WorldWideScience

Sample records for administering zoledronic acid

  1. Dosing of zoledronic acid with its anti-tumor effects in breast cancer

    Directory of Open Access Journals (Sweden)

    Xinmin Zhao

    2015-09-01

    Full Text Available Bisphosphonates have played an important role in the treatment of breast cancer, mainly in patients with bone metastasis, by reducing the risk of fracture, spinal cord compression, and hypercalcemia. Zoledronic acid, the most frequently used intravenous agent, has been traditionally administered on a monthly dosing schedule. Preclinical studies have demonstrated that zoledronic acid can inhibit angiogenesis, invasion, and adhesion of tumor cells. Several clinical studies of different timings and schedules of zoledronic acid therapy have demonstrated its anti-tumor effects, as well as its protective effect on bone health, in postmenopausal women during adjuvant breast cancer therapy. In general, early initiation of zoledronic acid, concomitantly with adjuvant therapy, has been found to be most beneficial. However, questions remain over the most effective schedule of treatment and relative potency of zoledronic acid. Therefore, we review the existing clinical studies to examine the influence of dosing of zoledronic acid therapy on clinical outcomes in patients with breast cancer.

  2. Zoledronic acid in the treatment of osteoporosis: indications for use

    Directory of Open Access Journals (Sweden)

    Nataliya Vladimirovna Toroptsova

    2011-06-01

    Full Text Available The mechanism of action of the third-generation bisphosphonate zoledronic acid (Aclasta is described; the data of randomized clinical trials of its efficacy and tolerability are given. It is concluded that zoledronic acid intravenously administered once a year may be the drug of choice for increasing patients' adherence to therapy, particularly in polypharmacy that is common in the elderly and in cognitive disorders. In addition, the drug may be given to postmenopausal women once every 2 years for the prevention of osteoporosis.

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

    Directory of Open Access Journals (Sweden)

    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. [Effects of zoledronic acid on osteoporosis patients in Japan.

    Science.gov (United States)

    Tanaka, Sakae

    2017-01-01

    Zoledronic acid is a bisphosphonate with the most potent anti-bone resorbing activity. Several previous studies demonstrated that zoledronic acid once a year significantly reduced the risk of vertebral, non-vertebral, and hip fractures in postmenopausal women. In a phase Ⅲ 2-year placebo-controlled, randomized, double-blind comparative study in Japan(ZONE study)demonstrated that once-yearly infusion of zoledronic acid 5 mg increased lumbar spine and proximal femoral BMD, and reduced the incidence of vertebral and non-vertebral fractures in Japanese patients with primary osteoporosis compared to placebo.

  5. Once-yearly zoledronic acid in the prevention of osteoporotic bone fractures in postmenopausal women

    Directory of Open Access Journals (Sweden)

    Irene Lambrinoudaki

    2008-09-01

    Full Text Available Irene Lambrinoudaki, Sophia Vlachou, Fotini Galapi, Dimitra Papadimitriou, K Papadias2nd Department of Obstetrics and Gynecology, University of Athens, Aretaieio Hospital, GreeceAbstract: Zoledronic acid is a nitrogen-containing, third-generation bisphosphonate that has recently been approved for the treatment of postmenopausal osteoporosis as an annual intravenous infusion. Zoledronic acid is an antiresorptive agent which has a high affinity for mineralized bone and especially for sites of high bone turnover. Zoledronic acid is excreted by the kidney without further metabolism. Zoledronic acid administered as a 5 mg intravenous infusion annually increases bone mineral density in the lumbar spine and femoral neck by 6.7% and 5.1% respectively and reduces the incidence of new vertebral and hip fractures by 70% and 41% respectively in postmenopausal women with osteoporosis. Most common side effects are post-dose fever, flu-like symptoms, myalgia, arthralgia, and headache which usually occur in the first 3 days after infusion and are self-limited. Rare adverse effects include renal dysfunction, hypocalcemia, atrial fibrillation, and osteonecrosis of the jaw.Keywords: zoledronic acid, postmenopausal osteoporosis, bisphosphonate

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  7. [Efficacy of zoledronic acid for osteoporosis:evidence from studies abroad.

    Science.gov (United States)

    Inoue, Daisuke

    2017-01-01

    Zoledronic acid is a nitrogen-containing bisphosphonate that has the strongest and the most persistent anti-resorptive activity. Once-yearly zoledronic acid has recently been approved for the treatment of osteoporosis in Japan. This overview summarizes abundant evidence of zoledronic acid, obtained from studies abroad, for its efficacy for postmenopausal, male and glucocorticoid-induced osteoporosis.

  8. 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

    receiving zoledronic acid were pyrexia, myalgia, and bone and musculoskeletal pain. No cases of osteonecrosis of the jaw were reported, and no adverse effects on the healing of fractures were noted. The rates of renal and cardiovascular adverse events, including atrial fibrillation and stroke, were similar...

  9. Unilateral anterior uveitis complicating zoledronic acid therapy in breast cancer

    Directory of Open Access Journals (Sweden)

    El Saghir Nagi S

    2005-12-01

    Full Text Available Abstract Background Zoledronic acid is very widely used in patients with metastatic bone disease and osteoporosis. Only one case of bilateral uveitis was recently reported related to its use. Case presentation We report the first case of severe unilateral anterior uveitis in a patient with breast cancer and an intraocular lens. Following zoledronic acid infusion, the patient developed severe and dramatic right eye pain with decreased visual acuity within 24 hours and was found to have a fibrinous anterior uveitis of moderate severity The patient was treated with topical prednisone and atropine eyedrops and recovered slowly over several months. Conclusion Internists, oncologists, endocrinologists, and ophtalmologists should be aware of uveitis as a possible complication of zoledronic acid therapy. Patients should be instructed to report immediately to their physicians and treatment with topical prednisone and atropine eyedrops should be instituted immediately at the onset of symptoms. This report documents anterior uveitis as a complication of zoledronic acid therapy. This reaction could be an idiosyncratic one but further research may shed more light on the etiology.

