacement (P0.05). Within two or three days after medication, nine patients suffered from varying degrees of muscle aches and fever in the observation group, and above symptoms were lessened after taking acetaminophen. These results verify that after total hip replacement, zoledronic acid injection can effectively prevent bone loss around the prosthesis in early stage after replacement, but fever symptoms may occur within a week after replacement. Thus, it is recommended that zoledronic acid injection can be given at 1 week after replacement. If fever and other symptoms appear, acetaminophen can be given.

  1. Pharmacokinetics of amoxicillin and clavulanic acid administered alone and in combination.

    OpenAIRE

    D. Adam; Visser, I.; Koeppe, P

    1982-01-01

    The pharmacokinetics of amoxicillin and clavulanic acid, administered alone and in combination, were studied in six male and six female normal human volunteers. Each ingested 500 mg of amoxicillin or 125 mg of clavulanic acid or the above agents in combination in randomized sequences. The results indicate that most of the parameters tested for either substance are essentially independent of the presence of the other one.

  2. A Longitudinal Study of Skeletal Histomorphometry at 6 and 24 Months Across Four Bone Envelopes in Postmenopausal Women With Osteoporosis Receiving Teriparatide or Zoledronic Acid in the SHOTZ Trial.

    Science.gov (United States)

    Dempster, David W; Zhou, Hua; Recker, Robert R; Brown, Jacques P; Bolognese, Michael A; Recknor, Christopher P; Kendler, David L; Lewiecki, E Michael; Hanley, David A; Rao, Sudhaker D; Miller, Paul D; Woodson, Grattan C; Lindsay, Robert; Binkley, Neil; Alam, Jahangir; Ruff, Valerie A; Gallagher, Eileen R; Taylor, Kathleen A

    2016-07-01

    Previously, we reported the effects of teriparatide (TPTD) and zoledronic acid (ZOL) on bone formation based on biochemical markers and bone histomorphometry of the cancellous envelope at month 6 in postmenopausal women with osteoporosis who participated in the 12-month primary Skeletal Histomorphometry in Subjects on Teriparatide or Zoledronic Acid Therapy (SHOTZ) study. Patients were eligible to enter a 12-month extension on their original treatment regimen: TPTD 20 μg/day (s.c. injection) or ZOL 5 mg/year (i.v. infusion). A second biopsy was performed at month 24. Here we report longitudinal changes between and within each treatment group in the cancellous, endocortical, intracortical, and periosteal bone envelopes in patients with evaluable biopsies at months 6 and 24 (paired data set: TPTD, n = 10; ZOL, n = 9). Between-group differences are also reported in the larger set of patients with evaluable biopsies at month 6 (TPTD, n = 28; ZOL, n = 30). Data from the cancellous envelope at month 6 or month 24 provided a reference to compare differences across envelopes within each treatment group. The 24-month results extend our earlier report that TPTD and ZOL possess different tissue-level mechanisms of action. Moreover, these differences persisted for at least 2 years in all four bone envelopes. Few longitudinal differences were observed within or across bone envelopes in ZOL-treated patients, suggesting that the low bone formation indices at month 6 persisted to month 24. Conversely, the magnitude of the effect of TPTD on bone formation varied across individual envelopes: median values for mineralizing surface (MS/BS) and bone formation rate (BFR/BS) at month 6 were approximately 3-fold to 5-fold higher in the endocortical and intracortical envelopes compared to the cancellous envelope. Although MS/BS and BFR/BS declined in these envelopes at month 24, median values continued to exceed, or were not significantly different from, those in the

  3. Clinical Efficacy Research on Zoledronic Acid Combined with Capecitabine in Treating Breast Cancer with Multiple Bone Metastases%唑来磷酸联合卡培他滨治疗乳腺癌多发骨转移临床疗效研究

    Institute of Scientific and Technical Information of China (English)

    张明帅; 张国庆; 欧江华; 艾司克尔·阿尤甫; 蒋威华; 倪多

    2011-01-01

    目的 探讨唑来磷酸联合卡培他滨治疗乳腺癌多发骨转移的效果及安全性.方法 将48例乳腺癌骨转移患者随机分为唑来磷酸联合卡培他滨组 (治疗组)及单用唑来磷酸组(对照组),分别对两组进行镇痛效果、生存质量改善评价、骨转移灶治疗效果评价及观察不良反应.结果 两组患者治疗后骨痛的镇痛效果评价、患者生存质量改善评价,差异均无统计学意义(P>0.05);两组骨转移灶治疗效果评价,差异有统计学意义(P<0.05);两组患者的乏力、发热、恶心、呕吐、腹泻发生率比较,差异均无统计学意义(P>0.05).结论 唑来磷酸联合卡培他滨对乳腺癌骨多发转移较单用唑来磷酸有较好的治疗效果.%Objective To investigate the efficacy and safety of zoledronic acid combined with capecitabine in treating breast cancer patients with multiple bone metastases. Methods 48 breast cancer patients with multiple bone metastases were randomly divided into two groups: group zoledronic acid plus capecitabine ( treatment group ) and group zoledronic acid alone ( control group ). Analgesic effect, quality of life improvement, effect of the treatment for bone metastases and toxicity were compared between two groups. Results There was no significant difference in terms of analgesic effect and quality of life improvement between two groups ( P >0. 05 ). The response rate of bone metastases between two groups showed significant difference ( P0. 05 ). Conclusion Zoledronic acid combined with capecitabine in treating breast cancer patients with bone metastases shows a better efficacy than zoledronic acid.

  4. Effects of Folic Acid on the Growth of the Offspring of Ethanol-Administered Rats

    Directory of Open Access Journals (Sweden)

    Melvis Taylín Zumeta Dubé

    2013-07-01

    Full Text Available Background: ethanol consumption among adolescent women has increased and consequently, the complications associated with it, such as fetal alcohol syndrome. Effects of this syndrome on the central nervous system have been extensively studied, unlike its consequences for growth during postnatal life. Objective: to determine the effects of fetal alcohol syndrome on the growth of the rats’ offspring and to assess therapeutic actions of folic acid. Methods: 24 pregnant Wistar rats divided into four groups A: control, B: treated with folic acid, C: treated with ethanol and D: treated with ethanol and folic acid were used. Treatment was administered by intragastric cannulation throughout the pregnancy period until delivery. The study offspring were weighed and measured at 3, 7, 14 and 21 days old. Body weight and height values were used in order to assess the gain curves of both parameters. Results: ethanol administered during pregnancy did not modify the offspring weight and height. Treatment with folic acid caused an increase in tail weight and length of the rats’ offspring. Conclusions: ethanol administration to pregnant rats is not sufficient to trigger stature-ponderal retardation in their offspring; folic acid causes tail growth in the offspring, which is a valuable indicator in the nutritional assessment of rats.

  5. The Combination Therapy with Zoledronic Acid and Propranolol Improves the Trabecular Microarchitecture and Mechanical Property in an Rat Model of Postmenopausal Osteoporosis

    Directory of Open Access Journals (Sweden)

    Deepak Kumar Khajuria

    2014-01-01

    Full Text Available We conducted the present study to investigate the therapeutic effects of propranolol (PRO, alone and in combination with the antiresorptive agent ZOL, in a rat model of postmenopausal osteoporosis. Female Wistar rats were OVX or sham-operated at 3 months of age. Twelve weeks after surgery, rats were randomized into six groups: (1 sham + vehicle, (2 OVX + vehicle, (3 OVX + ZOL (100 μg/kg, i.v. single dose, (4 OVX + ZOL (50 μg/kg, i.v. single dose, (5 OVX + PRO (0.1 mg/kg, s.c. 5 days per week, and (6 OVX + ZOL (50 μg/kg, i.v. single dose + PRO (0.1 mg/kg, s.c. 5 days per week for 12 weeks. At the end of treatment study, various bone parameters were evaluated. With respect to improvement in the mechanical strength of the lumbar spine and the femoral mid-shaft, the combination treatment of ZOL and PRO was more effective than each drug administered as a monotherapy. Moreover, combination therapy using ZOL and PRO preserved the trabecular microarchitecture better than single-drug therapy using ZOL or PRO in OVX rats. These data suggest that combination therapy with ZOL plus PRO represents a potentially useful therapeutic option for patients with osteoporosis.

  6. The effect of zoledronate during bone healing

    OpenAIRE

    Matos, Marcos Almeida; Tannuri, Uenis; Guarniero, Roberto

    2010-01-01

    Background Bisphosphonates have become the treatment of choice for a variety of bone diseases in which excessive osteoclastic activity is an important pathologic feature. However, inhibition of osteoclastic activity could lead to inhibition of remodeling during bone healing or repair. The objective of this study is to investigate the effect of zoledronate (the most potent bisphosphonate) in the biological process of bone healing. Methods Thirty immature male rabbits were divided into two grou...

  7. Effect of local zoledronate on implant osseointegration in a rat model

    OpenAIRE

    Back David A; Pauly Stephan; Rommel Lisa; Haas Norbert P; Schmidmaier Gerhard; Wildemann Britt; Greiner Stefan H

    2012-01-01

    Abstract Background An implant coating with poly(D, L-lactide) (PDLLA) releasing incorporated Zoledronic acid (ZOL) has already proven to positively effect osteoblasts, to inhibit osteoclasts and to accelerate fracture healing. Aim of this study was to investigate the release kinetics of the chosen coating and the effect of different concentrations of ZOL locally released from this coating on the osseointegration of implants. Methods For release kinetics the release of C14-labled ZOL out of t...

  8. Measurement of the incorporation of orally administered arachidonic acid into tissue lipids

    International Nuclear Information System (INIS)

    The applicability of a stable isotope method to monitor the mixing of dietary arachidonic acid with endogenous arachidonic acid in tissue lipids was evaluated. Rats were fed octadeuterated arachidonic acid during a 20-day period, and the entry of the dietary acid into lipid esters of various tissues was examined by gas chromatography-mass spectrometric (GC-MS) analysis of their fatty acids. The rats were maintained on a fat-free diet from weaning until 63 days old to enhance the ratio of the dietary acid to endogenous arachidonate. Three separate forms of eicosatetraenoic acid in the tissue lipids could be distinguished by GC-MS: octadeuterated arachidonic acid (recent dietary origin), unlabeled arachidonic acid (maternal origin) and unlabeled 4,7,10,13-eicosatetraenoic acid (originating from palmitoleic acid). The total eicosatetraenoic acid in the tissue lipids contained about 90% arachidonate from recent dietary origin in lung, kidney, heart and fat, 70% in muscle and liver and 27% in brain. The n-7 isomer of eicosatetraenoic acid was estimated to make up 6% or less of the total eicosatetraenoic acid in lung, kidney, brain, muscle and heart tissue lipids, but it comprised around 15% of the total eicosatetraenoic acid in liver. The unlabeled arachidonic acid of maternal origin thus comprised only about 10% of the eicosatetraenoic acid in all tissues examined except muscle and brain, where it was 24% and 70% of the eicosatetraenoic acid, respectively

  9. Serum biochemical activities and muscular soreness in transported goats administered with ascorbic acid during the hot-dry season

    OpenAIRE

    Ndazo S Minka; Olusegun J Ayo

    2010-01-01

    The effects of handling, loading and 12 h of road transportation during the hot-dry season on muscular metabolism of 20 experimental goats administered orally with 100 mg/kg body weight of ascorbic acid (AA) dissolved in 10 ml of sterile water, and other 20 control goats given equivalent of sterile water 40 min prior to transportation were investigated. The result obtained post-transportation showed that handling, loading and transportation were stressful to the goats, especially the control ...

  10. TRAPEZE: a randomised controlled trial of the clinical effectiveness and cost-effectiveness of chemotherapy with zoledronic acid, strontium-89, or both, in men with bony metastatic castration-refractory prostate cancer.

    Science.gov (United States)

    James, Nicholas; Pirrie, Sarah; Pope, Ann; Barton, Darren; Andronis, Lazaros; Goranitis, Ilias; Collins, Stuart; McLaren, Duncan; O'Sullivan, Joe; Parker, Chris; Porfiri, Emilio; Staffurth, John; Stanley, Andrew; Wylie, James; Beesley, Sharon; Birtle, Alison; Brown, Janet; Chakraborti, Prabir; Russell, Martin; Billingham, Lucinda

    2016-01-01

    BACKGROUND: Bony metastatic castration-refractory prostate cancer is associated with a poor prognosis and high morbidity. TRAPEZE was a two-by-two factorial randomised controlled trial of zoledronic acid (ZA) and strontium-89 (Sr-89), each combined with docetaxel. All have palliative benefits, are used to control bone symptoms and are used with docetaxel to prolong survival. ZA, approved on the basis of reducing skeletal-related events (SREs), is commonly combined with docetaxel in practice, although evidence of efficacy and cost-effectiveness is lacking. Sr-89, approved for controlling metastatic pain and reducing need for subsequent bone treatments, is generally palliatively used in patients unfit for chemotherapy. Phase II analysis confirmed the safety and feasibility of combining these agents. TRAPEZE aimed to determine the clinical effectiveness and cost-effectiveness of each agent. METHODS: Patients were randomised to receive six cycles of docetaxel plus prednisolone: alone, with ZA, with a single Sr-89 dose after cycle 6, or with both. Primary outcomes were clinical progression-free survival (CPFS: time to pain progression, SRE or death) and cost-effectiveness. Secondary outcomes were SRE-free interval (SREFI), total SREs, overall survival (OS) and quality of life (QoL). Log-rank test and Cox regression modelling were used to determine clinical effectiveness. Cost-effectiveness was assessed from the NHS perspective and expressed as cost per additional quality-adjusted life-year (QALY). An additional analysis was carried out for ZA to reflect the availability of generic ZA. RESULTS: PATIENTS: 757 randomised (median age 68.7 years; Eastern Cooperative Oncology Group scale score 0, 40%; 1, 52%; 2, 8%; prior radiotherapy, 45%); median prostate-specific antigen 143.78 ng/ml (interquartile range 50.8-353.9 ng/ml). Stratified log-rank analysis of CPFS was statistically non-significant for either agent (Sr-89, p = 0.11; ZA, p = 0.45). Cox regression

  11. Clinical Effect of Xeloda Combined with Zoledronic Acid on Treatment of Multiple Bone Metastasis of Breast Cancer%希罗达和唑来膦酸联合治疗乳腺癌多发骨转移的临床效果研究

    Institute of Scientific and Technical Information of China (English)

    闫睿

    2015-01-01

    Objective:To study and analyze the clinical effect of Xeloda combined with zoledronic acid on treatment of multiple bone metastasis of breast cancer.Method: 40 breast cancer patients with multiple bone metastases in our hospital were selected from December 1, 2011 to December 1,2014 ,they were randomly divided into combined treatment group and single drug group by using random number table method, 20 cases in each group.Single drug group was given capecitabine, combination treatment group was given intravenous zoledronic acid on the base of control group, two groups curative effect were recorded.Result:The analgesic effective rate of combination treatment group was 85.00% obvious higher than single drug group of 55.00%; bone metastasis therapy effective rate of combination treatment group was 65.00% obvious than single drug group of 35.00%, the differences were statistically significant (P<0.05).Conclusion:The clinical effect of Xeloda combined with zoledronic acid has obvious effect on treatment of breast cancer multiple bone metastases,it is worthy of promotion.%目的:研究分析希罗达和唑来磷酸联合治疗乳腺癌多发骨转移的临床效果。方法:选取2011年12月1日-2014年12月1日经本院诊断并治疗的乳腺癌多发骨转移患者40例,采用随机数字表法将患者分为联合用药组和单一用药组,每组各20例。单一用药组给予希罗达,联合用药组在单一用药组的基础上给予静脉注射唑来磷酸治疗,分别记录两组患者治疗后的效果。结果:根据分析可得出联合用药组止痛有效率为85.00%,单一用药组止痛有效率为55.00%,联合用药组有效率明显高于单一用药组;且联合用药组骨转移灶治疗总有效率为65.00%明显高于单一用药组的35.00%,两组比较差异均有统计学意义(P<0.05)。结论:希罗达和唑来磷酸联合治疗乳腺癌多发骨转移效果好,安全性高,可以及时缓解疾病对患者造

  12. Effect of three low-dose fish oil supplements, administered during pregnancy, on neonatal long-chain polyunsaturated fatty acid status at birth

    NARCIS (Netherlands)

    Velzing-Aarts, FV; van der Klis, FRM; van der Dijs, FPL; van Beusekom, CM; Landman, H; Capello, JJ; Muskiet, FAJ

    2001-01-01

    Adequate long-chain polyunsaturated fatty acid (LCP) status during pregnancy is important. We studied the effect of three low-dose fish oil supplements, administered during uncomplicated pregnancy, on neonatal LCP status at term delivery. Supplements were administered from the second trimester to de

  13. Increased plasma free fatty acid and triglyceride levels after single administation of toluene in rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Setsunori; Tanabe, Koichi; Shiono, Hiroshi (Shimane Medical Univ., Izumo (Japan)); Maseda, Chikatoshi (Shimane Prefectural Police Headquarters, Matsue (Japan)); Fukui, Yuko (Kyoto Univ. (Japan))

    1988-01-01

    Changes of plasma lipids (triglyceride, TG: total cholesterol, Cho; and phospholipids, PL), free fatty acid (FFA), and blood glucose (BG) were studied in male rabbits after toluene administration (0.5 g/kg per os). Hypertriglyceridemia was observed at and after 2 h. Plasma FFA and BG were elevated temporarily during the early stage and lowered gradually thereafter. Initially, plasma Cho and PL were virtually unchanged, by the Cho levels increased slowly after 6 h. The hypertriglyceridemia observed may have some adverse effects on heart function.

  14. Acute delirium in an elderly woman following zoledronate administration

    Directory of Open Access Journals (Sweden)

    Mohammad Nasiruddin

    2014-01-01

    Full Text Available Zoledronate is a third-generation bisphosphonate having distinctive profile of high potency as well as prolonged duration of action. Intravenous zoledronate is the recently approved bisphosphonate for the treatment of osteoporosis and has an attractive once-yearly regimen for the treatment of osteoporosis. Here we report, for the first time, a case of acute delirium following zoledronate administration for osteoporosis. An 86-year-old female patient presented to orthopedics out-patient department (OPD with complaints of pain and unable to bear weight on left thigh with history of fall from bed 2 months back. She was diagnosed as fracture neck of femur with severe osteoporosis and treated conservatively. She was given zoledronate IV 5 mg infusion over 30 min. After 10-12 h of zoledronate infusion, patient became confused, disorientated, and agitated. A septic work-up was negative. Electrolyte disturbances were excluded with normal sodium, potassium, calcium, and magnesium levels. Computed tomography of the brain was unremarkable. A metabolic cause could not be found for the change in her mental state. Patient was referred to medicine department where she was diagnosed as drug-induced acute delirium probably due to zoledronate. Patient was advised injections haloperidol and torsemide. In the following 48 h, her confusion got cleared and mental status was improved. According to the Naranjo′s scale, the effect of zoledronate in our patient was scored 6 indicating a probable likelihood of causing delirium. It was a probable cause of acute delirium according to World Health Organization (WHO causality scale.

  15. Serum biochemical activities and muscular soreness in transported goats administered with ascorbic acid during the hot-dry season

    Directory of Open Access Journals (Sweden)

    Ndazo S Minka

    2010-12-01

    Full Text Available The effects of handling, loading and 12 h of road transportation during the hot-dry season on muscular metabolism of 20 experimental goats administered orally with 100 mg/kg body weight of ascorbic acid (AA dissolved in 10 ml of sterile water, and other 20 control goats given equivalent of sterile water 40 min prior to transportation were investigated. The result obtained post-transportation showed that handling, loading and transportation were stressful to the goats, especially the control goats and resulted into muscular damage and the development of delayed-onset-muscular-soreness (DOMS, which may lead to dark-firm-dry (DFD syndrome meat with undesirable effects on its quality. In the experimental goats administered AA such transportation effects were minimal or completely abolished. The result demonstrated that AA reduced the incidence of DOMS and muscular damage in transported goats, therefore it may be used to improve the welfare and quality of meat obtained from goats subjected to long period of road transportation under adverse climatic conditions.

  16. Effect of packing on changes in erythrocyte osmotic fragility and malondialdehyde concentration in donkeys administered with ascorbic acid

    Directory of Open Access Journals (Sweden)

    Folashade Olaifa

    2012-02-01

    Full Text Available Experiments were performed with the aim of investigating the effect of packing on erythrocyte osmotic fragility (EOF and malondialdehyde (MDA concentration in donkeys, and the effect of ascorbic acid (AA. Twelve apparently healthy donkeys raised under the traditional extensive system served as experimental subjects. Six donkeys administered orally with AA (200 mg/kg and subjected to packing were used as experimental animals, whilst six others not administered with AA served as controls. Blood samples were collected pre- and post-packing from all the donkeys for the determination of MDA and EOF. At 0.3% Sodium Chloride (NaCl concentration, the percentage haemolysis was 93.69% ± 2.21% in the control donkeys and the value was significantly (P < 0.05 higher than the value of 71.31% ± 8.33%, recorded in the experimental donkeys. The post-packing MDA concentration obtained in the control donkeys was 39.62 µmol ± 4.16 µmol, and was not significantly different (P > 0.05 from the value of 35.97 µmol ± 2.88 µmol recorded in the experimental donkeys. In conclusion, the increase in haemolysis obtained in the donkeys suggested that packing induced oxidative stress, which was ameliorated by AA administration.

  17. Antioxidant responses and renal crystal formation in rainbow trout treated with melamine administered individually or in combination with cyanuric acid.

    Science.gov (United States)

    Pacini, Nicole; Prearo, Marino; Abete, Maria Cesarina; Brizio, Paola; Dörr, Ambrosius Josef Martin; Reimschuessel, Renate; Andersen, Wendy; Gasco, Laura; Righetti, Marzia; Elia, Antonia Concetta

    2013-01-01

    In 2007 and 2008, renal stone formation and kidney damage in human infants were linked to consumption of melamine (MEL)-contaminated infant formula, as well as renal failure and death in pets due to pet food containing both MEL and cyanuric acid (CYA). The aim of this study was to examine the effects of MEL and CYA administered individually or in combination on concentrations of certain metabolites and enzyme activities that serve as markers for oxidative stress in kidney and liver of rainbow trout. In addition, the levels of muscle MEL and renal crystal formation were determined. Trout were fed MEL and/or CYA for 8 wk at 250, 500, or 1000 mg of each compound/kg in feed. Fish muscle residues of MEL exhibited a dose-response relationship. Coexposure of trout to MEL and CYA at the highest dose led to lower MEL residue concentrations in muscle compared to exposure to MEL alone. Renal MEL-CYA complexes were found in kidneys of fish treated with combined MEL and CYA. A dose response was evident with respect to both (1) number of trout displaying renal crystals and (2) number of crystals per fish. Changes in concentration of antioxidant parameters, such as glutathione, superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase, were recorded in both tissues of MEL- and CYA-dosed trout. Lipid peroxidation was more pronounced in kidney than liver. Therefore, feed contaminated with both MEL and CYA could be problematic for fish, as MEL administered to trout, individually or in combination with CYA, may facilitate the onset of oxidative damage in trout. PMID:23721584

  18. In Vivo Curative and Protective Potential of Orally Administered 5-Aminolevulinic Acid plus Ferrous Ion against Malaria

    Science.gov (United States)

    Suzuki, Shigeo; Hikosaka, Kenji; Balogun, Emmanuel O.; Komatsuya, Keisuke; Niikura, Mamoru; Kobayashi, Fumie; Takahashi, Kiwamu; Tanaka, Tohru; Nakajima, Motowo

    2015-01-01

    5-Aminolevulinic acid (ALA) is a naturally occurring amino acid present in diverse organisms and a precursor of heme biosynthesis. ALA is commercially available as a component of cosmetics, dietary supplements, and pharmaceuticals for cancer diagnosis and therapy. Recent reports demonstrated that the combination of ALA and ferrous ion (Fe2+) inhibits the in vitro growth of the human malaria parasite Plasmodium falciparum. To further explore the potential application of ALA and ferrous ion as a combined antimalarial drug for treatment of human malaria, we conducted an in vivo efficacy evaluation. Female C57BL/6J mice were infected with the lethal strain of rodent malaria parasite Plasmodium yoelii 17XL and orally administered ALA plus sodium ferrous citrate (ALA/SFC) as a once-daily treatment. Parasitemia was monitored in the infected mice, and elimination of the parasites was confirmed using diagnostic PCR. Treatment of P. yoelii 17XL-infected mice with ALA/SFC provided curative efficacy in 60% of the mice treated with ALA/SFC at 600/300 mg/kg of body weight; no mice survived when treated with vehicle alone. Interestingly, the cured mice were protected from homologous rechallenge, even when reinfection was attempted more than 230 days after the initial recovery, indicating long-lasting resistance to reinfection with the same parasite. Moreover, parasite-specific antibodies against reported vaccine candidate antigens were found and persisted in the sera of the cured mice. These findings provide clear evidence that ALA/SFC is effective in an experimental animal model of malaria and may facilitate the development of a new class of antimalarial drug. PMID:26324278

  19. Safety of docosahexaenoic acid (DHA) administered as DHA ethyl ester in a 9-month toxicity study in dogs.

    Science.gov (United States)

    Dahms, Irina; Beilstein, Paul; Bonnette, Kimberly; Salem, Norman

    2016-06-01

    DHA Ethyl Ester (DHA-EE) is a 90% concentrated ethyl ester of docosahexaenoic acid manufactured from the microalgal oil. The objective of the 9-month study was to evaluate safety of DHA-EE administered to beagle dogs at dose levels 150, 1000 and 2000 mg/kg bw/day by oral gavage and to determine reversibility of any findings after a 2-month recovery period. DHA-EE was well tolerated at all doses. There were observations of dry flaky skin with occasional reddened areas at doses ≥1000 mg/kg bw/day. These findings lacked any microscopic correlate and were no longer present after the recovery period. There were no toxicologically relevant findings in body weights, body weight gains, food consumption, ophthalmological examinations, and ECG measurements. Test article-related changes in hematology parameters were limited to decreases in reticulocyte count in the high-dose males and considered non-adverse. In clinical chemistry parameters, dose-related decreases in cholesterol and triglycerides levels were observed at all doses in males and females and attributed to the known lipid-lowering effects of DHA. There were no effects on other clinical chemistry, urinalysis or coagulation parameters. There were no abnormal histopathology findings attributed to test article. The No-Observable-Adverse-Effect Level of DHA-EE was established at 2000 mg/kg bw/day for both genders. PMID:27036332

  20. Unexpected effects of peripherally administered kynurenic acid on cortical spreading depression and related blood–brain barrier permeability

    Directory of Open Access Journals (Sweden)

    Oláh G

    2013-09-01

    Full Text Available Gáspár Oláh,1 Judit Herédi,1 Ákos Menyhárt,1 Zsolt Czinege,2 Dávid Nagy,1 János Fuzik,1 Kitti Kocsis,1 Levente Knapp,1 Erika Krucsó,1 Levente Gellért,1 Zsolt Kis,1 Tamás Farkas,1 Ferenc Fülöp,3 Árpád Párdutz,4 János Tajti,4 László Vécsei,4 József Toldi1 1Department of Physiology, Anatomy and Neuroscience, 2Department of Software Engineering, 3Institute of Pharmaceutical Chemistry and MTA-SZTE Research Group for Stereochemistry, 4Department of Neurology and MTA-SZTE Neuroscience Research Group, University of Szeged, Szeged, Hungary Abstract: Cortical spreading depression (CSD involves a slowly-propagating depolarization wave in the cortex, which can appear in numerous pathophysiological conditions, such as migraine with aura, stroke, and traumatic brain injury. Neurons and glial cells are also depolarized transiently during the phenomena. CSD is followed by a massive increase in glutamate release and by changes in the brain microcirculation. The aim of this study was to investigate the effects of two N-methyl-D-aspartate receptor antagonists, endogenous kynurenic acid (KYNA and dizocilpine, on CSD and the related blood–brain barrier (BBB permeability in rats. In intact animals, KYNA hardly crosses the BBB but has some positive features as compared with its precursor L-Kynurenine, which is frequently used in animal studies (KYNA cannot be metabolized to excitotoxic agents such as 3-hydroxy-L-kynurenine and quinolinic acid. We therefore investigated the possible effects of peripherally administered KYNA. Repetitive CSD waves were elicited by the application of 1 M KCl solution to the cortex. Direct current-electrocorticograms were measured for 1 hour. Four parameters of the waves were compared. Evans blue dye and fluorescent microscopy were used to study the possible changes in the permeability of the BBB. The results demonstrated that N-methyl-D-aspartate receptor antagonists can reduce the number of CSD waves and decrease

  1. Absorbed dose assessment of 177Lu-zoledronate and 177Lu-EDTMP for human based on biodistribution data in rats

    OpenAIRE

    Yousefnia, Hassan; Zolghadri, Samaneh; Jalilian, Amir Reza

    2015-01-01

    Over the past few decades, several bone-seeking radiopharmaceuticals including various bisphosphonate ligands and β-emitting radionuclides have been developed for bone pain palliation. Recently, 177Lu was successfully labeled with zoledronic acid (177Lu-ZLD) as a new generation potential bisphosphonate and demonstrated significant accumulation in bone tissue. In this work, the absorbed dose to each organ of human for 177Lu-ZLD and 177Lu-ethylenediaminetetramethylene phosphonic acid (177Lu-EDT...

  2. Humulus lupus Beta-acids Administered Through Water Reduce Clostridium perfringens Challenge Strains in the Chicken Intestinal Tract Midgut and Ceca.

    Science.gov (United States)

    The antimicrobial activity activity of extracts of the hop plant Humulus lupus was studied in chickens fed diets without antibiotic growth promotants. Beta-acid resins of the hop plant were administered by water to 13 day old chickens subsequently challenged per so with necrotic enteritis-associate...

  3. The neurotoxic effect of clindamycin - induced gut bacterial imbalance and orally administered propionic acid on DNA damage assessed by the comet assay: protective potency of carnosine and carnitine

    OpenAIRE

    El-Ansary, Afaf; Shaker, Ghada H; El-Gezeery, Amina R; Al-Ayadhi, Laila

    2013-01-01

    Background Comet assay is a quick method for assessing DNA damage in individual cells. It allows the detection of single and double DNA strand breaks, which represent the direct effect of some damaging agents. This study uses standard comet quantification models to compare the neurotoxic effect of orally administered propionic acid (PA) to that produced as a metabolite of bacterial overgrowth induced by clindamycin. Additionally, the protective effect of carnosine and carnitine as natural die...

  4. Treatment of Spinal Vertebra Metastases Pain with Combination of Prcutaneous Vertebroplasty and Zoledronic Acid%经皮椎体成形术联合唑来膦酸治疗脊椎骨转移癌疼痛

    Institute of Scientific and Technical Information of China (English)

    李宇清; 何明基; 吴学成; 段俊

    2012-01-01

      目的 观察经皮椎体成形术联合双膦酸盐治疗脊椎骨转移癌的疗效及不良反应.方法 将46例脊椎骨转移癌患者分为治疗组和对照组,治疗组21例行经皮椎体成形术治疗,同时静脉滴注唑来膦酸4mg每4周1次,连续2次后评价疗效和不良反应;对照组25例给予常规止痛药物治疗.结果 治疗组脊椎骨转移癌患者的骨痛完全缓解8例,部分缓解9例,有效率为81.0%,生活质量改善有效率为95.2%,与对照组相比差异有统计学意义(P<0.05);治疗组主要不良反应有发热、恶心、呕吐等.结论 经皮椎体成形术联合双膦酸盐治疗脊椎骨转移癌的止痛疗效迅速,可防止骨转移癌的进展,提高生活质量,其不良反应患者可以耐受.%  Objective  To evaluate the efficacy and side events of the treatment of spinal vertebra metastases with combination of percutaneous vertebroplasty and bisphosphonates. Methods  46 patients suffered from spinal vertebra metastases were observed in the research.21 cases in surgeon group were given percutaneous vertebroplasty, and meanwhile intravenous infusion of Zoledronic Acid was given as 4mg every 4 weeks. We evaluate the efficacy and side events of the treatment after percutaneous vertebroplasty and 2 cycles of Zoledronic Acid.On the other hand, 25 cases in control group were given normal anti-pain treatment. Results  Out of the 21 patients in surgeon group, 8 cases achieved complete remission and 9 cases achieved partial remission.Bone pain relief provided by the treatment was 81.0% and the efficacy in increasing quality of life was 95.2%.There

  5. Effect of bullfrog (Rana catesbeiana oil administered by gavage on the fatty acid composition and oxidative stress of mouse liver

    Directory of Open Access Journals (Sweden)

    L.P. Silva

    2004-10-01

    Full Text Available The aim of the present study was to investigate the effects of daily intragastric administration of bullfrog oil (oleic, linoleic and palmitoleic acid-rich oil, corresponding to 0.4% of body weight for four weeks, on fatty acid composition and oxidative stress (lipid peroxidation and catalase activity in mouse liver. The activities of aspartate aminotransferase (AST, alkaline phosphatase (ALP, alanine aminotransferase (ALT, and gamma-glutamyltransferase (GGT, biomarkers of tissue injury, were determined in liver homogenates and serum. The proportions of 18:2n-6, 20:4n-6, 20:5n-3, and 22:6n-3 (polyunsaturated fatty acids, from 37 to 60% in the total fatty acid content were increased in the liver of the bullfrog oil-treated group (P < 0.05 compared to control. At the same time, a significant decrease in the relative abundance of 14:0, 16:0, and 18:0 (saturated fatty acids, from 49 to 25% was observed. The hepatic content of thiobarbituric acid reactive substances (TBARS was increased from 2.3 ± 0.2 to 12.3 ± 0.3 nmol TBA-MDA/mg protein and catalase activity was increased from 840 ± 32 to 1110 ± 45 µmol reduced H2O2 min-1 mg protein-1 in the treated group. Bullfrog oil administration increased AST and ALP activities in the liver (from 234.10 ± 0.12 to 342.84 ± 0.13 and 9.38 ± 0.60 to 20.06 ± 0.27 U/g, respectively and in serum (from 95.41 ± 6.13 to 120.32 ± 3.15 and 234.75 ± 11.5 to 254.41 ± 2.73 U/l, respectively, suggesting that this treatment induced tissue damage. ALT activity was increased from 287.28 ± 0.29 to 315.98 ± 0.34 U/g in the liver but remained unchanged in serum, whereas the GGT activity was not affected by bullfrog oil treatment. Therefore, despite the interesting modulation of fatty acids by bullfrog oil, a possible therapeutic use requires care since some adverse effects were observed in liver.

  6. Effect of tolbutamide, glyburide and glipizide administered supraspinally on CA3 hippocampal neuronal cell death and hyperglycemia induced by kainic acid in mice.

    Science.gov (United States)

    Kim, Chea-Ha; Park, Soo-Hyun; Sim, Yun-Beom; Kim, Sung-Su; Kim, Su-Jin; Lim, Su-Min; Jung, Jun-Sub; Suh, Hong-Won

    2014-05-20

    Sulfonylureas are widely used oral drugs for the treatment of type II diabetes mellitus. In the present study, the effects of sulfonylureas administered supraspinally on kainic acid (KA)-induced hippocampal neuronal cell death and hyperglycemia were studied in ICR mice. Mice were pretreated intracerebroventricularly (i.c.v.) with 30μg of tolbutamide, glyburide or glipizide for 10min and then, mice were administered i.c.v. with KA (0.1μg). The neuronal cell death in the CA3 region in the hippocampus was assessed 24h after KA administration and the blood glucose level was measured 30, 60, and 120min after KA administration. We found that i.c.v. pretreatment with tolbutamide, glyburide or glipizide attenuated the KA-induced neuronal cell death in CA3 region of the hippocampus and hyperglycemia. In addition, KA administered i.c.v. caused an elevation of plasma corticosterone level and a reduction of the plasma insulin level. The i.c.v. pretreatment with tolbutamide, glyburide or glipizide attenuated KA-induced increase of plasma corticosterone level. Furthermore, i.c.v. pretreatment with tolbutamide, glyburide or glipizide causes an elevation of plasma insulin level. Glipizide, but not tolbutamide or glyburide, pretreated i.c.v. caused a reversal of KA-induced hypoinsulinemic effect. Our results suggest that supraspinally administered tolbutamide, glyburide and glipizide exert a protective effect against KA-induced neuronal cells death in CA3 region of the hippocampus. The neuroprotective effect of tolbutamide, glyburide and glipizide appears to be mediated by lowering the blood glucose level induced by KA. PMID:24713348

  7. Influence of dietary triacylglycerol structure and level of n-3 fatty acids administered during development on brain phospholipids and memory and learning ability of rats

    DEFF Research Database (Denmark)

    Hartvigsen, M.S.; Mu, Huiling; Hougaard, K.S.;

    2004-01-01

    22:6n-3 adding up to a total of 2 mol% n-3 fatty acids. The effects of the experimental diets were compared to the effect of a chow diet. Results: The amount of 22:6n-3 in brain phosphatidyl ethanolamine (PE) and phosphatidyl serine (PS) of dams and offspring (3 and 13 weeks of age) was not affected......The objective of this study was to examine the effects of triacylglycerol (TAG) structure and level of n-3 fatty acids on fatty acid profile of brain phospholipids (PL) of dams and offspring, and the memory and learning ability of the offspring, when administered during initial development of the...... by the six different diets. 18:2n-6, but not 18:3n-3, was detected in brain PL, suggesting a specificity of the tissues in the metabolism of n-3 and n-6 fatty acids. The level of monounsaturated fatty acids (MUFA) increased with increasing age of the pups, indicating an enhanced myelinization. No...

  8. Photosensitization of experimental hepatocellular carcinoma with protoporphyrin synthesized from administered δaminolevulinic acid. Studies with cultured cells and implanted tumors

    International Nuclear Information System (INIS)

    Background/Aims: Photodynamic therapy using porphyrins or related compounds and laser light is an investigational treatment for neoplasms. The aim of this study was to establish whether this might be applicable for hepatocellular carcinoma using protoporphyrin synthesized in the tissue from administered δ-aminolevulinic acid. Methods: We measured porphyrin accumulation in normal rat hepatocytes and Morris hepatoma cells in culture, and in subcutaneously implanted hepatomas and other tissues of the rat after administration of δ-aminolevulinic acid, and assessed cell and tissue damage after application of laser light. Results: Porphyrin accumulation after δ-aminolevulinic acid was added to the medium was greater and continued to increase for a longer period of time in hepatoma cells than in hepatocytes (1337±42 vs 513±31 fluorescence units/cell at 8 h, means±SE, p<0.001). After intraperitoneal injection of δaminolevulinic acid to rats with subcutaneously growing hepatomas, porphyrin content in tumor and liver was similar at 4 h but was higher in tumor at 6 h. Laser light caused necrosis of normal and malignant liver cells in culture and subcutaneous hepatomas in vivo. Conclusions: We conclude from these in vitro and in vivo studies that porphyrin accumulation after administration of δaminolevulinic acid in this hepatoma is substantial and time dependent, and delivery of laser light locally can cause tumor photosensitization and necrosis. (au) 41 refs

  9. Effect of Intraperitoneal Administered Ginseng Total Saponins on Hyperalgesia Induced by Repeated Intramuscular Injection of Acidic Saline in Rats

    OpenAIRE

    Kim, Won Joong; Kang, Hyun; Kim, Jung Eun; Choi, Geun Joo; Shin, Hwa Yong; Baek, Chong Wha; Jung, Yong Hun; Woo, Young Choel; Kim, Su Hyun; Lee, Jeong Hyuk

    2014-01-01

    The aim of this study was to assess the antinociceptive activity of ginseng total saponins (GTS) on hyperalgesia induced by repeated intramuscular injections of acidic saline in rats and to examine the mechanisms involved. Rats were injected intraperitoneally with a 0.9% saline vehicle or various doses of GTS after the development of hyperalgesia. Rats were then injected with N-methyl-D-aspartate (NMDA) or naloxone 10 min before GTS injection. The mechanical withdrawal threshold (MWT) was ass...

  10. Pharmacokinetic and therapeutic efficacy of intrapulmonary administration of zoledronate for the prevention of bone destruction in rheumatoid arthritis.

    Science.gov (United States)

    Katsumi, Hidemasa; Mozume, Takunori; Yanagi, Shin-Ichiro; Hasei, Tomohiro; Watanabe, Tetsushi; Sakane, Toshiyasu; Yamamoto, Akira

    2016-07-01

    Zoledronate, a third-generation nitrogen-containing bisphosphonate, is a new therapeutic agent for the prevention of joint destruction in rheumatoid arthritis (RA). Due to the poor oral absorption of zoledronate, the intravenous route has been the preferred method of administration. To evaluate whether the lung is a promising alternative route of zoledronate administration for the prevention of joint destruction in RA, we examined the pharmacokinetics, safety and therapeutic potential of zoledronate after intrapulmonary administration. The bioavailability of zoledronate was 55% after intrapulmonary administration in rats. In a collagen-induced RA mouse model, an intrapulmonary administration of zoledronate given 7 d before the 2nd collagen immunization effectively suppressed bone loss and joint destruction to a level similar to that achieved with intravenous injection at 21 d after the 2nd collagen immunization. Zoledronate only slightly affected lactate dehydrogenase activity in bronchoalveolar lavage fluid 4 h after intrapulmonary administration of the therapeutic dose in rats. Moreover, zoledronate only slightly changed the plasma level of creatinine after intrapulmonary administration while creatinine significantly increased after intravenous injection of zoledronate in mice. These results indicate that the lung is a promising alternative route of zoledronate administration for the treatment and prevention of joint destruction in RA. PMID:26508267

  11. Influence of dietary triacylglycerol structure and level of n-3 fatty acids administered during development on brain phospholipids and memory and learning ability of rats

    DEFF Research Database (Denmark)

    Hartvigsen, M.S.; Mu, Huiling; Hougaard, K.S.; Lund, S.P.; Xu, Xuebing; Høy, Carl-Erik

    2004-01-01

    structured oil, alpha-linolenic acid (18:3n-3) was predominantly located in the sn-2 position of the triacylglycerols and the level of 18:3n-3 was 2 mol or 10 mol%. In the linseed oil diets the level of 18:3n-3 was 2 mol or 10 mol% as well. Finally, the fish oil diet contained 18:3n-3 as well as 20:5n-3 and......The objective of this study was to examine the effects of triacylglycerol (TAG) structure and level of n-3 fatty acids on fatty acid profile of brain phospholipids (PL) of dams and offspring, and the memory and learning ability of the offspring, when administered during initial development of the...... 22:6n-3 adding up to a total of 2 mol% n-3 fatty acids. The effects of the experimental diets were compared to the effect of a chow diet. Results: The amount of 22:6n-3 in brain phosphatidyl ethanolamine (PE) and phosphatidyl serine (PS) of dams and offspring (3 and 13 weeks of age) was not affected...

  12. Lipoprotein lipase expression, serum lipid and tissue lipid deposition in orally-administered glycyrrhizic acid-treated rats

    Directory of Open Access Journals (Sweden)

    Ton So

    2009-07-01

    Full Text Available Abstract Background The metabolic syndrome (MetS is a cluster of metabolic abnormalities comprising visceral obesity, dyslipidaemia and insulin resistance (IR. With the onset of IR, the expression of lipoprotein lipase (LPL, a key regulator of lipoprotein metabolism, is reduced. Increased activation of glucocorticoid receptors results in MetS symptoms and is thus speculated to have a role in the pathophysiology of the MetS. Glycyrrhizic acid (GA, the bioactive constituent of licorice roots (Glycyrrhiza glabra inhibits 11β-hydroxysteroid dehydrogenase type 1 that catalyzes the activation of glucocorticoids. Thus, oral administration of GA is postulated to ameliorate the MetS. Results In this study, daily oral administration of 50 mg/kg of GA for one week led to significant increase in LPL expression in the quadriceps femoris (p p > 0.05 of the GA-treated rats compared to the control. Decrease in adipocyte size (p > 0.05 in both the visceral and subcutaneous adipose tissue depots accompanies such selective induction of LPL expression. Consistent improvement in serum lipid parameters was also observed, with decrease in serum free fatty acid, triacylglycerol, total cholesterol and LDL-cholesterol but elevated HDL-cholesterol (p > 0.05. Histological analysis using tissue lipid staining with Oil Red O showed significant decrease in lipid deposition in the abdominal muscle and quadriceps femoris (p p > 0.05. Conclusion Results from this study may imply that GA could counteract the development of visceral obesity and improve dyslipidaemia via selective induction of tissue LPL expression and a positive shift in serum lipid parameters respectively, and retard the development of IR associated with tissue steatosis.

  13. Zoledronate upregulates MMP-9 and -13 in rat vascular smooth muscle cells by inducing oxidative stress

    Science.gov (United States)

    Arun, Mehmet Zuhuri; Reel, Buket; Sala-Newby, Graciela B; Bond, Mark; Tsaousi, Aikaterini; Maskell, Perry; Newby, Andrew C

    2016-01-01

    Background Bisphosphonates, including zoledronate, target osteoclasts and are widely used in the treatment of osteoporosis and other bone resorption diseases, despite side effects that include damaging the stomach epithelium. Beneficial and adverse effects on other organ systems, including the cardiovascular system, have also been described and could impact on the use of bisphosphonates as therapeutic agents. Vascular smooth muscle cells (VSMCs) are major constituents of the normal vascular wall and have a key role in intimal thickening and atherosclerosis, in part by secreting MMPs that remodel the extracellular matrix and cleave cell surface proteins or secreted mediators. In this study, we investigated the effects of zoledronate on MMP expression. Methods Rat VSMCs were stimulated by PDGF (50 ng/mL) plus TNF-α (10 ng/mL) or left unstimulated for a further 24 hours in serum-free medium. In other series of experiments, cells were pre-treated either with SC-514 (50 μM) or with apocynin (20 nM) for 2 hours, then zoledronate (100 μM) was added into 2% fetal calf serum containing medium for 24 hours. Results and discussion Using isolated rat VSMCs in culture, zoledronate (100 μM) increased MMP-9 and -13 mRNA expressions but inhibited MMP-2 expression. MMP-9 and MMP-13 up-regulation was shown to depend on the NF-κB pathway; and this was activated by zoledronate. Furthermore, zoledronate elevated the levels of reactive oxygen species detected by either dichlorofluorescein in isolated VSMCs or lucigenin enhanced chemiluminescence in rat aortic rings in vitro. Apocynin, an inhibitor of NADPH oxidase, reversed NF-κB activation and MMP-9 and MMP-13 up-regulation by zoledronate. Conclusion We conclude that zoledronate increases MMP-9 and MMP-13 expressions in rat VSMCs dependent upon stimulation of the NF-κB pathway by reactive oxygen species. Effects on MMP expression may contribute to the pharmacologic profile of bisphosphonates.

  14. Validity of Estimated Dietary Eicosapentaenoic Acid and Docosahexaenoic Acid Intakes Determined by Interviewer-Administered Food Frequency Questionnaire Among Older Adults With Mild-to-Moderate Cognitive Impairment or Dementia

    OpenAIRE

    Arsenault, Lisa N.; Matthan, Nirupa; Scott, Tammy M.; Dallal, Gerard; Lichtenstein, Alice H; Folstein, Marshal F.; Rosenberg, Irwin; Tucker, Katherine L.

    2009-01-01

    Epidemiologic research is increasingly being focused on elderly persons, many of whom exhibit mild-to-moderate cognitive impairment. This presents a challenge for collection and interpretation of self-reported dietary data. There are few reports on the impact of cognitive function and dementia on the validity of self-reported dietary intakes. Using plasma phospholipid fatty acid profiles as a biomarker of intake, the authors assessed the validity of an interviewer-administered food frequency ...

  15. Effects of dietary pantethine levels on contents of fatty acids and thiobarbituric acid reactive substances in the liver of rats orally administered varying amounts of autoxidized linoleate.

    Science.gov (United States)

    Hiramatsu, N; Kishida, T; Hamano, T; Natake, M

    1991-02-01

    The effects of dietary pantethine levels on the contents and compositions of fatty acids and on the levels of lipid peroxides were investigated with rat liver and its S-9 fraction under administration of 0 (non), 0.2 (low dose), and 0.35 ml (high dose) of autoxidized linoleate (AL) per 100 g body weight of the rats per day for 5 days. AL having 800 meq/kg of peroxide value (PV) and 1,700 meq/kg of carbonyl value (CV) was dosed to the rats of each group given drinking water containing 0 mg% (deficient), 6.25 mg% (adequate), and 125 mg% pantethine (excess). In the pantethine-deficient and -adequate groups, the contents of fatty acids both in the liver homogenate and in the S-9 fraction were correspondingly decreased by increasing dose levels of AL, and the decrease was remarkable especially in the pantethine-deficient group, but was not significant in the pantethine-excess group even by a high dose of AL. Particularly, in the high dose of AL, the notable decreases of oleic acid (C18:1) contents in both the liver and the S-9 fraction were observed in rats of the pantethine-deficient and -adequate groups. The thiobarbituric acid (TBA) values in the liver homogenate and the S-9 fraction were increased correspondingly by increasing dose levels of AL, and the increases were repressed in the pantethine-excess group. PMID:1880633

  16. 唑来膦酸与γδ TCR单抗体外扩增HIV感染者Vδ2 T细胞的效果比较%The comparison between HIV-infected patients' Vdelta2 T cells expansion efficiencies by zoledronic acid and gammadelta TCR monoclonal antibody in vitro

    Institute of Scientific and Technical Information of China (English)

    许文; 武晓丽; 谢杨新; 杨俊连; 聂为民; 赵敏; 陈威巍

    2012-01-01

    目的 观察唑来膦酸和γδ TCR单抗两种诱导方法对HIV感染者的Vδ2 T细胞的扩增效果,探讨效率更高的扩增方法.方法 选择65例HIV感染者和38例健康对照者,应用唑来膦酸法和γδ TCR单抗法分别诱导其外周血单个核细胞(PBMC),分别在培养的0d、7d、14 d应用流式细胞术检测其γδ T细胞及其亚群的百分率及Vδ2 T细胞增殖情况,比较两种方法的诱导效果.结果 外周血中HIV感染者Vδ2 T细胞的数量和比例与健康对照相比显著下降;扩增14 d后,γδ TCR单抗法诱导HIV感染者和健康对照者的Vδ2 T细胞占CD3+细胞的百分比分别为(17.6±19.8)%和(64.3±4.5)%,Vδ2 T细胞扩增倍数分别为54±40和74±29;而采用唑来膦酸法的诱导结果分别为(69.6±21.2)%和(97.3±1.7)%以及538±11和5984±721.结论 唑来膦酸法可诱导HIV感染者及健康对照者Vδ2 T细胞大量增殖,其效率显著高于γδ TCR单抗诱导法.%Objective To find out the more efficient induction method through investigating the expansion efficiencies of HIV-infected patients' Vdelta2 T cells induced by zoledronic acid (Zol) or gammadelta TCR monoclonal antibody (mAb).Methods 38 healthy control subjects (HC group) and 65 HIV infected patients (HIV group) were enrolled in this research.Peripheral blood mononuclear cells (PBMCs) of individuals were stimulated by Zol or γδ TCR mAb respectively for 14 days at 2.0 × 107 cells/well,and then γδ T cells and Vδ2 subsets frequencies were measured by flow cytometry (FCM) on 0,7 and 14 day.The absolute numbers of Vδ2 T cells were calculated and the Vδ2 T cell expansion efficiencies by these two methods were compared.Results The absolute numbers and frequencies of Vδ2 T cell of HIV groups were lower than those of HC groups significantly on 0 day.After 14 days,the frequencies of Vδ2 T cell of HIV group and HC group were(17.6 ± 19.8)% and(64.3 ± 4.5) % respectively,and the expansion indexes of Vδ2

  17. Vitamin D status and parathyroid hormone concentrations influence the skeletal response to zoledronate and denosumab.

    Science.gov (United States)

    Mosali, P; Bernard, L; Wajed, J; Mohamed, Z; Ewang, M; Moore, A; Fogelman, I; Hampson, G

    2014-05-01

    Studies suggest that optimal vitamin D status is required for the maximal effect of antiresorptive agents. We investigated the relationship between vitamin D status, serum parathyroid hormone (PTH) concentrations, and change in bone mineral density (BMD) following iv zoledronate and denosumab. We carried out a retrospective analysis of 111 patients, mean age 70 (SD 13) years, 89 women and 22 men, prescribed zoledronate and 43 postmenopausal women treated with denosumab for osteoporosis. We measured BMD at the lumbar spine (LS) and total hip (TH), serum 25 (OH) vitamin D, PTH, and bone turnover markers (plasma CTX, P1NP) at 1 year. In patients on zoledronate, BMD increased at the LS and TH (mean LS change [SEM] = 2.6 % [0.5 %], mean TH change = 1.05 % [0.5 %], p vitamin D of nmol/L, respectively. The mean PTH concentration in patients with 25 (OH) vitamin D nmol/L was 44 ng/L (SEM 16.6). Patients with PTH concentration ng/L had significantly higher increases in TH BMD compared to those with PTH >44 ng/L (zoledronate 1.9 [0.83] vs. -0.43 [0.81], p = 0.04; denosumab 4.1 [0.054] vs. -1.7 [0.04], p = 0.004). Optimal vitamin D status and PTH concentrations improve the skeletal response to zoledronate and denosumab. PMID:24509506

  18. Local delivery of zoledronate from a poly (D,L-lactide)-Coating increases fixation of press-fit implants.

    Science.gov (United States)

    Jakobsen, Thomas; Bechtold, Joan E; Søballe, Kjeld; Jensen, Thomas; Greiner, Stefan; Vestermark, Marianne T; Baas, Jørgen

    2016-01-01

    Early secure fixation of total joint replacements is crucial for long-term survival. Antiresorptive agents such as bisphosphonates have been shown to increase implant fixation. We investigated whether local delivery of zoledronate from poly-D, L-lactide (PDLLA)-coated implants could improve implant fixation and osseointegration. Experimental titanium implants were bilaterally inserted press-fit into the proximal tibiae of 10 dogs. On one side the implant was coated with PDLLA containing zoledronate. The contralateral implant was uncoated and used as control. Observation period was 12 weeks. Implant fixation was evaluated with histomorphometry and biomechanical push-out test. We found an approximately twofold increase in all biomechanical parameters when comparing data from the zoledronate group with their respective controls. Histomorphometry showed increased amount of preserved bone and increased bone formation around the zoledronate implants. This study indicates that local delivery of zoledronate from a PDDLA coating has the potential to increase implant fixation. PMID:26177742

  19. Effect of local zoledronate on implant osseointegration in a rat model

    Directory of Open Access Journals (Sweden)

    Back David A

    2012-03-01

    Full Text Available Abstract Background An implant coating with poly(D, L-lactide (PDLLA releasing incorporated Zoledronic acid (ZOL has already proven to positively effect osteoblasts, to inhibit osteoclasts and to accelerate fracture healing. Aim of this study was to investigate the release kinetics of the chosen coating and the effect of different concentrations of ZOL locally released from this coating on the osseointegration of implants. Methods For release kinetics the release of C14-labled ZOL out of the coating was monitored over a period of six weeks in vitro. For testing the osseointegration, titanium Kirschner wires were implanted into the medullary canal of right femurs of 100 Sprague Dawley rats. The animals were divided into five groups receiving implants either uncoated or coated with PDLLA, PDLLA/ZOL low (1.2% w/w or PDLLA/ZOL high (2% w/w. Additionally, a group with uncoated implants received ZOL intravenously (i.v.. After 56 days animals were sacrificed, femurs dissected and either strength of fixation or histological bone/implant contacts and newly formed bone around the implants were determined. Results Release kinetics revealed an initial peak in the release of C14-ZOL with a slight further progression over the following weeks. There was no significant enhancement of osseointegration for both groups who received ZOL-coated implants or ZOL i.v. compared to the controls in biomechanical or histological analyses, except for a significant raise in strength of fixation of ZOL i.v. versus PDLLA. Conclusions Even though the investigated local ZOL application did not enhance the osseointegration of the implant, the findings might support its application in fracture treatment, since fracture stabilization devices are often explanted after consolidation.

  20. Township Administered Roads

    Data.gov (United States)

    Minnesota Department of Natural Resources — This data set contains roadway centerlines for township administered roads found on the USGS 1:24,000 mapping series. In some areas, these roadways are current...

  1. Chemometrics-assisted Spectrofluorimetric Determination of Two Co-administered Drugs of Major Interaction, Methotrexate and Aspirin, in Human Urine Following Acid-induced Hydrolysis.

    Science.gov (United States)

    Maher, Hadir M; Ragab, Marwa A A; El-Kimary, Eman I

    2015-01-01

    Methotrexate (MTX) is widely used to treat rheumatoid arthritis (RA), mostly along with non-steroidal anti-inflammatory drugs (NSAIDs), the most common of which is aspirin or acetyl salicylic acid (ASA). Since NSAIDs impair MTX clearance and increase its toxicity, it was necessary to develop a simple and reliable method for the monitoring of MTX levels in urine samples, when coadministered with ASA. The method was based on the spectrofluorimetric measurement of the acid-induced hydrolysis product of MTX, 4-amino-4-deoxy-10-methylpteroic acid (AMP), along with the strongly fluorescent salicylic acid (SA), a product of acid-induced hydrolysis of aspirin and its metabolites in urine. The overlapping emission spectra were resolved using the derivative method (D method). In addition, the corresponding derivative emission spectra were convoluted using discrete Fourier functions, 8-points sin xi polynomials, (D/FF method) for better elimination of interferences. Validation of the developed methods was carried out according to the ICH guidelines. Moreover, the data obtained using derivative and convoluted derivative spectra were treated using the non-parametric Theil's method (NP), compared with the least-squares parametric regression method (LSP). The results treated with Theil's method were more accurate and precise compared with LSP since the former is less affected by the outliers. This work offers the potential of both derivative and convolution using discrete Fourier functions in addition to the effectiveness of using the NP regression analysis of data. The high sensitivity obtained by the proposed methods was promising for measuring low concentration levels of the two drugs in urine samples. These methods were efficiently used to measure the drugs in human urine samples following their co-administration. PMID:26234512

  2. Source inference of exogenous gamma-hydroxybutyric acid (GHB) administered to humans by means of carbon isotopic ratio analysis: novel perspectives regarding forensic investigation and intelligence issues.

