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Sample records for administering zoledronic acid

  1. Zoledronic Acid Injection

    Science.gov (United States)

    ... blood cells that produce substances needed to fight infection)] or by cancer that began in another part of the body but has spread to the bones. Zoledronic acid (Zometa) is not cancer chemotherapy, and it will not slow or stop the ...

  2. 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...

  3. 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.

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

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    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....

  5. 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

  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

    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 assi...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

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

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

    2010-01-01

    Patients in the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) Recurrent Fracture Trial were assessed for evidence of delayed hip fracture healing. No association was observed between zoledronic acid (ZOL) and delayed healing. We conclude that ZOL has no clinical...

  9. 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

  10. 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

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

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    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

  12. 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.

  13. [Separation of zoledronic acid and its related substances by ion-pair reversed-phase high performance liquid chromatography].

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    Zhang, Xiaoqing; Jiang, Ye; Xu, Zhiru

    2004-07-01

    A rapid and simple ion-pair reversed-phase high performance liquid chromatographic method (HPLC) has been established for the routine analysis of zoledronic acid and its related substances. The chromatographic conditions were optimized based on the satisfactory separation of zoledronic acid from imidazol-1-ylacetic acid, their retention times and peak shape. The excellent separation of zoledronic acid from its related substances, including the remaining imidazol-1-ylacetic acid used in the synthesis of zoledronic acid and other impurities of oxidation and decomposition, was achieved within 9 min on a Hypersil C8 column with UV detection at 220 nm. The mobile phase was a mixture of methanol (20%) and 5 mmo/L phosphate buffer (80%) that contains 6 mmol/L tetrabutylammonium bromide. The resolution factor of zoledronic acid from its adjacent peak was more than 2.5. This is a simple and rapid method for the routine assay of zoledronic acid.

  14. 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.

  15. 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.

  16. Zoledronic acid induces apoptosis and autophagy in cervical cancer cells.

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    Wang, I-Te; Chou, Shou-Chu; Lin, Ying-Chin

    2014-12-01

    Cervical cancer is one of the most common gynecological cancers in association with high mortality and morbidity. The present study was aimed to investigate the in vitro effects of zoledronic acid (ZA) on viability and induction of apoptosis and autophagy as well as inflammatory effects in three human cervical cancer cell lines (HeLa, SiHa, and CaSki). Cell viability was measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay. Induction of apoptosis was determined by quantitation of expression level of B cell lymphoma 2 (Bcl-2) and Bax messenger RNA (mRNA) and identification of the proteolytic cleavage of poly (ADP)-ribose polymerase (PARP) and caspase-3. Autophagic effects were examined by quantitation of mRNA expression of autophagy protein 5 (ATG5) and beclin1 and identifying accumulation of microtubule-associated protein 1 light chain 3 (LC3)-II. Inflammatory effect was determined by measuring expression and production of IL-6 and cyclooxygenase-2 (Cox-2). The results showed ZA significantly inhibited cell viability of cervical cancer cells. ZA-induced cell death displayed features characteristic to both apoptosis and autophagy and was associated with different changes in the levels of Bcl-2 and Bax in the various cervical cancer lines. Expression of metastatic cytokines, IL-6 and Cox-2, was upregulated in the presence of ZA at low concentration. Our data revealed that ZA inhibits cervical cancer cells through the synergistic effect of apoptosis induction and autophagy activation.

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

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    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

  18. 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 ...

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

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    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...

  20. 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.

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    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.

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

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    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.

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

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    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...... or more previous administrations). On average, 62% of the administered Zol was retained in the skeleton of both MM and BC patients and independently of the number of treatments. WBrt of Zol did not correlate with cross-linked C-telopeptide (CTX) levels, but linear regression analyses showed that WBrt...

  3. 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.

  4. Zoledronic acid cooperates with a cyclooxygenase-2 inhibitor and gefitinib in inhibiting breast and prostate cancer.

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    Melisi, Davide; Caputo, Rosa; Damiano, Vincenzo; Bianco, Roberto; Veneziani, Bianca Maria; Bianco, A Raffaele; De Placido, Sabino; Ciardiello, Fortunato; Tortora, Giampaolo

    2005-12-01

    Biphosphonates (BPs) are widely used to inhibit osteoclastic activity in malignant diseases such as bone metastatic breast and prostate carcinoma. Recent studies reported that BPs could also cause a direct antitumor effect, probably due to their ability to interfere with several intracellular signalling molecules. The enzyme cyclooxygenase-2 (COX-2) and the epidermal growth factor receptor (EGFR) play an important role in the control of cancer cell growth and inhibitors of COX-2 and EGFR have shown antitumor activity in vitro and in vivo in several tumor types. We, and others, have previously shown that EGFR and COX-2 may be directly related to each other and that their selective inhibitors may have a cooperative effect. In the present study we have evaluated the combined effect of zoledronic acid, the most potent nitrogen-containing BP, with the COX-2 inhibitor SC-236 and the selective EGFR-tyrosine kinase inhibitor gefitinib, on breast and prostate cancer models in vitro and in xenografted nude mice. We show that combination of zoledronic acid with SC-236 and gefitinib causes a cooperative antitumor effect accompanied by induction of apoptosis and regulation of the expression of mitogenic factors, proangiogenic factors and cell cycle controllers both in vitro and in xenografted nude mice. The modulatory effect on protein expression and the inhibitory effect on tumor growth is much more potent when the three agents are used together. Since studies are ongoing to explore the antitumor effect of zoledronic acid, our results provide new insights into the mechanism of action of these agents and a novel rationale to translate this feasible combination treatment strategy into a clinical setting.

  5. 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.

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

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

    2016-01-01

    , 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...

  7. 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

    Annual infusions of zoledronic acid (5 mg) significantly reduced the risk of vertebral, hip, and nonvertebral fractures in a study of postmenopausal women with osteoporosis and significantly reduced clinical fractures and all-cause mortality in another study of women and men who had recently unde...

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

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    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

  9. A Modified method for reducing renal injury in zoledronic acid treatment of hypercalcemia and adverse skeletal events

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    Jiang Liu

    2013-01-01

    Full Text Available Aims: In this paper, we have reported a previously undescribed risk factor of deterioration of renal function in zoledronic acid treatment of skeletal metastasis - high serum calcium level. Based on this consideration, a modified method of treatment of hypercalcemia (HCM with zoledronic acid is suggested in this paper. Material and Methods: Bone scan findings of 1090 cancer patients were analyzed, of which 26 had intense renal parenchymal uptake as a result of HCM or bone metastases. Subsequently, a total of 56 bone metastases patients with zoledronic acid treatment were divided into three groups: HCM group who were pre-treated to normal serum calcium level (13 patients, HCM group (19 patients, and normal serum calcium group (24 patients. Results: More patients with intense renal parenchymal uptake were hyperglycemic, statistically significantly (18/26 versus 19/1064, P = 2.1, E-78. No more patients with intense renal parenchymal uptake were associated with bone metastases (14/26 versus 438/1064, P = 0.20. Subsequently, more HCM patients receiving zoledronic acid treatment showed renal injury compared to patients with normal serum calcium level (5/15 versus 2/24, P < 0.05 and HCM patients with pre-treatment to normal serum calcium level (5/15 versus 1/17, P < 0.05. Conclusions: Intense renal parenchymal uptake of bisphosphonates is closely related to HCM rather than to bone metastases in cancer patients. The serum calcium should be measured and reduced to normal level before zoledronic acid is used in managements of adverse skeletal events in order to decrease the risk of renal injury.

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

    DEFF Research Database (Denmark)

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

    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...... = 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 

  11. Zoledronic acid enhances Vδ2 T-lymphocyte antitumor response to human glioma cell lines.

    Science.gov (United States)

    Cimini, E; Piacentini, P; Sacchi, A; Gioia, C; Leone, S; Lauro, G M; Martini, F; Agrati, C

    2011-01-01

    Glioblastoma multiforme (GBM), the most frequent and aggressive primary brain tumor in humans, responds modestly to treatment: most patients survive less than one year after diagnosis, despite both classical and innovative treatment approaches. A recent paper focused on γδ T-cell response in GBM patients, suggesting the application of an immunomodulating strategy based on γδ T-cells which is already in clinical trials for other tumors. Human Vγ2 T-cells recognize changes in the mevalonate metabolic pathway of transformed cells by activating cytotoxic response, and by cytokine and chemokine release. Interestingly, this activation may also be induced in vivo by drugs, such as zoledronic acid, that induce the accumulation of Vγ2 T-cell ligand Isopentenyl-pyrophosphate by blocking the farnesyl pyrophosphate synthase enzyme. The aim of our work is to confirm whether bisphosphonate treatment would make glioma cell lines more susceptible to lysis by in vitro expanded γδ T-cells, improving their antitumor activity. We expanded in vitro human Vγ2 T-cells by phosphoantigen stimulation and tested their activity against glioma cell lines. Co-culture with glioma cells induced Vγ2 T-cell differentiation in effector/memory cells, killing glioma cells by the release of perforin. Interestingly, glioma cells were directly affected by zoledronic acid; moreover, treatment increased their activating ability on Vγ2 T-cells, inducing an effective antitumor cytotoxic response. Taken together, our results show that aminobisphosphonate drugs may play a dual role against GBM, by directly affecting tumor cells, and by enhancing the antitumor response of Vγ2 T-cells. Our results confirm the practicability of this approach as a new immunotherapeutic strategy for GBM treatment.

  12. 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

  13. 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 ...

  14. 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

  15. Lip ulceration associated with intravenous administration of zoledronic acid: report of a case.

    Science.gov (United States)

    Andreadis, Dimitrios; Mauroudis, Stergios; Poulopoulos, Athanasios; Markopoulos, Anastasios; Epivatianos, Apostolos

    2012-06-01

    Although osteonecrosis of the jaw is a well-known adverse reaction of bisphosphonates (BPs), random cases of oral mucosal ulceration after per os administration of BP-aledronate have been attributed to prolonged mucosal irritation. This report, for the first time, describes the mucosal ulceration related to intravenous use of zoledronic acid (ZA). A 52-year-old female patient presented with painful ulcers on both cutaneous/mucosal surfaces of the lower lip and a 2-month history of osteonecrosis of the mandible beside the right lower canine. Her medical record included intravenous administration of ZA for 10 months for primary breast cancer metastatic to bone. Examination of the peripheral blood showed severe anemia and a slightly increased white blood cell count, due to urinary tract infection by E. coli, but no evidence of a viral infection. The treatment of anemia and E. coli infection did not improve the labial ulcers. Biopsy from the mucosal lesion revealed a non-specific ulceration with moderate inflammatory infiltration. There was no evidence of infection or malignancy. ZA administration was discontinued and within 3 months the lesions were resolved after treatment with systemic antibiotics (amoxicillin), vitamins A and E, chlorexidine and H(2)O(2) (hydrogen peroxide) solutions and local pantothenic acid/vitamin A creams. Recurrence was detected a month after ZA re-administration. Nevertheless, after new treatment, the patient was free of oral/skin lesions 18 months later. This case, which is the first report of ulceration associated with intravenous administration of bisphosphonates, suggests that systemic mechanisms may be implicated in BP-induced oral mucosal ulceration. Furthermore, ZA appears to cause the same oral mucosal manifestations as alendronate. This emphasizes the need for oral examination in all cases of BP therapy, whether per os or intravenously administrated. PMID:22105344

  16. 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.

  17. 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

  18. Guided bone regeneration with local zoledronic acid and titanium barrier: An experimental study

    Science.gov (United States)

    Dundar, Serkan; Ozgur, Cem; Yaman, Ferhan; Cakmak, Omer; Saybak, Arif; Ozercan, Ibrahim Hanifi; Alan, Hilal; Artas, Gokhan; Nacakgedigi, Onur

    2016-01-01

    The aim of this study was to evaluate the effects on new bone formation of autogenous blood alone or in combination with zoledronic acid (ZA), a β-tricalcium phosphate (β-TCP) graft or ZA plus a β-TCP graft placed under titanium barriers. For this purpose, eight adult male New Zealand white rabbits were used in the study, each with four titanium barriers fixed around four sets of nine holes drilled in the calvarial bones. The study included four groups, each containing 2 rabbits. In the autogenous blood (AB group), only autogeneous blood was placed under the titanium barriers. The three experimental groups were the AB+ZA group, with autogenous blood plus ZA, the AB+β-TCP group, with autogeneous blood plus a β-TCP graft, and the AB+β-TCP+ZA group, with autogeneous blood plus a β-TCP graft and ZA mixture under the titanium barriers. The animals were sacrificed after 3 months. The amounts of new bone formation identified histomorphometrically were found to be higher after 3 months than at the time of surgery in all groups. The differences between the groups were examined with histomorphometric analysis, and statistically significant differences were identified at the end of the 3 months. The bone formation rate in the AB+β-TCP+ZA group was determined to be significantly higher than that in the other groups (P<0.05). In the AB+ZA and AB+β-TCP groups, the bone formation rate was determined to be significantly higher than that in the AB group (P<0.05). No statistically significant difference in bone formation rate was observed between the AB+β-TCP and AB+ZA groups. Local ZA used with autogeneous blood and/or graft material appears to be a more effective method than the use of autogeneous blood or graft alone in bone augmentation executed with a titanium barrier. PMID:27698687

  19. Mono- and Combined Therapy of Metastasizing Breast Carcinoma 4T1 with Zoledronic Acid and Doxorubicin.

    Science.gov (United States)

    Baklaushev, V P; Grinenko, N F; Yusubalieva, G M; Gubskii, I L; Burenkov, M S; Rabinovich, E Z; Ivanova, N V; Chekhonin, V P

    2016-08-01

    The efficiency of monotherapy with zoledronic acid (Resorba), doxorubicin, and their combination was studied on the model of metastasizing breast carcinoma in BALB/c mice. Doxorubicin monotherapy was accompanied by a significant increase in median survival up to 57 days (vs. 34 and 35 days in control groups); 27% animals survived for 90 days (duration of the study). Bioluminescence area of the primary tumor significantly decreased on days 21 and 28; the total number of visceral metastases also decreased according to magnetic-resonance imaging data. Resorba monotherapy produced no general toxic effect, the median survival increased to 64 days, and 90-day survival was 33%. Imaging techniques (magnetic-resonance imaging, microtomography, bioluminescent analysis) showed that Resorba delayed the development of the primary tumor (regression of luminescence area on days 21 and 28, regression of standardized bioluminescence intensity on day 28) and significantly reduced the number of visceral metastases in comparison with the control. Combination therapy was less effective than monotherapy with the same medications. Median survival was 55 days, 90-day survival was 13%, but magnetic-resonance imaging and bioluminescence analysis after combination therapy also showed delayed growth of the primary tumor and reduced number of visceral metastases. Microtomography revealed bone metastases in ~30% animals of the control group; in experimental groups, no bone metastases were found. The experiment with periosteal (distal epiphysis of the femur) injection of 4T1-Luc2 tumor cells demonstrated pronounced selective effectiveness of Resorba in relation to bone metastases. Monotherapy with Resorba can prevent the development of not only bone, but also visceral metastases of breast cancer. PMID:27590765

  20. 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;

    2009-01-01

    Background: Intravenous bisphosphonate therapy is associated with preservation of femoral head sphericity and congruence in 77% of children with traumatic avascular necrosis. The aim was to describe the systemic effects of intravenous zoledronic acid (ZA) on bone and mineral metabolism in otherwise....... Conclusion: We here report that ZA in otherwise healthy children with femoral head AVN increases BMD - most pronounced in the LCPD group - and reduces bone modeling and turnover. Further efficacy and safety data are required before this therapy can be widely recommended....

  1. 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...

  2. Effect of zoledronic acid injection combined with radiopharmaceutical 89SrCI2 therapy on the growth and clinical symptoms of lung cancer bone metastasis

    Institute of Scientific and Technical Information of China (English)

    Jia-Lun Zhu; Zhi-Yong Deng; Chuan-Zhou Yang

    2016-01-01

    Objective:To find the effect of zoledronic acid injection combined with radiopharmaceutical 89SrCI2 therapy on the growth and clinical symptoms of lung cancer bone metastasis.Methods: A total of 102 lung cancer patients with bone metastases were included in the study and randomly divided into observation group and control group (n=51) according to different treatment they received. Control group received zoledronic acid injection therapy alone, observation group received zoledronic acid injection combined with radiopharmaceutical 89SrCI2 therapy, and then differences in the growth of lung cancer bone metastasis, bone metabolism, tumor markers and alkaline phosphatase, pain score and pain-related mediator levels,etc. were compared between two groups.Results: Number of metastases of observation group after treatment was less than that of control group, and serum bone metabolism indexes OPG, BSP, TRACP-5b, ICTP and BAP levels, serum tumor markers CYFRA21-1, CEA, NSE, CA125 and BALP levels as well as serum pain-related mediators PGE2, ET-1 and TNF-α levels were lower than those of control group (P<0.05).Conclusions:Zoledronic acid injection combined with radiopharmaceutical89SrCI2 therapy can contain the growth of lung cancer bone metastasis, optimize bone metabolism state while alleviate patients’ perception of pain.

  3. Efficacy and Safety of Single Dose Zoledronic Acid for Osteoporosis in Frail Seniors: A Randomized Clinical Trial

    Science.gov (United States)

    Greenspan, Susan L.; Perera, Subashan; Ferchak, Mary Anne; Nace, David A.; Resnick, Neil M.

    2016-01-01

    Importance 85% of institutionalized elderly have osteoporosis, with fracture rates 8–9 fold higher than observed among community-dwelling elderly. Yet most are untreated and excluded from pivotal osteoporosis trials. Objective Determine the efficacy and safety of zoledronic acid in frail elderly women. Design 2-year, randomized, placebo-controlled, double-blinded study conducted between December 2007 and March 2012. Setting Nursing home and assisted living facilities. Participants 181 women ≥ age 65 with osteoporosis including those with cognitive impairment, immobility, and multimorbidity. Intervention One 5 mg dose of zoledronic acid or placebo IV and daily calcium and vitamin D. Main Outcomes (1) Hip and spine bone mineral density (BMD) at 12 and 24 months and (2) adverse events. Results There were no baseline differences in age (mean=85.4±0.6 years), BMD, or functional or cognitive status, but the treatment group included more subjects with frailty, falls history, diabetes, and anticonvulsant use. BMD was available for 87% of participants at 12 months and 73% at 24 months. BMD changes were greater in the treatment group (p< 0.01): 3.2 ± 0.7 and 3.9 ± 0.7 percentage point differences (mean ± SE) in the total hip at 12 and 24 months respectively, and 1.8 ± 0.7 and 3.6 ± 0.7 at the spine (p<0.01); adjusted analyses were similar. The treatment and placebo groups’ fracture rates were 20% and 16%, respectively (OR=1.30; 95% CI=0.61–2.78); mortality rates were 16% and 13% (OR=1.24; 95% CI=0.54–2.86). Groups did not differ in the proportion of single fallers (28% vs. 24%; OR=1.24; 95% CI=0.64–2.42; p=0.52) but more subjects in the treatment group had multiple falls (49% vs. 35%; OR=1.83; 95% CI=1.01–3.33; p=0.047); this was no longer significant when adjusted for baseline frailty. Conclusions and Relevance In this group of frail, osteoporotic women, one dose of zoledronic acid improved BMD over 2 years. The clinical importance of nonsignificant

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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)

  10. Zoledronic acid-encapsulating self-assembling nanoparticles and doxorubicin: a combinatorial approach to overcome simultaneously chemoresistance and immunoresistance in breast tumors.

    Science.gov (United States)

    Kopecka, Joanna; Porto, Stefania; Lusa, Sara; Gazzano, Elena; Salzano, Giuseppina; Pinzòn-Daza, Martha Leonor; Giordano, Antonio; Desiderio, Vincenzo; Ghigo, Dario; De Rosa, Giuseppe; Caraglia, Michele; Riganti, Chiara

    2016-04-12

    The resistance to chemotherapy and the tumor escape from host immunosurveillance are the main causes of the failure of anthracycline-based regimens in breast cancer, where an effective chemo-immunosensitizing strategy is lacking.The clinically used aminobisphosphonate zoledronic acid (ZA) reverses chemoresistance and immunoresistance in vitro. Previously we developed a nanoparticle-based zoledronic acid-containing formulation (NZ) that allowed a higher intratumor delivery of the drug compared with free ZA in vivo. We tested its efficacy in combination with doxorubicin in breast tumors refractory to chemotherapy and immune system recognition as a new combinatorial approach to produce chemo- and immunosensitization.NZ reduced the IC50 of doxorubicin in human and murine chemoresistant breast cancer cells and restored the doxorubicin efficacy against chemo-immunoresistant tumors implanted in immunocompetent mice. By reducing the metabolic flux through the mevalonate pathway, NZ lowered the activity of Ras/ERK1/2/HIF-1α axis and the expression of P-glycoprotein, decreased the glycolysis and the mitochondrial respiratory chain, induced a cytochrome c/caspase 9/caspase 3-dependent apoptosis, thus restoring the direct cytotoxic effects of doxorubicin on tumor cell. Moreover, NZ restored the doxorubicin-induced immunogenic cell death and reversed the tumor-induced immunosuppression due to the production of kynurenine, by inhibiting the STAT3/indoleamine 2,3 dioxygenase axis. These events increased the number of dendritic cells and decreased the number of immunosuppressive T-regulatory cells infiltrating the tumors.Our work proposes the use of nanoparticle encapsulating zoledronic acid as an effective tool overcoming at the same time chemoresistance and immunoresistance in breast tumors, thanks to the effects exerted on tumor cell and tumor-infiltrating immune cells. PMID:26980746

  11. 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

  12. 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.

  13. Can the microRNA expression profile help to identify novel targets for zoledronic acid in breast cancer?

    Science.gov (United States)

    Insalaco, Lavinia; Incorvaia, Lorena; Barraco, Nadia; Castiglia, Marta; Rizzo, Sergio; Santini, Daniele; Giordano, Antonio; Castorina, Sergio; Russo, Antonio

    2016-01-01

    Zoledronic acid (ZOL), belonging to third generation bisphosphonate family, is a potent inhibitor of osteoclast-mediated bone resorption, widely used to effectively prevent osteolysis in breast cancer patients who develop bone metastases. Low doses of ZOL have been shown to exhibit a direct anticancer role, by inhibiting cell adhesion, invasion, cytoskeleton remodelling and proliferation in MCF-7 breast cancer cells. In order to identify the molecular mechanisms and signaling pathways underlying the anticancer activity exerted by ZOL, we analyzed for the first time the microRNA expression profile in breast cancer cells. A large-scale microarray analysis of 377 miRNAs was performed on MCF7 cells treated with 10 μM ZOL for 24 h compared to untreated cells. Furthermore, the expression of specific ZOL-induced miRNAs was analyzed in MCF-7 and SkBr3 cells through Real-time PCR. Low-dose treatment with ZOL significantly altered expression of 54 miRNAs. Nine upregulated and twelve downregulated miRNAs have been identified after 24 h of treatment. Also, ZOL induced expression of 11 specific miRNAs and silenced expression of 22 miRNAs. MiRNA data analysis revealed the involvement of differentially expressed miRNAs in PI3K/Akt, MAPK, Wnt, TGF-β, Jak-STAT and mTOR signaling pathways, and regulation of actin cytoskeleton. Our results have been shown to be perfectly coherent with the recent findings reported in literature concerning changes in expression of some miRNAs involved in bone metastasis formation, progression, therapy resistance in breast cancer. In conclusion, this data supports the hypothesis that ZOL-induced modification of the miRNA expression profile contributes to the anticancer efficacy of this agent. PMID:27081088

  14. 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

  15. 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].

  16. Zoledronic acid inhibits the pentose phosphate pathway through attenuating the Ras-TAp73-G6PD axis in bladder cancer cells.

    Science.gov (United States)

    Wang, Xiaolin; Wu, Guang; Cao, Guangxin; Yang, Lei; Xu, Haifei; Huang, Jian; Hou, Jianquan

    2015-09-01

    Zoledronic acid (ZA) is the current standard of care for the therapy of patients with bone metastasis or osteoporosis. ZA inhibits the prenylation of small guanosine‑5'-triphosphate (GTP)‑binding proteins, such as Ras, and thus inhibit Ras signaling. The present study demonstrated that ZA inhibited cell proliferation and the pentose phosphate pathway (PPP) in bladder cancer cells. In addition, the expression of glucose‑6‑phosphate dehydrogenase (G6PD, the rate‑limiting enzyme of the PPP) was found to be inhibited by ZA. Furthermore, the stability of TAp73, which activates the expression G6PD was decreased in zoledronic acid treated cells. Decreased levels of Ras‑GTP and phosphorylated‑extracellular signal-regulated kinase 1/2 were also observed following treatment with ZA. This may be due to the fact that activated Ras was reported to stabilize TAp73 inducing its accumulation. The inhibition of Ras activity by PT inhibitor II also significantly reduced the levels of TAp73 and G6PD and the PPP flux. Moreover, knockdown of TAp73, attenuated the PPP flux and eliminated the affection of ZA on the PPP flux. In conclusion, it was proposed that ZA can inhibit stability of TAp73 and attenuate the PPP via blocking Ras signaling in bladder cancer cells.

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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, rs...

  2. Mechanism of cisplatin combined with zoledronic acid on lung cancer A549 cells%顺铂联合唑来膦酸对肺癌A549细胞增殖的影响及其机制

    Institute of Scientific and Technical Information of China (English)

    茆勇; 马凤锦; 黄朝晖; 许林; 游庆军; 华东

    2011-01-01

    Objective To investigate the function of cisplatin combined with Zoledronic acid on proliferation and mechanisms of A549 cells.Methods ( 1 ) Methyl thiazol tetrazolium (MTT) assay and Annexin V-FITC/PI double-staining flow cytometry were employed to observe the effects of cisplatin combined with Zoledronic acid upon anti-proliferation and apoptosis respectively.Reverse transcription-polymerase chain reaction (RT-PCR) was applied to assay mRNA expression of MDC1 among different groups.Results Inhibition of the cell proliferation was observed under the treatment of combined cisplatin and zoledronic acid (39.16 ±4.94)%,superior to the treatment of zoledronic acid ( 19.66 ±4.57)% or cisplatin ( 16.87 ± 2.50) %.Combined group induced A549 cells apoptosis ( 32.30 ± O.50 ) %,compared with cisplatin (23.90 ± 2.46) %,zoledronic acid ( 18.87 ± 3.04 ) %,the difference was statistically significant; cisplatin after zoledronic acid treatment of A549 cells M DC1 mRNA expression (0.134 ± 0.037 )was significantly decreased compared with single-drug,zoledronic acid ( 0.208 ± 0.040 ) and cisplatin (0.356 ± 0.033) ( P < 0.05 ).Conclusion Zoledronic acid or cisplatin can significantly inhibit A549 cell proliferation and markedly induce the apoptosis.Zoledronic acid and cisplatin in a synergistic way inhibited the cell proliferation and induced apoptosis on A549 cell.The downregulated expression level of MDC1 mRNA may involved in the mechanism of synergistic effect.%目的 观察顺铂联合唑来膦酸对肺癌A-549细胞增殖的影响并探讨其作用机制.方法 以噻唑蓝(MTT)比色法观察顺铂联合唑来膦酸对A549细胞增殖的影响,以Annexin-V/PI双染法检测细胞凋亡,逆转录-聚合酶链反应(RT-PCR)检测DNA损伤检查点蛋白调节因子1(MDC1)mRNA的表达.结果 顺铂联合唑来膦酸对A549细胞增殖的抑制率(39.16±4.94)%高于顺铂(16.87±2.50)%、唑来膦酸(19.66±4.57)%;联合用药诱导A549

  3. 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.

  4. The curative effect of zoledronic acid and pamidronic acid on treating ostealgia in malignant tumor with bone metastases and its side effects on serum calcium and phosphorus*%双膦酸盐对骨转移癌骨痛治疗及血清钙磷影响

    Institute of Scientific and Technical Information of China (English)

    Yuedi Dai; Meixing Wang; Li Tao; Anqi Li; Haixia Wu; Mi Xiao

    2011-01-01

    Objective: Bisphosphonates were widely used with the rate of malignant tumor with bone metastases increasing rapidly. The aim of this study was to evaluate zoledronic acid and pamidronic acid on treating ostealgia of malignant tumor with bone metastases and serum calcium, phosphorus and alkaline phosphorus movement. Methods: One Hundred cancer patients with bone metastases were diagnosed according to pathological and imaging methods. After zoledronic acid or pamidronic acid intravenous infusion one and two months, ostealgia degree, serum calcium, serum phosphorus and alkaline phosphorus were observed before bisphosphonates treatment, one and two months after treatment, respectively. Results:Ostealgia degree did not change significantly after diphosphonates treatment from one to two months (P > 0.05). The linear correlation between serum calcium and serum phosphorus on bone metastases cancer patients before therapy was dismissed after bisphosphonates treatment one month and did not recover in two months. The incidence of hypo-calcium after diphosphonate treatment one month (54%) and two months (56%) were significantly increased than that before treatment (36%) (x2 = 6.55, P = 0.011; x2 = 8.05, P = 0.005). Serum calcium and serum phosphorus were both decreased after treatment one month (t = 4.39, P = 0.000; t = 2.50, P = 0.014) and two months (t = 4.32, P = 0.000; t = 2.49, P = 0.010). There had no difference between zoledronic acid and pamidronic acid on treating of ostealgia and serum calcium and phosphorus changing.Conclusion: Zoledronic acid and pamidronic acid can relief ostealgia of cancer patients with bone metastases and induce hypo-calcium, break the linear relationship between calcium and phosphorus. There have no difference between zoledronic acid and pamidronic acid on treating ostealgia and inducing hypo-calcium and hypo-phosphorus.