  10. Use of Zoledronic Acid in Paediatric Craniofacial Fibrous Dysplasia

    Directory of Open Access Journals (Sweden)

    Chiara Di Pede

    2016-01-01

    Full Text Available We describe a case of a paediatric patient affected by mandibular fibrous dysplasia (FD with severe and chronic pain who was successfully treated with zoledronic acid (ZOL: a third-generation bisphosphonate. Further research is needed to assess its safety and efficacy as a treatment option for FD in the paediatric population.

  11. Zoledronic acid infusion for prevention and treatment of osteoporosis

    OpenAIRE

    Sunyecz, John A

    2010-01-01

    John A SunyeczLaurel Highlands Ob/Gyn, Hopwood, Pennsylvania, USA and MenopauseRx, Inc., Uniontown, PA, USAAbstract: Osteoporotic fractures are associated with significant morbidity, reduced quality of life, increased mortality, and high health care costs. Bisphosphonates are standard therapy for treatment of osteoporosis. However, patient compliance and persistence with oral weekly or monthly bisphosphonate therapy are suboptimal and may lead to reduced effectiveness. Zoledronic acid (ZOL) i...

  12. 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.)

  13. 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

    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...

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    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...

  15. Assessment of the Effects of Zoledronic Acid Therapy on Bone Metabolic Indicators in Hormone-Resistant Prostate Cancer Patients with Bone Metastatasis

    Science.gov (United States)

    Demirtas, Abdullah; Sahin, Nurettin; Caniklioglu, Mehmet; Kula, Mustafa; Ekmekcioglu, Oguz; Tatlisen, Atila

    2011-01-01

    Purpose. Assessment of effects of zoledronic acid therapy on bone metabolic indicators in hormone-resistant prostate cancer patients with bone metastasis. Material and Methods. Hormone-resistant prostate cancer patients who were identified to have metastases in their bone scintigraphy were taken to trial group. Before administration of zoledronic acid, routine tests for serum calcium, total alkalen phosphates were studied. Sample sera for bone metabolic indicators BALP, PINP, and ICTP were collected. Bone pain was assessed via visual analogue scale and performance via Karnofsky performance scale. Four mg zoledronic acid was administered intravenously once a month. Results. When serum levels of bone forming indicators PINP; BALP were compared before and after therapy, there were insignificant decreases (P = .33, P = .21, resp.). Serum levels of bone destruction indicator ICTP was compared, and there was a significant decrease after zoledronic acid therapy (P = .04). When performances of the patients were compared during therapy period, performances decreased significantly due to progress of illness (P = .01). All patients had ostalgia caused by bone metastases at various degrees. Significant decrease in pain scores was observed (P < .01). Conclusion. Zoledronic acid therapy decreased bone destruction and was effective in palliation of pain in patient with bone metastasis. Using bone metabolic indicators during followup of zoledronic acid therapy might be useful. PMID:22084798

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. [Sunitinib and zoledronic acid induced osteonecrosis of the jaw].

    Science.gov (United States)

    Soós, Balázs; Vajta, László; Szalma, József

    2015-11-15

    The tendency for bisphosphonate and non-bisphosphonate (eg.: antiresorptive or anti-angiogenesis drugs) induced osteonecrosis is increasing. Treatment of these patients is a challenge both for dentists and for oral and maxillofacial surgeons. Cooperation with the drug prescribing general medicine colleagues to prevent osteonecrosis is extremely important. Furthermore, prevention should include dental focus elimination, oral hygienic instructions and education, dental follow-up and, in case of manifest necrosis, referral to maxillofacial departments. Authors outline the difficulties of conservative and surgical treatment of a patient with sunitinib and zoledronic acid induced osteonecrosis. The patient became symptomless and the operated area healed entirely six and twelve months postoperatively. A long term success further follow-up is necessary to verify long-term success.

  20. Zoledronic acid in the management of metastatic bone disease.

    Science.gov (United States)

    Santini, Daniele; Fratto, Maria Elisabetta; Vincenzi, Bruno; Galluzzo, Sara; Tonini, Giuseppe

    2006-12-01

    Bisphosphonate therapy has become a standard of therapy for patients with malignant bone disease. Moreover, in vivo preclinical and preliminary clinical data suggest that bisphosphonates may prevent cancer treatment-induced bone loss and the onset of malignant bone disease in patients with early-stage cancer. This comprehensive review critically reports the several preclinical evidences of action of bisphosphonates on osteoclasts, lymphocytes and tumour cells. In addition, all the clinical trials evaluating the effects of principal bisphosphonates on skeletal disease progression in patients with breast cancer, prostate cancer, non-small cell lung cancer and other cancers have been reported. Of the available bisphosphonates, intravenous zoledronic acid has demonstrated the broadest clinical activity and is actually approved for the treatment of bone metastases from any solid tumour in many countries. Renal safety is an important consideration for oncologists who are treating patients with bisphosphonates. This issue and the other topics relating to the safety of bisphosphonates are discussed in this review.

  1. Vitamin D reduces musculoskeletal pain after infusion of zoledronic acid for postmenopausal osteoporosis.

    Science.gov (United States)

    Catalano, Antonino; Morabito, Nancy; Atteritano, Marco; Basile, Giorgio; Cucinotta, Domenico; Lasco, Antonino

    2012-04-01

    The acute-phase response (APR) is a frequent occurrence after infusion of zoledronic acid and is caused by activation of γδ T cells. Vitamin D receptor is expressed in immune cells, and vitamin D has immunomodulatory properties. The aim of this prospective study was to test the effect of vitamin D (cholecalciferol) on the incidence of APR and intensity of pain in women undergoing infusion of zoledronic acid for postmenopausal osteoporosis. 60 women were enrolled and randomized into two groups. At baseline, 30 women received an oral bolus of cholecalciferol (300,000 IU), while another 30 women received placebo. On day 5 both groups were treated with a single infusion of zoledronic acid (5 mg) and received a daily supplementation of calcium (1,000 mg) and vitamin D (800 IU). Patients were clinically evaluated and inflammatory markers were assayed before zoledronic acid administration and every 24 h for the following 2 days. The onset of APR has been defined by the occurrence of fever or at least one of the typical symptoms, such as musculoskeletal pain after zoledronic acid infusion. Intensity of pain was measured by a one-dimensional scale (0 = no pain, 10 = unbearable pain). APR developed in 66.6% of patients, with no significant difference between groups. The vitamin group experienced less musculoskeletal pain [median 1 (0-4) vs. 2 (1-8), P osteoporosis.