    Science.gov (United States)

    Marclay, François; Saudan, Christophe; Vienne, Julie; Tafti, Mehdi; Saugy, Martial

    2011-05-01

    γ-Hydroxybutyric acid (GHB) is an endogenous short-chain fatty acid popular as a recreational drug due to sedative and euphoric effects, but also often implicated in drug-facilitated sexual assaults owing to disinhibition and amnesic properties. Whilst discrimination between endogenous and exogenous GHB as required in intoxication cases may be achieved by the determination of the carbon isotope content, such information has not yet been exploited to answer source inference questions of forensic investigation and intelligence interests. However, potential isotopic fractionation effects occurring through the whole metabolism of GHB may be a major concern in this regard. Thus, urine specimens from six healthy male volunteers who ingested prescription GHB sodium salt, marketed as Xyrem(®), were analysed by means of gas chromatography/combustion/isotope ratio mass spectrometry to assess this particular topic. A very narrow range of δ(13)C values, spreading from -24.81‰ to -25.06‰, was observed, whilst mean δ(13)C value of Xyrem(®) corresponded to -24.99‰. Since urine samples and prescription drug could not be distinguished by means of statistical analysis, carbon isotopic effects and subsequent influence on δ(13)C values through GHB metabolism as a whole could be ruled out. Thus, a link between GHB as a raw matrix and found in a biological fluid may be established, bringing relevant information regarding source inference evaluation. Therefore, this study supports a diversified scope of exploitation for stable isotopes characterized in biological matrices from investigations on intoxication cases to drug intelligence programmes. PMID:21455654

  3. Effect of aspartame and protein, administered in phenylalanine-equivalent doses, on plasma neutral amino acids, aspartate, insulin and glucose in man.

    Science.gov (United States)

    Møller, S E

    1991-05-01

    Six human males each received 0.56 g phenylalanine (Phe) in the form of 1.0 g aspartame or 12.2 g bovine albumin in 200 ml water or water alone. Venous blood samples collected before consumption and during the following 4 hr were assayed for plasma levels of large, neutral amino acids (LNAA), aspartate, insulin and glucose. The area under the curve for plasma Phe was 40% greater, although not significant, after aspartame compared with albumin intake. The indicated increased clearance rate of plasma Phe after albumin may be caused by the significant increase of insulin, on which aspartame had no effect. There was a significant main effect of aspartame for plasma tyrosine but not for tryptophan, valine, isoleucine or leucine. Plasma aspartate was significantly increased at 0.25 hr after the aspartame intake. The percentage Phe/LNAA decreased slightly in response to albumin but increased 55% after aspartame and remained significantly increased for 2 hr. Tyrosine/LNAA increased and tryptophan/LNAA decreased modestly after aspartame intake. The study showed that the intake of aspartame in a not unrealistically high dose produced a marked and persistent increase of the availability of Phe to the brain, which was not observed after protein intake. The study indicated, furthermore, that Phe was cleared faster from the plasma after consumption of protein compared with aspartame. PMID:1946186

  4. Effects of Zoledronate and Mechanical Loading during Simulated Weightlessness on Bone Structure and Mechanical Properties

    Science.gov (United States)

    Scott, R. T.; Nalavadi, M. O.; Shirazi-Fard, Y.; Castillo, A. B.; Alwood, J. S.

    2016-01-01

    Space flight modulates bone remodeling to favor bone resorption. Current countermeasures include an anti-resorptive drug class, bisphosphonates (BP), and high-force loading regimens. Does the combination of anti-resorptives and high-force exercise during weightlessness have negative effects on the mechanical and structural properties of bone? In this study, we implemented an integrated model to mimic mechanical strain of exercise via cyclical loading (CL) in mice treated with the BP Zoledronate (ZOL) combined with hindlimb unloading (HU). Our working hypothesis is that CL combined with ZOL in the HU model induces additive structural and mechanical changes. Thirty-two C57BL6 mice (male,16 weeks old, n8group) were exposed to 3 weeks of either HU or normal ambulation (NA). Cohorts of mice received one subcutaneous injection of ZOL (45gkg), or saline vehicle, prior to experiment. The right tibia was axially loaded in vivo, 60xday to 9N in compression, repeated 3xweek during HU. During the application of compression, secant stiffness (SEC), a linear estimate of slope of the force displacement curve from rest (0.5N) to max load (9.0N), was calculated for each cycle once per week. Ex vivo CT was conducted on all subjects. For ex vivo mechanical properties, non-CL left femurs underwent 3-point bending. In the proximal tibial metaphysis, HU decreased, CL increased, and ZOL increased the cancellous bone volume to total volume ratio by -26, +21, and +33, respectively. Similar trends held for trabecular thickness and number. Ex vivo left femur mechanical properties revealed HU decreased stiffness (-37),and ZOL mitigated the HU stiffness losses (+78). Data on the ex vivo Ultimate Force followed similar trends. After 3 weeks, HU decreased in vivo SEC (-16). The combination of CL+HU appeared additive in bone structure and mechanical properties. However, when HU + CL + ZOL were combined, ZOL had no additional effect (p0.05) on in vivo SEC. Structural data followed this trend with

  5. The bisphosphonate zoledronate prevents vertebral bone loss in mature estrogen-deficient rats as assessed by micro-computed tomography

    Directory of Open Access Journals (Sweden)

    Glatt M.

    2001-01-01

    Full Text Available The effect of long-term treatment with the bisphosphonate zoledronate on vertebral bone architecture was investigated in estrogen-deficient mature rats. 4-month-old rats were ovariectomized and development of cancellous osteopenia was assessed after 1 year. The change of bone architectural parameters was determined with a microtomographic instrument of high resolution. After 1 year of estrogen-deficiency, animals lost 55% of vertebral trabecular bone in comparison to sham operated control animals. Trabecular number (Tb.N and trabecular thickness (Tb.Th were significantly reduced in ovariectomized animals, whereas trabecular separation (Tb.Sp, bone surface to volume fraction (BS/BV and trabecular bone pattern factor (TBPf were significantly increased, indicating a loss of architectural integrity throughout the vertebral body. 3 groups of animals were treated subcutaneously with zoledronate for 1 year with 0.3, 1.5 and 7.5 microgram/kg/week to inhibit osteoclastic bone degradation. Administration started immediately after ovariectomy and treatment dose-dependently prevented the architectural bone deterioration and completely suppressed the effects of estrogen deficiency at the higher doses. The results show that microtomographic determination of static morphometric parameters can be used to quantitate the effects of drugs on vertebral bone architecture in small laboratory animals and that zoledronate is highly effective in this rat model.

  6. The effect of nitrogen containing bisphosphonates, zoledronate and alendronate, on the production of pro-angiogenic factors by osteoblastic cells.

    Science.gov (United States)

    Ishtiaq, S; Edwards, S; Sankaralingam, A; Evans, B A J; Elford, C; Frost, M L; Fogelman, I; Hampson, G

    2015-02-01

    Bisphosphonates (BPs) have been shown to influence angiogenesis. This may contribute to BP-associated side-effects such as osteonecrosis of the jaw (ONJ) or atypical femoral fractures (AFF). The effect of BPs on the production of angiogenic factors by osteoblasts is unclear. The aims were to investigate the effect of (1) alendronate on circulating angiogenic factors; vascular endothelial growth factor (VEGF) and angiopoietin-1 (ANG-1) in vivo and (2) zoledronate and alendronate on the production of VEGF and ANG-1 by osteoblasts in vitro. We studied 18 post-menopausal women with T score⩽-2 randomized to calcium/vitamin D only (control arm, n=8) or calcium/vitamin D and alendronate 70mg weekly (treatment arm, n=10). Circulating concentrations of VEGF and ANG-1 were measured at baseline, 3, 6 and 12months. Two human osteoblastic cell lines (MG-63 and HCC1) and a murine osteocytic cell line (MLO-Y4) were treated with zoledronate or alendronate at concentrations of 10(-12)-10(-6)M. VEGF and ANG-1 were measured in the cell culture supernatant. We observed a trend towards a decline in VEGF and ANG-1 at 6 and 12months following treatment with alendronate (p=0.08). Production of VEGF and ANG-1 by the MG-63 and HCC1 cells decreased significantly by 34-39% (p<0.01) following treatment with zoledronate (10(-9)-10(-6)M). Treatment of the MG-63 cells with alendronate (10(-7) and 10(-6)) led to a smaller decrease (25-28%) in VEGF (p<0.05). Zoledronate (10(-10)-10(-)(6)M) suppressed the production of ANG-1 by MG-63 cells with a decrease of 43-49% (p<0.01). Co-treatment with calcitriol (10(-8)M) partially reversed this zoledronate-induced inhibition. BPs suppress osteoblastic production of angiogenic factors. This may explain, in part, the pathogenesis of the BP-associated side-effects. PMID:25461393

  7. Calcium phosphate cement delivering zoledronate decreases bone turnover rate and restores bone architecture in ovariectomized rats

    International Nuclear Information System (INIS)

    Patients sustaining bony fractures frequently require the application of bone graft substitutes to fill the bone defects. In the meantime, anti-osteoporosis drugs may be added in bone fillers to treat osteoporosis, especially in postmenopausal women and the elderly. The effects of zoledronate-impregnated calcium phosphate cement (ZLN/CPC) on ovariectomized (OVX) rats were evaluated. OVX rats were implanted with ZLN/CPC, containing 0.025 mg ZLN in the greater omentum. Afterward the clinical sign of toxicity was recorded for eight weeks. The rats were sacrificed and blood samples were collected for hematology and serum bone turnover markers analyses. The four limbs of the rats were harvested and micro-computer tomography (micro-CT) scanning and bone ash analyses were performed. No clinical toxicity was observed in the treated rats. Compared to the OVX rats, levels of bone resorption markers (fragments of C-telopeptides of type I collagen) and bone formation markers (alkaline phosphatase and osteocalcin) decreased significantly in the treated rats. Osteopontin, which mediates the anchoring of osteoclasts to the mineral matrix of bones, also decreased significantly. Micro-CT scanning and histologic examinations of the distal femoral metaphyses showed that the cancellous bone architectures were restored, with a concomitant decrease in bone porosity. The bone mineral content in the bone ashes also increased significantly. This study indicates that ZLN-impregnated CPC reduces bone turnover rate and restores bone architecture in OVX rats. CPC may be an appropriate carrier to deliver drugs to treat osteoporosis, and this approach may also reduce rates of post-dosing symptoms for intravenous ZLN delivery. (paper)

  8. Effects of local delivery of BMP2, zoledronate and their combination on bone microarchitecture, biomechanics and bone turnover in osteoporotic rabbits.

    Science.gov (United States)

    Jing, Da; Hao, Xuguang; Xu, Fang; Liu, Jian; Xu, Fei; Luo, Erping; Meng, Guolin

    2016-01-01

    The hip fracture is one major clinical challenge associated with osteoporosis, resulting in heavy socioeconomic burdens and high mortality. Systemic therapies of anti-osteoporosis drugs are expensive, time-consuming and also evoke substantial side effects, which fails to provide early protection from fractures. Accumulating evidence demonstrates the high bioavailability and therapeutic efficacy of local drug delivery in accelerating facture healing and bone defect repair. This study aims at investigating the effects of local delivery of BMP2 and zoledronate (two promising anabolic/anti-catobolic reagents) encapsulated by fibrin sealants into femoral necks on regulating bone quality and remodeling in osteoporotic rabbits subjected to combined ovariectomy and glucocorticoid injection. We show that 6-week BMP2 delivery exhibited more prominent effect on mitigating trabecular bone microarchitecture deterioration and mechanical strength reduction of femoral necks than local zoledronate treatment. BMP2 plus zoledronate showed more significant improvement of bone microstructure, mechanical strength and bone formation rate at 12 weeks post injection than single BMP2 or zoledronate delivery via μCT, biomechanical, histomorphometric and serum biochemical analyses. This study enriches our knowledge for understanding the availability of local drug delivery for improving bone quantity and quality, which may lead to earlier, safer and more efficient protection from osteoporosis-induced fractures in clinics. PMID:27329730

  9. Zoledronate blocks geranylgeranylation not farnesylation to suppress human osteosarcoma U2OS cells metastasis by EMT via Rho A activation and FAK-inhibited JNK and p38 pathways

    Science.gov (United States)

    Cheng, Hsin-Lin; Lin, Chiao-Wen; Yang, Jia-Sin; Hsieh, Ming-Ju; Yang, Shun-Fa; Lu, Ko-Hsiu

    2016-01-01

    Zoledronate is a standard treatment for preventing skeletal complications of osteoporosis and some types of cancer associated with bone metastases, but we little know whether the effect of zoledronate on metastasis of osteosarcoma. Here, we investigated the inhibitory effects of zoledronate on cell viability, motility, migration and invasion of 4 osteosarcoma cell lines (Saos2, MG-63, HOS and U2OS) by affecting cell morphology, epithelial-mesenchymal transition (EMT) and cytoskeletal organization as well as induction of E-cadherin and reduction of N-cadherin with activation of transcription factors Slug and Twist, especially in U2OS cells. Zoledronate decreased JNK and p38 phosphorylation and upper streams of focal adhesion kinase (FAK) and Src to suppress the motility, invasiveness and migration of U2OS cells. In addition to zoledronate-inhibited Rho A and Cdc42 membrane translocation and GTPγS activities, the anti-metastatic effects in U2OS cells including inhibition of adhesion were reversed by geranylgeraniol, but not farnesol. In conclusion, Zoledronate blocks geranylgeranylation not farnesylation to suppress human osteosarcoma U2OS cell-matrix and cell-cell interactions, migration potential, the invasive activity, and the adhesive ability by EMT via Rho A activation and FAK-inhibited JNK and p38 pathways. PMID:26848867

  10. Zoledronate blocks geranylgeranylation not farnesylation to suppress human osteosarcoma U2OS cells metastasis by EMT via Rho A activation and FAK-inhibited JNK and p38 pathways.

    Science.gov (United States)

    Cheng, Hsin-Lin; Lin, Chiao-Wen; Yang, Jia-Sin; Hsieh, Ming-Ju; Yang, Shun-Fa; Lu, Ko-Hsiu

    2016-03-01

    Zoledronate is a standard treatment for preventing skeletal complications of osteoporosis and some types of cancer associated with bone metastases, but we little know whether the effect of zoledronate on metastasis of osteosarcoma. Here, we investigated the inhibitory effects of zoledronate on cell viability, motility, migration and invasion of 4 osteosarcoma cell lines (Saos2, MG-63, HOS and U2OS) by affecting cell morphology, epithelial-mesenchymal transition (EMT) and cytoskeletal organization as well as induction of E-cadherin and reduction of N-cadherin with activation of transcription factors Slug and Twist, especially in U2OS cells. Zoledronate decreased JNK and p38 phosphorylation and upper streams of focal adhesion kinase (FAK) and Src to suppress the motility, invasiveness and migration of U2OS cells. In addition to zoledronate-inhibited Rho A and Cdc42 membrane translocation and GTPγS activities, the anti-metastatic effects in U2OS cells including inhibition of adhesion were reversed by geranylgeraniol, but not farnesol. In conclusion, Zoledronate blocks geranylgeranylation not farnesylation to suppress human osteosarcoma U2OS cell-matrix and cell-cell interactions, migration potential, the invasive activity, and the adhesive ability by EMT via Rho A activation and FAK-inhibited JNK and p38 pathways. PMID:26848867

  11. Eicosapentaenoic Acid Inhibits Oxidation of ApoB-containing Lipoprotein Particles of Different Size In Vitro When Administered Alone or in Combination With Atorvastatin Active Metabolite Compared With Other Triglyceride-lowering Agents.

    Science.gov (United States)

    Mason, R Preston; Sherratt, Samuel C R; Jacob, Robert F

    2016-07-01

    Eicosapentaenoic acid (EPA) is a triglyceride-lowering agent that reduces circulating levels of the apolipoprotein B (apoB)-containing lipoprotein particles small dense low-density lipoprotein (sdLDL), very-low-density lipoprotein (VLDL), and oxidized low-density lipoprotein (LDL). These benefits may result from the direct antioxidant effects of EPA. To investigate this potential mechanism, these particles were isolated from human plasma, preincubated with EPA in the absence or presence of atorvastatin (active) metabolite, and subjected to copper-initiated oxidation. Lipid oxidation was measured as a function of thiobarbituric acid reactive substances formation. EPA inhibited sdLDL (IC50 ∼2.0 μM) and LDL oxidation (IC50 ∼2.5 μM) in a dose-dependent manner. Greater antioxidant potency was observed for EPA in VLDL. EPA inhibition was enhanced when combined with atorvastatin metabolite at low equimolar concentrations. Other triglyceride-lowering agents (fenofibrate, niacin, and gemfibrozil) and vitamin E did not significantly affect sdLDL, LDL, or VLDL oxidation compared with vehicle-treated controls. Docosahexaenoic acid was also found to inhibit oxidation in these particles but over a shorter time period than EPA. These data support recent clinical findings and suggest that EPA has direct antioxidant benefits in various apoB-containing subfractions that are more pronounced than those of other triglyceride-lowering agents and docosahexaenoic acid. PMID:26945158

  12. Nurse-administered propofol sedation for endoscopy

    DEFF Research Database (Denmark)

    Jensen, J T; Vilmann, P; Horsted, T;

    2011-01-01

    The aim of the present study was to perform a risk analysis during the implementation phase of nurse-administered propofol sedation (NAPS) and to validate our structured training program.......The aim of the present study was to perform a risk analysis during the implementation phase of nurse-administered propofol sedation (NAPS) and to validate our structured training program....

  13. 22 CFR 196.4 - Administering office.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Administering office. 196.4 Section 196.4 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL COMMERCIAL ARBITRATION THOMAS R. PICKERING FOREIGN AFFAIRS/GRADUATE FOREIGN AFFAIRS FELLOWSHIP PROGRAM § 196.4 Administering office. The Department of...

  14. Role of acid sphingomyelinase in the age-dependent dysregulation of sphingolipids turnover in the tissues of rats.

    Science.gov (United States)

    Babenko, Nataliya A; Garkavenko, Vladimir V; Storozhenko, Galina V; Timofiychuk, Olga A

    2016-04-01

    Old age-associated pathologies usually coincide with altered sphingolipid metabolism. In the present article, the role of acid sphingomyelinase (ASMase) in the age-dependent changes of sphingomyelin (SM) and ceramide contents in the tissues has been investigated by means of ASMase inhibitors, imipramine and zoledronic acid. It has been determined that ceramide content and ceramide/SM ratio increased, while SM level decreased in the heart, liver, blood serum and skeletal muscles of 24-month old rats in contrast to 3-month old animals. Injections of imipramine or zoledronic acid to 24-month old rats resulted in significant downregulation of ASMase in the liver and skeletal and heart muscles. The both inhibitors decreased the ceramide content and ceramide/SM ratio and increased the SM content in all tissues studied, except the heart, of old rats to the levels close to those observed in the young animals. Long-term treatment of rats by inhibitors, which have different mechanisms of action on ASMase, exerts the similar, but not equal effects on enzyme activity and SM turnover. In summary, the data above strongly suggest that the age-dependent up-regulation of ASMase plays an important role in the modulation of ceramide and SM contents in rat tissues and that imipramine and zoledronic acid are useful tools for SM turnover manipulation at old age. PMID:26830134

  15. Systemic effects of zoledronic acid in children with traumatic femoral head avascular necrosis and Legg-Calve-Perthes disease

    DEFF Research Database (Denmark)

    Johannesen, Jesper; Briody, Julie; McQuade, Mary; Little, David G; Cowell, Christopher T; Munns, Craig F

    2009-01-01

    normal children and adolescents with femoral head AVN. Material and methods: 37 children (age 10.8+/-2.76 years) diagnosed with avascular necrosis AVN (Slipped Capital Femoral Epiphysis (SCFE), N=20 or Legg-Calve-Perthes disease (LCPD), N=17) were treated with at least 12 months of ZA. Bone mineral...

  16. [Corrigendum] Cisplatin in combination with zoledronic acid: A synergistic effect in triple-negative breast cancer cell lines.

    Science.gov (United States)

    Ibrahim, Toni; Liverani, Chiara; Mercatali, Laura; Sacanna, Emanuele; Zanoni, Michele; Fabbri, Francesco; Zoli, Wainer; Amadori, Dino

    2016-09-01

    Following the publication of the above article, an interested reader drew an anomaly associated with the presentation of Fig. 7 to our attention. Essentially, the panel showing the Cis 0.001 data at T0 for the BRC-230 cell line was the same as that showing the Cis 0.01 data. After having re-examined our data, we realized that an error must have occurred when preparing Fig. 7. A duplication of the photo corresponding to BRC-230 Cis 0.001 T0 was incorrectly placed in the position corresponding to BRC-230 Cis 0.01 T0, while the correct BRC-230 Cis 0.01 T0 figure was erroneously positioned in the BRC-230 Cis 0.01 T1 slot. Fortunately, we had retained all of the data on our computer and were able to find the correct photos representing the conditions of BRC-230 Cis 0.01 T0 and T1. The findings and conclusions of this paper are still supported by our experimental data and are not affected by this error. We sincerely apologize for this oversight and thank the reader for drawing this matter to our attention. We regret any inconvenience caused by our mistake. [the original article was published in the International Journal of Oncology 42: 1263-1270, 2013; DOI: 10.3892/ijo.2013.1809]. PMID:27573164

  17. 唑来膦酸钠应用近期安全性观察%The observation of short-term safety of zoledronic sodium application

    Institute of Scientific and Technical Information of China (English)

    袁元杏; 李青; 张非; 赵成毅; 梅治; 张爱明; 姚海燕

    2012-01-01

    目的 了解唑来膦酸钠用药后的近期副反应.方法 自2009年11月至2012年2月对156例骨质疏松症患者应用唑来膦酸钠治疗,观察患者自用药1个月以来的临床表现,重点包括疼痛、发热及其他不良事件.同期观察因脊柱骨折行椎体成形术而未应用唑来膦酸钠治疗的患者107例,比较两组相应事件发生的差异.结果 本组患者全部得到随访,结果显示唑来膦酸钠组疼痛发生率17.3%,发热发生率12.8%,对照组疼痛发生率1.87%,发热发生率0.93%,两组差异有显著性(P < 0.001).另外唑来膦酸钠组出现1例皮肤过敏,1例心肌缺血、心绞痛.1例多发性骨髓瘤病情加重.1例出现肺炎呼吸衰竭死亡.结论 唑来膦酸钠在骨质疏松症治疗的应用中,有疼痛加重、发热等副反应,甚至可能有致皮肤过敏,心绞痛、多发性骨髓瘤病情加重、肺炎呼吸衰竭等不良事件,建议在用药当天密切监护下使用,并加强用药后2 w内的随访.%Objective To investigate the short-term side effects after the medication of zoledronic sodium. Methods One hundred and fifty-six osteoporosis patients from November 2009 to February 2012 were treated with zoledronic sodium. Clinical manifestations were observed in patients within 1 month after the medication, including pain, fever, and other adverse events. One hundred and seven patients with spinal fractures treated with vertebroplasty but without the medication of zoledronic sodium were observed simultaneously. The difference of the incidence of side effects between the two groups was compared . Results All the patients were followed up. The results revealed that in zoledronic sodium group , the incidence of pain and fever was 17. 3% and 12. 8% , respectively. In control group, the incidence of pain and fever was 1. 87% and 0. 93% , respectively. The difference between the two groups was significant (P < 0. 001). In addition, in zoledronic sodium group , one patient with

  18. Best Practices for Administering Concept Inventories

    CERN Document Server

    Madsen, Adrian; Sayre, Eleanor C

    2014-01-01

    There are a plethora of concept inventories in physics available for faculty to use, but it is not always clear exactly why you would use these tests, or how you should administer them and interpret the results. These multiple-choice research-based tests about physics concepts are valuable because they allow for standardized comparisons among institutions, instructors, or over time. In order for these comparisons to be meaningful, you should use best practices for administering the tests. Here we discuss best practices for administering concept inventories including background on these types of tests and specifics of how to give them online or in-class. We also discuss advantages and disadvantages of different incentives you could give your students, interpretation of scores and common concerns you may have about using concept inventories.

  19. Nurse-administered propofol sedation for endoscopy

    DEFF Research Database (Denmark)

    Jensen, J T; Vilmann, P; Horsted, T;

    2011-01-01

    endoscopists and for endoscopy nurses who were administering propofol sedation. The nurses' program comprised a 6-week course including theoretical and practical training in airway management, and the endoscopists' program consisted of 2.5 h of theory and a short course in practical airway management. In the......BACKGROUND AND STUDY AIMS: The aim of the present study was to perform a risk analysis during the implementation phase of nurse-administered propofol sedation (NAPS) and to validate our structured training program. PATIENTS AND METHODS: A structured training program was developed both for...

  20. Administering the Labor Agreement. Manager Development Series.

    Science.gov (United States)

    Department of the Army, Washington, DC.

    Prepared under the direction of Headquarters, Department of the Army with the aid of subject matter specialists and technicians, this guide was designed to facilitate the preparation for and presentation of a course in administering local labor agreements. The five sessions, intended for first-line supervisors involved in day-to-day administration…

  1. Hepatocellular carcinoma cell sensitivity to Vγ9Vδ2 T lymphocyte-mediated killing is increased by zoledronate.

    Science.gov (United States)

    Sugai, Shiori; Yoshikawa, Toshiaki; Iwama, Tatsuaki; Tsuchiya, Nobuhiro; Ueda, Norihiro; Fujinami, Norihiro; Shimomura, Manami; Zhang, Rong; Kaneko, Shin; Uemura, Yasushi; Nakatsura, Tetsuya

    2016-05-01

    The limited efficacy of vaccines in hepatocellular carcinoma (HCC), due to the low frequency of tumor-infiltrating cytotoxic T lymphocytes (CTLs), indicates the importance of innate immune surveillance, which assists acquired immunity by directly recognizing and eliminating HCC. Innate Vγ9Vδ2 T cells have major histocompatibility complex-unrestricted antitumor activity and are activated by phosphoantigens, which are upregulated in cancer cells by the nitrogen-containing bisphosphonate, zoledronate (Zol). A better understanding of HCC susceptibility to Zol and downstream γδ T cell-mediated killing is essential to optimize γδ T cell-mediated immunotherapy. This study systematically examined the interactions between γδ T cells and Zol-treated HCC cell lines (HepG2, HLE, HLF, HuH-1, JHH5, JHH7, and Li-7) in vitro. All HCC cell lines expressed the DNAX accessory molecule-1 ligands, poliovirus receptor, and Nectin-2, and γδ T cell-mediated killing of these cells was significantly enhanced by Zol. Small interfering RNA-mediated knockdown of these ligands did not affect the susceptibility to γδ T cell lysis. This killing activity was partly inhibited by mevastatin, an inhibitor of the mevalonate pathway, and markedly reduced by a monoclonal antibody to γ- and δ-chain T cell receptor, indicating that this is crucial for Zol-induced HCC killing. In addition, Zol-treated HCC cell lines triggered γδ T cell proliferation and induced production of Th1 and Th2, but not Th17, cytokines. The Zol concentration that enhanced HCC cell susceptibility to γδ T cell killing was lower than that required to directly inhibit HCC proliferation. Thus, γδ T cells may be important effector cells in the presence of Zol, especially where there are insufficient number of cancer antigen-specific CTLs to eliminate HCC. Our in vitro data support the proposal that Zol-treatment, combined with adaptive γδ T cell immunotherapy, may provide a feasible and effective

  2. Bioavailability of rectally administered carbamazepine mixture.

    OpenAIRE

    Neuvonen, P J; Tokola, O.

    1987-01-01

    The relative bioavailability of carbamazepine mixture was studied after oral and rectal administration to healthy subjects. The absorption was significantly slower after the rectal than after the oral route but the total bioavailability was similar provided the mixture was not defaecated within 2 h of administration. We conclude that carbamazepine can be administered rectally, e.g. to postoperative patients in doses corresponding with oral doses.

  3. Patient biodistribution of intraperitoneally administered yttrium-90-labeled antibody.

    Science.gov (United States)

    Hnatowich, D J; Chinol, M; Siebecker, D A; Gionet, M; Griffin, T; Doherty, P W; Hunter, R; Kase, K R

    1988-08-01

    Although 90Y is one of the best radionuclides for radioimmunotherapeutic applications, the lack of gamma rays in its decay complicates the estimation of radiation dose since its biodistribution cannot be accurately determined by external imaging. A limited clinical trial has been conducted with tracer doses (1 mCi) of 90Y in five patients who then received second-look surgery such that tissue samples were obtained for accurate radioactivity quantitation by in vitro counting. The anti-ovarian antibody OC-125 as the F(ab')2 fragment was coupled with diethylenetriaminepentaacetic acid, radiolabeled with 90Y and administered intraperitoneally to patients with suspected or documented ovarian cancer. Size exclusion and ion exchange high performance liquid chromatography analysis of patient ascitic fluid and serum samples showed no evidence of radiolabel instability although a high molecular weight species (presumably immune complex) was observed in three patients. Total urinary excretion of radioactivity prior to surgery averaged 7% of the administered radioactivity while at surgery the mean organ accumulation was 8% of the administered radioactivity in serum, 10% in liver, 7% in bone marrow, and 19% in bone with large patient to patient variation. The mean tumor/normal tissue radioactivity ratio varied between 3 and 25. On the assumption that the above radioactivity levels were achieved immediately following administration, that the radioactivity remained in situ until decayed and that the dimensions of tumor were sufficient to completely attenuate the emissions of 90Y, the dose to tumor for a 1-mCi administration would be approximately 50 rad with normal tissues receiving approximately 8 rad. PMID:3404257

  4. Distribution of rare earths in liver of mice administered with chloride compounds of 12 rare earths

    International Nuclear Information System (INIS)

    Full text: Rare earths are used in high technology field, however, the information on their biological effects are not sufficient. The behaviour of rare earths in biology is of interest in connection with their toxicity. In the present study, the distribution of rare earths in liver of mice administered with these elements was investigated. The effects on Ca and other biological essential elements were also determined. Male mice (5 weeks old) were injected with one of 12 kinds of rare earths (chlorides of Y, La, Ce, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er and Yb) at the dose of 25 mg/KXg body weight. After 20 hours of administration, mice were sacrificed, then liver and other organs were taken out. Liver was homogenized and separated by centrifugation. The concentrations of rare earths administered were measured by microwave-induced plasma-mass spectrometry (MIP-MS) after acid digestion. The concentrations of administered elements in whole liver were about 100μg/g (wet weight), where the difference between elements was few. Distribution amounts of elements administered in four fractions were following order; 700μg precipitate > mitocondrial fraction > microsomal fraction > cytosol. The relative contents in these fractions, however, was different depending on the element administered. Calcium concentrations in liver of administered mice were higher than those of control mice. Increase of Ca concentrations were observed in all four fractions and the increase ratio was also dependent on the elements administered

  5. The radiation dosimetry of intrathecally administered radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Stabin, M.G. [Oak Ridge Inst. for Science and Education, TN (United States); Evans, J.F. [Ohio State Univ., Columbus, OH (United States)

    1999-01-01

    The radiation dose to the spine, spinal cord, marrow, and other organs of the body from intrathecal administration of several radiopharmaceuticals was studied. Anatomic models were developed for the spine, spinal cerebrospinal fluid (CSF), spinal cord, spinal skeleton, cranial skeleton, and cranial CSF. A kinetic model for the transport of CSF was used to determine residence times in the CSF; material leaving the CSF was thereafter assumed to enter the bloodstream and follow the kinetics of the radiopharmaceutical as if intravenously administered. The radiation transport codes MCNP and ALGAMP were used to model the electron and photon transport and energy deposition. The dosimetry of Tc-99m DTPA and HSA, In-111 DTPA, I-131 HSA, and Yb-169 DTPA was studied. Radiation dose profiles for the spinal cord and marrow in the spine were developed and average doses to all other organs were estimated, including dose distributions within the bone and marrow.

  6. Tumour targeting with systemically administered bacteria.

    LENUS (Irish Health Repository)

    Morrissey, David

    2012-01-31

    Challenges for oncology practitioners and researchers include specific treatment and detection of tumours. The ideal anti-cancer therapy would selectively eradicate tumour cells, whilst minimising side effects to normal tissue. Bacteria have emerged as biological gene vectors with natural tumour specificity, capable of homing to tumours and replicating locally to high levels when systemically administered. This property enables targeting of both the primary tumour and secondary metastases. In the case of invasive pathogenic species, this targeting strategy can be used to deliver genes intracellularly for tumour cell expression, while non-invasive species transformed with plasmids suitable for bacterial expression of heterologous genes can secrete therapeutic proteins locally within the tumour environment (cell therapy approach). Many bacterial genera have been demonstrated to localise to and replicate to high levels within tumour tissue when intravenously (IV) administered in rodent models and reporter gene tagging of bacteria has permitted real-time visualisation of this phenomenon. Live imaging of tumour colonising bacteria also presents diagnostic potential for this approach. The nature of tumour selective bacterial colonisation appears to be tumour origin- and bacterial species- independent. While originally a correlation was drawn between anaerobic bacterial colonisation and the hypoxic nature of solid tumours, it is recently becoming apparent that other elements of the unique microenvironment within solid tumours, including aberrant neovasculature and local immune suppression, may be responsible. Here, we consider the pre-clinical data supporting the use of bacteria as a tumour-targeting tool, recent advances in the area, and future work required to develop it into a beneficial clinical tool.

  7. The effect of orally administered ranitidine and once-daily or twice-daily orally administered omeprazole on intragastric pH in cats

    OpenAIRE

    Šutalo, S; Ruetten, M.; Hartnack, S; Reusch, C E; Kook, P H

    2015-01-01

    BACKGROUND: Gastric acid suppressants frequently are used in cats with acid-related gastric disorders. However, it is not known if these drugs effectively increase intragastric pH in cats. OBJECTIVES: To examine the effects of PO administered ranitidine and omeprazole on intragastric pH in cats and to compare the efficacy of once-daily versus twice-daily dosage regimens for omeprazole. ANIMALS: Eight domestic shorthair cats. METHODS: Using a randomized 4-way cross-over design, cats were g...

  8. Who should administer awards, and how?

    International Nuclear Information System (INIS)

    This paper examines the problems related to the administration of compensation awards following a nuclear accident, and suggests ways in which these problems could be addressed. The author first describes the existing legislation in Switzerland governing nuclear third party liability and its financial guarantee, namely the 1983 Act on Nuclear Third Party Liability and its Implementing Ordinance. He then provides an outline of the principles underlying the administration of compensation in Switzerland, describing in particular issues related to the information of the public, the organisation of a first estimate of damage three months after the incident, and the procedure applicable to accidents of catastrophic proportions, including the drafting of special legislation to govern the indemnization regime. The author further notes that in the context of the international third party liability regime, the Paris Convention does not regulate the administration of claims in detail, but rather refers to the national legislation of the accident state to determine such measures (Article 11). It does provide, however, that the distribution of compensation should be equitable in nature. The Vienna Convention contains similar provisions, although its Amending Protocol provides in certain cases for a priority system in favour of victims who have lost their lives or suffered personal injury. He points out that although Switzerland is not a Party to either of these Conventions, it has concluded a reciprocal agreement with Germany in this field, in light of the similarities in their national legislation. The author concludes by expressing his agreement with the approach taken by the Swiss legislator in avoiding the adoption of detailed regulations governing the administration of awards in advance. He notes that a case-by-case approach in response to the particular circumstances of a nuclear accident provides those responsible with the flexibility necessary to administer compensation

  9. Who Should Administer Energy-Efficiency Programs?

    Energy Technology Data Exchange (ETDEWEB)

    Blumstein, Carl; Goldman, Charles; Barbose, Galen L.

    2003-05-01

    The restructuring of the electric utility industry in the US created a crisis in the administration of ratepayer-funded energy-efficiency programs. Before restructuring, nearly all energy-efficiency programs in the US were administered by utilities and funded from utility rates. Restructuring called these arrangements into question in two ways. First, the separation of generation from transmission and distribution undermined a key rationale for utility administration. This was the Integrated Resource Planning approach in which the vertically integrated utility was given incentives to provide energy services at least cost. Second, questions were raised as to whether funding through utility rates could be sustained in a competitive environment and most states that restructured their electricity industry adopted a system benefits charge. The crisis in administration of energy-efficiency programs produced a variety of responses in the eight years since restructuring in the US began in earn est. These responses have included new rationales for energy-efficiency programs, new mechanisms for funding programs, and new mechanisms for program administration and governance. This paper focuses on issues related to program administration. It describes the administrative functions and some of the options for accomplishing them. Then it discusses criteria for choosing among the options. Examples are given that highlight some of the states that have made successful transitions to new governance and/or administration structures. Attention is also given to California where large-scale energy-efficiency programs have continued to operate, despite the fact that many of the key governance/administration issues remain unresolved. The conclusion attempts to summarize lessons learned.

  10. The Effect of Interferon-γ and Zoledronate Treatment on Alpha-Tricalcium Phosphate/Collagen Sponge-Mediated Bone-Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Peiqi Li

    2015-10-01

    Full Text Available Inflammatory responses are frequently associated with the expression of inflammatory cytokines and severe osteoclastogenesis, which significantly affect the efficacy of biomaterials. Recent findings have suggested that interferon (IFN-γ and zoledronate (Zol are effective inhibitors of osteoclastogenesis. However, little is known regarding the utility of IFN-γ and Zol in bone tissue engineering. In this study, we generated rat models by generating critically sized defects in calvarias implanted with an alpha-tricalcium phosphate/collagen sponge (α-TCP/CS. At four weeks post-implantation, the rats were divided into IFN-γ, Zol, and control (no treatment groups. Compared with the control group, the IFN-γ and Zol groups showed remarkable attenuation of severe osteoclastogenesis, leading to a significant enhancement in bone mass. Histomorphometric data and mRNA expression patterns in IFN-γ and Zol-injected rats reflected high bone-turnover with increased bone formation, a reduction in osteoclast numbers, and tumor necrosis factor-α expression. Our results demonstrated that the administration of IFN-γ and Zol enhanced bone regeneration of α-TCP/CS implants by enhancing bone formation, while hampering excess bone resorption.

  11. Noninvasive Imaging of Administered Progenitor Cells

    Energy Technology Data Exchange (ETDEWEB)

    Steven R Bergmann, M.D., Ph.D.

    2012-12-03

    -99% pure population of leukocytes. Viability was assessed using Trypan blue histological analysis. We successfully isolated and labeled ~25-30 x 10{sup 7} CD34+ lymphocytes in cytokine mobilized progenitor cell apharesis harvests. Cells were also subjected to a stat gram stain to look for bacterial contamination, stat endotoxin LAL to look for endotoxin contamination, flow cytometry for evaluation of the purity of the cells and 14-day sterility culture. Colony forming assays confirm the capacity of these cells to proliferate and function ex-vivo with CFU-GM values of 26 colonies/ 1 x 10{sup 4} cells plated and 97% viability in cytokine augmented methylcellulose at 10-14 days in CO{sub 2} incubation. We developed a closed-processing system for the product labeling prior to infusion to maintain autologous cell integrity and sterility. Release criteria for the labeled product were documented for viability, cell count and differential, and measured radiolabel. We were successful in labeling the cells with up to 500 uCi/10{sup 8} cells, with viability of >98%. However, due to delays in getting the protocol approved by the FDA, the cells were not infused in humans in this location (although we did successfully use CD34+ cells in humans in a study in Australia). The approach developed should permit labeling of progenitor cells that can be administered to human subjects for tracking. The labeling approach should be useful for all progenitor cell types, although this would need to be verified since different cell lines may have differential radiosensitivity.

  12. [What lipid emulsion should be administered to ICU patients?].

    Science.gov (United States)

    Kreymann, G

    2014-01-01

    The review deals with a question what lipid emulsion should be administered to ICU patients according to recently published official parenteral and enteral nutrition guidelines. Classic lipid emulsions based on omega-6 fatty acids are immunosuppressive and should not be used with ICU patients. The olive/soy emulsion is immunoneutral and can be used for most patients. Many ICU patients are in an inflammatory state (e.g. sepsis, ARDS, pancreatitis). A common belief is that this "hyperinflammed patient population" would profit from an anti-inflammatory lipid component of their parenteral nutrition solution, such as fish oil. On the other hand, every anti-inflammatory therapy has the disadvantage of also being immunosuppressive. Inflammation is a necessary part of the host defense against infection and any correct anti-inflammatory medication presupposes the exact immunologic knowledge that there is too much inflammation for a given situation. This "too much" is certainly not fulfilled in every patient with sepsis, ARDS or pancreatitis. At the bedside it is nearly impossible to determine the degree of "hyper" inflammation. In reality, a number of these patients may be adequately inflamed or, in fact, even hypoinflammed. Specific emulsions which can be used in hyper- or hypoinflammation should be developed in the future. As long as these difficulties in the immunologic diagnosis prevail, the clinician might be best advised to use an immunoneutral lipid emulsion when choosing a lipid preparation for the ICU patients. PMID:25306684

  13. Pharmacokinetics of Three Benzimidazoles Suspended in Oleic Acid,Soybean Oil or 1% Tragacanth,and Administered Orally to Mice at A Single Dose%小鼠口服3种苯并咪唑类药物的油酸、大豆油和1%西黄耆胶混悬剂的药动学

    Institute of Scientific and Technical Information of China (English)

    姜斌; 张皓冰; 刘丛珊; 陶奕

    2012-01-01

    OBJECTIVE To determine the pharmacokinetics of three benzimidazoles ( albendazole, fenbendazole and fluben-dazole) suspended in three different media [oleic acid, soybean oil or 1% tragacanth (served as control) ] in mice, and observe the correlation of those pharmacokinetic parameters with the solubilities of the three benzimidazoles in corresponding medium. METHODS Albendazole, fenbendazole and flubendazole suspened in oleic acid, soybean oil or 1% tragacanth were prepared by ball grinding mill. Groups of 45 - 54 mice were administered orally with one of aforementioned benzimidazole suspensions at a single dose of 100 mg·kg-1 ( albendazole) or 50 mg·kg-1 (fenbendazole and flubendazole). Subgroups with 5-6 mice in each group were bled at varying intervals within 24 h. Plasma was then separated from heparin-anticoagulated blood, and evaluated for the presence of the drug by high performance liquid chromatography ( HPLC ). Pharmacokinetic parameters of each drug were calculated using DAS ( Drug AnaLyze System). RESULTS After oral administration of three benzimidazoles suspended in oleic acid, soybean oil or 1% tragacanth, the pharmacokinetic parameters of each drug were described as follows; albendazole, the MRT (average retention time) were (3. 91 ± 0.29), (3.70±0.09) and (1. 59 ± 0. 14) h, ρmax (maximum concentration) were (0.66±0.08), (0.29±0.05) and (0. 34±0. 09) mg·L-1 , AUC (area under the concentration-time curve) were (3. 19 ±0.40) , (1. 25 ±0.09) and (0. 50 ±0. 05) mg·L·h-1, F (relative bioavailability, the AUC compared with that of 1% tragacanth group) were 6. 38 and 2. 50; fenbendazole, the MRT were (5. 72 ±0. 14) , (4. 83 ±0.38) and (3. 85 ±0.25) h, ρmax were( 0. 70 ± 0. 11) , (0.20 ±0.05) and (0. 12 ±0.03) mg·L-1 , AUC were (5. 02 ±0.73) , (1.08 ±0.21) and (0.52 ±0.07) mg·h·L-1 , F were 9.65 and 2.08; flubendazole, the MRT were (5.71 ±0.37), (4.59±0.39) and (3. 34 ±0.20) h, pmax were (0.93 ±0. 14), (0.58 ±0.09) and (0

  14. 40 CFR 147.3000 - EPA-administered program.

    Science.gov (United States)

    2010-07-01

    ... administered by EPA. (The term “Indian lands” is defined at 40 CFR 144.3.) The Navajo Indian lands are in the... Utah. This program consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program....

  15. Methods of administering oral formulations and child acceptability

    NARCIS (Netherlands)

    van Riet-Nales, Diana A; Ferreira, José A; Schobben, Alfred F A M; de Neef, Barbara J; Egberts, Toine C G; Rademaker, Carin M A

    2015-01-01

    INTRODUCTION: Children may be unable or unwilling to swallow medicines. In order to avoid or accommodate any such problems, parents may decide to administer medicines other than intended. The aim of this study was to investigate how parents administered four oral placebo formulations to infants and

  16. Methods of administering oral formulations and child acceptability

    NARCIS (Netherlands)

    Van Riet-Nales, Diana A.; Ferreira, José A.; Schobben, Alfred F A M; De Neef, Barbara J.; Egberts, Toine C G; Rademaker, Carin M A

    2015-01-01

    Abstract Introduction Children may be unable or unwilling to swallow medicines. In order to avoid or accommodate any such problems, parents may decide to administer medicines other than intended. The aim of this study was to investigate how parents administered four oral placebo formulations to infa

  17. Lymphatic fat absorption varies among rats administered dairy products differing in physiochemical properties

    DEFF Research Database (Denmark)

    Fruekilde, Maj-Britt; Høy, Carl-Erik

    2004-01-01

    We examined in rats the intestinal absorption of fat from dairy products differing in physiochemical properties. Five dairy products (cream cheese, cream, sour cream, butter, and mixed butter) with minor differences in fatty acid composition were administered by gavage to rats, and lymphatic fat...... results demonstrated different lymphatic absorption patterns of fat from dairy products differing in physiochemical properties. Because the fatty acid composition of the dairy products differed only slightly, other factors such as viscosity, type of emulsion, particle size, and likely also protein content...

  18. The bioavailability of an orally administered medroxyprogesterone acetate suspension.

    Science.gov (United States)

    Antal, E J; Gillespie, W R; Albert, K S

    1983-05-01

    The relative bioavailability of an orally administered aqueous suspension of medroxyprogesterone acetate (MPA) intended for intramuscular injection (Depo-Provera) was determined in relation to orally administered tablets. Serum levels of MPA were determined by radioimmunoassay following the administration of 400-mg doses to 19 adult male volunteers in a crossover design after an overnight fast. The two treatments were judged bioequivalent based upon a comparison of the resultant MPA serum levels and the derived bioavailability parameters. Hence, the intramuscular suspension administered orally offers an alternative means of achieving optimal serum levels of MPA in patients requiring high dose therapy. PMID:6222996

  19. Local treatment of a bone graft by soaking in zoledronic acid inhibits bone resorption and bone formation. A bone chamber study in rats.

    OpenAIRE

    Belfrage Ola; Isaksson Hanna; Tägil Magnus

    2012-01-01

    ABSTRACT: BACKGROUND: Bone grafts are frequently used in orthopaedic surgery. Graft remodelling is advantageous but can occur too quickly, and premature bone resorption might lead to decreased mechanical integrity of the graft. Bisphosphonates delay osteoclastic bone resorption but may also impair formation of new bone. We hypothesize that these effects are dose dependent. In the present study we evaluate different ways of applying bisphosphonates locally to the graft in a bone...

  20. Findings from Survey Administered to Weatherization Training Centers

    Energy Technology Data Exchange (ETDEWEB)

    Conlon, Brian [Univ. of Tennessee, Knoxville, TN (United States); Tonn, Bruce Edward [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-03-01

    This report summarizes results of a survey administered to directors of weatherization training centers that receive funding from the U.S. Department of Energy. The survey presents results related to questions on training offered and future plans.

  1. Prophylactic Effect of Gossypin Against Percutaneously Administered Sulfur Mustard

    Institute of Scientific and Technical Information of China (English)

    ANSHOO GAUTAM; R.VIJAYARAGHAVAN

    2007-01-01

    Objective To evaluate the protective efficacy of gossypin(3,3',4',5,7,8-hexahydroxyflavone 8-glucoside)by administering it intraperitoneally,for dose,time,and vehicle dependent effects against sulphur mustard(SM),administered through percutaneous route in mice.Methods SM(diluted in PEG-300)was administered percutaneously.The protective efficacy of gossypin was evaluated by administering it intraperitoneally(50,100,200,and 400 mg/kg),in various vehicles (water,PEG-300 and DMSO),and time intervals(30 min prior,simultaneous and 2 h post).The time dependent protection of gossypin(200 mg/kg in PEG-300;i.p.)was also evaluated using selected biochemical variables(GSH,GSSG,MDA,total antioxidant status,Hb,WBC count,RBC count,glutathione peroxidase,glutathione reductase,and superoxide dismutase)and liver histology.The protection of gossypin by oral route was also evaluated against percutaneously administered SM.Results The protection against systemic toxicity of SM(LD50 8.1 mg/kg)was beRer when gossypin was given with PEG-300 (8.0 folds)than DMSO(5.7 folds).No protection was observed when gossypin was administered with water.Good protection (8.0 folds)was observed when gossypin was administered(200 mg/kg in PEG-300;i.p.)at 30 min prior or simultaneous to SM exposure,but no protection was observed when gossypin was administered 2 h post to SM exposure.A significant weight loss was observed 7 days after SM administration(2 LD50),with a significant increase in RBC and Hb.A significant decrease in total antioxidant status of plasma,liver GSH and GSSG levels,and in the activities of glutathione peroxidase,glutathione reductase and superoxide dismutase was also observed 7 days after SM administration.SM treated mouse liver also showed necrosis.A significant protection was observed when gossypin(200 mg/kg in PEG-300;i.p.)was administered either as a pretreatment(30 min before)or simultaneous treatment,and not as a post treatment(2 h).The protective efficacy of gossypin was better

  2. Comparison of quality of induction of anaesthesia between intramuscularly administered ketamine, intravenously administered ketamine and intravenously administered propofol in xylazine premedicated cats

    Directory of Open Access Journals (Sweden)

    T.B. Dzikiti

    2007-06-01

    Full Text Available The quality of induction of general anesthesia produced by ketamine and propofol, 2 of the most commonly used anaesthetic agents in cats, was assessed. Eighteen cats admitted for elective procedures were randomly assigned to 3 groups and then premedicated with xylazine 0.75 mg/kg intramuscularly before anaesthesia was induced with ketamine 15 mg/kg intramuscularly (KetIM group, ketamine 10 mg/kg intravenously (KetIV group or propofol 4 mg/kg intravenously (PropIV group. Quality of induction of general anaesthesia was determined by scoring ease of intubation, degree of struggling, and vocalisation during the induction period. The quality of induction of anaesthesia of intramuscularly administered ketamine was inferior to that of intravenously administered ketamine, while intravenously administered propofol showed little difference in quality of induction from ketamine administered by both the intramuscular and intravenous routes. There were no significant differences between groups in the ease of intubation scores, while vocalisation and struggling were more common in cats that received ketamine intramuscularly than in those that received intravenously administered ketamine or propofol for induction of anaesthesia. Laryngospasms occurred in 2 cats that received propofol. The heart rates and respiratory rates decreased after xylazine premedication and either remained the same or decreased further after induction for all 3 groups, but remained within normal acceptable limits. This study indicates that the 3 regimens are associated with acceptable induction characteristics, but administration of ketamine intravenously is superior to its administration intramuscularly and laryngeal desensitisation is recommended to avoid laryngospasms.

  3. Comparison of quality of induction of anaesthesia between intramuscularly administered ketamine, intravenously administered ketamine and intravenously administered propofol in xylazine premedicated cats.

    Science.gov (United States)

    Dzikiti, T B; Chanaiwa, S; Mponda, P; Sigauke, C; Dzikiti, L N

    2007-12-01

    The quality of induction of general anesthesia produced by ketamine and propofol, 2 of the most commonly used anaesthetic agents in cats, was assessed. Eighteen cats admitted for elective procedures were randomly assigned to 3 groups and then premedicated with xylazine 0.75 mg/kg intramuscularly before anaesthesia was induced with ketamine 15 mg/kg intramuscularly (KetIM group), ketamine 10 mg/kg intravenously (KetIV group) or propofol 4 mg/kg intravenously (PropIV group). Quality of induction of general anaesthesia was determined by scoring ease of intubation, degree of struggling, and vocalisation during the induction period. The quality of induction of anaesthesia of intramuscularly administered ketamine was inferior to that of intravenously administered ketamine, while intravenously administered propofol showed little difference in quality of induction from ketamine administered by both the intramuscular and intravenous routes. There were no significant differences between groups in the ease of intubation scores, while vocalisation and struggling were more common in cats that received ketamine intramuscularly than in those that received intravenously administered ketamine or propofol for induction of anaesthesia. Laryngospasms occurred in 2 cats that received propofol. The heart rates and respiratory rates decreased after xylazine premedication and either remained the same or decreased further after induction for all 3 groups, but remained within normal acceptable limits. This study indicates that the 3 regimens are associated with acceptable induction characteristics, but administration of ketamine intravenously is superior to its administration intramuscularly and laryngeal desensitisation is recommended to avoid laryngospasms. PMID:18507218

  4. Lymphatic fat absorption varies among rats administered dairy products differing in physiochemical properties

    DEFF Research Database (Denmark)

    Fruekilde, Maj-Britt; Høy, Carl-Erik

    2004-01-01

    We examined in rats the intestinal absorption of fat from dairy products differing in physiochemical properties. Five dairy products (cream cheese, cream, sour cream, butter, and mixed butter) with minor differences in fatty acid composition were administered by gavage to rats, and lymphatic fat...... absorption was examined. Absorption was followed for 8 h after administration of 300 mg fat from the dairy products. Administration of cream and sour cream resulted in faster lymphatic fat absorption than cream cheese, butter, and mixed butter, and at 8 h the accumulated absorption of fat was significantly...... higher. The lymphatic absorption of fat after cream cheese administration was similar to the absorption after butter and mixed butter administration up to the 4-h time point; then it increased to a level between that of rats administered cream or sour cream and butter or mixed butter. Overall, these...

  5. An Umbrella for Acid Rain.

    Science.gov (United States)

    Randal, Judith

    1979-01-01

    The Environmental Protection Agency has awarded several grants to study effects of and possible solutions to the problem of "acid rain"; pollution from atmospheric nitric and sulfuric acids. The research program is administered through North Carolina State University at Raleigh and will focus on biological effects of acid rain. (JMF)

  6. Safety and Efficacy Study of Intramuscularly Administered Sea buckthorn (Hippophae Rhamnoides L. Oil as Depot Formulation

    Directory of Open Access Journals (Sweden)

    ALI RASHID

    2011-06-01

    Full Text Available The present study was performed to assess the sub-chronic toxicity and efficacy study of seabuckthorn (Hippophae rhamnoides L oil administered intramuscularly in New Zealand white rabbits. Seabuckthorn oil was administered intramuscularly, at doses of 0.5, 1 and 1.5 ml/kg body weight in three groups of animals and the dose was scheduled once in a week up to seven weeks. Total antioxidant status was studied after the first intramuscular administration of oil that act as depot and provide sustained effect for prolong period of time. The clinical signs of toxicity data were collected and observed daily. No mortality was seen in any of the treatment groups during the course of study. Various physiological, hematological, biochemical (AST, ALT, ALP, Uric acid, Urea and creatinine as well as histopathological parameters were studied and found not to be changed significantly, indicating that intramuscular seabuckthorn oil is non toxic even at higher dose level in rabbits. The studies revealed significant increase (p<0.05 in total antioxidant activity in the serum sample with increase in doses. Overall safety and tolerability profile of seabuckthorn oil administered intramuscularly is proved good and does not appear to carry risk of serious adverse effects. The results obtained also indicates efficacy of oil in terms of total antioxidant capacity and may be used as a vehicle for sustained release formulations

  7. Orally administered DTPA penta-ethyl ester for the decorporation of inhaled (241)Am.

    Science.gov (United States)

    Sueda, Katsuhiko; Sadgrove, Matthew P; Huckle, James E; Leed, Marina G D; Weber, Waylon M; Doyle-Eisele, Melanie; Guilmette, Raymond A; Jay, Michael

    2014-05-01

    Diethylenetriaminepentaacetic acid (DTPA) is an effective decorporation agent to facilitate the elimination of radionuclides from the body, but its permeability-limited oral bioavailability limits its utility in mass-casualty emergencies. To overcome this limitation, a prodrug strategy using the penta-ethyl ester form of DTPA is under investigation. Pharmacokinetic and biodistribution studies were conducted in rats by orally administering [(14) C]DTPA penta-ethyl ester, and this prodrug and its hydrolysis products were analyzed as a single entity. Compared with a previous reporting of intravenously administered DTPA, the oral administration of this prodrug resulted in a sustained plasma concentration profile with higher plasma exposure and lower clearance. An assessment of the urine composition revealed that the bioactivation was extensive but incomplete, with no detectable levels of the penta- or tetra-ester forms. Tissue distribution at 12 h was limited, with approximately 73% of the administered dose being associated with the gastrointestinal tract. In the efficacy study, rats were exposed to aerosols of (241) Am nitrate before receiving a single oral treatment of the prodrug. The urinary excretion of (241) Am was found to be 19% higher than with the control. Consistent with prior reports of DTPA, the prodrug was most effective when the treatment delays were minimized. PMID:24619514

  8. 40 CFR 282.92 - Tennessee State-Administered Program.

    Science.gov (United States)

    2010-07-01

    ..., and 40 CFR part 281, subpart E. If Tennessee obtains approval for the revised requirements pursuant to... Storage Tanks, 4th Floor, L&C Tower, 401 Church Street, Nashville, Tennessee 37243-1541. (1) State... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Tennessee State-Administered...