  5. 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

    2013-01-01

    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.

  6. 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.

  7. 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

  8. 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

  9. 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

  10. Enhanced anti-tumor effect of zoledronic acid combined with temozolomide against human malignant glioma cell expressing O6-methylguanine DNA methyltransferase.

    Directory of Open Access Journals (Sweden)

    Junya Fukai

    Full Text Available Temozolomide (TMZ, a DNA methylating agent, is widely used in the adjuvant treatment of malignant gliomas. O6-methylguanine-DNA methyltranferase (MGMT, a DNA repair enzyme, is frequently discussed as the main factor that limits the efficacy of TMZ. Zoledronic acid (ZOL, which is clinically applied to treat cancer-induced bone diseases, appears to possess direct anti-tumor activity through apoptosis induction by inhibiting mevalonate pathway and prenylation of intracellular small G proteins. In this study, we evaluated whether ZOL can be effectively used as an adjuvant to TMZ in human malignant glioma cells that express MGMT. Malignant glioma cell lines, in which the expression of MGMT was detected, did not exhibit growth inhibition by TMZ even at a longer exposure. However, combination experiment of TMZ plus ZOL revealed that a supra-additive effect resulted in a significant decrease in cell growth. In combined TMZ/ZOL treatment, an increased apoptotic rate was apparent and significant activation of caspase-3 and cleavage of poly-(ADP-ribose polymerase were observed compared with each single drug exposure. There were decreased amounts of Ras-GTP, MAPK and Akt phosphorylation and MGMT expression in the ZOL-treated cells. Subcutanous xenograft models showed significant decrease of tumor growth with combined TMZ/ZOL treatment. These results suggest that ZOL efficaciously inhibits activity of Ras in malignant glioma cells and potentiates TMZ-mediated cytotoxicity, inducing growth inhibition and apoptosis of malignant glioma cells that express MGMT and resistant to TMZ. Based on this work, combination of TMZ with ZOL might be a potential therapy in malignant gliomas that receive less therapeutic effects of TMZ due to cell resistance.

  11. 载唑来膦酸胶原膜的制备及表征%Preparation of Zoledronic-acid-loaded Collagen Membrane

    Institute of Scientific and Technical Information of China (English)

    孟艳华; 梁星; 彭燕; 陈悦; 王航; 黄棣; 臧程程

    2010-01-01

    目的 制备一种载破骨细胞抑制剂的胶原屏障膜,评价其载药能力及药物释放性能.方法 用两种成品胶原膜(Bio-Gide膜与BME-10X膜)作为载体,吸附唑来膦酸(zoledronic acid,ZA),制备载ZA胶原膜.使用扫描电镜、X射线能谱、红外光谱、高效液相色谱,对其超微结构、官能团分布、药物释放性能进行表征.结果 载药后,Bio-Gide膜胶原纤维表面缝隙消失,BME-10X膜纤维表面出现类晶体样物质.两种膜内均出现了磷元素的谱峰,其酰胺集团吸收峰出现偏移.同等载药条件下,Bio-Gide膜比BME-10X膜拥有更高的载药量和ZA缓释量.载药处理不会影响胶原膜的纤维排列及降解性能.结论 两种胶原膜均具有一定的载ZA及ZA缓释能力.两种胶原膜相比,Bio-Gide膜比BME-10X膜具有更好的载药及缓释性能.

  12. 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

  13. 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;

    2012-01-01

    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......, n=20) for 18 month in an open label, non-randomized study. A group of postmenopausal osteoporotic women receiving zoledronic acid (5 mg infusion once yearly, n=33) was also included. Anabolic therapy increased cortical porosity in radius (PTH 1-34 32±37%, PTH 1-84 39±32%, both p...

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 5-Caffeoylquinic acid and caffeic acid orally administered suppresses P-selectin expression on mouse platelets

    Science.gov (United States)

    Caffeic acid and 5-caffeoylquinic acid are a naturally occurring phenolic acid and its ester found in human diets. In this paper, potential effects of caffeic acid and 5-caffeoylquinic acid found in coffee and other plant sources on platelet activation were studied via investigating P-selectin expre...

  1. 唑来膦酸、降钙素对骨生化标志物BAP、N-MID、β-CTX的影响%Effect of zoledronic acid and calcitonin on bone metabolic biochemical markers, BAP, N-MID, and β-CTX

    Institute of Scientific and Technical Information of China (English)

    孔西建; 吴丹; 叶进; 廉杰

    2013-01-01

    目的 通过监测绝经后骨质疏松症患者使用唑来膦酸、降钙素治疗前后骨代谢生化标志物的变化来分析二者对骨代谢的影响.方法 回顾性分析绝经后骨质疏松症病例115例,55例使用唑来膦酸(5mg静滴一次),60例使用鲑鱼降钙素(50IU隔日一次肌注,治疗90日),检测每个病例治疗前和开始治疗后4周、8周、12周的BAP、N-MID、β-CTX,并进行统计学分析.结果 降钙素组治疗4周后BAP、β-CTX与治疗前相比降低(P<0.05),骨转换率降低;治疗8周、12周后β-CTX仍明显降低(P<0.05),但BAP与治疗前相比变化无统计学意义;唑来膦酸组治疗4周、8周后BAP、N-MID、β-CTX与治疗前相比均明显降低(P<0.05),骨转换率明显降低;治疗后12周后BAP、β-CTX仍明显降低(P<0.05);与降钙素组相比,唑来膦酸组治疗后4周、8周BAP、N-MID、β-CTX降低更明显(P<0.05),骨转换率降低更明显;治疗后12周BAP、β-CTX仍明显降低(P<0.05).两种药物均具有较好的安全性.结论 降钙素组、唑来膦酸组均可有效抑制骨吸收,降低骨转换率;与降钙素相比,唑来膦酸抑制骨吸收的作用更迅速、更稳定,病人低骨转换持续时间更久.%Objective To analyze the effect of zoledronic acid or calcitonin on bone metabolism by monitoring the changes of bone metabolic markers before and after the treatment of zoledronic acid or calcitonin in patients with postmenopausal osteoporosis. Methods The data of 115 patients with postmenopausal osteoporosis was analyzed retrospectively. Fifty-five patients were treated with zoledronic acid ( 5mg intravenous drip once ). Sixty patients were treated with salmon calcitonin ( 50U intramuscular injection every other day, lasting for 90 days ). BAP, N-MID , and β-CTX was tested before and 4-, 8-, and 12-week after the treatment. All the results were analyzed statistically. Result BAP and β-CTX in patients in calcitonin treatment group after 4-week treatment were

  2. Excitability scores of goats administered ascorbic acid and transported during hot-dry conditions.

    Science.gov (United States)

    Ayo, J O; Minka, N S; Mamman, M

    2006-06-01

    In this study, we investigated the effect of ascorbic acid (AA) administration on goat excitability due to transportation. Ten goats administered AA (p.o.) at 100 mg/kg of body weight before transportation served as the experimental group, and seven goats administered only 10 ml/kg of sterile water (p.o.) served as controls. Excitability scores were recorded for each goat; when weighed, before, immediately after, and 3 h after 8 h of transportation. A score of one to four was allocated to each goat; higher scores represent greater excitability. Immediately after transportation, excitability scores decreased significantly, especially those of control goats (p 0.05) different from their pre-transportation normal values, whereas those of control goats were significantly lower (p < 0.01). The correlation i.e. the relationship between excitability score values and percent excitability (percentage of goat with particular excitability score) for different excitability score group 3 h post-transportation was positive and highly significant (p < 0.001), in both experimental and control goats. Our results indicate that road transportation induces considerable stress (depression) in goats as evidenced by a lower excitability score posttransportation. Moreover, the administration of AA pretransportation facilitated the transition from a state of depression to excitation. In conclusion, AA administration to animals prior to transportation may ameliorate the depression often encountered after road transportation.

  3. The fate of the orally administered bile acid sequestrant, polidexide, in humans.

    Science.gov (United States)

    Simons, L A

    1976-01-01

    1. The metabolic fate of the insoluble bile acid sequestrant polidexide, (poly-[2-(diethylamino)ethyl] polyglycerylenedextran hydrochloride), was studied in four adult humans following the oral administration of the 14C-labelled substance. 2. The mean cumulative recovery of 14C in faeces was 95-3% (s.e.m. = 1-1) of the administered dose, while mean cumulative recovery in urine was 0-37% (s.e.m. = 0-13) of the oral dose. 3. Only background levels of radioactivity were detectable in plasma samples taken 1-3 days after administration of tracer. 4. The findings suggested that polidexide was not absorbed from the gastrointestinal in man to any significant degree.

  4. 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.

  5. Pharmacokinetic and pharmacodynamic modelling of marbofloxacin administered alone and in combination with tolfenamic acid in goats.

    Science.gov (United States)

    Sidhu, P K; Landoni, M F; Aliabadi, F S; Lees, P

    2010-05-01

    In a four-period cross-over study, the fluoroquinolone antibacterial drug marbofloxacin (MB) was administered to goats intramuscularly (IM) at a dose rate of 2 mg/kg, both alone and in combination with the non-steroidal anti-inflammatory drug tolfenamic acid (TA), also administered IM at a dose rate of 2 mg/kg. Using a tissue cage model of inflammation, based on the irritant actions of carrageenan, the pharmacokinetics (PK) of MB and MB in combination with TA were determined. MB mean values of area under concentration-time curve (AUC) were similar for serum (5.60 microg h/mL), inflamed tissue cage fluid (exudate; 5.32 microg h/mL) and non-inflamed tissue cage fluid (transudate; 4.82 microg h/mL). Values of mean residence time (MRT) of MB in exudate (15.5 h) and transudate (15.8 h) differed significantly from serum MRT (4.23 h). Co-administration of TA did not affect the PK profile of MB. The pharmacodynamics of MB were investigated using a caprine strain of Mannheimia haemolytica. Integration of PK data with ex vivo bacterial time-kill curve data for serum, exudate and transudate provided AUC(24h)/minimum inhibitory concentration (MIC) ratios of 160, 133 and 121 h, respectively, for the strain of organism used. Modelling of the ex vivo time-kill data to the sigmoid E(max) equation provided AUC(24h)/MIC values required for bacteriostatic and bactericidal actions of MB and for virtual eradication of the organism of 27.6, 96.2 and 147.3 h, respectively. Corresponding values for MB+TA were 20.5, 66.5 and 103.0 h. These data were used to predict once daily dosage schedules of MB for subsequent clinical evaluation.

  6. 唑来膦酸联合化疗治疗多发性骨髓瘤的系统评价%Zoledronic Acid Combined with Chemotherapy for Multiple Myeloma: a Systematic Review

    Institute of Scientific and Technical Information of China (English)

    柳汝明; 钱懿轶; 何瑾; 张峻

    2012-01-01

    目的:系统评价唑来膦酸联合化疗治疗多发性骨髓瘤(MM)的有效性和安全性.方法:计算机检索PubMed、Cochrane图书馆、EMbase、ISI Web of Knowledge、中国知网学术文献总库(CNKI)、中文科技期刊全文数据库(维普)、中国生物医学数据库(CBM)、万方数据库,按Cochrane Handbook 5.0推荐的方法评价纳入研究的质量,并进行Meta分析.结果:共纳入6项研究,合计267例患者.Meta分析结果显示,联合组骨相关事件发生率低于单纯组[RR=0.45,95%CI(0.24,0.85),P=0.01],患者的完全缓解率高于单纯组[RR=3.83,95%CI(1.14,12.84),P=0.03],骨痛缓解总有效率高于单纯组[RR=1.34,95%CI(1.04,1.75),P=0.03],2组比较差异均有统计学意义;联合组不良反应发生率较单纯组高[RR=5.20,95%CI(1.74,15.49),P=0.003],2组比较差异有统计学意义.结论:唑来膦酸联合化疗可减少MM患者骨相关事件,提高完全缓解率,缓解患者骨痛,但不良反应发生率也较高.由于纳入研究存在方法学质量问题,此结论尚待高质量、大样本随机对照试验进一步证实.%OBJECTIVE: To evaluate the effectiveness and safety of zoledronic acid combined with chemotherapy vs. chemotherapy alone in the treatment of multiple myeloma systematically. METHODS: The literatures were retrieved from PubMed, Co-chrane library, EMbase, ISI Web of Knowledge, CNKI, VIP, CBM, Wanfang database. The qualities of included studies were evaluated according to Cochrane handbook 5.0, and Meta-analysis was performed. RESULTS: 6 RCT were included in this study, with a total of 267 patients. Meta-analysis showed that the incidence of skeletal-related events in combination group was lower than in pure therapy group[RR= 0.45, 95%CI(0.24, 0.85), P=0.01], while complete remission rate[RR= 3.83, 95%CI(1.14, 12.48), P=0.03] and pain relief rate [RR=1.34, 95%CI(1.04, 1.75), P=0.03]were higher than in pure therapy group, there were statistically significance between 2

  7. Analysis on the curative effect of combination therapy with zoledronic acid and 89SrCL2 on bone tumor with breast cancer metastasis%89SrCL2与唑来膦酸联合治疗乳腺癌转移性骨肿瘤的疗效分析

    Institute of Scientific and Technical Information of China (English)

    刘超; 邓智勇; 刘鹏杰; 贾莉

    2014-01-01

    Objective To discuss the clinical effects of radionuclide 89SrCl2 combined zoledronic acid treatment for hormone dependent breast neoplasm metastatic osteoma. Methods Clinical data of 64 patients with hormone dependent breast neoplasm metastatic osteoma were analyzed retrospectively. All of these patients were divided into 3 groups:one group of 22 cases treated with 89SrCl2(89SrCl2 group);another group of 21 cases treated with zoledronic acid(zoledronic acid group);and the last group of 21 cases treat-ed with 89SrCl2 and zoledronic acid(combination group). Then patients′metastatic lesion curative effects, the condition of bone pain remission, quality of life and bone marrow inhibitory reaction after treatment were observed. Results The effective rate, visual analogue scale decline rate, whole body KPS score in-crease rate and bone marrow inhibitory reaction rate of the 89SrCl2 group were 36.4%(8/22), 77.3%(17/22), 63.6%(14/22), 27.2%(6/22), and which were 33.3%(7/21), 71.4%(15/21), 52.4%(11/21), 19.0%(4/21) and 42.9%(9/21), 90.5%(19/21), 90.5%(19/21), 33.3%(7/21) in zoledronic acid group and combination group respectively. Conclusion 89SrCl2 combined with zoledronic acid on treating hormone dependent breast neoplasm metastatic osteoma has significant curative effect, and can relieve pain with less adverse reactions, and the combined treatment effects are better than that of 89SrCl2 or zoledronic acid alone.%目的:探讨放射性核素二氯化锶(89SrCl2)联合唑来膦酸治疗激素依赖型乳腺癌转移性骨肿瘤的临床疗效。方法回顾性分析64例激素依赖型乳腺癌转移性骨肿瘤患者的临床资料,将所有患者分为3组:89SrCl2治疗组22例;唑来膦酸治疗组21例;89SrCl2联合唑来膦酸治疗组21例;观察治疗后转移病灶疗效、骨痛缓解情况、生活质量状况、骨髓抑制反应情况。结果89SrCl2治疗骨转移病灶有效率为36.4%(8/22),视觉模拟评分下降率为77.3%(17

  8. Immunotoxicity of dibromoacetic acid administered via drinking water to female B₆C₃F₁ mice.

    Science.gov (United States)

    Smith, Matthew J; Germolec, Dori R; Luebke, Robert W; Sheth, Christopher M; Auttachoat, Wimolnut; Guo, Tai L; White, Kimber L

    2010-01-01

    Dibromoacetic acid (DBA) is a disinfection by-product commonly found in drinking water as a result of chlorination/ ozonation processes. The Environmental Protection Agency estimates that more than 200 million people consume disinfected water in the United States. This study was conducted to evaluate the potential immunotoxicological effects of DBA exposure when administered for 28 days via drinking water to B₆C₃F₁ mice, at concentrations of 125, 500, and 1000 mg/L. Multiple endpoints were evaluated to assess innate, humoral, and cell-mediated immune components, as well as host resistance. Standard toxicological parameters were unaffected, with the exception of a dose-responsive increase in liver weight and a decrease in thymus weight at the two highest exposure levels. Splenocyte differentials were affected, although the effects were not dose-responsive. Exposure to DBA did not significantly affect humoral immunity (immunoglobulin M [IgM] plaque assay and serum IgM anti-sheep erythrocyte titers) or cell-mediated immunity (mixed-leukocyte response). No effects were observed on innate immune function in either interferon-γ-induced in vitro macrophage cytotoxic activity or basal natural killer (NK)-cell activity. Augmented NK-cell activity (following exposure to polyinosinic-polycytidylic acid) was decreased at the low dose, however the effect was not dose-responsive. Finally, DBA exposure had no effect on resistance to infection with either Streptococcus pneumoniae or Plasmodium yoelii, or challenge with B16F10 melanoma cells. With the exception of changes in thymus weight, these results indicate that DBA exposure resulted in no immunotoxic effects at concentrations much larger than those considered acceptable in human drinking water.

  9. Pharmacokinetic and pharmacodynamic modelling of marbofloxacin administered alone and in combination with tolfenamic acid in calves.

    Science.gov (United States)

    Sidhu, P K; Landoni, M F; Aliabadi, M H S; Toutain, P L; Lees, P

    2011-08-01

    In a four-period, cross-over study, the fluoroquinolone antibacterial drug marbofloxacin (MB) was administered to calves, alone and in combination with the nonsteroidal anti-inflammatory drug tolfenamic acid (TA). Both drugs were administered intramuscularly (IM) at doses of 2 mg/kg. A tissue cage model of inflammation, based on the actions of the mild irritant carrageenan, was used to evaluate the pharmacokinetics (PK) of MB and MB in combination with TA. MB mean values of area under concentration-time curve (AUC) were 15.1 μg·h/mL for serum, 12.1 μg·h/mL for inflamed tissue cage fluid (exudate) and 9.6 μg·h/mL for noninflamed tissue cage fluid (transudate). Values of C(max) were 1.84, 0.35 and 0.31 μg/mL, respectively, for serum, exudate and transudate. Mean residence time (MRT) of 23.6 h (exudate) and 22.6 h (transudate) also differed significantly from serum MRT (8.6 h). Co-administration of TA did not affect the PK profile of MB. The pharmacodynamics of MB was investigated using a bovine strain of Mannheimia haemolytica. Time-kill curves were established ex vivo on serum, exudate and transudate samples. Modelling the ex vivo serum time-kill data to the sigmoid E(max) equation provided AUC(24 h) /MIC values required for bacteriostatic (18.3 h) and bactericidal actions (92 h) of MB and for virtual eradication of the organism was 139 h. Corresponding values for MB + TA were 20.1, 69 and 106 h. These data were used to predict once daily dosage schedules for a bactericidal action, assuming a MIC(90) value of 0.24 μg/mL, a dose of 2.6 mg/kg for MB and 2.19 mg/kg for MB + TA were determined, which are similar to the currently recommended dose of 2.0 mg/kg.

  10. Effects of Zoledronate on Mortality and Morbidity after Surgical Treatment of Hip Fractures

    Science.gov (United States)

    Cengiz, Ömer; Polat, Gökhan; Karademir, Gökhan; Tunç, Oytun Derya; Erdil, Mehmet; Tuncay, İbrahim; Şen, Cengiz

    2016-01-01

    We aimed to evaluate the effects of intertrochanteric femoral fractures on mortality, morbidity, and cost of zoledronate treatment in elderly patients treated by osteosynthesis. Based on Evans classification, 114 patients with unstable intertrochanteric femoral fractures were treated with osteosynthesis. After the surgical treatment of intertrochanteric fractures, the treatment group (M/F, 24/32; mean age, 76.7 ± SD years) received zoledronate infusion, and the control group (M/F, 20/38; mean age, 80.2 ± SD years) received placebo. Postoperative control visits were performed at 6-week, 3-month, 6-month, and 12-month time points. Functional level of patients was evaluated by the modified Harris hip score and Merle d'Aubigné hip score. By 12 months, the mean HHS in treatment and control groups was 81.93 and 72.9, respectively. For time of death of the patients, mortality was found to be 57.1% (16/28) on the first 3 months and 92.9% (26/28) on the first six months. The mortality rate in the treatment and control groups was 14.3% (8/56) and 34.5% (20/58), respectively. The use of zoledronic acid after surgical treatment of intertrochanteric femoral fractures in osteoporotic elderly patients is a safe treatment modality which helps to reduce mortality, improves functional outcomes, and has less side effects with single dose use per year. PMID:27092280

  11. 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 ...

  12. 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

  13. 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

  14. 唑来膦酸治疗老年男性原发性骨质疏松的临床效果评估%Assessment of Clinical Efficacy of Zoledronic Acid for the Treatment of Elderly Male Patients with Primary Osteoporosis

    Institute of Scientific and Technical Information of China (English)

    熊茂强; 陈宇; 罗展标

    2014-01-01

    [Objective]To evaluate clinical efficacy of zoledronic acid for the treatment of elderly male pa-tients with primary osteoporosis.[Methods]A total of 76 male patients with primary osteoporosis were ran-domly divided into 2 groups.The control group(n=39)was supplemented with calcium and vitamin D daily, while the treatment group(n=37)was given an intravenous drip infusion of zoledronic acid 5mg once based on the treatment of control group.The changes of bone mineral density and bone metabolism markers of all pa-tients were observed after 1 2 months of follow up.[Results]Bone mineral density of lumbar spine,total hip and femoral neck in treatment group was significantly higher than that in control group.Serum levels of bone metabolism markers such asβ-C-terminal telopeptide of type I collagen(β-CTx),procollagen type I N-terminal propeptide(PINP)and bone-specific alkaline phosphatase(BSAP)in treatment group were significantly lower than those in control group(P0.05).[Conclusion]Zoledronic acid treatment for 1 year can markedly increase bone mineral density,decrease serum levels of bone metabolism markers and reduce the risk of fracture in elderly male patients with primary osteoporosis.%【目的】评估唑来膦酸治疗老年男性原发性骨质疏松患者的临床效果。【方法】将76名年龄≥70岁的男性原发性骨质疏松患者随机分为两组。对照组(n=39)每日补充钙剂和维生素D,治疗组(n=37)在对照组的基础上给予一次静脉滴注唑来膦酸5 mg。随访12个月后观察所有研究对象骨密度和骨代谢标记物水平变化。【结果】治疗组的椎骨、全髋骨和股骨颈骨密度均显著高于对照组(P<0.05);血液骨代谢标记物β-CTx、PINP和BSAP水平则显著低于对照组(P <0.05),两组严重不良反应发生率分别为24.32%和23.08%,差异无统计学意义(P>0.05)。【结论】唑来膦酸治疗一年后可以显著提高患者骨

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. Haematology and behaviour of pullets transported by road and administered with ascorbic acid during the hot-dry season.

    Science.gov (United States)

    Minka, N S; Ayo, J O

    2008-10-01

    The effects of ascorbic acid (AA) on pullets transported by road for 6h during the hot-dry season were investigated. Forty Shika Brown pullets administered orally with AA just before transportation served as experimental, while another 40 pullets given sterile water only served as control. Blood samples analyzed before and after transportation in control pullets showed a decrease (P0.05) from those obtained pre-transportation. The result showed that the transportation was stressful in control pullets. The behavioural activities of the pullets' post-transportation period indicated that AA facilitated the transition of the state of depression that followed excitation back to excitation immediately after transportation. In conclusion, AA administration ameliorated the adverse effect of road transportation stress during the hot-dry season.

  1. 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

  2. Zoledronic Acid Incorporated in Chitosan/Calcium Phosphate Ceramic: Characterization and in vitro Response of Osteoblast Cells%载唑来膦酸壳聚糖/磷酸钙陶瓷表征及对成骨细胞的影响

    Institute of Scientific and Technical Information of China (English)

    臧程程; 滕敏华; 翟浚江; 廖运茂; 廖健; 孙宁远; 梁星

    2012-01-01

    Objective To develop a new local delivery system, zoledronic-acid-loaded chitosan/calcium phosphate ceramic, and to determine its characterization and in vitro response of osteoblast cells. Methods Zoledronic-acid-loaded chitosan/calcium phosphate ceramic were prepared by solution casting method at a concentration of 10-5, 10-4, and 10-3 mol/L, respectively. The physicochemical properties of the resulting materials were determined using SEM and FTIR. Drug absorbance was measured using CCK-8 colorimetric assay and alkaline phosphatase assay to detect the effect of drug-loaded materials on the proliferation and differentiation of osteoblasts. Results After ZOL loading, SEM showed that porous calcium phosphate ceramic was coated with chitosan evenly. The IR spectra indicated that drug absorption peaks were shifted and a new one was formed for the drug-loaded biomaterials. The material at the highest concentration could inhibit the proliferation and alkaline phosphatase activities of osteoblast cells, but no such effect was found at a drug-loading concentration of 10-4-10-5 mol/L. Conclusion We confirmed that the local delivery system in this study has ability of loading ZOL. The biomaterial with high drug concentrations inhibits the proliferation and differentiation of osteoblasts, but not when the drug concentrations are low.%目的 研制一种载唑来膦酸(ZOL)的壳聚糖/磷酸钙陶瓷材料,并对其表征及对成骨细胞的影响进行探讨.方法 使用溶剂蒸发法制备载ZOL浓度分别为10-5、10-4、10-3 mol/L的壳聚糖/磷酸钙陶瓷材料.使用扫描电镜和红外光谱对其超微结构和官能团分布进行分析.并检测载药材料在第1、3、5、7d对大鼠成骨细胞增殖和碱性磷酸酶活性的影响.结果 扫描电镜结果显示,壳聚糖可以较均匀覆盖于多孔陶瓷表面.各浓度载药材料的红外光谱波峰有偏移,且有新波峰出现.较高浓度(10-3 mol/L)的ZOI载药材料明显抑制成骨细

  3. 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

  4. Toxicity of 50-nm polystyrene particles co-administered to mice with acetaminophen, 5-aminosalicylic acid or tetracycline.

    Science.gov (United States)

    Isoda, K; Nozawa, T; Tezuka, M; Ishida, I

    2014-09-01

    We investigated whether nano-sized polystyrene particles affect drug-induced toxicity. The particles, which are widely used industrially, had diameters of 50 (NPP50), 200 (NPP200) or 1000 (NPP1000) nm. The toxic chemicals tested were acetaminophen (APAP), 5-aminosalicylic acid (5-ASA), tetracycline (TC), and sodium valproate (VPA). All treatments in the absence of the nanoparticles were non-lethal and did not result in severe toxicity. However, when mice were injected with APAP, 5-ASA or TC together with polystyrene particles, synergistic, enhanced toxicity was observed in mice injected with NPP50. These synergic effects were not observed in mice co-injected with NPP200 or NPP1000. On the other hand, co-administration of VPA and NPP50, NPP200 or NPP1000 did not elevate toxicity. The results show that NPP50 differs in hepatotoxicity depending on the drug co-administered. These findings suggest that further evaluation of the interactions between polystyrene nanoparticles and drugs is a critical prerequisite to the pharmaceutical application of nanotechnology.

  5. 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...

  6. 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

  7. 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...

  8. 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

  9. 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.

  10. 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...

  11. 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

  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. Rectal temperature responses of donkeys administered with ascorbic acid and subjected to load carrying (packing) during the harmattan season in Nigeria.