  2. Zoledronic Acid May Reduce Intraoperative Bleeding in Spinal Tumors: A Prospective Cohort Study

    Directory of Open Access Journals (Sweden)

    Juan Wu

    2015-01-01

    Full Text Available Between June 2010 and June 2011, 176 patients were divided into 2 groups: a group with spinal metastasis of solid tumors (n=157 and a group with multiple myeloma (n=19. Both groups were further divided into 2 subgroups: a group receiving zoledronic acid before surgery and a control group. The zoledronic acid subgroup of the solid tumors group was group A (n=81, the control subgroup of the solid tumors group was group B (n=76, the zoledronic acid subgroup of the multiple myeloma group was group C (n=10, and the control subgroup of the multiple myeloma group was group D (n=9. The average intraoperative blood loss during spinal surgery was as follows: 1311±691 mL in group A and 1752±740 mL in group B (P=0.000 and 1994±810 mL in group C and 3134±795 mL in group D (P=0.000. Patients receiving zoledronic acid before surgery had significantly less intraoperative bleeding than those who did not receive it. Preoperative use of zoledronic acid can effectively reduce intraoperative bleeding during surgery for the treatment of spinal tumors.

  3. Zoledronic Acid may reduce intraoperative bleeding in spinal tumors: a prospective cohort study.

    Science.gov (United States)

    Wu, Juan; Zheng, Wei; Tan, Yan; Hu, Xiao-Yuan; Huang, Quan; Fan, Kai-Hua; Ma, Jie; Xiao, Wen-Jing; Ren, Jian-Dong; Hou, Jun; Xiao, Jian-Ru

    2015-01-01

    Between June 2010 and June 2011, 176 patients were divided into 2 groups: a group with spinal metastasis of solid tumors (n = 157) and a group with multiple myeloma (n = 19). Both groups were further divided into 2 subgroups: a group receiving zoledronic acid before surgery and a control group. The zoledronic acid subgroup of the solid tumors group was group A (n = 81), the control subgroup of the solid tumors group was group B (n = 76), the zoledronic acid subgroup of the multiple myeloma group was group C (n = 10), and the control subgroup of the multiple myeloma group was group D (n = 9). The average intraoperative blood loss during spinal surgery was as follows: 1311 ± 691 mL in group A and 1752 ± 740 mL in group B (P = 0.000) and 1994 ± 810 mL in group C and 3134 ± 795 mL in group D (P = 0.000). Patients receiving zoledronic acid before surgery had significantly less intraoperative bleeding than those who did not receive it. Preoperative use of zoledronic acid can effectively reduce intraoperative bleeding during surgery for the treatment of spinal tumors.

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

    Science.gov (United States)

    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.

  5. Zoledronic acid-associated symmetrical drug-related intertriginous and flexural exanthema (SDRIFE): report of baboon syndrome in a woman with recurrent metastatic breast cancer after receiving zoledronic acid

    OpenAIRE

    Cohen, Philip R.

    2015-01-01

    Background:  Baboon syndrome is a distinctive skin reaction in which the patient typically develops erythematous buttocks that appear similar to those of a baboon.  The non-contact allergenic variant of baboon syndrome is also referred to as symmetrical drug-related intertriginous and flexural exanthema (SDRIFE).  Zoledronic acid is a bisphosphonate that is used in patients with metastatic cancer to prevent bone complications. Purpose:  Zoledronic acid-associated baboon syndrome is ...

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

    Directory of Open Access Journals (Sweden)

    Xi-Yuan Ge

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

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

    Directory of Open Access Journals (Sweden)

    Abdulmohsen H. Al Elq

    2013-03-01

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

  8. 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.

  9. Treatment of osteoporotic intertrochanteric fractures by zoledronic acid injection combined with proximal femoral nail anti-rotation

    Institute of Scientific and Technical Information of China (English)

    Yong Li; Wen-Bo Zhao; De-Li Wang; Qing He; Qin Li; Fu-Xing Pei; Lei Liu

    2016-01-01

    Objective:To observe the clinical results of proximal femoral nail anti-rotation (PFNA) combined with zoledronic acid injection in the treatment of osteoporotic intertrochanteric fractures in the elderly.Methods:60 elderly patients with osteoporotic intertrochanteric fractures were diagnosed using a dual energy X-ray bone density instrument.Patients were randomly divided into treatment or control groups (30 cases in each group).Patients in both groups were treated by closed/open reduction and internal fixation using PFNA.In the treatment group,patients received one zoledronic phosphonic acid injection of 5 mg/100 ml via intravenous drip,in addition to 600 mg of Caltrate D (qd) and 0.25 μg of alpha ossification alcohol (qd).The control group received 600 mg of Caltrate D (qd) and 0.25 μg of alpha ossification alcohol (qd).The oral drugs were administered for 12 months.Bone pain relief was observed,and changes in the bone mineral density (BMD) of the lumbar and health-side hip were recorded.Clinical results were evaluated using the Visual Analogue Scale (VAS),Harris joint function score,and Osteoporosis Quality of Life Scale (OQOLS).Results:Compared with the control group,bone pain symptoms were significantly alleviated (p < 0.05) in the treatment group.In the treatment and control groups,both between-group and within-group differences in BMD were significantly increased in L1-4,femoral neck and trochanter (p < 0.05).No significant differences were found between the two groups in regard to the involved hip or the total rate of improvement at the end of the follow-up period,although cases in the treatment group had higher OQOLS scores than those of the controls (p =0.04).Cases in the treatment group healed more quickly than those in the control group [(13 ± 3.2) weeks vs (15 ± 4.6) weeks,p =0.02].During the follow-up period,cases in the treatment group had no new fractures,whereas 2 new cases of hip fracture and 2 cases of distal radial fractures were observed

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

    Science.gov (United States)

    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.