  9. Distribution of intratracheally administered plutonium-239 within the skeleton bones

    International Nuclear Information System (INIS)

    The data are presented on distribution of the intratracheally administered plutonium-239 within the skeleton bones. Plutonium was found to be distributed non-uniformly within the skeleton: it was concentrated mainly in the bones where the trabecular fraction of the bone tissue was most manifest. The results obtained were supported by the correlation analysis

  10. PHARMACOKINETIC AND PHARMACODYNAMIC STUDIES ON VAGINALLY ADMINISTERED LEVONORGESTREL

    Institute of Scientific and Technical Information of China (English)

    HEChang-Hai; XUJian-Qiu; ZHUYue-Hua; SHIYong-En

    1989-01-01

    Comparative studies on pharmacokinetics of vaginally and orally administered levonorgestrel (LNG) tablet (Postinor) in one single dose containing 0,75mg LNG were performed. The pharmacokinetics of LNG and its effects on ovarian functions werealso studied after repeated vaginal administration.

  11. Efficacy and safety of intravenous fentanyl administered by ambulance personnel

    DEFF Research Database (Denmark)

    Friesgaard, Kristian Dahl; Nikolajsen, Lone; Giebner, Matthias;

    2016-01-01

    BACKGROUND: Management of pain in the pre-hospital setting is often inadequate. In 2011, ambulance personnel were authorized to administer intravenous fentanyl in the Central Denmark Region. The aim of this study was to evaluate the efficacy and safety of intravenous fentanyl administered by...... ambulance personnel. METHODS: Pre-hospital medical charts from 2348 adults treated with intravenous fentanyl by ambulance personnel during a 6-month period were reviewed. The primary outcome was the change in pain intensity on a numeric rating scale (NRS) from before fentanyl treatment to hospital arrival....... Secondary outcomes included the number of patients with reduction in pain intensity during transport (NRS ≥ 2), the number of patients with NRS > 3 at hospital arrival, and potential fentanyl-related side effects. RESULTS: Fentanyl reduced pain from before treatment (8, IQR 7-9) to hospital arrival (4, IQR...

  12. Pharmacokinetics of cefmetazole administered intramuscularly and intravenously to healthy adults.

    OpenAIRE

    Rodriguez-Barbero, J; Mariño, E L; Dominguez-Gil, A

    1985-01-01

    The pharmacokinetics of cefmetazole, a new parenteral cephalosporin, administered intravenously and intramuscularly at a dose of 30 mg/kg to two groups of seven healthy volunteers were studied. Concentrations in serum were monitored over 8 h by a high-pressure liquid chromatography technique. The plasma concentration-time data were statistically fitted to a biexponential equation for both administration routes, and the data were analyzed by a two- and one-compartment kinetic model, respective...

  13. Computer Administering of the Psychological Investigations: Set-relational Representation

    OpenAIRE

    Yordzhev, Krasimir; Peneva, Ivelina

    2012-01-01

    Computer administering of a psychological investigation is the computer representation of the entire procedure of psychological assessments - test construction, test implementation, results evaluation, storage and maintenance of the developed database, its statistical processing, analysis and interpretation. A mathematical description of psychological assessment with the aid of personality tests is discussed in this article. The set theory and the relational algebra are used in this descripti...

  14. Use of professionally administered topical fluorides in Asia

    OpenAIRE

    Tenuta, LMA; Fox, CH; Lo, ECM

    2012-01-01

    Professionally applied topical fluoride varnish, gel, and solution have been shown to be effective in preventing and in arresting dental caries. Their use in different countries in Asia varies greatly and may not correlate with the dental caries situation of the populations in the countries. In the higher-income countries, use of fluoride varnish and gel is common among dental professionals. In contrast, the use of professionally administered topical fluorides is not common in the lower-incom...

  15. The group administered interactive questionnaire: An alternative to individual interviews

    OpenAIRE

    Yerushalmi, Edit; Henderson, Charles R.; Mamudi, William; Singh, Chandralekha; Lin, Shih-Yin

    2016-01-01

    Individual interviews are often considered to be the gold standard for researchers to understand how people think about phenomena. However, conducting and analyzing interviews is very time consuming. This paper presents the Group Administered Interactive Questionnaire (GAIQ) as an alternative to individual interviews and discusses the pros and cons of each data collection method. Use of GAIQ will be discussed in the context of a study that seeks to understand teaching assistants' reasons for ...

  16. The group administered interactive questionnaire: An alternative to individual interviews

    CERN Document Server

    Yerushalmi, Edit; Mamudi, William; Singh, Chandralekha; Lin, Shih-Yin

    2016-01-01

    Individual interviews are often considered to be the gold standard for researchers to understand how people think about phenomena. However, conducting and analyzing interviews is very time consuming. This paper presents the Group Administered Interactive Questionnaire (GAIQ) as an alternative to individual interviews and discusses the pros and cons of each data collection method. Use of GAIQ will be discussed in the context of a study that seeks to understand teaching assistants' reasons for the design of problem solutions for introductory physics.

  17. Paradata: a new data source from web-administered measures.

    Science.gov (United States)

    Sowan, Azizeh K; Jenkins, Louise S

    2010-01-01

    Web administration of measures offers numerous advantages as well as some drawbacks; the efficiency of collecting data in this way is dramatic. An important by-product of Web administration of measures is the option of creating paradata that offer information about how respondents access a measure (server-side paradata) and navigate within the online environment (client-side paradata) to complete the measure. Paradata can play a critical role in developing and piloting measures as well as refining the measurement process. Uses of paradata in Web-administered measures include (1) informing the choice of response formats, (2) examining the extent of changing response options, (3) examining the extent of following a prescribed sequence in completing a measure, (4) tracking the response process, (5) aiding in designing a Web-administered measure and its layout, and (6) assisting in determining the most appropriate log-in procedure. Because of the potential value of this new type of useful data to researchers in nursing and health, this article focuses on paradata within the context of Web-administered measures. More specifically, the article focuses on the definition, generation, and uses of paradata, as well as the ethical issues and other concerns in obtaining and using paradata. Uses of paradata to test the usability of information systems used in nursing and health practices are also included. PMID:20978403

  18. A randomized controlled trial to compare the efficacy of bisphosphonates in the management of painful bone metastasis

    Directory of Open Access Journals (Sweden)

    Krishnangshu Bhanja Choudhury

    2011-01-01

    Conclusion: The use of bisphosphonates for 6 months or more results in a statistical significant improvement in bone pain, more so with zoledronic acid. Hypercalcemia, an SRE, was significantly less in the zoledronic acid arm.

  19. A parent-administered program to reduce children's television viewing

    OpenAIRE

    Wolfe, David A.; Mendes, Maria G.; Factor, David

    1984-01-01

    A parent-administered program to reduce television viewing of primary school-aged children was tested on two boys and three girls from three different families who were heavy viewers of television. Children were given 20 unearned tokens each week by their parents, which they could exchange for up to 10 hours of viewing time. The child earned a gold token for viewing in accordance with the rules for 4 consecutive weeks, which was exchanged for a reward. Parents were given instructions to follo...

  20. Prototype of a glass to administer liquid to newborns

    Directory of Open Access Journals (Sweden)

    Suzana Lopes de Melo

    2014-09-01

    Full Text Available The aim of this study was to describe the evaluation of health professionals about a prototype glass to administer liquids to newborns. It was a descriptive, exploratory study, which was carried out at the maternity of a university hospital, in Uberaba, MG, Brazil. Semi-structured questionnaires were applied to 75 health professionals, after administering a glass of milk to newborns, in the months of July and August, 2011. Quantitative data were analyzed descriptively and subjected to qualitative content analysis, three categories emerged: positive aspects, with 269 of the register units; negative aspects, with 11 units and suggestions to improve the glass, with six. Statistical analysis showed that the concepts ‘good’ and ‘excellent’, related to the prototype glass, presented rates over 90%. The perception of the participants demonstrated a positive evaluation of the prototype glass, which proved to be a practical tool, the design and safe material for the execution of the ‘technique of the little glass’.

  1. Administering truncated receive functions in a parallel messaging interface

    Energy Technology Data Exchange (ETDEWEB)

    Archer, Charles J; Blocksome, Michael A; Ratterman, Joseph D; Smith, Brian E

    2014-12-09

    Administering truncated receive functions in a parallel messaging interface (`PMI`) of a parallel computer comprising a plurality of compute nodes coupled for data communications through the PMI and through a data communications network, including: sending, through the PMI on a source compute node, a quantity of data from the source compute node to a destination compute node; specifying, by an application on the destination compute node, a portion of the quantity of data to be received by the application on the destination compute node and a portion of the quantity of data to be discarded; receiving, by the PMI on the destination compute node, all of the quantity of data; providing, by the PMI on the destination compute node to the application on the destination compute node, only the portion of the quantity of data to be received by the application; and discarding, by the PMI on the destination compute node, the portion of the quantity of data to be discarded.

  2. [Spontaneous reporting system data analysis of parenterally administered Shenmai].

    Science.gov (United States)

    Wang, Lian-Xin; Xiang, Yong-Yang; Xie, Yan-Ming; Shen, Hao; Ai, Qing-Hua

    2013-09-01

    Spontaneous reporting system (SRS) datais currently an important source of monitoring and finding ADRs signals throughout the world. This method can promptly and effectively discover ADR signals, thus preventing and avoiding ADRs effectively. Parenterally administered Shenmai has the functions of benefiting vital energy, nourishing Yin and generating body fluids, and activating the pulse. Clinically it is used in various diseases including shock, coronary heart disease, viral myocarditis, chronic pulmonary heart disease, and granulocytopenia. The large, national SRS database of ADRs needs effective evaluation methods. We report on the use of Bayesian confidence propagation neural network method (BCPNN) and proportional reporting ration (PRR) with propensity score to control for confounding variables. Early warning signs of an ADR are, a feeling of suffocation (difficulty exhaling), anaphylactoid reactions and flushing. Furthermore, relevant relationships between the different factors is analysed by association rules (AR). It is found that there is a close relationship between past history of ADRs, a family history of ADRs and itching. PMID:24471317

  3. Interactions of conjugate vaccines and co-administered vaccines.

    Science.gov (United States)

    Findlow, H; Borrow, R

    2016-01-01

    Conjugate vaccines play an important role in the prevention of infectious diseases such as those caused by the bacteria Haemophilus influenzae (Hi) type b (Hib), Neisseria meningitidis, and Streptococcus pneumoniae. Vaccines developed against these 3 pathogens utilize 3 main carrier proteins, non-toxic mutant of diphtheria toxin (CRM197), diphtheria toxoid (DT) and tetanus toxoid (TT). Current pediatric immunisation schedules include the administration of several vaccines simultaneously, therefore increasing the potential for immune interference (both positively and negatively) to the antigens administered. Knowledge of vaccine interactions is principally derived from clinical trials, these are reviewed here to explore immune interference which may result of from carrier-specific T-cell helper interactions, bystander interference and carrier induced epitopic suppression. PMID:26619353

  4. Registered nurse-administered sedation for gastrointestinalendoscopic procedure

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    The rising use of nonanesthesiologist-administeredsedation for gastrointestinal endoscopy has clinicalsignificances. Most endoscopic patients require someforms of sedation and/or anesthesia. The goals ofthis sedation are to guard the patient's safety, minimizephysical discomfort, to control behavior and todiminish psychological responses. Generally, moderatesedation for these procedures has been offered by thenon-anesthesiologist by using benzodiazepines and/oropioids. Anesthesiologists and non-anesthesiologistpersonnel will need to work together for these challengesand for safety of the patients. The sedationtraining courses including clinical skills and knowledgeare necessary for the registered nurses to facilitate thepatient safety and the successful procedure. However,appropriate patient selection and preparation, adequatemonitoring and regular training will ensure that the useof nurse-administered sedation is a feasible and safetechnique for gastrointestinal endoscopic procedures.

  5. Moderate and deep nurse-administered propofol sedation is safe

    DEFF Research Database (Denmark)

    Jensen, Jeppe Thue; Møller, Ann; Hornslet, Pernille; Konge, Lars; Vilmann, Peter

    2015-01-01

    INTRODUCTION: Non-anaesthesiologist-administered propofol sedation (NAPS/NAAP) is increasingly used in many countries. Most regimens aim for light or moderate sedation. Little evidence on safety of deep NAPS sedation is available. The aim of this study was to explore the safety of intermittent deep...... propofol dose was 331.6 mg (standard deviation = 179.4 mg). The overall rate of hypoxia was 3.2%, and the rate ofhypotension was 3.1%. Assisted ventilation was needed in 0.5%. Age (p < 0.001), American Society of Anesthesiologists (ASA) class 3 (p = 0.017) and total propofol dose (p = 0.001) were...... associated with a higher rate of adverse events. CONCLUSION: Safety during intermittent deep sedation with NAPS was good. Age, ASA class 3 and total propofol dose were correlated with a higher rate of adverse events. Patients aged 60 years or more needed more handling during adverse events. FUNDING: Arvid...

  6. Moderate and deep nurse-administered propofol sedation is safe

    DEFF Research Database (Denmark)

    Jensen, Jeppe Thue; Møller, Ann; Hornslet, Pernille; Konge, Lars; Vilmann, Peter

    2015-01-01

    INTRODUCTION: Non-anaesthesiologist-administered propofol sedation (NAPS/NAAP) is increasingly used in many countries. Most regimens aim for light or moderate sedation. Little evidence on safety of deep NAPS sedation is available. The aim of this study was to explore the safety of intermittent deep...... propofol dose was 331.6 mg (standard deviation = 179.4 mg). The overall rate of hypoxia was 3.2%, and the rate of hypotension was 3.1%. Assisted ventilation was needed in 0.5%. Age (p < 0.001), American Society of Anesthesiologists (ASA) class 3 (p = 0.017) and total propofol dose (p = 0.001) were...... associated with a higher rate of adverse events. CONCLUSION: Safety during intermittent deep sedation with NAPS was good. Age, ASA class 3 and total propofol dose were correlated with a higher rate of adverse events. Patients aged 60 years or more needed more handling during adverse events. FUNDING: Arvid...

  7. Orally administered nicotine induces urothelial hyperplasia in rats and mice

    International Nuclear Information System (INIS)

    Highlights: • Rats and mice orally administered with nicotine tartrate for total of 4 weeks. • No treatment-related death or whole body toxicity observed in any of the groups. • Urothelium showed simple hyperplasia in treated rats and mice. • No significant change in BrdU labeling index or SEM classification of urothelium. - Abstract: Tobacco smoking is a major risk factor for multiple human cancers including urinary bladder carcinoma. Tobacco smoke is a complex mixture containing chemicals that are known carcinogens in humans and/or animals. Aromatic amines a major class of DNA-reactive carcinogens in cigarette smoke, are not present at sufficiently high levels to fully explain the incidence of bladder cancer in cigarette smokers. Other agents in tobacco smoke could be excreted in urine and enhance the carcinogenic process by increasing urothelial cell proliferation. Nicotine is one such major component, as it has been shown to induce cell proliferation in multiple cell types in vitro. However, in vivo evidence specifically for the urothelium is lacking. We previously showed that cigarette smoke induces increased urothelial cell proliferation in mice. In the present study, urothelial proliferative and cytotoxic effects were examined after nicotine treatment in mice and rats. Nicotine hydrogen tartrate was administered in drinking water to rats (52 ppm nicotine) and mice (514 ppm nicotine) for 4 weeks and urothelial changes were evaluated. Histopathologically, 7/10 rats and 4/10 mice showed simple hyperplasia following nicotine treatment compared to none in the controls. Rats had an increased mean BrdU labeling index compared to controls, although it was not statistically significantly elevated in either species. Scanning electron microscopic visualization of the urothelium did not reveal significant cytotoxicity. These findings suggest that oral nicotine administration induced urothelial hyperplasia (increased cell proliferation), possibly due to a

  8. Balanced propofol sedation administered by nonanesthesiologists: The first Italian experience

    Institute of Scientific and Technical Information of China (English)

    Alessandro Repici; Eva Vitetta; Daniel de Paula Pessoa Ferreira; Silvio Danese; Massimo Arosio; Alberto Malesci; Nico Pagano; Cesare Hassan; Alessandra Carlino; Giacomo Rando; Giuseppe Strangio; Fabio Romeo; Angelo Zullo; Elisa Ferrara

    2011-01-01

    AIM: To assess the efficacy and safety of a balanced approach using midazolam in combination with propofol, administered by non-anesthesiologists, in a large series of diagnostic colonoscopies.METHODS: Consecutive patients undergoing diagnostic colonoscopy were sedated with a single dose of midazolam (0.05 mg/kg) and low-dose propofol (starter bolus of 0.5 mg/kg and repeated boluses of 10 to 20 mg). Induction time and deepest level of sedation, adverse and serious adverse events, as well as recovery times, were prospectively assessed. Cecal intubation and adenoma detection rates were also collected.RESULTS: Overall, 1593 eligible patients were included. The median dose of propofol administered was 70 mg (range: 40-120 mg), and the median dose of midazolam was 2.3 mg (range: 2-4 mg). Median induction time of sedation was 3 min (range: 1-4 min), and median recovery time was 23 min (range: 10-40 min). A moderate level of sedation was achieved in 1561 (98%) patients, whilst a deep sedation occurred in 32 (2%) cases. Transient oxygen desaturation requiring further oxygen supplementation occurred in 8 (0.46%; 95% CI: 0.2%-0.8%) patients. No serious adverse event was observed. Cecal intubation and adenoma detection rates were 93.5% and 23.4% (27.8% for male and 18.5% for female, subjects), respectively.CONCLUSION: A balanced sedation protocol provided a minimalization of the dose of propofol needed to target a moderate sedation for colonoscopy, resulting in a high safety profile for non-anesthesiologist propofol sedation.

  9. Human metabolism of orally administered radioactive cobalt chloride

    International Nuclear Information System (INIS)

    This study investigated the human gastrointestinal uptake (f1) and subsequent whole-body retention of orally administered inorganic radioactive cobalt. Of eight adult volunteers aged between 24 and 68 years, seven were given solutions of 57Co (T1/2 = 272 d) containing a stable cobalt carrier, and six were given carrier-free 58Co (T1/2 = 71 d). The administered activities ranged between 25 and 103 kBq. The observed mean f1, based on 6 days accumulated urinary excretion sampling and whole-body counting, was 0.028 ± 0.0048 for carrier-free 58Co, and 0.016 ± 0.0021 for carrier-associated 57Co. These values were in reasonable agreement with values reported from previous studies involving a single intake of inorganic cobalt. The time pattern of the total retention (including residual cobalt in the GI tract) included a short-term component with a biological half-time of 0.71 ± 0.03 d (average ± 1 standard error of the mean for the two nuclides), an intermediate component with a mean half-time of 32 ± 8.5 d, and a long-term component (observed in two volunteers) with half-times ranging from 80 to 720 d for the two isotopes. From the present data we conclude that for the short-lived 57Co and 58Co, more than 95% of the internal absorbed dose was delivered within 7 days following oral intake, with a high individual variation influenced by the transit time of the unabsorbed cobalt through the gastro-intestinal tract. - Highlights: • Gastrointestinal (GI) uptake, f1, of inorganic radioactive cobalt varies between 0.007 and 0.043 among humans. • Mean f1 among human volunteers was found to be 0.022 ± 0.003. • More than 95% of the estimated internal absorbed dose occurs within 7 d for the short-lived radionuclides 57Co and 58Co. • More than 60% of the time integrated absorbed dose from ingestion of 60Co occurs within 7 d. • Residence time of cobalt in the human GI-tract strongly influences the time integrated internal absorbed dose

  10. Administering and Detecting Protein Marks on Arthropods for Dispersal Research.

    Science.gov (United States)

    Hagler, James R; Machtley, Scott A

    2016-01-01

    Monitoring arthropod movement is often required to better understand associated population dynamics, dispersal patterns, host plant preferences, and other ecological interactions. Arthropods are usually tracked in nature by tagging them with a unique mark and then re-collecting them over time and space to determine their dispersal capabilities. In addition to actual physical tags, such as colored dust or paint, various types of proteins have proven very effective for marking arthropods for ecological research. Proteins can be administered internally and/or externally. The proteins can then be detected on recaptured arthropods with a protein-specific enzyme-linked immunosorbent assay (ELISA). Here we describe protocols for externally and internally tagging arthropods with protein. Two simple experimental examples are demonstrated: (1) an internal protein mark introduced to an insect by providing a protein-enriched diet and (2) an external protein mark topically applied to an insect using a medical nebulizer. We then relate a step-by-step guide of the sandwich and indirect ELISA methods used to detect protein marks on the insects. In this demonstration, various aspects of the acquisition and detection of protein markers on arthropods for mark-release-recapture, mark-capture, and self-mark-capture types of research are discussed, along with the various ways that the immunomarking procedure has been adapted to suit a wide variety of research objectives. PMID:26863574

  11. Recovery of cholinesterase activity in mallard ducklings administered organophosphorus pesticides

    Science.gov (United States)

    Fleming, W.J.; Bradbury, S.P.

    1981-01-01

    Oral doses of the organophosphorus pesticides acephate, dicrotophos, fensulfothion, fonofos, malathion, and parathion were administered to mallard ducklings (Anas platyrhynchos), and brain and plasma cholinesterase (ChE) activities were determined for up to 77 d after dosing. In vivo recovery of brain ChE activity to within 2 standard deviations of the mean activity of undosed birds occurred within 8 d, after being depressed an average of 25-58% at 24 h after dosing. In vivo recovery of plasma ChE appeared as fast as or faster than that of brain, but the pattern of recovery was more erratic and therefore statistical comparison with brain ChE recovery was not attempted. In vitro tests indicated that the potential for dephosphorylation to contribute to in vivo recovery of inhibited brain ChE differed among chemical treatments. Some ducklings died as a result of organophosphate dosing. In an experiment in which ducklings within each treatment group received the same dose (mg/kg), the brain ChE activity in birds that died was less than that in birds that survived. Brain ChE activities in ducklings that died were significantly different among pesticide treatments: fensulfothion > parathion> acephate > malathion (p < 0.05).

  12. 34 CFR 461.1 - What is the Adult Education State-administered Basic Grant Program?

    Science.gov (United States)

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false What is the Adult Education State-administered Basic... (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION ADULT EDUCATION STATE-ADMINISTERED BASIC GRANT PROGRAM General § 461.1 What is the Adult Education State-administered Basic...

  13. Antinociceptive effects of Cremophor EL orally administered to mice

    Directory of Open Access Journals (Sweden)

    Z. Tabarelli

    2003-01-01

    Full Text Available Surfactants are frequently used to improve solubilization of lipophilic drugs. Cremophor EL (CrEL is a polyoxyethylated castor oil surfactant used to solubilize water-insoluble drugs such as anesthetic, antineoplastic, immunosuppressive and analgesic drugs, vitamins and new synthetic compounds, including potential analgesics. The antinociceptive effect of CrEL (3.2, 6.4 and 10.6 g/kg, in 10 ml/kg body weight, by gavage on the abdominal writhing response induced by intraperitoneal administration of acetic acid (0.8%, 10 ml/kg body weight and on the tail immersion test was investigated in mice. Control animals received castor oil (10 ml/kg body weight or saline (0.9% NaCl, 10 ml/kg body weight. CrEL reduced nociception in a dose-dependent manner in both tests. At 10.6 g/kg, CrEL caused antinociception similar to that induced by dipyrone (300 mg/kg, by gavage in the abdominal writhing test, and antinociception similar to that induced by morphine (20 mg/kg, by gavage in the tail immersion test. The effect of castor oil was similar to that of saline in both assays. These data indicate that the appropriate controls should be used when evaluating the effects of potential antinociceptive agents dissolved in CrEL.

  14. Development of Teacher-Administered Tests for the SWRL Reading Programs.

    Science.gov (United States)

    Niedermeyer, Fred C.; Sullivan, Howard J.

    To investigate the type of classroom testing format most appropriate for the Southwest Regional Laboratory (SWRL) Mod 2 Reading Program, three types of teacher-administered tests for the SWRL Second-Year Communication Skills Program were developed and tried out during the 1970-71 school year. The tests were administered by the classroom teacher as…

  15. Nurse administered propofol sedation for pulmonary endoscopies requires a specific protocol

    DEFF Research Database (Denmark)

    Jensen, Jeppe Thue; Banning, Anne-Marie; Clementsen, Paul; Hammering, Anne; Hornslet, Pernille; Horsted, Tina; Vilmann, Peter

    2012-01-01

    This study provides an evaluation and risk analysis of propofol sedation for endoscopic pulmonary procedures according to our unit's "gastroenterologic nurse-administered propofol sedation (NAPS) guideline".......This study provides an evaluation and risk analysis of propofol sedation for endoscopic pulmonary procedures according to our unit's "gastroenterologic nurse-administered propofol sedation (NAPS) guideline"....

  16. Differing effects of PTH 1-34, PTH 1-84 and zoledronic acid on bone microarchitecture and estimated strength in postmenopausal women with osteoporosis. An 18 month open-labeled observational study using HR-pQCT

    DEFF Research Database (Denmark)

    Hansen, Stinus; Hauge, Ellen Margrethe; Jensen, Jens-Erik Beck; Brixen, Kim

    2012-01-01

    computed tomography (HR-pQCT) to detail effects on compartmental geometry, density and microarchicture as well as finite element (FE) estimated integral strength at the distal radius and tibia in postmenopausal osteoporotic women treated with PTH 1-34 (20 µg sc. daily, n=18) or PTH 1-84 (100 µg sc. daily......Whereas the beneficial effects of intermittent treatment with parathyroid hormone (PTH) (intact PTH 1-84 or fragment PTH 1-34, teriparatide) on vertebral strength is well documented, treatment may not be equally effective in the peripheral skeleton. We used high resolution peripheral quantitative...

  17. The influence of menopausal status on bone turnover and disease control in breast cancer patients with metastatic bone disease treated with chemotherapy plus zoledronic acid : an exploratory retrospective cohort study

    OpenAIRE

    Ferreira, Arlindo Rebelo da Silva

    2015-01-01

    RESUMO: Introdução: Uma meta-análise recente demonstrou que uso adjuvante de ácido zoledrónico (AZ) em mulheres pós-menopáusicas com cancro da mama precoce (CM) conduz a redução do risco de morte por CM em 17%. Investigámos o efeito do estado hormonal (pré [PrM] vs pós-menopausa tardia [PoM]) na remodelação óssea e controlo de doença em mulheres com CM e metástases ósseas (MO) tratadas com AZ e quimioterapia (QT). Métodos: Neste estudo de coorte retrospetivo, colhemos variáveis clinico...

  18. Tracer experiment administering L-phenylalanine-U-14C and L-tyrosine-U-14C to the tissue slices of bamboo shoots

    International Nuclear Information System (INIS)

    Uniformly 14C-labeled L-phenylalanine and L-tyrosine were administered to tissue slices of both top and base sections of bamboo shoots. Alcohol soluble substances were extracted and then separated into organic acid, sugar and amino acid fractions by ion exchange chromatography. The homogentisic acid fraction among the organic acids was collected by high-performance liquid chromatography (HPLC) and its radioactivity was measured, while the alcohol insoluble residue was used for the analysis of lignin aldehyde by the method of alkaline nitrobenzene oxidation. 1. The two labeled amino acids were steadily incorporated into the tissues during incubation and rapidly converted to organic acid, sugar and alcohol insoluble residue, especially the latter. 2. On determining the amount of phenylalanine converted to tyrosine, it was found that this was extremely small. 3. The incorporation of phenylalanine-U-14C into alcohol insoluble residue was higher than that of tyrosine in both sections. 4. Although the conversion into lignin aldehyde from phenylalanine-U-14C was higher than that from tyrosine-U-14C, it was found that tyrosine incorporated into the shoots was converted to a remarkable extent for formation of lignin aldehyde. 5. The incorporation of phenylalanine and tyrosine into homogentisic acid was very low. From these results, we assume that the conversion of phenylalanine to tyrosine or of tyrosine to homogentisic acid is very small, and that a part of the high amount of tyrosine in the shoots may be used for formation of lignin

  19. Open-label, multicenter study of self-administered icatibant for attacks of hereditary angioedema

    DEFF Research Database (Denmark)

    Aberer, W; Maurer, M; Reshef, A; Longhurst, H; Kivity, S; Bygum, Anette; Caballero, T; Bloom, B; Nair, N; Malbrán, A

    2014-01-01

    Historically, treatment for hereditary angioedema (HAE) attacks has been administered by healthcare professionals (HCPs). Patient self-administration could reduce delays between symptom onset and treatment, and attack burden. The primary objective was to assess the safety of self...

  20. Psychological sources of response effects in self-administered and telephone surveys

    OpenAIRE

    Schwarz, Norbert; Bishop, George F.; Hippler, Hans-J.; Strack, Fritz

    1989-01-01

    The impact of mode of data collection (self-administered questionnaire vs. telephone interview) on the emergence of response effects and the accuracy of recall from memory was explored in a cross-cultural experiment, conducted in the U.S. and the Federal Republic of Germany. As predicted on the basis of psychological considerations, question order effects were obtained under telephone interview conditions but not under self-administered conditions, where question order is eliminated by the op...

  1. Metrological aspects in the estimate of the administered activity in nuclear medicine patients

    International Nuclear Information System (INIS)

    In order to investigate the performance quality of routine measurements of Nuclear Medicine Services (NMS), the National Metrology Laboratory of Ionizing Radiation/Institute of Radiation Protection and Dosimetry (LNMRI/IRD) has been conducting, since 1998, a program of comparison for activity measurements of radiopharmaceuticals administered to patients in nuclear medicine. Correction factors are determined from the result of performance analysis in order to determine with better accuracy the activity to be administered to the patients. (author)

  2. Telephone-administered psychotherapy for depression in MS patients: moderating role of social support

    OpenAIRE

    Beckner, Victoria; Howard, Isa; Vella, Lea; Mohr, David C.

    2009-01-01

    Depression is common in individuals with multiple sclerosis (MS). While psychotherapy is an effective treatment for depression, not all individuals benefit. We examined whether baseline social support might differentially affect treatment outcome in 127 participants with MS and depression randomized to either Telephone-administered Cognitive-Behavioral Therapy (T-CBT) or Telephone-administered Emotion-Focused Therapy (T-EFT). We predicted that those with low social support would improve more ...

  3. Dose Dependence of the Anticoagulant Effect of Intravenously Administered Cellulose Sulfate.

    Science.gov (United States)

    Drozd, N N; Kuznetsova, S A; Kalinina, T B; Vasilieva, N Yu

    2016-04-01

    Experiments on rabbits showed that increasing the dose of intravenously administered cellulose sulfate from wheat straw (dynamic viscosity 3.4 cP, sulfur content 14.1%) increased plasma clotting time in some coagulation tests and plasma anticoagulant activity. When cellulose sulfate was administered in the dose of 1 mg/kg, plasma clotting time in the presence of the anticoagulant (5 min after administration) was ~3-fold higher than after saline administration. PMID:27165079

  4. Present status of medical study on thorotrast-administered patients in Japan

    International Nuclear Information System (INIS)

    Three-fourths of all thorotrast-administered cases in Japan was warwounded ex-servicemen and their dates of thorotrast injections were concentrated between 1932 and 1945. An epidemiological follow-up study on 147 thorotrast-administered warwounded ex-servicemen whose protocols, contained records of thorotrast-administration, were kept at four former military hospitals, was initiated in 1963. At the end of 1983 the total number of their protocols discovered has increased to 282. On December 31, 1983, the authors found 50 malignant hepatic tumors, 25 other malignant tumors, 16 liver cirrhosis, and 4 blood diseases in 261 intravascularly thorotrast-administered cases. In the remaining 21 cases who had been given thorotrast by the route other than intravascularly, no significant difference was observed in the incidence of any diseases when compared with the controls. In 270 throtrast-administered autopsy cases reported during 1945-1983, 267 had been injected with thorotrast intravascularly and the remaining 3 had been given by other routes. Of the 267 intravascularly thorotrast-administered autopsy cases, 180 were malignant hepatic tumors, 20 liver cirrhosis, 16 leukemias, 5 aplastic anemias, 5 lung cancers, 3 sarcomas of thorotrast injected site, 2 metholiomas, 1 hemangioendothelioma of the spleen, 1 malignant lymphoma, and 1 osteosarcoma. The dosimetry of 96 intravascularly thorotrast-administered autopsy cases was performed for an estimate of the absorbed dose of critical organs, such as the liver, spleen, and bone marrow. (orig./MG)

  5. Validation of a self-administered questionnaire for assessing occupational and environmental exposures of pregnant women

    International Nuclear Information System (INIS)

    The present investigation sought to determine whether a self-administered questionnaire could be used to obtain occupational information from pregnant women attending the obstetrical clinics at the University of California, San Francisco from July to November 1986. The authors compared the accuracy of responses of 57 women on the self-administered questionnaire with those obtained on a detailed clinical interview by an occupational health professional. The self-administered questionnaire and the clinical interview included information on the woman's job title, the type of company she worked for, the level of physical activity, her exposures on the job and at home, and her partner's occupation. The authors also examined whether the validity of the self-administered questionnaire could be improved on review by an industrial hygienist. The questionnaire took less than 20 minutes to complete, with over 90% of the women answering three-quarters of it. It was substantially accurate in obtaining information on number of hours worked during pregnancy, type of shift worked, and stress level in the workplace; exposure to radiation, video display terminals, fumes, gases, and cigarette smoke in the workplace; and exposure to pesticides, paint, and cigarette smoke at home. On those variables for which the responses on the self-administered questionnaire were less accurate, review by the industrial hygienist improved the level of accuracy considerably. These findings suggest that a self-administered questionnaire can be used to obtain valid information from pregnant women attending a prenatal clinic

  6. Amino acids

    Science.gov (United States)

    Amino acids are organic compounds that combine to form proteins . Amino acids and proteins are the building blocks of life. When proteins are digested or broken down, amino acids are left. The human body uses amino acids ...

  7. Postoperative intravenously administered iron sucrose versus postoperative orally administered iron to treat post-bariatric abdominoplasty anaemia (ISAPA): the study protocol for a randomised controlled trial

    OpenAIRE

    Montano-Pedroso, Juan Carlos; Garcia, Elvio Bueno; Novo, Neil Ferreira; Veiga, Daniela Francescato; Ferreira, Lydia Masako

    2016-01-01

    Background Anaemia and iron deficiency are common complications following post-bariatric abdominoplasty. Given the low oral absorbability of iron resulting from bariatric surgery, it has been hypothesised that postoperative intravenously administered iron supplementation could be used to treat anaemia and to prevent the development of iron deficiency in these patients. Methods/Design In this multicentre open-label randomised clinical trial, 56 adult women undergoing post-bariatric anchor-line...

  8. Challenges in converting an interviewer-administered food probe database to self-administration in the National Cancer Institute Automated Self-administered 24-Hour Recall (ASA24)

    OpenAIRE

    Zimmerman, Thea Palmer; Hull, Stephen G.; McNutt, Suzanne; Mittl, Beth; Islam, Noemi; Guenther, Patricia M.; Thompson, Frances E; Potischman, Nancy A.; Subar, Amy F.

    2009-01-01

    The National Cancer Institute (NCI) is developing an automated, self-administered 24-hour dietary recall (ASA24) application to collect and code dietary intake data. The goal of the ASA24 development is to create a web-based dietary interview based on the US Department of Agriculture (USDA) Automated Multiple Pass Method (AMPM) instrument currently used in the National Health and Nutrition Examination Survey (NHANES). The ASA24 food list, detail probes, and portion probes were drawn from the ...

  9. Effects of chelating agent CBMIDA on the toxicity of depleted uranium administered subcutaneously in rats

    International Nuclear Information System (INIS)

    We examined the acute toxicity of depleted uranium (DU) after subcutaneous injection as a simulated wounds model, and the effects of the chelating agent catechol-3,6-bis(methyleiminodiacetic acid) (CBMIDA), by local treatment in rats. First, to examine the initial behavior and toxicity of uranium of different chemical forms, male Wistar rats were subcutaneously injected with 4 and 16 mg/kg DU (pH 1) in a solution of pH 1 and 7, respectively, and were killed 1, 3, 6 and 24 hours later. After the injection of DU(pH1), about 60 % of the uranium was retained for first 1-3 hours at the injected sites, and then decreased to 16% at 24 hours in the 4 mg/kg DU group; however, the uranium did not change significantly in the 16 mg/kg DU group. Urinary excretion rates of uranium increased in a time-independent manner after the injection. Depositions of uranium in the liver, kidneys and femur were found at 1 hour after DU injection, with significant increases in serum and urinary biochemical markers indicating acute and severe damage. The results of the DU (pH 7) injection were useful for estimating the toxicity of uranium by the chemical changes in the body. Second, CBMIDA (480mg/kg) was infused into the DU-injected site at 0, 10, 30, 60 min and 24 hours after the subcutaneous injection of 4 mg/kg DU (pH 1 and 7). When CBMIDA was administered within 120 min after DU (pH 1) injection, the uranium at the injected sites decreased to 4-17% of that in the no-treatment DU (pH 1) group, and was excreted effectively in the urine and feces, with decreased levels in the kidneys and femur. The results indicated that the subcutaneously injected uranium acutely induced severe damage in the DU-injected sites and organs after DU intake, relating to chemical forms of uranium by pH and that local treatment of CBMIDA was effective in decreasing the acute toxicity of uranium if carried out as early as possible (at least within 2 hours) after DU administration. (author)

  10. Safety Evaluation of CNS Administered Biologics-Study Design, Data Interpretation, and Translation to the Clinic.

    Science.gov (United States)

    Vuillemenot, Brian R; Korte, Sven; Wright, Teresa L; Adams, Eric L; Boyd, Robert B; Butt, Mark T

    2016-07-01

    Many central nervous system (CNS) diseases are inadequately treated by systemically administered therapies due to the blood brain barrier (BBB), which prevents achieving adequate drug concentrations at sites of action. Due to the increasing prevalence of neurodegenerative diseases and the inability of most systemically administered therapies to cross the BBB, direct CNS delivery will likely play an increasing role in treatment. Administration of large molecules, cells, viral vectors, oligonucleotides, and other novel therapies directly to the CNS via the subarachnoid space, ventricular system, or parenchyma overcomes this obstacle. Clinical experience with direct CNS administration of small molecule therapies suggests that this approach may be efficacious for the treatment of neurodegenerative disorders using biological therapies. Risks of administration into the brain tissue or cerebrospinal fluid include local damage from implantation of the delivery system and/or administration of the therapeutic and reactions affecting the CNS. Preclinical safety studies on CNS administered compounds must differentiate between the effects of the test article, the delivery device, and/or the vehicle, and assess exacerbations of reactions due to combinations of effects. Animal models characterized for safety assessment of CNS administered therapeutics have enabled human trials, but interpretation can be challenging. This manuscript outlines the challenges of preclinical intrathecal/intracerebroventricular/intraparenchymal studies, evaluation of results, considerations for special endpoints, and translation of preclinical findings to enable first-in-human trials. Recommendations will be made based on the authors' collective experience with conducting these studies to enable clinical development of CNS-administered biologics. PMID:27354708

  11. 75 FR 7440 - Oil and Gas Leasing on Lands Administered by the Dixie National Forest, Supplemental Information...

    Science.gov (United States)

    2010-02-19

    ... Forest Service Oil and Gas Leasing on Lands Administered by the Dixie National Forest, Supplemental... report to the Oil and Gas Leasing on Lands Administered by the Dixie National Forest Final Environmental... considered, the FS must receive written comments on the Oil and Gas Leasing on Lands Administered by...

  12. 38 CFR 2.3 - Delegation of authority to employees to take affidavits, to administer oaths, etc.

    Science.gov (United States)

    2010-07-01

    ... to employees to take affidavits, to administer oaths, etc. 2.3 Section 2.3 Pensions, Bonuses, and... employees to take affidavits, to administer oaths, etc. (a) An employee to whom authority is delegated by... from the Secretary to employees to take affidavits, to administer oaths, etc., will be evidenced by...

  13. 34 CFR 692.80 - How does a State administer its community service work-study program?

    Science.gov (United States)

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false How does a State administer its community service work... Its Community Service Work-Study Program? § 692.80 How does a State administer its community service work-study program? When administering its community service work-study program, a State must...

  14. Celecoxib plus hormone therapy versus hormone therapy alone for hormone-sensitive prostate cancer: first results from the STAMPEDE multiarm, multistage, randomised controlled trial

    OpenAIRE

    James, Nicholas D.; Sydes, Matthew R.; Mason, Malcolm D; Clarke, Noel W; Anderson, John; Dearnaley, David P; Dwyer, John; Jovic, Gordana; Ritchie, Alastair WS; Russell, J Martin; Sanders, Karen; Thalmann, George N; Bertelli, Gianfilippo; Birtle, Alison J; O'Sullivan, Joe M

    2012-01-01

    Summary Background Long-term hormone therapy alone is standard care for metastatic or high-risk, non-metastatic prostate cancer. STAMPEDE—an international, open-label, randomised controlled trial—uses a novel multiarm, multistage design to assess whether the early additional use of one or two drugs (docetaxel, zoledronic acid, celecoxib, zoledronic acid and docetaxel, or zoledronic acid and celecoxib) improves survival in men starting first-line, long-term hormone therapy. Here, we report the...

  15. [Technical specifications for rational clinical use of parenterally administered Chinese medicine (draft version for comments)].

    Science.gov (United States)

    Xie, Yan-Ming; Li, Ming-Quan; Zhang, Yun-Ling; Ma, Rong; Xian, Shao-Xiang; Liu, Jian; Li, Su-Yun; Zhao, Yu-Bin

    2013-09-01

    The regulations on basic clinical use of parenterally administered Chinese medicine, issued jointly in 2008, by the ministry of health (MOH), China food and drug administration (SFDA) and the state administration of traditional Chinese medicine (SATCM). Integrating actual clinical practice, these presented doctors and nurses with detailed specifications for the safe use of parenterally administered Chinese medicine. The regulations emphasize the use of Chinese medicine pattern differentiation, use in strict accordance with instructions, and they prohibit use combined with other medicines. The emphasis of the regulations are practicality and operability, and provide meaningful guidance to doctors and nurses for the rational and safe use of parenterally administered Chinese medicine, to reduce adverse reactions/adverse events caused by improper use. PMID:24471306

  16. Safety and efficiency of prehospital pain management with fentanyl administered by emergency medical technicians

    DEFF Research Database (Denmark)

    Nielsen, Niels Dalsgaard; Brogaard, Kjeld; Dahl, Michael; Hansen, Poul Anders

    Introduction: In our region Advanced Emergency Medical Technicians (AEMTs) respond to acutely ill or injured patients in rural areas. The AEMTs have been authorized to administer fentanyl intravenously in doses up to 2 μg/kg to selected groups of patients in pain. Higher doses can be allowed by a...... physician after a teleconference. We examined the effect of intravenous (IV) fentanyl treatment, expressed as pain reduction on a 10-point Numeric Rating Scale (NRS). Moreover we examined the occurrence of negative coincident events to assess whether it was safe to let non-medical staff administer potent...... considered minor, and were not treated with naloxone.   Conclusions: Our results suggest that non-medical personnel safely can administer IV fentanyl to selected groups of patients with a satisfactory result in terms of a considerable reduction in pain score and an acceptable rate of negative coincident...

  17. Comparative Discussion on Psychophysiological Effect of Self-administered Facial Massage by Treatment Method

    Science.gov (United States)

    Nozawa, Akio; Takei, Yuya

    The aim of study was to quantitatively evaluate the effects of self-administered facial massage, which was done by hand or facial roller. In this study, the psychophysiological effects of facial massage were evaluated. The central nerves system and the autonomic nervous system were administered to evaluate physiological system. The central nerves system was assessed by Electroencephalogram (EEG). The autonomic nervous system were assessed by peripheral skin temperature(PST) and heart rate variability (HRV) with spectral analysis. In the spectral analysis of HRV, the high-frequency components (HF) were evaluated. State-Trait Anxiety Inventory (STAI), Profile of Mood Status (POMS) and subjective sensory amount with Visual Analog Scale (VAS) were administered to evaluate psychological status. These results suggest that kept brain activity and had strong effects on stress alleviation.

  18. Prophylactic efficacy of lithium administered every second day: a WHO multicentre study

    DEFF Research Database (Denmark)

    Plenge, P; Amin, M; Agarwal, A K; Greil, W; Kim, M J; Panteleyeva, G; Park, J M; Prilipko, L; Rayushkin, V; Sharma, M; Mellerup, E

    1999-01-01

    OBJECTIVES: To study the prophylactic efficacy of lithium administered every second day to patients with bipolar disorder or recurrent unipolar depressive disorder. METHODS: The study was carried out as a WHO multicentre study in five different psychiatric clinics: Russia (Moscow), Canada (Montreal...... recurrences. The mean 12-h standard serum lithium concentration was lower in the patients who had recurrences than in those who stayed euthymic. The results suggest that to be effective when administered every second day, lithium must be given in a dose leading to a 12-h standard serum lithium concentration...

  19. Patient protection in nuclear medicine due to optimization of the administered activity

    International Nuclear Information System (INIS)

    The possibility of a radiological risk reduction in Nuclear Medicine patients is studied through the reduced absorbed doses in organs and tissues, and whole-body effective dose due to optimization of the administered radionuclide activities. Activity values, optimized for equipments and radiopharmaceuticals available in Cuba, are compared with the IAEA recommended values and with the routinary activities in medical practice. All doses were calculated using MIRDOSE 3.0 code for each activity and medical assay. The activity optimization permits to reduce in a 50% the doses administered to patients of the major part of studied medical assays. (Author)

  20. Pharmacokinetic and pharmacodynamic effects of methylphenidate and MDMA administered alone or in combination

    OpenAIRE

    Hysek, C M; Simmler, L. D.; Schillinger, N.; De Meyer, N.; Schmid, Y; Donzelli, M; Grouzmann, E.; Liechti, M. E.

    2014-01-01

    Methylphenidate and 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') are widely misused psychoactive drugs. Methylphenidate increases brain dopamine and norepinephrine levels by blocking the presynaptic reuptake transporters. MDMA releases serotonin, dopamine and norepinephrine through the same transporters. Pharmacodynamic interactions of methylphenidate and MDMA are likely. This study compared the pharmacodynamic and pharmacokinetic effects of methylphenidate and MDMA administered alone ...

  1. Comparing Two Conditions of Administering the Six-Minute Walk Test in People with Multiple Sclerosis

    OpenAIRE

    Brian M. Sandroff; Pilutti, Lara A.; Dlugonski, Deirdre; Learmonth, Yvonne C.; Pula, John H.; Motl, Robert W.

    2014-01-01

    Objective: This quasi-experimental study was conducted to determine whether differences existed in the total distance walked and energy expended between two conditions of administering the 6-Minute Walk test (6MW) across different levels of disability in people with multiple sclerosis (MS).

  2. 34 CFR 650.41 - How are institutional payments to be administered?

    Science.gov (United States)

    2010-07-01

    ... Consumer Price Index for the previous calendar year. (b) If the institution of higher education charges and... 34 Education 3 2010-07-01 2010-07-01 false How are institutional payments to be administered? 650.41 Section 650.41 Education Regulations of the Offices of the Department of Education...

  3. High efficacy with deep nurse-administered propofol sedation for advanced gastroenterologic endoscopic procedures

    DEFF Research Database (Denmark)

    Jensen, Jeppe Thue; Hornslet, Pernille; Konge, Lars;

    2016-01-01

    BACKGROUND AND STUDY AIMS: Whereas data on moderate nurse-administered propofol sedation (NAPS) efficacy and safety for standard endoscopy is abundant, few reports on the use of deep sedation by endoscopy nurses during advanced endoscopy, such as Endoscopic Retrograde Cholangiopancreatography (ER...

  4. Telephone-Administered Cognitive Behavioral Therapy for Veterans Served by Community-Based Outpatient Clinics

    Science.gov (United States)

    Mohr, David C.; Carmody, Timothy; Erickson, Lauren; Jin, Ling; Leader, Julie

    2011-01-01

    Objective: Multiple trials have found telephone-administered cognitive behavioral therapy (T-CBT) to be effective for the treatment of depression. The aim of this study was to evaluate T-CBT for the treatment of depression among veterans served by community-based outpatient clinics (CBOCs) outside of major urban areas. Method: Eighty-five veterans…

  5. Bronchodilator effect of disodium cromoglycate administered as a dry powder in exercise induced asthma.

    OpenAIRE

    Horn, C R; Jones, R.M.; Lee, D.; Brennan, S. R.

    1984-01-01

    A double-blind, placebo controlled study of the effects of disodium cromoglycate (DSCG), administered as a dry powder via the spinhaler, in established exercise-induced asthma, was carried out. DSCG resulted in an increase in the rate of recovery compared with placebo. The findings confirm that DSCG has bronchodilator properties.

  6. 20 CFR 664.610 - How is the summer employment opportunities element administered?

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false How is the summer employment opportunities... Opportunities § 664.610 How is the summer employment opportunities element administered? Chief elected officials... used to provide summer youth employment opportunities, these providers must be selected by awarding...

  7. 40 CFR 147.52 - State-administered program-Hydraulic Fracturing of Coal Beds.

    Science.gov (United States)

    2010-07-01

    ...) The Program Description for the Regulation of Hydraulic Fracturing of Coal Beds As required by 40 CFR... Register on January 19, 2000 in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. Copies may be obtained... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered...

  8. Higher Education in Federally Administered Tribal Areas of Pakistan after 9/11: Problems and Prospects

    Science.gov (United States)

    Ahmad, Syed Hafeez; Junaid, Fatima A.

    2010-01-01

    The troubled state of affairs in the Federally Administered Tribal Areas (FATA) of Pakistan portends serious repercussions and grave consequences, destined to affect education particularly higher education in the entire tribal belt. Ironically, no extensive study has been conducted, to investigate those dimensions of FATA higher education which…

  9. Development and validation of a self-administered Food Allergy Quality of Life Questionnaire for children

    NARCIS (Netherlands)

    Flokstra-de Blok, B. M. J.; DunnGalvin, A.; Vlieg-Boerstra, B. J.; Oude Elberink, J. N. G.; Duiverman, E. J.; Hourihane, J. O'B.; Dubois, A. E. J.

    2009-01-01

    Having a food allergy may affect health-related quality of life (HRQL). Currently, no validated, self-administered, disease-specific HRQL questionnaire exists for children with food allergy. The aim of this study was to develop and validate the Food Allergy Quality of Life Questionnaire - Child Form

  10. Development and validation of the self-administered Food Allergy Quality of Life Questionnaire for adolescents

    NARCIS (Netherlands)

    Flokstra-de Blok, Bertine M J; DunnGalvin, Audrey; Vlieg-Boerstra, Berber J; Oude Elberink, Joanne N G; Duiverman, Eric J; Hourihane, Jonathan O'Brien; Dubois, Anthony E J

    2008-01-01

    BACKGROUND: Food allergy can affect health-related quality of life (HRQL). Currently, no validated, self-administered, disease-specific HRQL questionnaire for adolescents with food allergy exists. OBJECTIVE: We sought to develop and validate the Food Allergy Quality of Life Questionnaire-Teenager Fo

  11. Development and validation of the self-administered Food Allergy Quality of Life Questionnaire for adolescents

    NARCIS (Netherlands)

    Flokstra-de Blok, Bertine M J; DunnGalvin, Audrey; Vlieg-Boerstra, Berber J; Oude Elberink, Joanne N G; Duiverman, Eric J; Hourihane, Jonathan O'Brien; Dubois, Anthony E J

    2008-01-01

    Background: Food allergy can affect health-related quality of life (HRQL). Currently, no validated, self-administered, disease-specific HRQL questionnaire for adolescents with food allergy exists. Objective: We sought to develop and validate the Food Allergy Quality of Life Questionnaire-Teenager Fo

  12. 21 CFR 1306.07 - Administering or dispensing of narcotic drugs.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Administering or dispensing of narcotic drugs. 1306.07 Section 1306.07 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE... an incidental adjunct to medical or surgical treatment of conditions other than addiction, or...

  13. Depression in People with Intellectual Disability: An Evaluation of a Staff-Administered Treatment Program

    Science.gov (United States)

    McGillivray, Jane A.; McCabe, Marita P.; Kershaw, Mavis M.

    2008-01-01

    The prevalence of co-morbid depression in people with intellectual disability (ID) provides a strong rationale for the early identification and treatment of individuals at risk. The aim of this study was to evaluate a staff-administered group CBT program for the treatment of depression in people with mild ID. A sample of 13 staff employed at two…

  14. Administered activity and estimated radiation doses from nuclear medicine diagnostic procedures to the Israeli population

    International Nuclear Information System (INIS)

    The current levels of administered activity of radiopharmaceuticals in several common nuclear medicine diagnostic procedures and their contribution to the radiation doses to the Israeli population in 1998-2000 were analyzed. Diagnostic reference levels and the concept of effective dose per capita are discussed as relevant parameters to optimize patient protection. (author)

  15. 20 CFR 668.120 - How must INA programs be administered?

    Science.gov (United States)

    2010-04-01

    ... 25 U.S.C. section 450a, as well as the Department of Labor's “American Indian and Alaska Native... administer INA programs through a single organizational unit and consistent with the requirements in section...) within the Employment and Training Administration (ETA) as this single organizational unit required...

  16. 22 CFR 196.2 - How is the Fellowship Program administered?

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false How is the Fellowship Program administered? 196.2 Section 196.2 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL COMMERCIAL ARBITRATION THOMAS R. PICKERING FOREIGN AFFAIRS/GRADUATE FOREIGN AFFAIRS FELLOWSHIP PROGRAM § 196.2 How is the Fellowship...

  17. Efficacy of recombinant factor VIIa administered by continuous infusion to haemophilia patients with inhibitors

    NARCIS (Netherlands)

    Mauser-Bunschoten, EP; Koopman, MMW; Goede-Bolder, ADE; Leebeek, FWG; Van der Meer, J; Kooij, GMV; Van der Linden, PWG

    2002-01-01

    We have prospectively monitored treatment of haemophilia patients with inhibitors by recombinant factor VIIa (rFVIIa) administered by continuous infusion to obtain more insight in the underlying factors of the clinical efficacy of this administration method. At present, 43 treatment episodes of 14 d

  18. Stress Management for Special Educators: The Self-Administered Tool for Awareness and Relaxation (STAR)

    Science.gov (United States)

    Williams, Krista; Poel, Elissa Wolfe

    2006-01-01

    The Self-Administered Tool for Awareness and Relaxation (STAR) is a stress management strategy designed to facilitate awareness of the physical, mental, emotional, and physiological effects of stress through the interconnectedness of the brain, body, and emotions. The purpose of this article is to present a stress-management model for teachers,…

  19. Psychomotor and Motor Speed in Power Athletes Self-Administering Testosterone and Anabolic Steroids.

    Science.gov (United States)

    Era, Pertti; And Others

    1988-01-01

    Self-administered testosterone and anabolic steroids resulted in insignificant improvement in psychomotor and motor speed tests of power athletes. This study is part of a larger study on the effects of such drugs on endocrinology, metabolism and neuromuscular functions. Methodolgy and results are discussed. (Author/JL)

  20. Nucleic acid delivery with microbubbles and ultrasound.

    Science.gov (United States)

    Rychak, Joshua J; Klibanov, Alexander L

    2014-06-01

    Nucleic acid-based therapy is a growing field of drug delivery research. Although ultrasound has been suggested to enhance transfection decades ago, it took a combination of ultrasound with nucleic acid carrier systems (microbubbles, liposomes, polyplexes, and viral carriers) to achieve reasonable nucleic acid delivery efficacy. Microbubbles serve as foci for local deposition of ultrasound energy near the target cell, and greatly enhance sonoporation. The major advantage of this approach is in the minimal transfection in the non-insonated non-target tissues. Microbubbles can be simply co-administered with the nucleic acid carrier or can be modified to carry nucleic acid themselves. Liposomes with embedded gas or gas precursor particles can also be used to carry nucleic acid, release and deliver it by the ultrasound trigger. Successful testing in a wide variety of animal models (myocardium, solid tumors, skeletal muscle, and pancreas) proves the potential usefulness of this technique for nucleic acid drug delivery. PMID:24486388

  1. Infra Red Dye and Endostar Loaded Poly Lactic Acid Nano Particles as a Novel Theranostic Nanomedicine for Breast Cancer.

    Science.gov (United States)

    Zhang, Qian; Du, Yang; Jing, Lijia; Liang, Xiaolong; Li, Yaqian; Li, Xiaofeng; Dai, Zhifei; Tian, Jie

    2016-03-01

    Endostar, a novel recombinant human endostatin, has been proven to inhibit tumor angiogenesis and is utilized as an anticancer drug. While free drugs can display limited efficacy, nanoscaled anticancer drugs have been fabricated and proven to possess superior therapeutic effects. Poly(lactic acid) (PLA) is a FDA-approved biomaterial displaying excellent biocompatibility and low toxicity. In this study, Endostar-loaded PLA nanoparticles (EPNPs) were first prepared, and a near-infrared (NIR) dye, IRDye 800CW, was conjugated to the surface for detecting nanoparticle biodistribution through fluorescence molecular imaging (FMI) using an orthotopic breast tumor mouse model. The antitumor efficacy of EPNPs was examined using bioluminescence imaging (BLI) and immunohistology. To further improve the antitumor effects, we combined EPNPs with zoledronic acid monohydrate (ZA), which is known to decrease the tumor-associated macrophages (TAM) and inhibit tumor progression. We found that EPNPs decreased human umbilical vein endothelial cell (HUVEC) viability by inhibiting tumor growth gene expression more significantly than free Endostar in vitro. In vivo, EPNPs displayed better tumor growth inhibitory effects compared with free Endostar, and the combination of EPNPs with ZA exhibited more significant antitumor effects. As confirmed by CD31 and CD11b immunohistochemistry, the combination of EPNPs and ZA showed synergistic effects in reducing tumor angiogenesis and TAM accumulation in tumor regions. Taken together, this study presents a novel and effective form of nanoscaled Endostar for the treatment of breast cancer that displays synergistic antitumor effects in combination with ZA. PMID:27280247

  2. Acid Rain.

    Science.gov (United States)

    Openshaw, Peter

    1987-01-01

    Provides some background information on acid deposition. Includes a historical perspective, describes some effects of acid precipitation, and discusses acid rain in the United Kingdom. Contains several experiments that deal with the effects of acid rain on water quality and soil. (TW)

  3. Rapid and complete urinary elimination of [14C]-5-hydroxymethyl-2-furaldehyde administered orally or intravenously to rats

    International Nuclear Information System (INIS)

    5-Hydroxymethyl-2-furaldehyde (HMF), is a major product of sugar degradation found in food and solutions used in parenteral nutrition. Labeled [14C]HMF was synthesized by dehydration of [14C]fructose on ion-exchange resin and administered per os (po) and intravenously (iv) to rats. Metabolic balance of radioactivity demonstrated that HMF or its metabolites are rapidly eliminated in the urine with a recovery of 95-100% after 24 h. Literature reported, in some cases, 50% retention in the body. HMF was completely converted to two metabolites, which have been identified by nuclear magnetic resonance (NMR) and mass spectroscopy (MS) as 5-hydroxymethyl-2-furoic acid and N-(5-hydroxymethyl-2-furoyl)glycine. Administration of high doses of HMF showed a similar rapid elimination, but a proportional reduction of the amount of the glycine conjugate produced. Whole-animal-body autoradiography confirm that shortly after administration radioactive material was present in the liver but was mostly in the kidney and the bladder. The only significant difference between po and iv administration was the presence of a higher level of radioactive material in the brain of iv-treated rats

  4. [Effect of exogenously administered ATP on heart function and energy status].