    Science.gov (United States)

    Olaifa, Folashade; Ayo, Joseph Olusegun; Ambali, Suleiman Folorunsho; Rekwot, Peter Ibrahim; Minka, Ndazo Salka

    2013-02-01

    The aim of the experiment was to evaluate the effect of 4-h load carrying (packing) on donkeys administered with ascorbic acid (AA) during the harmattan season. Six donkeys administered orally with ascorbic acid (200 mg/kg) and subjected to packing served as experimental animals, while six others given only distilled water served as control animals. The rectal temperature (RT) of each donkey and dry-bulb temperature (DBT) and relative humidity (RH) of the research pen were recorded at 0600 hours pre-packing; while post-packing, the values were obtained at 1430, 1600 and 1800 hours. The DBT values (ranges) recorded before, during and after packing were 13.7 ± 1.3 °C (11-15 °C), 28.4 ± 1.0 °C (22.7-30.3 °C) and 30.6 ± 3.0 °C (19.8-45 °C), respectively. The highest temperature-humidity index (THI) of 83.4 ± 6.9 was obtained at 1430 hours after packing, and the value decreased to 64.2 ± 5.8 at 1800 hours. The thermal environmental conditions were outside the thermoneutral zone for the donkeys. The RT values recorded immediately after packing did not differ (P > 0.05) in experimental and control donkeys; but at 1600 and 1800 hours, values obtained in control donkeys (38.48 ± 0.12 and 38.12 ± 0.12 °C, respectively) were significantly higher (P < 0.05) than those recorded in experimental donkeys (38.16 ± 0.14 and 37.85 ± 0.14 °C, respectively). In conclusion, administration of ascorbic acid reduced the rise in RT due to packing and may be of value in the amelioration of adverse effects of heat stress associated with work in donkeys.

  14. Assessment of thermal load on transported goats administered with ascorbic acid during the hot-dry conditions.

    Science.gov (United States)

    Minka, N S; Ayo, J O

    2012-03-01

    The major factor in the induction of physiological stress during road transportation of livestock is the complex fluctuations of the thermal transport microenvironment, encountered when animals are transported across different ecological zones. Recommended guidelines on optimum "on-board" conditions in which goats should be transported are lacking, and there are no acceptable ranges and limits for the thermal loads to which goats may be subjected during long-distance road transportation in hot-dry conditions. Panting score (PS), rectal temperature (RT), heart rate (HR) and respiratory rate (RR) were employed as reliable stress indices to assess the effects of different thermal loads, measured as temperature humidity index (THI), encountered in the vehicle during 12 h of road transportation of 40 goats, and to suggest the administration of 100 mg/kg body weight of ascorbic acid (AA) as an ameliorating agent. The results obtained showed that the PS, RT, HR and RR rose above normal reference values with increase in the THI and journey duration. The rise in PS value, which is a visual indicator of the severity of thermal load, was the most pronounced. The results suggest that values of THI in the vehicle up to 94.6 constitute no risk, while at of 100 it presents a moderate risk and above 100 may result in severe stress. The relationships between the thermal load and the physiological variables were positive and significant (P < 0.05). They reflect the degree of stress imposed by each THI value during the transportation, and may be used as recommended ranges and limit thermal load values in transported goats. The results demonstrated that administration of 100 mg/kg body weight of AA before road transportation mitigated the risk of adverse effects of high THI values and other stress factors due to road transportation in goats.

  15. Assessment of thermal load on transported goats administered with ascorbic acid during the hot-dry conditions

    Science.gov (United States)

    Minka, N. S.; Ayo, J. O.

    2012-03-01

    The major factor in the induction of physiological stress during road transportation of livestock is the complex fluctuations of the thermal transport microenvironment, encountered when animals are transported across different ecological zones. Recommended guidelines on optimum "on-board" conditions in which goats should be transported are lacking, and there are no acceptable ranges and limits for the thermal loads to which goats may be subjected during long-distance road transportation in hot-dry conditions. Panting score (PS), rectal temperature (RT), heart rate (HR) and respiratory rate (RR) were employed as reliable stress indices to assess the effects of different thermal loads, measured as temperature humidity index (THI), encountered in the vehicle during 12 h of road transportation of 40 goats, and to suggest the administration of 100 mg/kg body weight of ascorbic acid (AA) as an ameliorating agent. The results obtained showed that the PS, RT, HR and RR rose above normal reference values with increase in the THI and journey duration. The rise in PS value, which is a visual indicator of the severity of thermal load, was the most pronounced. The results suggest that values of THI in the vehicle up to 94.6 constitute no risk, while at of 100 it presents a moderate risk and above 100 may result in severe stress. The relationships between the thermal load and the physiological variables were positive and significant ( P < 0.05). They reflect the degree of stress imposed by each THI value during the transportation, and may be used as recommended ranges and limit thermal load values in transported goats. The results demonstrated that administration of 100 mg/kg body weight of AA before road transportation mitigated the risk of adverse effects of high THI values and other stress factors due to road transportation in goats.

  16. 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 ...

  17. 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

  18. 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

  19. 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

  20. 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

  1. Time-and pH-dependent colon-specific drug delivery for orally administered diclofenac sodium and 5-aminosalicylic acid

    Institute of Scientific and Technical Information of China (English)

    Gang Cheng; Feng An; Mei-Juan Zou; Jin Sun; Xiu-Hua Hao; Yun-Xia He

    2004-01-01

    AIM: To investigate Time- and pH-dependent colon-specific drug delivery systems (CDDS) for orally administered diclofenac sodium (DS) and 5-aminosalicylic acid (5-ASA), respectively.METHODS: DS tablets and 5-ASA pellets were coated by ethylcellulose (EC) and methacrylic acid copolymers (Eudragit[] L100 and S100), respectively. The in vitro release behavior of the DS coated tablets and 5-ASA coated pellets were examined, and then in vivo absorption kinetics of DS coated tablets in dogs were further studied.RESULTS: Release profile of time-dependent DS coated tablets was not influenced by pH of the dissolution medium,but the lag time of DS release was primarily controlled by the thickness of the coating layer. The thicker the coating layer, the longer the lag time of DS release is. On the contrary, in view of the pH-dependent 5-ASA coated pellets,5-ASA release was significantly governed by pH. Moreover,the 5-ASA release features from the coated pellets depended upon both the combination ratio of the Eudragit[] L100 and S100 pH-sensitive copolymers in the coating formulation and the thickness of the coating layer. The absorption kinetic studies of the DS coated tablets in dogs demonstrated that in vivo lag time of absorption was in a good agreement with in vitro lag time of release.CONCLUSION: Two types of CDDS, prepared herein by means of the regular coating technique, are able to achieve site-specific drug delivery targeting at colon following oral administration, and provide a promising strategy to control drug release targeting the desired lower gastrointestinal region.

  2. 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.

  3. 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...

  4. 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

  5. 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

    . In the 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...... of the nervous system. Methods: Pregnant rats were fed experimental diets from the 8th day of pregnancy throughout lactation. After weaning and until 13 weeks of age, the pups were fed the same diet as their dams. The experimental diets contained either a structured oil, a linseed oil, or a fish oil...... 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...

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. A dual-isotope-labeling method of studying the bioavailablity of hexaglutamyl folic acid relative to that of monoglutamyl folic acid in humans by using multiple orally administered low doses

    NARCIS (Netherlands)

    Boonstra, A.; Verhoef, P.; West, C.E.; Rhijn, van J.A.; Breemen, van R.B.; Lasaroms, J.J.P.; Garbis, S.D.; Katan, M.B.; Kok, F.J.

    2006-01-01

    Background: The bioavailability of dietary folate may be hampered by the need of the glutamate moieties to be deconjugated before absorption. Previous studies comparing the bioavailabilities of polyglutamyl and monoglutamyl folic acid had inconsistent results. Objective: The objective was to estimat

  11. Biomarkers in Tissue Samples From Patients With Newly Diagnosed Breast Cancer Treated With Zoledronic Acid

    Science.gov (United States)

    2016-07-12

    Estrogen Receptor-positive Breast Cancer; Invasive Ductal Breast Carcinoma; Progesterone Receptor-positive Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

  12. 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

  13. Systemic but no local effects of combined zoledronate and parathyroid hormone treatment in experimental autoimmune arthritis.

    Directory of Open Access Journals (Sweden)

    Kresten Krarup Keller

    Full Text Available INTRODUCTION: Local bone erosions and osteoporosis in rheumatoid arthritis (RA are the result of a more pronounced bone resorption than bone formation. Present treatment strategies for RA inhibit inflammation, but do not directly target bone erosions. The aim of the study was in experimental arthritis to investigate the juxtaarticular and systemic effects of simultaneous osteoclast inhibition with zoledronate (ZLN and osteoblast stimulation with parathyroid hormone (PTH. METHODS: Arthritis was induced in 36 SKG mice. The mice were randomized to three treatment groups and an untreated group: ZLN, PTH, PTH+ZLN, and untreated. Arthritis score and ankle width measurements were performed. Histological sections were cut from the right hind paw, and design-based stereological estimators were used to quantify histological variables of bone volume and bone formation and resorption. The femora were DXA- and μCT-scanned, and the bone strength was determined at the femoral neck and mid-diaphysis. RESULTS: Locally, we found no differences in arthritis score or ankle width throughout the study. Similarly, none of the treatments inhibited bone erosions or stimulated bone formation in the paw. Systemically, all treatments improved bone mineral density, strength of the femoral neck and mid-diaphysis, and μCT parameters of both cortical and trabecular bone. In addition, there was an additive effect of combination treatment compared with single treatments for most trabecular parameters including bone mineral density and bone volume fraction. CONCLUSIONS: No local effect on bone was found by the combined action of inhibiting bone resorption and stimulating bone formation. However, a clear systemic effect of the combination treatment was demonstrated.

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

    Science.gov (United States)

    Wu, Chang-Chin; Wang, Chen-Chie; Lu, Dai-Hua; Hsu, Li-Ho; Yang, Kai-Chiang; Lin, Feng-Huei

    2012-06-01

    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.

  15. 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)

  16. 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

  17. 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

  18. 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

  19. Distinct effect of zoledronate and clodronate on circulating levels of DKK1 and sclerostin in women with postmenopausal osteoporosis.

    Science.gov (United States)

    Gatti, Davide; Viapiana, Ombretta; Idolazzi, Luca; Fracassi, Elena; Ionescu, Claudio; Dartizio, Carmela; Troplini, Sonila; Kunnathully, Vidya; Adami, Silvano; Rossini, Maurizio

    2014-10-01

    The coupling of bone formation to bone resorption during treatment of postmenopausal osteoporosis with antiresorbers might be related to changes in Wnt/b-catenin signaling. We compared the effects of two bisphosphonate treatments on two Wnt-inhibitors Sclerostin (SOST) and Dickkopf-related protein 1 (DKK1). The study population included 74 women with postmenopausal osteoporosis participating simultaneously in two multicenter, placebo controlled trials. The patients were randomized to: intramuscular clodronate 100mg/week (CLO) (N=36), and yearly intravenous therapy with 5mg zoledronate (ZOL) (N=18) and placebo (N=20). Bone turnover markers (intact N-propeptide of type I collagen [P1NP], C-terminal telopeptide of type I collagen [CTX]) remained unchanged in the placebo group while they significantly decreased during treatment with the two bisphosphonates, versus both placebo and baseline. In CLO treated patients serum DKK1 remained stable over the entire period of observation while serum SOST levels increased significantly after 12months of treatment both versus placebo group (posteoporosis with intermittent yearly ZOL is associated with transient and declining increases in DKK1 while continuous treatment with CLO, results in a late increase in serum SOST. These preliminary results and further ad hoc studies might contribute to shed light on our understanding of the bone coupling effects taking place during treatment of osteoporosis with different anti-resorbers or with different treatment regimens.

  20. Additive effect of PTH (1-34) and zoledronate in the prevention of disuse osteopenia in rats.

    Science.gov (United States)

    Vegger, Jens Bay; Nielsen, Esben Sommer; Brüel, Annemarie; Thomsen, Jesper Skovhus

    2014-09-01

    Immobilization is known to cause a rapid bone loss due to increased osteoclastic bone resorption and decreased osteoblastic bone formation. Zoledronate (Zln) is a potent anti-resorptive pharmaceutical, while intermittent PTH is a potent bone anabolic agent. The aim of the present study was to investigate whether PTH or Zln alone or in combination could prevent immobilization-induced osteopenia. Immobilization was achieved by injecting 4IU Botox (BTX) into the right hind limb musculature. Seventy-two 16-week-old female Wistar rats were randomized into 6 groups; baseline (Base), control (Ctrl), BTX, BTX+PTH, BTX+Zln, and BTX+PTH+Zln. PTH (1-34) (80μg/kg) was given 5days/week and Zln (100μg/kg) was given once at study start. The animals were killed after 4weeks of treatment. The bone properties were evaluated using DEXA, μCT, dynamic bone histomorphometry, and mechanical testing. BTX resulted in lower femoral trabecular bone volume fraction (BV/TV) (-25%, pTV (+31%, pTV (+36%, pTV (+70%, pled to lower BV/TV, BFR/BS, and Fmax. In general, PTH or Zln alone prevented the BTX-induced osteopenia, whereas PTH and Zln given in combination not only prevented, but also increased BV/TV and BFR/BS, and maintained Fmax at the distal femoral metaphysis compared with Ctrl. PMID:24970039

  1. 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....

  2. 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;

    2011-01-01

    This study evaluated the benefits of ZOL versus placebo on health-related quality of life (HRQoL) among patients from HORIZON-RFT. At month 24 and end of the study visit, ZOL significantly improved patients' overall health state compared to placebo as assessed by the EQ-5D VAS. INTRODUCTION: To e...

  3. [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

  4. Zoledronic acid treatment in an adult patient with Osteogenesis Imperfecta: A case report and review of the literature

    OpenAIRE

    Yazmalar, Levent; Batmaz, İbrahim; Dağlı, Abdullah Zübeyr; Hattapoğlu, Erkam; sarıyıldız, Mustafa Akif

    2014-01-01

    Osteogenesis Imperfecta (OI) is a rare heritable condition characterized by bone fragility and reduced bone mass. This pathology is characterized by disruption of biosynthesis of Type I collagen, and production of limited amount of defective and imperfect collagens. This causes decrease in bone mass of human body, bones become fragile and brittle, resulting in unreasonable multiple fractures. Other manifestations include hyperextensibility of the joints, blue sclera, hearing loss, short statu...

  5. 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

  6. 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

  7. 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.

  8. Nurse-administered propofol sedation for endoscopy

    DEFF Research Database (Denmark)

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

    2011-01-01

    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 endosco...

  9. Folate-targeted pH-responsive calcium zoledronate nanoscale metal-organic frameworks: Turning a bone antiresorptive agent into an anticancer therapeutic.

    Science.gov (United States)

    Au, Kin Man; Satterlee, Andrew; Min, Yuanzeng; Tian, Xi; Kim, Young Seok; Caster, Joseph M; Zhang, Longzhen; Zhang, Tian; Huang, Leaf; Wang, Andrew Z

    2016-03-01

    Zoledronate (Zol) is a third-generation bisphosphonate that is widely used as an anti-resorptive agent for the treatment of cancer bone metastasis. While there is preclinical data indicating that bisphosphonates such as Zol have direct cytotoxic effects on cancer cells, such effect has not been firmly established in the clinical setting. This is likely due to the rapid absorption of bisphosphonates by the skeleton after intravenous (i.v.) administration. Herein, we report the reformulation of Zol using nanotechnology and evaluation of this novel nanoscale metal-organic frameworks (nMOFs) formulation of Zol as an anticancer agent. The nMOF formulation is comprised of a calcium zoledronate (CaZol) core and a polyethylene glycol (PEG) surface. To preferentially deliver CaZol nMOFs to tumors as well as facilitate cellular uptake of Zol, we incorporated folate (Fol)-targeted ligands on the nMOFs. The folate receptor (FR) is known to be overexpressed in several tumor types, including head-and-neck, prostate, and non-small cell lung cancers. We demonstrated that these targeted CaZol nMOFs possess excellent chemical and colloidal stability in physiological conditions. The release of encapsulated Zol from the nMOFs occurs in the mid-endosomes during nMOF endocytosis. In vitro toxicity studies demonstrated that Fol-targeted CaZol nMOFs are more efficient than small molecule Zol in inhibiting cell proliferation and inducing apoptosis in FR-overexpressing H460 non-small cell lung and PC3 prostate cancer cells. Our findings were further validated in vivo using mouse xenograft models of H460 and PC3. We demonstrated that Fol-targeted CaZol nMOFs are effective anticancer agents and increase the direct antitumor activity of Zol by 80-85% in vivo through inhibition of tumor neovasculature, and inhibiting cell proliferation and inducing apoptosis.

  10. 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

  11. 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.

  12. 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.

  13. THE EXCLUSION OF ILEGALLY ADMINISTERED EVIDENCE

    Directory of Open Access Journals (Sweden)

    Eliza Emanuela IONIŢĂ

    2015-07-01

    Full Text Available Both judicial practice and specialized texts have brought up the problem of what the punishment for breaking the legal provisions in the activity of evidence administration is, if a matter of fact had been presented by means that are not legally specified or if a piece of evidence was administered by means that are legally specified, but with the violation of legal provisions. Romania has adhered to the most important international juridical instruments adopted in the sphere of human rights by the adoption, modification or completion of internal legislation. As such, for the first time in Romanian criminal procedural legislation, a sanction for the exclusion of evidence has been introduced, as a corollary for the principle of legality and of loyalty in administering evidence. The New Criminal Procedure Code provides the sanction of exclusion as well, but this time the legislator didn’t resume his or herself to a mere conceptual regulation of the sanction, providing both a specific invalidation procedure as well as procedural solutions. In the New Criminal Procedure Code it is shown that in the sphere of evidence-showing a set of rules has been introduced that establishes the principle of loyalty in the obtainment of evidence. These rules, that provide the sanction of excluding evidence obtained through illegal or unloyal means, will determined the growth of professionalism in the ranks of the judiciary bodies on the subject of obtaining evidence and, on the other hand, will guarantee the firm upholding of the parties rights to a fair trial. “Truth, like all other good things, may be loved unwisely – may be pursued too keenly – may cost too much…” Lord Justice Sir James Lewis Knight-Bruce ”It is a deeply ingrained value in our democratic system that the ends do not justify the means. In particular, evidence or convictions may, at times, be obtained at too high a price”. – Antonio Lamer Former Chief Justice of the Supreme Court

  14. 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.

  15. 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.

  16. 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

  17. [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

  18. 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....

  19. 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

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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...

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

    DEFF Research Database (Denmark)

    Jensen, Jeppe Thue; Møller, Ann; Hornslet, Pernille;

    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...

  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. 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.

  10. 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)

  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. 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.

  13. Fetal Tachycardia Treated Successfully with Maternally Administered Propylthiouracil

    Directory of Open Access Journals (Sweden)

    Barbara V. Parilla

    2014-01-01

    Full Text Available Background. Fetal tachycardia may result from the transplacental passage of thyroid stimulating immunoglobulins in a patient with hypothyroidism secondary to ablation of Graves’ disease. Case. A 32-year-old woman, gravida 4, para 2, and abortus 1, with hypothyroidism and a history of Graves’ disease, presented at 23 6/7 weeks of gestation with a persistent fetal tachycardia. The treatment of the fetal tachycardia with maternally administered digoxin and Sotalol was unsuccessful. Maternal thyroid stimulating immunoglobulins were elevated, and treatment with maternally administered propylthiouracil (PTU resulted in a normal sinus rhythm for the remainder of the pregnancy. An induction of labor was performed at 37 weeks. Four to five days after delivery, the neonate exhibited clinical signs of hyperthyroidism necessitating treatment. Conclusion. Fetal tachycardia resulting from the transplacental passage of thyroid stimulating immunoglobulins can be successfully treated with maternally administered PTU. The neonate needs to be followed up closely as clinical signs of hyperthyroidism may occur as thyroid stimulating immunoglobulins continue to circulate in the neonate, while the serum levels of PTU decline.

  14. 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.

  15. Pharmacokinetics of tetraplatin administered intraperitoneally with reduced glutathione in mice.

    Science.gov (United States)

    Kido, Y; Khokhar, A R; Yoshida, M; Thai, G W; Siddik, Z H

    1994-01-01

    Tetraplatin (Ormaplatin) has been developed as a second generation platinum complex because of its good antitumor activity against some cisplatin-resistant tumor cell lines. It is currently in clinical trials. Its reduction to diaminocyclohexane (DACH)-dichloroplatinum(II) [DACH-Pt(II)Cl2] or closely similar species is essential for binding to DNA to produce the desired antitumor effects. We have studied the pharmacokinetics of tetraplatin in mice after intraperitoneal administration with the reducing agent glutathione (GSH). The systemic absorption of tetraplatin (5 mg/kg) with GSH (31 mg/kg) was faster than of tetraplatin alone. Peak plasma platinum (Pt) levels of 0.89 and 1.44 micrograms Pt/ml were observed at 15 min and 2 hr after administration of tetraplatin with and without GSH, respectively, and the Pt then decayed biphasically when administered with GSH and monophasically when administered alone. The plasma Pt level was 4-fold lower (0.17 vs. 0.71 micrograms Pt/ml) by 24 hr when tetraplatin was administered with GSH compared with its administration alone. DACH-Pt(II)Cl2 (4.21 mg/kg, ip) gave similar plasma Pt kinetics to that seen with the combination of tetraplatin and GSH. Pt levels in kidney 24 hr after administration of tetraplatin+GSH or of DACH-Pt(II)Cl2 were lower (1.6-fold) than after tetraplatin alone. Plasma and ascitic fluid from tumor-bearing mice demonstrated equivalent abilities to reduce tetraplatin rapidly. However, tetraplatin treatment of intraperitoneal-inoculated L1210/0 (parent) or L1210/DDP (cisplatin-resistant) tumor cells was unaffected by GSH. As GSH lowered systemic tetraplatin exposure in vivo without compromising antitumor activity against peritoneal tumor models, the combination of thiol and tetraplatin may be clinically useful in the treatment of intraperitoneal disseminated cancers. PMID:8013287

  16. Absorption and distribution of orally administered jojoba wax in mice.

    Science.gov (United States)

    Yaron, A; Samoiloff, V; Benzioni, A

    1982-03-01

    The liquid wax obtained from the seeds of the arid-land shrub jojoba (Simmondsia chinensis) is finding increasing use in skin treatment preparations. The fate of this wax upon reaching the digestive tract was studied. 14C-Labeled wax was administered intragastrically to mice, and the distribution of the label in the body was determined as a function of time. Most of the wax was excreted, but a small amount was absorbed, as was indicated by the distribution of label in the internal organs and the epididymal fat. The label was incorporated into the body lipids and was found to diminish with time.

  17. Orally administered bisphenol a in rainbow trout (Oncorhynchus mykiss): estrogenicity, metabolism, and retention.

    Science.gov (United States)

    Bjerregaard, Poul; Andersen, Sidsel B; Pedersen, Knud L; Pedersen, Søren N; Korsgaard, Bodil

    2007-09-01

    The estrogenic effect of orally administered bisphenol A (BPA) was investigated in a rainbow trout (Oncorhynchus mykiss) test system. Bisphenol A was administered orally to sexually immature rainbow trout every second day for up to 12 d in doses between 1.8 and 258 mg/kg every second day (/2d). Plasma vitellogenin was measured before and during the exposures, and the concentrations of BPA in plasma, liver, and muscle and the plasma concentrations of BPA glucuronic acid (BPAGA) were determined at the end of the experiments. Increases in average plasma vitellogenin levels were seen at oral exposure to 24 mg BPA/kg/2d; the most sensitive fish responded to 9.3 mg/kg/2d. At day 12, the 10, 50, and 90% effective doses for increase in vitellogenin synthesis were 13, 19, and 25 mg/kg/2d, respectively. Bisphenol A could be detected in liver, muscle, and plasma at the end of the exposure, generally in increasing concentrations with increasing doses; liver concentrations generally were higher than muscle concentrations. Four to five hours after the last feeding of doses between 3.6 and 24 mg BPA/kg, plasma BPA concentrations ranged between 400 and 1,200 nM, whereas BPAGA concentrations were between 2- and 10-fold higher. The difference between BPA and BPAGA concentrations increased with increasing BPA dose. Bisphenol A showed little tendency to bioaccumulate in rainbow trout; less than 1% of the total amount of BPA administered orally at doses between 1.8 and 258 mg/ kg/2d over the 10- or 12-d experimental period was retained in muscle and liver at 5 or 24 h after the end of the experiments.

  18. 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’.

  19. 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.

  20. 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.

  1. 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

  2. Techniques to administer oral, inhalational, and IV sedation in dentistry

    Directory of Open Access Journals (Sweden)

    Diana Krystyna Harbuz

    2016-02-01

    Full Text Available Background Sedation in dentistry is a controversial topic given the variety of opinions regarding its safe practice. Aims This article evaluates the various techniques used to administer sedation in dentistry and specific methods practiced to form a recommendation for clinicians. Methods An extensive literature search was performed using PubMed, Medline, Google Scholar, Google, and local library resources. Results Most of the literature revealed a consensus that light sedation on low-risk American Society of Anesthesiologists (ASA groups, that is ASA I, and possibly II, is the safest method for sedation in a dental outpatient setting. Conclusion Formal training is essential to achieve the safe practice of sedation in dentistry or medicine. The appropriate setting for sedation should be determined as there is an increased risk outside the hospital setting. Patients should be adequately assessed and medication titrated appropriately, based on individual requirements.

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

    DEFF Research Database (Denmark)

    Jensen, Jeppe Thue; Møller, Ann; Hornslet, Pernille;

    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...... 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 ... 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 Nilsson...

  4. [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

  5. Opponent process properties of self-administered cocaine.

    Science.gov (United States)

    Ettenberg, Aaron

    2004-01-01

    Over the past decade, data collected in our laboratory have demonstrated that self-administered cocaine produces Opponent-Process-like behavioral effects. Animals running a straight alley once each day for IV cocaine develop over trials an approach-avoidance conflict about re-entering the goal box. This conflict behavior is characterized by a stop in forward locomotion (usually at the very mouth of the goal box) followed by a turn and 'retreat' back toward the goal box. The results of a series of studies conducted over the past decade collectively suggest that the behavioral ambivalence exemplified by rats running the alley for IV cocaine stems from concurrent and opponent positive (rewarding) and negative (anxiogenic) properties of the drug--both of which are associated with the goal box. These opponent properties of cocaine have been shown to result from temporally distinct affective states. Using a conditioned place preference test, we have been able to demonstrate that while the initial immediate effects of IV cocaine are reinforcing, the state present 15 min post-injection is aversive. In our most recent work, the co-administration of IV cocaine with either oral ethanol or IV heroin was found to greatly diminish the development and occurrence of retreat behaviors in the runway. It may therefore be that the high incidence of co-abuse of cocaine with either ethanol or heroin, stems from the users' motivation to alleviate some of the negative side effects of cocaine. It would seem then that the Opponent Process Theory has provided a useful conceptual framework for the study of the behavioral consequences of self-administered cocaine including the notion that both positive and negative reinforcement mechanisms are involved in the development and maintenance of cocaine abuse. PMID:15019422

  6. Opponent process properties of self-administered cocaine.

    Science.gov (United States)

    Ettenberg, Aaron

    2004-01-01

    Over the past decade, data collected in our laboratory have demonstrated that self-administered cocaine produces Opponent-Process-like behavioral effects. Animals running a straight alley once each day for IV cocaine develop over trials an approach-avoidance conflict about re-entering the goal box. This conflict behavior is characterized by a stop in forward locomotion (usually at the very mouth of the goal box) followed by a turn and 'retreat' back toward the goal box. The results of a series of studies conducted over the past decade collectively suggest that the behavioral ambivalence exemplified by rats running the alley for IV cocaine stems from concurrent and opponent positive (rewarding) and negative (anxiogenic) properties of the drug--both of which are associated with the goal box. These opponent properties of cocaine have been shown to result from temporally distinct affective states. Using a conditioned place preference test, we have been able to demonstrate that while the initial immediate effects of IV cocaine are reinforcing, the state present 15 min post-injection is aversive. In our most recent work, the co-administration of IV cocaine with either oral ethanol or IV heroin was found to greatly diminish the development and occurrence of retreat behaviors in the runway. It may therefore be that the high incidence of co-abuse of cocaine with either ethanol or heroin, stems from the users' motivation to alleviate some of the negative side effects of cocaine. It would seem then that the Opponent Process Theory has provided a useful conceptual framework for the study of the behavioral consequences of self-administered cocaine including the notion that both positive and negative reinforcement mechanisms are involved in the development and maintenance of cocaine abuse.

  7. 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.