  11. 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.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    , 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...

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

    NARCIS (Netherlands)

    Lam, M.G.E.H.; Dahmane, Amel; Stevens, W.H.M.; Rijk, Peter P. van; Klerk, J.M.H. de; Zonnenberg, Bernard A.

    2008-01-01

    Purpose: 153Sm-ethylenediaminetetramethylenephosphonic acid (EDTMP; Quadramet®) is indicated for the treatment of painful bone metastases, whereas zoledronic acid (Zometa®) is indicated for the prevention of skeletal complications. Because of the different therapeutic effects, combining the treatmen

  14. Evaluating results from the multiple myeloma patient subset treated with denosumab or zoledronic acid in a randomized phase 3 trial.

    Science.gov (United States)

    Raje, N; Vadhan-Raj, S; Willenbacher, W; Terpos, E; Hungria, V; Spencer, A; Alexeeva, Y; Facon, T; Stewart, A K; Feng, A; Braun, A; Balakumaran, A; Roodman, G D

    2016-01-08

    In a phase 3 trial of denosumab vs zoledronic acid in patients (n=1776) with bone metastases and solid tumors or multiple myeloma, denosumab was superior to zoledronic acid for the primary end point of prevention of skeletal-related events. There was no difference in overall survival between the two groups; however, an ad hoc overall survival analysis in the multiple myeloma subset of patients (n=180) favored zoledronic acid (hazard ratio (HR) 2.26; 95% confidence interval (CI) 1.13-4.50; P=0.014). In the present analysis, we found imbalances between the groups with respect to baseline risk characteristics. HRs with two-sided 95% CIs were estimated using the Cox model. After adjustment in a covariate analysis, the CI crossed unity (HR 1.86; 95% CI 0.90-3.84; P=0.0954). Furthermore, we found a higher rate of early withdrawals for the reasons of lost to follow-up and withdrawal of consent in the zoledronic acid group; after accounting for these, the HR was 1.31 (95% CI 0.80-2.15; P=0.278). In conclusion, the survival results in multiple myeloma patients in this trial were confounded and will eventually be resolved by an ongoing phase 3 trial.

  15. 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...

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

    Directory of Open Access Journals (Sweden)

    Luca Dalle Carbonare

    2010-08-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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.

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

    OpenAIRE

    2008-01-01

    Purpose 153Sm-ethylenediaminetetramethylenephosphonic acid (EDTMP; Quadramet®) is indicated for the treatment of painful bone metastases, whereas zoledronic acid (Zometa®) 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. Methods Patients with hormone-refractory prostate cancer ...

  20. Treatment of painful bone metastases in hormone-refractory prostate cancer with zoledronic acid and samarium-153-ethylenediaminetetramethylphosphonic acid combined.

    Science.gov (United States)

    Lam, Marnix G E H; de Klerk, John M H; Zonnenberg, Bernard A

    2009-07-01

    Abstract Bone-seeking radiopharmaceuticals and bisphosphonates may be indicated in patients with cancer with painful osseous metastases to palliate pain symptoms or to prevent skeletal-related events. Both pharmaceuticals may have an additive or even synergistic palliative effect. The combined use of bone-seeking radiopharmaceuticals and bisphosphonates is, however, controversial because of assumed competition between both phosphonate-compounds at the bone level. We report a case of hormone-refractory prostate cancer (HRPC) with multiple painful osseous metastases. The patient was treated with samarium-153-ethylenediaminetetramethylphosphonic acid ((153)Sm-EDTMP; Quadramet, CIS bio International, Saclay, France) in combination with zoledronic acid (Zometa, Novartis, Stein, Switzerland). He was treated for 6 months with 4 weekly intervals of zoledronic acid in combination with 3 monthly intervals of (153)Sm-EDTMP. No negative interaction was found, toxicity was low, and efficacy high. He experienced a total relief of pain, a significant decrease of prostate-specific antigen (PSA) and, surprisingly, a significant decrease of tumor burden.

  1. Evaluation of the efficacy of zoledronic acid and amifostine on radiation induced bone loss in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Wook; Lee, Sueum; Kang, Sohi; Moon, Cahng Jong; Kim, Jong Choon; Kim, Sung Ho [College of Veterinary Medicine, Chonnam National University, Gwangju (Korea, Republic of); Jung, Uhee; Jo, Sung Kee [Advanced Radiation Technology Institute, Jeungeup (Korea, Republic of); Jang, Jong Sik [College of Ecology and Environmental Science, Kyungpook National University, Sangju (Korea, Republic of)

    2016-09-15

    This study investigated the effects of zoledronic acid (ZA) on radiation-induced bone loss in C3H/HeN mice. C3H/HeN mice were divided into sham control and three irradiated groups (3 Gy, gamma ray). The irradiated mice were treated for 12 weeks with vehicle, amifostine (intraperitoneal injection), or ZA (subcutaneous injection). Grip strength, uterus weight, and serum alkaline phosphatase (ALP), and tartrate-resistant acid phosphatase (TRAP) levels were measured. Tibiae were analyzed using micro-computed tomography. Treatment of ZA (100 μg·kg{sup -1}·week{sup -1}) significantly preserved trabecular bone volume, trabecular thickness, trabecular number, trabecular separation, bone mineral density of proximal tibia metaphysic, and cortical bone volume, but did not alter the uterus weight of the mice. The administration of ZA for 12 weeks lowered serum ALP and TRAP levels in irradiated mice, suggesting that ZA can reduce the bone turnover rate in mice. No differences were apparent between the amifostine-treated group and the irradiation control group. The results indicate that ZA can prevent radiation-induced bone loss in mice.