    Science.gov (United States)

    Chernikov, V S; Darbinian, T M; Bakuleva, N P

    1993-01-01

    It has been shown that ATP (24.10(-6) M) administered once into the circulating solution improved strength and speed characteristics of aerobically perfused hearts. The increasing demands of the hearts in oxygen and energy substrates were satisfied due to coronary vessels dilatation without harming the energy status of the myocardium. When the functional parameters of the hearts in the test and control groups did not differ, an exogenously administered ATP was included into the energy metabolism and increased considerably ATP and CP tissue levels, the sum of high-energy phosphates and ATP/ADP ratio. Artificial supplementation of tissue energy resources was accompanied by a decrease in energy-dependent end-diastolic pressure and diastolic left ventricular elasticity and by increased extensibility of the heart muscle, which may improve functional parameters. PMID:8185075

  5. Serum growth hormone (GH) profiles after nasally administered GH in normal subjects and GH deficient patients

    DEFF Research Database (Denmark)

    Møller, Jens; Laursen, Torben; Mindeholm, Linda;

    1994-01-01

    Abstract OBJECTIVE: GH-deficient patients are at present treated with daily subcutaneous GH injections. Further improvements in patient compliance and effects of treatment may occur with nasal administration. We have examined the absorption of nasally administered GH in healthy subjects and in GH...... deficient patients in two separate studies. DESIGN: Healthy subjects and GH deficient patient were examined in the morning after an overnight fast. Twelve IU of GH in a powder containing didecanoyl-L-alpha-phosphatidylcholine as enhancer were administered in the nostrils (6 IU in each nostril) at the...... beginning of the study in the healthy subjects. The GH deficient subjects received a total of 6 IU GH/m2 intranasally. Blood was frequently sampled for up to 4 hours. Before and after nasal application anterior rhinoscopy was performed. PATIENTS: Eight normal subjects and 7 GH deficient patients...

  6. Administered activities of 18F-FDG PET clinics in pediatrics patients in Brazil- preliminary study

    International Nuclear Information System (INIS)

    A survey was conducted among the Brazilian clinical PET, with the purpose of investigating the activities administered to pediatric oncology patients and assess whether significant differences between the protocols adopted. In addition, this survey can cooperate to the suggestion diagnostic reference levels (DRLs) in nuclear medicine. Although the methodology for delivering doses by most clinics be based on patient's weight, the results showed variations of up to 191, 6% between the activities administered in clinics, even for similar devices. The average value of the distribution of activities reported was 4.46 ± 1,6 MBq /kg. These data demonstrate the need for harmonization and optimization of 18F-FDG/PET procedures, as well as training for professionals involved in the clinical routine

  7. Clinical evaluation of three techniques for administering low-dose heparin.

    Science.gov (United States)

    Vanbree, N S; Hollerbach, A D; Brooks, G P

    1984-01-01

    The purpose of this study was to investigate the effect of three techniques for administering subcutaneous low-dose heparin on the formation of bruises at the injection site in adult postoperative cardiothoracic surgery patients. Forty-three subjects comprised the sample. All received subcutaneous injections of heparin, 5,000 units every 12 hours postsurgery. Three subcutaneous injection techniques, identified to study the variables of needle manipulation and tracking of the medication, were administered randomly to each subject. Forty-eight hours after the third injection, the sites were observed and bruises, if present, were measured. Data were analyzed by means of the Friedman test, and a 0.569 level of significance was obtained. It was concluded that, for this sample, none of the three techniques appeared clearly superior in yielding smaller or fewer bruises. PMID:6560416

  8. Radiation dose calculations for orally administered radio-pharmaceuticals in upper gastrointestinal disease

    International Nuclear Information System (INIS)

    Radiation burden estimates for upper gastrointestinal function studies employing the following orally administered radiopharmaceuticals are reported. Technetium 99m sulfur colloid (Tc-99m-SC) in water, Indium-111-DTPA in water, Tc-99m-DTPA in water, Indium-113m DTPA in water, Tc-99m Ovalbumin, Tc-99m sulfur colloid in a cooked egg, Tc-99m sulfur colloid in vivo labeled chicken liver, and Indium-111 colloid in vivo labeled chicken liver. Orally administered radiopharmaceuticals for upper gastrointestinal studies afford clinician and investigator valuable clinical and physiologic information not previously obtainable using other techniques. The radiation burden to the patient from single or sequential studies is acceptable in comparison to fluoroscopy which results in approximately 5000 millirem per minute of exposure. The variety of preparations listed above should make these types of studies available in any routinely equipped nuclear medicine radiopharmacy laboratory

  9. Psychology of computer use: IX. A menu of self-administered microcomputer-based neurotoxicology tests

    Science.gov (United States)

    Kennedy, R. S.; Baltzley, D. R.; Wilkes, R. L.; Kuntz, L. A.

    1989-01-01

    This study examined the feasibility of repeated self-administration of a newly developed battery of mental acuity tests which may have application in screening for fitness-for-duty or for persons who may be exposed to environmental stress, toxic agents, or disease. 16 subjects self-administered 18 microcomputer-based tests (13 new, 5 "core"), without proctors, over 10 sessions. The hardware performed well throughout the study and the tests appeared to be easily self-administered. Stabilities and reliabilities of the tests from the "core" battery were comparable to those obtained previously under more controlled experimental conditions. Eight of the new tests exceeded minimum criteria for metric and practical requirements and can be recommended as additions to the menu. Although the average retest reliability was high, cross-correlations between tests were low, implying factorial diversity. The menu can be used to form batteries with flexible total testing time which are likely to tap different mental processes and functions.

  10. Enhancing older adults’ eyewitness memory for present and future events with the self-administered interview

    OpenAIRE

    Gawrylowicz, Julie; Memon, Amina; Scoboria, Alan; Hope, Lorraine; Gabbert, Fiona

    2014-01-01

    Older adults’ memory reports are often less complete and accurate than those by younger adults. The current study assessed the suitability of the Self-Administered Interview (SAI) as retrieval support for older eyewitnesses, and examines whether experience with the SAI leads to improved performance on subsequent events where the SAI is not used. Participants recalled an event with the SAI or free recall instructions. After 1-week, all participants watched a second event and freely recalled it...

  11. Comparison between web-based and paper versions of a self-administered anthropometric questionnaire

    OpenAIRE

    Touvier, Mathilde; Méjean, Caroline; Kesse-Guyot, Emmanuelle; Pollet, Clothilde; Malon, Aurélie; Castetbon, Katia; Hercberg, Serge

    2010-01-01

    Abstract Online data collection could advantageously replace paper-and-pencil questionnaires in epidemiological studies by reducing the logistic burden, the cost and the duration of data processing. However, there is a need for studies comparing these new instruments to traditional ones. Our objective was to compare the web-based version of the NutriNet-Sante self-administered anthropometric questionnaire to the paper-based version. The questionnaire included 17 questions divided i...

  12. Effect of self-administered auricular acupressure on smoking cessation --a pilot study

    OpenAIRE

    Leung Lawrence; Neufeld Troy; Marin Scott

    2012-01-01

    Abstract Background Tobacco smoking is still a worldwide health risk. Current pharmacotherapies have at best, a success rate of no more than 50%. Auricular (ear) acupressure has been purported to be beneficial in achieving smoking cessation in some studies, while in others has been deemed insignificant. We hereby describe the protocol for a three-arm randomised controlled trial to examine the possible benefits of self-administered acupressure for smoking cessation. Methods Sixty consenting pa...

  13. Self-administered acupressure for treating adult psychiatric patients with constipation: a randomized controlled trial

    OpenAIRE

    Wong, Wai Kit; Chien, Wai Tong; Lee, Wai Ming

    2015-01-01

    Background Constipation has a high prevalence rate (>30 %) in psychiatric patients with psychotropic drugs. Common pharmacological and non-pharmacological interventions for constipation might have longer-term negative and adverse effects that would outweigh their short-term efficacy in symptom reduction. This randomized controlled trial aims to investigate the effect of self-administered acupressure for the management of constipation, in hospitalized psychiatric patients. Methods Seventy-eigh...

  14. Directly Administered Antiretroviral Therapy: Pilot Study of a Structural Intervention in Methadone Maintenance

    OpenAIRE

    Sorensen, JL; Haug, NA; Larios, S; Gruber, VA; Tulsky, J; Powelson, E; Logan, DP; Shapiro, B.

    2012-01-01

    Devising interventions to provide integrated treatment for addiction and medical problems is an urgent issue. This study piloted a structural intervention, Directly Administered Antiretroviral Therapy (DAART), to assist methadone-maintenance patients in HIV medication adherence. Twenty-four participants received: (1) antiretroviral medications at the methadone clinic daily before receiving their methadone; (2) take-home antiretroviral medication for days they were not scheduled to attend the ...

  15. [Analysis of adverse reactions and pharmacovigilance research to parenterally administered shuxuening].

    Science.gov (United States)

    Yang, Wei; Xiang, Yong-Yang; Xie, Yan-Ming; Shen, Hao

    2013-09-01

    Parenterally administered Shuxuening is a commonly used Chinese medicine. There is a need to understand the characteristics of adverse drug reactions (ADRs) to it. 9 601 ADR cases reports were collected from the national adverse drug reaction monitoring center reported between January, 2005 and December, 2012. These included 326 serious ADR cases, accounting for 3.93% of the total. It was found that ADR reports increased annually from 2005, reaching a peak in the third quarter of 2009. The number of ADR cases reports were greatest in the third quarter of each year. ADRs in patients aged 60-74, accounted for 3 348 (34.87%) of all cases. 9 391(97.81%) cases were administered by intravenous infusion. In 8 431 cases, the dosage was in accordance with instructions. 61.61% ADR cases occurred on first administration. The ten most frequent symptoms were, rashes, itching, dizziness, palpitations, chills, allergic reactions, shortness of breath, nausea, phlebitis and vomiting. Systemic damage mainly affected the skin and its accessories damage, or the nervous system damage. Through the use of proportional reporting ratio (PRR) and Bayesian confidence propagation neural network (BCPNN) and propensity score applying generalized boosted models (GBM) to control for 17 confounding factors, analysis of the 10 kinds of ADRs found that for the ADR signals of dizziness, palpitations, phlebitis, and vomiting, BCPNN found that dizziness and phlebitis were early warning signals. This research found that in the 60-89 age group, higher dosages of parenterally administered Shuxuening gave rise to more phlebitis. This study provides important information for parenterally administered Shuxuening research, and guidance for its risk management. PMID:24471322

  16. Psychometric Assessment of a Self-Administered Version of the Significant Other Survey

    OpenAIRE

    Benishek, Lois A.; Carter, Meridith; Clements, Nicolle T.; Allen, Cassandra; Salber, Kristin E.; Dugosh, Karen; Kirby, Kimberly C.

    2012-01-01

    While there are a number of general measures that assess interpersonal and psychological distress experienced by individuals who are in a close relationship with a substance abusing adult, until recently the field has lacked a psychometrically sound, self-administered multidimensional measure explicitly designed to measure the problems of non-substance abusing adults who are concerned about a substance using loved one. This study examined the psychometric properties of a 54-item, self-adminis...

  17. The effects of four different drugs administered through catheters on slime production in coagulase negative Staphylococci

    OpenAIRE

    J. Sedef Göçmen; Ünase Büyükkoçak; Alpay Azap; Yasemin Ö. Pekuz; Osman Çağlayan

    2012-01-01

    Objectives: Higher rate of slime production has been found in pathogen bacteria strains. Accordingly, the factors thatcontribute to higher slime production rate increase the infection risk, while the factors that reduce the slime productionrate will reduce the infection risk. The effect of some drugs that are administered through catheters in intensive careunits on slime production with coagulase negative Staphylococci was investigated.Materials and methods: In this study, the effect of four ...

  18. The effects of four different drugs administered through catheters on slime production in coagulase negative Staphylococci

    OpenAIRE

    Göçmen, Julide Sedef; Büyükkoçak, Ünase; AZAP, Alpay; Pekuz, Yasemin; Çağlayan, Osman

    2012-01-01

    Objective: Higher rate of slime production has been found in pathogen bacteria strains. Accordingly, the factors that contribute to higher slime production rate increase the infection risk, while the factors that reduce the slime production rate will reduce the infection risk. The effect of some drugs that are administered through catheters in intensive care units on slime production with coagulase negative Staphylococci was investigated. Methods: In this study, the effect of four differe...

  19. Willingness to administer mouth-to-mouth ventilation in a first response program in rural Bangladesh

    OpenAIRE

    Mecrow, Tom Stefan; Rahman, Aminur; Mashreky, Saidur Rahman; Rahman, Fazlur; Nusrat, Nahida; Scarr, Justin; Linnan, Michael

    2015-01-01

    Background Timely mouth-to-mouth ventilation is critical to resuscitate drowning victims. While drowning is frequent, there are no lay persons trained in cardio-pulmonary resuscitation (CPR) in rural Bangladesh. As part of a feasibility study to create a first response system in a conservative Islamic village environment, a pilot was undertaken to examine willingness to provide mouth-to-mouth ventilation for drowning resuscitation. Methods A questionnaire was administered to 721 participants ...

  20. Randomized, controlled trial of ibuprofen syrup administered during febrile illnesses to prevent febrile seizure recurrences

    OpenAIRE

    van Stuijvenberg, Margriet; Derksen-Lubsen, Gerarda; Steyerberg, Ewout; Habbema, Dik; Moll, Henriëtte

    1998-01-01

    textabstractOBJECTIVES: Febrile seizures recur frequently. Factors increasing the risk of febrile seizure recurrence include young age at onset, family history of febrile seizures, previous recurrent febrile seizures, time lapse since previous seizure /=38.5 degrees C). Parents were instructed to take the child's rectal temperature immediately when the child seemed ill or feverish and to promptly administer the study medication when the temperature was >/=38.5 degrees C. Doses were to be admi...

  1. Development of a self-administered questionnaire to screen patients for cervical myelopathy

    Directory of Open Access Journals (Sweden)

    Sekiguchi Yasufumi

    2010-11-01

    Full Text Available Abstract Background In primary care, it is often difficult to diagnose cervical myelopathy. However, a delay in treatment could cause irreversible aftereffects. With a brief and effective self-administered questionnaire for cervical myelopathy, cervical myelopathy may be screened more easily and oversight may be avoided. As there is presently no screening tool for cervical myelopathy, the aim of this study was to develop a self-administered questionnaire for the screening of cervical myelopathy. Methods A case-control study was performed with the following two groups at our university hospital from February 2006 to September 2008. Sixty-two patients (48 men, 14 women with cervical myelopathy who underwent operative treatment were included in the myelopathy group. In the control group, 49 patients (20 men, 29 women with symptoms that could be distinguished from those of cervical myelopathy, such as numbness, pain in the upper extremities, and manual clumsiness, were included. The underlying conditions were diagnosed as carpal tunnel syndrome, cubital tunnel syndrome, thoracic outlet syndrome, tarsal tunnel syndrome, diabetes mellitus neuropathy, cervical radiculopathy, and neuralgic amyotrophy. Twenty items for a questionnaire in this study were chosen from the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire, which is a new self-administered questionnaire, as an outcome measure for patients with cervical myelopathy. Data were analyzed by univariate analysis using the chi-square test and by multiple logistic regression analysis. According to the resulting odds ratio, β-coefficients, and p value, items were chosen and assigned a score. Results Eight items were chosen by univariate and multiple logistic regression analyses and assigned a score. The Hosmer-Lemeshow statistic showed p = 0.805. The area under the receiver operation characteristic curve was 0.86. The developed questionnaire had a sensitivity of 93.5% and a

  2. Validity and reliability of a self-administered foot evaluation questionnaire (SAFE-Q)

    OpenAIRE

    Niki, Hisateru; Tatsunami, Shinobu; Haraguchi, Naoki; Aoki, Takafumi; Okuda, Ryuzo; Suda, Yasunori; Takao, Masato; Tanaka, Yasuhito

    2013-01-01

    Background The Japanese Society for Surgery of the Foot (JSSF) is developing a QOL questionnaire instrument for use in pathological conditions related to the foot and ankle. The main body of the outcome instrument (the Self-Administered Foot Evaluation Questionnaire, SAFE-Q version 2) consists of 34 questionnaire items, which provide five subscale scores (1: Pain and Pain-Related; 2: Physical Functioning and Daily Living; 3: Social Functioning; 4: Shoe-Related; and 5: General Health and Well-...

  3. Intravascularly Administered RGD-Displaying Measles Viruses Bind to and Infect Neovessel Endothelial Cells In Vivo

    OpenAIRE

    Ong, Hooi Tin; Trejo, Theodore R; Pham, Linh D.; Oberg, Ann L.; Russell, Stephen J.; Peng, Kah-Whye

    2009-01-01

    Systemically administered vectors must cross the endothelial lining of tumor blood vessels to access cancer cells. Vectors that interact with markers on the lumenal surface of these endothelial cells might have enhanced tumor localization. Here, we generated oncolytic measles viruses (MVs) displaying αvβ3 integrin-binding peptides, cyclic arginine-glycine-aspartate (RGD) or echistatin, on the measles hemagglutinin protein. Both viruses had expanded tropisms, and efficiently entered target cel...

  4. Effect of Sulfonylureas Administered Centrally on the Blood Glucose Level in Immobilization Stress Model

    OpenAIRE

    Sharma, Naveen; Sim, Yun-Beom; Park, Soo-hyun; Lim, Su-Min; Kim, Sung-Su; Jung, Jun-Sub; Hong, Jae-Seung; Suh, Hong-Won

    2015-01-01

    Sulfonylureas are widely used as an antidiabetic drug. In the present study, the effects of sulfonylurea administered supraspinally on immobilization stress-induced blood glucose level were studied in ICR mice. Mice were once enforced into immobilization stress for 30 min and returned to the cage. The blood glucose level was measured 30, 60, and 120 min after immobilization stress initiation. We found that intracerebroventricular (i.c.v.) injection with 30 µg of glyburide, glipizide, glimepir...

  5. Phase I trial of intramuscularly administered tumor necrosis factor in patients with advanced cancer.

    Science.gov (United States)

    Jakubowski, A A; Casper, E S; Gabrilove, J L; Templeton, M A; Sherwin, S A; Oettgen, H F

    1989-03-01

    A phase I trial of intramuscularly administered recombinant human tumor necrosis factor (rTNF) was conducted in 19 adult patients with advanced solid tumors. The agent was administered daily for up to five consecutive days every other week for two to four courses. Doses of rTNF ranged from 5 to 200 micrograms/m2/d. Dose-limiting toxicities were encountered at doses greater than 100 micrograms/m2/d. Toxicities included tenderness, erythema and induration at the site of injection, fatigue, fever, chills, headache, anorexia, nausea, vomiting, and diarrhea. Moderate to marked reductions in WBC and platelet counts were observed regularly at the highest dose levels, but none were clinically significant. Hepatic enzyme elevation was seen frequently, and two patients developed hyperbilirubinemia. Only one of seven patients treated with doses greater than 100 micrograms/m2/d completed the planned course of therapy. Even at the highest dose levels, serum concentrations of rTNF could only rarely be detected in the serum. No therapeutic responses were observed. The maximal tolerated dose (MTD) of rTNF in this trial was 150 micrograms/m2/d, administered for two courses. PMID:2918329

  6. [The hypertensive effect of vasopressin administered into the median eminence of the hypothalamus in rats].

    Science.gov (United States)

    Gindeva, R; Pencheva, T

    1991-01-01

    Data about direct effect of vasopressin (VP) on the central arterial pressure (AP) orientated us to investigate the effect of its local administration in the median eminence (ME) of the hypothalamus in rats. For this purpose VP was administered in ME under micropellet form. AP was measured indirectly on the tail of rats up to 96th hour after operation. After implantation of VP there was an elevation of AP with maximum in the first hour, which was statistically significant (p less than 0.01). Identical manipulation (sham operation) was performed to control the lesion effect. Transitory lowering of AP with maximum in the first hour was also established and it was statistically significant (p less than 0.001), For exclusion a nonspecific systemic effect of VP the same dose was administered in the parietal cortex, during which transitory and short-lasting reaction occurred in the first hour after the operation. The data indicate that the peptide, administered in ME under micropellet form, could induce a longlasting hypertensive effect. PMID:1884687

  7. Treatment of verb anomia in aphasia: efficacy of self-administered therapy using a smart tablet.

    Science.gov (United States)

    Lavoie, Monica; Routhier, Sonia; Légaré, Annie; Macoir, Joël

    2016-01-01

    Aphasia is a chronic condition that usually requires long-term rehabilitation. However, even if many effective treatments can be offered to patients and families, speech therapy services for individuals with aphasia often remain limited because of logistical and financial considerations, especially more than 6 months after stroke. Therefore, the need to develop tools to maximize rehabilitation potential is unquestionable. The aim of this study was to test the efficacy of a self-administered treatment delivered with a smart tablet to improve written verb naming skills in CP, a 63-year-old woman with chronic aphasia. An ABA multiple baseline design was used to compare CP's performance in verb naming on three equivalent lists of stimuli trained with a hierarchy of cues, trained with no cues, and not trained. Results suggest that graphemic cueing therapy, done four times a week for 3 weeks, led to better written verb naming compared to baseline and to the untrained list. Moreover, generalization of the effects of treatment was observed in verb production, assessed with a noun-to-verb production task. Results of this study suggest that self-administered training with a smart tablet is effective in improving naming skills in chronic aphasia. Future studies are needed to confirm the effectiveness of new technologies in self-administered treatment of acquired language deficits. PMID:26007615

  8. Ghrelin and gastric acid secretion

    Institute of Scientific and Technical Information of China (English)

    Koji Yakabi; Junichi Kawashima; Shingo Kato

    2008-01-01

    Ghrelin, a novel growth hormone-releasing peptide, was originally isolated from rat and human stomach. Ghrelin has been known to increase the secretion of growth hormone (GH), food intake, and body weight gain when administered peripherally or centrally. Ghrelin is also known to stimulate the gastric motility and the secretion of gastric acid. In the previous studies, the action of ghrelin on acid secretion was shown to be as strong as that of histamine and gastrin in-vivo experiment. In the studies, the mechanism for the action of ghrelin was also investigated. It was shown that vagotomy completely inhibited the action of ghrelin on the secretion of gastric acid suggesting that vagal nerve is involved in the mechanism for the action of ghrelin on acid secretion. As famotidine did not inhibit ghrelin-in-duced acid secretion in the study by Masuda et al, they concluded that histamine was not involved in the action of ghrelin on acid secretion. However, we have shown that famotidine completely inhibited ghrelin-induced acid secretion and histidine decarboxylase (HDC) mRNA was increased in gastric mucosa by ghrelin injection which is inhibited by vagotomy Our results indicate that histamine is involved in the action of ghrelin on acid secretion. Furthermore synergistic action of gastrin and ghrelin on gastric add secretion was shown. Although gastrin has important roles in postprandial secretion of gastric acid, ghrelin may be related to acid secretion during fasting period or at night. However, further studies are needed to elucidate the physiological role of ghrelin in acid secretion.

  9. Folic Acid

    Science.gov (United States)

    ... found naturally in some foods, including leafy vegetables, citrus fruits, beans (legumes), and whole grains. Folic acid ... mcg of folic acid every day for good health. But older adults need to be sure they ...

  10. Dietary Hyaluronic Acid Migrates into the Skin of Rats

    Directory of Open Access Journals (Sweden)

    Mariko Oe

    2014-01-01

    Full Text Available Hyaluronic acid is a constituent of the skin and helps to maintain hydration. The oral intake of hyaluronic acid increases water in the horny layer as demonstrated by human trials, but in vivo kinetics has not been shown. This study confirmed the absorption, migration, and excretion of 14C-labeled hyaluronic acid (14C-hyaluronic acid. 14C-hyaluronic acid was orally or intravenously administered to male SD rats aged 7 to 8 weeks. Plasma radioactivity after oral administration showed the highest level 8 hours after administration, and orally administered 14C-hyaluronic acid was found in the blood. Approximately 90% of 14C-hyaluronic acid was absorbed from the digestive tract and used as an energy source or a structural constituent of tissues based on tests of the urine, feces, expired air, and cadaver up to 168 hours (one week after administration. The autoradiographic results suggested that radioactivity was distributed systematically and then reduced over time. The radioactivity was higher in the skin than in the blood at 24 and 96 hours after administration. The results show the possibility that orally administered hyaluronic acid migrated into the skin. No excessive accumulation was observed and more than 90% of the hyaluronic acid was excreted in expired air or urine.

  11. Reliability Analysis for the Internationally Administered 2002 Series GED Tests. GED Testing Service[R] Research Studies, 2009-3

    Science.gov (United States)

    Setzer, J. Carl; He, Yi

    2009-01-01

    Reliability Analysis for the Internationally Administered 2002 Series GED (General Educational Development) Tests Reliability refers to the consistency, or stability, of test scores when the authors administer the measurement procedure repeatedly to groups of examinees (American Educational Research Association [AERA], American Psychological…

  12. 27 CFR 70.41 - Rewards for information relating to violations of tax laws administered by the Bureau.

    Science.gov (United States)

    2010-04-01

    ... relating to violations of tax laws administered by the Bureau. 70.41 Section 70.41 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY (CONTINUED... Powers and Duties § 70.41 Rewards for information relating to violations of tax laws administered by...

  13. 20 CFR 641.400 - What entities are eligible to apply to the Department for funds to administer SCSEP community...

    Science.gov (United States)

    2010-04-01

    ... Department for funds to administer SCSEP community service projects? 641.400 Section 641.400 Employees... COMMUNITY SERVICE EMPLOYMENT PROGRAM Grant Application, Eligibility, and Award Requirements § 641.400 What entities are eligible to apply to the Department for funds to administer SCSEP community service...

  14. 8 CFR 337.2 - Oath administered by the Immigration and Naturalization Service or an Immigration Judge.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Oath administered by the Immigration and Naturalization Service or an Immigration Judge. 337.2 Section 337.2 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY NATIONALITY REGULATIONS OATH OF ALLEGIANCE § 337.2 Oath administered by the Immigration...

  15. Validity and reproducibility of self-administered joint counts. A prospective longitudinal followup study in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    Prevoo, MLL; Kuper, IH; vantHof, MA; vanLeeuwen, MA; vandePutte, LBA; vanRiel, PLCM

    1996-01-01

    Objective. To investigate the reproducibility and validity of self-administered joint counts (JC), measuring tenderness, swelling and the combination of both, in a longitudinal study, Methods. At the outpatient department a form self-administered by patients (SAI-form), was used to measure joint inv

  16. Evaluation of dexamethasone on fetal maturation and delivery in mares when administered on days 305 to 307 of gestation

    Science.gov (United States)

    In many species corticosteroids are administered to the dam to induce precocious fetal maturation when the pregnancy is at risk; however in the mare this has met with mixed results. Previously we showed that 24 mg betamethasone administered to pregnant mares on d305 to 307 of pregnancy tended to...

  17. Validation of the Portuguese self-administered computerised 24-hour dietary recall among second-, third- and fourth-grade children

    Science.gov (United States)

    Current methods for assessing children's dietary intake, such as interviewer-administered 24-h dietary recall (24-h DR), are time consuming and resource intensive. Self-administered instruments offer a low-cost diet assessment method for use with children. The present study assessed the validity of ...

  18. Plasma Pharmacokinetics of Sulfadiazine Administered Twice Daily versus Four Times Daily Are Similar in Human Immunodeficiency Virus-Infected Patients†

    OpenAIRE

    Jordan, M. Kelli; Burstein, Aaron H.; Rock-Kress, Diane; Alfaro, Raul M.; Pau, Alice K.; Kovacs, Joseph A.; Piscitelli, Stephen C.

    2004-01-01

    The pharmacokinetics of 2,000 mg of sulfadiazine administered twice daily (BID) versus those of 1,000 mg administered four times a day were compared in eight human immunodeficiency virus-infected patients. No differences in pharmacokinetic parameters were detected between the regimens. These data provide a pharmacokinetic rationale for BID dosing of sulfadiazine for the treatment and suppression of toxoplasmosis.

  19. Serum metabolites of proanthocyanidin-administered rats decrease lipid synthesis in HepG2 cells.

    Science.gov (United States)

    Guerrero, Ligia; Margalef, Maria; Pons, Zara; Quiñones, Mar; Arola, Lluis; Arola-Arnal, Anna; Muguerza, Begoña

    2013-12-01

    The regular consumption of flavonoids has been associated with reduced mortality and a decreased risk of cardiovascular diseases. The proanthocyanidins found in plasma are very different from the original flavonoids in food sources. The use of physiologically appropriate conjugates of proanthocyanidins is essential for the in vitro analysis of flavonoid bioactivity. In this study, the effect of different proanthocyanidin-rich extracts, which were obtained from cocoa (CCX), French maritime pine bark (Pycnogenol extract, PYC) and grape seed (GSPE), on lipid homeostasis was evaluated. Hepatic human cells (HepG2 cells) were treated with 25 mg/L of CCX, PYC or GSPE. We also performed in vitro experiments to assess the effect on lipid synthesis that is induced by the bioactive GSPE proanthocyanidins using the physiological metabolites that are present in the serum of GSPE-administered rats. For this, Wistar rats were administered 1 g/kg of GSPE, and serum was collected after 2 h. The semipurified serum of GSPE-administered rats was fully characterized by liquid chromatography tandem triple quadrupole mass spectrometry (LC-QqQ/MS(2)). The lipids studied in the analyses were free cholesterol (FC), cholesterol ester (CE) and triglycerides (TG). All three proanthocyanidin-rich extracts induced a remarkable decrease in the de novo lipid synthesis in HepG2 cells. Moreover, GSPE rat serum metabolites reduced the total percentage of CE, FC and particularly TG; this reduction was significantly higher than that observed in the cells directly treated with GSPE. In conclusion, the bioactivity of the physiological metabolites that are present in the serum of rats after their ingestion of a proanthocyanidin-rich extract was demonstrated in Hep G2 cells. PMID:24231101

  20. Indomethacin administered early in the postnatal period results in reduced glomerular number in the adult rat.

    Science.gov (United States)

    Kent, A L; Koina, M E; Gubhaju, L; Cullen-McEwen, L A; Bertram, J F; Lynnhtun, J; Shadbolt, B; Falk, M C; Dahlstrom, J E

    2014-11-15

    Indomethacin and ibuprofen are administered to close a patent ductus arteriosus (PDA) during active glomerulogenesis. Light and electron microscopic glomerular changes with no change in glomerular number were seen following indomethacin and ibuprofen treatment during glomerulogenesis at 14 days after birth in a neonatal rat model. This present study aimed to determine whether longstanding renal structural changes are present at 30 days and 6 mo (equivalent to human adulthood). Rat pups were administered indomethacin or ibuprofen antenatally on days 18-20 (0.5 mg·kg(-1)·dose(-1) indomethacin; 10 mg·kg(-1)·dose(-1) ibuprofen) or postnatally intraperitoneally from day 1 to 3 or day 1 to 5 (0.2 mg·kg(-1)·dose(-1) indomethacin; 10 mg·kg(-1)·dose(-1) ibuprofen). Control groups received no treatment or normal saline intraperitoneally. Pups were killed at 30 days of age and 6 mo of age. Tissue blocks from right kidneys were prepared for light and electron microscopic examination, while total glomerular number was determined in left kidneys using unbiased stereology. Eight pups were included in each group from 14 maternal rats. At 30 days and 6 mo, there were persistent electron microscopy abnormalities of the glomerular basement membrane in those receiving postnatal indomethacin and ibuprofen. There were no significant light microscopy findings at 30 days or 6 mo. At 6 mo, there were significantly fewer glomeruli in those receiving postnatal indomethacin but not ibuprofen (P = 0.003). In conclusion, indomethacin administered during glomerulogenesis appears to reduce the number of glomeruli in adulthood. Alternative options for closing a PDA should be considered including ibuprofen as well as emerging therapies such as paracetamol. PMID:25186294

  1. Interviewer versus self-administered health-related quality of life questionnaires - Does it matter?

    Directory of Open Access Journals (Sweden)

    Ackatz Lori E

    2011-05-01

    Full Text Available Abstract Background Patient-reported outcomes are measured in many epidemiologic studies using self- or interviewer-administered questionnaires. While in some studies differences between these administration formats were observed, other studies did not show statistically significant differences important to patients. Since the evidence about the effect of administration format is inconsistent and mainly available from cross-sectional studies our aim was to assess the effects of different administration formats on repeated measurements of patient-reported outcomes in participants with AIDS enrolled in the Longitudinal Study of Ocular Complications of AIDS. Methods We included participants enrolled in the Longitudinal Study of Ocular Complications in AIDS (LSOCA who completed the Medical Outcome Study [MOS] -HIV questionnaire, the EuroQol, the Feeling Thermometer and the Visual Function Questionnaire (VFQ 25 every six months thereafter using self- or interviewer-administration. A large print questionnaire was available for participants with visual impairment. Considering all measurements over time and adjusting for patient and study site characteristics we used linear models to compare HRQL scores (all scores from 0-100 between administration formats. We defined adjusted differences of ≥0.2 standard deviations [SD] to be quantitatively meaningful. Results We included 2,261 participants (80.6% males with a median of 43.1 years of age at enrolment who provided data on 23,420 study visits. The self-administered MOS-HIV, Feeling Thermometer and EuroQol were used in 70% of all visits and the VFQ-25 in 80%. For eight domains of the MOS-HIV differences between the interviewer- and self- administered format were Conclusions Our large study provides evidence that administration formats do not have a meaningful effect on repeated measurements of patient-reported outcomes. As a consequence, longitudinal studies may not need to consider the effect of

  2. Serum pharmacokinetics of clindamycin hydrochloride in normal dogs when administered at two dosage regimens.

    Science.gov (United States)

    Saridomichelakis, Manolis N; Athanasiou, Labrini V; Salame, Michel; Chatzis, Manolis K; Katsoudas, Vassilis; Pappas, Ioannis S

    2011-10-01

    The aim of this cross-over study was to compare clindamycin pharmacokinetics in the serum of clinically normal dogs when administered orally at two dosage regimens (5.5 mg/kg, twice daily, and 11 mg/kg, once daily), separated by a 1 week wash-out period. Serum samples were obtained from six clinically normal laboratory beagles before, 3, 6, 9 and 12 h after the first and fifth dose of clindamycin at 5.5 mg/kg, twice daily, and before, 3, 6, 9, 12, 18 and 24 h after the first and third dose at 11 mg/kg, once daily. Serum clindamycin concentrations were determined by reverse-phase liquid chromatography coupled with mass spectrometry. Results were analysed using Student's paired t-test, at a 5% level of significance. Values of pharmacokinetic parameters that differed significantly between the two dosage regimens included the following: maximal concentration and area under the concentration-time curve were higher at 11 mg/kg, once daily, than at 5.5 mg/kg, twice daily; and, more importantly, the ratio of AUC(0-24) to the minimal inhibitory concentration (MIC) value of 0.5 μg/mL for a 24 h period (AUC(0-24)/MIC) was higher when clindamycin was administered at 11 than at 5.5 mg/kg, at least during the first day of drug administration. Therefore, a better pharmacokinetic profile may be expected when clindamycin is administered at 11 mg/kg, once daily, for the treatment of canine pyoderma caused by Staphylococcus pseudintermedius. PMID:21418348

  3. [Dynamic analysis of pharmacokinetics of orally administered drugs using positron emission tomography].

    Science.gov (United States)

    Kataoka, Makoto

    2012-01-01

    Positron emission tomography (PET) is a powerful and noninvasive technology for molecular imaging in living systems. Its high sensitivity and high spatial-temporal resolution make this technology particularly useful to analyze the disposition of drugs in the body. PET technology could be applied to analyze the process of distribution of orally administered drugs on the basis of time-profiles of radioactivity in vivo. Kinetic analysis of radioactivity derived from 18F-labeled 2-fluoro-2-deoxy-D-glucose administered orally to rats under several conditions indicated that not only gastric emptying and intestinal transit but also the rate constant of intestinal absorption and limited process of oral absorption could be evaluated quantitatively. After oral administration of 11C-labeled telmisartan with or without non-radiolabeled telmisartan, systemic bioavailability and hepatic distribution of radioactivity significantly increased non-linearly with dose. In the intestinal lumen, telmisartan and its glucuronide, converted by UDP-glucuronosyl transferase (UGT), were detected and the ratio of telmisartan decreased at a high dose of telmisartan. In vitro permeation study revealed that telmisartan is a substrate of P-glycoprotein (P-gp). It was reported that hepatic uptake of telmisartan is mediated by organic anion transporting polypeptide 1B3 (OATP1B3) and most of the hepatic radioactivity in the liver is derived from telmisartan. These results indicated that P-gp for intestinal absorption, OATP1B3 for hepatic uptake and UGT for glucuronidation could be considered as limiting steps of orally administered telmisartan. Therefore, PET study is highly anticipated to be a potent tool for better understanding of gastrointestinal absorption and the subsequent tissue distribution of various drugs and candidates. PMID:22864349

  4. Dietary Hyaluronic Acid Migrates into the Skin of Rats

    OpenAIRE

    Mariko Oe; Koichi Mitsugi; Wataru Odanaka; Hideto Yoshida; Ryosuke Matsuoka; Satoshi Seino; Tomoyuki Kanemitsu; Yasunobu Masuda

    2014-01-01

    Hyaluronic acid is a constituent of the skin and helps to maintain hydration. The oral intake of hyaluronic acid increases water in the horny layer as demonstrated by human trials, but in vivo kinetics has not been shown. This study confirmed the absorption, migration, and excretion of 14C-labeled hyaluronic acid (14C-hyaluronic acid). 14C-hyaluronic acid was orally or intravenously administered to male SD rats aged 7 to 8 weeks. Plasma radioactivity after oral administration showed the highe...

  5. Crossover study of the pharmacokinetics of ceftriaxone administered intravenously or intramuscularly to healthy volunteers.

    OpenAIRE

    Meyers, B R; Srulevitch, E S; Jacobson, J; Hirschman, S Z

    1983-01-01

    The pharmacokinetics of ceftriaxone were investigated in six healthy adults. One-gram doses were administered either intramuscularly or intravenously in a crossover design study. Mean peak ceftriaxone concentrations in plasma of 79.2 and 123.2 micrograms/ml were achieved with intramuscular injection and intravenous infusion, respectively, with plasma half-lives of 5.4 and 5.8 h. The urinary recovery of ceftriaxone in the first 24 h was 37% after intravenous infusion and 25% after intramuscula...

  6. Orally administered moxifloxacin prolongs QTc in healthy Chinese volunteers: a randomized, single-blind, crossover study

    OpenAIRE

    Chen, Qian; Liu, Yan-Mei; Liu, Yun; Mendzelevski, Boaz; Chanter, Dennis; Pu, Hua-hua; Liu, Gang-yi; Weng, Onglee; Hu, Chao-Ying; Wang, Wei; Yu, Chen; Jia, Jing-Ying

    2015-01-01

    Aim: To investigate the QT/QTc effects of orally administered moxifloxacin in healthy Chinese volunteers. Methods: This was a single-blinded, randomized, single-dose, placebo-controlled, two-period cross-over study. A total of 24 healthy Chinese volunteers were enrolled, randomly assigned to two groups: one group received moxifloxacin (400 mg, po) followed by placebo with a 7-d interval, another group received placebo followed by moxifloxacin with a 7-d interval. On the days of dosing, 12-lea...

  7. Relative bioavailability of methadone hydrochloride administered in chewing gum and tablets

    DEFF Research Database (Denmark)

    Christrup, Lona Louring; Angelo, H.R.; Bonde, J.;

    1990-01-01

    Methadone administered in chewing gum in doses of 16.7-22.6 mg to seven patients in a study using an open balanced cross-over design, was compared with 20 mg of methadone given perorally as tablets. There was no significant difference in the AUC/D obtained after administration of chewing gum and...... tablets (p>0.05). It is concluded that the chewing gum formulation should be considered for further testing with respect to suppression of abstinence syndrome in narcotic addicts....

  8. The Comparison of Doxycycline Residue in the Meat of Broiler Chickens Administered in Feed and Water

    OpenAIRE

    A. D. Wijayanti; Wihandoyo; A. W. Rosetyadewi

    2011-01-01

    The purpose of this research was to investigate the effect of doxycycline (a tetracycline derivative) administered at disease-prevention dose given daily in the feed and drinking water on the residue level in the broiler-chicken meat. Doxycycline at concentration of 100 ppm was mixed in the drinking water (1 g of doxycycline in 10 L of drinking water) and feed (1 g of doxycycline in 10 kg of feed). Samples of chicken meat were taken every week to measure their residue level. Analysis of doxyc...

  9. Current role of non-anesthesiologist administered propofol sedation in advanced interventional endoscopy

    DEFF Research Database (Denmark)

    Burtea, Daniela Elena; Dimitriu, Anca; Maloş, Anca Elena;

    2015-01-01

    the patients and medical personnel. Current guidelines support the use of propofol sedation, which has the same rate of adverse effects as traditional sedation with benzodiazepines and/or opioids, but decreases the procedural and recovery time. Non-anesthesiologist administered propofol sedation has become...... an option in most of the countries, due to limited anesthesiology resources and the increasing evidence from prospective studies and meta-analyses that the procedure is safe with a similar rate of adverse events with traditional sedation. The advantages include a high quality of endoscopic examination...

  10. Reduced administered activity, reduced acquisition time, and preserved image quality for the new CZT camera.

    OpenAIRE

    Oddstig, Jenny; Hedeer, Fredrik; Jögi, Jonas; Carlsson, Marcus; Hindorf, Cecilia; Engblom, Henrik

    2013-01-01

    BACKGROUND: For a 1-day myocardial perfusion SPECT (MPS) the recommendations for administered activity stated in the EANM guidelines results in an effective dose of up to 16 mSv per patient. Recently, a gamma camera system, based on cadmium zinc telluride (CZT) technology, was introduced. This technique has the potential to reduce the effective dose and scan time compared to the conventional NaI gamma camera. The aim of this study was to investigate if the effective dose can be reduced with a...

  11. Characterization of acute biliary hyperplasia in Fisher 344 Rats administered the Indole-3-Carbinol Analog, NSC-743380

    Energy Technology Data Exchange (ETDEWEB)

    Eldridge, Sandy R.; Covey, Joseph; Morris, Joel [Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, MD, 20892 (United States); Fang, Bingliang [The University of Texas MD Anderson Cancer Center, Houston, TX, 77030 (United States); Horn, Thomas L. [IIT Research Institute, Chicago, IL, 60616 (United States); Elsass, Karen E. [Battelle Columbus, Columbus, OH, 43201 (United States); Hamre, John R. [Investigative Toxicology Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702 (United States); McCormick, David L. [IIT Research Institute, Chicago, IL, 60616 (United States); Davis, Myrtle A., E-mail: myrtledavis@mail.nih.gov [Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, MD, 20892 (United States)

    2014-12-15

    NSC-743380 (1-[(3-chlorophenyl)-methyl]-1H-indole-3-carbinol) is in early stages of development as an anticancer agent. Two metabolites reflect sequential conversion of the carbinol functionality to a carboxaldehyde and the major metabolite, 1-[(3-chlorophenyl)-methyl]-1H-indole-3-carboxylic acid. In an exploratory toxicity study in rats, NSC-743380 induced elevations in liver-associated serum enzymes and biliary hyperplasia. Biliary hyperplasia was observed 2 days after dosing orally for 2 consecutive days at 100 mg/kg/day. Notably, hepatotoxicity and biliary hyperplasia were observed after oral administration of the parent compound, but not when major metabolites were administered. The toxicities of a structurally similar but pharmacologically inactive molecule and a structurally diverse molecule with a similar efficacy profile in killing cancer cells in vitro were compared to NSC-743380 to explore scaffold versus target-mediated toxicity. Following two oral doses of 100 mg/kg/day given once daily on two consecutive days, the structurally unrelated active compound produced hepatic toxicity similar to NSC-743380. The structurally similar inactive compound did not, but, lower exposures were achieved. The weight of evidence implies that the hepatotoxicity associated with NSC-743380 is related to the anticancer activity of the parent molecule. Furthermore, because biliary hyperplasia represents an unmanageable and non-monitorable adverse effect in clinical settings, this model may provide an opportunity for investigators to use a short-duration study design to explore biomarkers of biliary hyperplasia. - Highlights: • NSC-743380 induced biliary hyperplasia in rats. • Toxicity of NSC-743380 appears to be related to its anticancer activity. • The model provides an opportunity to explore biomarkers of biliary hyperplasia.

  12. Toxicity of Hypericum perforatum (St. John's wort) administered during pregnancy and lactation in rats

    International Nuclear Information System (INIS)

    The popularity of St. John's wort (Hypericum perforatum) for the treatment of depression is increasing and, in recent years, concerns about its use during pregnancy and breastfeeding have emerged. The purpose of this study was to investigate, in Wistar rats, the effects of a treatment with hypericum administered prenatally and during breastfeeding (from 2 weeks before mating to 21 days after delivery). Two doses of the extract were chosen, 100 mg/kg per day, which, based on surface area, is comparable to the dose administered to humans, and 1000 mg/kg per day. A microscopical analysis of livers, kidneys, hearts, lungs, brains, and small bowels was performed. A severe damage was observed in the livers and kidneys of animals euthanized postnatally on days 0 and 21. The lesions were more severe with the higher dose and in animals that were breastfed for 21 days; however, an important renal and hepatic damage was evident also with the dose of 100 mg/kg per day. In addition, similar serious hepatic and renal lesions were evident also in animals that were exposed to hypericum only during breastfeeding. In particular, a focal hepatic damage, with vacuolization, lobular fibrosis, and disorganization of hepatic arrays was evident; in the kidney, a reduction in glomerular size, disappearance of Bowman's space, and hyaline tubular degeneration were found. The results obtained in this study indicate that further, appropriate histological studies should be performed in other animal species to better evaluate the safety of hypericum extracts taken during pregnancy and breastfeeding

  13. Population pharmacokinetic and pharmacodynamic modeling of epinephrine administered using a mobile inhaler.

    Science.gov (United States)

    Frechen, Sebastian; Suleiman, Ahmed Abbas; Mohammad Nejad Sigaroudi, Ali; Wachall, Bertil; Fuhr, Uwe

    2015-12-01

    Inhaled epinephrine is a potential alternative to self-administered intramuscular epinephrine in imminent anaphylactic reactions. The objective was to develop a pharmacokinetic-pharmacodynamic model describing exposure and effects on heart rate of inhaled epinephrine. Data from a 4-phase cross-over clinical trial in 9 healthy volunteers including 0.3 mg intramuscular epinephrine, two doses of inhaled epinephrine (4 mg/mL solution administered during [mean] 18 and 25 min, respectively) using a mobile pocket inhaler, and an inhaled placebo were analyzed using mixed-effects modeling. Inhaled epinephrine was available almost immediately and more rapidly than via the intramuscular route (absorption half-live 29 min). Epinephrine plasma concentrations declined rapidly after terminating inhalation (elimination half-life 4.1 min) offering the option to stop exposure in case of adverse events. While the expected maximum concentration was higher for inhaled epinephrine, this was not associated with safety concerns due to only moderate additional hemodynamic effects compared to intramuscular administration. Bioavailability after inhalation (4.7%) was subject to high interindividual and interoccasional variability highlighting that training of inhalation would be essential for patients. The proposed model suggests that the use of a highly concentrated epinephrine solution via inhalation may offer an effective treatment option in anaphylaxis, while efficacy in patients remains to be shown. PMID:26615448

  14. Bioavailability of detomidine administered sublingually to horses as an oromucosal gel.

    Science.gov (United States)

    Kaukinen, H; Aspegrén, J; Hyyppä, S; Tamm, L; Salonen, J S

    2011-02-01

    The objective of the study was to determine the absorption, bioavailability and sedative effect of detomidine administered to horses as an oromucosal gel compared to intravenous and intramuscular administration of detomidine injectable solution. The study was open and randomized, with three sequences crossover design. Nine healthy horses were given 40 μg/kg detomidine intravenously, intramuscularly or administered under the tongue with a 7-day wash-out period between treatments. Blood samples were collected before and after drug administration for the measurement of detomidine concentrations in serum. The effects of the route of administration on heart rate and rhythm were evaluated and the depth of sedation assessed. Mean (±SD) bioavailability of detomidine was 22% (±5.3%) after sublingual administration and 38.2% (±7.9%) after intramuscular administration. The sedative effects correlated with detomidine concentrations regardless of the route of administration. We conclude that less detomidine is absorbed when given sublingually than when given intramuscularly, because part of it does not reach the circulation. Sublingual administration of detomidine oromucosal gel at 40 μg/kg produces safe sedation in horses. Slow absorption leads to fewer and less pronounced adverse effects than the more rapid absorption after intramuscular injection. PMID:21219348

  15. Preliminary results of the analysis of the administered activities in diagnostic studies of nuclear medicine

    International Nuclear Information System (INIS)

    The worldwide use of Nuclear Medicine diagnostic procedures and the tendency to its increment, infers an important exposure of the population to ionising radiation; it has motivated that the IAEA in the International Basic Safety Standards (BSS), emits recommendations for the establishment of guidance levels of activities administered to the patients in diagnostic procedures. Taking into account the above-mentioned and that in Cuba there exist 20 departments of Nuclear Medicine that in the majority possess equipment with more than 20 years of operation, which influences directly the medical exposure. A survey was designed and applied in 10 of these departments. The survey evaluates the compliance with the BSS requirements, and specifically, the activities administered to the patients in Nuclear Medicine diagnostic procedures are analysed. In the present work the obtained preliminary results of the statistical analysis carried out on the activity values used in Nuclear Medicine departments are presented, and comparisons made for a proposal of guidance levels for the national practice, which is compared with those recommended internationally. (author)

  16. The effects of four different drugs administered through catheters on slime production in coagulase negative Staphylococci

    Directory of Open Access Journals (Sweden)

    J. Sedef Göçmen

    2012-12-01

    Full Text Available Objectives: Higher rate of slime production has been found in pathogen bacteria strains. Accordingly, the factors thatcontribute to higher slime production rate increase the infection risk, while the factors that reduce the slime productionrate will reduce the infection risk. The effect of some drugs that are administered through catheters in intensive careunits on slime production with coagulase negative Staphylococci was investigated.Materials and methods: In this study, the effect of four different preparations containing Glyceryl trinitrate (Perlinganit®, Dexmedetomidine (Precedex®, Esmolol (Brevibloc®, and Propofol (Propofol® on slime production of 24Staphylococcus epidermidis strains isolated from blood cultures of patients, and reference strain were investigated. Slimeproduction was determined using ‘the quantitative microdilution plaque test’ described by Christensen.Results: Under controlled medium, eight strains formed slimes, and in the media containing esmolol, glyceryl trinitrate,dexmedetomidine, and propofol slimes were positive for five, 21, 15, and 18 strains, respectively. The rate of slime productionin glyceryl trinitrate, dexmedetomidine, and propofol containing media were higher than that of the controls.Conclusions: In the light of the results of this study, it is concluded that the drugs and/or additives increase the rate ofslime production. The effects of the preparations administered through catheters on slime production should be investigated,and these effects should be kept in mind during their use. J Microbiol Infect Dis 2012; 2(4: 150-154Key words: Slime Production, Coagulase Negative Staphyloccoci, Parenteral drugs

  17. Assessing the relationship between antigenicity and immunogenicity of human rabies vaccines when administered by intradermal route

    Science.gov (United States)

    Bilagumba, Gangaboraiah; Ravish, Haradanahalli Shankarappa; Narayana, Hanumanthappa Ashwath Doddabele

    2010-01-01

    The metadata of 10 published studies and 3 vaccine trial reports comprising of 19 vaccine cohorts from four countries conducted over a period of 23 years (1986–2009) was used for metaanalysis. The vaccines studied were purified chick embryo cell vaccine (Rabipur, India and Germany), purified vero cell rabies vaccine (Verorab, France; Indirab, India) and human diploid cell vaccine (MIRV, France). The potency of these vaccines varied from 0.55 IU to 2.32 IU per intradermal dose of 0.1 ml per site. The vaccines were administered to 1,011 subjects comprising of 19 cohorts and using five different ID regimens. The immunogenicity was measured by assays of rabies virus neutralizing antibody (RVNA) titres using rapid fluorescent focus inhibition test (RFFIT) [15 cohorts] and mouse neutralization test (MNT) [4 cohorts]. The statistical analysis of the data was done by Karl Pearson's correlation coefficient to measure the relationship between antigenicity and immunogenicity. It was revealed that, there was no significant linear relationship between antigenicity and immunogenicity of rabies vaccines when administered by intradermal route (p > 0.230 and p > 0.568). PMID:20523131

  18. Anaesthetic and cardiopulmonary effects of intramuscular morphine, medetomidine and ketamine administered to telemetered cats.

    Science.gov (United States)

    Wiese, Ashley J; Muir, William W

    2007-04-01

    The quality and duration of anaesthesia, cardiorespiratory effects and recovery characteristics of a morphine, medetomidine, ketamine (MMK) drug combination were determined in cats. Six healthy, adult female cats were administered 0.2 mg/kg morphine sulphate, 60 microg/kg medetomidine hydrochloride, and 5 mg/kg ketamine hydrochloride intramuscularly. Atipamezole was administered intramuscularly at 120 min after MMK administration. Time to lateral recumbency, intubation, extubation and sternal recumbency were recorded. Cardiorespiratory variables and response to a noxious stimulus were recorded before and at 3 min and 10 min increments after drug administration until sternal recumbency. The time to lateral recumbency and intubation were 1.9+/-1.2 and 4.3+/-1.2 min, respectively. Body temperature and haemoglobin saturation with oxygen remained unchanged compared to baseline values throughout anaesthesia. Respiratory rate, tidal volume, minute volume, heart rate, and blood pressure were significantly decreased during anaesthesia compared to baseline values. One cat met criteria for hypotension (systolic blood pressure cat remained non-responsive to noxious stimuli from 3 to 120 min. Time to extubation and sternal recumbency following atipamezole were 2.9+/-1.1 and 4.7+/-1.0 min, respectively. MMK drug combination produced excellent short-term anaesthesia and analgesia with minimal cardiopulmonary depression. Anaesthesia lasted for at least 120 min in all but one cat and was effectively reversed by atipamezole. PMID:17198759

  19. Efficacy of self-administered treatments for pathological academic worry: A randomized controlled trial.

    Science.gov (United States)

    Wolitzky-Taylor, Kate B; Telch, Michael J

    2010-09-01

    Research on treatments for reducing pathological worry is limited. In particular, academic worry is a common theme in generalized anxiety disorder (GAD) samples as well as non-clinical student samples. Given the high cost of anxiety disorders to society, research is needed to examine the efficacy of self-administered treatments designed to reduce pathological worry. The primary goal of this study was to investigate the benefits of three self-administered interventions for reducing academic worry. College students (N = 113) experiencing clinically significant academic worry were randomized to either: (a) worry exposure (WE); (b) expressive writing (EW); (c) relaxation consisting of pulsed audio-photic stimulation (APS); or (d) waitlist control (WLC). Participants were instructed to practice their interventions three times per week for one month and completed home practice logs online to track treatment adherence. Academic worry, general anxiety, and perceived stress were assessed at baseline and post-treatment. Academic worry and general anxiety were also assessed at a three-month follow-up. Those assigned to the WE and APS conditions showed significant improvement relative to EW and WLC at post-treatment. All treatment conditions showed continued improvement by follow-up, with no between-group differences. Treatment and public health implications are discussed. PMID:20663491

  20. Mood changes by self-administered acupressure in Japanese college students: a randomized controlled trial.

    Science.gov (United States)

    Horiuchi, Satoshi; Tsuda, Akira; Honda, Yasuhiro; Kobayashi, Hisanori; Naruse, Mayu; Tsuchiyagaito, Aki

    2015-01-01

    The aim of this 2-week study was to examine the effects of self-administered acupressure intervention onlevels of mood of 54 students (34 males and 20 females) majoring in acupuncture and moxibustion medicineat a college located in Fukuoka, Japan. Eligibility criteria were the ability to complete the intervention accurately and no history of psychiatric diseases. The students were randomly assigned to one of the two groups: an intervention group (IG, n = 28) and a control group (CG, n = 26). The IG participants completed fiveacupressure sessions three times a day (morning, noon, and night), involving the application of pressure to six acupuncture points (GB12, SI17, and LI18 according to 2008 World Health OrganizationRegional Office in the Western Pacific standard), three on the left and three on the right side of the neck for 5 s each. The CG participants were requested to spend their time as usual. Self-reported levels of tension-anxiety, depression-dejection, anger-hostility, vigor, fatigue, and confusion over the past week were measured before and after the study as the main outcomes. Side effects were not predicted and not assessed. The retention rate of this trial was 100%. Improvements in mood, defined as a change from baseline to 2 weeks later, were significantly greater in IG. Our results showed that self-administered intervention had the ability to alter mood levels in college students. PMID:25946916

  1. Single-dose and steady-state pharmacokinetics of diltiazem administered in two different tablet formulations

    DEFF Research Database (Denmark)

    Christrup, Lona Louring; Bonde, J; Rasmussen, S N;

    1992-01-01

    Single-dose and steady state pharmacokinetics of diltiazem administered in two different oral formulations were assessed with particular reference to rate and extent of absorption. Following single dose administration a significant difference in tmax was observed (2.9 +/- 1.9 and 6.8 +/- 2.6 hr r...... the steady-state study do not differ significantly from 1.0, the confidence limits exceed the acceptable values given by Poulsen & Juul (personal communication 1990) (a 20% decrease or increase of the ratio to 0.8 or 1.2).......Single-dose and steady state pharmacokinetics of diltiazem administered in two different oral formulations were assessed with particular reference to rate and extent of absorption. Following single dose administration a significant difference in tmax was observed (2.9 +/- 1.9 and 6.8 +/- 2.6 hr...... respectively) whereas differences in AUC, t1/2 and Cmax were not significant. The AUC (mean +/- S.D.) values following single dose administration of Cardil and Cardizem were 678.4 +/- 321.5 and 948.6 +/- 580.6 ng.ml-1.hr respectively. The mean and the 95% confidence limits for the observed ratio AUCCardil...