  8. 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

  9. Inducing and administering Tregs to treat human disease

    Directory of Open Access Journals (Sweden)

    Ana Luisa Perdigoto

    2016-01-01

    Full Text Available Regulatory T cells control unwanted immune responses including those that mediate tolerance to self as well as to foreign antigens. Their mechanisms of action include direct and indirect effects on effector T cells and important functions in tissue repair and homeostasis. Regulatory T cells express a number of cell surface markers and transcriptional factors that have been instrumental in defining their origins and potentially their function. A number of immune therapies such as rapamycin, IL-2, as well as anti-T cell antibodies are able to induce regulatory T cells and are being tested for their efficacy in diverse clinical settings with exciting preliminary results. However, a balance exists with the use of some, such as IL-2 that may have effects on unwanted populations as well as promoting expansion and survival of regulatory T cells requiring careful selection of dose for clinical use. The use of cell surface markers has enabled investigators to isolate and expand ex vivo regulatory T cells more than 500-fold routinely. Clinical trials have begun, administering these expanded regulatory T cells to patients as a means of suppressing autoimmune and alloimmune response and potentially inducing immune tolerance. Studies in the future are likely to build on these initial technical achievements and use combinations of agents to improve the survival and functional capacity of regulatory T cells.

  10. 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).

  11. 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...

  12. Pamidronate and zoledronate effects in the increment of bone mineral density and histomorphometry in rats Efeitos do pamidronato e zoledronato no incremento da densitometria óssea e histomorfometria em ratos

    Directory of Open Access Journals (Sweden)

    Antônio Fiel Cruz Júnior

    2011-04-01

    Full Text Available PURPOSE: To compare increment of bone mineral density (BMD with pamidronate, zoledronate and the isolated effect of proteinous diet in undernourished oophorectomized and non-oophorectomized female rats, besides validating BMD's indexes. METHODS: 60 young female Lewis rats were divided into five experimental groups and a control group, oophorectomized and non-oophorectomized. The administration of drugs were submitted to proteinous and aproteinous diets. The variables analyzed were weight, bone densitometry, histomorphometry and biochemical evolution. RESULTS: In weight evaluation, the first interval showed a statistically meaningful increase in oophorectomized sample. In densitometry evaluation, the first interval showed statistically meaningful decrease in four medicated groups and third showed a statistically meaningful increase in 2 non-oophorectomized groups. In laboratory evaluation, there were an increase of total proteins and globulin, decrease of alkaline phosphatase, phosphorus and calcium (except for the oophorectomized in four medicated groups and increase of phosphorus and calcium in 2 not medicated groups. In histomorphometric evaluation, the oophorectomized groups had smaller increment of BMD. CONCLUSIONS: The pamidronate and zoledronate have shown effectives in the increment of BMD. The proteinous diet itself possesses therapeutic effect in BMD though not significant compared with medicated animals. The results of histomorphometry allow validating BMD's indexes in this experimental model.OBJETIVO: Comparar o incremento de densidade mineral óssea (DMA com pamidronato, zoledronato e o efeito isolado de dieta protéica em ratas desnutridas ooforectomizadas e não ooforectomizadas, além de validar índices de DMA. MÉTODOS: 60 ratas jovens Lewis foram divididas em cinco grupos experimentais e um grupo controle, com e sem ooforectomia. A administração das drogas foi submetida às dietas protéica e aprotéica. As vari

  13. Maternal and fetal brain contents of docosahexaenoic acid (DHA) and arachidonic acid (AA) at various essential fatty acid (EFA), DHA and AA dietary intakes during pregnancy in mice

    NARCIS (Netherlands)

    van Goor, Saskia A; Dijck-Brouwer, D A Janneke; Fokkema, M Rebecca; van der Iest, Theo Hans; Muskiet, Frits A J

    2008-01-01

    We investigated essential fatty acids (EFA) and long-chain polyunsaturated fatty acids (LCP) in maternal and fetal brain as a function of EFA/LCP availability to the feto-maternal unit in mice. Diets varying in parent EFA, arachidonic acid (AA), and docosahexaenoic acid (DHA) were administered from

  14. Comparison of total costs of administering calcium polycarbophil and psyllium mucilloid in an institutional setting.

    Science.gov (United States)

    Mamtani, R; Cimino, J A; Cooperman, J M; Kugel, R

    1990-01-01

    The total cost of administering calcium polycarbophil per unit dose (two tablets) was compared with that of administering psyllium mucilloid (one packet dissolved in 8 oz of water) in 20 elderly nursing-home residents. Times for printing labels, checking and initialing labels, gathering materials needed, and preparing and administering the medications were recorded during at least 50 observations in each treatment group. Total cost included nurses' and pharmacists' time, materials, and medications. Calcium polycarbophil doses were prepared and administered more quickly (mean, 49.5 sec) than psyllium mucilloid (105.3 sec). The mean cost of preparing and administering a unit dose was 28.2 for calcium polycarbophil tablets and 59.9 for psyllium mucilloid. The results suggest that the use of calcium polycarbophil tablets would save time and money in institutions in which laxatives are frequently administered.

  15. 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.

  16. Alliance in Two Telephone-Administered Treatments: Relationship with Depression and Health Outcomes

    Science.gov (United States)

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

    2007-01-01

    The present study examined the relationship between therapeutic alliance and both depression and health outcomes in a randomized clinical trial of 2 telephone-administered treatments with 97 clients with multiple sclerosis (MS). The 16-week, manualized treatments compared were telephone-administered cognitive-behavioral therapy (T-CBT) and…

  17. 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…

  18. 40 CFR 131.8 - Requirements for Indian Tribes to administer a water quality standards program.

    Science.gov (United States)

    2010-07-01

    ... administer a water quality standards program. 131.8 Section 131.8 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS WATER QUALITY STANDARDS General Provisions § 131.8 Requirements for Indian Tribes to administer a water quality standards program. (a) The Regional Administrator,...

  19. 40 CFR 147.250 - State-administered program-Class II wells.

    Science.gov (United States)

    2010-07-01

    ... California § 147.250 State-administered program—Class II wells. The UIC program for Class II wells in the State of California, except those on Indian lands, is the program administered by the California... reference and made a part of the applicable UIC program under the SDWA for the State of California....

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

    DEFF Research Database (Denmark)

    Jensen, Jeppe Thue; Banning, Anne-Marie; Clementsen, Paul;

    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"....

  1. 42 CFR 447.520 - FFP: Conditions relating to physician-administered drugs.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false FFP: Conditions relating to physician-administered drugs. 447.520 Section 447.520 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF... § 447.520 FFP: Conditions relating to physician-administered drugs. (a) No FFP is available...

  2. 40 CFR 272.1601 - New Mexico State-Administered Program: Final Authorization.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false New Mexico State-Administered Program... (CONTINUED) SOLID WASTES (CONTINUED) APPROVED STATE HAZARDOUS WASTE MANAGEMENT PROGRAMS New Mexico § 272.1601 New Mexico State-Administered Program: Final Authorization. (a) Pursuant to section 3006(b) of...

  3. 47 CFR 64.1110 - State notification of election to administer FCC rules.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false State notification of election to administer FCC rules. 64.1110 Section 64.1110 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED... Telecommunications Service Providers § 64.1110 State notification of election to administer FCC rules. (a)...

  4. Rat nucleus accumbens core astrocytes modulate reward and the motivation to self-administer ethanol after abstinence.

    Science.gov (United States)

    Bull, Cecilia; Freitas, Kelen C C; Zou, Shiping; Poland, Ryan S; Syed, Wahab A; Urban, Daniel J; Minter, Sabrina C; Shelton, Keith L; Hauser, Kurt F; Negus, S Stevens; Knapp, Pamela E; Bowers, M Scott

    2014-11-01

    Our understanding of the active role that astrocytes play in modulating neuronal function and behavior is rapidly expanding, but little is known about the role that astrocytes may play in drug-seeking behavior for commonly abused substances. Given that the nucleus accumbens is critically involved in substance abuse and motivation, we sought to determine whether nucleus accumbens astrocytes influence the motivation to self-administer ethanol following abstinence. We found that the packing density of astrocytes that were expressing glial fibrillary acidic protein increased in the nucleus accumbens core (NAcore) during abstinence from EtOH self-administration. No change was observed in the nucleus accumbens shell. This increased NAcore astrocyte density positively correlated with the motivation for ethanol. Astrocytes can communicate with one another and influence neuronal activity through gap-junction hemichannels. Because of this, the effect of blocking gap-junction hemichannels on the motivation for ethanol was examined. The motivation to self-administer ethanol after 3 weeks abstinence was increased following microinjection of gap-junction hemichannel blockers into the NAcore at doses that block both neuronal and astrocytic channels. In contrast, no effect was observed following microinjection of doses that are not thought to block astrocytic channels or following microinjection of either dose into the nucleus accumbens shell. Additionally, the motivation for sucrose after 3 weeks abstinence was unaffected by NAcore gap-junction hemichannel blockers. Next, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) were selectively expressed in NAcore astrocytes to test the effect of astrocyte stimulation. DREADD activation increased cytosolic calcium in primary astrocytes, facilitated responding for rewarding brain stimulation, and reduced the motivation for ethanol after 3 weeks abstinence. This is the first work to modulate drug-seeking behavior with

  5. 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...

  6. 肿瘤深部热疗联合唑来膦酸治疗骨转移癌痛的临床疗效观察%Clinical observation of high frequency thermotherapy and zoledronic for pain relief in metastatic bone cancer

    Institute of Scientific and Technical Information of China (English)

    薛清萍

    2015-01-01

    目的:分析肿瘤深部热疗联合唑来膦酸治疗骨转移癌痛的临床疗效。方法:将46例伴有不同程度骨转移癌疼痛的患者随机分为观察组和对照组。对照组23例,单纯应用唑来膦酸治疗。观察组23例,在对照组治疗基础上给予肿瘤深部热疗。治疗后对两组患者疗效进行评估。结果:观察组患者治疗后 Karnofsky 行为状况评分为(70.1±5.2)分,而对照组为(61.4±4.9)分,对照组明显低于观察组,组间比较差异显著(P <0.05);观察组患者经治疗后的总有效率(86.96%)明显高于对照组(69.56%)(P <0.05);两组患者的不良反应无明显差异(P >0.05)。结论:肿瘤深部热疗联合唑来膦酸缓解癌症骨转移疼痛效果良好,安全性高,值得在临床上使用。%Objective:To observe the clinical effects of high frequency thermotherapy and zoledronic for pain relief in metastatic bone cancer.Methods:A retrospective analysis of clinical data was conducted in 46 patients with metastatic bone cancer who were admitted in our hospital,and they were randomly divided into observation group and control group,each group contained 23 cases.The control group were treated with zoledronic,the observation group were treated with high frequency thermotherapy and zoledronic.Results:After treatment,the observation group's Karnofsky behavior scorewas(70.1 ±5.2),and the control group's Karnofsky behavior score was (61.4 ±4.9),which was significantly lower than observation group(P 0.05).Conclusion:High frequency thermotherapy and zoledronic for pain relief in metastatic bone cancer have good effective and worthy of clinical use.

  7. 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 ...

  8. Intravenously administered lidocaine in therapeutic doses increases the intraspinal release of acetylcholine in rats

    DEFF Research Database (Denmark)

    Abelson, Klas S P; Höglund, A Urban

    2002-01-01

    the intraspinal release of acetylcholine. In the present study it was hypothesized that systemically administered lidocaine is acting through the same mechanisms as cholinergic agonists and affects the intraspinal release of acetylcholine. Microdialysis probes were placed in anesthetized rats for sampling...... of acetylcholine. Ten and 30 mg/kg lidocaine injected intravenously significantly increased the intraspinal release of acetylcholine. The effect of lidocaine could be reduced by pretreatment with intraspinally administered atropine or mecamylamine. Our results suggest that the antinociceptive effect produced...

  9. Effects of orally administered bovine lactoperoxidase on dextran sulfate sodium-induced colitis in mice.

    Science.gov (United States)

    Shin, Kouichirou; Horigome, Ayako; Yamauchi, Koji; Takase, Mitsunori; Yaeshima, Tomoko; Iwatsuki, Keiji

    2008-07-01

    The effect of lactoperoxidase (LPO) on dextran sulfate sodium-induced colitis was examined in mice. After 9 d of colitis induction, weight loss, colon shortening, and the histological score were significantly suppressed in mice orally administered LPO (62.5 mg/body/d) as compared to a group administered bovine serum albumin. These results suggest that LPO exhibits anti-inflammatory effects in the gastrointestinal tract.

  10. 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)

  11. 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

  12. 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)

  13. 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

  14. 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...

  15. 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...

  16. Comparing administered and market-based water allocation systems using an agent-based modeling approach

    Science.gov (United States)

    Zhao, J.; Cai, X.; Wang, Z.

    2009-12-01

    It also has been well recognized that market-based systems can have significant advantages over administered systems for water allocation. However there are not many successful water markets around the world yet and administered systems exist commonly in water allocation management practice. This paradox has been under discussion for decades and still calls for attention for both research and practice. This paper explores some insights for the paradox and tries to address why market systems have not been widely implemented for water allocation. Adopting the theory of agent-based system we develop a consistent analytical model to interpret both systems. First we derive some theorems based on the analytical model, with respect to the necessary conditions for economic efficiency of water allocation. Following that the agent-based model is used to illustrate the coherence and difference between administered and market-based systems. The two systems are compared from three aspects: 1) the driving forces acting on the system state, 2) system efficiency, and 3) equity. Regarding economic efficiency, penalty on the violation of water use permits (or rights) under an administered system can lead to system-wide economic efficiency, as well as being acceptable by some agents, which follows the theory of the so-call rational violation. Ideal equity will be realized if penalty equals incentive with an administered system and if transaction costs are zero with a market system. The performances of both agents and the over system are explained with an administered system and market system, respectively. The performances of agents are subject to different mechanisms of interactions between agents under the two systems. The system emergency (i.e., system benefit, equilibrium market price, etc), resulting from the performance at the agent level, reflects the different mechanism of the two systems, the “invisible hand” with the market system and administrative measures (penalty

  17. 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 ...

  18. 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…

  19. 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

  20. 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;

    2007-01-01

    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 events....

  1. 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...

  2. 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

  3. 24 CFR 511.50 - State election to administer a rental rehabilitation program.

    Science.gov (United States)

    2010-04-01

    ... rental rehabilitation program. 511.50 Section 511.50 Housing and Urban Development Regulations Relating... GRANT PROGRAM State Program § 511.50 State election to administer a rental rehabilitation program. (a) State allocations may be used to carry out eligible rehabilitation activities in accordance with...

  4. Employing Computer-Administered Exams in General Psychology: Student Anxiety and Expectations

    Science.gov (United States)

    Schult, Carolyn A.; McIntosh, John L.

    2004-01-01

    Computer-administered exams offer many advantages, but instructors may be reluctant to use them due to concerns that computer anxiety may increase student test anxiety. Introductory psychology students (N = 265) completed surveys prior to their first exam about their anxiety related to the upcoming exam, computers in general, and taking exams on…

  5. 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,…

  6. 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…

  7. Titanium dioxide nanoparticles decreases activity of rat brain when administered prenatally

    Directory of Open Access Journals (Sweden)

    Nikita Saraswat

    2016-06-01

    Conclusions: We studied the neurobehaviour of progenies, when the drug was administered to rat brain prenatally. The results showed that the titanium dioxide nanoparticles particles have decreased the brain activity of the rat brain by showing decreased brain activity in progenies also. [Int J Basic Clin Pharmacol 2016; 5(3.000: 733-738

  8. 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...

  9. 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...

  10. 48 CFR 904.804-1 - Closeout by the office administering the contract.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Closeout by the office administering the contract. 904.804-1 Section 904.804-1 Federal Acquisition Regulations System DEPARTMENT OF ENERGY GENERAL ADMINISTRATIVE MATTERS Government Contract Files 904.804-1 Closeout by the...

  11. Improving the Estimation of Moderating Effects by Using Computer-Administered Questionnaires.

    Science.gov (United States)

    Aguinis, Herman; And Others

    1996-01-01

    A program designed to administer questionnaires on IBM and IBM-compatible personal computers is described. The program prompts subjects to indicate responses by clicking on a graphic line segment or entering a numeric value. The program enhances accuracy in estimating moderating effects by overcoming transcriptional errors and scale coarseness.…

  12. 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...

  13. DEVELOPMENTAL EFFECTS OF TRICHLOROACETONITRILE ADMINISTERED IN CORN OIL TO PREGNANT LONG-EVANS RATS

    Science.gov (United States)

    Trichloroacetonitrile (TCAN) is a by-product of the chlorine disinfection of water containing natural organic material. When administered by gavage to pregnant Long-Evans rats in a medium-chain triglyceride vehicle, tricaprylin oil (Tricap), at a volume of 10 ml/kg, TCAN induced ...

  14. 9 CFR 103.2 - Disposition of animals administered experimental biological products or live organisms.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Disposition of animals administered experimental biological products or live organisms. 103.2 Section 103.2 Animals and Animal Products ANIMAL AND... PRODUCTS; ORGANISMS AND VECTORS EXPERIMENTAL PRODUCTION, DISTRIBUTION, AND EVALUATION OF...

  15. 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).

  16. 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.

  17. 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...

  18. 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

  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. 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

  1. 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…

  2. 76 FR 22412 - Fellowship Placement Pilot Program Requests for Expressions of Interests To Administer Pilot...

    Science.gov (United States)

    2011-04-21

    ... URBAN DEVELOPMENT Fellowship Placement Pilot Program Requests for Expressions of Interests To Administer Pilot Contact Information Correction AGENCY: Office of the General Counsel, HUD. ACTION: Notice. SUMMARY: On April 13, 2011, at 71 FR 20699, HUD published a notice announcing HUD's proposal to conduct...

  3. Simultaneous determination of three polyphenols in rat plasma after orally administering hawthorn leaves extract by the HPLC method.

    Science.gov (United States)

    Ying, Xixiang; Meng, Xiansheng; Wang, Siyuan; Wang, Dong; Li, Haibo; Wang, Bing; Du, Yang; Liu, Xun; Zhang, Wenjie; Kang, Tingguo

    2012-01-01

    A simple and sensitive HPLC method was developed to simultaneously determine three active compounds, vitexin-4″-O-glucoside (VG), vitexin-2″-O-rhamnoside (VR) and hyperoside (HP), in rat plasma after administering the hawthorn leaves extract (HLE). An HPLC assay with baicalin as the internal standard was carried out using a Phenomsil C₁₈ analytical column with UV detection at 332 nm. The mobile phase consisted of methanol-acetonitrile-tetrahydrofuran-1% glacial acetic acid (6 : 1.5 : 18.5 : 74, v/v/v/v). The calibration curves were linear over the range of 2.5-500, 0.2-25 and 0.25-12.5 µg mL⁻¹ for VG, VR and HP, respectively. The method was reproducible and reliable, with relative standard deviations of the intra- and inter-day precision between 1.2% and 13.2% for the analysis of the three analytes. The validated HPLC method herein described was successfully applied to the pharmacokinetic study of VG, VR and HP after oral administration of HLE to rats over the dose range of 2.5-10  mL kg⁻¹.

  4. 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

  5. Folic Acid

    Science.gov (United States)

    Folic acid is a B vitamin. It helps the body make healthy new cells. Everyone needs folic acid. For women who may get pregnant, it is really important. Getting enough folic acid before and during pregnancy can prevent major birth ...

  6. Repetitive immunization enhances the susceptibility of mice to peripherally administered prions.

    Directory of Open Access Journals (Sweden)

    Juliane Bremer

    Full Text Available The susceptibility of humans and animals to prion infections is determined by the virulence of the infectious agent, by genetic modifiers, and by hitherto unknown host and environmental risk factors. While little is known about the latter two, the activation state of the immune system was surmised to influence prion susceptibility. Here we administered prions to mice that were repeatedly immunized by two initial injections of CpG oligodeoxynucleotides followed by repeated injections of bovine serum albumin/alum. Immunization greatly reduced the required dosage of peripherally administered prion inoculum necessary to induce scrapie in 50% of mice. No difference in susceptibility was observed following intracerebral prion challenge. Due to its profound impact onto scrapie susceptibility, the host immune status may determine disease penetrance after low-dose prion exposure, including those that may give rise to iatrogenic and variant Creutzfeldt-Jakob disease.

  7. [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

  8. Regarding the inadvisability of administering postoperative analgesics in the drinking water of rats (Rattus norvegicus).

    Science.gov (United States)

    Speth, R C; Smith, M S; Brogan, R S

    2001-11-01

    The feasibility of administering the pain reliever acetaminophen to rats via their water bottles was examined in this study. Two different preparations of acetaminophen were used, a cherry-flavored suspension and an alcohol-containing solution. Both preparations of acetaminophen were diluted to 6 mg/ml by using normal drinking water. When healthy unmanipulated rats were exposed to either of the acetaminophen preparations for the first time, the animals showed a dramatic reduction in fluid intake. A marked reduction in food intake also was associated with the cherry-flavored preparation. These reductions appear to be an expression of the well-characterized neophobic response that can be demonstrated by rodents when they encounter a novel taste. This neophobic behavior suggests that administering pain relievers to rats via their drinking water is counterproductive as a means of providing pain relief.

  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. 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...

  11. Long-term evaluation of Leber's hereditary optic neuropathy-like symptoms in rotenone administered rats.

    Science.gov (United States)

    Zhang, Li; Liu, Laura; Philip, Ann L; Martinez, Juan C; Guttierez, Juan C; Marella, Mathieu; Patki, Gaurav; Matsuno-Yagi, Akemi; Yagi, Takao; Thomas, Biju B

    2015-01-12

    Leber's hereditary optic neuropathy (LHON) is an inherited disorder affecting the retinal ganglion cells (RGCs) and their axons that lead to the loss of central vision. This study is aimed at evaluating the LHON symptoms in rats administered with rotenone microspheres into the superior colliculus (SC). Optical coherence tomography (OCT) analysis showed substantial loss of retinal nerve fiber layer (RNFL) thickness in rotenone injected rats. Optokinetic testing in rotenone treated rats showed decrease in head-tracking response. Electrophysiological mapping of the SC surface demonstrated attenuation of visually evoked responses; however, no changes were observed in the ERG data. The progressive pattern of disease manifestation in rotenone administered rats demonstrated several similarities with human disease symptoms. These rats with LHON-like symptoms can serve as a model for future investigators to design and implement reliable tests to assess the beneficial effects of therapeutic interventions for LHON disease.

  12. 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...

  13. 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...

  14. 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...

  15. 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 ...

  16. 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...

  17. 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...

  18. 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 ...

  19. 6-Hydroxydopamine inhibits some effects of mescaline centrally administered to rabbits.

    Science.gov (United States)

    Ferri, S; Reina, R A; Braga, P

    1977-12-19

    The narcotic antagonist naloxone does not antagonize antinociception elicited in the rabbit by 100 microgram/kg of mescaline centrally administered, whereas pretreatment with 6-hydroxydopamine (6-OHDA) inhibits this mescaline effect. Stereotyped behavior of rabbits following central mescaline administration is also prevented by 6-hda pretreatment. Since 6-OHDA in known to produce a degeneration of catecholamine containing nerve terminals, a crucial role of catecholamines is suggested in the complex of effects seen in the rabbit after central administration of the hallucinogen.

  20. 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-...

  1. 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...

  2. 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

  3. 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...

  4. Amino acids

    Science.gov (United States)

    ... amino acids are: histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan , and valine. Nonessential amino acids "Nonessential" means that our bodies produce an amino ...

  5. Administering the MADRS by telephone or face-to-face: a validity study

    Directory of Open Access Journals (Sweden)

    van Dyck Richard

    2006-03-01

    Full Text Available Abstract Background The Montgomery Åsberg Depression Rating Scale (MADRS is a frequently used observer-rated depression scale. In the present study, a telephonic rating was compared with a face-to-face rating in 66 primary care patients with minor or mild-major depression. The aim of the present study was to assess the validity of the administration by telephone. Additional objective was to study the validity of the first item, 'apparent sadness', the only item purely based on observation. Methods The present study was a validity study. During an in-person interview at the patient's home a trained interviewer administered the MADRS. A few days later the MADRS was administered again, but now by telephone and by a different interviewer. The validity of the telephone rating was calculated through the appropriate intraclass correlation coefficient (ICC. Results Mean total score on the in-person administration was 24.0 (SD = 11.1, and on the telephone administration 23.5 (SD = 10.4. The ICC for the full scale was 0.65. Homogeneity analysis showed that the observation item 'apparent sadness' fitted well into the scale. Conclusion The full MADRS, including the observation item 'apparent sadness', can be administered reliably by telephone.

  6. Lysostaphin: immunogenicity of locally administered recombinant protein used in mastitis therapy.

    Science.gov (United States)

    Daley, M J; Oldham, E R

    1992-03-01

    A recombinant bactericidal protein, recombinant lysostaphin (r-lysostaphin), that may be useful as an intramammary therapeutic for Staphylococcus aureus mastitis in dairy cattle, was evaluated for immunogenicity to various hosts. Although immunogenicity could be demonstrated in a variety of other species when administered parenterally, oral administration failed to elicit a significant immunological response. Similarly, intramammary infusion of r-lysostaphin failed to elicit significant serum titers in the bovine until 18-21 infusions were administered (total administered dose of 2-3 g of protein). Antibody titers from dairy cattle which did develop an immune response were predominantly of the IgG1 subclass. Dairy cattle with significant anti-lysostaphin titers showed no deleterious symptoms (anaphylaxis, etc.) upon subsequent infusion, and these titers did not effect the in vitro bacteriostatic activity of r-lysostaphin. Intramammary infusion of r-lysostaphin does not elicit any observable effects on the host animal or on the potential efficacy of the recombinant molecule. Intramammary recombinant proteins may be suitable effective and safe infusion products that provide an alternative to classical antibiotic therapy.

  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.

  8. 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

  9. 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 ...

  10. 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

  11. 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...

  12. Estimating the Impacts of Educational Interventions Using State Tests or Study-Administered Tests. NCEE 2012-4016

    Science.gov (United States)

    Olsen, Robert B.; Unlu, Fatih; Price, Cristofer; Jaciw, Andrew P.

    2011-01-01

    This report examines the differences in impact estimates and standard errors that arise when these are derived using state achievement tests only (as pre-tests and post-tests), study-administered tests only, or some combination of state- and study-administered tests. State tests may yield different evaluation results relative to a test that is…

  13. 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...

  14. 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...

  15. 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;

    2016-01-01

    increase their total amount of administered antimicrobials. Based on Danish national register data, we performed a retrospective cohort study with three groups. The cohort of primary interest (Cohort Change) consisted of 50 finisher farms which changed their group treatment procedure from feed...... throughout the study period. Cohort Change experienced a significant increase in the total amount of prescribed antimicrobials between the years. This increase might be caused by the treatment of more pigs, since antimicrobials administered through the feed are mainly administered at the pen level, while...... antimicrobials administered in water are mainly administered at the section level. However, we cannot exclude that a change in clinical disease has influenced the amount of prescribed antimicrobials. No change was observed in the other two cohorts. Furthermore, the difference in the amount of prescribed...

  16. Osteopathic medical student administered smoking cessation counseling is an effective tool

    Directory of Open Access Journals (Sweden)

    Barbara Capozzi

    2016-01-01

    Full Text Available Background: Physician counseling on the risks of tobacco smoking and the benefits of cessation has been shown to be an effective method of increasing the rate of smoking cessation. Using the "Help Your Patients Quit Smoking: A Coaching Guide" also referred to as the "7A′s of Smoking Cessation" guideline from the New York City Department of Health and Mental Hygiene is thought to be effective to convey the importance of smoking cessation. Aim: To study the efficacy of the "7A′s of Smoking Cessation" guideline counseling conducted by osteopathic medical students. Materials and Methods: Osteopathic medical students were trained to counsel smokers for 3-10 min based on New York City Department of Health′s "7A′s of Smoking Cessation" guidelines by a licensed physician. Students then counseled health fair participants who were cigarette smokers for 3-10 min. Postcounseling, participants were administered an 4 question survey to evaluate the effect counseling had on their desire to quit smoking. Survey data were collected and analyzed. Institutional Review Board approval was obtained for this study. Results: A total of 13 anonymous health fair participants who were also smokers were administered both counseling sessions and surveys. 11/13 (84.6% participants stated that the session motivated them to quit smoking. 9/13 (69.2% participants responded that they were now motivated to discuss smoking cessation with their doctor after being counseled. Of these participants 12/13 (92.3% had previously attempted to quit smoking without success. Conclusion: Participants reported an increased willingness to stop smoking after being counseled by osteopathic medical students. Participants also reported an increased motivation to discuss smoking cessation with their physician. These findings indicate that smoking cessation counseling administered by osteopathic medical students effectively in encouraging smokers to consider reduction or cessation of tobacco

  17. 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

  18. [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

  19. Precautionary practices for administering anesthetic gases: A survey of physician anesthesiologists, nurse anesthetists and anesthesiologist assistants.