  2. Can we consider zoledronic acid a new antitumor agent? Recent evidence in clinical setting.

    Science.gov (United States)

    Santini, Daniele; Virzi, Vladimir; Fratto, Maria Elisabetta; Bertoldo, Francesco; Sabbatini, Roberto; Berardi, Rossana; Calipari, Nicola; Ottaviani, Davide; Ibrahim, Toni

    2010-02-01

    New emerging data suggest that bisphosphonates may exert antitumor properties. Preclinical studies have demonstrated that zoledronic acid (ZA) can induce direct and indirect antitumor activities such as inhibition of angiogenesis, invasion and adhesion of tumor cells, and overall tumor progression, stimulation of adoptive and innate immunity and emerging evidence suggests that the use of these agents may prevent the development of skeletal and extra skeletal metastases. This review will critically describe the new growing evidence of antitumor activity exerted by bisphosphonates in cancer patients, both in metastatic disease and in the adjuvant setting. The effects of bisphosphonates on survival in metastatic cancer patients will be described and evidence from retrospective analyses and prospective studies will be critically reported. The early evidence from prospective analyses of survival impact by ZA in the adjuvant setting in breast cancer will be discussed together with the recently published results of the ABCSG-12 study. A new "era" for bisphosphonates in the oncological setting is opening. The clinical data that will be reported in this review represent the first step in a path that will conduct us to explore new horizons in the field of adjuvant and metastatic cancer therapies.

  3. Efficacy of zoledronic acid in treatment of teoarthritis is dependent on the disease progression stage in rat medial meniscal tear model

    Institute of Scientific and Technical Information of China (English)

    De-gang YU; Shen LIU; Zhen-an ZHU; Bo YU; Yuan-qing MAO; Xin ZHAO; Xiao-qing WANG; Hui-feng DING; Lei CAO; Guang-wang LIU; Shao-bo NIE

    2012-01-01

    Aim:To investigate whether the stage of osteoarthritis (OA) progression influenced the efficacy of the third-generation bisphosphonate zoledronic acid in a rat medial meniscal tear model.Methods:Medial meniscal tear (MMT) was surgically induced in adult male Sprague Dawley rats.Zoledronic acid (ZOL,100 μg/kg,sc,twice a week) was administered starting immediately,early (from 4 weeks) or late (from 8 weeks) after OA induction.The degeneration of articular cartilage was evaluated with toluidine blue O staining.Subchondral bone remodeling was evaluated with X-ray micro-CT scanning.Joint pain was measured with respect to weight-bearing asymmetry.Calcitonin gene-related peptide (CGRP) expression in dorsal root ganglia (DRGs) was examined using immunofluorescence analysis.The afferent neurons in DRGs innervating the joint were identified by retrograde labeling with fluorogold.Results:Progressive cartilage loss was observed during 12 weeks after OA induction.Subchondral bone remodeling manifested as increased bone resorption at early stage (4 weeks),but as increased bone accretion at advanced stages (8 weeks).Immediately and early ZOL administration significantly improved subchondral microstructural parameters,attenuated cartilage degeneration,reduced weight-bearing asymmetry and CGRP expression,whereas the late ZOL administration had no significant effects.Conclusion:The stage of OA progression influences the efficacy of ZOL in treating joint degeneration and pain.To obtain the maximum efficacy,bisphosphonate treatment should be initiated in rat with early stages of OA pathogenesis.

  4. Cost-Effectiveness of Zoledronic Acid to Prevent and Treat Postmenopausal Osteoporosis in Comparison with Routine Medical Treatment

    Science.gov (United States)

    Golmohamdi, Fateme Rostami; Abbasi, Mahnaz; Karyani, Ali Kazemi; Sari, Ali Akbari

    2016-01-01

    Introduction Fractures caused by osteoporosis are prevalent among elderly females, which reduce quality of life significantly. This study aimed at comparing cost-effectiveness of Zoledronic acid in preventing and treating post-menopause osteoporosis as compared with routine medical treatment. Methods This cost-effectiveness study was carried out retrospectively from the Ministry of Health and insurance organizations perspective. Costs were evaluated based on the cost estimation of a sample of patients. Outcomes were obtained from a systematic review. The Cost-Effectiveness Ratio (CER) and incremental cost-effectiveness ratio (ICER) for outcome of femoral neck Bone Mineral Density (BMD), hip trochanter BMD, total hip BMD and lumbar spine BMD and cost-benefit of consuming Zoledronic Acid were calculated for fracture outcome obtained from reviewing hospital records. Results The results and the ICER calculated for study outcomes indicated that one percent increase of BMD on femoral neck BMD requires further cost of $386. One percent increase of BMD on hip trochanter BMD requires further cost of $264. One percent increase of BMD on total hip BMD requires further cost of $388, one percent increase of BMD on lumbar spine BMD requires further cost of $347. The Cost Benefit Analysis (CBA) calculated for vertebral and hip fracture, non-vertebral fracture, any clinical fracture, and morphometric fracture for a 36-month period were about 0.82, 0.57, and 1.06, respectively. Vertebral and hip fractures, and non-vertebral fractures or any clinical fracture for a 12-month period were calculated as 1.14 and 0.64, respectively. In other words, Zoledronic acid consumption approach is a cheaper and better approach based on an economic assessment, and it can be considered as a dominant approach. Conclusion According to the cost-effectiveness of zoledronic acid in the prevention and treatment of osteoporosis in women, despite the costs, it is recommended that insurance coverage for the

  5. Extracellular Ca(2+)-dependent enhancement of cytocidal potency of zoledronic acid in human oral cancer cells.

    Science.gov (United States)