  2. Stress-induced changes in the analgesic and thermic effects of morphine administered centrally.

    Science.gov (United States)

    Appelbaum, B D; Holtzman, S G

    1985-12-01

    Stress (e.g. restraint) potentiates analgesia and changes in body temperature induced by morphine administered systemically to rats. In order to determine if stress-induced potentiation of these effects of morphine are mediated within the central nervous system, restrained and unstressed groups of rats were injected in the lateral ventricle (i.c.v.) with graded doses of morphine, and their analgesic and body temperature responses were measured. Compared to unstressed animals, restrained rats had a greater analgesic response at each dose of morphine, characterized by an increase in both the magnitude and duration of the drug effect. The unstressed group of rats responded consistently to 1.0-100 micrograms of morphine with a 1.5-2.0 degrees C increase in core temperature. Restrained rats had either a smaller increase in body temperature or a hypothermia at these doses of morphine. Thus, restraint stress can modify the effects of morphine administered i.c.v. on analgesia and body temperature in a manner similar to that seen after systemic administration of morphine, indicating that this phenomenon is mediated centrally. PMID:4075121

  3. Peripherally administered nanoparticles target monocytic myeloid cells, secondary lymphoid organs and tumors in mice.

    Directory of Open Access Journals (Sweden)

    Iraklis C Kourtis

    Full Text Available Nanoparticles have been extensively developed for therapeutic and diagnostic applications. While the focus of nanoparticle trafficking in vivo has traditionally been on drug delivery and organ-level biodistribution and clearance, recent work in cancer biology and infectious disease suggests that targeting different cells within a given organ can substantially affect the quality of the immunological response. Here, we examine the cell-level biodistribution kinetics after administering ultrasmall Pluronic-stabilized poly(propylene sulfide nanoparticles in the mouse. These nanoparticles depend on lymphatic drainage to reach the lymph nodes and blood, and then enter the spleen rather than the liver, where they interact with monocytes, macrophages and myeloid dendritic cells. They were more readily taken up into lymphatics after intradermal (i.d. compared to intramuscular administration, leading to ∼50% increased bioavailability in blood. When administered i.d., their distribution favored antigen-presenting cells, with especially strong targeting to myeloid cells. In tumor-bearing mice, the monocytic and the polymorphonuclear myeloid-derived suppressor cell compartments were efficiently and preferentially targeted, rendering this nanoparticulate formulation potentially useful for reversing the highly suppressive activity of these cells in the tumor stroma.

  4. Drug: D01968 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D01968 Drug Zoledronic acid hydrate (JAN); Zoledronic acid (USAN); Zometa (TN) C5H10N2O7P2. H2O ... 290.0069 290.1049 D01968.gif Osteoporosis ... therapy adjunct Therapeutic category: 3999 ATC cod ... 900(2224) Terpenoid backbone biosynthesis map07047 Osteoporosis ... drugs Therapeutic category of drugs in Japan [BR:b ...

  5. Pharmacokinetics of ceftazidime administered to lactating and non-lactating goats

    Directory of Open Access Journals (Sweden)

    R. Rule

    2011-05-01

    Full Text Available The aim of this work was to determine the pharmacokinetics of intravenous (iv and intramuscular (im ceftazidime administered to lactating (LTG; n = 6 and non-lactating (NLTG; n=6 healthy Creole goats in 2 trials (T1 and T2. During T1 and T2, goats randomly received a single dose of im or iv ceftazidime (10 mg/kg. Serum concentration of iv ceftazidime in NLTG and LTG goats is best described by 2 and 3 compartment models, respectively. The pharmacokinetic parameters of iv and im ceftazidime administered to LTG and NLTG showed statistically significant differences (P<0.05 in the constants (λz, T1 vs T2 [iv] 0.5±0.1 vs 0.3±0.1 /h; T1 vs T2 [im] 0.5±0.2 vs 0.3±0.1 /h and in the mean times (t1/2, T 1 vs T 2 [iv] 1.6±0.3 vs 2.3±0.6 h; T 1 vs T 2 [im] 1.6±0.7 vs 2.6±0.9 h of elimination. The bioavailability of ceftazidime in LTG and NLTG was 113.0 ± 17.8 and 96.0 ± 18.0 %, respectively. Ceftazidime concentration in milk at 2 h was: iv = 1.9 ± 0.2 and im = 2.4 ± 0.5 μg/m ; the penetration in milk was iv = 18.3 ± 13.5 and im = 14.3 ± 10.6 %. Ninety-six hours after iv and im administration, residues of the drug were not found in milk. In conclusion, ceftazidime, when administered to goats, showed high concentration times in serum, good penetration into milk and a bioavailability that makes it suitable to be used by the im route.

  6. How do patients with inflammatory bowel disease want their biological therapy administered?

    Directory of Open Access Journals (Sweden)

    Lindsay Hannah

    2010-01-01

    Full Text Available Abstract Background Infliximab is usually administered by two monthly intravenous (iv infusions, therefore requiring visits to hospital. Adalimumab is administered by self subcutaneous (sc injections every other week. Both of these anti-TNF drugs appear to be equally efficacious in the treatment of Crohn's Disease and therefore the decision regarding which drug to choose will depend to some extent on patient choice, which may be based on the mode of administration. The aims of this study were to compare preferences in Inflammatory Bowel Disease (IBD patients for two currently available anti-TNF agents and the reasons for their choices. Methods An anonymous questionnaire was distributed to IBD patients who had attended the Gastroenterology service (Ulster Hospital, Dundonald, Belfast, N. Ireland. UK between January 2007 and December 2007. The patients were asked in a hypothetical situation if the following administering methods of anti-TNF drugs (intravenous or subcutaneous were available, which drug route of administration would they choose. Results One hundred and twenty-five patients fulfilled the inclusion criteria and were issued questionnaires, of these 78 questionnaires were returned (62 percent response. The mean age of respondent was 44 years. Of the total number of respondents, 33 patients (42 percent preferred infliximab and 19 patients (24 percent preferred adalimumab (p = 0.07. Twenty-six patients (33 percent did not indicate a preference for either biological therapy and were not included in the final analysis. The commonest reason cited for those who chose infliximab (iv was: "I do not like the idea of self-injecting," (67 percent. For those patients who preferred adalimumab (sc the commonest reason cited was: "I prefer the convenience of injecting at home," (79 percent. Of those patients who had previously been treated with an anti-TNF therapy (n = 10, all infliximab six patients stated that they would prefer infliximab if given

  7. Tissue distribution and excretion kinetics of orally administered silica nanoparticles in rats

    Directory of Open Access Journals (Sweden)

    Lee JA

    2014-12-01

    Full Text Available Jeong-A Lee,1 Mi-Kyung Kim,1 Hee-Jeong Paek,1 Yu-Ri Kim,2 Meyoung-Kon Kim,2 Jong-Kwon Lee,3 Jayoung Jeong,3 Soo-Jin Choi1 1Department of Food Science and Technology, Seoul Women’s University, Seoul, Republic of Korea; 2Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, Republic of Korea; 3Toxicological Research Division, National Institute of Food and Drug Safety Evaluation, Chungchungbuk–do, Republic of Korea Purpose: The effects of particle size on the tissue distribution and excretion kinetics of silica nanoparticles and their biological fates were investigated following a single oral administration to male and female rats. Methods: Silica nanoparticles of two different sizes (20 nm and 100 nm were orally administered to male and female rats, respectively. Tissue distribution kinetics, excretion profiles, and fates in tissues were analyzed using elemental analysis and transmission electron microscopy. Results: The differently sized silica nanoparticles mainly distributed to kidneys and liver for 3 days post-administration and, to some extent, to lungs and spleen for 2 days post-administration, regardless of particle size or sex. Transmission electron microscopy and energy dispersive spectroscopy studies in tissues demonstrated almost intact particles in liver, but partially decomposed particles with an irregular morphology were found in kidneys, especially in rats that had been administered 20 nm nanoparticles. Size-dependent excretion kinetics were apparent and the smaller 20 nm particles were found to be more rapidly eliminated than the larger 100 nm particles. Elimination profiles showed 7%–8% of silica nanoparticles were excreted via urine, but most nanoparticles were excreted via feces, regardless of particle size or sex. Conclusion: The kidneys, liver, lungs, and spleen were found to be the target organs of orally-administered silica nanoparticles in rats, and this organ

  8. Radiation exposure to nuclear medicine technologists from administering I-131 therapy dosages

    International Nuclear Information System (INIS)

    Full text: Therapeutic doses of I-131 for treatment of thyroid cancer are administered orally in liquid or capsule form. During the last few years, a total number of patients loaded in our isolation ward increased from 4 to 10 patients per week. When considering radiation safety precautions for attending technologists, it is preferable to use the dose in capsules. The purpose of this study is to compare radiation exposure to nuclear medicine technologists from administering I-131 therapy dosages in capsules and in liquid form in a closed system. Materials and Methods: Three year radiation exposure to technologists during I-131 administration was analyzed. From January 2004 to June 2005 dose administration was in liquid form (n=263) and from July 2005 to February 2007 in capsules (n=541). Radiation dose assessment was performed with an electronic personal dosimeter (PDM 112). The dose rate in μSv and time spent per patient were recorded. Results: Dose received per patient when I-131 was given in a liquid was 3.50 ± 1.67 μSv and 1.17 ± 0.66 μSv when given in capsules. Compared with the use of a liquid, capsules significantly reduced radiation dose to technologists by 66% (P < 0.001). These doses received depended not only on the administered activity but also on the time, distance and shielding. Time spent per patient, including a brief visit before the time of dosing to explain the procedure and answer questions was reduced slightly from 4.4 ± 2.2 to 3.7 ± 1.8 minutes (P < 0.01). These correspond to a reduction in a yearly dose to 1 technologist by 40%, from 0.63 mSv to 0.38 mSv from dosing to 175 and 325 patients respectively. Conclusions: The measured doses clearly showed that handling of I-131 therapy dosages either in a liquid form or capsules are not the major contributors to the technologist's radiation exposure in routine clinical practice. However, one has to be cautious and follow good work practice to avoid risk of radiation exposure and radioiodine

  9. How do patients with inflammatory bowel disease want their biological therapy administered?

    LENUS (Irish Health Repository)

    Allen, Patrick B

    2010-01-01

    BACKGROUND: Infliximab is usually administered by two monthly intravenous (iv) infusions, therefore requiring visits to hospital. Adalimumab is administered by self subcutaneous (sc) injections every other week. Both of these anti-TNF drugs appear to be equally efficacious in the treatment of Crohn\\'s Disease and therefore the decision regarding which drug to choose will depend to some extent on patient choice, which may be based on the mode of administration.The aims of this study were to compare preferences in Inflammatory Bowel Disease (IBD) patients for two currently available anti-TNF agents and the reasons for their choices. METHODS: An anonymous questionnaire was distributed to IBD patients who had attended the Gastroenterology service (Ulster Hospital, Dundonald, Belfast, N. Ireland. UK) between January 2007 and December 2007. The patients were asked in a hypothetical situation if the following administering methods of anti-TNF drugs (intravenous or subcutaneous) were available, which drug route of administration would they choose. RESULTS: One hundred and twenty-five patients fulfilled the inclusion criteria and were issued questionnaires, of these 78 questionnaires were returned (62 percent response). The mean age of respondent was 44 years. Of the total number of respondents, 33 patients (42 percent) preferred infliximab and 19 patients (24 percent) preferred adalimumab (p = 0.07). Twenty-six patients (33 percent) did not indicate a preference for either biological therapy and were not included in the final analysis. The commonest reason cited for those who chose infliximab (iv) was: "I do not like the idea of self-injecting," (67 percent). For those patients who preferred adalimumab (sc) the commonest reason cited was: "I prefer the convenience of injecting at home," (79 percent). Of those patients who had previously been treated with an anti-TNF therapy (n = 10, all infliximab) six patients stated that they would prefer infliximab if given the choice

  10. Ibotenic acid and thioibotenic acid

    DEFF Research Database (Denmark)

    Hermit, Mette B; Greenwood, Jeremy R; Nielsen, Birgitte;

    2004-01-01

    In this study, we have determined and compared the pharmacological profiles of ibotenic acid and its isothiazole analogue thioibotenic acid at native rat ionotropic glutamate (iGlu) receptors and at recombinant rat metabotropic glutamate (mGlu) receptors expressed in mammalian cell lines....... Thioibotenic acid has a distinct pharmacological profile at group III mGlu receptors compared with the closely structurally related ibotenic acid; the former is a potent (low microm) agonist, whereas the latter is inactive. By comparing the conformational energy profiles of ibotenic and thioibotenic acid with...... the conformations preferred by the ligands upon docking to mGlu1 and models of the other mGlu subtypes, we propose that unlike other subtypes, group III mGlu receptor binding sites require a ligand conformation at an energy level which is prohibitively expensive for ibotenic acid, but not for...

  11. Effect of afobazole administered to pregnant rats during organogenesis on prenatal development of fetuses.

    Science.gov (United States)

    Bugayova, L I; Denisova, T D; Morozova, Yu A; Sergeeva, S A; Kharlamov, I V

    2014-11-01

    Experiments on pregnant rats have demonstrated the absence of damaging effect of Afobazole administered during the antenatal period on organogenesis in fetuses. Afobazole in a dose of 5 mg/kg given to pregnant rats on gestation days 6-16 reduced pre- and post-implantation fetal mortality and improved fertility; 20-day-old embryos had no developmental abnormalities and did not differ from controls by craniocaudal size, body weight, and skeleton ossification. Afobazole in a dose of 100 mg/kg reduced pre- and post-implantation fetal mortality, but had no effect on fertility. No congenital malformations were found in the fetuses, but they were characterized by lower craniocaudal size, body weight, and number of ossification foci in the sternum and spine. PMID:25403398

  12. Metabolic effects of growth hormone administered subcutaneously once or twice daily to growth hormone deficient adults

    DEFF Research Database (Denmark)

    Laursen, Torben; Jørgensen, Jens Otto Lunde; Christiansen, Jens Sandahl

    1994-01-01

    -term metabolic effects in GH deficient patients. An improved growth response is obtained in GH deficient children when a fixed weekly GH dose is administered by daily subcutaneous injections instead of twice or thrice-weekly intramuscular injections. A more pulsatile pattern and serum GH levels above zero might...... MEASUREMENTS: In a cross-over study, 8 GH deficient patients (age 16-43 years) were treated with 3 IU/m2/24 h of human GH. The dose was injected in the evening for 4 weeks and for another 4 weeks two-thirds was injected in the evening and one-third in the morning. At the end of each period the patients were...

  13. Changes in Lipid Profile of Rats Administered with Ethanolic Leaf Extract of Mucuna pruriens (Fabaceae

    Directory of Open Access Journals (Sweden)

    E.D. Eze

    2012-03-01

    Full Text Available The study evaluated the effect of ethanolic leaf extract of Mucuna pruriens on some lipid profile parameters of normoglycemic Wistar rats. The acute oral toxicity studies were conducted. The animals were administered with the plant extract at graded doses of 100, 200 and 400 mg/kg b w and metformin 250 mg/kg bw orally for 21 days. Blood samples were collected from the animals at the end of the treatment period and assayed for the serum concentration of total cholesterol, triglyceride, low-density lipoprotein and high-density lipoprotein cholesterol. The results showed the extract significantly reduced (p0.05 in the lipid profile in the group treated with 400 and 250 mg/kg b w of metformin. In conclusion, the results of the present findings may be beneficial and of clinical importance to individuals at risks of cardiovascular problems.

  14. The role of capnography in endoscopy patients undergoing nurse-administered propofol sedation

    DEFF Research Database (Denmark)

    Slagelse, Charlotte; Vilmann, Peter; Hornslet, Pernille;

    2013-01-01

    . The existing literature on capnography for endoscopy patients sedated with nurse-administered propofol sedation (NAPS) is limited. Can the addition of capnography to standard monitoring during endoscopy with NAPS reduce the number, duration, and level of hypoxia. Materials and methods. This study was...... a randomized controlled trial with an intervention group (capnography) and a control group (without capnography). Eligible subjects were consecutive patients for endoscopy at Gentofte Hospital compliant with the criteria of NAPS. Results. Five hundred and forty patients, 263 with capnography and 277...... without capnography, were included in the analysis. The number and total duration of hypoxia was reduced by 39.3% and 21.1% in the intervention group compared to the control group (p > 0.05). No differences in actions taken against insufficient respiration were found. Changes in end-tidal carbon dioxide...

  15. Comparative efficacy of terbutaline administered by Nebuhaler and by nebulizer in young children with acute asthma.

    Science.gov (United States)

    Pendergast, J; Hopkins, J; Timms, B; Van Asperen, P P

    1989-10-01

    We compared the use of terbutaline sulphate that was delivered by a nebulizer with its delivery by a Nebuhaler at two dose levels in 27 children (nine children per group) of between three and six years of age with acute asthma. No significant difference was found in the mean baseline clinical score among the three groups, and a significant decline occurred in the mean clinical scores in all groups by 15 minutes which was maintained to 60 minutes after the dose was administered. The decline that was achieved with delivery of the drug by way of a Nebuhaler (at either dose level) was not significantly different from that with a nebulizer, although cooperation with Nebuhaler usage was not universal in the age-group. PMID:2677624

  16. Protecting eyewitness evidence: examining the efficacy of a self-administered interview tool.

    Science.gov (United States)

    Gabbert, Fiona; Hope, Lorraine; Fisher, Ronald P

    2009-08-01

    Given the crucial role of eyewitness evidence, statements should be obtained as soon as possible after an incident. This is not always achieved due to demands on police resources. Two studies trace the development of a new tool, the Self-Administered Interview (SAI), designed to elicit a comprehensive initial statement. In Study 1, SAI participants reported more correct details than participants who provided a free recall account, and performed at the same level as participants given a Cognitive Interview. In Study 2, participants viewed a simulated crime and half recorded their statement using the SAI. After a delay of 1 week, all participants completed a free recall test. SAI participants recalled more correct details in the delayed recall task than control participants. PMID:18561007

  17. Current role of non-anesthesiologist administered propofolsedation in advanced interventional endoscopy

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Complex and lengthy endoscopic examinations likeendoscopic ultrasonography and/or endoscopic retrogradecholangiopancreatography benefit from deepsedation, due to an enhanced quality of examinations,reduced discomfort and anxiety of patients, as well asincreased satisfaction for both the patients and medicalpersonnel. Current guidelines support the use ofpropofol sedation, which has the same rate of adverseeffects as traditional sedation with benzodiazepines and/or opioids, but decreases the procedural and recoverytime. Non-anesthesiologist administered propofolsedation has become an option in most of the countries,due to limited anesthesiology resources and theincreasing evidence from prospective studies and metaanalysesthat the procedure is safe with a similar rate ofadverse events with traditional sedation. The advantagesinclude a high quality of endoscopic examination,improved satisfaction for patients and doctors, as wellas decreased recovery and discharge time. Despitethe advantages of non-anesthesiologist administeredpropofol, there is still a continuous debate related to thesuccessful generalization of the procedures.

  18. Correlation of administered activity and dosimetric data in patients treated with 131MIBG therapy

    International Nuclear Information System (INIS)

    Full text of publication follows. Aims: the purpose of the study was to optimized 131-MIBG (or 131I-MIBG) therapy in children and adults patients with neural crest tumors, by correlating the administered pro/KXg activity to whole-body dosimetry and hematologic toxicity. Materials and methods: from September 2003, to June 2012 twenty-four patients (9 children, 15 adults) (13 neuroblastoma, 9 pheochromocytoma/paraganglioma, 2 medullary thyroid carcinoma) treated with 131I-MIBG were enrolled in the study. In each patient dosimetric estimation was carried out with MIRD method after patient therapy, using imaging acquisition or probe determination (from 1 to 168 hours). Hematological toxicity was evaluated according to WHO grade by weekly blood count for at least 6 weeks or until recovery. Whole Body Dose (WBD) was correlated with administered pro/KXg activity and bone marrow toxicity. Results: a total of forty-five dosimetric studies have been performed, 16/45 in children and 29/45 in adult patients. Administered activity ranged from 7.4 to 16.65 GBq, corresponding in children to 5-21 mCi/KXg (median 10 mCi/KXg) and in adults to 3-7 mCi/KXg. (median 5 mCi/KXg). In 4 patients (3 children, 1 adult) 2 weeks after 131I-MING therapy autologous stem cell transplantations were performed. Grade II-III hematological toxicity was observed in all children and in 6/15 adult patient. Whole Body Dose ranged from 1 Gy to 3.6 Gy (median 1.7 Gy) in children, meanwhile it ranged between 0.55 and 1.87 Gy (median 0.96 Gy) in adults. In 5/16 children studies WBD was about 2 Gy and one child received a dose of 3.6 Gy (0.4 Gy/GBq), corresponding to an activity of 18 mCi/KXg. Conclusion: contrary to published data in children the pro/KXg activity is not a good predictor of WBD. In these cases WBD calculation can be affected by the presence of large tumor masses which overestimates the absorbed dose. In any case the administration of activity superior to 15 mCi/KXg is known to be associated

  19. Analgesic and cardiopulmonary effects of intrathecally administered romifidine or romifidine and ketamine in goats (Capra hircus

    Directory of Open Access Journals (Sweden)

    H.P. Aithal

    2001-07-01

    Full Text Available The study was conducted to evaluate the effects of romifidine alone (50 µg/kg and a combination of romifidine (50 µg/kg and ketamine (2.5 mg/kg after intrathecal administration in goats. Ten adult goats of either sex weighing between 15 and 20 kg were randomly placed in 2 groups (groups I and II. The agents were administered at the lumbosacral subarachnoid space. Clinico-physiological parameters such as analgesia, motor incoordination, sedation, salivation, heart rate, respiratory rate, arterial pressure, central venous pressure and rectal temperature were studied. Other haematobiochemical parameters monitored were packed cell volume, haemoglobin, plasma proteins, glucose, urea and creatinine. The onset of analgesia was faster in group II (35.5 ±6.25 s compared to that of group I (5.2 ±0.54 min. Analgesia of the tail, perineum, hind limbs, flank and thorax was mild to moderate in group I, but complete analgesia of tail, perineum and hind limbs was recorded in group II. Motor incoordination was mild in group I and severe in group II. Significant reduction in heart rate (more pronounced in group I and respiratory rate (more pronounced in group II, and a significant increase in central venous pressure were recorded in both groups. Mean arterial pressure was reduced in both groups, but more markedly in group I. Sedation, electro-cardiogram, rectal temperature and haemato-biochemical parameters did not show significant differences between the 2 groups. The results of this study indicated a possible synergistic analgesic interaction between intrathecally administered romifidine and ketamine, without causing any marked systemic effects in goats.

  20. Centrally administered isoproterenol induces sympathetic outflow via brain prostaglandin E2-mediated mechanisms in rats.

    Science.gov (United States)

    Ando, Kazuo; Kondo, Fumio; Yamaguchi, Naoko; Tachi, Masahiko; Fukayama, Minoru; Yoshikawa, Kazuhiro; Gosho, Masahiko; Fujiwara, Yoshihiro; Okada, Shoshiro

    2015-05-01

    Brain β-adrenoceptor stimulation can induce elevations of plasma levels of noradrenaline. However, there have been no detailed studies related to signaling pathways downstream of β-adrenoceptors responsible for central sympathetic outflow. In the present study, we pharmacologically examined the possibility that centrally administered isoproterenol can induce elevations of plasma noradrenaline levels in a brain prostaglandin-dependent manner. In addition, we also examined whether or not intracerebroventricular administration of isoproterenol could release endogenously synthesized prostaglandin (PG) E2 in the hypothalamic paraventricular nucleus (PVN) by using the brain microdialysis technique combined with liquid chromatography-ion trap tandem mass spectrometry (LC-ITMS(n)). Under urethane anesthesia, a femoral venous line was inserted for infusion of saline and a femoral arterial line was inserted for collecting blood samples. Next, animals were placed in a stereotaxic apparatus for application of test agents. Catecholamines in the plasma were extracted by alumina absorption and were assayed by high-performance liquid chromatography with electrochemical detection. Quantification of PGE2 in rat PVN microdialysates was performed by the LC-ITMS(n) method. We demonstrated that centrally administered isoproterenol-induced elevations of plasma noradrenaline could be mediated via activation of β-adrenoceptors and the downstream phospholipase A2-cyclooxygenase pathway. Furthermore, PGE2 in the PVN and the PGE2 receptor EP3 subtype appear to play an important role in the process. Our results suggest that central isoproterenol-induced sympathetic outflow is mediated via brain PGE2 in a PGE2 receptor EP3 subtype-dependent manner. PMID:25549851

  1. Effect of self-administered auricular acupressure on smoking cessation --a pilot study

    Directory of Open Access Journals (Sweden)

    Leung Lawrence

    2012-02-01

    Full Text Available Abstract Background Tobacco smoking is still a worldwide health risk. Current pharmacotherapies have at best, a success rate of no more than 50%. Auricular (ear acupressure has been purported to be beneficial in achieving smoking cessation in some studies, while in others has been deemed insignificant. We hereby describe the protocol for a three-arm randomised controlled trial to examine the possible benefits of self-administered acupressure for smoking cessation. Methods Sixty consenting participants with confirmed habit of tobacco smoking will be recruited and randomized into three arms to receive either auricular acupressure at five true acupoints (NADA protocol, auricular acupressure at five sham points, or no auricular acupressure at all. Participants having auricular acupressure will exert firm pressure to each acupoint bilaterally via the bead in the attached plasters whenever they feel the urge to smoke. The treatment phase will last for six weeks during which all participants will be assessed weekly to review their smoking log, state of abstinence, end-exhalation carbon monoxide levels and possible adverse effects including withdrawal reactions and stress levels. At any time, a successful quit date will be defined with continuous abstinence for the following consecutive 7 days. From then on, participants will be evaluated individually for continuous abstinence rate (CAR, end-exhalation carbon monoxide levels and adverse effects of stress and withdrawal at specified intervals up to 26 weeks. Expectancy of treatment will be assessed with a four-item Borkovec and Nau self-assessment credibility scale during and after intervention. Discussion We incorporate validated outcome measures of smoking cessation into our randomised controlled trial design with the objectives to evaluate the feasibility and possible benefits of self-administered auricular acupressure as a non-invasive alternative to pharmacotherapy for smoking cessation. Trial

  2. Regulatory analysis on criteria for the release of patients administered radioactive material

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, S.; McGuire, S.A. [Nuclear Regulatory Commission, Washington, DC (United States). Div. of Regulatory Applications; Behling, U.H.; Behling, K.; Goldin, D. [Cohen (S.) and Associates, Inc., McLean, VA (United States)

    1994-05-01

    The Nuclear Regulatory Commission (NRC) has received two petitions to amend its regulations in 10 CFR Parts 20 and 35 as they apply to doses received by members of the public exposed to patients released from a hospital after they have been administered radioactive material. While the two petitions are not identical they both request that the NRC establish a dose limit of 5 millisieverts (0.5 rem) per year for individuals exposed to patients who have been administered radioactive materials. This Regulatory Analysis evaluates three alternatives. Alternative 1 is for the NRC to amend its patient release criteria in 10 CFR 35.75 to use the more stringent dose limit of 1 millisievert per year in 10 CFR 20.1301(a) for its patient release criteria. Alternative 2 is for the NRC to continue using the existing patient release criteria in 10 CFR 35.75 of 1,110 megabecquerels of activity or a dose rate at one meter from the patient of 0.05 millisievert per hour. Alternative 3 is for the NRC to amend the patient release criteria in 10 CFR 35.75 to specify a dose limit of 5 millisieverts for patient release. The evaluation indicates that Alternative 1 would cause a prohibitively large increase in the national health care cost from retaining patients in a hospital longer and would cause significant personal and psychological costs to patients and their families. The choice of Alternatives 2 or 3 would affect only thyroid cancer patients treated with iodine-131. For those patients, Alternative 3 would result in less hospitalization than Alternative 2. Alternative 3 has a potential decrease in national health care cost of $30,000,000 per year but would increase the potential collective dose from released therapy patients by about 2,700 person-rem per year, mainly to family members.

  3. Pharmacokinetics of Immediate and Sustained Release Cephalexin Administered by Different Routes to Llamas (Lama glama)

    Science.gov (United States)

    Kreil, Verónica; Ambros, Luis; Prados, Ana Paula; Tarragona, Lisa; Monfrinotti, Agustina; Bramuglia, Guillermo

    2016-01-01

    We investigate the pharmacokinetics of two different cephalexin formulations administered to llamas by the intravenous (IV), intramuscular (IM), and subcutaneous (SC) routes, the minimum inhibitory concentration (MIC) of cephalexin against some Escherichia coli and staphylococci isolated from llamas, and we apply the PK/PD modelling approach, so that effective dosage recommendations for this species could be made. Six llamas received immediate (10 mg/kg, IV, IM, and SC) and sustained (8 mg/kg IM, SC) release cephalexin. Pharmacokinetic parameters were calculated by noncompartmental approach. Immediate release SC administration produced a significantly longer elimination half-life as compared with the IV and IM administration (1.3 ± 0.2 versus 0.6 ± 0.1 and 0.6 ± 0.1 h, resp.) and higher mean absorption time as compared with the IM administration (1.7 ± 0.5 versus 0.6 ± 0.4 h). Absolute bioavailability was in the range of 72–89% for both formulations and routes of administration. Cephalexin MIC90 values against staphylococci and E. coli were 1.0 and 8.0 μg/mL, respectively. Our results show that the immediate release formulation (10 mg/kg) would be effective for treating staphylococcal infections administered every 8 h (IM) or 12 h (SC), whereas the sustained release formulation (8 mg/kg) would require the IM or SC administration every 12 or 24 h, respectively. PMID:27051418

  4. Development of a self-administered early inflammatory arthritis detection tool

    Directory of Open Access Journals (Sweden)

    Tugwell Peter

    2010-03-01

    Full Text Available Abstract Background Barriers to care limit the potential benefits of pharmacological intervention for inflammatory arthritis. A self-administered questionnaire for early inflammatory arthritis (EIA detection may complement contemporary triage interventions to further reduce delays to rheumatologic care. The objective of this study was to develop a self-administered EIA detection tool for implementation in pre-primary care settings. Methods A core set of dimensions and constructs for EIA detection were systematically derived from the literature and augmented by investigative team arbitration. Identified constructs were formulated into lay language questions suitable for self-administration. A three-round Delphi consensus panel of EIA experts and stakeholders evaluated the relevance of each question to EIA detection and suggested additional items. Questions accepted by less than 70% of respondents in rounds one or two were eliminated. In round three, questions accepted by at least 80% of the panel were selected for the tool. Results Of 584 citations identified, data were extracted from 47 eligible articles. Upon arbitration of the literature synthesis, 30 constructs encompassing 13 dimensions were formulated into lay language questions and posed to the Delphi panel. A total of 181 EIA experts and stakeholders participated on the Delphi panel: round one, 60; round two, 59; and, round three, 169; 48 participated in all three rounds. The panel evaluated the 30 questions derived from the literature synthesis, suggested five additional items, and eliminated a total of 24. The eleven-question instrument developed captured dimensions of articular pain, swelling, and stiffness, distribution of joint involvement, function, and diagnostic and family history. Conclusions An eleven-question, EIA detection tool suitable for self-administration was developed to screen subjects with six to 52 weeks of musculoskeletal complaints. Psychometric and performance

  5. Radioprotection of hemopoiesis conferred by Acanthopanax senticosus Harms (Shigoka) administered before or after irradiation

    International Nuclear Information System (INIS)

    Acanthopanax senticosus Harms (Shigoka) extract has been observed to have radioprotective effects on hemopoiesis of irradiated mice (CBA/olac) when administered before or after irradiation by 60Co. The mechanisms of action were explored by studying the following parameters: 1) survival after lethal doses of irradiation; 2) recovery of spleen colony-forming units (CFU-S); 3) protective effect on endogenous CFU-S; and 4) effect on self-renewal of CFU-S. 1) The 30-day mortality due to bone marrow failure after irradiation was significantly reduced in Shigoka-treated mice. The maximum effect of the extract (80% survival) at a dose of 5 mg was observed when given intraperitoneally 24 h before a lethal dose of irradiation (9.5 Gy) and it was still effective when administered as late as 12 h after irradiation (30% survival). The radioprotective effect of Shigoka extract given before irradiation was not due to an increase in the total number of CFU-S but probably due to quiescent CFU-S that entered DNA synthesis (S-phase) 24 h after the injection of Shigoka extract. 2) Recovery of CFU-S in mice given the extract within 15 min after 4.75 Gy of whole body irradiation was also enhanced, especially in the spleen. The number of CFU-S in the bone marrow 24 h after irradiation showed a marked decrease. It returned to normal values in the bone marrow at day 11 in Shigoka-treated mice and at day 15 in nontreated irradiated mice. CFU-S in the spleen recovered more rapidly with an overshoot from days 7 to 21 in the Shigoka-treated mice, whereas in control irradiated mice it did not reach the normal value until day 21. 3) Nine days after sublethal doses of irradiation (7.0 Gy) the number of endogenous spleen colonies (endogenous CFU-S) was highest in mice given the extract 24 h before irradiation

  6. Evaluation of computed tomographic enterography with an orally administered lactulose solution in clinically normal dogs.

    Science.gov (United States)

    Keh, Seoyeon; Sohn, Jungmin; Choi, Mihyun; Lee, Namsoon; Jang, Jaeyoung; Kim, Hyunwook; Chang, Dongwoo; Choi, Mincheol; Yoon, Junghee

    2016-04-01

    OBJECTIVE To determine optimal techniques for CT enterography in clinically normal dogs and to evaluate luminal distention after oral administration of lactulose solution as a contrast agent. ANIMALS 15 healthy dogs. PROCEDURES CT was performed in a control group (2 dogs that underwent CT to evaluate metastasis and 5 other dogs). In a bolus administration group (5 dogs from the control group), lactulose solution (1.34 g/mL) was administered (60 mL/kg) rapidly via gastric tube to anesthetized dogs, and CT was performed every 10 minutes for 1 hour. In a continuous administration group of 8 other dogs, lactulose solution (60 mL/kg) was administered slowly via nasoesophageal tube over a period of 45 minutes. Then, 15 minutes after anesthetic induction, CT was performed every 10 minutes for 1 hour. Luminal distention of the small intestines was evaluated qualitatively by use of a 3-point scale. RESULTS All small intestinal segments had poor luminal distention in the control group. The terminal ileum had poor luminal distention for the bolus administration group. Nearly all segments had good luminal distention for the continuous administration group with mild adverse effects. Luminal distention scores from 0 to 20 minutes after lactulose administration were significantly higher than scores from 30 to 60 minutes. Interobserver reproducibility was high for all intestinal segments. CONCLUSIONS AND CLINICAL RELEVANCE CT performed between 0 and 20 minutes after continuous administration of lactulose solution (60 mL/kg) may reveal adequate luminal distention for examination of small intestinal segments in dogs. PMID:27027835

  7. Pharmacokinetics of midazolam administered concurrently with ketamine after intravenous bolus or infusion in dogs.

    Science.gov (United States)

    Brown, S A; Jacobson, J D; Hartsfield, S M

    1993-12-01

    Midazolam, a water-soluble benzodiazepine tranquilizer, has been considered by some veterinary anaesthesiologists to be suitable as a combination anaesthetic agent when administered concurrently with ketamine because of its water solubility and miscibility with ketamine. However, the pharmacokinetics of midazolam have not been extensively described in the dog. Twelve clinically healthy mixed breed dogs (22.2-33.4 kg) were divided into two groups at random and were administered ketamine (10 mg/kg) and midazolam (0.5 mg/kg) either as an intravenous bolus over 30 s (group 1) or as an i.v. infusion in 0.9% NaCl (2 ml/kg) over 15 min. Blood samples were obtained immediately before the drugs were injected and periodically for 6 h afterwards. Serum concentrations were determined using gas chromatography with electron-capture detection. Serum concentrations were best described using a two-compartment open model and indicated a t1/2-alpha of 1.8 min and t1/2-beta of 27.8 min after i.v. bolus, and t1/2-alpha of 1.35 min and t1/2-beta of 31.6 min after i.v. infusion. The calculated pharmacokinetic coefficient B was significantly smaller after i.v. infusion (429 +/- 244 ng/ml) than after i.v. bolus (888 +/- 130 ng/ml, P = 0.004). Furthermore, AUC was significantly smaller after i.v. infusion (29,800 +/- 6120 ng/h/ml) than after i.v. bolus (42,500 +/- 8460 ng/h/ml, P infusion (17.4 +/- 4.00 ml/min/kg than after i.v. bolus (12.1 +/- 2.24 ml/min/kg, P < 0.05). No other pharmacokinetic value was significantly affected by rate of intravenous administration. PMID:8126758

  8. Antifertility effect of chronically administered Tabernaemontana divaricata leaf extract on male rats

    Institute of Scientific and Technical Information of China (English)

    Sachin Jain; Ankit Jain; Pritesh Paliwal; Shailendra Singh Solanki

    2012-01-01

    ABSTRACT Objective:To investigate the antifertility effect of chronically administeredTabernaemontana divaricata (T. divaricata) leaf extract on male rats.Methods:The effect of50% ethanol extract ofT. divaricata leaves on reproduction was studied on male rats.The study was divided into four groups of five animals each.The first groups(I) received vehicle alone to serve as control. The second, third and fourth groups(II,II andIV) of animals were administered theleaf extract daily at50 mg/kg body weight,p.o.,100 mg/kg body weight, p.o., and200 mg/kg body weight, p.o., respectively, for a period of60 days.Results:Significant decreases in the weight of testes, epididymis, seminal vesicle and ventral prostate were observed.A dose related reduction in the testicular sperm count, epididymal sperm count and motility, number of fertile male, ratio between delivered and inseminated females and numbers of pups were observed.The testis showed a clear correlation between the dose and severity of lesions of seminiferous epithelium. In general, the seminiferous tubules appear reduced in size with a frequently filled eosinophilic material.Spermatogenesis arrested at the secondary spermatocyte stage.Pachytene spermatocytes were undergoing degeneration.Disorganigation and sloughing of immature germ cell were visible. Leydinf cells were atrophied.No morphological changes were observed inSertoli cells.Significant reduction in serum concentration of luteinizing hormone and testosterone were observed.No distinct change in serumFSH concentration was recorded.The final body weights of all groups were elevated markedly.No alterations were recorded in any hematologiocal parameters. Conclusions:It is concluded that the50% ethanol extract ofT. divaricata leaf produced dose related effect on male reproduction without altering general body metabolism.

  9. Regulatory analysis on criteria for the release of patients administered radioactive material

    International Nuclear Information System (INIS)

    The Nuclear Regulatory Commission (NRC) has received two petitions to amend its regulations in 10 CFR Parts 20 and 35 as they apply to doses received by members of the public exposed to patients released from a hospital after they have been administered radioactive material. While the two petitions are not identical they both request that the NRC establish a dose limit of 5 millisieverts (0.5 rem) per year for individuals exposed to patients who have been administered radioactive materials. This Regulatory Analysis evaluates three alternatives. Alternative 1 is for the NRC to amend its patient release criteria in 10 CFR 35.75 to use the more stringent dose limit of 1 millisievert per year in 10 CFR 20.1301(a) for its patient release criteria. Alternative 2 is for the NRC to continue using the existing patient release criteria in 10 CFR 35.75 of 1,110 megabecquerels of activity or a dose rate at one meter from the patient of 0.05 millisievert per hour. Alternative 3 is for the NRC to amend the patient release criteria in 10 CFR 35.75 to specify a dose limit of 5 millisieverts for patient release. The evaluation indicates that Alternative 1 would cause a prohibitively large increase in the national health care cost from retaining patients in a hospital longer and would cause significant personal and psychological costs to patients and their families. The choice of Alternatives 2 or 3 would affect only thyroid cancer patients treated with iodine-131. For those patients, Alternative 3 would result in less hospitalization than Alternative 2. Alternative 3 has a potential decrease in national health care cost of $30,000,000 per year but would increase the potential collective dose from released therapy patients by about 2,700 person-rem per year, mainly to family members

  10. [Gastric Acid].

    Science.gov (United States)

    Ruíz Chávez, R

    1996-01-01

    Gastric acid, a product of parietal cells secretion, full fills multiple biological roles which are absolutely necessary to keep corporal homeostasis. The production of the acid depends upon an effector cellular process represented in the first step by histamine, acetilcholine and gastrin, first messengers of the process. These interact with specific receptors than in sequence activate second messengers -cAMP and the calcium-calmodulin system- which afterwards activate a kinase. An specific protein is then phosphorilated by this enzyme, being the crucial factor that starts the production of acid. Finally, a proton bomb, extrudes the acid towards the gastric lumen. The secretion process mentioned above, is progressive lyactivated in three steps, two of which are stimulators -cephalic and gastric phases- and the other one inhibitor or intestinal phase. These stages are started by mental and neurological phenomena -thought, sight, smell or memory-; by food, drugs or other ingested substances; and by products of digestion. Changes in regulation of acid secretion, in the structure of gastro-duodenal mucosal barrier by a wide spectrum of factors and agents including food, drugs and H. pylori, are the basis of acid-peptic disease, entity in which gastric acid plays a fundamental role. From the therapeutic point of view, so at the theoretical as at the practical levels, t is possible to interfere with the secretion of acid by neutralization of some of the steps of the effector cellular process. An adequate knowledge of the basics related to gastric acid, allows to create strategies for the clinical handling of associated pathology, specifically in relation to peptic acid disease in all of the known clinical forms. PMID:12165790

  11. Comparison of the Posttraumatic Stress Disorder Scale Versus the Clinician-Administered Posttraumatic Stress Disorder Scale in Domestic Violence Survivors

    OpenAIRE

    Griffin, Michael G.; Uhlmansiek, Mary H.; Resick, Patricia A.; Mechanic, Mindy B.

    2004-01-01

    The posttraumatic diagnostic scale (PDS) is a self-report instrument for PTSD that is simple to administer and has demonstrated good psychometric properties. We compared the PDS with the gold standard clinician administered PTSD scale (CAPS) diagnostic interview for PTSD. We assessed 138 women who were victims of domestic violence using both the PDS and the CAPS. Findings confirmed that PTSD develops at a high base rate in this sample. The PDS generally performed well in relation to the CAPS ...

  12. Folic acid

    Science.gov (United States)

    ... include leafy vegetables (such as spinach, broccoli, and lettuce), okra, asparagus, fruits (such as bananas, melons, and ... Pyrimethamine (Daraprim)Pyrimethamine (Daraprim) is used to treat parasite infections. Folic acid might decrease the effectiveness of ...

  13. Folic Acid

    Medline Plus

    Full Text Available ... March of Dimes Premature Birth Report Card Grades Cities, Counties; Focuses on Racial and Ethnic Disparities March ... your baby. Learn how you can get the right amout of folic acid before and during pregnancy ...

  14. ACID RAIN

    Science.gov (United States)

    Acid precipitation has become one of the major environmental problems of this decade. It is a challenge to scientists throughout the world. Researchers from such diverse disciplines as plant pathology, soil science, bacteriology, meteorology and engineering are investigating diff...

  15. Folic Acid

    Medline Plus

    Full Text Available ... Just a moment, please. You've saved this page It's been added to your dashboard . Folic acid ... Map Premature birth report card Careers Archives Health Topics Pregnancy Before or between pregnancies Nutrition, weight & fitness ...

  16. Folic Acid

    Medline Plus

    Full Text Available ... Folic acid Description | Related videos | Most played video E-mail to a friend Please fill in all fields. Please enter a valid e-mail address. Your information: Your recipient's information: Your ...

  17. Bispectral index monitoring as an adjunct to nurse-administered combined sedation during endoscopic retrograde cholangiopancreatography

    Institute of Scientific and Technical Information of China (English)

    Se Young Jang; Hyun Gu Park; Min Kyu Jung; Chang Min Cho; Soo Young Park; Seong Woo Jeon; Won Young Tak

    2012-01-01

    AIM:TO determine whether bispectral index (BIS)monitoring is useful for propofol administration for deep sedation during endoscopic retrograde cholangiopancreatography (ERCP).METHODS:Fifty-nine consecutive patients with a variety of reasons for ERCP who underwent the procedure at least twice between 1 July 2010 and 30 November 2010.This was a randomized cross-over study,in which each patient underwent ERCP twice,once with BIS monitoring and once with control monitoring.Whether BIS monitoring was done during the first or second ERCP procedure was random.Patients were intermittently administered a mixed regimen including midazolam,pethidine,and propofol by trained nurses.The nurse used a routine practice to monitor sedation using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale or the BIS monitoring.The total amount of midazolam and propofol used and serious side effects were compared between the BIS and control groups.RESULTS:The mean total propofol dose administered was 53.1 ± 32.2 mg in the BIS group and 54.9± 30.8 mg in the control group (P =0.673).The individual propofol dose received per minute during the ERCP procedure was 2.90 ± 1.83 mg/min in the BIS group and 3.44 ± 2.04 mg in the control group (P =0.103).The median value of the MOAA/S score during the maintenance phase of sedation was comparable for the two groups.The mean BIS values throughout the procedure (from insertion to removal of the endoscope) were 76.5 ± 8.7 for all 59 patients in using the BIS monitor.No significant differences in the frequency of < 80% oxygen saturation,hypotension (< 80 mmHg),or bradycardia (< 50 beats/min) were observed between the two study groups.Four cases of poor cooperation occurred,in which the procedure should be stopped to add the propofol dose.After adding the propofol,the procedure could be conducted successfully (one case in the BIS group,three cases in the control group).The endoscopist rated patient sedation as excellent for

  18. COMPARATIVE IMMUNOSUPPRESSION OF VARIOUS GLYCOL ETHERS ORALLY ADMINISTERED TO FISCHER 344 RATS

    Science.gov (United States)

    Oral dosing of adult rats F344 rats with the glycol ether 2-methoxyethanol (ME) or its principal metabolite 2-methoxyacetic acid (MAA) results in the suppression of the primary plaque-forming cell (PFC) response to trinitrophenyl-lipopolysaccharide (TNP_LPS). n the present study,...

  19. Antiviral Biologic Produced in DNA Vaccine/Goose Platform Protects Hamsters Against Hantavirus Pulmonary Syndrome When Administered Post-exposure.

    Directory of Open Access Journals (Sweden)

    Nicole Haese

    Full Text Available Andes virus (ANDV and ANDV-like viruses are responsible for most hantavirus pulmonary syndrome (HPS cases in South America. Recent studies in Chile indicate that passive transfer of convalescent human plasma shows promise as a possible treatment for HPS. Unfortunately, availability of convalescent plasma from survivors of this lethal disease is very limited. We are interested in exploring the concept of using DNA vaccine technology to produce antiviral biologics, including polyclonal neutralizing antibodies for use in humans. Geese produce IgY and an alternatively spliced form, IgYΔFc, that can be purified at high concentrations from egg yolks. IgY lacks the properties of mammalian Fc that make antibodies produced in horses, sheep, and rabbits reactogenic in humans. Geese were vaccinated with an ANDV DNA vaccine encoding the virus envelope glycoproteins. All geese developed high-titer neutralizing antibodies after the second vaccination, and maintained high-levels of neutralizing antibodies as measured by a pseudovirion neutralization assay (PsVNA for over 1 year. A booster vaccination resulted in extraordinarily high levels of neutralizing antibodies (i.e., PsVNA80 titers >100,000. Analysis of IgY and IgYΔFc by epitope mapping show these antibodies to be highly reactive to specific amino acid sequences of ANDV envelope glycoproteins. We examined the protective efficacy of the goose-derived antibody in the hamster model of lethal HPS. α-ANDV immune sera, or IgY/IgYΔFc purified from eggs, were passively transferred to hamsters subcutaneously starting 5 days after an IM challenge with ANDV (25 LD50. Both immune sera, and egg-derived purified IgY/IgYΔFc, protected 8 of 8 and 7 of 8 hamsters, respectively. In contrast, all hamsters receiving IgY/IgYΔFc purified from normal geese (n=8, or no-treatment (n=8, developed lethal HPS. These findings demonstrate that the DNA vaccine/goose platform can be used to produce a candidate antiviral

  20. Brachytherapy Application With In Situ Dose Painting Administered by Gold Nanoparticle Eluters

    Energy Technology Data Exchange (ETDEWEB)

    Sinha, Neeharika [Department of Sciences, Wentworth Institute of Technology, Boston, Massachusetts (United States); Cifter, Gizem [Department of Physics and Applied Physics, University of Massachusetts, Lowell, Massachusetts (United States); Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women' s Hospital and Harvard Medical School, Boston, Massachusetts (United States); Sajo, Erno [Department of Physics and Applied Physics, University of Massachusetts, Lowell, Massachusetts (United States); Kumar, Rajiv; Sridhar, Srinivas [Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women' s Hospital and Harvard Medical School, Boston, Massachusetts (United States); Electronic Materials Research Institute and Department of Physics, Northeastern University, Boston, Massachusetts (United States); Nguyen, Paul L.; Cormack, Robert A.; Makrigiorgos, G. Mike [Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women' s Hospital and Harvard Medical School, Boston, Massachusetts (United States); Ngwa, Wilfred, E-mail: wngwa@lroc.harvard.edu [Department of Physics and Applied Physics, University of Massachusetts, Lowell, Massachusetts (United States); Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women' s Hospital and Harvard Medical School, Boston, Massachusetts (United States)

    2015-02-01

    Purpose: Recent studies show promise that administering gold nanoparticles (GNP) to tumor cells during brachytherapy could significantly enhance radiation damage to the tumor. A new strategy proposed for sustained administration of the GNP in prostate tumors is to load them into routinely used brachytherapy spacers for customizable in situ release after implantation. This in silico study investigated the intratumor biodistribution and corresponding dose enhancement over time due to GNP released from such GNP-loaded brachytherapy spacers (GBS). Method and Materials: An experimentally determined intratumoral diffusion coefficient (D) for 10-nm nanoparticles was used to estimate D for other sizes by using the Stokes-Einstein equation. GNP concentration profiles, obtained using D, were then used to calculate the corresponding dose enhancement factor (DEF) for each tumor voxel, using dose painting-by-numbers approach, for times relevant to the considered brachytherapy sources' lifetimes. The investigation was carried out as a function of GNP size for the clinically applicable low-dose-rate brachytherapy sources iodine-125 (I-125), palladium-103 (Pd-103), and cesium-131 (Cs-131). Results: Results showed that dose enhancement to tumor voxels and subvolumes during brachytherapy can be customized by varying the size of GNP released or eluted from the GBS. For example, using a concentration of 7 mg/g GNP, significant DEF (>20%) could be achieved 5 mm from a GBS after 5, 12, 25, 46, 72, 120, and 195 days, respectively, for GNP sizes of 2, 5, 10, 20, 30, and 50 nm and for 80 nm when treating with I-125. Conclusions: Analyses showed that using Cs-131 provides the highest dose enhancement to tumor voxels. However, given its relatively longer half-life, I-125 presents the most flexibility for customizing the dose enhancement as a function of GNP size. These findings provide a useful reference for further work toward development of potential new brachytherapy application

  1. Brachytherapy Application With In Situ Dose Painting Administered by Gold Nanoparticle Eluters

    International Nuclear Information System (INIS)

    Purpose: Recent studies show promise that administering gold nanoparticles (GNP) to tumor cells during brachytherapy could significantly enhance radiation damage to the tumor. A new strategy proposed for sustained administration of the GNP in prostate tumors is to load them into routinely used brachytherapy spacers for customizable in situ release after implantation. This in silico study investigated the intratumor biodistribution and corresponding dose enhancement over time due to GNP released from such GNP-loaded brachytherapy spacers (GBS). Method and Materials: An experimentally determined intratumoral diffusion coefficient (D) for 10-nm nanoparticles was used to estimate D for other sizes by using the Stokes-Einstein equation. GNP concentration profiles, obtained using D, were then used to calculate the corresponding dose enhancement factor (DEF) for each tumor voxel, using dose painting-by-numbers approach, for times relevant to the considered brachytherapy sources' lifetimes. The investigation was carried out as a function of GNP size for the clinically applicable low-dose-rate brachytherapy sources iodine-125 (I-125), palladium-103 (Pd-103), and cesium-131 (Cs-131). Results: Results showed that dose enhancement to tumor voxels and subvolumes during brachytherapy can be customized by varying the size of GNP released or eluted from the GBS. For example, using a concentration of 7 mg/g GNP, significant DEF (>20%) could be achieved 5 mm from a GBS after 5, 12, 25, 46, 72, 120, and 195 days, respectively, for GNP sizes of 2, 5, 10, 20, 30, and 50 nm and for 80 nm when treating with I-125. Conclusions: Analyses showed that using Cs-131 provides the highest dose enhancement to tumor voxels. However, given its relatively longer half-life, I-125 presents the most flexibility for customizing the dose enhancement as a function of GNP size. These findings provide a useful reference for further work toward development of potential new brachytherapy application

  2. Determination of drug concentration in aqueous humor of cataract patients administered gatifloxacin ophthalmic gel

    Institute of Scientific and Technical Information of China (English)

    LIU Xuan; WANG Ning-li; WANG Yan-ling; MA Chen; MA Li; GAO Li-xin; HUANG Ying-xiang; XIONG Shi-hong; WANG Kang

    2010-01-01

    Background Ophthalmic gel has been developed to increase the drug concentration in aqueous humor and to retard the loss of drug from the conjunctival sac.The research was to compare the drug concentration in aqueous humor of cataract patients administered 0.3% gatifloxacin ophthalmic gel with that in patients administered 0.3% gatifloxacin ophthalmic solution.Methods Ninety-six patients with cataract (96 eyes) were randomly assigned to 8 groups.The patients in groups 1-4received topical gatifloxacin 0.3% ophthalmic gel and those in groups 5-8 received gatifloxacin 0.3% ophthalmic solution.The dose regimen was 1 drop, 4 times a day for 3 consecutive days prior to cataract surgery.On the day of surgery, 1drop was applied at 15, 30, 60 or 120 minutes before commencement of cataract surgery in groups 1 and 5, groups 2 and 6, goups 3 and 7, and groups 4 and 8, respectively.Aqueous humor was extracted during the cataract surgery for the analysis of gatifloxacin concentration..Results The concentrations of gatifloxacin in aqueous humor were (0.24±0.25) μg/ml, (1.11±0.74) μg/ml, (2.32±2.01)μg/ml and (1.85±1.14) μg/ml in groups 1 to 4, and (0.16±0.25) μg/ml, (0.31±0.24) μg/ml, (0.75±0.28) μg/ml and (0.33±0.22) μg/ml in groups 5 to 8, respectively.Patients receiving gatifloxacin ophthalmic gel showed greater mean values of gatifloxacin concentration in aqueous humor than those receiving gatifloxacin solution, and such differences were significant with P <0.05 for all comparisons except that between groups 1 and 5.Conclusion Topical gatifloxacin ophthalmic gel can attain significantly greater drug concentrations in human aqueous humor than gatifloxacin ophthalmic solution.

  3. Valproic Acid and Sleep Duration in Children with Epilepsy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2009-09-01

    Full Text Available Sleep duration and behavior were assessed in 46 children (age range 1.7-17.4 years before and after tapering valproic acid (VPA administered for more than 6 months for epilepsy, in a study at University Children's Hospital, Zurich, Switzerland.

  4. A randomised, open-label, comparative study of tranexamic acid microinjections and tranexamic acid with microneedling in patients with melasma

    OpenAIRE

    Leelavathy Budamakuntla; Eswari Loganathan; Deepak Hurkudli Suresh; Sharavana Shanmugam; Shwetha Suryanarayan; Aparna Dongare; Lakshmi Dammaningala Venkataramiah; Namitha Prabhu

    2013-01-01

    Background: Melasma is a common cause of facial hyperpigmentation with significant cosmetic deformity. Although several treatment modalities are available, none is satisfactory. Aim: To compare the therapeutic efficacy and safety of tranexamic acid (TA) microinjections versus tranexamic acid with microneedling in melasma. Materials and Methods: This is a prospective, randomised, open-label study with a sample size of 60; 30 in each treatment arms. Thirty patients were administered with locali...