    Science.gov (United States)

    Boiano, James M; Steege, Andrea L

    2016-10-01

    Scavenging systems and administrative and work practice controls for minimizing occupational exposure to waste anesthetic gases have been recommended for many years. Anesthetic gases and vapors that are released or leak out during medical procedures are considered waste anesthetic gases. To better understand the extent recommended practices are used, the NIOSH Health and Safety Practices Survey of Healthcare Workers was conducted in 2011 among members of professional practice organizations representing anesthesia care providers including physician anesthesiologists, nurse anesthetists, and anesthesiologist assistants. This national survey is the first to examine self-reported use of controls to minimize exposure to waste anesthetic gases among anesthesia care providers. The survey was completed by 1,783 nurse anesthetists, 1,104 physician anesthesiologists, and 100 anesthesiologist assistants who administered inhaled anesthetics in the seven days prior to the survey. Working in hospitals and outpatient surgical centers, respondents most often administered sevoflurane and, to a lesser extent desflurane and isoflurane, in combination with nitrous oxide. Use of scavenging systems was nearly universal, reported by 97% of respondents. However, adherence to other recommended practices was lacking to varying degrees and differed among those administering anesthetics to pediatric (P) or adult (A) patients. Examples of practices which increase exposure risk, expressed as percent of respondents, included: using high (fresh gas) flow anesthesia only (17% P, 6% A), starting anesthetic gas flow before delivery mask or airway mask was applied to patient (35% P; 14% A); not routinely checking anesthesia equipment for leaks (4% P, 5% A), and using a funnel-fill system to fill vaporizers (16%). Respondents also reported that facilities lacked safe handling procedures (19%) and hazard awareness training (18%). Adherence to precautionary work practices was generally highest among

  20. Surgeon-administered conscious sedation and local anesthesia for ambulatory anorectal surgery.

    Science.gov (United States)

    Hina, Miss; Hourigan, Jon S; Moore, Richard A; Stanley, J Daniel

    2014-01-01

    Anorectal procedures are often performed in an outpatient setting using a variety of anesthetic techniques. One technique that has not been well studied is surgeon-administered conscious sedation along with local anesthetic. The purpose of this study was to evaluate the use of this technique with emphasis on safety, efficacy, and patient satisfaction. Chart review was performed on 133 consecutive patients who had anorectal procedures at an outpatient surgery center. Additionally, 65 patients were enrolled prospectively and completed a satisfaction survey. Inclusively, charts of 198 patients who underwent outpatient anorectal surgery under conscious sedation and local anesthesia under the direction of a colorectal surgeon from 2004 through 2008 were reviewed. Parameters related to patient and procedural characteristics, safety, efficacy, and satisfaction were evaluated. Surgeon-administered sedation consisted of combined fentanyl and midazolam in 90 per cent. Eighty per cent of procedures were performed in the prone position and 23 per cent were in combination with an endoscopic procedure. Eighty-two per cent were classified as American Society of Anesthesiologists Grade 1 or 2. Transient mild hypoxemia or hypotension occurred in 4 and 3 per cent of the patients, respectively. Mean operative time was 29 minutes with a mean stay in the postanesthesia care unit of 37 minutes. There were no early major cardiac or respiratory complications. Ninety-seven per cent of the patients surveyed reported a high degree of satisfaction. Surgeon-administered conscious sedation with local anesthesia was well tolerated for outpatient anorectal surgeries. Additional studies are needed to confirm the safety and efficacy of this technique.

  1. Self-administered acupuncture as an alternative to deliberate self-harm: a feasibility study.

    Science.gov (United States)

    Davies, Susan; Bell, Diana; Irvine, Fiona; Tranter, Richard

    2011-12-01

    The aim of this mixed methods feasibility study was to demonstrate the acceptability, practicality, and safety of training patients who regularly use deliberate self harm (DSH) to self-administer acupuncture as an alternative coping skill for emotional distress. Ten adult patients with a diagnosis of emotionally unstable personality disorder who regularly self-harmed were recruited to the study following baseline assessment by a psychiatrist. An acupuncturist taught participants to self-acupuncture. During the 6-week intervention participants recorded their emotional distress, coping behaviors, thoughts, and feelings in a diary. Face-to-face interviews were used to explore participants' motives for DSH and their experience of acupuncture. Framework analysis was conducted on interview transcripts and diary entries to identify common themes. Mood at baseline and six weeks was measured using the BDI and changes in the use of coping behaviors and acupuncture were measured using diary entries. Subjects used acupuncture regularly through the six-week intervention and over this period there was a reduction in the frequency of DSH. Qualitative analysis identified two broad themes relating to the process and the effects of acupuncture. There was wide variation in the effects experienced by subjects which broadly mapped onto to the wide range of motives behind DSH. BDI scores showed a near significant reduction (p = 0.055) from 44.4. to 34.4 over the 6-week intervention. Patients presenting with deliberate self harm can be safely trained to self-administer acupuncture as an alternative coping skill. Acceptability and effectiveness may vary between patients depending on the complex motives underlying their self-harming behavior. While the pilot study was designed to explore the feasibility of the intervention, results from this limited sample suggest that use of self-administered acupuncture may reduce the frequency of self harming behavior and reduce emotional distress as

  2. 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

  3. 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

  4. 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

  5. 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....

  6. 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...

  7. Pharmacokinetics of sufentanil administered by target-controlled infusion in Chinese surgical patients

    Institute of Scientific and Technical Information of China (English)

    ZHAO Yan; WU Xin-min; DUAN Jing-li; SHENG Xiaoyan; LIU Wei; LU Wei; ZHANG Li-ping; XU Chuan-ya

    2009-01-01

    Background Target-controlled infusion (TCI) has been recently developed and successfully implemented in clinical practice. This study was conducted to determine the pharmacokinetics of TCI administered sufentanil in Chinese surgical patients.Methods The pharmacokinetics of sufentanil was investigated in 12 adult patients, aged 23-76 years, scheduled for prolonged surgery under general anesthesia. Anesthetic induction was carried out with propofol, rocuronium and TCI administered sufentanil aiming for target effect-site concentration of sufentanil 4 or 6 ng/ml. Sufentanil TCI lasted for 30 minutes. Frequent arterial blood samples (1.5 ml) were drawn during and up to 24 hours after sufentanil TCI. Plasma sufentanil concentrations were measured by liquid chromatography-tandem mass spectrometry; limit of sensitivity of mass spectrometry was 5 pg/ml. The data were analyzed with the nonlinear mixed-effect model program.Results The pharmacokinetics of TCI administered sufentanil were optimally described by a three-compartment model with the following parameters: the central volume of distribution (V1) = 5.4 L, the volume of distribution at steady-state (Vdss) = 195.4 L, systemic clearance (Cl1) = 1.10 L/min, and elimination half-life (t1/2 γ) = 271.8 minutes. Both age and gender affected the pharmacokinetic parameters. The rapid distribution clearance (Cl2) was negatively correlated with patient age, and the volume of slowly equilibrating compartment (V3) was positively correlated with age. The Cl2 and the volume of rapidly equilibrating compartment (V2) were influenced by gender with male patients showing higher values of Cl2 and V2 than female patients. There was no relationship of body weight, lean body mass, plasma albumin, or target effect-site concentration of sufentanil with any of the pharmacokinetic parameters studied.Conclusions The pharmacokinetics of TCI administered sufentanil in Chinese patients can be adequately described by a three-compartment model

  8. Intestinal absorption of coenzyme Q(10) administered in a meal or as capsules to healthy subjects

    DEFF Research Database (Denmark)

    Weber, Christine; Bysted, Anette; Hølmer, Gunhild Kofoed

    1997-01-01

    A randomized cross-over study by supplementation with single doses of coenzyme Q(10) (30 mg/person), administered either as a meal consisting of cooked pork heart or as 30 mg coenzyme Q(10) capsules was performed to investigate the bioavailability of dietary coenzyme Q(10) in humans. The increase...... in serum coenzyme Q(10) concentration was used as an index of the absorption, and reached a maximum six hours after the ingestion of either meal or capsules. Following intake of coenzyme Q(10) capsules, the serum coenzyme Q(10) concentrations increased significantly (p...

  9. Community Cognitive Screening Using the Self-Administered Gerocognitive Examination (SAGE).

    Science.gov (United States)

    Scharre, Douglas W; Chang, Shu Ing; Nagaraja, Haikady N; Yager-Schweller, Jennifer; Murden, Robert A

    2014-01-01

    This study investigated the functionality of the Self-Administered Gerocognitive Examination (SAGE) for cognitive screening in community settings and examined its characteristics as a cognitive screening assessment tool. From 45 community events, 1,047 individuals over age 50 were screened with SAGE. Cognitive impairment was identified in 28%. Principal-component and correlation analysis indicate that SAGE is an internally-consistent test that is very well balanced, with language, cognition, visuospatial, executive, and memory domains. Community cognitive screening using SAGE was found to be feasible and efficient in diverse settings with both small and large groups.

  10. 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...

  11. 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.

  12. Effect of centrally administered oxytocin on gastric and duodenal ulcers in rats%脑室注射催产素对大鼠胃和十二指肠溃疡的作用

    Institute of Scientific and Technical Information of China (English)

    Mohammed ASAD; Deepak Gopal; Kallasam KOUMARAVELOU; Benny K ABRAHAM; Sadashivam VASU; Subramanian RAMASWAMY

    2001-01-01

    AIM: To investigate the effect of centrally administered oxytocin and its receptor antagonist, atosiban, on gasuic acid secretion and on experimentally induced gastric and duodenal ulcers. METHODS: The acute gastric ulcer models, such as pylorus ligation, indomethacin-induced and ethanol-induced gastric ulcers were used. Chronic gastric ulcers were induced by acetic acid and duodenal ulcers by cysteamine HC1. RESULTS: In pylorus ligated rats, oxytocin ( 10 μg/kg, icv) showed signifi cant antisecretory and antiulcer activity (P<0.01 ). However, it aggravated the ethanol-induced gastric ulcers and did not show any effect on indomethacin-induced gas tric ulcers. Oxytocin increased gastric ulcer healing in acetic acid-induced chronic gastric ulcers. The effect of oxytocin was reversed by atosiban (10 μg/kg, icy), a selective oxytocin receptor antagonist. Atosiban when given alone increased gastric acid secretion and ulcer index in pylorus-ligated rats and also aggravated acetic acid-induced chronic gastric ulcers. It seems the antiul cer activity of oxytocin was due to its anti-secretory ef fect. CONCLUSION: Centrally administered oxytocin possesses gastric anti-secretory and anti-ulcer activity and oxytocin antagonist, atosiban, is pro-ulcerogenic in rats.

  13. 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.

  14. 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

  15. 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

  16. Fate of orally administered {sup 15}N-labeled polyamines in rats bearing solid tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Masaki; Samejima, Keijiro; Goda, Hitomi; Niitsu, Masaru [Josai Univ., Sakado, Saitama (Japan). Faculty of Pharmaceutical Sciences; Xu Yongji [Qingdao Univ. of Science and Technology (China). Inst. of Chemical and Molecular Technology; Takahashi, Masakazu [Sasaki Inst., Tokyo (Japan); Hashimoto, Yoshiyuki [Kyoritsu Coll. of Pharmacy, Tokyo (Japan)

    2003-03-01

    We studied absorption, distribution, metabolism, and excretion of polyamines (putrescine, spermidine, and spermine) in the gastrointestinal tract using {sup 15}N-labeled polyamines as tracers and ionspray ionization mass spectrometry (IS-MS). The relatively simple protocol using rats bearing solid tumors provided useful information. Three {sup 15}N-labeled polyamines that were simultaneously administered were absorbed equally from gastrointestinal tract, and distributed within tissues at various concentrations. The uptake of {sup 15}N-spermidine seemed preferential to that of {sup 15}N-spermine since the concentrations of {sup 15}N-spermidine in the liver and tumors were higher, whereas those of {sup 15}N-spermine were higher in the kidney, probably due to the excretion of excess extracellular spermine. Most of the absorbed {sup 15}N-putrescine seemed to be lost, suggesting blood and tissue diamine oxidase degradation. Concentrations of {sup 15}N-spermidine and {sup 15}N-spermine in the tumor were low. We also describe the findings from two rats that were administered with {sup 15}N-spermine. The tissue concentrations of {sup 15}N-spermine were unusually high, and significant levels of {sup 15}N-spermidine were derived from {sup 15}N-spermine in these animals. (author)

  17. 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

  18. 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.

  19. 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

  20. Administered activity optimization in renal static scanning using 99m-Tc DMSA

    Energy Technology Data Exchange (ETDEWEB)

    Perez, Marlen; Casas, Gladys [Universidad Central Marta Abreu de las Villas, Villa Clara (Cuba); Dopico, Rolando; Estevez, Eric; Cabrera, Orlando [Hospital Universitario Celestino Hernandez Robau, Villa Clara (Cuba)

    2001-07-01

    The aim of this study was to determine the optimum administered activity to patients, of the DMSA-Tc-99m looking for good image quality in gamma camera and a best radiological protection for the patient. Three protocols and two activity values in each protocol were tested (71.2 MBq and 132.8 MBq) in six patients each. An observer blinded to the administered activity, graded the rear view of both kidneys in the 36 patients. The relation of the Rois in kidney/bladder and kidney/liver, and the labeling yield were the most important parameters in the construction of a discriminatory function of image quality (r=0.56, r=0.33 and r=0.461 respectively). The correlation between the observer's opinion and the prediction of the function was r=0.429. The function classified 91.7% of the cases correctly. The best results for the patient's radiological protection were obtained by using 71.2 MBq and 700 k Counts as stopped criterion. When the labeling yield was lower than 98% it was better to applied 132.8 MBq and to stop the scanning after 3 minutes to guarantee a best image quality. (author)

  1. 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

  2. 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......-dose and 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...

  3. The social behavior of male rats administered an adult-onset calorie restriction regimen.

    Science.gov (United States)

    Govic, Antonina; Levay, Elizabeth A; Kent, Stephen; Paolini, Antonio G

    2009-03-23

    The behavioral outcomes of a calorie restricted diet are often neglected in favour of a more physiological examination of the consequences of calorie restriction (CR). This is especially the case with social behavior. A few findings within the maternal CR literature suggest that adult male social behavior is altered by this regimen. Despite the paucity of findings within the maternal CR literature, a systematic investigation of the behavioral phenotype of males administered an adult-onset CR is completely lacking and was the focus of the current study. Adult male hooded Wistar rats were administered a three week CR, with one group receiving a 25% CR and another group receiving a 50% CR before male-to-male social behavior was examined and compared with ad libitium fed males. Various behavioral elements were modulated by CR, both the CR25% and 50% group initiated contact sooner and engaged in greater social activity compared to the ad libitum fed controls. The CR25% group also demonstrated less non-social (self-grooming) behavior and a greater frequency of walkovers compared to all groups, indicating a propensity towards dominance. The CR50% group demonstrated greater environmental assessment/exploration, as measured by the frequency of rearing. As with the maternal CR literature, an adult-onset chronic CR induces a more socially active behavioral phenotype and reduces interest in non-social behavior in the moderately CR group. Taken together, the social behavioral phenotype can be modulated by a CR initiated and maintained during adulthood.

  4. Maternally administered sustained-release naltrexone in rats affects offspring neurochemistry and behaviour in adulthood.

    Directory of Open Access Journals (Sweden)

    Waleed O Farid

    Full Text Available Naltrexone is not recommended during pregnancy. However, sustained-release naltrexone implant use in humans has resulted in cases of inadvertent foetal exposure. Here, we used clinically relevant dosing to examine the effects of maternally administered sustained-release naltrexone on the rat brain by examining offspring at birth and in adulthood. Maternal treatment (naltrexone or placebo implant started before conception and ceased during gestation, birth or weaning. Morphometry was assessed in offspring at birth and adulthood. Adult offspring were evaluated for differences in locomotor behaviour (basal and morphine-induced, 10 mg/kg, s.c. and opioid neurochemistry, propensity to self-administer morphine and cue-induced drug-seeking after abstinence. Blood analysis confirmed offspring exposure to naltrexone during gestation, birth and weaning. Naltrexone exposure increased litter size and reduced offspring birth-weight but did not alter brain morphometry. Compared to placebo, basal motor activity of naltrexone-exposed adult offspring was lower, yet they showed enhanced development of psychomotor sensitization to morphine. Developmental naltrexone exposure was associated with resistance to morphine-induced down-regulation of striatal preproenkephalin mRNA expression in adulthood. Adult offspring also exhibited greater operant responding for morphine and, in addition, cue-induced drug-seeking was enhanced. Collectively, these data show pronounced effects of developmental naltrexone exposure, some of which persist into adulthood, highlighting the need for follow up of humans that were exposed to naltrexone in utero.

  5. Cardiovascular effects of histamine administered intracerebroventricularly in critical haemorrhagic hypotension in rats.

    Science.gov (United States)

    Jochem, J

    2000-06-01

    The study was designed to determine the cardiovascular effects of histamine administered intracerebroventricularly (icv) in a rat model of volume-controlled haemorrhagic shock. The withdrawal of approximately 50% of total blood volume resulted in the death of all control saline icv treated animals within 30 min. Icv injection of histamine produced a prompt dose-dependent (0.1-100 nmol) and long-lasting (10-100 nmol) increase in mean arterial pressure (MAP), pulse pressure (PP) and heart rate (HR), with a 100% survival of 2h after treatment (100 nmol). The increase in MAP and HR after histamine administration in bled rats in comparison to the normovolaemic animals was 2.7-3.3- and 1.3-3.6-fold higher, respectively. Pretreatment with chlorpheniramine (50 nmol icv), H1 receptor antagonist, inhibited the increase in MAP, PP, HR and survival rate produced by histamine, while chlorpheniramine given alone had no effect. Neither ranitidine (50 nmol icv), H2 histamine receptor antagonist, nor thioperamide (50 nmol icv), H3 receptor blocker, influenced the histamine action, however, when given alone, both evoked the pressor effect with elongation of survival time. It can be concluded that histamine administered icv reverses the haemorrhagic shock conditions, and histamine H1 receptors are involved.

  6. 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.

  7. 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 ...

  8. Effect of arginine and threonine administered in ovo on digestive organ developments and subsequent growth performance of broiler chickens.

    Science.gov (United States)

    Tahmasebi, S; Toghyani, M

    2016-10-01

    This trial was conducted to investigate the effect of arginine (Arg), threonine (Thr) and Arg + Thr administered in ovo on growth performance, digestive organs and intestinal morphology in broiler chickens. On day 14 of incubation, 400 fertile eggs were randomly allotted to five experimental treatments through injection in the amniotic fluid including: (i) control (none injected), (ii) sham (0.5 ml of 0.5% saline), (iii) Arg (35 mg/egg), (iv) Thr (25 mg/egg) and (v) Arg + Thr (35 + 25 mg/egg). After hatching, chicks were given a commercial corn-soya bean diet up to 42 days of age. Daily feed intake (FI) and body weight (BW) of chicks were measured during different periods of the trial. Digestive organs were measured for their relative weight and intestinal length on days 11 and 42 of age. Intestinal morphometric traits were evaluated on day 11 of the experiment. Supplementing amino acids affected the performance of broiler chicks as Thr significantly increased FI and BW across starter, grower and finisher periods compared with sham and control (p  0.05); however, amino acid supplemented groups had lower villus height than control in jejunum (p pancreas (r = -0.484; p = 0.030), duodenal (r = -0.577; p = 0.007) as well as ileal lengths (r = -0.471; p = 0.035) and FI of entire period. Otherwise, positive relationships were observed between duodenum (r = 0.580; p = 0.007) and ileum (r = 0.582; p = 0.007) weights on day 42 and FI of chickens across the entire phase. In conclusion, Arg and particularly Thr injection into amnion can improve FI and post-hatch growth performance of chickens which may be mediated by the development of digestive organs. PMID:26608576

  9. Effect of silver nanoparticles and hydroxyproline, administered in ovo, on the development of blood vessels and cartilage collagen structure in chicken embryos

    DEFF Research Database (Denmark)

    Beck, Iwona; Hotowy, Anna; Sawosz, Ewa;

    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, collage......, 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....... 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...

  10. 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

  11. INFLUENCE OF SUCCINYLCHOLINE ON THE DOSE-RESPONSE RELATIONSHIP OF SUBSEQUENTLY ADMINISTERED ROCURONIUN

    Institute of Scientific and Technical Information of China (English)

    陈锡明; 闻大翔; 杭燕南; 孙大金

    2005-01-01

    Objective To investigate the effect of succinylcholine on the dose-response relationship of subsequently administered rocuronium in healthy patients. Methods Forty-eight ASA physical status Ⅰ-Ⅱ patients,aged 17 -65 years, scheduled for elective general surgery, were randomly assigned to either the rocuronium treatment group (R) or succinylcholine-rocuronium treatment group (SR). General anesthesia was induced with thiopental 4 to 6mg/kg and fentanyl 2 to 5μg/kg intravenously and maintained with 60% nitrous oxide in oxygen. Additional doses of thiopental or fentanyl were administered as required. The dose-response relationship of rocuronium was determined by the single dose-response technique. In R group ( n =24) , rocuronium was given after induction of anesthesia. In SR group (n =24 ) , patients were intubated after 1.5mg/kg of succinylcholine and rocuronium was given after the complete recovery of neuromuscular blockade from succinylcholine. Patients were further randomly divided into 4 subgroups receiving 150, 200, 250 or 300μg/kg of rocuronium respectively in both groups. Neuromuscular function was assessed accelographically with train-of-four (TOF) stimulation at the wrist every 12s (using the TOF Guard(R) accelerometer). The relationship between probit-tranformed percentage depression of first twitch height (Th) of train-of-four stimulation and logarithm dose of rocuronium was analyzed using linear regression.Results The dose-response curve of rocuronium after succinylcholine was shifted to the left in a parallel fashion compared with that of rocuronium given alone. ED50 and ED95 of rocuronium were 193 ±69 and 367 ± 73μg/kg respectively in R group, and 158 ± 35 and 317 ± 80μg/kg respectively in SR group ( P < 0. 05 ). Conclusion Succinylcholine shifts the dose-response curve of rocuronium to the left and potentiates the effects of the neuromuscular blockade by about 15% of subsequently administered rocuronium. Lower doses of rocuronium are

  12. 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

  13. 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

  14. 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...

  15. The effect of spinally administered WIN 55,212-2, a cannabinoid agonist, on thermal pain sensitivity in diabetic rats

    Directory of Open Access Journals (Sweden)

    Samane Jahanabadi

    2016-04-01

    Conclusion: These data show that cannabinoids have potent antinociceptive effects through direct actions in the spinal dorsal horn of nociceptive pathway. This suggests that intrathecally administered cannabinoids may offer hopeful strategies for the treatment of diabetic neuropathic pain.

  16. 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; Lowder, Travis; Mathur, Shivani; Mercer, Megan

    2016-06-23

    This report is an economic study of utility-administered solar programs in Virginia and the Southeast region at large. It includes an assessment of soft cost reduction opportunities, community solar programs, and the investment tax credit.

  17. Safety of elevated dosages of a 0.24% diflubenzuron pellet administered orally to horses.

    Science.gov (United States)

    Ross, Douglas H; Heird, Charles; Byrd, John W; Beauchemin, Vivienne; Kiess, Wendy

    2007-01-01

    The safety of a feed-thru pellet formulation containing the insect growth regulator diflubenzuron (0.24%) for control of manure-breeding flies (Musca domestica L. and Stomoxys calcitrans L.) in horses was evaluated. Pellets were administered orally at 0, 1, 3, and 5 times the clinical dosage (0.12 to 0.20 mg/kg) on a daily basis for 31 consecutive days. Variables examined included daily clinical observations, hematology, coagulation, serum chemistry, acetylcholinesterase inhibition, body weights, and physical examinations. Horses remained healthy throughout the study, and no adverse reactions or events related to the pellets were observed. Statistically significant differences (P horses at 0.12 to 0.20 mg/kg for control of manure-breeding flies.

  18. 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.

  19. Reduction in the Nephrotoxicity of Amphotericin B when Administered in 20% Intralipid

    Directory of Open Access Journals (Sweden)

    Suzette Salama

    1997-01-01

    Full Text Available The administration of amphotericin B (AmB is often limited by the development of nephrotoxicity. In a pilot crossover trial, aqueous AmB followed by a new preparation of a mixture of AmB with 20% intralipid (AmB-IL was administered to 10 immunocompromised patients for systemic fungal infections caused by Candida species. Mean total dose and duration of therapy with AmB-IL exceeded that of aqueous AmB (649±165 mg versus 394±105 mg, P=0.061 and 13.2±2.5 days versus 9±2.1 days, P=0.31. However, mean creatinine clearance of the patients rose during AmB-IL therapy by 10.7±7.7 mL/min (P=0.03. AmB-IL warrants further investigation to assess its stability and efficacy for treating serious fungal infections.

  20. 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...

  1. Development of tolerance to the antinociceptive effect of mescaline intraventricularly administered to rabbits.

    Science.gov (United States)

    Ferri, S; Santagostino, A; Braga, P C

    1976-06-23

    Some effects of intraventricular injection of mescaline are examined in conscious rabbits. By means of electrical stimulation of the tooth pulp it is shown that an acute treatment with 70, 100, 150 mug/kg of mescaline elicits analgesia, the intensity of which is dose-dependent: with daily administration of 100 mug/kg for 5 days a complete tolerance develops to the antinociceptive effect. A tolerance also develops to the behavioral effects of mescaline after repeated administrations, with the exception of the stuporous state, a symptom which, on the contrary, is accentuated as the treatment proceeds. An EEG arousal is induced in the rabbit by acutely administered mescaline; the chronic treatment (100 mug/kg) makes the return of voltage to original levels progressively slower. Finally, the confrontation of certain of the mescaline-induced effects with those of morphine suggests some biochemical and neural patterns common to the 2 drugs.

  2. Influence of co-administered danshensu on pharmacokinetic fate and tissue distribution of paeonol in rats.

    Science.gov (United States)

    Li, Hua; Wang, Siwang; Zhang, Bangle; Xie, Yanhua; Wang, Jianbo; Yang, Qian; Cao, Wei; Hu, Jing; Duan, Linrui

    2012-01-01

    Cortex Moutan (root bark of Paeonia suffruticosa Andrew) and Radix Salviae miltiorrhizae (root and rhizome of Salvia miltiorrhiza Bunge) are two herbs widely used in traditional Chinese medicine (TCM) to treat cerebrovascular and cardiovascular diseases. In clinical practice, these two herbs are prescribed together. Studies on the pharmacokinetic interaction between the active constituents of these two herbs (paeonol and danshensu, respectively) can provide substantial foundation for understanding its mechanism and empirical evidence to support the clinical practice. A simple and sensitive high-performance liquid chromatographic (HPLC) method coupled with ultraviolet detector was developed for determination of paeonol in plasma and different tissues (heart, liver, spleen, lung, kidney, and brain) of male Sprague-Dawley rats. When co-administering danshensu, the peak plasma concentration of paeonol was decreased (p brain, and lung were dramatically increased (p brain, providing substantial foundation for the investigation of the impact of danshensu on paeonol in clinical applications.

  3. 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

  4. 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.

  5. 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

  6. 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

  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. 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

  9. Differential Gene Expression across Breed and Sex in Commercial Pigs Administered Fenbendazole and Flunixin Meglumine.

    Science.gov (United States)

    Howard, Jeremy T; O'Nan, Audrey T; Maltecca, Christian; Baynes, Ronald E; Ashwell, Melissa S

    2015-01-01

    Characterizing the variability in transcript levels across breeds and sex in swine for genes that play a role in drug metabolism may shed light on breed and sex differences in drug metabolism. The objective of the study is to determine if there is heterogeneity between swine breeds and sex in transcript levels for genes previously shown to play a role in drug metabolism for animals administered flunixin meglumine or fenbendazole. Crossbred nursery female and castrated male pigs (n = 169) spread across 5 groups were utilized. Sires (n = 15) of the pigs were purebred Duroc, Landrace, Yorkshire or Hampshire boars mated to a common sow population. Animals were randomly placed into the following treatments: no drug (control), flunixin meglumine, or fenbendazole. One hour after the second dosing, animals were sacrificed and liver samples collected. Quantitative Real-Time PCR was used to measure liver gene expression of the following genes: SULT1A1, ABCB1, CYP1A2, CYP2E1, CYP3A22 and CYP3A29. The control animals were used to investigate baseline transcript level differences across breed and sex. Post drug administration transcript differences across breed and sex were investigated by comparing animals administered the drug to the controls. Contrasts to determine fold change were constructed from a model that included fixed and random effects within each drug. Significant (P-value fenbendazole, respectively. The current analysis found transcript level differences across swine breeds and sex for multiple genes, which provides greater insight into the relationship between flunixin meglumine and fenbendazole and known drug metabolizing genes.