    Inoue, Sayaka; Arai, Naoya; Tomihara, Kei; Takashina, Michinori; Hattori, Yuichi; Noguchi, Makoto

    2015-08-15

    Direct antitumor effects of bisphosphonates (BPs) have been demonstrated in various cancer cells in vitro. However, the effective concentrations of BPs are typically much higher than their clinically relevant concentrations. Oral cancers frequently invade jawbone and may lead to the release of Ca(2+) in primary lesions. We investigated the effects of the combined application of zoledronic acid (ZA) and Ca(2+) on proliferation and apoptosis of oral cancer cells. Human oral cancer cells, breast cancer cells, and colon cancer cells were treated with ZA at a wide range of concentrations in different Ca(2+) concentration environments. Under a standard Ca(2+) concentration (0.6mM), micromolar concentrations of ZA were required to inhibit oral cancer cell proliferation. Increasing extracellular Ca(2+) concentrations greatly enhanced the potency of the ZA cytocidal effect. The ability of Ca(2+) to enhance the cytocidal effects of ZA was negated by the Ca(2+)-selective chelator EGTA. In contrast, the cytocidal effect of ZA was less pronounced in breast and colon cancer cells regardless of whether extracellular Ca(2+) was elevated. In oral cancer cells incubated with 1.6mM Ca(2+), ZA up-regulated mitochondrial Bax expression and increased mitochondrial Ca(2+) uptake. This was associated with decreased mitochondrial membrane potential and increased release of cytochrome c. We suggest that ZA can specifically produce potent cytocidal activity in oral cancer cells in an extracellular Ca(2+)-dependent manner, implying that BPs may be useful for treatment of oral squamous cell carcinoma with jawbone invasion leading to the hypercalcemic state.

  6. 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

  7. Clomipramine causes osteoporosis by promoting osteoclastogenesis via E3 ligase Itch, which is prevented by Zoledronic acid

    Science.gov (United States)

    Li, Xing; Sun, Wen; Li, Jinbo; Wang, Mengmeng; Zhang, Hengwei; Pei, Lingpeng; Boyce, Brendan F.; Wang, Zhiyu; Xing, Lianping

    2017-01-01

    Patients taking antidepressants, including Clomipramine (CLP), have an increased risk of osteoporotic fracture. However, the effects of CLP on bone metabolism are unknown. Here, we demonstrate that WT mice treated with CLP for 2 weeks had significantly reduced trabecular bone volume and cortical bone thickness, associated with increased osteoclast (OC) numbers, but had no change in osteoblast numbers or bone formation rate. Bone marrow cells from CLP-treated mice had normal OC precursor frequency, but formed significantly more OCs when they were cultured with RANKL and M-CSF. CLP promoted OC formation and bone resorption and expression of OC-associated genes. CLP-induced bone loss was prevented by Zoledronic acid. At the molecular level, CLP inhibited the activity of the ubiquitin E3 ligase Itch. CLP did not promote OC formation from bone marrow cells of Itch−/− mice in vitro nor induce bone loss in Itch−/− mice. Our findings indicate that CLP causes bone loss by enhancing Itch-mediated osteoclastogenesis, which was prevented by Zoledronic acid. Thus, anti-resorptive therapy could be used to prevent bone loss in patients taking antidepressants, such as CLP. PMID:28145497

  8. 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.

  9. 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

  10. 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

  11. Antitumor activity of zoledronic acid in primary breast cancer cells determined by the ATP tumor chemosensitivity assay

    Directory of Open Access Journals (Sweden)

    Fehm Tanja

    2012-07-01

    Full Text Available Abstract Background The NeoAzure study has demonstrated that the use of the bisphosphonate zoledronic acid (Zol in the neoadjuvant setting increases the rate of complete response in primary breast cancer and therefore indicates direct antitumor activity. The purpose of this study was to compare the antitumor effect of Zol with standard chemotherapy in primary breast cancer cells using ATP-tumor chemosensitivity assay (ATP-TCA. Methods Breast cancer specimens were obtained from patients with breast cancer who underwent primary breast cancer surgery at the Department of Obstetrics and Gynecology, Tübingen, Germany, between 2006 through 2009. Antitumor effects of Zol, TAC (Docetaxel, Adriamycin, Cyclophosphamide and FEC (5-Fluorouracil, Epirubicin, Cyclophosphamide were tested in 116 fresh human primary breast cancer specimens using ATP-TCA. ATP-TCA results were analyzed with different cut-off levels for the half maximal inhibitory concentration (IC50, for IC90 and for the sensitivity index (IndexSUM. Each single agent or combination was tested at six doubling dilutions from 6.25, 12.5, 25, 50, 100, and 200% of test drug concentrations (TDC derived from the plasma peak concentrations determined by pharmacokinetic data. The assay was carried out in duplicate wells with positive and negative controls. Results The median IndexSUM value was lower for Zol than for the combined regimen FEC (36.8% and TAC (12.9%, respectively, indicating increased antitumor activity of Zol in primary breast cancer cells. The difference regarding Zol and FEC was significant (p  Conclusion Zoledronic acid has a strong antitumor effect on primary breast cancer cells in vitro which is equal or superior to commonly used chemotherapeutic regimens for treating breast cancer.