  5. Nephropathy induced by intramuscularly administered glycerol and contrast media in rats

    International Nuclear Information System (INIS)

    Urine profiles (albumin, glucose, NAG, LDH, GGT, sodium, and phosphate) were followed for 14 days after intravenous injection of either diatrizoate, iohexol, ioxilan, or saline in 24 Wistar rats with a glomerular and tubular dysfunction induced by intramuscularly (i.m.) administered glycerol. Another 6 rats exposed to neither glycerol nor contrast media served as controls. The effect of ioxilan and saline on the albumin excretion was similar, whereas diatrizoate and iohexol increased it significantly. The contrast media had no further inhibitory effect on the reabsorption of glucose. Iohexol caused significantly increased excretion of all three enzymes, ioxilan of NAG and LDH, whereas diatrizoate only increased the excretion of LDH. The sodium excretion was further increased by ioxilan and diatrizoate, whereas none of the contrast media affected the phosphaturia. Both ioxilan and iohexol caused a round cell response around the tubules shown by light microscopy whereas diatrizoate caused no further changes. It is concluded that diatrizoate and iohexol increase glomerular dysfunction induced by glycerol i.m.; all three contrast media cause some further increase in the tubular dysfunction. Neither diatrizoate, iohexol nor ioxilan prolong nephropathy induced by glycerol i.m. determined by the chemical analyses. The histologic finding indicates a direct toxic effect of non-ionic low osmolar contrast media in this animal model of nephropathy. (orig.)

  6. Regulatory analysis on criteria for the release of patients administered radioactive material. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, S.; McGuire, S.A.

    1997-02-01

    This regulatory analysis was developed to respond to three petitions for rulemaking to amend 10 CFR parts 20 and 35 regarding release of patients administered radioactive material. The petitions requested revision of these regulations to remove the ambiguity that existed between the 1-millisievert (0.1-rem) total effective dose equivalent (TEDE) public dose limit in Part 20, adopted in 1991, and the activity-based release limit in 10 CFR 35.75 that, in some instances, would permit release of individuals in excess of the current public dose limit. Three alternatives for resolution of the petitions were evaluated. Under Alternative 1, NRC would amend its patient release criteria in 10 CFR 35.75 to match the annual public dose limit in Part 20 of 1 millisievert (0.1 rem) TEDE. Alternative 2 would maintain the status quo of using the activity-based release criteria currently found in 10 CFR 35.75. Under Alternative 3, the NRC would revise the release criteria in 10 CFR 35.75 to specify a dose limit of 5 millisieverts (0.5 rem) TEDE.

  7. Tissue Culture of Trigeminal Nerves from Rats Administered Transplacentally with Ethylnitrosourea

    Directory of Open Access Journals (Sweden)

    Hayashi,Kazuhiko

    1983-08-01

    Full Text Available The morphological and biological changes in long term culture cells of normal-appearing trigeminal nerves from 2, 8, and 30-day-old S-D rats administered transplacentaLly with 75 mg ENU/kg were examined. After a marked degeneration of cells, crisscross multiple proliferative foci of transformed spindle cells appeared at the 3rd passage culture from 2 and 8-day-old rats, but not form 30-day-old rats. The transformed cells with S-100 protein and basal lamina had Schwann cell characteristics. Transformed spindle cells continued to form a crisscross pattern more than 700 days and some transformed spindle cells became round in shape 3-6 months after the primary culture. These transformed cells were transplantable to newborn S-D rats and the transplanted tumors were histologically similar to those of malignant Schwannoma of trigeminal nerves induced by ENU. Round-shaped transformed cells were more malignant than spindle-shaped cells and produced rapidly growing transplanted tumors. Spontaneous transformation with multinucleated giant cells occurred in one of the control cultures. These results indicate that the sequential changes of ENU-treated trigeminal nerves in vitro were corresponded to developmental changes of malignant Schwannoma in vivo induced by ENU. This system will be useful for analysis of ENU-carcinogenesis.

  8. The ABCs of LDAP how to install, run, and administer LDAP services

    CERN Document Server

    Voglmaier, Reinhard E

    2004-01-01

    Until now, it has been difficult to find the right source of information on LDAP and directory server implementations: books on the subject are overly product-specific, and a search on the Web results in information overload. The ABCs of LDAP: How to Install, Run, and Administer LDAP Services strikes the right balance, providing a synopsis of LDAP fundamentals without getting wrapped up in one particular implementation.This book is for network and systems administrators who want to begin using LDAP more extensively. It delivers the theoretical background needed to understand how these servers work, resulting in clear, concise examples of implementations in both commercial and OpenLDAP environments.The text is structured so that each chapter can stand on its own, with brief descriptions of terms supplemented by references to more detailed explanations in other chapters. You also benefit from a concise overview of how to design a directory, preparing you to execute directory deployments for email, PKI, DNS, NIS...

  9. Safety evaluation of intravenously administered mono-thioated aptamer against E-selectin in mice

    International Nuclear Information System (INIS)

    The medical applications of aptamers have recently emerged. We developed an antagonistic thioaptamer (ESTA) against E-selectin. Previously, we showed that a single injection of ESTA at a dose of 100 μg inhibits breast cancer metastasis in mice through the functional blockade of E-selectin. In the present study, we evaluated the safety of different doses of intravenously administered ESTA in single-dose acute and repeat-dose subacute studies in ICR mice. Our data indicated that intravenous administration of up to 500 μg ESTA did not result in hematologic abnormality in either study. Additionally, intravenous injection of ESTA did not affect the levels of plasma cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, GM-CSF, IFN-γ, and TNF-α) or complement split products (C3a and C5a) in either study. However, repeated injections of ESTA slightly increased plasma ALT and AST activities, in accordance with the appearance of small necrotic areas in the liver. In conclusion, our data demonstrated that intravenous administration of ESTA does not cause overt hematologic, organs, and immunologic responses under the experimental conditions. - Highlights: • Intravenous administration of ESTA was well tolerated. • ESTA up to 500 μg does not cause hematologic, organs, and immunologic responses. • ESTA-mediated hepatic abnormality was considered minor

  10. Regulatory analysis on criteria for the release of patients administered radioactive material. Final report

    International Nuclear Information System (INIS)

    This regulatory analysis was developed to respond to three petitions for rulemaking to amend 10 CFR parts 20 and 35 regarding release of patients administered radioactive material. The petitions requested revision of these regulations to remove the ambiguity that existed between the 1-millisievert (0.1-rem) total effective dose equivalent (TEDE) public dose limit in Part 20, adopted in 1991, and the activity-based release limit in 10 CFR 35.75 that, in some instances, would permit release of individuals in excess of the current public dose limit. Three alternatives for resolution of the petitions were evaluated. Under Alternative 1, NRC would amend its patient release criteria in 10 CFR 35.75 to match the annual public dose limit in Part 20 of 1 millisievert (0.1 rem) TEDE. Alternative 2 would maintain the status quo of using the activity-based release criteria currently found in 10 CFR 35.75. Under Alternative 3, the NRC would revise the release criteria in 10 CFR 35.75 to specify a dose limit of 5 millisieverts (0.5 rem) TEDE

  11. Adverse reactions to iodinated contrast media administered at the time of endoscopic retrograde cholangiopancreatography (ERCP).

    Science.gov (United States)

    Pan, Jen-Jung; Draganov, Peter V

    2009-03-01

    Adverse reactions after intravascular administration of iodine contrast media are common and prophylactic regiments consisting of the use of steroids and low osmolality contrast media are highly effective in significantly decreasing the adverse reactions rate. The same type of contrast media are also used for opacification of the biliary tree and the pancreatic duct at the time of endoscopic retrograde cholangiopancreatography (ERCP). Systemic absorption of contrast media after ERCP routinely occurs. Although the adverse reaction rate appears to be very low the exact incidence remains unknown due to the retrospective nature of all reports. Despite the lack of formal recommendations, numerous prophylactic regiments are routinely used prior to ERCP in patients with history of prior reaction to intravascular contrast media. Moreover, the use of prophylaxis has even expanded to patients with no prior reaction to intravascular contrast media who are somehow perceived to be at increase risk (e.g. shellfish allergy). Recently, the first large scale prospective study reported exceedingly low incidence of adverse reaction to high oslmolality iodine-containing contrast media administered at the time of ERCP done without prophylactic premedication even in patients considered to be at the highest risk (prior severe reaction to intravascular contrast media administration). These data suggest that the use of prophylactic regiments prior to ERCP appears to be unnecessary. PMID:19275689

  12. Tissue and subcellular distribution of zinc-65 in normal and zinc sulphate administered rats

    International Nuclear Information System (INIS)

    Uptake of 65Zn by various organs of normal and ZnSO4 administered rats has been studied. Except duodenum and blood all the organs show low 65Zn incorporation in treated rats. The lower 65Zn incorporation in the tissues of ZnSO4 treated rats is due to the active turnover of zinc in these tissues. The maximum activity of 65Zn is exhibited by skin, followed in decreasing order by liver, intestine, spleen, rectum, kidney, prostate, urinary bladder, stomach, pancreas, adrenals, trachea, lungs, heart, thymus, seminal vesicles, testis, cauda epididymis, caput epididymis, brain, and muscle. Since ZnSO4 administration enhanced the levels of inert zinc in liver and intestine it is likely that accumulated inert zinc in the tissues may inhibit the further incorporation of 65Zn in these tissues. At subcellular level, the cytosol fraction (11000 g supernatant fraction) exhibits the higher 65Zn activity, followed in decreasing order by 300 g fraction (cell membranes and cell debris), 900 g fraction (nuclei), 6000 g fraction (heavy mitochondria) and 1000 g fraction (light mitochondria). The 65Zn activity/mgprotein in 11000 g fraction (light mitochondria) is more than the 900 g fraction (nuclei) and 6000 g fraction (heavy mitochondria). Subcellular distribution pattern of 65Zn in liver, intestine, kidney and testis is similar. ZnSO4 administration does not change the tissue and subcellular distribution pattern of 65Zn. (author). 18 refs., 3 tables

  13. The effects of centrally administered fluorocitrate via inhibiting glial cells on working memory in rats

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Although prefrontal and hippocampal neurons are critical for spatial working memory,the function of glial cells in spatial working memory remains uncertain.In this study we investigated the function of glial cells in rats’ working memory.The glial cells of rat brain were inhibited by intracerebroventricular(icv) injection of fluorocitrate(FC).The effects of FC on the glial cells were examined by using electroencephalogram(EEG) recordings and delayed spatial alternation tasks.After icv injection of 10 μL of 0.5 nmol/L or 5 nmol/L FC,the EEG power spectrum recorded from the hippocampus increased,but the power spectrum for the prefrontal cortex did not change,and working memory was unaffected.Following an icv injection of 10 μL of 20 nmol/L FC,the EEG power spectra in both the prefrontal cortex and the hippocampus increased,and working memory improved.The icv injection of 10 μL of 50 nmol/L FC,the EEG power spectra in both the prefrontal cortex and in the hippocampus decreased,and working memory was impaired.These results suggest that spatial working memory is affected by centrally administered FC,but only if there are changes in the EEG power spectrum in the prefrontal cortex.Presumably,the prefrontal glial cells relate to the working memory.

  14. In vivo release of bupivacaine from subcutaneously administered oily solution. Comparison with in vitro release

    DEFF Research Database (Denmark)

    Larsen, Dorrit Bjerg; Joergensen, Stig; Olsen, Niels Vidiendal;

    2002-01-01

    A non-randomized cross-over study was performed with bupivacaine HCl (5 mg x ml(-1)) aqueous solution and bupivacaine free base (4.44 mg x ml(-1)) in Viscoleo/castor oil 2:1 (v/v) administered s.c. to male Wistar rats. Plasma levels were analyzed by LC-MS. Plasma profiles obtained after...... 25,000+/-3000 ng min x ml(-1), respectively, while the corresponding data for the oil solution were 368+/-89 min, 334+/-186 min, 36+/-25 ng x ml(-1) and 25,000+/-6000 ng x min x ml(-1). The present data indicate the potential of designing an oil formulation of bupivacaine with a prolonged local...... analgetic effect exhibiting a minimum of systemic toxicity. In vivo release of bupivacaine from the oil solution was evaluated by a numerical deconvolution method. In vivo release kinetics was found to be first-order and corresponded well with in vitro release kinetics found using a rotating dialysis cell...

  15. OCCURRENCE OF CONSANGUINEOUS MARRIAGE IN BAJAUR AGENCY, FEDERALLY ADMINISTERED TRIBAL AREAS, KHYBER PAKHTUNKHWA, PAKISTAN

    Directory of Open Access Journals (Sweden)

    Farzana Perveen

    2012-01-01

    Full Text Available In consanguineous marriage, the genetic and medical disorders are increased in the offspring with passage of time. It is a big challenge for our society to get complete information of their prevalence, their risk factors and to control these disorders. The present survey was conducted during January-March 2012 in different areas of the Bajaur Agency, Federally Administered Tribal Areas (FATA, Khyber Pakhtunkhwa (KP, Pakistan including Alijan, Anatkali, Chamerkand, Gandaw, Loisam, Manudera, Nawagai, Nawaikali, Raghagan and Sadiqabad where they are dominant. Data were collected from 123 consanguineous married couples through questionnaire comprised of information about complete history and risk factors of the medical and genetic disorders. During cousin marriages, the couples’ parents were married to their 1st cousin 52% while married to their 2nd cousin 49%. The couples participated themselves were 1st cousin 87% while 2nd cousin 13%. They were obese 34%, weak 48%, and normal 18% while age was minimum 14 and maximum 30 years, however, maximum marriages were observed at the age of 20 year. The couples having genetic disorders like anemia, obesity and thalassemia were 20, 23 and 20%, respectively; however, non-genetic disorders, bone diseases, depressive illness and respiratory diseases were 21, 20 and 25 %, respectively. Such communities may require comprehensive genetic education and premarital genetic counseling programs for awareness and education.

  16. Comparative bioavailability study of cefixime administered as tablets or aqueous solution.

    Science.gov (United States)

    Montay, G; Masala, F; Le Roux, Y; Le Liboux, A; Uhlrich, J; Chassard, D; Thebault, J J; Roche, G; Frydman, A

    1991-01-01

    The relative bioavailability of cefixime was studied in 24 healthy male volunteers, with each subject receiving a single 400mg dose of cefixime administered as an aqueous solution, a 400mg tablet and two 200mg tablets, in a randomised crossover sequence. Serum and urine samples were analysed using high-performance liquid chromatography. Peak cefixime levels were achieved 3 hours after administration of the solution vs 4 hours for the 2 tablet formulations; however, the extent of absorption was only slightly improved with the solution (by 14 and 7% compared with the 1 x 400 and 2 x 200mg tablets, respectively). The 400mg and 2 x 200mg tablets were found to be bioequivalent. The pharmacokinetic profile of the 400mg cefixime tablet (mean maximum plasma concentrations of 4.4 mg/L at 4 hours, area under the concentration-time curve of 34.4 mg/L.h, and apparent terminal elimination half-life of 3.7 hours) supports the clinical evaluation of a 400mg once-daily dosage regimen for cefixime. PMID:1725153

  17. Lethal poisoning with theophylline in the form of rectally administered tablets.

    Science.gov (United States)

    Kopacz, P; Kula, K

    2014-01-01

    The paper discusses the case of death of a 56-year-old man who died in a municipal hospital from which his body was taken to the Chair and Department of Forensic Medicine, Jagiellonian University Medical College, Krakow. The man was said to have been found unconscious by accidental passers-by. While being transported to the hospital's emergency department, he suffered an attack of convulsions and went into cardiac arrest. He was subsequently successfully resuscitated. A physical examination performed at the hospital revealed the presence of multiple, only slightly dissolved tablets in the man's rectum. The patient died on the 25th day of hospitalization. A toxicological analysis showed a toxic concentration of theophylline (25 mg/l) in the man's blood. Theophylline was identified as the main ingredient of the tablets. The cause of death was thus given as theophylline poisoning. The reported case is unusual in that the poisoning occurred as a result of overdosing on an oral drug which was administered by the victim rectally, and in that the chosen substance currently is not very commonly used in medicine, and does not cause symptoms of intoxication. PMID:25693173

  18. Effects of orally administered yeast-derived beta-glucans: a review.

    Science.gov (United States)

    Samuelsen, Anne Berit C; Schrezenmeir, Jürgen; Knutsen, Svein H

    2014-01-01

    Yeast-derived beta-glucans (Y-BG) are considered immunomodulatory compounds suggested to enhance the defense against infections and exert anticarcinogenic effects. Specific preparations have received Generally Recognized as Safe status and acceptance as novel food ingredients by European Food Safety Authority. In human trials, orally administered Y-BG significantly reduced the incidence of upper respiratory tract infections in individuals susceptible to upper respiratory tract infections, whereas significant differences were not seen in healthy individuals. Increased salivary IgA in healthy individuals, increased IL-10 levels in obese subjects, beneficial changes in immunological parameters in allergic patients, and activated monocytes in cancer patients have been reported following Y-BG intake. The studies were conducted with different doses (7.5-1500 mg/day), using different preparations that vary in their primary structure, molecular weight, and solubility. In animal models, oral Y-BG have reduced the incidence of bacterial infections and levels of stress-induced cytokines and enhanced antineoplastic effects of cytotoxic agents. Protective effects toward drug intoxication and ischemia/reperfusion injury have also been reported. In conclusion, additional studies following good clinical practice principles are needed in which well-defined Y-BG preparations are used and immune markers and disease endpoints are assessed. Since optimal dosing may depend on preparation characteristics, dose-response curves might be assessed to find the optimal dose for a specific preparation. PMID:24019098

  19. Effectiveness of a self-administered intervention for criminal thinking: Taking a Chance on Change.

    Science.gov (United States)

    Folk, Johanna B; Disabato, David J; Daylor, Jordan M; Tangney, June P; Barboza, Sharen; Wilson, John S; Bonieskie, Lynda; Holwager, James

    2016-08-01

    The current study tested the effectiveness of a self-administered, cognitive-behavioral intervention targeting criminal thinking for inmates in segregated housing: Taking a Chance on Change (TCC). Participants included 273 inmates in segregated housing at state correctional institutions. Reductions in criminal thinking, as assessed by the Psychological Inventory of Criminal Styles-Simplified Version, were found in the general criminal thinking score as well as the proactive and reactive composite scores. Examination of demographic predictors of change (i.e., age, years of education, length of sentence) revealed older and more educated participants decreased in criminal thinking more than younger and less educated participants. For a subset of 48 inmates, completion of TCC was associated with significant reduction of disciplinary infractions. Reductions in reactive criminal thinking predicted reductions in disciplinary infractions. Although further research is needed to determine the effectiveness of TCC in reducing recidivism, the reductions in criminal thinking and disordered conduct suggest this is a promising intervention and mode of treatment delivery. By utilizing self-directed study at an accessible reading level, the intervention is uniquely suited to a correctional setting where staff and monetary resources are limited and security and operational issues limit the feasibility of traditional cognitive-behavioral group treatment. (PsycINFO Database Record PMID:27243111

  20. Safety evaluation of intravenously administered mono-thioated aptamer against E-selectin in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Shin-Ae; Tsolmon, Bilegtsaikhan [Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE, 10th, Oklahoma City, OK 73104 (United States); Mann, Aman P. [Institute of Molecular Medicine, Department of NanoMedicine and Biomedical Engineering, University of Texas Health Science Center at Houston, 1825 Hermann Pressler, Houston, TX 77030 (United States); Zheng, Wei; Zhao, Lichao; Zhao, Yan Daniel [Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE, 10th, Oklahoma City, OK 73104 (United States); Volk, David E.; Lokesh, Ganesh L.-R. [Institute of Molecular Medicine, Department of NanoMedicine and Biomedical Engineering, University of Texas Health Science Center at Houston, 1825 Hermann Pressler, Houston, TX 77030 (United States); Morris, Lynsie; Gupta, Vineet; Razaq, Wajeeha [Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE, 10th, Oklahoma City, OK 73104 (United States); Rui, Hallgeir [Thomas Jefferson University, 1020 Locust St, Philadelphia, PA 19107 (United States); Suh, K. Stephen [John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ 07601 (United States); Gorenstein, David G. [Institute of Molecular Medicine, Department of NanoMedicine and Biomedical Engineering, University of Texas Health Science Center at Houston, 1825 Hermann Pressler, Houston, TX 77030 (United States); Tanaka, Takemi, E-mail: takemi-tanaka@ouhsc.edu [Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE, 10th, Oklahoma City, OK 73104 (United States)

    2015-08-15

    The medical applications of aptamers have recently emerged. We developed an antagonistic thioaptamer (ESTA) against E-selectin. Previously, we showed that a single injection of ESTA at a dose of 100 μg inhibits breast cancer metastasis in mice through the functional blockade of E-selectin. In the present study, we evaluated the safety of different doses of intravenously administered ESTA in single-dose acute and repeat-dose subacute studies in ICR mice. Our data indicated that intravenous administration of up to 500 μg ESTA did not result in hematologic abnormality in either study. Additionally, intravenous injection of ESTA did not affect the levels of plasma cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, GM-CSF, IFN-γ, and TNF-α) or complement split products (C3a and C5a) in either study. However, repeated injections of ESTA slightly increased plasma ALT and AST activities, in accordance with the appearance of small necrotic areas in the liver. In conclusion, our data demonstrated that intravenous administration of ESTA does not cause overt hematologic, organs, and immunologic responses under the experimental conditions. - Highlights: • Intravenous administration of ESTA was well tolerated. • ESTA up to 500 μg does not cause hematologic, organs, and immunologic responses. • ESTA-mediated hepatic abnormality was considered minor.

  1. Individually administered or co-prescribed thiopurines and mesalamines for inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    Giovanni C Actis, Rinaldo Pellicano, Mario Rizzetto, Muhammad Ayoubi, Nicola Leone, Gianfranco Tappero, Paola Pazienza, Floriano Rosina

    2009-03-01

    Full Text Available Data from both basic research and clinical experience continue to suggest that mesalamines and thiopurines are effective and efficient for the maintenance of remission of inflammatory bowel diseases. Several decades following the formalization of their indications, attention on these two drugs has been fostered by recent achievements. Demonstration of the ability of mesalamine to activate a colonocyte differentiation factor has shed light on its chemopreventive effects on colorectal cancer; in addition to their anti-proliferative efficacy, thiopurines have been shown to be specific regulators of apoptosis. The two drugs are often co-administered in clinical practice. Recent advancements have shown that mesalamines exert a positive synergism in this context, insofar as they can inhibit side-methylation of thiopurines and hasten the function of the main immunosuppressive pathways. Considering that up to 40% of patients cannot tolerate thiopurines, such renovated targets have stimulated efforts to improve compliance by research on the toxicity mechanisms. The definition of genetic polymorphisms in the enzymes of thiopurine metabolism, and the uncovering of synergistic drug interactions, such as that with allopurinol, are just two of the results of such efforts. Interaction between basic research and clinical practice has continued to inform indications and refine the prescriptions of mesalamines and thiopurines; these have not been restrained (they have been implemented in some cases by the advent of the novel biological molecules with anti-cytokine activity.

  2. Comparison of radioisotopic studied calcium metabolism in the orally administered and inhaled cadmium rat

    International Nuclear Information System (INIS)

    The radioisotopic study of calcium metabolism in the rat after oral administration of cadmium, 8 mg/kg during 13 weeks, has shown two different effects of this ion: 1) in the intestine, cadmium inhibits the absorption of calcium by active transport; 2) in the deep bone compartment, the decrease of the bone calcium used for the crystallization and slowly exchangeable with the calcium central pool (serum, extracellular and soft tissues calcium) is combined with a reduction of the exchange rates between the two compartments. When administered through a microparticle aerosol inhalation (1 mg/m3 of air, 30 mn a day, during 12 weeks), cadmium's main target organ is the deep bone compartment. For both modes of administration, the slowing down of osteogenesis is confirmed by a drop in serum alkaline phosphatase after a four weeks period which reflects a decrease of the osteoblastic activity. Therefore it appears that the effects on bones observed during the chronic oral cadmium administration, do not result from a malabsorption of intestine calcium but also from the very action the Cd++ ion on the bone crystallization process

  3. Tissular localization and excretion of intravenously administered silica nanoparticles of different sizes

    Energy Technology Data Exchange (ETDEWEB)

    Xie Guangping; Sun Jiao, E-mail: jiaosun59@yahoo.com [Shanghai Jiaotong University School of Medicine, Shanghai Biomaterials Research and Testing Center, Shanghai Ninth People' s Hospital (China); Zhong Gaoren [Fudan University, School of Pharmacy (China)

    2012-01-15

    The nanotoxicology as a new subdiscipline of nanotechnology needs to be studied in vivo. To do so, it is essential to understand certain pharmacological information of the nanoparticles in vivo. Silica nanoparticles (SiNPs) have been developed for a number of biomedical uses; however, research on their tissular localization and excretion has been limited. In this study, we analyzed the localization of intravenously administered SiNPs with sizes of 20 and 80 nm in liver and spleen and quantitatively investigated the excretion of SiNPs through urine and feces. The results of the tissular localization study showed that the SiNPs were located in liver evenly; however, they were mainly accumulated in the white pulp of spleen. The quantitative excretory assay found the renal excretion being the main excretion pathway of SiNPs and indicated that the accumulated excretory rate of 80 nm SiNPs through urine was higher than that of 20 nm SiNPs because of the higher hemoconcentration. Further analysis of radioactive substances in the excreta showed the convincing confirmatory evidence that the SiNPs of both the sizes of 20 and 80 nm could be excreted through urine. These results provide important information on in vivo distribution and excretion of SiNPs.

  4. Analgesic and thermic responses to intravenously administered morphine in 8- and 24-week-old rats.

    Science.gov (United States)

    Bhargava, H N; Villar, V M

    1991-01-01

    The analgesic and thermic responses to morphine (5 and 10 mg/kg) injected intravenously to 8- and 24-week-old male Sprague-Dawley rats were determined. Greater analgesic and lower hyperthermic responses to morphine in 24-week-old rats in comparison to 8-week-old rats were observed. The pharmacokinetic parameters of morphine administered intravenously were also determined. Cmax for 5 and 10 mg/kg doses of morphine were smaller in 24-week-old rats in comparison to 8-week-old rats; however, AUC0----infinity was smaller only for 5 mg/kg dose. For 10 mg/kg dose, mean residence time (MRT) and the apparent steady state volume of distribution (Vss) for the older rats were higher than for the younger ones, but for 5 mg/kg dose the values did not differ. The enhanced responses to morphine in older age group of rats for 5 mg/kg dose cannot be explained solely on the basis of pharmacokinetics. However, for 10 mg/kg dose of morphine, the greater responses in 24-week-old rats could probably be related to increases in MRT and Vss. Factors other than serum kinetics, like kinetics of morphine in the brain as well as the brain opiate receptors, may also be involved in the differential effects of morphine in rats of different ages. PMID:1784625

  5. Nurses and subordination: a historical study of mental nurses' perceptions on administering aversion therapy for 'sexual deviations'.

    Science.gov (United States)

    Dickinson, Tommy; Cook, Matt; Playle, John; Hallett, Christine

    2014-12-01

    This study aimed to examine the meanings that nurses attached to the 'treatments' administered to cure 'sexual deviation' (SD) in the UK, 1935-1974. In the UK, homosexuality was considered a classifiable mental illness that could be 'cured' until 1992. Nurses were involved in administering painful and distressing treatments. The study is based on oral history interviews with fifteen nurses who had administered treatments to cure individuals of their SD. The interviews were transcribed for historical interpretation. Some nurses believed that their role was to passively follow any orders they had been given. Other nurses limited their culpability concerning administering these treatments by adopting dehumanising and objectifying language and by focussing on administrative tasks, rather than the human beings in need of their care. Meanwhile, some nurses genuinely believed that they were acting beneficently by administering these distinctly unpleasant treatments. It is envisaged that this study might act to reiterate the need for nurses to ensure their interventions have a sound evidence base and that they constantly reflect on the moral and value base of their practice and the influence that science and societal norms can have on changing views of what is considered 'acceptable practice'. PMID:23876127

  6. Incretin effect after oral amino Acid ingestion in humans

    DEFF Research Database (Denmark)

    Lindgren, Ola; Pacini, Giovanni; Tura, Andrea;

    2015-01-01

    also present after amino acid ingestion is not known. OBJECTIVE: The objective of the study was to explore insulin secretion and incretin hormones after oral and iv amino acid administration at matched total amino acid concentrations in healthy subjects. DESIGN: An amino acid mixture (Vaminolac) was...... administered orally or iv at a rate resulting in matching total amino acid concentrations to 12 male volunteers with age 22.5 ± 1.4 years and a body mass index 22.4 ± 1.4 kg/m(2), who had no history of diabetes. MAIN OUTCOME MEASURES: Main outcome measures were area under the 120-minute curve for insulin, C...... after oral than after iv amino acid challenges (P = .006), whereas there was no significant difference in the glucagon response. Intact and total GIP rose after oral but not after iv amino acid administration, whereas intact and total GLP-1 levels did not change significantly in either test. CONCLUSION...

  7. Pharmacology of ketoprofen administered orally to pigs : an experimental and clinical study

    OpenAIRE

    Mustonen, Katja

    2012-01-01

    Ketoprofen is a non-steroidal anti-inflammatory drug belonging to the 2-arylpropionic acid group. It has been widely used in domestic animals because of its anti-inflammatory, antipyretic and analgesic actions. Ketoprofen is a chiral compound existing in two enantiomeric forms, S (+) and R (-) ketoprofen. Each enantiomer has different pharmacodynamic and pharmacokinetic properties. The commercial products in veterinary medicine are 50:50 racemic mixtures of both enantiomers. Ketoprofen underg...

  8. Duodenal administered seal oil for patients with subjective food hypersensitivity: an explorative open pilot study

    OpenAIRE

    Gregersen, Kine; Lind, Ragna A; Valeur, Jørgen; Bjørkkjær, Tormod; Berstad, Arnold; Lied, Gülen Arslan

    2010-01-01

    Short-term duodenal administration of n-3 polyunsaturated fatty acid (PUFA)-rich seal oil may improve gastrointestinal complaints in patients with subjective food hypersensitivity, as well as joint pain in patients with inflammatory bowel disease (IBD). The aim of the present explorative pilot study was to investigate whether 10-day open treatment with seal oil, 10 mL self-administrated via a nasoduodenal tube 3 times daily, could also benefit nongastrointestinal complaints and quality of lif...

  9. Duodenal administered seal oil for patients with subjective food hypersensitivity: an explorative open pilot study

    OpenAIRE

    Gregersen, Kine; Lind, Ragna Anne; Valeur, Jørgen; Bjørkkjær, Tormod; Berstad, Arnold; Lied, Gülen Arslan

    2010-01-01

    Short-term duodenal administration of n-3 polyunsaturated fatty acid (PUFA)-rich seal oil may improve gastrointestinal complaints in patients with subjective food hypersensitivity, as well as joint pain in patients with inflammatory bowel disease (IBD). The aim of the present explorative pilot study was to investigate whether 10-day open treatment with seal oil, 10 mL self-administrated via a nasoduodenal tube 3 times daily, could also benefit nongastrointestinal complaints and...

  10. Differential effects of whole-body γ-irradiation on antinociception induced by morphine and β-endorphin administered intracerebroventricularly in the mouse

    International Nuclear Information System (INIS)

    Two separate lines of evidence suggested the present study. First, intracerebroventricularly (i.c.v.) administered morphine (a μ-opioid receptor agonist) and β-endorphin (an ε-opioid receptor agonist) produce antinociception by activating different descending pain inhibitory systems. Second, γ-irradiation attenuates the acute antinociceptive action of i.c.v. injected morphine, but not DPLPE (a δ-opioid receptor agonist), in mice. These findings prompted us to investigate the effect of γ-irradiation on the antinociception produced by i.c.v. injected morphine and β-endorphin in male ICR mice. In one group, mice were exposed to whole-body irradiation at a dose of 5 Gy from a 60Co γ-source and the antinociceptive effects were tested 5, 30, 60,90 and 180 min after irradiation using the 1% acetic acid-induced writhing test (10 ml/kg). The antinociceptive effect was produced time-dependently and reached its maximum at 90 min after irradiation. Thus, time was fixed in the following studies. In another group, mice were irradiated with 5 Gy and tested 90 minutes later for antinociception produced by i.c.v. administration of morphine (50 and 100 ng/mouse) or β-endorphin (31 ng/mouse). Irradiation significantly potentiated the antinociception produced by β-endorphin. However, the antinociception produced by morphine was not affected by irradiation. These results demonstrate a differential sensitivity of μ- and ε-opioid receptors to γ-irradiation, in addition, support the hypothesis that morphine and β-endorphin administered supraspinally produce antinociception by different neuronal mechanisms. (author)

  11. Differential effects of whole-body {gamma}-irradiation on antinociception induced by morphine and {beta}-endorphin administered intracerebroventricularly in the mouse

    Energy Technology Data Exchange (ETDEWEB)

    Kim, J.K. [Korea Atomic Energy Research Inst., Taejon (Korea, Republic of); Chung, K.M.; Park, T.W.

    2000-05-01

    Two separate lines of evidence suggested the present study. First, intracerebroventricularly (i.c.v.) administered morphine (a {mu}-opioid receptor agonist) and {beta}-endorphin (an {epsilon}-opioid receptor agonist) produce antinociception by activating different descending pain inhibitory systems. Second, {gamma}-irradiation attenuates the acute antinociceptive action of i.c.v. injected morphine, but not DPLPE (a {delta}-opioid receptor agonist), in mice. These findings prompted us to investigate the effect of {gamma}-irradiation on the antinociception produced by i.c.v. injected morphine and {beta}-endorphin in male ICR mice. In one group, mice were exposed to whole-body irradiation at a dose of 5 Gy from a {sup 60}Co {gamma}-source and the antinociceptive effects were tested 5, 30, 60,90 and 180 min after irradiation using the 1% acetic acid-induced writhing test (10 ml/kg). The antinociceptive effect was produced time-dependently and reached its maximum at 90 min after irradiation. Thus, time was fixed in the following studies. In another group, mice were irradiated with 5 Gy and tested 90 minutes later for antinociception produced by i.c.v. administration of morphine (50 and 100 ng/mouse) or {beta}-endorphin (31 ng/mouse). Irradiation significantly potentiated the antinociception produced by {beta}-endorphin. However, the antinociception produced by morphine was not affected by irradiation. These results demonstrate a differential sensitivity of {mu}- and {epsilon}-opioid receptors to {gamma}-irradiation, in addition, support the hypothesis that morphine and {beta}-endorphin administered supraspinally produce antinociception by different neuronal mechanisms. (author)

  12. Silent hepatic lesions detected with computed tomography in aplastic anemia patients administered androgens for a long period

    International Nuclear Information System (INIS)

    Macroscopic liver lesions were investigated with the use of computed tomography (CT) and radionuclide imaging (RN) in 15 aplastic anemia patients who were administered anabolic steroids for over one year and who showed no apparent physical and biochemical sign of liver tumor. In 3 patients, CT scans showed radiolucent areas in the liver. Contrast enhancements revealed these lesions to be well vascularized, suggesting they were not cysts but probably tumors. RN imaging could not demonstrate any definite space occupying lesions. Total dose of AS administered to each of the three patients exceeded 30,000 mg. It was felt that attention should be paid to the possible development of hepatic tumor when the dose of AS administered exceeds 30,000 mg. (author)

  13. Dose estimation and radiation control measures for individuals having close contact with patients administered in vivo nuclear medicine

    International Nuclear Information System (INIS)

    Patients who have been administered radiopharmaceuticals become a source of exposure to a non-occupational individual helping in support and comfort of these patients. We measured external dose rates at several distances from 84 adult patients administered radiopharmaceuticals, and urinary excretion of radioactivity in their patients. And we estimated the maximal dose for persons having close contact with patients administered radiopharmaceuticals from the combination of these measurement data and scenarios of contact with patients. On the basis of the estimated values, we proposed the following dose constraint for care givers. (1) The dose constraint for a non-occupational care givers to an adult nuclear medicine patient should in no case exceed 300 μSv per patient per examination of any kind. (2) The dose constraint in ordinary examinations employing a radionuclide should not be greater than 15 μSv per patient per examination. (3 tabs.)

  14. Changes in group treatment procedures of Danish finishers and its influence on the amount of administered antimicrobials

    DEFF Research Database (Denmark)

    Fertner, Mette Ely; Boklund, Anette; Dupont, Nana Hee; Toft, Nils

    2016-01-01

    When treating groups of pigs orally, antimicrobials can be administered through either feed or water. During the last decade, the group treatment procedure for finishers has shifted from feed to water administration. We hypothesized that farms implementing this change in treatment procedure would...... administration to water administration between 2008 and 2009. In addition, we identified 221 farms where treatment was administered through feed (Cohort Feed), and another 553 farms where treatment was administered through water (Cohort Water). Both of these groups retained their original treatment procedure...... antimicrobials between the years was significantly different in Cohort Change when compared to both Cohort Water and Cohort Feed. Results from this study demonstrate that farms changing their procedure of group treatment from feed administration to water administration may increase their overall use of...

  15. Making instruction and assessment responsive to diverse students' progress: group-administered dynamic assessment in teaching mathematics.

    Science.gov (United States)

    Jeltova, Ida; Birney, Damian; Fredine, Nancy; Jarvin, Linda; Sternberg, Robert J; Grigorenko, Elena L

    2011-01-01

    This study entailed a 3 (instructional intervention) × 2 (assessment-type) between-subjects experimental design employing a pretest-intervention-posttest methodology. The instructional interventions were administered between subjects in three conditions: (a) dynamic instruction, (b) triarchic or theory of successful intelligence-control instruction, and (c) standard-control instruction. The assessment-type consisted between subjects of either (a) a group-administered dynamic posttest or (b) the same group-administered posttest interspersed with a control filler activity. Performance in different mathematics content areas taught in fourth grade was investigated. In total, 1,332 students and 63 classroom teachers in 24 schools across six school districts participated in the study. The results indicate the advantages of using dynamic instruction and assessment in regular classrooms while teaching mathematics, especially when the student body is highly ethnically diverse. PMID:21965254

  16. Silent hepatic lesions detected with computed tomography in aplastic anemia patients administered androgens for a long period

    Energy Technology Data Exchange (ETDEWEB)

    Yamagishi, Morihisa (Shiga Univ., Otsu (Japan)); Hiraoka, Atsumobu; Uchino, Haruto

    1982-07-01

    Macroscopic liver lesions were investigated with the use of computed tomography (CT) and radionuclide imaging (RN) in 15 aplastic anemia patients who were administered anabolic steroids for over one year and who showed no apparent physical and biochemical sign of liver tumor. In 3 patients, CT scans showed radiolucent areas in the liver. Contrast enhancements revealed these lesions to be well vascularized, suggesting they were not cysts but probably tumors. RN imaging could not demonstrate any definite space occupying lesions. Total dose of AS administered to each of the three patients exceeded 30,000 mg. It was felt that attention should be paid to the possible development of hepatic tumor when the dose of AS administered exceeds 30,000 mg.

  17. Bupivacaine administered intrathecally versus rectally in the management of intractable rectal cancer pain in palliative care

    Directory of Open Access Journals (Sweden)

    Zaporowska-Stachowiak I

    2014-10-01

    Full Text Available Iwona Zaporowska-Stachowiak,1,2 Grzegorz Kowalski,3 Jacek Łuczak,2 Katarzyna Kosicka,4 Aleksandra Kotlinska-Lemieszek,3 Maciej Sopata,3 Franciszek Główka4 1Chair and Department of Pharmacology, Poznan University of Medical Sciences, Poznan, Poland; 2Palliative Medicine In-patient Unit, University Hospital of Lord's Transfiguration, Poznan University of Medical Sciences, Poznan, Poland; 3Palliative Medicine Chair and Department, Poznan University of Medical Sciences, Poznan, Poland; 4Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, Poznan, Poland Background: Unacceptable adverse effects, contraindications to and/or ineffectiveness of World Health Organization step III "pain ladder" drugs causes needless suffering among a population of cancer patients. Successful management of severe cancer pain may require invasive treatment. However, a patient's refusal of an invasive procedure necessitates that clinicians consider alternative options. Objective: Intrathecal bupivacaine delivery as a viable treatment of intractable pain is well documented. There are no data on rectal bupivacaine use in cancer patients or in the treatment of cancer tenesmoid pain. This study aims to demonstrate that bupivacaine administered rectally could be a step in between the current treatment options for intractable cancer pain (conventional/conservative analgesia or invasive procedures, and to evaluate the effect of the mode of administration (intrathecal versus rectal on the bupivacaine plasma concentration.Cases: We present two Caucasian, elderly inpatients admitted to hospice due to intractable rectal/tenesmoid pain. The first case is a female with vulvar cancer, and malignant infiltration of the rectum/vagina. Bupivacaine was used intrathecally (0.25–0.5%, 1–2 mL every 6 hours. The second case is a female with ovarian cancer and malignant rectal infiltration. Bupivacaine was adminstered rectally (0.05–0.1%, 100 m

  18. Okadaic acid

    DEFF Research Database (Denmark)

    Danielsen, E Michael; Hansen, Gert H; Severinsen, Mai C K

    2014-01-01

    Okadaic acid (OA) is a polyether fatty acid produced by marine dinoflagellates and the causative agent of diarrhetic shellfish poisoning. The effect of OA on apical endocytosis in the small intestine was studied in organ cultured porcine mucosal explants. Within 0.5-1 h of culture, the toxin caused...... endosomes (TWEEs) occurred unimpeded in the presence of OA, FM condensed in larger subapical structures by 1 h, implying a perturbed endosomal trafficking/maturation. The fluorescent lysosomotropic agent Lysotracker revealed induction of large lysosomal structures by OA. Endocytosis from the brush border...

  19. Development and validation of a theoretical test in non-anaesthesiologist-administered propofol sedation for gastrointestinal endoscopy

    DEFF Research Database (Denmark)

    Jensen, Jeppe Thue; Savran, Mona Meral; Møller, Ann Merete;

    2016-01-01

    OBJECTIVE: Safety with non-anaesthesiologist-administered propofol sedation (NAAP) during gastrointestinal (GI) endoscopy is related to theoretical knowledge. A summative testing of knowledge before attempting supervised nurse-administered propofol sedation (NAPS) in the clinic is advised. The aims...... II questions. The 50 MCQs showed mean (SD) intergroup differences (p = 0.001) between novices = 28.6 (4.82), intermediates = 36.8 (5.43) and experienced = 41.8 (4.65) and provided a pass score of 35.2. The course with pre-course test had significant effect on the knowledge of nurses (18% increase...

  20. Influence of caffeine administered at 45 °C on bone tissue development

    Directory of Open Access Journals (Sweden)

    Marek Tomaszewski

    2014-11-01

    Full Text Available [b]introduction and objective[/b]. Caffeine is one of the world’s most commonly ingested alkaloids which easily permeates the placenta. The teratogenic and embryotoxic influence of large doses of caffeine has been established in many experimental studies on animals. The objective of this work was to assess the influence of caffeine, administered at 45 °C, on the development of the bone tissue of rats, with particular reference to elemental bone composition using an X-ray microprobe. [b]materials and methods[/b]. The research was conducted on white rats of the Wistar strain. The fertilized females were divided into two groups: an Experimental Group (Group E and a Control Group (Group C. The females in Group E were given caffeine orally (at 45 °C in 30 mg/day doses from the 8 [sup]th [/sup] to the 21 [sup]st[/sup] day of pregnancy. The females in Group C were given water at the same temperature. The fetuses were used to assess the growth and mineralization of the skeleton. A qualitative analysis of the morphology and mineralization of bones was conducted using the alcian-alizarin method. For calcium and potassium analysis, an X-ray microprobe was used. [b]results.[/b] By staining the skeleton using the alcian-alizarin method, changes in 52 of Group E fetuses were observed. The frequency of the development variants in the Group E rats was statistically higher, compared with Group C. [b]conclusions[/b]. Receiving caffeine at a higher temperature may result in different pharmacodynamics and significantly change tolerance to it. In Group E, a significant decrease in the calcium level, as well as an increase in the potassium level, was observed. The X-ray microprobe can be a perfect complement to the methods which enable determination of the mineralization of osseous tissue.

  1. Radiosensitizing activity and pharmacokinetics of multiple dose administered KU-2285 in peripheral nerve tissue in mice

    International Nuclear Information System (INIS)

    In a clinical trial in which a 2-nitroimidazole radiosensitizer was administered repeatedly, the dose-limiting toxicity was found to be peripheral neuropathy. In the present study, the in vivo radiosensitizing activity of KU-2285 in combination with radiation dose fractionation, and the pharmacokinetics of cumulative dosing of KU-2285 in the peripheral nerves were examined. The ability of three nitroimidazoles, misonidazole (MISO), etanidazole (SR-2508) and KU-2285, to sensitize SCCVII tumors to radiation treatment has been compared for drug doses in the range 0-200 mg/kg. Single radiation doses or two different fractionation schedules (6 Gy/fractions x three fractions/48 h or 5 Gy/fractions x five fractions/48 h) were used; the tumor cell survival was determined using an in vivo/in vitro colony assay. The pharmacokinetics in the sciatic nerves were undertaken, when KU-2285 or etanidazole were injected at a dose of 200 mg/kg intravenously one, two, three, or four times at 2-h intervals. At less than 100 mg/kg, KU-2285 sensitized SCCVII tumors more than MISO and SR-2508 by fractionated irradiation. Evaluation of pharmacokinetics in the peripheral nerves showed that the apparent biological half-life of SR-2508 increased with the increases in the number of administrations, whereas that of KU-2285 became shorter. Since most clinical radiotherapy is given in small multiple fractions, KU-2285 appears to be a hypoxic cell radiosensitizer that could be useful in such regimens, and that poses no risk of chronic peripheral neurotoxicity. 12 refs., 5 figs., 1 tab

  2. Gender and estrous cycle influences on behavioral and neurochemical alterations in adult rats neonatally administered ketamine.

    Science.gov (United States)

    Célia Moreira Borella, Vládia; Seeman, Mary V; Carneiro Cordeiro, Rafaela; Vieira dos Santos, Júnia; Romário Matos de Souza, Marcos; Nunes de Sousa Fernandes, Ethel; Santos Monte, Aline; Maria Mendes Vasconcelos, Silvânia; Quinn, John P; de Lucena, David F; Carvalho, André F; Macêdo, Danielle

    2016-05-01

    Neonatal N-methyl-D-aspartate (NMDA) receptor blockade in rodents triggers schizophrenia (SCZ)-like alterations during adult life. SCZ is influenced by gender in age of onset, premorbid functioning, and course. Estrogen, the hormone potentially driving the gender differences in SCZ, is known to present neuroprotective effects such as regulate oxidative pathways and the expression of brain-derived neurotrophic factor (BDNF). Thus, the aim of this study was to verify if differences in gender and/or estrous cycle phase during adulthood would influence the development of behavioral and neurochemical alterations in animals neonatally administered ketamine. The results showed that ketamine-treated male (KT-male) and female-in-diestrus (KTF-diestrus, the low estrogen phase) presented significant deficits in prepulse inhibition of the startle reflex and spatial working memory, two behavioral SCZ endophenotypes. On the contrary, female ketamine-treated rats during proestrus (KTF-proestrus, the high estradiol phase) had no behavioral alterations. This correlated with an oxidative imbalance in the hippocampus (HC) of both male and KTF-diestrus female rats, that is, decreased levels of GSH and increased levels of lipid peroxidation and nitrite. Similarly, BDNF was decreased in the KTF-diestrus rats while no alterations were observed in KTF-proestrus and male animals. The changes in the HC were in contrast to those in the prefrontal cortex in which only increased levels of nitrite in all groups studied were observed. Thus, there is a gender difference in the adult rat HC in response to ketamine neonatal administration, which is based on the estrous cycle. This is discussed in relation to neuropsychiatric conditions and in particular SCZ. PMID:26215537

  3. Intranasally administered mesenchymal stem cells promote a regenerative niche for repair of neonatal ischemic brain injury.

    Science.gov (United States)

    Donega, Vanessa; Nijboer, Cora H; van Tilborg, Geralda; Dijkhuizen, Rick M; Kavelaars, Annemieke; Heijnen, Cobi J

    2014-11-01

    Previous work from our group has shown that intranasal MSC-treatment decreases lesion volume and improves motor and cognitive behavior after hypoxic-ischemic (HI) brain damage in neonatal mice. Our aim was to determine the kinetics of MSC migration after intranasal administration, and the early effects of MSCs on neurogenic processes and gliosis at the lesion site. HI brain injury was induced in 9-day-old mice and MSCs were administered intranasally at 10days post-HI. The kinetics of MSC migration were investigated by immunofluorescence and MRI analysis. BDNF and NGF gene expression was determined by qPCR analysis following MSC co-culture with HI brain extract. Nestin, Doublecortin, NeuN, GFAP, Iba-1 and M1/M2 phenotypic expression was assessed over time. MRI and immunohistochemistry analyses showed that MSCs reach the lesion site already within 2h after intranasal administration. At 12h after administration the number of MSCs at the lesion site peaks and decreases significantly at 72h. The number of DCX(+) cells increased 1 to 3days after MSC administration in the SVZ. At the lesion, GFAP(+)/nestin(+) and DCX(+) expression increased 3 to 5days after MSC-treatment. The number of NeuN(+) cells increased within 5days, leading to a dramatic regeneration of the somatosensory cortex and hippocampus at 18days after intranasal MSC administration. Interestingly, MSCs expressed significantly more BDNF gene when exposed to HI brain extract in vitro. Furthermore, MSC-treatment resulted in the resolution of the glial scar surrounding the lesion, represented by a decrease in reactive astrocytes and microglia and polarization of microglia towards the M2 phenotype. In view of the current lack of therapeutic strategies, we propose that intranasal MSC administration is a powerful therapeutic option through its functional repair of the lesion represented by regeneration of the cortical and hippocampal structure and decrease of gliosis. PMID:24945601

  4. Enhanced anxiety in the male offspring of sires that self-administered cocaine.

    Science.gov (United States)

    White, Samantha L; Vassoler, Fair M; Schmidt, Heath D; Pierce, R Christopher; Wimmer, Mathieu E

    2016-07-01

    We previously showed that paternal cocaine exposure reduced the reinforcing efficacy of cocaine in male offspring. Here, we sought to determine whether paternal cocaine experience could also influence anxiety levels in offspring. Male rats were allowed to self-administer cocaine (controls received saline passively) for 60 days and then were bred with naïve females. Measures of anxiety and cocaine-induced anxiogenic effects were assessed in the adult offspring. Cocaine-sired male offspring exhibited increased anxiety-like behaviors, as measured using the novelty-induced hypophagia and defensive burying tasks, relative to saline-sired males. In contrast, sire cocaine experience had no effect on anxiety-like behaviors in female offspring. When challenged with an anxiogenic (but not anorectic) dose of cocaine (2.5 mg/kg, i.p.), anxiety-like behavior was enhanced in all animals to an equal degree regardless of sire drug experience. Since anxiety and depression are often co-morbid, we also assessed measures of depressive-like behavior. Sire cocaine experience had no effect on depression-like behaviors, as measured by the forced swim task, among male offspring. In a separate group of naïve littermates, select neuronal correlates of anxiety were measured. Male offspring of cocaine-experienced sires showed increased mRNA and protein expression of corticotropin-releasing factor receptor 2 in the hippocampus. Together, these results indicate that cocaine-experienced sires produce male progeny that have increased baseline anxiety, which is unaltered by subsequent cocaine exposure. PMID:25923597

  5. Market surveillance panel monitoring report on the IMO-administered electricity markets : Executive summary

    International Nuclear Information System (INIS)

    The electricity market in Ontario was opened on May 1, 2002. This document provides the executive summary for the first monitoring report prepared by the Market Surveillance Panel covering the period May to August 2002. In the introductory chapter of the main report, explanations are provided on why competition, when effective, benefits consumers, as well as touching on the conditions for the design of an effective competitive electricity market with special emphasis on the electricity market in Ontario and its operations. For the period under review, the report presents a description and analysis of the activities and operations of the Independent Electricity Market Operator (IMO)-administered markets (focus on energy markets). Rising costs for hydroelectric power and very high temperatures combined in July and August resulting in record levels of demand. It became apparent that the province relies on imports to satisfy demand. The figures reveal that reliability in July and August depended on imports 21 per cent of the time. A serious shortage of generating capacity exists in Ontario and steps to rectify the situation should be initiated to ensure reliability of electricity supply for next summer. Prospective entrants in the electricity market in Ontario may not be receiving clear, credible and consistent signals. Effective use of existing or potential transmission capacity may not always be made by the system. The lowering of consumption by consumers is difficult since consumers are not properly equipped, resulting in their lack of power to discipline price increases from suppliers. The future evolution of the market must be planned and measures implemented to enhance the effectiveness of competition. The incentives effects for some aspects of the market design do not completely satisfy the Panel

  6. Pharmacokinetics and Pharmacodynamics of Intranasal Insulin Spray (Nasulin™) Administered to Healthy Male Volunteers:

    Science.gov (United States)

    Leary, Andrew C.; Dowling, Muiris; Cussen, Kathleen; O'Brien, Jackie; Stote, Robert M.

    2008-01-01

    Background The pharmacokinetics and pharmacodynamics of a Bentley Pharmaceuticals proprietary intranasal (IN) insulin formulation (Nasulin™) were studied in healthy volunteers. Methods Thirteen fasting healthy male volunteers received five doses of medication (one dose of 4 international units [IU] subcutaneous (SC) regular insulin and four doses of 25 IU IN insulin) at least 48 h apart. Serum insulin, serum C-peptide, and plasma glucose were measured in the 4 h after dosing. Profiles were compared for IN insulin spray following administration into the dominant nostril (more open at time of dosing) and into the nondominant nostril (less open at time of dosing). Results The formulation was generally well tolerated. A rise in serum insulin levels accompanied by a decrease in plasma glucose was seen following all doses. For IN doses, peak insulin levels were generally attained in 10–20 min and remained elevated for approximately 40–50 min; the resultant effect on glucose peaked at 40 min and waned approximately 2 h postdosing. As reported in other studies, the interindividual response to insulin was variable. The comparative absorption of IN insulin relative to SC insulin was 12.0% (dominant nostril) or 15.4% (nondominant nostril) over 2 h. This increased somewhat if sneezers and volunteers with moderately blocked nostrils were removed from the analysis. Conclusions This IN formulation was generally well tolerated and relatively well absorbed. While both insulin data (maximal plasma concentration and area under the plasma concentration time curve) and glucose data (% fall) support a trend toward better absorption from the nondominant nostril, this did not reach statistical significance. Nasulin can be administered without reference to the nasal cycle. PMID:19885293

  7. Safety of Curcuma aromatica oil gelatin microspheres administered via hepatic artery

    Institute of Scientific and Technical Information of China (English)

    Shi-Gui Deng; Zhi-Feng Wu; Wei-Ying Li; Zhi-Gang Yang; Gang Chang; Fan-Zhe Meng; Li-Li Mo

    2004-01-01

    AIM: To evaluate the safety of Curcuma aromatica oilgelatin microspheres (CAO-GMS) infused via hepatic artery against primary liver cancer.METHODS: The safety of CAO-GMS was evaluated in view of its acute toxicity in rats, long-term toxicity in Beagle dogs and general pharmacology in rats and mongrel dogs. RESULTS: The 50% lethal dose (LD50) of CAO-GMS infusedvia the hepatic artery was 17.19 mg/kg, and the serum biochemical indices of dying rats after the administration changed markedly while those of survived rats did not. Subsequent pathological examination of the tissues from the dead rats indicated improper embolism. Similar edema and small necrotic foci in the hepatic Iobule were found in the hepatic tissue of rats receiving 10 and 5 mg/kg CAO GMS and GMS 60 d after the last administration, while not in the rats of the blank control group, indicating that microspheres infused via the hepatic artery may induce irreversible liver damage dose-dependently. General pharmacological study showed that the activities (postureand gait), respiration frequency, blood pressure or heart rate of the dogs were not affected by CAO-GMS, nor were salivation, tremor or pupil changes of the rats observed or their balancing ability compromised, suggesting CAO-GMSinfused via the hepatic artery did not significantly affect the nervous, respiratory and cardiovascular systems. CONCLUSION: CAO-GMS embolization administered via the hepatic artery is safe but undesired embolization induced by vascular variation should be given due attention in its clinical application. Individualized embolization dosage and super-selective catheterization technique are recommended to avoid undesired embolism and reduce complications.

  8. Human pharmacokinetics and toxicity of high-dose metronidazole administered orally and intravenously

    International Nuclear Information System (INIS)

    This study is part of a clinical program to assess the use of nitroimidazoles as radiosensitizers of hypoxic tumor cells. A total of 37 patients with malignant tumors have been entered into the study to receive oral high-dose metronidazole in conjunction with radiation. Twenty-eight patients with malignant brain tumors received 6 gm/m2 three times a week for 3 weeks (a mean total dose of 5.3 gm/m2). Maximum mean plasma drug concentration of 1 mM was obtained at 4 hours after drug ingestion with a mean half-life of 13 hours. Tissue and cerebrospinal fluid levels of 80% to 90% of the plasma levels were obtained at 4 to 6 hours. A linear relationship between increased drug dose and increased plasma concentration was observed at doses of 2.5 gm/m2 up to 6 gm/m2. Acute gastrointestinal and central nervous system toxicity was the dose-limiting factor (50% and 25%, respectively, at total doses of 5.3 gm/m2). Pharmacokinetic studies of intravenous metronidazole were performed in eight consenting patients. Single doses of 0.5, 1, 1.5, and 2 gm were administered intravenously by zero-order infusion pump. Seven of the eight patients received a second identical dose orally 1 week later and the results were compared. Open two-compartment kinetic characteristics of metronidazole were computed from simultaneous plasma infusion and urine excretion rate equations, by use of a nonlinear least-squares regression analysis program (NONLIN). The mean (+/- SD) for alpha half-life was 1.2 +/- 1.3 hours, and that for the beta half-life was 9.8 +/- 5.9 hours. The absolute oral bioavailability was estimated to approximate 100%

  9. Administer and collect medical questionnaires with Google documents: a simple, safe, and free system

    Directory of Open Access Journals (Sweden)

    Rakib Uddin RAYHAN

    2013-09-01

    Full Text Available Aim: Questionnaires are an invaluable resource for clinical trials. They serve to estimate disease burden and clinical parameters associated with a particular study. However, current researchers are tackling budget constraints, loss of funding opportunities, and rise of research associated fees. We aimed at exploring alternative avenues taking advantage of the free Google docs software for questionnaire administration. This presents an opportunity to reduce costs while simultaneously increasing efficiency and data fidelity. Material and Methods: Google documents were used as a platform to create online questionnaires that were automatically hosted via a unique URL. Password protected access to the URL link and a unique study ID gave patients around the clock access from anywhere in the world. Unique study ID ensured confidentially of all self-reported data. Patient responses were secured using a “Cloud” database where the data was automatically sorted, scaled and scored by custom Excel formulas. Researchers downloaded real-time questionnaire responses in multiple formats (e.g. excel which was then analyzed with a statistical software of choice. Results: This simple workflow provided instant questionnaire scores that eliminated the use for paper-based responses and subsequent manual entry of data. Ease of access to online questionnaires provided convenience to patients leading to better response rates and increase in data fidelity. The system also allowed for real time monitoring of patient’s progress on completing questionnaires. Online questionnaires had 100% completion rate compared to paper-based questionnaires. Conclusions: Google docs can serve as an efficient and free platform to administer questionnaires to a clinical population without sacrificing quality, security, and fidelity of data.