  10. Optimising Controlled Human Malaria Infection Studies Using Cryopreserved P. falciparum Parasites Administered by Needle and Syringe.

    Directory of Open Access Journals (Sweden)

    Susanne H Sheehy

    Full Text Available Controlled human malaria infection (CHMI studies have become a routine tool to evaluate efficacy of candidate anti-malarial drugs and vaccines. To date, CHMI trials have mostly been conducted using the bite of infected mosquitoes, restricting the number of trial sites that can perform CHMI studies. Aseptic, cryopreserved P. falciparum sporozoites (PfSPZ Challenge provide a potentially more accurate, reproducible and practical alternative, allowing a known number of sporozoites to be administered simply by injection.We sought to assess the infectivity of PfSPZ Challenge administered in different dosing regimens to malaria-naive healthy adults (n = 18. Six participants received 2,500 sporozoites intradermally (ID, six received 2,500 sporozoites intramuscularly (IM and six received 25,000 sporozoites IM.Five out of six participants receiving 2,500 sporozoites ID, 3/6 participants receiving 2,500 sporozoites IM and 6/6 participants receiving 25,000 sporozoites IM were successfully infected. The median time to diagnosis was 13.2, 17.8 and 12.7 days for 2,500 sporozoites ID, 2,500 sporozoites IM and 25,000 sporozoites IM respectively (Kaplan Meier method; p = 0.024 log rank test.2,500 sporozoites ID and 25,000 sporozoites IM have similar infectivities. Given the dose response in infectivity seen with IM administration, further work should evaluate increasing doses of PfSPZ Challenge IM to identify a dosing regimen that reliably infects 100% of participants.ClinicalTrials.gov NCT01465048.

  11. 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

  12. 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.

  13. 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.

  14. 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; Rebuelto, Marcela

    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

  15. 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.

  16. 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 thioibotenic acid...

  17. Synthesis and Characterization of Fatty Acid Conjugates of Niacin and Salicylic Acid.

    Science.gov (United States)

    Vu, Chi B; Bemis, Jean E; Benson, Ericka; Bista, Pradeep; Carney, David; Fahrner, Richard; Lee, Diana; Liu, Feng; Lonkar, Pallavi; Milne, Jill C; Nichols, Andrew J; Picarella, Dominic; Shoelson, Adam; Smith, Jesse; Ting, Amal; Wensley, Allison; Yeager, Maisy; Zimmer, Michael; Jirousek, Michael R

    2016-02-11

    This report describes the synthesis and preliminary biological characterization of novel fatty acid niacin conjugates and fatty acid salicylate conjugates. These molecular entities were created by covalently linking two bioactive molecules, either niacin or salicylic acid, to an omega-3 fatty acid. This methodology allows the simultaneous intracellular delivery of two bioactives in order to elicit a pharmacological response that could not be replicated by administering the bioactives individually or in combination. The fatty acid niacin conjugate 5 has been shown to be an inhibitor of the sterol regulatory element binding protein (SREBP), a key regulator of cholesterol metabolism proteins such as PCSK9, HMG-CoA reductase, ATP citrate lyase, and NPC1L1. On the other hand, the fatty acid salicylate conjugate 11 has been shown to have a unique anti-inflammatory profile based on its ability to modulate the NF-κB pathway through the intracellular release of the two bioactives.

  18. Phase I trial of orally administered pentosan polysulfate in patients with advanced cancer.

    Science.gov (United States)

    Marshall, J L; Wellstein, A; Rae, J; DeLap, R J; Phipps, K; Hanfelt, J; Yunmbam, M K; Sun, J X; Duchin, K L; Hawkins, M J

    1997-12-01

    Tumor angiogenesis is critically important to tumor growth and metastasis. We have shown that pentosan polysulfate (PPS) is an effective inhibitor of heparin-binding growth factors in vitro and can effectively inhibit the establishment and growth of tumors in nude mice. Following completion of our Phase I trial of s.c. administered PPS, we performed a Phase I trial of p.o. administered PPS in patients with advanced cancer to determine the maximum tolerated dose (MTD) and toxicity profile and to search for any evidence for biological activity in vivo. Patients diagnosed with advanced, incurable malignancies who met standard Phase I criteria and who did not have a history of bleeding complications were enrolled, in cohorts of three, to receive PPS p.o. t.i.d., at planned doses of 180, 270, 400, 600, and 800 mg/m2. Patients were monitored at least every 2 weeks with physical exams and weekly with hematological, chemistry, stool hemoccult, and coagulation blood studies, and serum and urine samples for PPS and basic fibroblastic growth factor (bFGF) levels were also taken. The PPS dose was escalated in an attempt to reach the MTD. Eight additional patients were enrolled at the highest dose to further characterize the toxicity profile and biological in vivo effects of PPS. A total of 21 patients were enrolled in the three cohorts of doses 180 (n = 4), 270 (n = 3), and 400 (n = 14) mg/m2. The most severe toxicities seen were grade 3 proctitis and grade 4 diarrhea; however, 20 of the 21 patients had evidence of grade 1 or 2 gastrointestinal (GI) bleeding. These toxicities became evident at a much earlier time point as the dose was increased, but their severities were similar at all dose levels. There were no objective responses, although three patients had prolonged stabilization of previously progressing disease. Pharmacokinetic analysis suggested marked accumulation of PPS upon chronic administration. Serum and urine bFGF levels failed to show a consistent, interpretable

  19. 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

  20. Differential Gene Expression across Breed and Sex in Commercial Pigs Administered Fenbendazole and Flunixin Meglumine.

    Directory of Open Access Journals (Sweden)

    Jeremy T Howard

    Full Text Available Characterizing the variability in transcript levels across breeds and sex in swine for genes that play a role in drug metabolism may shed light on breed and sex differences in drug metabolism. The objective of the study is to determine if there is heterogeneity between swine breeds and sex in transcript levels for genes previously shown to play a role in drug metabolism for animals administered flunixin meglumine or fenbendazole. Crossbred nursery female and castrated male pigs (n = 169 spread across 5 groups were utilized. Sires (n = 15 of the pigs were purebred Duroc, Landrace, Yorkshire or Hampshire boars mated to a common sow population. Animals were randomly placed into the following treatments: no drug (control, flunixin meglumine, or fenbendazole. One hour after the second dosing, animals were sacrificed and liver samples collected. Quantitative Real-Time PCR was used to measure liver gene expression of the following genes: SULT1A1, ABCB1, CYP1A2, CYP2E1, CYP3A22 and CYP3A29. The control animals were used to investigate baseline transcript level differences across breed and sex. Post drug administration transcript differences across breed and sex were investigated by comparing animals administered the drug to the controls. Contrasts to determine fold change were constructed from a model that included fixed and random effects within each drug. Significant (P-value <0.007 basal transcript differences were found across breeds for SULT1A1, CYP3A29 and CYP3A22. Across drugs, significant (P-value <0.0038 transcript differences existed between animals given a drug and controls across breeds and sex for ABCB1, PS and CYP1A2. Significant (P <0.0038 transcript differences across breeds were found for CYP2E1 and SULT1A1 for flunixin meglumine and fenbendazole, respectively. The current analysis found transcript level differences across swine breeds and sex for multiple genes, which provides greater insight into the relationship between flunixin

  1. Differential Gene Expression across Breed and Sex in Commercial Pigs Administered Fenbendazole and Flunixin Meglumine

    Science.gov (United States)

    Howard, Jeremy T.; O’Nan, Audrey T.; Maltecca, Christian; Baynes, Ronald E.; Ashwell, Melissa S.

    2015-01-01

    Characterizing the variability in transcript levels across breeds and sex in swine for genes that play a role in drug metabolism may shed light on breed and sex differences in drug metabolism. The objective of the study is to determine if there is heterogeneity between swine breeds and sex in transcript levels for genes previously shown to play a role in drug metabolism for animals administered flunixin meglumine or fenbendazole. Crossbred nursery female and castrated male pigs (n = 169) spread across 5 groups were utilized. Sires (n = 15) of the pigs were purebred Duroc, Landrace, Yorkshire or Hampshire boars mated to a common sow population. Animals were randomly placed into the following treatments: no drug (control), flunixin meglumine, or fenbendazole. One hour after the second dosing, animals were sacrificed and liver samples collected. Quantitative Real-Time PCR was used to measure liver gene expression of the following genes: SULT1A1, ABCB1, CYP1A2, CYP2E1, CYP3A22 and CYP3A29. The control animals were used to investigate baseline transcript level differences across breed and sex. Post drug administration transcript differences across breed and sex were investigated by comparing animals administered the drug to the controls. Contrasts to determine fold change were constructed from a model that included fixed and random effects within each drug. Significant (P-value <0.007) basal transcript differences were found across breeds for SULT1A1, CYP3A29 and CYP3A22. Across drugs, significant (P-value <0.0038) transcript differences existed between animals given a drug and controls across breeds and sex for ABCB1, PS and CYP1A2. Significant (P <0.0038) transcript differences across breeds were found for CYP2E1 and SULT1A1 for flunixin meglumine and fenbendazole, respectively. The current analysis found transcript level differences across swine breeds and sex for multiple genes, which provides greater insight into the relationship between flunixin meglumine and

  2. 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

  3. 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.

  4. 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

  5. Effect of the bile-acid sequestrant colestipol on postprandial serum bile-acid concentration: evaluation by bioluminescent enzymic analysis.

    Science.gov (United States)

    Rossi, S S; Wayne, M L; Smith, R B; Wright, C E; Andreadis, N A; Hofmann, A F

    1989-02-01

    Chronic ingestion of bile-acid sequestrants has been shown to decrease the serum cholesterol concentration and coronary events in hypercholesterolaemic patients. To develop improved sequestrants, a rapid, convenient method for testing the bile-acid binding efficacy of sequestrants is needed. Serum bile-acid concentrations could be used to detect bile-acid binding by an administered sequestrant, since the serum bile-acid concentration is determined largely by the rate of intestinal absorption in healthy individuals. To test this, serum bile-acid concentrations were measured at frequent intervals over 24 h in five otherwise healthy hypercholesterolaemic subjects during the ingestion of three standard meals, with or without the addition of 5 g colestipol granules administered 30 min before each meal. Total serum bile-acid concentration was measured with a previously reported bioluminescent enzymic assay, that uses a 3 alpha-hydroxysteroid dehydrogenase, an oxido-reductase, and a bacterial luciferase co-immobilized on to Sepharose beads. Bile acids in 1 ml of serum were isolated by solid-phase extraction chromatography with reversed-phase C18 cartridges. Colestipol lowered the postprandial elevation of serum bile acids by one half, with a subsequent decrease in the cumulative area under the curve. The data suggest that measurement of serum bile-acid concentrations by bioluminescence is a rapid, simple way to document the efficacy of bile-acid sequestrants.

  6. Immunoprophylactic effects of administering honeybee (Apis melifera) venom spray against Salmonella gallinarum in broiler chicks.

    Science.gov (United States)

    Jung, Bock-Gie; Lee, Jin-A; Park, Seong-Beom; Hyun, Pung-Mi; Park, Jin-Kyu; Suh, Guk-Hyun; Lee, Bong-Joo

    2013-10-01

    Antibiotics continue to be used as growth promoters in the poultry industry. Honeybee (Apis melifera) venom (HBV) possesses a number of beneficial biological activities, particularly for regulating the immune system. The aim of the present study was to evaluate the immunoprophylactic effects of HBV against Salmonella Gallinarum in broiler chicks as an initial step towards developing eco-friendly alternatives to reduce antibiotic use. HBV was administered using a spray technique. HBV improved body weight gain, particularly in the presence of infection. Moreover, HBV enhanced antibody production activity against formalin-killed S. Gallinarum. The CD4(+):CD8(+) T lymphocyte ratio, relative mRNA expression levels of interleukin-18 and interferon-γ, and serum lysozyme activity also increased following HBV administration before the infection period as well as during infection. HBV reinforced bacterial clearance and increased survivability against S. Gallinarum. Corresponding pathological analyses demonstrated that the HBV-sprayed group displayed mild and less severe abnormal changes compared with those in the control group. It was presumed that the prophylactic effects of HBV against S. Gallinarum were associated with its non-specific immune response stimulating activity. Thus, HBV may provide an alternative to reduce antibiotic use in the poultry industry. PMID:23719751

  7. Tissue biodistribution and blood clearance rates of intravenously administered carbon nanotube radiotracers

    Science.gov (United States)

    Singh, Ravi; Pantarotto, Davide; Lacerda, Lara; Pastorin, Giorgia; Klumpp, Cédric; Prato, Maurizio; Bianco, Alberto; Kostarelos, Kostas

    2006-02-01

    Carbon nanotubes (CNT) are intensively being developed for biomedical applications including drug and gene delivery. Although all possible clinical applications will require compatibility of CNT with the biological milieu, their in vivo capabilities and limitations have not yet been explored. In this work, water-soluble, single-walled CNT (SWNT) have been functionalized with the chelating molecule diethylentriaminepentaacetic (DTPA) and labeled with indium (111In) for imaging purposes. Intravenous (i.v.) administration of these functionalized SWNT (f-SWNT) followed by radioactivity tracing using gamma scintigraphy indicated that f-SWNT are not retained in any of the reticuloendothelial system organs (liver or spleen) and are rapidly cleared from systemic blood circulation through the renal excretion route. The observed rapid blood clearance and half-life (3 h) of f-SWNT has major implications for all potential clinical uses of CNT. Moreover, urine excretion studies using both f-SWNT and functionalized multiwalled CNT followed by electron microscopy analysis of urine samples revealed that both types of nanotubes were excreted as intact nanotubes. This work describes the pharmacokinetic parameters of i.v. administered functionalized CNT relevant for various therapeutic and diagnostic applications. nanomedicine | blood circulation half-life | drug delivery | pharmacokinetics | nanotoxicology

  8. 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

  9. 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......) and 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...

  10. Recovery of Cognitive Dysfunction via Orally Administered Redox-Polymer Nanotherapeutics in SAMP8 Mice.

    Directory of Open Access Journals (Sweden)

    Pennapa Chonpathompikunlert

    Full Text Available Excessively generated reactive oxygen species are associated with age-related neurodegenerative diseases. We investigated whether scavenging of reactive oxygen species in the brain by orally administered redox nanoparticles, prepared by self-assembly of redox polymers possessing antioxidant nitroxide radicals, facilitates the recovery of cognition in 17-week-old senescence-accelerated prone (SAMP8 mice. The redox polymer was delivered to the brain after oral administration of redox nanoparticles via a disintegration of the nanoparticles in the stomach and absorption of the redox polymer at small intestine to the blood. After treatment for one month, levels of oxidative stress in the brain of SAMP8 mice were remarkably reduced by treatment with redox nanoparticles, compared to that observed with low-molecular-weight nitroxide radicals, resulting in the amelioration of cognitive impairment with increased numbers of surviving neurons. Additionally, treatment by redox nanoparticles did not show any detectable toxicity. These findings indicate the potential of redox polymer nanotherapeutics for treatment of the neurodegenerative diseases.

  11. 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.

  12. 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.

  13. Development of a self-administered web-based test for longitudinal cognitive assessment

    Science.gov (United States)

    Ruano, Luis; Sousa, Andreia; Severo, Milton; Alves, Ivânia; Colunas, Márcio; Barreto, Rui; Mateus, Cátia; Moreira, Sandra; Conde, Eduardo; Bento, Virgílio; Lunet, Nuno; Pais, Joana; Tedim Cruz, Vítor

    2016-01-01

    Sequential testing with brief cognitive tools has been recommended to improve cognitive screening and monitoring, however the few available tools still depend on an external evaluator and periodic visits. We developed a self-administered computerized test intended for longitudinal cognitive testing (Brain on Track). The test can be performed from a home computer and is composed of several subtests, expected to evaluate different cognitive domains, all including random elements to minimize learning effects. An initial (A) and a refined version of the test (B) were applied to patients with mild cognitive impairment or early dementia (n = 88) and age and education-matched controls. A subsample of a population-based cohort (n = 113) performed the test at home every three months to evaluate test-retest reliability. The test’s final version Cronbach’s alpha was 0.90, test scores were significantly different between patients and controls (p = 0.001), the area under the receiver operating characteristic curve was 0.75 and the smallest real difference (43.04) was lower than the clinical relevant difference (56.82). In the test-retest reliability analysis 9/10 subtests showed two-way mixed single intraclass consistency correlation coefficient >0.70. These results imply good internal consistency, discriminative ability and reliability when performed at home, encouraging further longitudinal clinical and population-based studies. PMID:26743329

  14. 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

  15. Lack of selective developmental toxicity of three butanol isomers administered by inhalation to rats.

    Science.gov (United States)

    Nelson, B K; Brightwell, W S; Khan, A; Burg, J R; Goad, P T

    1989-04-01

    As part of an ongoing study of the developmental toxicology of industrial alcohols, this report presents the results of the teratology assessments of 1-butanol, 2-butanol, and t-butanol administered by inhalation to rats. Groups of approximately 15 Sprague-Dawley rats were exposed at 8000, 6000, 3500, or 0 ppm 1-butanol, 7000, 5000, 3500, or 0 ppm 2-butanol, or 5000, 3500, 2000, or 0 ppm t-butanol for 7 hr/day on Gestation Days 1-19 (sperm = 0). In each case, the highest concentration was selected to produce maternal toxicity. Dams were sacrificed on Gestation Day 20, and fetuses were individually weighed, tagged, and examined for external malformations. One-half of the fetuses were stained and examined for skeletal abnormalities, and the other half were examined for visceral defects using the Wilson technique. For each butanol isomer examined, the highest concentration (and the intermediate in some cases) was maternally toxic, as manifest by reduced weight gain and feed intake. Even at a maternally toxic dose, and in spite of a dose-dependent reduction in fetal weights for each isomer, the only teratogenicity observed was a slight increase in skeletal malformations (primarily rudimentary cervical ribs), seen with the highest concentration of 1-butanol. Thus, although teratogenicity was observed at 8000 ppm 1-butanol, and developmental toxicity was observed with each of the butyl alcohol isomers studied, concentrations 50 times the current permissible exposure limits for these three butanol isomers do not produce teratogenicity in rats.

  16. Toxic effects of methoxychlor administered subcutaneously on the hypothalamic-pituitary-testicular axis in adult rats.

    Science.gov (United States)

    Lafuente, A; Cabaleiro, T; Caride, A; Esquifino, A I

    2008-05-01

    This study was undertaken to evaluate the effects of methoxychlor MTX at the hypothalamic-pituitary-testicular axis in adult male rats. This global objective comprises three major aims: (1) to analyze the possible differential MTX effects in norepinephrine and serotonin concentration an in serotoninergic metabolism in anterior, mediobasal and posterior hypothalamus and median eminence; (2) to evaluate effects induced by MTX exposure on gonadotropins and testosterone; 93 to elucidate whether the regulatory interactions in the hypothalamic-pituitary-testicular axis are modified by this pesticide. Animals were administered subcutaneously 25mg/kg/day of MTX for 1 month. MTX increased norepinephrine and serotonin content in anterior hypothalamus (P < or = 0.05), but decreased serotonin concentration in posterior hypothalamus (P < or = 0.05). MTX diminished serotonin turnover in anterior hypothalamus (P < or = 0.01) and decreased plasma LH (P < or = 0.001) and testosterone (P < or = 0.05) levels but those of FSH remained unmodified. We can conclude that MTX exposure: (1) could exert differential effects in norepinephrine and serotonin concentration an in serotoninergic metabolism in anterior, mediobasal and posterior hypothalamus and median eminence, being the anterior hypothalamus the most sensitive region to the pesticide; (2) could inhibit LH and testosterone secretion without changing FSH; (3) four potential pathways might be involved in MTX effects on testosterone secretion (changing LH secretion; modifying serotonin and norepinephrine at the hypothalamic level; alterating the direct neural pathway between brain and testes; and/or by a direct effect in testes).

  17. 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

  18. Reducing children's social anxiety symptoms: exploring a novel parent-administered cognitive bias modification training intervention.

    Science.gov (United States)

    Lau, Jennifer Y F; Pettit, Eleanor; Creswell, Cathy

    2013-07-01

    Social fears and worries in children are common and impairing. Yet, questions have been raised over the efficacy, suitability and accessibility of current frontline treatments. Here, we present data on the effectiveness of a novel parent-administered Cognitive Bias Modification of Interpretations (CBM-I) training tool. CBM-I capitalises on findings demonstrating an association between anxiety symptoms and biased interpretations, the tendency to interpret ambiguous situations negatively. Through CBM-I training, participants are exposed to benign resolutions, and reinforced for selecting these. In adults and adolescents, CBM-I training is effective at reducing symptoms and mood reactivity. In the present study, we developed a novel, child-appropriate form of CBM-I training, by presenting training materials within bedtime stories, read by a parent to the child across three consecutive evenings. Compared to a test-retest control group (n = 17), children receiving CBM-I (n = 19) reported greater endorsement of benign interpretations of ambiguous situations post-training (compared to pre-training). These participants (but not the test-retest control group) also showed a significant reduction in social anxiety symptoms. Pending replication and extensions to a clinical sample, these data may implicate a cost-effective, mechanism-driven and developmentally-appropriate resource for targeting social anxiety problems in children.

  19. A Novel Application of RFID in Hospitals for Involuntary Administering to Incorporate Authentication and Tracking

    Directory of Open Access Journals (Sweden)

    A.Mohamed Syed Ali

    2014-03-01

    Full Text Available Today many hospitals use RFID system to monitor the health records for patient to update the patient information to doctors and patients relatives. In this system Customers can view and update their personal medical information via the web site, which seamlessly sync with one another. RFID is a total system, as opposed to a single product. It provides electronic identity to any object. Electronic information about the object is stored in RFID chip embedded of attached to the object. With an RFID reader the electronic identity can be read wirelessly. We have analyzed completely about the various applications of the RFID and we have come to a conclusion that the RFID can be effectively implemented in the hospitals to manage and monitor various systems of the hospitals automatically. This project is too costly to be implemented now, but the rates of the RFID accessories are expected to come down in the near future. For this automated administering the project needs a Central Monitoring Unit which we have decided to be controlled by software made in a high level language (C. For the reference of the reader we have attached the implementation files with this paper. This paper explains the basics of RFID, its working and our contribution towards RFID.

  20. 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...

  1. The antinociceptive efficacy of buprenorphine administered through the drinking water of rats

    DEFF Research Database (Denmark)

    Jessen, L; Bjerrum, Ole Jannik; Christensen, Sten

    2007-01-01

    Postoperative pain management in laboratory animals is important for animal welfare and required under law in many countries. Frequent injection of analgesics to rodents after surgery is stressful for the animals and labour-intensive for animal care personnel. An alternative dosing scheme such as...... water may be a viable treatment option for the relief of pain in laboratory rats, but at the doses used in this study in pain-free rats it was associated with a decrease in water intake and some behavioural changes....... such as administration of analgesics in the drinking water would be desirable. However, the efficacy of a chronic oral analgesic treatment via this route has not yet been documented. This study investigated the antinociceptive efficacy of buprenorphine administered ad libitum via the drinking water of laboratory rats....... The antinociceptive efficacy of buprenorphine in drinking water was compared with repeated subcutaneous injections. A comparison was also made between buprenorphine in drinking water and the combination of one single subcutaneous injection of buprenorphine followed by buprenorphine in drinking water. Antinociception...

  2. 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

  3. 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

  4. Subcutaneously Administered Self-Cleaving Hydrogel-Octreotide Conjugates Provide Very Long-Acting Octreotide.

    Science.gov (United States)

    Schneider, Eric L; Henise, Jeff; Reid, Ralph; Ashley, Gary W; Santi, Daniel V

    2016-07-20

    We developed a long-acting drug-delivery system that supports subcutaneous administration of the peptidic somatostatin agonist octreotide-a blockbuster drug used to treat acromegaly and neuroendocrine tumors. The current once-a-month polymer-encapsulated octreotide, Sandostatin LAR, requires a painful intragluteal injection through a large needle by a health-care professional. To overcome such shortcomings, Tetra-PEG hydrogel microspheres were covalently attached to the α-amine of d-Phe(1) or the ε-amine of Lys(5) of octreotide by a self-cleaving β-eliminative linker; upon subcutaneous injection in the rat using a small-bore needle, octreotide was slowly released. The released drug from the ε-octreotide conjugate showed a remarkably long serum half-life that exceeded two months. The α-octreotide conjugate had a half-life of ∼2 weeks, and showed an excellent correlation of in vitro and in vivo drug release. Pharmacokinetic models indicate these microspheres should support once-weekly to once-monthly self-administered subcutaneous dosing in humans. The hydrogel-octreotide conjugate shows the favorable pharmacokinetics of Sandostatin LAR without its drawbacks. PMID:27253622

  5. Uncaria tomentosa (Willd. ex. Roem. & Schult.) DC. and Eucalyptus globulus Labill. interactions when administered with diazepam.

    Science.gov (United States)

    Quílez, A M; Saenz, M T; García, M D

    2012-03-01

    The safety of natural drugs is defined by their side effects and toxicity as well as any interactions that may occur if taken together with other drugs. In particular, it is essential to identify synergies, antagonisms and other types of interference with other drugs so that the correct choice can be made from the range of phytomedicines available. The aim of this work was to investigate changes in the pharmacological effect of diazepam (2 mg/kg) on the CNS when administered together with a medicinal plant: Eucalyptus globulus Labill. (eucalyptus 6 mg/kg and 3.25 mg/kg) or Uncaria tomentosa (Willd. ex Roem. & Schult). DC. (cat's claw, 7.14 mg/kg and 3.54 mg/kg). Various different psychopharmacological effects were evaluated through assessing exploratory behavior, muscle relaxation and spontaneous motor activity. Both phytodrugs interacted with the benzodiazepine. Eucalyptus had an inhibitory effect at both doses and could be useful at the highest dose in cases where the desired effect of the depressant is moderate anxiolytic activity without marked muscle relaxation. Cat's claw, at both doses, enhanced the action of diazepam on spontaneous motor activity and, at the lowest dose, exploratory ability. These herbal drugs could be useful for their antiinflammatory activity in musculoskeletal pathologies treated with benzodiazepines.

  6. 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.

  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. Factors determining the ability of parents to effectively administer intramuscular adrenaline to food allergic children.

    Science.gov (United States)

    Arkwright, Peter D; Farragher, Alex J

    2006-05-01

    Intramuscular adrenaline is the treatment of choice for food-related anaphylactic reactions. Although auto-injectable adrenaline devices are routinely prescribed for patients at risk of serious reactions, previous studies have shown that only one-third to one and a half of patients or their carers are able to properly use these devices. The aim of this study was to determine which factors are most strongly associated with the effective use of these devices. A 122 children with food allergies who had previously been prescribed EpiPens and were attending a single specialist pediatric allergy center in the UK. were studied prospectively. A 69% of parents were unable to use the EpiPen, did not have it available, or did not know when it should be administered. A prior practical demonstration was associated with a 4-5 fold greater chance that parents would be able to use the device (p EpiPens to be used safely and effectively it is essential to educate the carer at the time the device is prescribed.

  9. 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

  10. Pharmacokinetics and metabolism of orally administered firocoxib, a novel second generation coxib, in horses.

    Science.gov (United States)

    Kvaternick, V; Pollmeier, M; Fischer, J; Hanson, P D

    2007-06-01

    The primary objective of this study was to determine the pharmacokinetic profile of firocoxib, a novel second generation coxib, in horses. Horses were administered either a single oral or intravenous dose of firocoxib at 0.1 mg/kg in a two-period crossover study with 12 animals. The dosage was based on previously determined pharmacodynamic parameters. Oral firocoxib was well absorbed with an average bioavailability (absolute) of 79% and a Cmax of 75 ng/mL at 3.9 h. The average elimination half-life was 30 h. Following intravenous administration the average Cmax was 210 ng/mL and the elimination half-life was 34 h. The area under the curve [AUC(0-tlast)] was 1.8 microg.h/mL for the oral dose and 2.3 microg.h/mL for the intravenous dose. Firocoxib was widely distributed with a volume of distribution value of 1.7 L/kg for the intravenous dose. Biotransformation of firocoxib was via dealkylation and glucuronidation to inactive metabolites, namely descyclopropylmethylfirocoxib and its glucuronide conjugate. Urinary excretion was the major route of elimination, and the clearance rate was 37 mL/h/kg. PMID:17472652

  11. 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.