  12. A comparative study of zoledronic acid and once weekly Alendronate in the management of acute Charcot arthropathy of foot in patients with diabetes mellitus

    Directory of Open Access Journals (Sweden)

    R Bharath

    2013-01-01

    Full Text Available Aim: The aim of this study was to assess and compare the response to two forms of treatment-immobilization with zoledronic acid injection and immobilization with oral weekly Alendronate, in patients with diabetes mellitus and acute Charcot arthropathy (CA of foot in terms of clinical and radiological parameters. Material and Methods: Patients attending the endocrinology and podiatry clinic with history of diabetes mellitus and Acute CA were taken for study. The patients were randomized into two treatment groups. Group Z-zoledronic acid injection along with total contact cast (TCC. Group A-Tab. Alendronate 70 mg. once a week till the complete clinical resolution of acute CA along with TCC. Forty-five patients were randomized and 40 of them completed the study. The primary end point was complete clinical resolution of acute CA-defined as temperature difference between normal and affected foot <1oF. Results: Among the 40 patients, 30 (75% had complete clinical resolution. The mean number of days taken for complete clinical resolution since the initiation of treatment (either Zoledronic acid or Alendronate was approximately 122 days. There was no significant difference in a number of days required for complete clinical resolution, between the two forms of therapy. There was more than 50% reduction in the visual score between the baseline and the final scan. The target to non-target ratio in the skeletal phase also showed an average of 40% reduction from the baseline to the final skeletal scintigraphy. Conclusion: Both Intravenous Zoledronic acid and oral alendronate had comparable efficacy with respect to the time taken for attaining complete clinical resolution of acute CA of foot. However, Alendronate therapy was cost effective among the two. 99m Tc MDP bone scan can be used as an adjuvant to the clinical parameters in assessing the response to therapy.

  13. The BH3-mimetic ABT-737 targets the apoptotic machinery in cholangiocarcinoma cell lines resulting in synergistic interactions with zoledronic acid

    OpenAIRE

    ROMANI, ANTONELLO A.; Desenzani, Silvia; Morganti, Marina M.; Baroni, Maria Cristina; Borghetti, Angelo F.; Soliani, Paolo

    2010-01-01

    Abstract Purpose In TFK-1 and EGI-1 cholangiocarcinoma cell lines, zoledronic acid (ZOL) determines an S-phase block without apoptosis. Here, we investigated the occurrence of apoptosis stigmata when ZOL is associated to the BH3-mimetic ABT-737. Methods In EGI-1 and TFK-1 cholangiocarcinoma cell lines untreated or treated with ABT-737 alone or in combination with ZOL, the pro-survival protein?s pattern (BC...

  14. A ssessment of the malignant biology and bone metabolism after transcatheter vertebral arterial chemoembolization combined with zoledronic acid treatment of vertebral metastasis from lung cancer

    Institute of Scientific and Technical Information of China (English)

    Wei Lu; Zhe Zhang; Chao Yang; Jia-Cheng Zhang; Jun-Peng Ma; Peng Du; Jian Yang; Fu-Qiang Jiang; Xin-Li Jin; Peng Xie

    2016-01-01

    Objective:To study the malignant biology and bone metabolism after transcatheter vertebral arterial chemoembolization combined with zoledronic acid treatment of vertebral metastasis from lung cancer.Methods: A total of 46 cases of patients with vertebral metastasis from lung cancer treated in our hospital between May 2012 and December 2015 were selected and divided into two groups, observation group (n=23) received transcatheter vertebral arterial chemoembolization combined with zoledronic acid treatment and control group only received transcatheter vertebral arterial chemoembolization therapy. Eight weeks after treatment, serum was collected to determine the levels of tumor markers, invasive molecules and bone transformation indicators.Results:8 weeks after treatment, serum CEA, NSE, Cyfra21-1, TK1, RCAS1, CatB, CatD, CatX, MMP7, MMP9, MMP13, N-MID, BALP, OC, PINP,β-CTX, NTX, ICTP and TRACP5b levels of observation group were significantly lower than those of control group.Conclusions:Transcatheter vertebral arterial chemoembolization combined with zoledronic acid treatment can more effectively kill the cancer cells in vertebral metastases, inhibit the secretion of protease and regulate bone metabolism balance.

  15. A novel {sup 99m}Tc-labeled dimethyl-substituted zoledronic acid (DMIDP) with improved bone imaging efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Qiu, L.; Lin, J.; Luo, S.; Wang, Y.; Cheng, W.; Zhang, S. [Jiangsu Institute of Nuclear Medicine, Wuxi (China). Key Laboratory of Nuclear Medicine

    2012-07-01

    A novel zoledronic acid (ZL) derivative, 1-hydroxy-2-(2,4-dimethyl-1H-imidazol-1-yl)-ethane-1,1-diyldiphosphonic acid (DMIDP, dimezoledronate), was successfully prepared and labeled with {sup 99m}Tc in a high labeling yield. The biodistribution in mice shows that {sup 99m}Tc-DMIDP has significant advantage regarding bone resorption and clearance from soft tissues compared with {sup 99m}Tc-ZL and the clinically widely-used bone-imaging agent {sup 99m}Tc-MDP (methylenediphosphonic acid). Kinetics of blood clearance displayed that distribution half-life (T{sub 1/2{alpha}}) and elimination half-life (T{sub 1/2{beta}}) of {sup 99m}Tc-DMIDP were 2.53 min and 23.53 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 from {sup 99m}Tc-DMIDP, which was faster than {sup 99m}Tc-ZL and {sup 99m}Tc-MDP. The present findings indicate that {sup 99m}Tc-DMIDP possesses excellent potential for application as a novel bone scanning agent. (orig.)