  10. Long-lived effects of administering β-glucans: Indications for trained immunity in fish.

    Science.gov (United States)

    Petit, Jules; Wiegertjes, Geert F

    2016-11-01

    Over the past decades, it has become evident that immune-modulation of fish with β-glucans, using injection, dietary or even immersion routes of administration, has stimulating but presumed short-lived effects on both intestinal and systemic immunity and can increase protection against a subsequent pathogenic challenge. Although the exact effects can be variable depending on, among others, fish species and administration route, the immune-stimulating effects of β-glucans on the immune system of fish appear to be universal. This review provides a condensed update of the most recent literature describing the effects of β-glucans on the teleost fish immune system. We shortly discuss possible mechanisms influencing immune-stimulation by β-glucans, including microbial composition of the gut, receptor recognition and downstream signalling. Of interest, in mammalian monocytes, β-glucans are potent inducers of trained immunity. First, we screened the literature for indications of this phenomenon in fish. Criteria that we applied include indications for at least one out of three features considered characteristic of trained immunity; (i) providing protection against a secondary infection in a T- and B-lymphocyte independent manner, (ii) conferring increased resistance upon re-infection and, (iii) relying on key roles for innate immune cell types such as natural killer cells and macrophages. We conclude that several indications exist that support the notion that the innate immune system of teleost fish can be trained. Second, we screened the literature for indications of long-lived effects on innate immunity of fish after administering β-glucans, a criterion which could help to identify key roles for macrophages on resistance to infection. We discuss whether β-glucans, as well-known immune-stimulants, are able to train the immune system of fish and argue in favour of further studies designed to specifically investigate this phenomenon in fish. PMID:26945622

  11. Pharmacokinetics of ketamine and propofol combination administered as ketofol via continuous infusion in cats.

    Science.gov (United States)

    Zonca, A; Ravasio, G; Gallo, M; Montesissa, C; Carli, S; Villa, R; Cagnardi, P

    2012-12-01

    The pharmacokinetics of the extemporaneous combination of low doses of ketamine and propofol, known as 'ketofol', frequently used for emergency procedures in humans to achieve safe sedation and analgesia was studied in cats. The study was performed to assess propofol, ketamine and norketamine kinetics in six female cats that received ketamine and propofol (1:1 ratio) as a loading dose (2 mg/kg each, IV) followed by a continuous infusion (10 mg/kg/h each, IV, 25 min of length). Blood samples were collected during the infusion period and up to 24 h afterwards. Drug quantification was achieved by HPLC analysis using UV-visible detection for ketamine and fluorimetric detection for propofol. The pharmacokinetic parameters were deduced by a two-compartment bolus plus infusion model for propofol and ketamine and a monocompartmental model for norketamine. Additional data were derived by a noncompartmental analysis. Propofol and ketamine were quantifiable in most animals until 24 and 8 h after the end of infusion, respectively. Propofol showed a long elimination half-life (t(1/2λ2) 7.55 ± 9.86 h), whereas ketamine was characterized by shorter half-life (t(1/2λ2) 4 ± 3.4 h) owing to its rapid biotransformation into norketamine. The clinical significance of propofol's long elimination half-life and low clearance is negligible when the drug is administered as short-term and low-dosage infusion. The concurrent administration of ketamine and propofol in cats did not produce adverse effects although it was not possible to exclude interference in the metabolism. PMID:22283551

  12. Peripherally administered oxytocin modulates latent inhibition in a manner consistent with antipsychotic drugs

    Science.gov (United States)

    Feifel, D.; Shilling, P. D.; Hillman, J.; Maisel, M.; Winfield, J.; Melendez, G.

    2014-01-01

    Background Peripherally administered oxytocin (OT) has produced antipsychotic drug (APD)-like effects in animal tests that are predictive of APD efficacy. However, these effects have mainly been demonstrated using animal models of schizophrenia-like deficits in prepulse inhibition (PPI) of the startle reflex. Another schizophrenia-relevant abnormality that is the basis of a predictive animal test for APD efficacy is deficient latent inhibition (LI). LI is the normal suppression of a classically conditioned response when the subject is pre-exposed to the conditioned stimulus (CS) before it is paired with the unconditioned stimulus (UCS). Conditioned taste aversion (CTA), the normal avoidance of ingesting a food or liquid by animals when its taste is associated with an aversive experience, was used to test whether OT facilitates LI consistent with APDs. Methods Brown Norway rats, known to naturally display attenuated LI, were aversively conditioned on two consecutive exposures to flavored drinking water (0.1% saccharin) by pairing it with malaise-inducing lithium chloride injections. Concurrent with conditioning, rats received subcutaneous OT (0.02, 0.1, 0.5 mg/kg) or saline. Some rats were pre-exposed to the flavored water prior to its aversive conditioning (pre-exposed) while others were not (non pre-exposed). Two days after aversive conditioning the amount of flavored water consumed during a 20-minute session was recorded. Results As expected, LI, defined as greater consumption by pre-exposed vs. non pre-exposed rats was only weakly exhibited in Brown Norway rats and OT enhanced LI by reducing CTA in pre-exposed rats in a dose-dependent manner, with the 0.02 mg/kg dose producing the strongest effect. Conclusions The facilitation of LI by OT is consistent with the effects produced by APDs and provides further support for the notion that OT has therapeutic potential for schizophrenia. PMID:25447298

  13. Perfluorooctanoic acid

    NARCIS (Netherlands)

    P. de Voogt

    2014-01-01

    Perfluorooctanoic acid (PFOA, 335-67-1) is used in fluoropolymer production and firefighting foams and persists in the environment. Human exposure to PFOA is mostly through the diet. PFOA primarily affects the liver and can cause developmental and reproductive toxic effects in test animals.

  14. Ascorbic Acid

    Science.gov (United States)

    Cevi-Bid® ... If you become pregnant while taking ascorbic acid, call your doctor. ... In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call ...

  15. Stearic Acid

    Science.gov (United States)

    Young, Jay A.

    2004-01-01

    A chemical laboratory information profile (CLIP) is presented for the chemical, stearic acid. The profile lists the chemical's physical and harmful characteristics, exposure limits, and symptoms of major exposure, for the benefit of teachers and students, who use the chemical in the laboratory.

  16. Mefenamic Acid

    Science.gov (United States)

    Mefenamic acid comes as a capsule to take by mouth. It is usually taken with food every 6 hours as needed for up to 1 week. Follow ... pain vomit that is bloody or looks like coffee grounds black, tarry, or bloody stools slowed breathing ...

  17. The antihypertensive effect of orally administered nifedipine-loaded nanoparticles in spontaneously hypertensive rats

    OpenAIRE

    Il Kim, Young; Fluckiger, Laurence; Hoffman, Maurice; Lartaud-Idjouadiene, Isabelle; Atkinson, Jeffrey; Maincent, Philippe

    1997-01-01

    The therapeutic use of nifedipine is limited by the rapidity of the onset of its action and its short biological half-life. In order to produce a form devoid of these disadvantages we made nanoparticles of nifedipine from three different polymers, poly-ε-caprolactone (PCL), polylactic and glycolic acid (1 : 1) copolymers (PLAGA), and Eudragit RL/RS (Eudragit). Nifedipine in polyethylene glycol 400 (PEG) solution was used as a control.The average diameters of the nanoparticles ranged from 0.12...

  18. Duodenal administered seal oil for patients with subjective food hypersensitivity: an explorative open pilot study

    OpenAIRE

    Gregersen,, K.

    2010-01-01

    Kine Gregersen1,2, Ragna A Lind1, Jørgen Valeur1,3, Tormod Bjørkkjær2, Arnold Berstad1,3, Gülen Arslan Lied1,31Institute of Medicine, University of Bergen, Bergen, Norway; 2National Institute of Nutrition and Seafood Research (NIFES), Bergen, Norway; 3Section for Gastroenterology, Department of Medicine, Haukeland University Hospital, Bergen, NorwayAbstract: Short-term duodenal administration of n-3 polyunsaturated fatty acid (PUFA)-rich seal oil may i...

  19. Metabolism of lithocholic and chenodeoxycholic acids in the squirrel monkey

    International Nuclear Information System (INIS)

    Metabolism of lithocholic acid (LCA) and chenodeoxycholic acid (CDCA) was studied in the squirrel monkey to clarify the mechanism of the lack of toxicity of CDCA in this animal. Radioactive LCA was administered to squirrel monkeys with biliary fistula. Most radioactivity was excreted in the bile in the form of unsulfated lithocholyltaurine. The squirrel monkey thus differs from humans and chimpanzees, which efficiently sulfate LCA, and is similar to the rhesus monkey and baboon in that LCA is poorly sulfated. When labeled CDCA was orally administered to squirrel monkeys, less than 20% of the dosed radioactivity was recovered as LCA and its further metabolites in feces over 3 days, indicating that bacterial metabolism of CDCA into LCA is strikingly less than in other animals and in humans. It therefore appears that LCA, known as a hepatotoxic secondary bile acid, is not accumulated in the squirrel monkey, not because of its rapid turnover through sulfation, but because of the low order of its production

  20. Metabolism of lithocholic and chenodeoxycholic acids in the squirrel monkey

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, H.; Hamada, M.; Kato, F.

    1985-09-01

    Metabolism of lithocholic acid (LCA) and chenodeoxycholic acid (CDCA) was studied in the squirrel monkey to clarify the mechanism of the lack of toxicity of CDCA in this animal. Radioactive LCA was administered to squirrel monkeys with biliary fistula. Most radioactivity was excreted in the bile in the form of unsulfated lithocholyltaurine. The squirrel monkey thus differs from humans and chimpanzees, which efficiently sulfate LCA, and is similar to the rhesus monkey and baboon in that LCA is poorly sulfated. When labeled CDCA was orally administered to squirrel monkeys, less than 20% of the dosed radioactivity was recovered as LCA and its further metabolites in feces over 3 days, indicating that bacterial metabolism of CDCA into LCA is strikingly less than in other animals and in humans. It therefore appears that LCA, known as a hepatotoxic secondary bile acid, is not accumulated in the squirrel monkey, not because of its rapid turnover through sulfation, but because of the low order of its production.

  1. Assessment of lower urinary tract symptoms in women by a self-administered questionnaire: test-retest reliability

    DEFF Research Database (Denmark)

    Bernstein, Inge Thomsen; Sejr, T; Able, I;

    1996-01-01

    A self-administered questionnaire assessing female lower urinary tract symptoms and their impact on quality of life is described and validated, on 56 females in six participating departments. The patients answered two identical questionnaires on separate occasions before treatment. Test-retest re...

  2. Amelioration of radiation esophagitis by orally administered p53/Mdm2/Mdm4 inhibitor (BEB55) or GS-nitroxide

    NARCIS (Netherlands)

    Kim, Hyun; Bernard, Mark E.; Epperly, Michael W.; Shen, Hongmei; Amoscato, Andrew; Dixon, Tracy M.; Doemling, Alexander S.; Li, Song; Gao, Xiang; Wipf, Peter; Wang, Hong; Zhang, Xichen; Kagan, Valerian E.; Greenberger, Joel S.

    2011-01-01

    Background/Aim: Esophagitis is a significant toxicity of radiation therapy for lung cancer. In this study, reduction of irradiation esophagitis in mice, by orally administered p53/Mdm2/Mdm4 inhibitor, BEB55, or the GS-nitroxide, JP4-039, was evaluated. Materials and Methods: BEB55 or JP4-039 in F15

  3. Rationale and Specifications for a Prototype, Group-Administered End-of-Unit Assessment Instrument for the SWRL Reading Program.

    Science.gov (United States)

    Okada, Masahito; Besel, Ronald

    This document describes the purposes, rationale, and specifications of a prototype group-administered criterion exercise to be used with blocks 1-8 of the Southwest Regional Laboratory (SWRL) Reading Program. A description of the sampling domains, sampling procedures, and the methods employed in the construction of test items is presented. Also…

  4. 7 CFR 1.29 - Subpoenas relating to investigations under statutes administered by the Secretary of Agriculture.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Subpoenas relating to investigations under statutes administered by the Secretary of Agriculture. 1.29 Section 1.29 Agriculture Office of the Secretary of Agriculture ADMINISTRATIVE REGULATIONS Departmental Proceedings § 1.29 Subpoenas relating to...

  5. The Computer-Assisted Hypnosis Scale: Standardization and Norming of a Computer-Administered Measure of Hypnotic Ability.

    Science.gov (United States)

    Grant, Carolyn D.; Nash, Michael R.

    1995-01-01

    In a counterbalanced, within subjects, repeated measures design, 130 undergraduates were administered the Computer-Assisted Hypnosis Scale (CAHS) and the Stanford Hypnotic Susceptibility Scale and were hypnotized. The CAHS was shown to be a psychometrically sound instrument for measuring hypnotic ability. (SLD)

  6. Silver nanoparticles administered to chicken affect VEGFA and FGF2 gene expression in breast muscle and heart

    DEFF Research Database (Denmark)

    Hotowy, Anna Malgorzata; Sawosz, Ewa; Pineda, Lane Manalili;

    2012-01-01

    Nanoparticles of colloidal silver (AgNano) can influence gene expression. Concerning trials of AgNano application in poultry as antimicrobial and metabolic agents, it is useful to reveal whether they affect the expression of genes crucial for bird development. AgNano were administered to broiler...

  7. An Evaluation of a Self-Instructional Manual for Teaching Individuals How to Administer the Revised ABLA Test

    Science.gov (United States)

    Boris, Ashley L.; Awadalla, Nardeen; Martin, Toby L.; Martin, Garry L.; Kaminski, Lauren; Miljkovic, Morena

    2015-01-01

    The Assessment of Basic Learning Abilities (ABLA) is a tool that is used to assess the learning ability of individuals with intellectual disability (ID) and children with autism. The ABLA was recently revised and is now referred to as the ABLA-Revised (ABLA-R). A self-instructional manual was prepared to teach individuals how to administer the…

  8. 40 CFR 147.2400 - State-administered program-Class I, II, III, IV, and V wells.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class I, II, III, IV, and V wells. 147.2400 Section 147.2400 Protection of Environment ENVIRONMENTAL PROTECTION... between the Washington Department of Ecology and Department of Social and Health Services, Related to...

  9. Pharmacokinetics of nasally administered tobramycin, colistin sulphomethate sodium and a combination of tobramycin and colistin sulphomethate sodium

    NARCIS (Netherlands)

    Van Velzen, A.J.; Berkhout, M.C.; Touw, D.J.; De Kok, B.M.; Heijerman, H.G.M.

    2014-01-01

    The paranasal sinuses can constitute a niche for bacteria which can migrate to the lungs. Nasal administration of antibiotics may be effective, but safety of this treatment has to be established first. Objectives: Investigation of the pharmacokinetics (PK) of nasally administered tobramycin (T), col

  10. Protocol compliance of administering parenteral medication in Dutch hospitals: an evaluation and cost-estimation of the implementation.

    NARCIS (Netherlands)

    Schilp, J.; Boot, S.; Blok, C. de; Spreeuwenberg, P.; Wagner, C.

    2014-01-01

    Objectives: Preventable adverse drug events (ADEs) are closely related to administration processes of parenteral medication. The Dutch Patient Safety Program provided a protocol for administering parenteral medication to reduce the amount of ADEs. The execution of the protocol was evaluated and a co

  11. 40 CFR 147.1601 - State-administered program-Class I, III, IV and V wells.

    Science.gov (United States)

    2010-07-01

    ..., are also part of the approved State-administered UIC program: (1) Water Quality Act, New Mexico Statutes Annotated sections 74-6-1 through 74-6-13 (1978 and Supp. 1982); (2) Geothermal Resources Conservation Act, New Mexico Statutes Annotated sections 71-5-1 through 71-5-24 (1978 and Supp. 1982);...

  12. 40 CFR 147.2200 - State-administered program-Class I, III, IV, and V wells.

    Science.gov (United States)

    2010-07-01

    ..., and 281. (ii) Vernon's Texas Codes Annotated, Water Code, Chapters 5, 7, 26, and 32, Health and Safety... the Texas Natural Resource Conservation Commission a predecessor to the Texas Commission on... AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND...

  13. Satisfaction with Therapist-Delivered vs. Self-Administered Online Cognitive Behavioural Treatments for Depression Symptoms in College Students

    Science.gov (United States)

    Richards, Derek; Timulak, Ladislav

    2013-01-01

    Participants with symptoms of depression received either eight sessions of therapist-delivered email cognitive behaviour therapy (eCBT; n = 37), or eight sessions of computerised CBT self-administered treatment (cCBT; n = 43). At post-treatment participants completed a questionnaire to determine what they found satisfying about their online…

  14. Political, Economic, Socio-Cultural, and Educational Challenges of Administering a Sino-US Joint Venture Campus in China

    Science.gov (United States)

    Ozturgut, Osman

    2008-01-01

    This qualitative study explored the political, economic, socio-cultural, and educational challenges of administering a Sino-U.S. joint-venture campus in the People's Republic of China. China American University (CAU) is an educational joint venture between China Investment Company (CIC) and American University (AU) in the U.S. that resulted in…

  15. Making Instruction and Assessment Responsive to Diverse Students' Progress: Group-Administered Dynamic Assessment in Teaching Mathematics

    Science.gov (United States)

    Jeltova, Ida; Birney, Damian; Fredine, Nancy; Jarvin, Linda; Sternberg, Robert J.; Grigorenko, Elena L.

    2011-01-01

    This study entailed a 3 (instructional intervention) x 2 (assessment-type) between-subjects experimental design employing a pretest-intervention-posttest methodology. The instructional interventions were administered between subjects in three conditions: (a) dynamic instruction, (b) triarchic or theory of successful intelligence-control…

  16. 8 CFR 1337.2 - Oath administered by the Immigration and Naturalization Service or an Immigration Judge.

    Science.gov (United States)

    2010-01-01

    ... 8 CFR chapter I. Such ceremonies shall be conducted at regular intervals as frequently as necessary... applicant's name shall be removed from the list of eligible persons as provided in § 335.5 of 8 CFR chapter... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Oath administered by the Immigration...

  17. Endoscopy nurse-administered propofol sedation performance. Development of an assessment tool and a reliability testing model

    DEFF Research Database (Denmark)

    Jensen, Jeppe Thue; Konge, Lars; Møller, Ann;

    2014-01-01

    training and for future certification. The aim of this study was to develop an assessment tool for measuring competency in propofol sedation and to explore the reliability and validity of the tool. MATERIAL AND METHODS: The nurse-administered propofol assessment tool (NAPSAT) was developed in a Delphi...

  18. Measuring Sensory Reactivity in Autism Spectrum Disorder: Application and Simplification of a Clinician-Administered Sensory Observation Scale

    Science.gov (United States)

    Tavassoli, Teresa; Bellesheim, Katherine; Siper, Paige M.; Wang, A. Ting; Halpern, Danielle; Gorenstein, Michelle; Grodberg, David; Kolevzon, Alexander; Buxbaum, Joseph D.

    2016-01-01

    Sensory reactivity is a new DSM-5 criterion for autism spectrum disorder (ASD). The current study aims to validate a clinician-administered sensory observation in ASD, the Sensory Processing Scale Assessment (SPS). The SPS and the Short Sensory Profile (SSP) parent-report were used to measure sensory reactivity in children with ASD (n = 35) and…

  19. Response of shortgrass Plains vegetation to chronic and seasonally administered gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Fraley, L. Jr.

    1971-08-01

    In order to determine the effect of radiation on the structure of native shortgrass plains vegetation, an 8750 Ci 137Cs source was installed on the Central Plains Experimental Range near Nunn, Colorado; The experimental area was divided into 6 treatment sectors, a control, 2 sectors for chronic exposure (irradiation initiated April 1969 and continuing as of August 1971), and one each for spring, summer and late fall seasonal semi-acute (30 day), exposures which were administered during April, July and December, 1969, respectively. Community structure was measured by coefficient of community and diversity index. Yield was determined by clipping plots in September 1970 and visual estimates in September 1969 and 1970 for the grass-sedge component of the vegetation. Individual species sensitivity was determined by density data recorded in April, June and September of 1969 and 1970 and by a phenological index recorded at weekly intervals during the 1969 and 1970 growing seasons. The response of the vegetation was similar whether determined by coefficient of community or diversity with diversity being a more sensitive measure of effects. In the chronically exposed sectors, the exposure rate which resulted in a 50 per cent reduction in these 2 parameters (CC50 or D50) was still decreasing the second growing season and was approximately 18 R/hr for the CC50 as of June 1970 and 10 R/hr for the D50 as of September 1970. For the seasonally exposed sectors, the late fall period (December, 1969) was the most sensitive, summer (July, 1969) the least sensitive and spring (April, 1969) intermediate with CC50 and D50 values of 195 and 90, 240 and 222, and 120 and 74 R/hr for the spring, summer and late fall exposed sectors, respectively. Yield and density data indicated a rapid revegetation of the spring and summer exposed sectors during 1970 as a result of an influx of invader species such as Salsola kali tenuifolia, Chenopodium leptophyllum and Lepidium densiflorum and the

  20. Pharmacokinetics of Budesonide Administered with Surfactant in Premature Lambs: Implications for Neonatal Clinical Trials.

    Science.gov (United States)

    Roberts, Jessica K; Stockmann, Chris; Dahl, Mar Janna; Albertine, Kurt H; Egan, Edmund; Lin, Zhenjian; Reilly, Christopher A; Ballard, Philip L; Ballard, Roberta A; Ward, Robert M

    2016-01-01

    Bronchopulmonary dysplasia (BPD) is a chronic lung disease of premature human infants, which may persist through adulthood. Airway inflammation has been firmly established in the pathogenesis of BPD. Previous studies to reduce airway inflammation with high-dose dexamethasone demonstrated adverse neurological outcomes, despite lower incidences of BPD. Instillation of budesonide and surfactant can facilitate early extubation and reduce the incidence of BPD and death among very low birth weight infants. However, the pharmacokinetics of budesonide and its distribution into the lung and brain are unknown. Therefore, 5 premature lambs were administered 0.25 mg/kg budesonide, with surfactant as the vehicle. Plasma and tissue samples were taken from the lambs for measurement of budesonide, 16α- hydroxy prednisolone, and budesonide palmitate using LC/MS/MS. Peak plasma budesonide concentrations were inversely correlated with the oxygenation index (correlation coefficient of -0.75). plasma budesonide concentrations were extremely low (~10% of expected) for two lambs that had high oxygenation indices and were excluded from further analyses. For the remaining 5 premature lambs, a non-compartmental analysis demonstrated an AUCinf of 148.77 ± 28.16 h*μg/L, half-life of 4.76 ± 1.79 h, and Cmax of 46.17 ± 17.71 µg/L. Using population pharmacokinetic methods, a onecompartment model with exponential residual error and first-order absorption adequately described the data. The apparent clearance and apparent volume of distribution of budesonide were estimated at 6.29 L/h (1.99 L/h/kg) and 29.1 L (9.2 L/kg), respectively. Budesonide and budesonide palmitate, but not 16α-hydroxy prednisolone, were detected in lung tissue. In this study, budesonide and its metabolites were not detected in the brain, which suggests that intratracheal instillation suggests that after local pulmonary deposition, there is no evidence of budesonide accumulation in the central nervous system. Overall

  1. Subchronic chloroform priming protects mice from a subsequently administered lethal dose of chloroform

    International Nuclear Information System (INIS)

    Protection offered by pre-exposure priming with a small dose of a toxicant against the toxic and lethal effects of a subsequently administered high dose of the same toxicant is autoprotection. Although autoprotection has been extensively studied with diverse toxicants in acute exposure regimen, not much is known about autoprotection after priming with repeated exposure. The objective of this study was to investigate this concept following repeated exposure to a common water contaminant, chloroform. Swiss Webster (SW) mice, exposed continuously to either vehicle (5% Emulphor, unprimed) or chloroform (150 mg/kg/day po, primed) for 30 days, were challenged with a normally lethal dose of chloroform (750 mg chloroform/kg po) 24 h after the last exposure. As expected, 90% of the unprimed mice died between 48 and 96 h after administration of the lethal dose in contrast to 100% survival of mice primed with chloroform. Time course studies indicated lower hepato- and nephrotoxicity in primed mice as compared to unprimed mice. Hepatic CYP2E1, glutathione levels (GSH), and covalent binding of 14C-chloroform-derived radiolabel did not differ between livers of unprimed and primed mice after lethal dose exposure, indicating that protection in liver is neither due to decreased bioactivation nor increased detoxification. Kidney GSH and glutathione reductase activity were upregulated, with a concomitant reduction in oxidized glutathione in the primed mice following lethal dose challenge, leading to decreased renal covalent binding of 14C-chloroform-derived radiolabel, in the absence of any change in CYP2E1 levels. Buthionine sulfoximine (BSO) intervention led to 70% mortality in primed mice challenged with lethal dose. These data suggest that higher detoxification may play a role in the lower initiation of kidney injury observed in primed mice. Exposure of primed mice to a lethal dose of chloroform led to 40% lower chloroform levels (AUC15-360min) in the systemic circulation

  2. Gold nanoparticles and diclofenac diethylammonium administered by iontophoresis reduce inflammatory cytokines expression in Achilles tendinitis

    Directory of Open Access Journals (Sweden)

    Dohnert MB

    2012-03-01

    Full Text Available Marcelo B Dohnert1,2, Mirelli Venâncio1, Jonathann C Possato1, Rodrigo C Zeferino1, Luciana H Dohnert2, Alexandra I Zugno1, Cláudio T De Souza1, Marcos MS Paula1, Thais F Luciano11Postgraduation Program in Health Sciences, Programa de Pós-graduação em Ciências da Saúde PPGCS, Universidade do Extremo Sul Catarinense, Criciúma, Santa Catarina, 2Department of Physiotherapy, Universidade Luterana do Brasil, Torres, Rio Grande do Sul, BrazilIntroduction: Tendinitis affects a substantial number of people in several occupations involving repetitive work or direct trauma. Iontophoresis is a therapeutic alternative used in the treatment of injury during the inflammatory phase. In recent years, gold nanoparticles (GNP have been studied due to their therapeutic anti-inflammatory capacity and as an alternative to the transport of several proteins. Purpose: This study evaluates the therapeutic effects of iontophoresis using GNPs and diclofenac diethylammonium on inflammatory parameters in rats challenged with traumatic tendinitis.Methods: Wistar rats were divided in three treatment groups (n = 15: (1 iontophoresis + diclofenac diethylammonium; (2 iontophoresis + GNP; and (3 iontophoresis + diclofenac diethylammonium + GNP. External control was formed by challenged tendons without treatment (n = 15. Iontophoresis was administered using 0.3 mA direct current on 1.5 cm² electrodes. Results: The levels of both inflammatory cytokines were significantly higher in untreated challenged rats, when compared with the control (5.398 ± 234 for interleukin 1 beta and 6.411 ± 432 for tumor necrosis factor alpha, which confirms the occurrence of an inflammatory stage in injury (P < 0.05. A significant decrease was observed in expression of cytokines interleukin 1 beta in the three treatment groups, in comparison with untreated challenged tendons, although, in the group treated with diclofenac and GNP, results were similar to the control (1.732 ± 239 (P < 0

  3. Distribution and histologic effects of intravenously administered amorphous nanosilica particles in the testes of mice

    International Nuclear Information System (INIS)

    Highlights: ► There is rising concern regarding the potential health risks of nanomaterials. ► Few studies have investigated the effect of nanomaterials on the reproductive system. ► Here, we evaluated the intra-testicular distribution of nanosilica particles. ► We showed that nanosilica particles can penetrate the blood-testis barrier. ► These data provide basic information on ways to create safer nanomaterials. -- Abstract: Amorphous nanosilica particles (nSP) are being utilized in an increasing number of applications such as medicine, cosmetics, and foods. The reduction of the particle size to the nanoscale not only provides benefits to diverse scientific fields but also poses potential risks. Several reports have described the in vivo and in vitro toxicity of nSP, but few studies have examined their effects on the male reproductive system. The aim of this study was to evaluate the testicular distribution and histologic effects of systemically administered nSP. Mice were injected intravenously with nSP with diameters of 70 nm (nSP70) or conventional microsilica particles with diameters of 300 nm (nSP300) on two consecutive days. The intratesticular distribution of these particles 24 h after the second injection was analyzed by transmission electron microscopy. nSP70 were detected within sertoli cells and spermatocytes, including in the nuclei of spermatocytes. No nSP300 were observed in the testis. Next, mice were injected intravenously with 0.4 or 0.8 mg nSP70 every other day for a total of four administrations. Testes were harvested 48 h and 1 week after the last injection and stained with hematoxylin–eosin for histologic analysis. Histologic findings in the testes of nSP70-treated mice did not differ from those of control mice. Taken together, our results suggest that nSP70 can penetrate the blood-testis barrier and the nuclear membranes of spermatocytes without producing apparent testicular injury.

  4. Distribution and histologic effects of intravenously administered amorphous nanosilica particles in the testes of mice

    Energy Technology Data Exchange (ETDEWEB)

    Morishita, Yuki [Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Yoshioka, Yasuo, E-mail: yasuo@phs.osaka-u.ac.jp [Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Satoh, Hiroyoshi; Nojiri, Nao [Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Nagano, Kazuya [Laboratory of Biopharmaceutical Research, National Institute of Biomedical Innovation, 7-6-8 Saitoasagi, Ibaraki, Osaka 567-0085 (Japan); Abe, Yasuhiro [Cancer Biology Research Center, Sanford Research/USD, 2301 E. 60th Street N, Sioux Falls, SD 57104 (United States); Kamada, Haruhiko; Tsunoda, Shin-ichi [Laboratory of Biopharmaceutical Research, National Institute of Biomedical Innovation, 7-6-8 Saitoasagi, Ibaraki, Osaka 567-0085 (Japan); The Center for Advanced Medical Engineering and Informatics, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Nabeshi, Hiromi [Division of Foods, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya-ku, Tokyo 158-8501 (Japan); Yoshikawa, Tomoaki [Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Tsutsumi, Yasuo, E-mail: ytsutsumi@phs.osaka-u.ac.jp [Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Laboratory of Biopharmaceutical Research, National Institute of Biomedical Innovation, 7-6-8 Saitoasagi, Ibaraki, Osaka 567-0085 (Japan); The Center for Advanced Medical Engineering and Informatics, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan)

    2012-04-06

    Highlights: Black-Right-Pointing-Pointer There is rising concern regarding the potential health risks of nanomaterials. Black-Right-Pointing-Pointer Few studies have investigated the effect of nanomaterials on the reproductive system. Black-Right-Pointing-Pointer Here, we evaluated the intra-testicular distribution of nanosilica particles. Black-Right-Pointing-Pointer We showed that nanosilica particles can penetrate the blood-testis barrier. Black-Right-Pointing-Pointer These data provide basic information on ways to create safer nanomaterials. -- Abstract: Amorphous nanosilica particles (nSP) are being utilized in an increasing number of applications such as medicine, cosmetics, and foods. The reduction of the particle size to the nanoscale not only provides benefits to diverse scientific fields but also poses potential risks. Several reports have described the in vivo and in vitro toxicity of nSP, but few studies have examined their effects on the male reproductive system. The aim of this study was to evaluate the testicular distribution and histologic effects of systemically administered nSP. Mice were injected intravenously with nSP with diameters of 70 nm (nSP70) or conventional microsilica particles with diameters of 300 nm (nSP300) on two consecutive days. The intratesticular distribution of these particles 24 h after the second injection was analyzed by transmission electron microscopy. nSP70 were detected within sertoli cells and spermatocytes, including in the nuclei of spermatocytes. No nSP300 were observed in the testis. Next, mice were injected intravenously with 0.4 or 0.8 mg nSP70 every other day for a total of four administrations. Testes were harvested 48 h and 1 week after the last injection and stained with hematoxylin-eosin for histologic analysis. Histologic findings in the testes of nSP70-treated mice did not differ from those of control mice. Taken together, our results suggest that nSP70 can penetrate the blood-testis barrier and the

  5. Incorporated fish oil fatty acids prevent action potential shortening induced by circulating fish oil fatty acids

    Directory of Open Access Journals (Sweden)

    Hester M Den Ruijter

    2010-11-01

    Full Text Available Increased consumption of fatty fish, rich in omega-3 polyunsaturated fatty acids (3-PUFAs reduces the severity and number of arrhythmias. Long term 3-PUFA-intake modulates the activity of several cardiac ion channels leading to cardiac action potential shortening. Circulating 3-PUFAs in the bloodstream and incorporated 3-PUFAs in the cardiac membrane have a different mechanism to shorten the action potential. It is, however, unknown whether circulating 3-PUFAs in the bloodstream enhance or diminish the effects of incorporated 3-PUFAs. In the present study, we address this issue. Rabbits were fed a diet rich in fish oil (3 or sunflower oil (9, as control for 3 weeks. Ventricular myocytes were isolated by enzymatic dissociation and action potentials were measured using the perforated patch clamp technique in the absence and presence of acutely administered 3-PUFAs. Plasma of 3 fed rabbits contained more free eicosapentaenoic acid (EPA and isolated myocytes of 3 fed rabbits contained higher amounts of both EPA and docosahexaenoic acid (DHA in their sarcolemma compared to control. In the absence of acutely administered fatty acids, 3 myocytes had a shorter action potential with a more negative plateau than 9 myocytes. In the 9 myocytes, but not in the 3 myocytes, acute administration of a mixture of EPA+DHA shortened the action potential significantly. From these data we conclude that incorporated 3-PUFAs into the sarcolemma and acutely administered 3 fatty acids do not have a cumulative effect on action potential duration and morphology. As a consequence, patients with a high cardiac 3-PUFA status will probably not benefit from short term 3 supplementation as an antiarrhythmic therapy.

  6. Hydroxycarboxylic acids and salts

    Energy Technology Data Exchange (ETDEWEB)

    Kiely, Donald E; Hash, Kirk R; Kramer-Presta, Kylie; Smith, Tyler N

    2015-02-24

    Compositions which inhibit corrosion and alter the physical properties of concrete (admixtures) are prepared from salt mixtures of hydroxycarboxylic acids, carboxylic acids, and nitric acid. The salt mixtures are prepared by neutralizing acid product mixtures from the oxidation of polyols using nitric acid and oxygen as the oxidizing agents. Nitric acid is removed from the hydroxycarboxylic acids by evaporation and diffusion dialysis.

  7. Activity of mevalonate pathway inhibitors against breast and ovarian cancers in the ATP-based tumour chemosensitivity assay

    International Nuclear Information System (INIS)

    Previous data suggest that lipophilic statins such as fluvastatin and N-bisphosphonates such as zoledronic acid, both inhibitors of the mevalonate metabolic pathway, have anti-cancer effects in vitro and in patients. We have examined the effect of fluvastatin alone and in combination with zoledronic acid in the ATP-based tumour chemosensitivity assay (ATP-TCA) for effects on breast and ovarian cancer tumour-derived cells. Both zoledronic acid and fluvastatin showed activity in the ATP-TCA against breast and ovarian cancer, though fluvastatin alone was less active, particularly against breast cancer. The combination of zoledronic acid and fluvastatin was more active than either single agent in the ATP-TCA with some synergy against breast and ovarian cancer tumour-derived cells. Sequential drug experiments showed that pre-treatment of ovarian tumour cells with fluvastatin resulted in decreased sensitivity to zoledronic acid. Addition of mevalonate pathway components with zoledronic acid with or without fluvastatin showed little effect, while mevalonate did reduced inhibition due to fluvastatin. These data suggest that the combination of zoledronic acid and fluvastatin may have activity against breast and ovarian cancer based on direct anti-cancer cell effects. A clinical trial to test this is in preparation

  8. Clinical Analysis of Bisphosphonates Treatment on Bone Metastases and Hypercalcemia of Malignancy in Advanced Solid Tumor

    Institute of Scientific and Technical Information of China (English)

    MING Shu-hong; SUN Tie-ying

    2007-01-01

    Objective: To evaluate the efficacy and toleration of bisphosphonates therapy in patients with bone metastases and hypercalcemia of malignancy in advanced solid tumor. Methods: Patients with histologically or cytologically confirmed cancer and hypercalcemia with bone metastases were designed to open treatment with either 4mg zoledronic acid or 90mg pamidronate. The primary efficacy parameters were pain scores(NRS), Corrected serum calcium(CSC) and CSC effective rate. The vital signs, biochemical and hematological parameters were determined. Results: Twenty patients were enrolled in this study, twelve patients in zoledronic acid group and eight in pamidronate group. Zoledronic acid and pamidronate significantly palliated pain. Pain scores were significantly lower at end-point after Zoledronic acid or pamidronate infusion(5.92 vs 3.25,P<0.01;6.13 vs 4.38, P<0.01, respectively). The mean CSC level decreased significantly after Zoledronic acid or pamidronate infusion from 12.86 to 10.28mg/dl and 13.19 to 10.36mg/dl respectively. The CSC effective rate was about 90% at 14 days after infusion in two groups. There was no statistical significance for all primary efficacy parameters in zoledronic acid group compared with pamidronate group. An adverse reaction was mild fever after pamidronate infusion and then completely reversible. Conclusion: Zoledronic acid and pamidronate disodium were well tolerated and effective for bone metastases and hypercalcemia of malignancy in advanced solid tumor.

  9. Toxicity of colloidal silica nanoparticles administered orally for 90 days in rats

    Directory of Open Access Journals (Sweden)

    Kim YR

    2014-12-01

    Full Text Available Yu-Ri Kim,1,* Seung-Young Lee,3,* Eun Jeong Lee,1 Sung Ha Park,4 Nak-won Seong,3 Heung-Sik Seo,3 Sung-Sup Shin,3 Seon-Ju Kim,3 Eun-Ho Meang,3 Myeong-Kyu Park,3 Min-Seok Kim,3 Cheol-Su Kim,5 Soo-Ki Kim,5 Sang Wook Son,2 Young Rok Seo,6 Boo Hyon Kang,7 Beom Seok Han,8 Seong Soo A An,9 Beom-Jun Lee,10 Meyoung-Kon Kim1 1Department of Biochemistry and Molecular Biology, 2Department of Dermatology, Korea University Medical School and College, 3General Toxicology Team, Korea Testing and Research Institute, Seoul, Republic of Korea; 4Department of Biochemistry, University of Bath, Bath, UK; 5Department of Microbiology, Wonju College of Medicine, Yonsei University, Gangwon, 6Department of Life Science, Institute of Environmental Medicine for Green Chemistry, Dongguk University, Seoul, 7Nonclinical Research Institute, Chemon Inc, Gyeonggi, 8Toxicological Research Center, Hoseo University, Chungnam, 9Department of Bionanotechnology, Gachon University, Gyeonggi, 10College of Veterinary Medicine, Chungbuk National University, Chungbuk, Republic of Korea *These authors contributed equally to this work Abstract: This study was undertaken to investigate the potential toxicity and establish the no observed adverse effect level (NOAEL and target organ(s of negatively charged colloidal silica particles of different sizes, ie, SiO2EN,20(- (20 nm or SiO2EN,100(- (100 nm, administered by gavage in Sprague-Dawley rats. After verification of the physicochemical properties of the SiO2 particles to be tested, a preliminary dose range-finding study and 90-day repeated dose study were conducted according to the Organisation for Economic Cooperation and Development test guideline. Based on the results of the 14-day dose range-finding study, a high dose was determined to be 2,000 mg/kg, and middle and low doses were set at 1,000 and 500 mg/kg, respectively. In the 90-day toxicity study, there were no animal deaths in relation to administration of SiO2 particles of

  10. Effect of administered radioactive dose level on image quality of brain perfusion imaging with 99mTc-HMPAO

    Directory of Open Access Journals (Sweden)

    I.Armeniakos

    2008-01-01

    Full Text Available Brain perfusion imaging by means of 99mTc-labeled hexamethyl propylene amine oxime (HMPAO is a well-established Nuclear Medicine diagnostic procedure. The administered dose range recommended by the supplying company and reported in bibliography is rather wide (approximately 9.5-27 mCi. This fact necessitates further quantitative analysis of the technique, so as to minimise patient absorbed dose without compromising the examination diagnostic value. In this study, a quantitative evaluation of the radiopharmaceutical performance for different values of administered dose (10, 15, 20 mCi was carried out. Subsequently, a generic image quality index was correlated with the administered dose, to produce an overall performance indicator. Through this cost-to-benefit type analysis, the necessity of administration of higher radioactive dose levels in order to perform the specific diagnostic procedure was examined.Materials & methods: The study was based on a sample of 78 patients (56 administered with 10 mCi, 10 with 15 mCi and 12 with 20 mCi. Some patients were classified as normal, while others presented various forms of pathology. Evaluation of image quality was based on contrast, noise and contrast-to-noise ratio indicators, denoted CI, NI and CNR respectively. Calculation of all indicators was based on wavelet transform. An overall performance indicator (denoted PI, produced by the ratio of CNR by administered dose, was also calculated.Results: Calculation of skewness parameter revealed the normality of CI, NI and non-normality of CNR, PI populations. Application of appropriate statistical tests (analysis of variance for normal and Kruskal-Wallis test for non-normal populations showed that there is a statistically significant difference in CI (p0.05 values. Application of Tukey test for normal populations CI, NI led to the conclusion that CI(10 mCi = CI(20 mCiNI(20 mCi, while NI(15 mCi can not be characterised. Finally, application of non

  11. Intravenously administered gold nanoparticles pass through the blood-retinal barrier depending on the particle size, and induce no retinal toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jeong Hun; Kim, Jin Hyoung; Yu, Young Suk [Department of Ophthalmology, Seoul National University College of Medicine and Seoul Artificial Eye Center, Clinical Research Institute, Seoul National University Hospital, Seoul 151744 (Korea, Republic of); Kim, Kyu-Won [NeuroVascular Coordination Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151742 (Korea, Republic of); Kim, Myung Hun, E-mail: hunin315@paran.com, E-mail: ysyu@snu.ac.kr [Department of Chemistry, Yonsei University, 134 Shinchon-dong, Seodaemun-ku, Seoul 120749 (Korea, Republic of)

    2009-12-16

    The retina maintains homeostasis through the blood-retinal barrier (BRB). Although it is ideal to deliver the drug to the retina via systemic administration, it is still challenging due to the BRB strictly regulating permeation from blood to the retina. Herein, we demonstrated that intravenously administered gold nanoparticles could pass through the BRB and are distributed in all retinal layers without cytotoxicity. After intravenous injection of gold nanoparticles into C57BL/6 mice, 100 nm nanoparticles were not detected in the retina whereas 20 nm nanoparticles passed through the BRB and were distributed in all retinal layers. 20 nm nanoparticles in the retina were observed in neurons (75 {+-} 5%), endothelial cells (17 {+-} 6%) and peri-endothelial glial cells (8 {+-} 3%), where nanoparticles were bound on the membrane. In the retina, cells containing nanoparticles did not show any structural abnormality and increase of cell death compared to cells without nanoparticles. Gold nanoparticles never affected the viability of retinal endothelial cells, astrocytes and retinoblastoma cells. Furthermore, gold nanoparticles never led to any change in expression of representative biological molecules including zonula occludens-1 and glut-1 in retinal endothelial cells, neurofilaments in differentiated retinoblastoma cells and glial fibrillary acidic protein in astrocytes. Therefore, our data suggests that small gold nanoparticles (20 nm) could be an alternative for drug delivery across the BRB, which could be safely applied in vivo.

  12. Effect of silver nanoparticles and hydroxyproline, administered in ovo, on the development of blood vessels and cartilage collagen structure in chicken embryos.

    Science.gov (United States)

    Beck, Iwona; Hotowy, Anna; Sawosz, Ewa; Grodzik, Marta; Wierzbicki, Mateusz; Kutwin, Marta; Jaworski, Sławomir; Chwalibog, André

    2015-01-01

    It has been considered that concentrations of certain amino acids in the egg are not sufficient to fully support embryonic development of modern broilers. In this study we evaluated embryo growth and development with particular emphasis on one of the major components of connective tissue, collagen. Experiments were performed on Ross 308 chicken embryos from 160 fertilised eggs. Experimental solutions of silver nanoparticles (Ag), hydroxyproline solution (Hyp) and a complex of silver nanoparticles with hydroxyproline (AgHyp) were injected into albumen, and embryos were incubated until day 20. An assessment of the mass of embryo and selected organs was carried out followed by measurements of the expression of the key signalling factors' fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor-A (VEGF-A). Finally, an evaluation of collagen microstructure using scanning electron microscopy was performed. Our results clearly indicate that Hyp, Ag and AgHyp administered in ovo to chicken embryos did not harm embryos. Comparing to the control group, Hyp, Ag and the AgHyp complex significantly upregulated expression of the FGF-2 at the mRNA and protein levels. Moreover, Hyp, Ag and, in particular, the complex of AgHyp significantly increased blood vessel size, cartilage collagen fibre lattice size and bundle thickness. The general conclusion from this study is that AgHyp treatment may help to build a stronger and longer lasting form of collagen fibres. PMID:25530495

  13. Intermittently Administered Parathyroid Hormone [1–34] Promotes Tendon-Bone Healing in a Rat Model

    Directory of Open Access Journals (Sweden)

    Fanggang Bi

    2014-09-01

    Full Text Available The objective of this study was to investigate whether intermittent administration of parathyroid hormone [1–34] (PTH[1–34] promotes tendon-bone healing after anterior cruciate ligament (ACL reconstruction in vivo. A rat model of ACL reconstruction with autograft was established at the left hind leg. Every day, injections of 60 μg PTH[1–34]/kg subcutaneously were given to the PTH group rats (n = 10 for four weeks, and the controls (n = 10 received saline. The tendon-bone healing process was evaluated by micro-CT, biomechanical test, histological and immunohistochemical analyses. The effects of PTH[1–34] on serum chemistry, bone microarchitecture and expression of the PTH receptor (PTH1R and osteocalcin were determined. Administration of PTH[1–34] significantly increased serum levels of calcium, alkaline phosphatase (AP, osteocalcin and tartrate-resistant acid phosphatase (TRAP. The expression of PTH1R on both osteocytes and chondrocyte-like cells at the tendon-bone interface was increased in the PTH group. PTH[1–34] also enhanced the thickness and microarchitecture of trabecular bone according to the micro-CT analysis. The results imply that systematically intermittent administration of PTH[1–34] promotes tendon-bone healing at an early stage via up-regulated PTH1R. This method may enable a new strategy for the promotion of tendon-bone healing after ACL reconstruction.

  14. Distribution and elimination of intravenously administered atrial natriuretic hormone(ANH) to normal and nephrectomized rats

    International Nuclear Information System (INIS)

    The 24 amino acid peptide, ANH(5-28), was N-terminally labeled with I-125 Bolton-Hunter reagent, iodo-N-succinimidyl 3-(4-hydroxyphenyl)propionate. The I-125 peptide plus 1μg/kg of the I-127 Bolton-Hunter peptide was injected into normal and nephrectomized anesthetized (Nembutal) rats. Blood samples were drawn into a cocktail developed to inhibit plasma induced degradation. Radiolabeled peptides were analyzed by HPLC. A biphasic curve of I-125 ANH(5-28) elimination was obtained, the first phase (t 1/2 = 15 sec) representing in vivo distribution and the second phase (t 1/2 = 7-10 min) a measurement of elimination. This biphasic elimination curve was similar in normal and nephrectomized rats. The apparent volumes of distribution were 15-20 ml for the first phase and > 300 ml for the second phase. In order to examine the tissue distribution of the peptide, animals were sacrificed at 2 minutes and the I-125 tissue contents were quantitated. The majority of the label was located in the liver (50%), kidneys (21%) and the lung (5%). The degradative peptides appearing in the plasma and urine of normal rats were identical. No intact radiolabeled ANH(5-28) was found in the urine. In conclusion, iodinated Bolton-Hunter labeled ANH(5-28) is rapidly removed from the circulation by the liver and to a lesser extent by the kidney, but the rate of elimination is not decreased by nephrectomy

  15. [Hypnosis and self-hypnosis administered and taught by nurses for relief of chronic pain: a controlled clinical trial].

    Science.gov (United States)

    Buchser, E

    1999-02-01

    In this controlled clinical trial hypnosis and self-hypnosis were evaluated when used as an adjuvant treatment to instrumental and pharmacological management of chronic pain. The study took place in a hospital specialized in the treatment of outpatients suffering from chronic pain. Hypnosis and self-hypnosis were administered and taught by nurses who had been trained just recently for this very purpose. Under the conditions of the study it was not possible to measure an effect of hypnosis on pain despite some subjective feeling of usefulness. However, it should be taken into account that this form of adjuvant therapy was used for the first time in that hospital for the purpose of the study and, therefore, took place in an artificial setting. It could well be that the same therapy administered in the proper therapeutic environment of a specialized institution could show beneficial effects on pain. PMID:10077717

  16. Bronchodilation and bronchoprotection in asthmatic preschool children from formoterol administered by mechanically actuated dry-powder inhaler and spacer

    DEFF Research Database (Denmark)

    Nielsen, K G; Bisgaard, H

    2001-01-01

    We evaluated the bronchodilatory and the bronchoprotective effect of the long-acting beta(2)-agonist formoterol administered as dry powder from a mechanically actuated dry-powder inhaler (DPI) using spacer in 12 asthmatic children 2 to 5 yr of age. Lung function was measured as the specific airway...... resistance (sRaw) in a whole body plethysmograph. Hyperventilation of cold, dry air was used as bronchial challenge, and the responsiveness was estimated as change in sRaw. The bronchoprotective effect of formoterol Turbohaler 9 microg was compared with salbutamol 200 microg and placebo at 15 min, 4 and 8 h...... postdose in a randomized, double-blind, placebo-controlled, crossover study. All treatments were administered from DPI (Turbohaler) actuated mechanically into a spacer. Formoterol and salbutamol caused similar and significant bronchodilation at the first measurement 3 min postdose. Formoterol offered a...

  17. Directly Observed versus Self-administered Antiretroviral Therapies: Preference of HIV-Positive Jailed Inmates in San Francisco

    OpenAIRE

    Saberi, Parya; Caswell, Nikolai H.; Jamison, Ross; Estes, Milton; Tulsky, Jacqueline P.

    2012-01-01

    Directly observed therapy (DOT) of antiretroviral (ARV) medications has beneficial effects on HIV treatment for incarcerated inmates but has been associated with limited continuation after release and inadvertent disclosure of HIV status. Guided self-administered therapy (g-SAT) may be a preferred method of ARV delivery and may encourage medication-taking behavior. We surveyed the preference of 102 HIV-positive jailed inmates at the San Francisco City and County Jails regarding receiving ARVs...

  18. Training Self-Administered Acupressure Exercise among Postmenopausal Women with Osteoarthritic Knee Pain: A Feasibility Study and Lessons Learned

    OpenAIRE

    Yan Zhang; Chwan-Li Shen; Kim Peck; Jean-Michel Brismée; Susan Doctolero; Di-Fan Lo; Yik Lim; Lixing Lao

    2012-01-01

    Background. Osteoarthritis (OA) is more prevalent in women, particularly after menopausal age. Women are more likely to seek complementary and alternative medicine (CAM) approaches. We examined the feasibility of training self-administered acupressure exercise and assessed its impact on OA symptoms among women with knee OA. Methods. Thirty-six eligible postmenopausal women were randomly assigned in the acupressure exercise group (n = 15) or the control group (n = 21) for 12 weeks. Feasibility...

  19. Development and Reliability of a Telephone-Administered Perceived Racism Scale (TPRS): A Tool for Epidemiological Use

    OpenAIRE

    Vines, Anissa I.; McNeilly, Maya Dominguez; Stevens, June; Hertz-Picciotto, Irva; Bohlig, Michael; Baird, Donna D.

    2001-01-01

    The conceptualization of perceived racism as a chronic stressor is relatively new to epidemiology. The Telephone-Administered Perceived Racism Scale (TPRS) captures the complexity of racism within five scales: Experience of Racism (by Blacks as a group and by the respondent), Emotional Responses, Behavioral Responses, Concern for Child(ren), and Past Experiences of Racism. The TPRS was developed for employed Black women. Exploratory factor analyses and tests of internal consistency were compl...

  20. Assessment of pain in patients with dementia. Development of a staff-administered behavioural pain assessment tool

    OpenAIRE

    Husebø, Bettina Sandgathe

    2008-01-01

    Aims: The aim of this thesis is to develop a staff-administered behavioural pain assessment tool for older persons with dementia, to test the instrument with respect to reliability and validity, and to use it in the clinical setting of an entire nursing home (NH) population. Methods: In Paper I, the development of the Mobilization-Observation-Behaviour-Intensity-Dementia (MOBID) Pain Scale was described. In MOBID, the assessment of inferred pain intensity was based on the...

  1. Patient Impression and Satisfaction of a Self-administered, Automated Medical History Taking Device in the Emergency Department

    OpenAIRE

    Arora, Sanjay; Goldberg, Andrew D.; Menchine, Michael

    2014-01-01

    Introduction: We evaluated patient impressions and satisfaction of an innovative self-administered, hand-held touch-screen tablet to gather detailed medical information from emergency department (ED) patients in the waiting room prior to physician contact. Methods: Adult, medically stable patients presenting to the ED at Los Angeles County Hospital used the PatientTouche system to answer a series of questions about their current history of present illness and past medical/surgical hi...

  2. NOTE FOR EDITOR: Administering Examinations For Quality Control In Distance Education: 
The National Open University Of Nigeria Perspective

    OpenAIRE

    IBARA, E. C.

    2008-01-01

    Examination is an important tool for evaluating students learning outcome and require proper planning to meet high standards. This paper therefore examines the processes leading to administration of face-to-face examination in distance education with focus on the National Open University of Nigeria. It highlighted some procedures such as test development, test administration and post test administration/award procedures. It also identified some quality control practices adopted in administer...

  3. Prophylactic Efficacy of Amifostine, DRDE-07, and their Analogues against Percutaneously Administered Nitrogen Mustards and Sulphur Mustard

    OpenAIRE

    Manoj Sharma; Vijayaraghavan, R.; Uma Pathak; K. Ganesan

    2009-01-01

    Nitrogen mustards (HN-1, HN-2 and HN-3) and sulphur mustard are alkylating and blister-inducing chemical warfare agents. This study was aimed at investigating the prophylactic efficacy of amifostine, DRDE-07, and their analogues and some recommended antidotes against dermally-applied nitrogen mustards and sulphur mustard in preventing their systemic toxicity in mice. The antidotes were administered as single oral dose, 30 min prior to the mustard agent application. For DRDE-07, 0.2 LD50 (249 ...

  4. Pharmacokinetics of concomitant cisplatin and paclitaxel administered by hyperthermic intraperitoneal chemotherapy to patients with peritoneal carcinomatosis from epithelial ovarian cancer

    OpenAIRE

    Ansaloni, L.; Coccolini, F.; Morosi, L; Ballerini, A; Ceresoli, M; Grosso, G.; P. Bertoli; Busci, L M; Lotti, M.; Cambria, F; Pisano, M; Rossetti, D; Frigerio, L; D'Incalci, M; Zucchetti, M

    2014-01-01

    Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) is advised as a treatment option for epithelial ovarian cancer (EOC) with peritoneal carcinomatosis. This study was designed to define the pharmacokinetics of cisplatin (CDDP) and paclitaxel (PTX) administered together during HIPEC. Methods: Thirteen women with EOC underwent cytoreductive surgery (CRS) and HIPEC, with CDDP and PTX. Blood, peritoneal perfusate and tissue samples were harvested to determine drug exposure by high-perf...

  5. Comparison of the efficacy of administering a combination of ezetimibe plus fenofibrate versus atorvastatin monotherapy in the treatment of dyslipidemia

    OpenAIRE

    Lahey Karen A; Kumar Shoba; Day Andrew; LaHaye Stephen A

    2009-01-01

    Abstract Background This trial compares the efficacy of administering a combination of ezetimibe plus fenofibrate as an alternative to statin monotherapy for the treatment of dyslipidemia. In this randomized, unblinded crossover study, 43 patients with documented hypercholesterolemia requiring pharmacotherapy were randomized to receive six weeks of either a combination of 10 mg of ezetimibe plus 160 mg of fenofibrate (combination) or 10 mg of atorvastatin monotherapy (atorvastatin). The prima...

  6. Evaluating the effectiveness of the self-administered interview© for witnesses with autism spectrum disorder

    OpenAIRE

    Maras, K. L.; Mulcahy, S.; Memon, A; Picariello, F.; Bowler, D. M.

    2014-01-01

    The widely used evidence-based police interviewing technique, the Cognitive Interview, is not effective for witnesses with autism spectrum disorder (ASD). The present study examined whether a modification of the Cognitive Interview that removes the social element, the Self-Administered Interview©, is more useful in facilitating recall by ASD witnesses. One of the main components of the Cognitive Interview is context reinstatement, where the witness follows verbal instructions from the intervi...

  7. Comparison of Two Brief Parent-Training Interventions for Child Distress During Parent-Administered Needle Procedures

    OpenAIRE

    Slifer, Keith J.; DeMore, Melissa; Vona-Messersmith, Natalie; Pulbrook-Vetter, Valerie; Beck, Melissa; Dalhquist, Lynnda; Bellipanni, Kimberly; Johnson, Elizabeth

    2009-01-01

    This randomized clinical trial employed a 2-group (general child behavior management training vs. distraction for pain management training) design across repeated parent-administered needle procedures. Forty-seven children with a chronic illness requiring recurrent injections were observed at baseline and 2 intervention sessions. Videotaped observations of parent–child interactions were coded for child behavioral distress and parents’ use of behavior management strategies. Across groups, many...