  12. Diphtheria-tetanus-pertussis vaccination administered after measles vaccine: increased female mortality?

    Science.gov (United States)

    Benn, Christine Stabell; Aaby, Peter

    2012-10-01

    In low-income countries, children should receive 3 doses of diphtheria-tetanus-pertussis vaccine (DTP) at 6, 10 and 14 weeks of age, and measles vaccine at 9 months of age. However, there is often a delay in administering the vaccines, and DTP is often given after measles vaccine. Previous observations suggest that this practice is associated with increased mortality for female, but not for male children. Within a vitamin A trial in Guinea-Bissau, vaccination status was registered at the time of measles vaccination at 9 months; 141 (31%) of 455 children were missing 1 or more DTP vaccines and were likely to receive them afterward. We examined whether missing DTP vaccine at this time point was associated with sex-differential effects on mortality. In female children, missing DTP was associated with 3.55 (95% confidence interval: 1.23-10.26) times higher risk of dying before 36 months of age, whereas it made no difference in male children (0.97 [0.34-2.80]). The result supports that receiving DTP after measles vaccine affects female children negatively.

  13. Assessment of the toxicity of cyclohexanone administered intravenously to Wistar and Gunn rats.

    Science.gov (United States)

    Greener, Y; Martis, L; Indacochea-Redmond, N

    1982-09-01

    The toxicity of cyclohexanone, used as a solvent cement in polyvinyl chloride medical devices, was assessed in Wistar and Gunn rats. The Gunn rat was used because it has a negligible activity of UDP glucuronosyltransferase toward bilirubin and certain other aglycones. Cyclohexanone was administered iv for 28 consecutive days to Wistar and Gunn rats in two doses (50 and 100 mg/kg), using solutions containing 0.25 and 0.50 g per 100 ml, respectively, at a constant volume of 20 mg/kg. Saline (0.9% NaCl) was used as the control. Daily observations for signs of toxicity showed no adverse effects in Wistar or Gunn rats injected with either dose. Daily weight changes of control and test animals were similar. Ophthalmologic examinations revealed no treatment-related structural lesions. No adverse effects were noted when the data from the hemogram or clinical chemistry parameters were evaluated. Gross pathological and histopathologic assessment showed no alterations due to cyclohexanone treatment. Urinary excretions of total and glucuronide conjugates of cyclohexanol were similar for Wistar and Gunn rats; less than 1% was excreted as free cyclohexanone and cyclohexanol. It is concluded that the Gunn rat is capable of forming glucuronides of cyclohexanol and that cyclohexanone at these doses has a negligible toxic potential.

  14. Pharmacokinetics and penetration into synovial fluid of systemical and electroporation administered sinomenine to rabbits.

    Science.gov (United States)

    Yan, Huan; Yan, Miao; Li, Huan-De; Jiang, Pei; Deng, Yang; Cai, Hua-Lin

    2015-06-01

    Sinomenine is an anti-rheumatoid arthritis (RA) drug derived from the Sinomenium acutum. The major site of RA treatment is within the synovial compartment. However, the pharmacokinetic and penetration into synovial fluid (SF) of sinomenine have not been reported. In our study, the pharmacokinetics and penetration into SF of systemic and electroporation administered sinomenine were investigated by microdialysis incorporated with HPLC-MS/MS. Sinomenine went into plasma and SF more rapidly with higher peak concentration (Cmax ) by intramuscular injection compared with oral administration. The area under the concentration-time graph (AUC0-∞ ) of intramuscularly injected sinomenine was 1,403,294.75 ± 125,534.567 ng min/mL in plasma and 456,116.37 ± 62,648.36 ng min/mL in SF, which were equivalent with those for an oral dose. These results indicated that equal amounts of sinomenine could penetrate into SF by the two administration routes, and the permeation ratios were approximately 1:3. The AUC0-∞ and Cmax were lower with electroporation compared with systemic administration, but the CSF /CPlasma (concentration of sinomenine in SF vs that of plasma) at 90, 120, 150, 180, 240 and 480 min by electroporation was 3- to 10-fold higher relative to systemic administration. This illustrated that sinomenine can be targeted into joints by electroporation, and electroporation is a potential technique for sinomenine's transdermal delivery.

  15. Treatment of hepatoma with liposome-encapsulated adriamycin administered into hepatic artery of rats

    Institute of Scientific and Technical Information of China (English)

    Dong-Sheng Sun; Jiang-Hao Chen; Rui Ling; Qing Yao; Ling Wang; Zhong Ma; Yu Li

    2006-01-01

    AIM: To observe the therapeutic effects of liposomeencapsulated adriamycin (LADM) on hepatoma in comparison with adriamycin solution (FADM) and adriamycin plus blank liposome (ADM + BL) administered into the hepatic artery of rats.METHODS: LADM was prepared by pH gradient-driven method. Normal saline, FADM (2 mg/kg), ADM+BL (2 mg/kg), and LADM (2 mg/kg) were injected via the hepatic artery in rats bearing liver W256 carcinosarcoma,which were divided into four groups randomly. The therapeutic effects were evaluated in terms of survival time,tumor enlargement ratio, and tumor necrosis degree.The difference was determined with ANOVA and Dunnett test and log rank test.RESULTS: Compared to FADM or ADM + BL, LADM produced a more significant tumor inhibition (tumor volume ratio: 1.243 ± 0.523 vs 1.883 ± 0.708, 1.847 ± 0.661,P < 0.01), and more extensive tumor necrosis. The increased life span was prolonged significantly in rats receiving LADM compared with FADM or ADM+BL (231.48 v's 74.66, 94.70) (P < 0.05).CONCLUSION: The anticancer efficacies of adriamycin on hepatoma can be strongly improved by liposomal encapsulation through hepatic arterial administration.

  16. 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.

  17. Intestinal interleukin-10 mobilization as a contributor to the anti-arthritis effect of orally administered madecassoside: a unique action mode of saponin compounds with poor bioavailability.

    Science.gov (United States)

    Wang, Ting; Wei, Zhifeng; Dou, Yannong; Yang, Yan; Leng, Dandan; Kong, Lingyi; Dai, Yue; Xia, Yufeng

    2015-03-01

    Madecassoside, a triterpenoid saponin present in Centella asiatica herbs with extremely low bioavailability, possesses excellent anti-rheumatoid arthritis property after oral administration. Such a disconnection between poor pharmacokinetic property and undoubted bioactivity also exists in many other herbal medicines. However, there is no reasonable explanation for this phenomenon to date. Here we showed that orally administered madecassoside displayed marked therapeutic effect on collagen-induced arthritis (CIA) in rats, which was accompanied by a systemic downregulation of inflammatory cytokines and an upregulation of anti-inflammatory cytokine IL-10. In vitro assays demonstrated that neither madecassoside nor its main metabolite madecassic acid could directly interfere with the secretion of inflammatory cytokines and IL-10. Intraperitoneal injection of madecassoside or madecassic acid was absent of significant effects on CIA progression, which further excluded the possibility of systemic action and highlighted the indispensable role of intestinal tracts. Notably, madecassoside could dramatically enhance the secretion of IL-10 from the small intestine of CIA rats probably through increasing the number of Foxp3(+) T lymphocytes in the lamina propria. In conclusion, madecassoside displays anti-arthritis property not by absorption into blood or by its metabolite, but through an intestine-dependent manner. The action can be mediated by, at least partially, the mobilization of IL-10 that originates from small intestines.

  18. Self-Administered Mind-Body Practices for Reducing Health Disparities: An Interprofessional Opinion and Call to Action.

    Science.gov (United States)

    Kinser, Patricia A; Robins, Jo Lynne W; Masho, Saba W

    2016-01-01

    Health disparities (HD) continue to persist in the United States which underscores the importance of using low-cost, accessible, evidence-based strategies that can improve health outcomes, especially for chronic conditions that are prevalent among underserved minority populations. Complementary/integrative health modalities, particularly self-administered mind-body practices (MBP), can be extremely useful in reducing HD because they are intrinsically patient-centered and they empower patients to actively engage in self-care of health and self-management of symptoms. Interprofessional healthcare providers and patients can engage in powerful partnerships that encompass self-administered MBP to improve health. This is a call to action for interprofessional researchers to engage in high-quality research regarding efficacy and cost-effectiveness of self-administered MBP, for practitioners to engage patients in self-administered MBP for health promotion, disease prevention, and symptom management, and for healthcare institutions to integrate self-administered MBP into conventional health practices to reduce HD in their communities. PMID:27672398

  19. Brain-Cocaine Concentrations Determine the Dose Self-Administered by Rats on a Novel Behaviorally Dependent Dosing Schedule

    Science.gov (United States)

    Zimmer, Benjamin A; Dobrin, Carson V; Roberts, David C S

    2011-01-01

    A novel behaviorally dependent dosing (BDD) schedule was used to examine the relationship between doses of cocaine self-administered by rats and brain drug levels within a session. The BDD schedule used a hold-down response to activate a syringe pump. The length of time the lever was held down determined the duration that the syringe pump was activated. In the first experiment, rats self-administered cocaine for daily 3 h sessions and brain levels of cocaine were modeled using well-established parameters. Although analysis revealed that rats self-administered doses within a predicted range, one extremely large dose was consistently observed at the beginning of each session when brain levels of cocaine were low. In the second experiment, we introduced a range of timeout periods (10–25 min) in order to produce variability in brain-cocaine concentrations. Animals self-administered larger doses immediately following each timeout period and the dose size was inversely correlated with the length of the timeout. These results show that the dose of cocaine that rats self-administer within a session is inversely related to the amount of drug on board. PMID:21849981

  20. Metabolism and transport of gamma-carboxyglutamic acid.

    Science.gov (United States)

    Shah, D V; Tews, J K; Harper, A E; Suttie, J W

    1978-03-01

    gamma-Carboxyglutamic acid residues have beeh shown to be present in prothrombin, the other vitamin K-dependent clotting factors, and more recently in bone and kidney proteins. This amino acid is formed by a posttranslational vitamin K-dependent carboxylation of glutamyl residues in polypeptide precursors of these protens. It has now been demonstrated that this amino acid, either in the free or peptide-bound form, is not metabolically degraded by the rat, but is quantitatively excreted in the urine. In nephrectomized rats, the tissue concentration of intravenously administered gamma-carboxyglutamic acid is increased, but there is still no evidence of any oxidative metabolism of this amino acid. These amino acid is transported by kidney slices against a concentration gradient, but does not accumulate in liver, intestinal or brain tissues. Preliminary data suggest that gamma-carboxyglutamic acid may be concentrated by a carrier system different from that utilized by other amino acids. PMID:629998

  1. [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

  2. 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...

  3. 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

  4. 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.

  5. 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.)

  6. 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)

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. Reduction of Pavlovian Bias in Schizophrenia: Enhanced Effects in Clozapine-Administered Patients.

    Directory of Open Access Journals (Sweden)

    Matthew A Albrecht

    Full Text Available The negative symptoms of schizophrenia (SZ are associated with a pattern of reinforcement learning (RL deficits likely related to degraded representations of reward values. However, the RL tasks used to date have required active responses to both reward and punishing stimuli. Pavlovian biases have been shown to affect performance on these tasks through invigoration of action to reward and inhibition of action to punishment, and may be partially responsible for the effects found in patients. Forty-five patients with schizophrenia and 30 demographically-matched controls completed a four-stimulus reinforcement learning task that crossed action ("Go" or "NoGo" and the valence of the optimal outcome (reward or punishment-avoidance, such that all combinations of action and outcome valence were tested. Behaviour was modelled using a six-parameter RL model and EEG was simultaneously recorded. Patients demonstrated a reduction in Pavlovian performance bias that was evident in a reduced Go bias across the full group. In a subset of patients administered clozapine, the reduction in Pavlovian bias was enhanced. The reduction in Pavlovian bias in SZ patients was accompanied by feedback processing differences at the time of the P3a component. The reduced Pavlovian bias in patients is suggested to be due to reduced fidelity in the communication between striatal regions and frontal cortex. It may also partially account for previous findings of poorer "Go-learning" in schizophrenia where "Go" responses or Pavlovian consistent responses are required for optimal performance. An attenuated P3a component dynamic in patients is consistent with a view that deficits in operant learning are due to impairments in adaptively using feedback to update representations of stimulus value.

  13. 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.

  14. 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

  15. 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

  16. Evaluation of the first pharmacist-administered vaccinations in Western Australia: a mixed-methods study

    Science.gov (United States)

    Hattingh, H Laetitia; Sim, T Fei; Parsons, R; Czarniak, P; Vickery, A; Ayadurai, S

    2016-01-01

    Objectives This study evaluated the uptake of Western Australian (WA) pharmacist vaccination services, the profiles of consumers being vaccinated and the facilitators and challenges experienced by pharmacy staff in the preparation, implementation and delivery of services. Design Mixed-methods methodology with both quantitative and qualitative data through surveys, pharmacy computer records and immuniser pharmacist interviews. Setting Community pharmacies in WA that provided pharmacist vaccination services between March and October 2015. Participants Immuniser pharmacists from 86 pharmacies completed baseline surveys and 78 completed exit surveys; computer records from 57 pharmacies; 25 immuniser pharmacists were interviewed. Main outcome measures Pharmacy and immuniser pharmacist profiles; pharmacist vaccination services provided and consumer profiles who accessed services. Results 15 621 influenza vaccinations were administered by immuniser pharmacists at 76 WA community pharmacies between March and October 2015. There were no major adverse events, and managed. Between 12% and 17% of consumers were eligible to receive free influenza vaccinations under the National Immunisation Program but chose to have it at a pharmacy. A high percentage of vaccinations was delivered in rural and regional areas indicating that provision of pharmacist vaccination services facilitated access for rural and remote consumers. Immuniser pharmacists reported feeling confident in providing vaccination services and were of the opinion that services should be expanded to other vaccinations. Pharmacists also reported significant professional satisfaction in providing the service. All participating pharmacies intended to continue providing influenza vaccinations in 2016. Conclusions This initial evaluation of WA pharmacist vaccination services showed that vaccine delivery was safe. Convenience and accessibility were important aspects in usage of services. There is scope to expand pharmacist

  17. Reduction of Pavlovian Bias in Schizophrenia: Enhanced Effects in Clozapine-Administered Patients.

    Science.gov (United States)

    Albrecht, Matthew A; Waltz, James A; Cavanagh, James F; Frank, Michael J; Gold, James M

    2016-01-01

    The negative symptoms of schizophrenia (SZ) are associated with a pattern of reinforcement learning (RL) deficits likely related to degraded representations of reward values. However, the RL tasks used to date have required active responses to both reward and punishing stimuli. Pavlovian biases have been shown to affect performance on these tasks through invigoration of action to reward and inhibition of action to punishment, and may be partially responsible for the effects found in patients. Forty-five patients with schizophrenia and 30 demographically-matched controls completed a four-stimulus reinforcement learning task that crossed action ("Go" or "NoGo") and the valence of the optimal outcome (reward or punishment-avoidance), such that all combinations of action and outcome valence were tested. Behaviour was modelled using a six-parameter RL model and EEG was simultaneously recorded. Patients demonstrated a reduction in Pavlovian performance bias that was evident in a reduced Go bias across the full group. In a subset of patients administered clozapine, the reduction in Pavlovian bias was enhanced. The reduction in Pavlovian bias in SZ patients was accompanied by feedback processing differences at the time of the P3a component. The reduced Pavlovian bias in patients is suggested to be due to reduced fidelity in the communication between striatal regions and frontal cortex. It may also partially account for previous findings of poorer "Go-learning" in schizophrenia where "Go" responses or Pavlovian consistent responses are required for optimal performance. An attenuated P3a component dynamic in patients is consistent with a view that deficits in operant learning are due to impairments in adaptively using feedback to update representations of stimulus value. PMID:27044008

  18. 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

  19. 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.

  20. Oncobiguanides: Paracelsus' law and nonconventional routes for administering diabetobiguanides for cancer treatment

    Science.gov (United States)

    Menendez, Javier A.; Quirantes-Piné, Rosa; Rodríguez-Gallego, Esther; Cufí, Sílvia; Corominas-Faja, Bruna; Cuyàs, Elisabet; Bosch-Barrera, Joaquim; Martin-Castillo, Begoña; Segura-Carretero, Antonio; Joven, Jorge

    2014-01-01

    “The dose makes the poison”, the common motto of toxicology first expressed by Paracelsus more than 400 years ago, may effectively serve to guide potential applications for metformin and related biguanides in oncology. While Paracelsus' law for the dose-response effect has been commonly exploited for the use of some anti-cancer drugs at lower doses in non-neoplastic diseases (e.g., methotrexate), the opposite scenario also holds true; in other words, higher doses of non-oncology drugs, such as anti-diabetic biguanides, might exert direct anti-neoplastic effects. Here, we propose that, as for any drug, there is a dose range for biguanides that is without any effect, one corresponding to “diabetobiguanides” with a pharmacological effect (e.g., insulin sensitization in type 2 diabetes, prevention of insulin-dependent carcinogenesis, indirect inhibition of insulin and growth factor-dependent cancer growth) but with minimal toxicity and another corresponding to “oncobiguanides” with pharmacological (i.e., direct and strong anticancer activity against cancer cells) as well as toxic effects. Considering that biguanides demonstrate a better safety profile than most oncology drugs in current use, we should contemplate the possibility of administering biguanides through non-conventional routes (e.g., inhaled for carcinomas of the lung, topical for skin cancers, intravenous as an adjunctive therapy, rectal suppositories for rectal cancer) to unambiguously investigate the therapeutic value of high-dose transient biguanide exposure in cancer. Perhaps then, the oncobiguanides, as we call them here, could be viewed as a mechanistically different type of anti-cancer drugs employed at doses notably higher than those used chronically when functioning as diabetobiguanides. PMID:24909934

  1. Biological Function of Acetic Acid-Improvement in Obesity and Glucose Tolerance by Acetic Acid in Type 2 Diabetic Rats.

    Science.gov (United States)

    Yamashita, Hiromi

    2016-07-29

    Fatty acids derived from adipose tissue are oxidized by β-oxidation to form ketone bodies as final products under the starving condition. Previously, we found that free acetic acid was formed concomitantly with the production of ketone bodies in isolated rat liver perfusion, and mitochondrial acetyl CoA hydrolase was appeared to be involved with the acetic acid production. It was revealed that acetic acid was formed as a final product of enhanced β-oxidation of fatty acids and utilized as a fuel in extrahepatic tissues under the starving condition. Under the fed condition, β-oxidation is suppressed and acetic acid production is decreased. When acetic acid was taken daily by obesity-linked type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats under the fed condition, it protected OLETF rats against obesity. Furthermore, acetic acid contributed to protect from the accumulation of lipid in the liver as well as abdominal fat in OLETF rats. Transcripts of lipogenic genes in the liver were decreased, while transcripts of myoglobin and Glut4 genes in abdominal muscles were increased in the acetic acid-administered OLETF rats. It is indicated that exogenously administered acetic acid would have effects on lipid metabolism in both the liver and the skeletal muscles, and have function that works against obesity and obesity-linked type 2 diabetes.

  2. Citraturic response to oral citric acid load

    Science.gov (United States)

    Sakhaee, K.; Alpern, R.; Poindexter, J.; Pak, C. Y.

    1992-01-01

    It is possible that some orally administered citrate may appear in urine by escaping oxidation in vivo. To determine whether this mechanism contributes to the citraturic response to potassium citrate, we measured serum and urinary citrate for 4 hours after a single oral load of citric acid (40 mEq.) in 6 normal subjects. Since citric acid does not alter acid-base balance, the effect of absorbed citrate could be isolated from that of alkali load. Serum citrate concentration increased significantly (p less than 0.05) 30 minutes after a single oral dose of citric acid and remained significantly elevated for 3 hours after citric acid load. Commensurate with this change, urinary citrate excretion peaked at 2 hours and gradually decreased during the next 2 hours after citric acid load. In contrast, serum and urinary citrate remained unaltered following the control load (no drug). Differences of the citratemic and citraturic effects between phases were significant (p less than 0.05) at 2 and 3 hours. Urinary pH, carbon dioxide pressure, bicarbonate, total carbon dioxide and ammonium did not change at any time after citric acid load, and did not differ between the 2 phases. No significant difference was noted in serum electrolytes, arterialized venous pH and carbon dioxide pressure at any time after citric acid load and between the 2 phases. Thus, the citraturic and citratemic effects of oral citric acid are largely accountable by provision of absorbed citrate, which has escaped in vivo degradation.

  3. Method for enhancing amidohydrolase activity of fatty acid amide hydrolase

    Energy Technology Data Exchange (ETDEWEB)

    John, George; Nagarajan, Subbiah; Chapman, Kent; Faure, Lionel; Koulen, Peter

    2016-10-25

    A method for enhancing amidohydrolase activity of Fatty Acid Amide Hydrolase (FAAH) is disclosed. The method comprising administering a phenoxyacylethanolamide that causes the enhanced activity. The enhanced activity can have numerous effects on biological organisms including, for example, enhancing the growth of certain seedlings. The subject matter disclosed herein relates to enhancers of amidohydrolase activity.

  4. Physicians' Knowledge of Alcohol, Tobacco and Folic Acid in Pregnancy

    Science.gov (United States)

    Lefebvre, L. G.; Ordean, A.; Midmer, D.; Kahan, M.; Tolomiczenko, G.

    2007-01-01

    Objective: To assess: (1) physicians' knowledge and clinical confidence regarding problematic substance use in pregnancy compared to folic acid, and (2) physicians' desire for education in this area and their preferred learning modalities tools. Design: Self-administered survey. Setting: "Family Medicine Forum 2004" in Toronto, Canada.…

  5. 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.

  6. Synthesis and pharmacology of 3-isoxazolol amino acids as selective antagonists at group I metabotropic glutamic acid receptors

    DEFF Research Database (Denmark)

    Madsen, U; Bräuner-Osborne, H; Frydenvang, Karla Andrea;

    2001-01-01

    to originate in (S)-11 (EC(50) = 395 microM, K(b) = 86 and 90 microM, respectively). Compound 9, administered icv, but not sc, was shown to protect mice against convulsions induced by N-methyl-D-aspartic acid (NMDA). Compounds 9 and 11 were resolved using chiral HPLC, and the configurational assignments...

  7. 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...

  8. Lymphatic fatty acids in canine with pharmaceutical formulations containing structured triacylglycerols

    DEFF Research Database (Denmark)

    Holm, R.; Porsgaard, Trine; Porter, C.J.H.;

    2006-01-01

    was generally higher than from the animals dosed with the MLM vehicle; however, statistically significant differences were only found for 18:0 and 18:3n-3. In conclusion, these results indicated that the fatty acid profile and intramolecular structure of administered TAG influenced the absorption of fatty acids...

  9. Furan fatty acids efficiently rescue brain cells from cell death induced by oxidative stress

    NARCIS (Netherlands)

    Teixeira, A.; Cox, R.C.; Egmond, M.R.

    2013-01-01

    Treatment of rat brain C6 astroglioma cells with furan fatty acid F6 prior to exposure to hydrogen peroxide shows a strong protective effect of F6 against cell death resulting from oxidative stress. This protective effect is obtained only for F6 administered as a free fatty acid and with an intact f

  10. 49 CFR 40.347 - What functions may C/TPAs perform with respect to administering testing?

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false What functions may C/TPAs perform with respect to... FOR TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Roles and Responsibilities of Service Agents § 40.347 What functions may C/TPAs perform with respect to administering testing? As a...

  11. 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…

  12. 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…

  13. 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...

  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. 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…

  16. 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);...

  17. 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

  18. Pharmacokinetics of human recombinant tissue-type plasminogen activator, administered intra-abdominally, in a rat peritonitis model

    NARCIS (Netherlands)

    van Goor, Harry; Bom, VJJ; van der Meer, J; Sluiter, WJ; Geerards, S; de Graaf, JS; Bleichrodt, RP; van der Schaaf, W

    1996-01-01

    Human recombinant tissue-type plasminogen activator (rtPA), administered intraperitoneally, may promote intraabdominal fibrinolysis in peritonitis, thereby preventing adhesion and abscess formation. The pharmacokinetics of a single intraperitoneal dose of 0.5 or 2.0 mg/ml human rtPA were assessed in

  19. 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...

  20. 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

  1. 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

  2. 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...

  3. 38 CFR 2.3 - Delegation of authority to employees to take affidavits, to administer oaths, etc.

    Science.gov (United States)

    2010-07-01

    ... with the execution of affidavits relative to fiscal vouchers and is not authorized to take acknowledgments to policy loan agreements and applications for cash surrender value to United States Government... force and effect as if administered or taken before a clerk of such court. (c) The delegated...

  4. 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…

  5. 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...

  6. 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…

  7. Influence of centrally administered α- and γ2-melanocyte-stimulating hormone on hypothalamic blood flow autoregulation in the rat

    NARCIS (Netherlands)

    Sandor, P.; Jong, Wybren de; Cox-van Put, J.; Wied, D. de

    1987-01-01

    The effect of intracerebroventricularly (i.c.v.) administered α-melanocyte-stimulating hormone (MSH) and γ2-MSH on hypothalamic blood flow autoregulation was studied in anesthetized rats at different levels of standardized arterial hypotension. Autoregulation was impaired upon i.c.v. administration

  8. Orally administered extract from Prunella vulgaris attenuates spontaneous colitis in mdr1a-/-mice

    Institute of Scientific and Technical Information of China (English)

    Kelley; MK; Haarberg; Meghan; J; Wymore; Brand; Anne-Marie; C; Overstreet; Catherine; C; Hauck; Patricia; A; Murphy; Jesse; M; Hostetter; Amanda; E; Ramer-Tait; Michael; J; Wannemuehler

    2015-01-01

    AIM: To investigate the ability of a Prunella vulgaris(P. vulgaris) ethanolic extract to attenuate spontaneous typhlocolitis in mdr1a-/- mice. METHODS: Vehicle(5% ethanol) or P. vulgaris ethanolic extract(2.4 mg/d) were administered daily by oral gavage to mdr1a-/- or wild type FVBWT mice from 6 wk of age up to 20 wk of age. Clinical signs of disease were noted by monitoring weight loss. Mice experiencingweight loss in excess of 15% were removed from the study. At the time mice were removed from the study, blood and colon tissue were collected for analyses that included histological evaluation of lesions, inflammatory cytokine levels, and myeloperoxidase activity. RESULTS: Administration of P. vulgaris extracts to mdr1a-/- mice delayed onset of colitis and reduced severity of mucosal inflammation when compared to vehicle-treated mdr1a-/- mice. Oral administration of the P. vulgaris extract resulted in reduced(P < 0.05) serum levels of IL-10(4.6 ± 2 vs 19.4 ± 4), CXCL9(1319.0 ± 277 vs 3901.0 ± 858), and TNFα(9.9 ± 3 vs 14.8 ± 1) as well as reduced gene expression by more than two-fold for Ccl2, Ccl20, Cxcl1, Cxcl9, IL-1 α, Mmp10, VCAM-1, ICAM, IL-2, and TNFα in the colonic mucosa of mdr1a-/- mice compared to vehicle-treated mdr1a-/-mice. Histologically, several microscopic parameters were reduced(P < 0.05) in P. vulgaris-treated mdr1a-/-mice, as was myeloperoxidase activity in the colon(2.49 ± 0.16 vs 3.36 ± 0.06, P < 0.05). The numbers of CD4+ T cells(2031.9 ± 412.1 vs 5054.5 ± 809.5) and germinal center B cells(2749.6 ± 473.7 vs 4934.0 ± 645.9) observed in the cecal tonsils of P. vulgaris-treated mdr1a-/- were significantly reduced(P < 0.05) from vehicle-treated mdr1a-/- mice. Vehicle-treated mdr1a-/- mice were found to produce serum antibodies to antigens derived from members of the intestinal microbiota, indicative of severe colitis and a loss of adaptive tolerance to the members of the microbiota. These serum antibodies were greatly reduced or

  9. 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

  10. 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

  11. 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

  12. 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

  13. Synthesis and Crystal Structure of 2-(2-Ethyl-lH-imidazol-1-yl)-1-hydroxy- ethane-1,1-diyldiphosphonic Acid (EIHDP)%Synthesis and Crystal Structure of 2-(2-Ethyl-lH-imidazol-1-yl)-1-hydroxy- ethane-1,1-diyldiphosphonic Acid (EIHDP)

    Institute of Scientific and Technical Information of China (English)

    WANG Hong-Yong; ZOU Pei; XIE Min-Hao; HE Yong-Jun; WU Jun; LIU~IL~gJ; WU Hao

    2011-01-01

    The crystal structure of the title compound (C7H14N2O7P2, Mr = 300.14) was determined by single-crystal X-ray diffraction. The crystal belongs to triclinic, space group P1 with a = 8.258(3), b = 8.886(3), c = 9.275(3) A, a = 96.669(3), β = 115,706(3), γ= 104.467(3)°, V= 573.8(3) A^3, Z = 2, Dc = 1.737 g/cm^3, 2(MoKa) = 0.71073, F(000) = 720,μ(MoKa) = 0.41 mm^-1 R = 0.030 and wR = 0.078. A total of 1970 unique reflections were collected, of which 1742 with I 〉 2σ(I) were observed. EIDHP has a structure similar to zoledronic acid (ZL). ZL is a potent bone antiresorptive bisphosphonate drug having significant activity against several parasitic protozoa. EIHDP has inner-salt character, consisting of a negatively charged PO3 group and a positively charged N(1) atom. The crystal structure is stabilized by interrnolecular hydrogen bonds of O-H…O and N-H…O.