  8. A Pharmacokinetic Study Comparing Eslicarbazepine Acetate Administered Orally as a Crushed or Intact Tablet in Healthy Volunteers.

    Science.gov (United States)

    Sunkaraneni, Soujanya; Kharidia, Jahnavi; Schutz, Ralph; Blum, David; Cheng, Hailong

    2016-07-01

    The relative bioequivalence of crushed versus intact eslicarbazepine acetate (ESL) tablets (800 mg) administered orally in healthy adults was evaluated in an open-label, randomized, 2-period crossover study with a 5-day washout between treatments. Sample blood levels of eslicarbazepine and (R)-licarbazepine were determined; pharmacokinetic parameters were derived for eslicarbazepine. Bioequivalence was established if the 90% confidence intervals (CIs) for the geometric mean treatment ratios of eslicarbazepine AUC(0-∞) and Cmax were within the prespecified 80%-125% range. Twenty-seven subjects in the intent-to-treat population (n = 28) completed both treatment periods. Eslicarbazepine exposure measures were similar for crushed versus intact ESL tablets: average Cmax , 11 700 versus 11 500 ng/mL; AUC(0-∞) , 225 000 versus 234 000 ng·h/mL; AUC(0-last) , 222 000 versus 231 000 ng·h/mL, respectively. Geometric least squares mean ratios (90%CIs) comparing eslicarbazepine exposure measures were within the 80%-125% range (Cmax , 102.63% [97.07%-108.51%]; AUC(0-∞) , 96.72% [94.36%-99.13%]; AUC0-last , 96.69% [94.24%-99.21%]). In conclusion, ESL administered orally as a crushed tablet sprinkled on applesauce, or intact were bioequivalent in healthy subjects. Eslicarbazepine bioavailability was not significantly altered by crushing, indicating that ESL tablets can be administered intact or crushed. PMID:27249205

  9. The in vivo situation of 3H-Aescin which had been administered orally and subcutaneously to rats

    International Nuclear Information System (INIS)

    The in vivo situation of the Aescin, a product of aesculus hippocastanum, was examined by administering the 3H labelled compounds to rats. The following results were obtained: 1) The intestinal absorption from oral administration was not so fast. The blood concentration was low, and its combination with plasma protein was slight. 2) As for the distribution in the organs after an oral administration, the affinity was relatively high in the following organs: Pancreas>heart>kidney>adrenal>gland>lung>muscle>liver. However, the concentrations were extremely low being shown by a ng unit per g tissue in the organs. 3) When it was administered orally to the pregnant rats, the concentrations which were transmitted to the fetuses were low. 4) On the 7th day after oral administration, excretion into the urine was less than 3% and in the feces was more than 70%. The bile excretion was also observed. 5) The metabolic products in the excretion after the oral administration were examined by the method. A large amount of Aescin was excreted in an unchanged form or in compounds. From this, Aescin is presumed to be metabolised by the activity of intestinal bacterial enzymes. 6) The absorption of this drug into the body was low when it was intracutaneously administered. (Saito, K.)

  10. Barriers to administering non-oral formulations in a paediatric population: A semi-structured interview study.

    Science.gov (United States)

    Venables, Rebecca; Batchelor, Hannah; Stirling, Heather; Marriott, John

    2016-01-30

    There is a paucity of research exploring barriers to non-oral medicines administration in paediatric patients; however, these undoubtedly influence medicines adherence. Studies conducted with healthcare professionals have identified various issues with the administration and acceptance of non-oral medicines and devices (Venables et al., 2012; Walsh et al., 2015). EMA (2014) guidelines specify that formulation teams should demonstrate 'acceptability' of paediatric formulations when developing pharmaceutical formulations. Semi-structured interviews exploring barriers to administering non-oral medicines were conducted with young persons and the parents/legal guardians of children (0-17 years) with chronic conditions at the University Hospital of Coventry and Warwickshire, UK. 90 children prescribed a total of 148 non-oral medicines were recruited to the study; 88 barriers to administering non-oral medicines were reported. The most commonly reported barriers were: poor acceptance of face mask/difficulties with spacer for inhaled formulations (38% of reports); disliking parenteral/preferring alternative formulations (38% of reports); greasy texture of topical preparations; difficulty with administering an ocular ointment and the large dose volume of a nasal preparation. Formulation teams should consider the use of child-friendly, age-appropriate designs to improve usability and acceptance, thus medicines adherence. These findings should be used to inform future development of non-oral formulations and devices, suitable in terms of safety, efficacy and acceptability to paediatric patients. PMID:26611666

  11. D1 dopamine receptor-mediated LTP at GABA synapses encodes motivation to self-administer cocaine in rats.

    Science.gov (United States)

    Krawczyk, Michal; Mason, Xenos; DeBacker, Julian; Sharma, Robyn; Normandeau, Catherine P; Hawken, Emily R; Di Prospero, Cynthia; Chiang, Cindy; Martinez, Audrey; Jones, Andrea A; Doudnikoff, Évelyne; Caille, Stephanie; Bézard, Erwan; Georges, François; Dumont, Éric C

    2013-07-17

    Enhanced motivation to take drugs is a central characteristic of addiction, yet the neural underpinning of this maladaptive behavior is still largely unknown. Here, we report a D1-like dopamine receptor (DRD1)-mediated long-term potentiation of GABAA-IPSCs (D1-LTPGABA) in the oval bed nucleus of the stria terminalis that was positively correlated with motivation to self-administer cocaine in rats. Likewise, in vivo intra-oval bed nucleus of the stria terminalis DRD1 pharmacological blockade reduced lever pressing for cocaine more effectively in rats showing enhanced motivation toward cocaine. D1-LTPGABA resulted from enhanced function and expression of G-protein-independent DRD1 coupled to c-Src tyrosine kinases and required local release of neurotensin. There was no D1-LTPGABA in rats that self-administered sucrose, in those with limited cocaine self-administration experience, or in those that received cocaine passively (yoked). Therefore, our study reveals a novel neurophysiological mechanism contributing to individual motivation to self-administer cocaine, a critical psychobiological element of compulsive drug use and addiction. PMID:23864683

  12. Self-administered sample collection for screening of sexually transmitted infection among reservation-based American Indian youth.

    Science.gov (United States)

    Tingey, Lauren; Strom, Rachel; Hastings, Ranelda; Parker, Anthony; Barlow, Allison; Rompalo, Anne; Gaydos, Charlotte

    2015-08-01

    American Indians suffer a disproportionate burden of sexually transmitted infection, particularly adolescents. Screening access barriers in rural and reservation-based communities necessitate alternatives to clinic-based options. Self-administered screening for three sexually transmitted infections was piloted among 32 American Indian adolescents aged 18 to 19. Participants self-collected in a private location; specimens were processed by trained, American Indian paraprofessionals and analysis was conducted by an outside laboratory. Participants testing positive were treated by a Public Health Nurse from the Indian Health Service. Results suggest high overall acceptability: 69% preferred a self-administered method over clinic-based screening, 75% would encourage their friends to use this method and 100% would use it again. A self-administered screening method has the ability to reach this and other high-risk populations that might not otherwise access screening, with added potential within the Indian Health Services system for uptake and dissemination in rural, reservation communities facing significant screening barriers. PMID:25228666

  13. Effect of hyaluronic acid on chondrocyte apoptosis

    OpenAIRE

    Barreto, Ronald Bispo; Sadigursky, David; de Rezende, Marcia Uchoa; Hernandez, Arnaldo José

    2015-01-01

    OBJECTIVE: To determine the percentage of apoptotic cells in a contusion model of osteoarthritis (OA) and to assess whether intra-articular injection of high doses of hyaluronic acid (HA) immediately after trauma reduces chondrocyte apoptosis. METHODS: Forty knees from adult rabbits were impacted thrice with a 1 kg block released through a 1 meter tall cylinder (29.4 Joules). Subsequently, 2 mL of HA was injected in one knee and 2 mL saline in the contra-lateral knee. Medication were administ...

  14. Comparative bioavailability study of two cefixime formulations administered orally in healthy male volunteers.

    Science.gov (United States)

    Zakeri-Milani, Parvin; Valizadeh, Hadi; Islambulchilar, Ziba

    2008-01-01

    The bioavailability of a new cefixime ((6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-(carboxymethoxyimino) acetamido]-8-oxo-3-vinyl-5-thia-1-azabicyclo-[4,2,0]-oct-2-ene-2-carboxylic acid, CAS 79350-37-1) tablet preparation (Loprax) was compared with that of a reference preparation of the drug in 24 healthy male volunteers. The trial was designed as an open, randomized, single-blind, two-sequence, two-period crossover study. Under fasting conditions, each subject received a single oral dose of 400 mg cefixime tablet as a test or reference formulation on 2 treatment days. The treatment periods were separated by a one-week washout period. The plasma concentrations of the drug were analyzed by a rapid and sensitive HPLC method with UV detection. The pharmacokinetic parameters included AUC0-24h, AUC0-infinity, Cmax, t1/2, and Ke. The mean AUC0-infinity of cefixime was 45008.7 +/- 10989.9 and 45221.3 +/- 2155.7 n x h/ml for the test and reference formulation, respectively. The maximum plasma concentration (Cmax) of cefixime was on average 4746.9 +/- 1284 ng/ml for the test and 4726.3 +/- 1206.9 ng/ml for the reference product. No statistical differences were observed for Cmax and the area under the plasma concentration-time curve for test and reference tablets. The calculated 90% confidence intervals based on the ANOVA analysis for the mean test/reference ratios of Cmax, AUC0-infinity and AUC0-24h of cefixime were in the bioequivalence range (94%-112%). Therefore, the two formulations were considered to be bioequivalent. PMID:18412024

  15. Understanding Acid Rain

    Science.gov (United States)

    Damonte, Kathleen

    2004-01-01

    The term acid rain describes rain, snow, or fog that is more acidic than normal precipitation. To understand what acid rain is, it is first necessary to know what an acid is. Acids can be defined as substances that produce hydrogen ions (H+), when dissolved in water. Scientists indicate how acidic a substance is by a set of numbers called the pH…

  16. Activities of radiopharmaceuticals administered for diagnostic and therapeutic procedures in nuclear medicine in Argentina: results of a national survey

    International Nuclear Information System (INIS)

    Nuclear medicine in Argentine is carried out at 292 centres, distributed all over the country, mainly concentrated in the capital cities of the provinces. With the purpose of knowing the activity levels of radiopharmaceuticals that were administered to patients for diagnostic and therapeutic procedures in nuclear medicine, a national survey was conducted, during 2001 and 2002. This survey was answered voluntarily by 107 centres. Sixty-four percent of the participants centres are equipped with SPECT system while the other centres have a gamma camera or scintiscanner. There were 37 nuclear medicine procedures, chosen among those most frequently performed, were included in the survey. In those diagnostic procedures were included tests for: bone, brain, thyroid, kidney, liver, lung and cardiovascular system; and also activities administered for some therapeutic procedures. The nuclear medicine physicians reported the different radiopharmaceutical activities administered to typical adult patients. In this paper are presented the average radiopharmaceutical activity administered for each of the diagnostic and therapeutic procedures included in the survey and the range and distribution of values. In order to place these data in a frame of reference, these average values were compared to the guidance levels for diagnostic procedures in nuclear medicine mentioned at the Safety Series no. 115. From this comparison it was noticed that the activities administered in the 40% of the diagnostic procedures included in the survey were between ±30% of the reference values. For those nuclear medicine procedures that could not be compared with the above mentioned guidance levels, the comparison was made with values published by UNSCEAR or standards recommended by international bodies. As a result of this study, it is important to point out the need to continue the gathering of data in a wider scale survey to increase the knowledge about national trends. It is also essential to widely

  17. Dehydroabietic acid

    Directory of Open Access Journals (Sweden)

    Xiao-Ping Rao

    2009-10-01

    Full Text Available The title compound [systematic name: (1R,4aS,10aR-7-isopropyl-1,4a-dimethyl-1,2,3,4,4a,9,10,10a-octahydrophenanthrene-1-carboxylic acid], C20H28O2, has been isolated from disproportionated rosin which is obtained by isomerizing gum rosin with a Pd-C catalyst.. Two crystallographically independent molecules exist in the asymmetric unit. In each molecule, there are three six-membered rings, which adopt planar, half-chair and chair conformations. The two cyclohexane rings form a trans ring junction with the two methyl groups in axial positions. The crystal structure is stabilized by intermolecular O—H...O hydrogen bonds.

  18. Quantitation of alpha-linolenic acid elongation to eicosapentaenoic and docosahexaenoic acid as affected by the ratio of n6/n3 fatty acids

    Directory of Open Access Journals (Sweden)

    Somoza Veronika

    2009-02-01

    Full Text Available Abstract Background Conversion of linoleic acid (LA and alpha-linolenic acid (ALA to their higher chain homologues in humans depends on the ratio of ingested n6 and n3 fatty acids. Design and methods In order to determine the most effective ratio with regard to the conversion of ALA to eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA, human hepatoma cells were incubated with varying ratios of [13C] labeled linoleic acid ([13C]LA- and alpha-linolenic acid ([13C]ALA-methylesters. Regulative cellular signal transduction pathways involved were studied by determinations of transcript levels of the genes encoding delta-5 desaturase (D5D and delta-6 desaturase (D6D, peroxisome proliferator-activated receptor alpha (PPARα and sterol regulatory element binding protein 1c (SREBP-1c. Mitogen-activated protein kinase kinase 1 (MEK1 and mitogen-activated protein kinase kinase kinase 1 (MEKK1 were also examined. Results Maximum conversion was observed in cells incubated with the mixture of [13C]LA/[13C]ALA at a ratio of 1:1, where 0.7% and 17% of the recovered [13C]ALA was converted to DHA and EPA, respectively. Furthermore, differential regulation of enzymes involved in the conversion at the transcript level, dependent on the ratio of administered n6 to n3 fatty acids in human hepatocytes was demonstrated. Conclusion Formation of EPA and DHA was highest at an administered LA/ALA ratio of 1:1, although gene expression of PPARα, SREBP-1c and D5D involved in ALA elongation were higher in the presence of ALA solely. Also, our findings suggest that a diet-induced enhancement of the cell membrane content of highly unsaturated fatty acids is only possible up to a certain level.

  19. A Further Examination of the Effects of Administering the Metropolitan Reading Tests in Spanish and English to Spanish-Speaking School Entrants.

    Science.gov (United States)

    Cruz, Sylvia; And Others

    In a study designed to assess effects of administering the Metropolitan Reading Test (MRT) in Spanish versus English, 100 Puerto Rican kindergarten pupils were randomly split into two groups. The MRT was administered in English to one group and in a Spanish translation to the other group. The group who took the Spanish version significantly…

  20. THE FAILURE OF CHLOROFORM ADMINISTERED IN THE DRINKING WATER TO INDUCE RENAL TUBULAR CELL NEOPLASIA IN MALE F344/N RATS

    Science.gov (United States)

    The failure of chloroform administered in drinking water to induce renal tubular cell neoplasia in male F344/N rats Chloroform (TCM) has been demonstrated to be a renal carcinogen in the male Osborne-Mendel rat when administered either by corn oil gavage or in drin...

  1. Constitutive Androstane Receptor-Mediated Changes in Bile Acid Composition Contributes to Hepatoprotection from Lithocholic Acid-Induced Liver Injury in MiceS⃞

    OpenAIRE

    Beilke, Lisa D.; Aleksunes, Lauren M.; Holland, Ricky D; Besselsen, David G; Beger, Rick D.; Klaassen, Curtis D.; Cherrington, Nathan J.

    2009-01-01

    Pharmacological activation of the constitutive androstane receptor (CAR) protects the liver during cholestasis. The current study evaluates how activation of CAR influences genes involved in bile acid biosynthesis as a mechanism of hepatoprotection during bile acid-induced liver injury. CAR activators phenobarbital (PB) and 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) or corn oil (CO) were administered to C57BL/6 wild-type (WT) and CAR knockout (CAR-null) mice ...

  2. Omega-3 Fatty Acids Protect Renal Functions by Increasing Docosahexaenoic Acid-Derived Metabolite Levels in SHR.Cg-Leprcp/NDmcr Rats, a Metabolic Syndrome Model

    Directory of Open Access Journals (Sweden)

    Masanori Katakura

    2014-03-01

    Full Text Available The omega-3 polyunsaturated fatty acids (ω-3 PUFAs docosahexaenoic acid (DHA and/or eicosapentaenoic acid (EPA protect against diabetic nephropathy by inhibiting inflammation. The aim of this study was to assess the effects of highly purified DHA and EPA or EPA only administration on renal function and renal eicosanoid and docosanoid levels in an animal model of metabolic syndrome, SHR.Cg-Leprcp/NDmcr (SHRcp rats. Male SHRcp rats were divided into 3 groups. Control (5% arabic gum, TAK-085 (300 mg/kg/day, containing 467 mg/g EPA and 365 mg/g DHA, or EPA (300 mg/kg/day was orally administered for 20 weeks. The urinary albumin to creatinine ratio in the TAK-085-administered group was significantly lower than that in other groups. The glomerular sclerosis score in the TAK-085-administered group was significantly lower than that in the other groups. Although DHA levels were increased in total kidney fatty acids, the levels of nonesterified DHA were not significantly different among the 3 groups, whereas the levels of protectin D1, resolvin D1, and resolvin D2 were significantly increased in the TAK-085-administered group. The results show that the use of combination therapy with DHA and EPA in SHRcp rats improved or prevented renal failure associate with metabolic syndrome with decreasing triglyceride levels and increasing ω-3 PUFA lipid mediators.

  3. A Rat Model of Hemidystonia Induced by 3-Nitropropionic Acid

    OpenAIRE

    Liu, Huan-Guang; Ma, Yu; Meng, Da-Wei; Yang, An-Chao; Zhang, Jian-Guo

    2013-01-01

    Objective Secondary dystonia commonly presents as hemidystonia and is often refractory to current treatments. We aimed to establish an inducible rat model of hemidystonia utilizing 3-nitropropionic acid (3-NP) and to determine the pathophysiology of this model. Methods Two different doses of 3-NP were stereotactically administered into the ipsilateral caudate putamen (CPu) of Wistar rats. Behavioral changes and alterations in the neurotransmitter levels in the basal ganglia were analyzed. We ...

  4. The Effect of Compressor-Administered Defibrillation on Peri-shock Pauses in a Simulated Cardiac Arrest Scenario

    Directory of Open Access Journals (Sweden)

    Joshua Glick

    2014-03-01

    Full Text Available Introduction: Coordination of the tasks of performing chest compressions and defibrillation can lead to communication challenges that may prolong time spent off the chest. The purpose of this study was to determine whether defibrillation provided by the provider performing chest compressions led to a decrease in peri-shock pauses as compared to defibrillation administered by a second provider, in a simulated cardiac arrest scenario. Methods: This was a randomized, controlled study measuring pauses in chest compressions for defibrillation in a simulated cardiac arrest model. We approached hospital providers with current CPR certification for participation between July, 2011 and October, 2011. Volunteers were randomized to control (facilitator-administered defibrillation or experimental (compressor-administered defibrillation groups. All participants completed one minute of chest compressions on a mannequin in a shockable rhythm prior to administration of defibrillation. We measured and compared pauses for defibrillation in both groups. Results: Out of 200 total participants, we analyzed data from 197 defibrillations. Compressor-initiated defibrillation resulted in a significantly lower pre-shock hands-off time (0.57 s; 95% CI: 0.47-0.67 compared to facilitator-initiated defibrillation (1.49 s; 95% CI: 1.35-1.64. Furthermore, compressor-initiated defibrillation resulted in a significantly lower peri-shock hands-off time (2.77 s; 95% CI: 2.58-2.95 compared to facilitator-initiated defibrillation (4.25 s; 95% CI: 4.08-4.43. Conclusion: Assigning the responsibility for shock delivery to the provider performing compressions encourages continuous compressions throughout the charging period and decreases total time spent off the chest. However, as this was a simulation-based study, clinical implementation is necessary to further evaluate these potential benefits. [West J Emerg Med. 2014;15(2:246–250.

  5. Antimicrobial Activity of Intraurethrally Administered Probiotic Lactobacillus casei in a Murine Model of Escherichia coli Urinary Tract Infection

    OpenAIRE

    Asahara, Takashi; Nomoto, Koji; Watanuki, Masaaki; Yokokura, Teruo

    2001-01-01

    The antimicrobial activity of the intraurethrally administered probiotic Lactobacillus casei strain Shirota against Escherichia coli in a murine urinary tract infection (UTI) model was examined. UTI was induced by intraurethral administration of Escherichia coli strain HU-1 (a clinical isolate from a UTI patient, positive for type 1 and P fimbriae), at a dose of 1 × 106 to 2 × 106 CFU in 20 μl of saline, into a C3H/HeN mouse bladder which had been traumatized with 0.1 N HCl followed immediate...

  6. Lack of action of exogenously administered T3 on the fetal rat brain despite expression of the monocarboxylate transporter 8

    OpenAIRE

    Grijota Martínez, María del Carmen; Díez, Diego; Morreale de Escobar, Gabriella; Bernal, Juan; Morte, Beatriz

    2011-01-01

    Mutations of the monocarboxylate transporter 8 gene (MCT8, SLC16A2) cause the Allan-Herndon-Dudley syndrome, an X-linked syndrome of severe intellectual deficit and neurological impairment. Mct8 transports thyroid hormones (T4 and T3), and the Allan-Herndon-Dudley syndrome is likely caused by lack of T3 transport to neurons during critical periods of fetal brain development. To evaluate the role of Mct8 in thyroid hormone action in the fetal brain we administered T4 or T3 to thyroidectomized ...

  7. Kinetics of sup(99m)Tc-EHDP administered by intramuscular injection in man and in experimental animals

    International Nuclear Information System (INIS)

    With the aim of assessing the kinetics of a diphosphonate administered by intramuscular injection, we have studied the behaviour of sup(99m)Tc-labelled 1-hydroxy-1, 1-diphosphonate in man and in experimental animals, after intramuscular injection. The curves of plasma and urine radioactivity were analyzed in a six-compartment kinetic model containing seven transition coefficients. The results show that the diphosphonate given by intramuscular injection is absorbed rapidly and completely. Therefore the possibility of using this way of administration should be considered in the pathological conditions in which diphosphonates are used as therapeutic agents. (orig.)

  8. How Valid Is the Self-Administered Visual Analogue Scale for Assessing the Health Status of Elderly People?

    OpenAIRE

    Kimura, Tomoaki; Hayashida, Kenshi; Araki, Yoshimitsu; Morita, Takako; Yamaguchi, Noboru; Eboshida, Akira

    2008-01-01

    The population of Japan is aging rapidly, and maintaining the quality of life of elderly people has become an important issue in contemporary Japan. This study was conducted to verify the validity of the self-administered visual analogue scale (VAS) for assessing the health status of elderly people. A survey was conducted in two villages in western Japan in 2003. A total of 2040 participants, aged between 60 and 75 years, completed questionnaires comprising the VAS and six Likert-type items f...

  9. Self-Administered Domiciliary tDCS Treatment for Tinnitus: A Double-Blind Sham-Controlled Study.

    Directory of Open Access Journals (Sweden)

    Petteri Hyvärinen

    Full Text Available Transcranial direct current stimulation (tDCS has shown potential for providing tinnitus relief, although positive effects have usually been observed only during a short time period after treatment. In recent studies the focus has turned from one-session experiments towards multi-session treatment studies investigating long-term outcomes with double-blinded and sham-controlled study designs. Traditionally, tDCS has been administered in a clinical setting by a healthcare professional but in studies involving multiple treatment sessions, often a trade-off has to be made between sample size and the amount of labor needed to run the trial. Also, as the number of required visits to the clinic increases, the dropout rate is likely to rise proportionally.The aim of the current study was to find out if tDCS treatment for tinnitus could be patient-administered in a domiciliary setting and whether the results would be comparable to those from in-hospital treatment studies. Forty-three patients with chronic (> 6 months tinnitus were involved in the study, and data on 35 out of these patients were included in final analysis. Patients received 20 minutes of left temporal area anodal (LTA or bifrontal tDCS stimulation (2 mA or sham stimulation (0.3 mA for ten consecutive days. An overall reduction in the main outcome measure, Tinnitus Handicap Inventory (THI, was found (mean change -5.0 points, p < 0.05, but there was no significant difference between active and sham treatment outcomes. Patients found the tDCS treatment easy to administer and they all tolerated it well. In conclusion, self-administered domiciliary tDCS treatment for tinnitus was found safe and feasible and gave outcome results similar to recent randomized controlled long-term treatment trials. The results suggest better overall treatment response-as measured by THI-with domiciliary treatment than with in-hospital treatment, but this advantage is not related to the tDCS variant. The study

  10. Agreement between a self-administered questionnaire on musculoskeletal disorders of the neck-shoulder region and a physical examination

    Directory of Open Access Journals (Sweden)

    Brisson Chantal

    2008-03-01

    Full Text Available Abstract Background In epidemiological studies on neck-shoulder disorders, physical examination by health professionals, although more expensive, is usually considered a better method of data collection than self-administered questionnaires on symptoms. However, little is known on the comparison of these two methods of data collection. The agreement between self-administered questionnaires and the physical examination on the presence of neck-shoulders disorders was assessed in the present study. Methods This study was conducted among clerical workers using video display units. Prevalent cases were workers for whom neck-shoulder symptoms were present for at least 3 days during the previous 7 days and for whom pain intensity was greater than 50 mm on a 100 mm visual analogue scale. All 85 workers meeting this definition and a random sample of 102 workers who did not meet this definition were selected. Physical examination included measures of active range of motion and musculoskeletal strength. Cohen's kappa and global percent agreement were calculated to compare the two methods of data collection. The effect on the agreement of different question and physical examination definitions and the importance of the time interval elapsed between the administrations of the tests were also evaluated. Results Kappa coefficients ranged from 0.19 to 0.54 depending on the definitions used to ascertain disorders. The agreement was highest when the two instruments were administered 21 days apart or less (Kappa = 0.54, global agreement = 77%. It was not substantially improved by the addition of criteria related to functional limitations or when comparisons were made with alternative physical examination definitions. Pain intensity recorded during physical examination maneuvers was an important element of the agreement between questionnaire and physical examination findings. Conclusion These results suggest a fair to good agreement between the presence of

  11. First Experimental Demonstration of the Multipotential Carcinogenic Effects of Aspartame Administered in the Feed to Sprague-Dawley Rats

    OpenAIRE

    Soffritti, Morando; Belpoggi, Fiorella; Esposti, Davide Degli; Lambertini, Luca; Tibaldi, Eva; Rigano, Anna

    2005-01-01

    The Cesare Maltoni Cancer Research Center of the European Ramazzini Foundation has conducted a long-term bioassay on aspartame (APM), a widely used artificial sweetener. APM was administered with feed to 8-week-old Sprague-Dawley rats (100–150/sex/group), at concentrations of 100,000, 50,000, 10,000, 2,000, 400, 80, or 0 ppm. The treatment lasted until natural death, at which time all deceased animals underwent complete necropsy. Histopathologic evaluation of all pathologic lesions and of all...

  12. Virginia Solar Pathways Project: Economic Study of Utility-Administered Solar Programs: Soft Costs, Community Solar, and Tax Normalization Considerations

    Energy Technology Data Exchange (ETDEWEB)

    Reiter, Emerson [National Renewable Energy Lab. (NREL), Golden, CO (United States); Lowder, Travis [National Renewable Energy Lab. (NREL), Golden, CO (United States); Mathur, Shivani [National Renewable Energy Lab. (NREL), Golden, CO (United States); Mercer, Megan [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2016-06-23

    This report presents economic considerations for solar development in support of the Virginia Solar Pathways Project (VSPP), an effort funded by the U.S. Department of Energy (DOE) SunShot Initiative that seeks to develop a collaborative utility-administered solar strategy for the Commonwealth of Virginia. The results presented are intended to be considered alongside the results of other studies conducted under the VSPP that evaluate the impacts of solar energy on the electric distribution, transmission, and generation systems in Virginia.

  13. A closed cabinet system with water flushers and a blender for breeding small animal administered 3HHO

    International Nuclear Information System (INIS)

    A closed cabinet system was developed for breeding small animals administered 3HHO. 3HHO vapor released from the animals in the chamber was absorbed with water in a water bubbler. Feces and urine which were washed out with water were ground in a blender, diluted, and then released. With this cabinet system we were successful in safely breeding mice even given a total single injection of 15.5 GBq (420 mCi) of 3HHO without storing the 3H-slops for a long time and without any significant leakage of 3H from the cabinet. (author)

  14. Influencing of resorption and side-effects of salicylic acid by complexing with β-cyclodextrin

    International Nuclear Information System (INIS)

    After oral administration of 14C-labelled salicylic acid and its β-cyclodextrin complex to rats, the radioactivity level of the blood reached its maximum during the first 2 h. The blood level obtained with the complex is somewhat but not significantly lower than with free acid. Since the resorption of cyclodextrin is a considerably slower process, it is very likely that the resorption of salicylic acid takes place in the form of free acid after dissociation of the complex. The urinary excretion cumulative curves showed that the free salicylic acid was completely excreted, while about 10% of the salicylic acid administered in the form of complex is lost. The cyclodextrin complex formation increased the pK values of all hydroxybenzoic acids. Direct observations revealed that complex formation decreased the stomach-irritating effect of salicylic acid. The ratio of radioactivity was nearly the same in the organs of animals treated by both free salicylic and cyclodextrin complex. (author)

  15. Retarded acid emulsion

    Energy Technology Data Exchange (ETDEWEB)

    Fast, C.R.; Rixe, F.H.; Duffield, E.L. Jr.

    1972-08-01

    Compositions for use in acidizing hydrocarbon-bearing formations are described. Retarded acid emulsions of prolonged stability make it possible for the acid in this form to be displaced substantial distances out into the formation before becoming spent. The action of acid emulsions for use in acidizing hydrocarbon-bearing formations is prolonged by employing as the principal emulsifying agent an amine salt of dodecylbenzene sulfonic acid. Acid emulsions employing the amine salt of dodecylbenzene sulfonic acid exhibit greater stability than those employing the free acid. (8 claims)

  16. Oxidative stress parameters and erythrocyte membrane adenosine triphosphatase activities in streptozotocin-induced diabetic rats administered aqueous preparation of Kalanchoe Pinnata leaves

    Directory of Open Access Journals (Sweden)

    Nikhil Menon

    2016-01-01

    Full Text Available Background: Diabetes mellitus is a chronic metabolic disease that according to the World Health Organization affects more than 382 million people. The rise in diabetes mellitus coupled with the lack of an effective treatment has led many to investigate medicinal plants to identify a viable alternative. Objective: To evaluate red blood cell (RBC membrane adenosine triphosphatase (ATPase activities and antioxidant levels in streptozotocin-induced diabetic rats administered aqueous preparation of Kalanchoe pinnata leaves. Materials and Methods: Diabetes mellitus was induced in rats by a single administration of streptozotocin (60 mg/kg. Diabetic rats were then treated with aqueous K. pinnata preparation (three mature leaves ~ 9.96 g/70 kg body weight or about 0.14 g/kg body weight/day for 30 days. Serum glucose, RBC membrane ATPase activities, and antioxidant levels were determined. Results: We noted weight loss and reduced food consumption in the treated diabetic group. Serum glucose levels were reduced in the treated diabetic group compared to the other groups. Superoxide dismutase activity and glutathione levels were not significantly elevated in the treated group compared to the diabetic group. However, serum catalase activity was significantly (P < 0.05 increased in the treated diabetic group compared to the other groups. Serum thiobarbituric acid reactive substances were not significantly altered among the groups. There was a significant (P < 0.05 increase in Mg2+ ATPase activity and a nonsignificant increase in Na+/K+ ATPase activity in the RBC membrane of the treated diabetic group compared to the diabetic group. Conclusion: The consumption of aqueous preparation of K. pinnata may accrue benefits in the management of diabetes by lowering oxidative stress often associated with the disease and improving the availability of cellular magnesium through an increase in the magnesium ATPase pump in the RBC membrane for increased cellular metabolism

  17. The effect of postirradiation application of aspartic acid salts on hemopoietic recovery in sublethally X-irradiated mice

    International Nuclear Information System (INIS)

    The effect of aspartic acid salts, especially of K and Mg aspartates, on certain hematological changes in the peripheral blood and hemopoietic organs of sublethally X-irratiated male mice of the strain C57Bl/10 was investigated. Salts of aspartic acid were administered in tap water after irradiation. A favorable effect of aspartic acid salts on erythropoietic recovery and on regeneration of thymus weight was found during the first two weeks after irradiation. (orig.)

  18. Self-administered outpatient parenteral antimicrobial therapy: a report of three years experience in the Irish healthcare setting.

    LENUS (Irish Health Repository)

    Kieran, J

    2012-02-01

    Outpatient parenteral antibiotic therapy (OPAT) was first reported in 1972. OPAT programmes are not well established in Ireland, with no reported outcomes in the literature. An OPAT programme was established at St. James Hospital in 2006. Demographics, diagnoses and outcomes of the first 60 courses are reported. A retrospective analysis of prospectively recorded data was performed on patients treated from March 2006 to February 2009. The data was analysed using SPSS v.17. Sixty OPAT courses were administered to 56 patients, 57 percent of which were male. The median age was 50 years, the median inpatient stay was 19 days, the median duration of OPAT was 16 days and 1,289 inpatient bed days were saved. The additional cost per day of OPAT was 167.60 euros. Vancomycin was the most prescribed antimicrobial, administered to 35%. Musculoskeletal infection was the indication for treatment in 50%. Confirmatory microbiological diagnosis was identified in 72%, most frequently due to Staphylococcus aureus (68%). Only minor adverse events were recorded. Clinical cure was achieved in 92.8%. A patient satisfaction survey showed high satisfaction. OPAT is a safe and effective way of providing parenteral antibiotic therapy in the Irish healthcare system. Better integration of funding and the appointment of Infectious Diseases specialists will facilitate its expansion.

  19. Training Self-Administered Acupressure Exercise among Postmenopausal Women with Osteoarthritic Knee Pain: A Feasibility Study and Lessons Learned

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    2012-01-01

    Full Text Available Background. Osteoarthritis (OA is more prevalent in women, particularly after menopausal age. Women are more likely to seek complementary and alternative medicine (CAM approaches. We examined the feasibility of training self-administered acupressure exercise and assessed its impact on OA symptoms among women with knee OA. Methods. Thirty-six eligible postmenopausal women were randomly assigned in the acupressure exercise group (n=15 or the control group (n=21 for 12 weeks. Feasibility outcomes (e.g., compliance and adverse effects and clinical outcomes (e.g., pain, stiffness, and physical function were assessed. Data were collected at baseline, 6 weeks and 12 weeks. Both per-protocol and intention-to-treat analysis were employed. Results. The training materials were well received. The feedback from participants suggests that self-administered acupressure exercise is easy to learn and safe to perform at home, although no statistically significant results of the clinical outcome were observed. Our findings didn’t reveal superiority or inferiority of acupressure compared with usual care. Conclusion. Acupressure exercise is feasible to be trained among postmenopausal women with knee osteoarthritis. Due to the limitations of this study such as small sample size and high attrition rate, acupressure’s efficacy needs to be further explored in larger scale studies with more rigorous design.

  20. Variability of [18F]FDG administered activities among patients undergoing PET examinations: an international multicenter survey

    International Nuclear Information System (INIS)

    Given the large number of [18F]fluorodeoxyglucose (FDG) PET examinations performed annually throughout the world, reduction of the administered activity without compromise of the clinical information being sought is encouraged. Guidelines issued by the SNMMI and European Association of Nuclear Medicine (EANM) differ greatly on the choice of the activity that should be administered to patients: the EANM suggests a personalised activity based on the patient's body weight, whereas the SNMMI recommends the administration of fixed activities. The authors analysed a database of 24 716 [18F]FDG administrations performed worldwide in 15 PET centres to assess the degree of heterogeneity, in relation to available technology, operational protocols and reference guidelines. Median activities based on the patients' body weight were 43 % lower than fixed-activity administrations (p < 0.001). When TOF scanners are available, the median activity is lowered, but when comparing centres with the same technology or those that use the same operational protocols, weight-based activities are still significantly lower than fixed activities. (authors)

  1. [Research on early warning signals of adverse drug reactions to parenterally administered xiyanping based on spontaneous reporting system (SRS) data].

    Science.gov (United States)

    Wang, Zhi-Fei; Xiang, Yong-Yang; Xie, Yan-Ming

    2013-09-01

    This article focused on early warning signals regarding the safety of parenterally administered Xiyanping. The study data was obtained from reports made between 2005-2012 from the national spontaneous reporting system (SRS). Proportion reporting ratio (PRR) and Bayesian confidence propagation neural network (BCPNN) algorithms were used to analyse: erythra, pruritus, anaphylactoid reactions and shiver with cold, these 4 adverse drug reactions had a total count of more than 500 events. The article found that Xiyanping's incidence rate of erythra was higher than for background-drugs in every year and in every season. Pruritus was an early warning signal in the second season of 2009, and anaphylactoid reaction was an early warning signal in the fourth season of 2011 and in the second season of 2012. There was however no early warning signal indicated by shiver with cold. This data indicates that erythra maybe an adverse drug reactions to parenterally administered Xiyanping, and if the incidence rate of pruritus and anaphylactoid reaction rises attention should be paid to its safety. PMID:24471321

  2. Safety profile and pharmacokinetic analyses of the anti-CTLA4 antibody tremelimumab administered as a one hour infusion

    Directory of Open Access Journals (Sweden)

    Ribas Antoni

    2012-11-01

    Full Text Available Abstract Background CTLA4 blocking monoclonal antibodies provide a low frequency but durable tumor responses in patients with metastatic melanoma, which led to the regulatory approval of ipilimumab based on two randomized clinical trials with overall survival advantage. The similarly fully human anti-CTLA4 antibody tremelimumab had been developed in the clinic at a fixed rate infusion, resulting in very prolonged infusion times. A new formulation of tremelimumab allowed testing a shorter infusion time. Methods A phase 1 multi-center study to establish the safety and tolerability of administering tremelimumab as a 1-hour infusion to patients with metastatic melanoma. Secondary endpoints included pharmacokinetic and clinical effects of tremelimumab. Results No grade 3 or greater infusion-related adverse events or other adverse events preventing the administration of the full tremelimumab dose were noted in 44 treated patients. The overall side effect profile was consistent with prior experiences with anti-CTLA4 antibodies. Objective tumor responses were noted in 11% of evaluable patients with metastatic melanoma, which is also consistent with the prior experience with CTLA4 antagonistic antibodies. Conclusions This study did not identify any safety concerns when tremelimumab was administered as a 1-hour infusion. These data support further clinical testing of the 1-hour infusion of tremelimumab. (Clinical trial registration number NCT00585000.

  3. Bone mineral density and the relationship between lipid profile and bone mineral density in the rats administered juniperus communis linn

    International Nuclear Information System (INIS)

    The aim of the study is to investigate the relationship of Juniperus Communis Lynn. with the bone mineral density in the rats fed with a high cholesterol (1%) diet. Thirty five Wistar albino rats weighed approximately 250-300 were used in this study. The rats are divided in five groups of seven each. Groups I and II were administered 0.5 ml of 0.5% Sodium Carboxy Methyl Cellulose (SCMC), while Groups II, IV and V administered 0.5 ml of juniperus communis linn dissolved in 25, 50, 100 mg/kg. Group I and Group II were fed with normal pellets while the other four groups were fed with pellets containing 1% cholesterol. Levels of lipid profile and High Density Lipoprotein Cholesterol (HDL-C) were defined in all the groups. Furthermore, bone mineral density (B M D) of the animals were obtained with DEXA scanner. BMD values of the rats did not show a different among the groups. Significant negative correlations were determined between BMD measurements and LDL-C levels in all groups connected with dose of Juniperus Communis oil. However, this relationship was not linear. (author)

  4. Assessing the relationship between antigenicity and immunogenicity of human rabies vaccines when administered by intradermal route: results of a metaanalysis.

    Science.gov (United States)

    Sudarshan, Mysore K; Gangaboraiah, Bilagumba; Ravish, Haradanahalli S; Narayana, Doddabele H Ashwath

    2010-07-01

    The metadata of 10 published studies and 3 vaccine trial reports comprising of 19 vaccine cohorts from four countries conducted over a period of 23 years (1986 - 2009) was used for metaanalysis. The vaccines studied were purified chick embryo cell vaccine (Rabipur, India & Germany), purified vero cell rabies vaccine (Verorab, France; Indirab, India) & human diploid cell vaccine (MIRV, France).The potency of these vaccines varied from 0.55 IU to 2.32 IU per intradermal dose of 0.1 ml per site. The vaccines were administered to 1,011 subjects comprising of 19 cohorts and using five different ID regimens. The immunogenicity was measured by assays of rabies virus neutralizing antibody (RVNA) titres using rapid fluorescent focus inhibition test (RFFIT) [15 cohorts] and mouse neutralization test (MNT) [4 cohorts]. The statistical analysis of the data was done by Karl Pearson's correlation coefficient to measure the relationship between antigenicity and immunogenicity. It was revealed that, there was no significant linear relationship between antigenicity and immunogenicity of rabies vaccines when administered by intradermal route. (p> 0.230 and p>0.568). PMID:20523131

  5. [Real-world study in analysis of effects on concomitant medications with parenterally administered shenmai for coronary heart disease].

    Science.gov (United States)

    Jiang, Jun-Jie; Tang, Hao; Xie, Yan-Ming; Yang, Hu; Zhuang, Yan

    2013-09-01

    In order to understand the treatment of coronary heart disease with parenterally administered Shenmai and the efficacy of combination therapies, the study selected 18 hospitals for analysis. Data from each hospital's hospital injection system (HIS) was collected. Data of in-patients receiving parenterally administered Shenmai for a diagnosis of coronary heart disease was analyzed using; the Apriori algorithm to model use, Clementine 12.0 linkage analysis to find correlations between various drugs, and chi-square test for commonly used combination therapies to ascertain the cure rate. In 5 583 patients with coronary heart disease, it was found that Shenmai was commonly used with isosorbide mononitrate, aspirin, clopidogrel hydrogen and common combinations of combination therapy, and that the cure rate was better in these combinations than for other treatment regimes. When Shenmai is used with combination therapies for coronary heart disease, treatment guidelines should be complied with. In clinical application, the types of concomitant medications and their interactions, should be observed so as to prevent of adverse reactions. PMID:24471341

  6. Retention and tissue distribution of 210Pb (NO3)2 administered orally to infant and adult monkeys

    International Nuclear Information System (INIS)

    The retention and tissue distribution of 210Pb were studied in 10-day-old, 150-day-old, and adult monkeys. Lead-210 nitrate was administered to the monkeys by gavage after a 12 hr fast and 210Pb excreted in urine and feces was monitored for 96 hr. All monkeys were necropsied 96 hr after dosing and the 210Pb concentrations of various tissues were deermined. The data demonstrated that infant monkeys retained 64.5 and 69.8% of the orally administered 210Pb at 10 and 150 days of age, respectively, while adult monkeys retained 3.2% of the 210Pb dose. Blood 210Pb levels 96 hr after dosing did not vary significantly between age groups. Of the 210Pb contained in blood, 98 to 99% was found in blood cells and 1 to 2% in blood plamsa; 5 to 8% of the Pb in blood cells was bound to blood cell membranes. None of these parameters varied significantly with age. The percentage of the lead dose excreted in urine did not vary significantly between age groups. Analysis of tissues for 210Pb revealed that both the tissue Pb concentrations and tissue Pb : blood Pb ratios were significantly higher in the bone structure of infants than adults. Brain Pb : blood Pb ratios were significantly greater in 10-day-old infants than 150-day-old infants or adults

  7. Effect of carbamazepine or phenytoin therapy on blood level of intravenously administered midazolam: a prospective cohort study.

    Science.gov (United States)

    Hayashi, Tomoko; Higuchi, Hitoshi; Tomoyasu, Yumiko; Ishii-Maruhama, Minako; Maeda, Shigeru; Miyawaki, Takuya

    2016-02-01

    Dental treatment of intellectually disabled patients is frequently performed under general anesthesia or sedation. Many of these patients have epilepsy and are medicated with antiepileptic drugs (AEDs). Carbamazepine (CBZ) and phenytoin (PHT) are known to promote the metabolism of midazolam, and the blood levels of midazolam in patients medicated with CBZ or PHT may be different from those in healthy individuals. In this study, we clarified the influences of CBZ and PHT on the blood level of intravenously administered midazolam in patients medicated with CBZ or PHT. The subjects were divided into the following groups: not medicated with AEDs (control group), medicated with only CBZ or PHT (mono CBZ/PHT group), and medicated with CBZ or PHT or both and other AEDs (poly CBZ/PHT group). General anesthesia was achieved using midazolam, propofol, and remifentanil, and then the blood midazolam level was measured at 10, 30, and 60 min after intravenous midazolam administration. According to the results, the blood midazolam level was significantly lower in the mono and poly CBZ/PHT groups than in the control group. This finding suggests that intravenously administered midazolam may have a weaker effect in patients medicated with CBZ or PHT. PMID:26272251

  8. The short- and long-term effects of orally administered high-dose reduced graphene oxide nanosheets on mouse behaviors.

    Science.gov (United States)

    Zhang, Ding; Zhang, Zheyu; Liu, Yayun; Chu, Maoquan; Yang, Chengyu; Li, Wenhao; Shao, Yuxiang; Yue, Yan; Xu, Rujiao

    2015-11-01

    Reduced graphene oxide (rGO), a carbon-based nanomaterial, has enormous potential in biomedical research, including in vivo cancer therapeutics. Concerns over the toxicity remain outstanding and must be investigated before clinical application. The effect of rGO exposure on animal behaviors, such as learning and memory abilities, has not been clarified. Herein, we explored the short- and long-term effects of orally administered rGO on mouse behaviors, including general locomotor activity level, balance and neuromuscular coordination, exploratory and anxiety behaviors, and learning and memory abilities using open-field, rotarod, and Morris water maze tests. Compared with mice administered buffer-dispersed mouse chow or buffer alone, mice receiving a high dose of small or large rGO nanosheets showed little change in exploratory, anxiety-like, or learning and memory behaviors, although general locomotor activity, balance, and neuromuscular coordination were initially affected, which the mechanisms (e.g. the influence of rGO exposure on the activity of superoxide dismutase in mouse serum) were discussed. The results presented in this work look to provide a deep understanding of the in vivo toxicity of rGO to animals, especially its effect on learning and memory and other behaviors. PMID:26276695

  9. Protection of live bacteria from bile acid toxicity using bile acid adsorbing resins.

    Science.gov (United States)

    Edwards, Alexander D; Slater, Nigel K H

    2009-06-12

    We previously demonstrated that a dry, room temperature stable formulation of a live bacterial vaccine was highly susceptible to bile, and suggested that this will lead to significant loss of viability of any live bacterial formulation released into the intestine using an enteric coating or capsule. We found that bile and acid tolerance is very rapidly recovered after rehydration with buffer or water, raising the possibility that rehydration in the absence of bile prior to release into the intestine might solve the problem of bile toxicity to dried cells. We describe here a novel formulation that combines extensively studied bile acid adsorbent resins with the dried bacteria, to temporarily adsorb bile acids and allow rehydration and recovery of bile resistance of bacteria in the intestine before release. Tablets containing the bile acid adsorbent cholestyramine release 250-fold more live bacteria when dissolved in a bile solution, compared to control tablets without cholestyramine or with a control resin that does not bind bile acids. We propose that a simple enteric coated oral dosage form containing bile acid adsorbent resins will allow improved live bacterial delivery to the intestine via the oral route, a major step towards room temperature stable, easily administered and distributed vaccine pills and other bacterial therapeutics. PMID:19490986

  10. Folic acid supplementation attenuates hyperhomocysteinemia-induced preeclampsia-like symptoms in rats

    Institute of Scientific and Technical Information of China (English)

    Jun Wang; Yan Cui; Jing Ge; Meijing Ma

    2012-01-01

    Folic acid participates in the metabolism of homocysteine and lowers plasma homocysteine levels directly or indirectly. To establish a hyperhomocysteinemic pregnant rat model, 2 mL of DL-homocysteine was administered daily by intraperitoneal injection at a dose of 200 mg/kg from day 10 to day 19 of gestation. Folic acid was administered by intragastric administration at a dose of 20 mg/kg during the period of preeclampsia induction. Results showed that systolic blood pressure, proteinuria/creatinine ratio, and plasma homocysteine levels in the hyperhomocysteinemic pregnant rats increased significantly, and that body weight and brain weight of rat pups significantly decreased. Folic acid supplementation markedly reversed the above-mentioned abnormal changes of hyperhomocysteinemic pregnant rats and rat pups. These findings suggest that folic acid can alleviate the symptoms of hyperhomocysteinemia- induced preeclampsia in pregnant rats without influencing brain development of rat pups.

  11. Radiopharmaceutical activities administered for diagnostic procedures in nuclear medicine in the first six months of the gamma camera use in the Clinical Center of Montenegro - Podgorica

    International Nuclear Information System (INIS)

    Nuclear medicine procedures have carried out in the Clinical Center of Montenegro - Podgorica since 2006 by the dual-headed SPECT and Digital gamma camera NUCLINE Spirit DH-V. In the first six months of the gamma camera use (from September 2006 to March 2007) examinations of skeleton, kidneys, thyroid and lung were performed. For diagnostic skeletal imaging (102 patients) the radiopharmaceutical 99mTc-MDP is used, and administered activities were in the range from 555 to 740 MBq. For thyroid imaging (203 patients) 99mTc-pertechnetate is used, and administered activities were in the range (37-111) MBq. Lung imaging is performed for 3 patients, using 99mTc-MAA and administered activities in the range (111-185) MBq. Renal imaging is carried out for 72 patients: 42 dynamic studies of kidneys were performed with 99mTc-DTPA and administered activities from 207 to 282 MBq, and 30 static kidneys scintigraphies were performed using the radiopharmaceutical 99mTc-DMSA. 6 patients in the last mentioned group were children with year of birth between 2000 and 2006, and administered activities were from 16.6 to 55.5 MBq. In the same group, activities 28.5 MBq, 74.4 MBq and 120 MBq were administered to three patients with age between 6 and 18 years, and in the other cases, administered activities to the patients (adults) were in the range (59.2 to 196) MBq. The administered activities presented here are basis for further estimations of cumulated activity and absorbed dose to the various organs, which is useful for comparison of the average dose to patient organs in various nuclear medicine procedures and calculation of effective dose equivalent and total effective dose, significant for an estimation of potential risk due to the radioactivity administered to a patient during nuclear medicine procedures. It is very important for procedures optimization and improvement of the radiation protection. (author)

  12. Plasma amino acids

    Science.gov (United States)

    Amino acids blood test ... types of methods used to determine the individual amino acid levels in the blood. ... test is done to measure the level of amino acids in the blood. An increased level of a ...

  13. Acid Lipase Disease

    Science.gov (United States)

    ... Enhancing Diversity Find People About NINDS NINDS Acid Lipase Disease Information Page Synonym(s): Cholesterol Ester Storage Disease, ... Related NINDS Publications and Information What is Acid Lipase Disease ? Acid lipase disease or deficiency occurs when ...

  14. Effects of oleic acid on pulmonary capillary leak and thromboxanes

    International Nuclear Information System (INIS)

    The role of arachidonic acid metabolites in oleic acid-induced lung injury in anesthetized dogs was investigated. Oleic acid was administered as a bolus injection into the pulmonary artery after either indomethacin (10 mg/kg iv) or vehicle. Measurements of hemodynamic parameters, mean systemic (MAP), pulmonary capillary wedge, and pulmonary artery pressures (PAP), cardiac output, arterial blood gases, extravascular lung waters (EVLW) by thermaldye double indicator dilution techniques and plasma immunoreactive thromboxane B2 (iTxB2), by radioimmunoassay were obtained at zero time (baseline) and 20 min following each oleic acid injection. A new noninvasive technique was employed to measure pulmonary capillary protein leak by the scintigraphic analysis of intravenously administered technetium-99m radiolabeled human serum albumin (99mTc -HSA) in the cardiac and lung regions. Oleic acid injection caused a significant dose related fall in MAP, arterial pO2, and cardiac output, and increases in EVLW and plasma iTxB2 in the vehicle pretreated animals, while mean PAP remained unchanged. In contrast, in the indomethacin pretreated dogs, MAP, EVLW, cardiac output, and plasma iTxB2 levels did not change from baseline values and there was an increase in mean PAP. Pulmonary vascular resistance was significantly elevated in both groups

  15. Bile acids trigger GLP-1 release predominantly by accessing basolaterally-located G-protein coupled bile acid receptors

    DEFF Research Database (Denmark)

    Brighton, Cheryl A; Rievaj, Juraj; Kuhre, Rune Ehrenreich; Glass, Leslie L; Schoonjans,, Kristina; Holst, Jens Juul; Gribbe, Fiona M; Reimann, Frank

    2015-01-01

    coupled bile acid transporter ASBT. The aim of this study was to identify pathways important for GLP-1 release, and whether bile acids target their receptors on GLP-1 secreting L-cells from the apical or basolateral compartment. Using transgenic mice expressing fluorescent sensors specifically in L...... significant effect in non-polarised primary cultures. Studies in the perfused rat gut confirmed that vascularly administered TDCA was more effective than luminalTDCA.Intestinal primary culturesandUssingchamber-mounted tissues from GPBAR1-knockout mice did not secrete GLP-1 in response to either TLCA or TDCA...

  16. POLYELEOSTEARIC ACID VESICLES

    Institute of Scientific and Technical Information of China (English)

    LI Zichen; XIE Ximng; FAN Qinghua; FANG Yifei

    1992-01-01

    α-Eleostearic acid and β-eleostearic acid formed vesicles in aqueous medium when an ethanol solutionofeleostearic acid was injected rapidly into a vigorously vortexed aqueous phase. Formation of the vesicles was demonstrated by electron microscopic observation and bromothymol blue encapsulation experiments. Polymerizations of the eleostearic acids in the formed vesicles carried out by UV irradiation produced poly-α-eleostearic acid and poly-β-eleostearic acid vesicles.

  17. Interaction of Peptide Transporter 1 With D-Glucose and L-Glutamic Acid; Possible Involvement of Taste Receptors.

    Science.gov (United States)

    Arakawa, Hiroshi; Ohmachi, Taichi; Ichiba, Kiko; Kamioka, Hiroki; Tomono, Takumi; Kanagawa, Masahiko; Idota, Yoko; Hatano, Yasuko; Yano, Kentaro; Morimoto, Kaori; Ogihara, Takuo

    2016-01-01

    We investigated the influence of sweet and umami (savory) tastants on the intestinal absorption of cephalexin (CEX), a substrate of peptide transporter 1 (PEPT1, SLC15A1) in rats. After oral administration of glucose or mannitol to rats, CEX was administered together with a second dose of glucose or mannitol. Western blot analysis indicated that expression of PEPT1 in rat jejunum membrane was decreased by glucose, compared to mannitol. Furthermore, the maximum plasma concentration (Cmax) of orally administered CEX was reduced by glucose compared to mannitol. The effect of glucose was diminished by nifedipine, a L-type Ca(2+) channel blocker. We also found that Cmax of orally administered CEX was reduced by treatment with L-glutamic acid, compared to D-glutamic acid. Thus, excessive intake of glucose and L-glutamic acid may impair oral absorption of PEPT1 substrates. PMID:26852864

  18. Efficacy of intravenous hydration drip versus amino acid drip in idiopathic oligohydramnios

    OpenAIRE

    Priti Kumar; Aniket S. Kakade; Savita Mehendale

    2016-01-01

    Background: Role of intravenous hydration and amino acid infusion is well documented for the treatment of foetal growth restriction and associated oligohydramnios. The present study concentrates on the efficacy of intravenous hydration and amino acid infusions in cases of isolated oligohydramnios. Methods: 30 antenatal mothers having isolated oligohydramnios and fulfilling the inclusion criteria were selected for the study. They were randomized and administered 6 drips of normal saline or ...

  19. Cardioprotective effects of gallic acid in diabetes-induced myocardial dysfunction in rats

    OpenAIRE

    Patel, Snehal S.; Goyal, Ramesh K.

    2011-01-01

    Background: Normalization of hyperglycemia, hyperlipidemia, and oxidative stress is an important objective in preventing diabetes-induced cardiac dysfunction. Objective: This study was undertaken to examine the effects of gallic acid in myocardial dysfunctions associated with type-1 diabetes. Materials and Methods: Diabetes was induced by single intravenous injection of streptozotocin (STZ, 50 mg/kg i.v.). Gallic acid was administered daily at three different doses (100, 50, and 25 mg/kg p.o....

  20. Comparative pharmacokinetics of chlorogenic acid after oral administration in rats

    Institute of Scientific and Technical Information of China (English)

    Wei Qi; Ting Zhao; Wen-Wen Yang; Guang-Hou Wang; Hua Yua; Hai-Xiao Zhao; Chen Yang; Li-Xin Suna

    2011-01-01

    The present study was aimed at the comparison of the pharmacokinetics of pure chlorogenic acid and extract of Solanum lyratum Thunb. The animals were allocated to two groups, and were administered chlorogenic acid or extract of S. lyratum Thunb. at a dose of 50.0 mg/kg orally. Blood samples were collected up to 8 h post-dosing. Plasma chlorogenic acid analyses were performed using an HPLC method with UV detector. The pharmacokinetic parameters were evaluated using non-compartmental assessment. Significant differences existed in the two groups for AUCo-t, AUCo-∞ and CLz/F. The reliable HPLC method was successfully applied to the determination of chlorogenic acid in rat plasma at dosting of 50.0 mg/kz.