  14. Amino acid analogs for tumor imaging

    Science.gov (United States)

    Goodman, M.M.; Shoup, T.

    1998-09-15

    The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is [{sup 18}F]-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an {alpha}-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of {alpha}-aminoisobutyric acid.

  15. Amino acid analogs for tumor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Goodman, Mark M. (Atlanta, GA); Shoup, Timothy (Decatur, GA)

    1998-09-15

    The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is ›.sup.18 F!-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an .alpha.-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of .alpha.-aminoisobutyric acid.

  16. Amino acid analogs for tumor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Goodman, Mark M. (Atlanta, GA); Shoup, Timothy (Decatur, GA)

    1998-10-06

    The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is ›.sup.18 F!-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an .alpha.-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of .alpha.-aminoisobutyric acid.

  17. Amino acid analogs for tumor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Goodman, M.M.; Shoup, T.

    1998-10-06

    The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is [{sup 18}F]-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an {alpha}-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of {alpha}-aminoisobutyric acid.

  18. Viper and cobra venom neutralization by alginate coated multicomponent polyvalent antivenom administered by the oral route.

    Directory of Open Access Journals (Sweden)

    Sourav Bhattacharya

    2014-08-01

    Full Text Available Snake bite causes greater mortality than most of the other neglected tropical diseases. Snake antivenom, although effective in minimizing mortality in developed countries, is not equally so in developing countries due to its poor availability in remote snake infested areas as, and when, required. An alternative approach in this direction could be taken by making orally deliverable polyvalent antivenom formulation, preferably under a globally integrated strategy, for using it as a first aid during transit time from remote trauma sites to hospitals.To address this problem, multiple components of polyvalent antivenom were entrapped in alginate. Structural analysis, scanning electron microscopy, entrapment efficiency, loading capacity, swelling study, in vitro pH sensitive release, acid digestion, mucoadhesive property and venom neutralization were studied in in vitro and in vivo models. Results showed that alginate retained its mucoadhesive, acid protective and pH sensitive swelling property after entrapping antivenom. After pH dependent release from alginate beads, antivenom (ASVS significantly neutralized phospholipaseA2 activity, hemolysis, lactate dehydrogenase activity and lethality of venom. In ex vivo mice intestinal preparation, ASVS was absorbed significantly through the intestine and it inhibited venom lethality which indicated that all the components of antivenom required for neutralization of venom lethality were retained despite absorption across the intestinal layer. Results from in vivo studies indicated that orally delivered ASVS can significantly neutralize venom effects, depicted by protection against lethality, decreased hemotoxicity and renal toxicity caused by russell viper venom.Alginate was effective in entrapping all the structural components of ASVS, which on release and intestinal absorption effectively reconstituted the function of antivenom in neutralizing viper and cobra venom. Further research in this direction can

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. Intraperitoneally administered biliverdin protects against UVB-induced skin photo-damage in hairless mice.

    Science.gov (United States)

    Bai, Bingxue; Liu, Yingdi; You, Yan; Li, Yuzhen; Ma, Liangjuan

    2015-03-01

    Oxidative stress is shown to be responsible for ultraviolet B (UVB) irradiation-induced skin cancer and premature aging. Biliverdin (BVD), a product of heme oxygenase-1, has strong anti-oxidant and anti-inflammatory properties. In the present study, we investigated the effects of BVD on UVB-induced skin photo-damage in hairless mice. Mice were divided into three groups: control group, UVB group (only UVB irradiation) and BVD+UVB group (mice were intraperitoneally injected with BVD before each UVB irradiation). Intraperitoneal BVD injection resulted in a significant photoprotective effect by reducing morphological and histopathological changes to the skin. BVD also exhibited a significant antioxidant effect by increasing the superoxide dismutase (SOD) level and decreasing the thiobarbituric acid reactive substances (TBARS) level compared with the control group. In addition, BVD activated biliverdin reductase (BVR) expression and inhibited the UVB-induced increase of p38 mitogen-activated protein kinase phosphorylation (p-p38MAPK), MMP (matrix metalloproteinase)-1 and MMP-3 expression (pskin photo-damage in hairless mice and that this is likely mediated by its antioxidant and anti-inflammatory mechanisms and cell signal regulatory action.

  7. 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

    of this study were to develop a theoretical test about propofol sedation, to gather validity evidence for the test and to measure the effect of a NAPS-specific training course. MATERIAL AND METHODS: A three-phased psychometric study on multiple choice questionnaire (MCQ) test development, gathering of validity......% increase; p = 0.001 and 0.001, respectively). CONCLUSIONS: Data supported the validity of the developed MCQ test. The NAPS-specific course with pre-course testing adds theoretical knowledge to already well-prepared participants.......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...

  8. 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

    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......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...... than 4 h. In conclusion, formoterol administered as dry powder in a single dose provided rapid and sustained bronchodilation and clinically significant bronchoprotection for at least 8 h in 2- to 5-yr-old asthmatic children. Furthermore, this study suggests that mechanical actuation of DPI using...

  9. Effects of surface-bound and intravenously administered heparin on cell-surface interactions: inflammation and coagulation.

    Science.gov (United States)

    Johnson, G; Curry, B; Cahalan, L; Prater, R; Biggerstaff, J; Hussain, A; Gartner, M; Cahalan, P

    2013-05-01

    Intravenous administration of heparin and heparin-bonded extracorporeal circuits are frequently used to mitigate the deleterious effects of blood contact with synthetic materials. The work described here utilized human blood in a micro-perfusion circuit to experimentally examine the effects of intravenous and surface-bound heparin on cellular activation. Activation markers of coagulation and of the inflammatory response were examined using flow cytometry; specifically, markers of platelet, monocyte, polymorphonuclear leukocyte (PMN), and lymphocyte activation were quantified. The results indicate that surface-bound heparin reduces the inflammatory response whereas systemically administered heparin does not. This finding has important implications for blood-contacting devices, particularly within the context of recently elucidated connections between inflammation pathways and coagulation disorders. Data presented indicate that surface-bound heparin and intravenously administered heparin play distinct, but vital roles in rendering biomaterial surfaces compatible with blood. PMID:23401339

  10. [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

  11. 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......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......, sexual function and social activities. Test-retest showed a repeat frequency of 50.0%-91.0% for symptoms and 44.6%-82.1% for trouble. A highly significant positive correlation was found between symptoms and trouble, which was most pronounced for questions concerning pain and incontinence...

  12. The effect of vitamin A supplementation administered with missing vaccines during national immunization days in Guinea-Bissau

    DEFF Research Database (Denmark)

    Benn, Christine Stabell; Martins, Cesario; Rodrigues, Amabelia;

    2009-01-01

    than VAS with diphtheria-tetanus-pertussis (DTP) vaccine. We assessed the effect of VAS administered with different vaccines during national immunization days (NIDs). METHODS: In 2003, VAS was distributed during NIDs in Guinea-Bissau. Children 6 months or older were given VAS, and if they were missing......BACKGROUND: WHO recommends high-dose Vitamin A supplementation (VAS) at vaccination contacts after 6 months of age. It has not been studied whether the effect of VAS on mortality depends on the type of vaccine. We have hypothesized that VAS administered with measles vaccine (MV) is more beneficial...... vaccines, these were often given as well. We compared survival between children who had received VAS alone, VAS with DTP or DTP + MV, or VAS with MV. We also compared the survival between participants and non-participants. We followed 6- to 17-month old children until 18 months of age and analysed survival...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. Evolocumab lowers LDL-C safely and effectively when self-administered in the at-home setting

    OpenAIRE

    Dent,Ricardo; Joshi, Raju; Stephen Djedjos, C.; Legg, Jason; Elliott, Mary; Geller, Michelle; Meyer, Dawn; Somaratne, Ransi; Recknor, Chris; Weiss, Robert

    2016-01-01

    Evolocumab has been shown to consistently reduce low-density lipoprotein cholesterol (LDL-C) across populations. The phase 3 studies included administration in the home-use and in-clinic settings but did not specifically evaluate the feasibility of home-use administration. Two clinical studies enrolled patients with hypercholesterolemia or mixed dyslipidemia on statin therapy and with/without ezetimibe received evolocumab in the home-use setting. Patients were randomized to self-administer ev...

  18. Dietary fats and pharmaceutical lipid excipients increase systemic exposure to orally administered cannabis and cannabis-based medicines

    Science.gov (United States)

    Zgair, Atheer; Wong, Jonathan CM; Lee, Jong Bong; Mistry, Jatin; Sivak, Olena; Wasan, Kishor M; Hennig, Ivo M; Barrett, David A; Constantinescu, Cris S; Fischer, Peter M; Gershkovich, Pavel

    2016-01-01

    There has been an escalating interest in the medicinal use of Cannabis sativa in recent years. Cannabis is often administered orally with fat-containing foods, or in lipid-based pharmaceutical preparations. However, the impact of lipids on the exposure of patients to cannabis components has not been explored. Therefore, the aim of this study is to elucidate the effect of oral co-administration of lipids on the exposure to two main active cannabinoids, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). In this study, oral co-administration of lipids enhanced the systemic exposure of rats to THC and CBD by 2.5-fold and 3-fold, respectively, compared to lipid-free formulations. In vitro lipolysis was conducted to explore the effect of lipids on the intestinal solubilisation of cannabinoids. More than 30% of THC and CBD were distributed into micellar fraction following lipolysis, suggesting that at least one-third of the administered dose will be available for absorption following co-administration with lipids. Both cannabinoids showed very high affinity for artificial CM-like particles, as well as for rat and human CM, suggesting high potential for intestinal lymphatic transport. Moreover, comparable affinity of cannabinoids for rat and human CM suggests that similar increased exposure effects may be expected in humans. In conclusion, co-administration of dietary lipids or pharmaceutical lipid excipients has the potential to substantially increase the exposure to orally administered cannabis and cannabis-based medicines. The increase in patient exposure to cannabinoids is of high clinical importance as it could affect the therapeutic effect, but also toxicity, of orally administered cannabis or cannabis-based medicines. PMID:27648135

  19. 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 ...

  20. 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...

  1. 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...

  2. 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...

  3. Self-administered C1 esterase inhibitor concentrates for the management of hereditary angioedema: usability and patient acceptance

    Directory of Open Access Journals (Sweden)

    Li HH

    2016-09-01

    Full Text Available Huamin Henry Li Institute for Asthma and Allergy, Chevy Chase, MD, USA Abstract: Hereditary angioedema (HAE is a rare genetic disease characterized by episodic subcutaneous or submucosal swelling. The primary cause for the most common form of HAE is a deficiency in functional C1 esterase inhibitor (C1-INH. The swelling caused by HAE can be painful, disfiguring, and life-threatening. It reduces daily function and compromises the quality of life of affected individuals and their caregivers. Among different treatment strategies, replacement with C1-INH concentrates is employed for on-demand treatment of acute attacks and long-term prophylaxis. Three human plasma-derived C1-INH preparations are approved for HAE treatment in the US, the European Union, or both regions: Cinryze®, Berinert®, and Cetor®; however, only Cinryze is approved for long-term prophylaxis. Postmarketing studies have shown that home therapy (self-administered or administered by a caregiver is a convenient and safe option preferred by many HAE patients. In this review, we summarize the role of self-administered plasma-derived C1-INH concentrate therapy with Cinryze at home in the prophylaxis of HAE. Keywords: C1-INH concentrate, hereditary angioedema, disease management, first line, prophylaxis, self-administration 

  4. 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.

  5. 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

  6. Self-Administered, Home-Based SMART (Sensorimotor Active Rehabilitation Training) Arm Training: A Single-Case Report.

    Science.gov (United States)

    Hayward, Kathryn S; Neibling, Bridee A; Barker, Ruth N

    2015-01-01

    This single-case, mixed-method study explored the feasibility of self-administered, home-based SMART (sensorimotor active rehabilitation training) Arm training for a 57-yr-old man with severe upper-limb disability after a right frontoparietal hemorrhagic stroke 9 mo earlier. Over 4 wk of self-administered, home-based SMART Arm training, the participant completed 2,100 repetitions unassisted. His wife provided support for equipment set-up and training progressions. Clinically meaningful improvements in arm impairment (strength), activity (arm and hand tasks), and participation (use of arm in everyday tasks) occurred after training (at 4 wk) and at follow-up (at 16 wk). Areas for refinement of SMART Arm training derived from thematic analysis of the participant's and researchers' journals focused on enabling independence, ensuring home and user friendliness, maintaining the motivation to persevere, progressing toward everyday tasks, and integrating practice into daily routine. These findings suggest that further investigation of self-administered, home-based SMART Arm training is warranted for people with stroke who have severe upper-limb disability.

  7. Evolocumab lowers LDL-C safely and effectively when self-administered in the at-home setting.

    Science.gov (United States)

    Dent, Ricardo; Joshi, Raju; Stephen Djedjos, C; Legg, Jason; Elliott, Mary; Geller, Michelle; Meyer, Dawn; Somaratne, Ransi; Recknor, Chris; Weiss, Robert

    2016-01-01

    Evolocumab has been shown to consistently reduce low-density lipoprotein cholesterol (LDL-C) across populations. The phase 3 studies included administration in the home-use and in-clinic settings but did not specifically evaluate the feasibility of home-use administration. Two clinical studies enrolled patients with hypercholesterolemia or mixed dyslipidemia on statin therapy and with/without ezetimibe received evolocumab in the home-use setting. Patients were randomized to self-administer evolocumab using one of two injection devices biweekly over 6 weeks (autoinjector or prefilled syringe; n = 149; ClinicalTrials.gov, NCT01849497) or monthly over 12 weeks (autoinjector or automated minidoser; n = 164; NCT01879319). The first self-administration occurred in the in-clinic setting, and two more were performed in the at-home setting. Patients were successful in self-administering evolocumab in the home-use setting in approximately 95 % of attempts and experienced LDL-C reductions from baseline to week 6 or the mean of weeks 10 and 12 of approximately 65 %. Rates of successful self-administration and LDL-C reduction were similar across dosing schedules and study devices. Adverse events were similar between randomized groups and generally mild in severity. In two clinical studies, therefore, patients were able to successfully self-administer evolocumab in both the in-clinic and at-home settings regardless of which dosing schedule or device they used.

  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. Dopamine decreases NMDA currents in the oval bed nucleus of the stria terminalis of cocaine self-administering rats☆

    Science.gov (United States)

    Krawczyk, Michal; deBacker, Julian; Mason, Xenos; Jones, Andrea A.; Dumont, Éric C.

    2014-01-01

    Dopamine (DA) and N-methyl-D-aspartate receptors (NMDARs) contribute in the neural processes underlying drug-driven behaviors. DA is a potent modulator of NMDAR, but few studies have investigated the functional interaction between DA and NMDAR in the context of substance abuse. We combined the rat model of cocaine self-administration with brain slice electrophysiology to study DA modulation of NMDA currents in the oval bed nucleus of the stria terminalis (ovBNST), a dense DA terminal field involved in maintenance of cocaine self-administration amongst other drug related behaviors. Long-Evans rats self-administered intravenous cocaine (0.75 mg/kg/injection) on a progressive ratio (PR) schedule of reinforcement for 15 days and whole-cell patch-clamp recordings were done on the 16th day. DA reduced NMDA currents in brain-slices from cocaine self-administering rats, but not in those of drug-naïve and sucrose self-administering, or when cocaine exposure was passive (yoked), revealing a mechanism unique to voluntary cocaine intake. DA reduced NMDA currents by activating G-protein-coupled D1- and D2-like receptors that converged on phospholipase C and protein phosphatases. Accordingly, our study reveals a mechanism that may contribute to dysfunctional synaptic plasticity associated with drug-driven behaviors during acute withdrawal. PMID:24472317

  10. 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.

    2014-01-01

    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

  11. 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.

  12. Anti-inflammatory activity of orpanoxin administered orally and topically to rodents.

    Science.gov (United States)

    Brooks, R R; Bonk, K R; Decker, G E; Miller, K E

    1985-07-01

    Orpanoxin, a nonsteroidal anti-inflammatory drug (NSAID) lacking gastric ulcerogenic effects in the therapeutic dose range in rats, was compared with six reference NSAIDs for oral activity in the rat paw carrageenin-induced edema assay. Tested NSAIDs were ranked on the basis of oral mg/kg ED50 values: piroxicam, 0.55; orpanoxin, 35.6; diflunisal, 59.6; benoxaprofen, greater than 300; tolmetin sodium, greater than 300; and sulindac, greater than 300. Zomepirac sodium was inactive. Only the three most potent compounds produced greater than 60% inhibition of edema. Inhibition was generally greater at 4 h than at 6 h post carrageenin for all compounds. Oral activity of orpanoxin was also demonstrated in the guinea-pig u.v.-induced erythema model (ED50 = 24.2 mg/kg p.o. when given 1 h before irradiation) and in the mouse ear croton oil induced edema test (ED50 value = 131 mg/kg p.o.). Topical activity of orpanoxin was assessed in both the guinea-pig and mouse models. In the guinea-pig u.v.-induced erythema model, application (1 h after u.v.) of 1, 5, and 10% (w/v) orpanoxin creams (containing 10% urea) significantly inhibited erythema at 2, 3, and 4 h post-irradiation. Orpanoxin, mefenamic acid, and indomethacin as 1% creams inhibited total erythema scores 70, 92 and 74%, respectively. Evidence for topical activity in the mouse ear assay was also obtained for orpanoxin in diethyl ether or 10% urea cream, but not in dimethylsulfoxide. It was concluded that orpanoxin has anti-inflammatory activity comparable to reference NSAIDs in the rat paw edema test, is active orally in rat, mouse, and guinea-pig models, and shows topical activity in the guinea-pig and the mouse.

  13. Effect of beryllium chloride on porphyrin metabolism in pregnant mice administered by subcutaneous injection.

    Science.gov (United States)

    Sakaguchi, S; Sakaguchi, T; Nakamura, I; Aminaka, M; Tanaka, T; Kudo, Y

    1997-04-11

    The effect of beryllium (Be) compounds on porphyrins was investigated in pregnant mice. The blood protoporphyrin (Proto) and zinc protoporphyrin (Zn Proto) concentrations were increased in pregnancy. Regardless of pregnancy or nonpregnancy, the Proto concentration was decreased after Be injection. Delta-aminolevulinic acid dehydratase (ALA-D) and porphobilinogen deaminase (PBG-D) activities in blood were significantly elevated in the pregnant untreated (Con-pregnant) group, compared to the nonpregnant mice untreated (Con-nonpregnant) and nonpregnant mice treated with Be (Be-nonpregnant) groups. The blood ALA-D activity of the pregnant mice treated with Be (Be-pregnant group) tended to decrease, compared to Con-pregnant group. The blood PBG-D activity in the Be-pregnant group was significantly lower compared with that of the Con-pregnant group. The ALA-D and PBG-D activities in the spleen were also significantly elevated in the Con-pregnant group, compared to nonpregnant groups. However, it was noted that these values in the Be-pregnant group were almost the same as that of the Con-nonpregnant group and were significantly lower than that in the Con-pregnant group. The elevation of ALA-D and PBG-D activities in the blood and spleen, which play a role in the hematopoietic function of mice, was observed in the Con-pregnant mice compared to the nonpregnant mice. However, the phenomenon was not observed in the Be-pregnant mice, it suggesting that Be suppressed the pregnancy-induced increase in hematopoietic function.

  14. 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.

  15. Kinetics of microbial methionine metabolism in continuous cultures administered different methionine sources.

    Science.gov (United States)

    Firkins, J L; Fowler, C M; Devillard, E; Bequette, B J

    2015-02-01

    The Met precursor 2-hydroxy-4-(methylthio) butanoic acid (HMB) is expected to be more extensively degraded in the rumen than its isopropyl ester (HMBi). A control and 3 isomolar treatments-0.097% dl-methionine, 0.11% HMBi (HMBi), and 0.055% HMBi plus 0.048% Met (Met + HMBi)-were dosed every 8h simultaneously with 3-times-daily feeding into continuous cultures. Starting on d 9, for 6 consecutive doses, both [1-(13)C]-l-Met and [methyl-(2)H3]-l-Met replaced part of the unlabeled dl-Met, [(13)C5]-dl-HMBi replaced a portion of the unlabeled dl-HMBi, and [1-(13)C]-l-Met plus [(13)C5]-dl-HMBi replaced a portion of the respective unlabeled doses for the Met + HMBi treatment. After the sixth dose (d 11), unlabeled Met or HMBi provided 100% of the doses to follow elimination kinetics of the labels in HMBi, free Met, and bacterial Met compartments. The free [1-(13)C]-l-Met recycled more and was recovered in bacterial Met to a lesser extent than was the free [methyl-(2)H3]-l-Met recycling and that was recovered in bacterial Met. Increasing HMBi inclusion (0, 50, and 100% substitution of the exogenously dosed Met on a molar equivalent basis) tended to increase HMBi escape from 54.7 to 71.3% for the 50 and 100% HMBi treatments, respectively. Despite HMBi substituting for and decreasing the dosage of Met, increasing HMBi increased accumulation of free Met in fermenter fluid. The HMBi (after de-esterification of the isopropyl group) presumably produces Met through the intermediate α-ketomethylthyiobutyrate with an aminotransferase that also has high affinity for branched-chain AA. We provide evidence that the HMBi-derived Met is likely released from bacterial cells and accumulates rather than being degraded, potentially as a result of lagging d-stereoisomer metabolism. More research is needed to evaluate racemization and metabolism of stereoisomers of HMBi, Met, and other AA in ruminal microbes.

  16. Effects of amoxicillin/clavulanic acid on the pharmacokinetics of valproic acid.

    Science.gov (United States)

    Lee, Soo-Yun; Huh, Wooseong; Jung, Jin Ah; Yoo, Hye Min; Ko, Jae-Wook; Kim, Jung-Ryul

    2015-01-01

    Valproic acid (VPA) is mainly metabolized via glucuronide, which is hydrolyzed by β-glucuronidase and undergoes enterohepatic circulation. Amoxicillin/clavulanic acid (AMC) administration leads to decreased levels of β-glucuronidase-producing bacteria, suggesting that these antibiotics could interrupt enterohepatic circulation and thereby alter the pharmacokinetics of VPA. This study aimed to evaluate the effects of AMC on the pharmacokinetics of VPA. This was an open-label, two-treatment, one-sequence study in 16 healthy volunteers. Two treatments were evaluated; treatment VPA, in which a single dose of VPA 500 mg was administered, and treatment AMC + VPA, in which multiple doses of AMC 500/125 mg were administered three times daily for 7 days and then a single dose of VPA was administered. Blood samples were collected up to 48 hours. Pharmacokinetic parameters were calculated using noncompartmental methods. Fifteen subjects completed the study. Systemic exposures and peak concentrations of VPA were slightly lower with treatment AMC + VPA than with treatment VPA (AUClast, 851.0 h·mg/L vs 889.6 h·mg/L; C max, 52.1 mg/L vs 53.0 mg/L). There were no significant between-treatment effects on pharmacokinetics (95% confidence interval [CI]) of AUClast and C max (95.7 [85.9-106.5] and 98.3 [91.6-105.6], respectively). Multiple doses of AMC had no significant effects on the pharmacokinetics of VPA; thus, no dose adjustment is necessary.

  17. 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…

  18. 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...

  19. Continuous Enteral Administration Can Enable Normal Amino Acid Absorption in Rats with Methotrexate-Induced Gastrointestinal Mucositis

    NARCIS (Netherlands)

    Fijlstra, Margot; Schierbeek, Henk; Voortman, Gardi; Dorst, Kristien Y.; van Goudoever, Johannes B.; Rings, Edmond H. H. M.; Tissings, Wim J. E.

    2012-01-01

    It is unknown what feeding strategy to use during chemotherapy-induced gastrointestinal mucositis, which causes weight loss and possibly malabsorption. To study the absorptive capacity of amino acids during mucositis, we determined the plasma availability of enterally administered amino acids (AA),

  20. 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.

  1. TCRαβ+/CD19+ Depleted Haploidentical HSCT + Zoledronate

    Science.gov (United States)

    2016-08-22

    Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Hodgkin Lymphoma; Non-Hodgkin Lymphoma; Myelodysplastic Syndrome; Myeloproliferative Syndrome; Rhabdomyosarcoma; Ewing Sarcoma; Primitive Neuroectodermal Tumor; Osteosarcoma; Neuroblastoma

  2. 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...

  3. 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.

  4. Optimization method for the administered activity to patients in Tc-99-HMPAO cerebral blood flow SPECT in adults

    Energy Technology Data Exchange (ETDEWEB)

    Perez Diaz, Marlen [Central University of Las Villas, Santa Clara (Cuba). Physics Dept.; Diaz Rizo, Oscar [Institute for Nuclear Sciences and Technology, Havana (Cuba); Estevez Aparicio, Eric; Roque Diaz, Reinaldo; Hernandez Rodriguez, Carlos [University Hospital Celestino Hernandez, Santa Clara (Cuba)

    2002-07-01

    A method based on the construction of an image quality discriminant function is proposed. The parameters which characterise it are selected among the typical ones measured in a Tc{sup 99m} - HMPAO cerebral blood flow SPECT. The results are compared among groups of patient's studies who received different activity (430, 640 and 807 MBq), looking for the minimum that guaranty good image quality. A reduction in the administered {sup 99m} Tc-HMPAO activity to the patient down to 430 MBq was possible without affecting the tomographic image quality. The labelling yield was the main parameter that determined the image quality. (author)

  5. Directly observed versus self-administered antiretroviral therapies: preference of HIV-positive jailed inmates in San Francisco.

    Science.gov (United States)

    Saberi, Parya; Caswell, Nikolai H; Jamison, Ross; Estes, Milton; Tulsky, Jacqueline P

    2012-10-01

    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 via DOT versus g-SAT while incarcerated. Participants overwhelmingly preferred g-SAT over DOT. PMID:22547327

  6. 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

  7. Motor effects of locally administered pinaverium bromide in the sigmoid tract of patients with irritable bowel syndrome.

    Science.gov (United States)

    Passaretti, S; Sorghi, M; Colombo, E; Mazzotti, G; Tittobello, A; Guslandi, M

    1989-01-01

    The effects of pinaverium bromide, a non-absorbable antispasmodic agent, administered locally, on sigmoid-rectal motility was investigated in 20 patients with irritable bowel syndrome. The influence of either pinaverium (10 subjects) or placebo (10 subjects) on a neostigmine-induced increase of sigmoid pressure was assessed and compared by means of computerized electromanometry. The drug was found to counteract significantly the motor effects of neostigmine, thus appearing to be an effective compound for the treatment of functional disorders of the colon. PMID:2744907

  8. 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...

  9. Hydrofluoric acid poisoning

    Science.gov (United States)

    Fluorhydric acid ... stomach, or intestine have holes (perforations) from the acid. ... Hydrofluoric acid is especially dangerous. The most common accidents involving hydrofluoric acid cause severe burns on the skin ...

  10. Incretin effect after oral amino Acid ingestion in humans

    DEFF Research Database (Denmark)

    Lindgren, Ola; Pacini, Giovanni; Tura, Andrea;

    2015-01-01

    is 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......CONTEXT: The incretin effect is the augmented insulin secretion by oral vs iv glucose at matching glucose levels. We previously demonstrated an augmented insulin secretion when fat is given orally rather than iv, suggesting an incretin effect also after fat. However, whether an incretin effect......) 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...

  11. 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…

  12. 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.

  13. 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

  14. Okadaic acid

    DEFF Research Database (Denmark)

    Danielsen, E Michael; Hansen, Gert H; Severinsen, Mai C K

    2014-01-01

    was studied at the electron microscopic level using the membrane-impermeable marker Ruthenium Red (RR). Like FM dye, RR was taken up into TWEEs and multivesicular bodies (MVBs). However, OA induced the formation of a large number of lamellar bodies (LBs), a type of lysosome-related organelles. LBs...... hyper protein phosphorylation, but no detectable loss of cell polarity or cytoskeletal integrity of the enterocytes. Using a fluorescent membrane marker, FM dye, endocytosis from the brush border was affected by the toxin. Although constitutive uptake into subapical terminal web-localized early...... in acidic organelles, implying a different toxic mechanism of action. We propose that rapid induction of LBs, an indicator of phospholipidosis, should be included in the future toxicity profile of OA....

  15. 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.

  16. 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.

  17. 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.

  18. 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)

  19. [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

  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)