  16. Development of superior bone scintigraphic agent from a series of {sup 99m}Tc-labeled zoledronic acid derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Lin Jianguo [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 (China); Qiu Ling, E-mail: qiulingwx@gmail.com [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 (China); Cheng Wen [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 (China); Luo Shineng, E-mail: shineng914@yahoo.com.cn [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 (China); Xue Li; Zhang Shu [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 (China)

    2012-05-15

    Two novel zoledronic acid (ZL) derivatives, 1-hydroxy-4-(1H-imidazol-1-yl)butane-1,1-diyldiphosphonic acid (IBDP) and 1-hydroxy-5-(1H-imidazol-1-yl)pentane-1,1-diyldiphosphonic acid (IPeDP), were prepared and labeled with the radionuclide technetium-99m in a high labeling yield. In vitro stabilities of these radiolabeled complexes were measured by the radio-HPLC analysis as a function of time, which showed excellent stability with the radiochemical purity of over 95% at 6 h post preparation. Their in vivo biological performances were evaluated and compared with those of {sup 99m}Tc-ZL and {sup 99m}Tc-MDP (methylenediphosphonic acid). The biodistribution in mice and scintigraphic images of the rabbit showed that the tracer agent {sup 99m}Tc-IPeDP had highly selective uptake in the skeletal system and rapid clearance from the blood and soft tissues and an excellent scintigraphic image can be obtained in a shorter time post injection with clear visualization of the skeleton and low soft tissue activity. These preclinical studies suggest that {sup 99m}Tc-IPeDP would be a novel superior bone scintigraphic agent. - Highlights: Black-Right-Pointing-Pointer Two novel diphosphonic acids were labeled with the {sup 99m}Tc in high labeling yield. Black-Right-Pointing-Pointer {sup 99m}Tc-IPeDP had high uptake in skeletal system and rapid clearance from blood. Black-Right-Pointing-Pointer {sup 99m}Tc-IPeDP reveals attractive biological features as superior bone scanning agent.

  17. Potentiated suppression of Dickkopf-1 in breast cancer by combined administration of the mevalonate pathway inhibitors zoledronic acid and statins.

    Science.gov (United States)

    Göbel, Andy; Browne, Andrew J; Thiele, Stefanie; Rauner, Martina; Hofbauer, Lorenz C; Rachner, Tilman D

    2015-12-01

    The Wnt-inhibitor dickkopf-1 (DKK-1) promotes cancer-induced osteolytic bone lesions by direct inhibition of osteoblast differentiation and indirect activation of osteoclasts. DKK-1 is highly expressed in human breast cancer cells and can be suppressed by inhibitors of the mevalonate pathway such as statins and amino-bisphosphonates. However, supraphysiological concentrations are required to suppress DKK-1. We show that a sequential mevalonate pathway blockade using statins and amino-bisphosphonates suppresses DKK-1 more significantly than the individual agents alone. Thus, the reduction of the DKK-1 expression and secretion in the human osteotropic tumor cell lines MDA-MB-231, MDA-MET, and MDA-BONE by zoledronic acid was potentiated by the combination with low concentrations of statins (atorvastatin, simvastatin, and rosuvastatin) by up to 75% (p cancer-derived DKK-1-mediated inhibition of osteogenic markers in C2C12 cells (p pathway blockade allows for the combined use of low concentration of statins and amino-bisphosphonates. This combination still significantly suppresses breast cancer-derived DKK-1 to levels where it can no longer inhibit Wnt-mediated osteoblast differentiation.

  18. 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.

  19. Bone Loss after Allogeneic Haematopoietic Stem Cell Transplantation: A Pilot Study on the Use of Zoledronic Acid

    Directory of Open Access Journals (Sweden)

    Andreas Hausmann

    2012-01-01

    Full Text Available Purpose. Bone loss is a common phenomenon following allogeneic haematopoietic stem cell transplantation (allo-HSCT. The study aimed on tolerance and efficacy of zoledronic acid (ZA in patients after allo-HSCT. Methods. 40 patients’ with osteoporosis or osteopenia were recruited on this phase II study. ZA was given at a dose of 4 mg IV every 3 months for 2 years (yrs. BMD was determined by dual-energy X-ray absorptiometry (LS lumbar spine, FH femur hip. Patients were evaluated for deoxypyridinoline (Dpd and calcium excretion by longitudinal measurements. Results. 36 patients who had received at least 3 doses of ZA were evaluable. 26 patients had at least two BMD measurements since baseline (BMD group. Among these patients, BMD increased from 0.97±0.15 to 1.10±0.18 g/cm² (LS baseline—2 yrs, Δ+11.6±6.0%, P<0.001 and from 0.82±0.10 to 0.91±0.10 g/cm² (FH baseline—2 yrs, Δ+7.5±7.0%, P<0.001. Factors associated with an increase in BMD were younger age, female donor sex, and immunosuppression with CSA/MTX. Conclusion. ZA was generally well tolerated; it increases BMD and reduces Dpd excretion significantly in patients with bone loss after allo-HSCT.

  20. 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

    2016-01-01

    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

  1. 14例唑来膦酸不良反应文献分析%Literature Analysis of 14 Cases of Adverse Drug Reactions Induced by Zoledronic Acid

    Institute of Scientific and Technical Information of China (English)

    韩一萱

    2014-01-01

    Objective:To analyze the general rules and characteristics of the adverse drug reactions(ADRs)induced by zoledronic acid so as to provide a reference for rational drug use in clinical practice.Methods:ADRs of zoledronic acid were retrieved from CNKI and VIP database since it was put into market in China and the data was analyzed statistically. Results:Totally 14 cases of ADRs(including 3 men and 11 women)caused by zoledronic acid were collected. The youngest patient was 43 years old and the oldest was 78 years old. The patients over the age of 50 showed the highest incidence(n= 11,78.6%). Their ADRs were involved in systemic damage such as musculo-skeletal system damage, metabolic and nutritional disorders, and hepatobiliary system damage,etc.Conclusion:Clinicians and pharmacists should understand the rules and characteristics of the ADRs induced by zoledronic acid and strengthen monitoring on drug use so as to reduce the incidence of ADR.%目的:分析唑来膦酸不良反应发生的规律及特点,为合理用药提供参考。方法:检索唑来膦酸在中国上市以来中国学术期刊全文数据库(CNKI)、维普中文科技期刊数据库(VIP)收载的不良反应文献进行统计分析。结果:唑来膦酸不良反应的个案报道共14例,男性3例,女性11例,年龄最小为43岁,最大为78岁,年龄50岁以上发生率较高(11例,78.6%);不良反应分别涉及全身性损害、肌肉骨骼系统损害、代谢和营养障碍、肝胆系统损害等。结论:临床医师和药师应了解唑来膦酸致不良反应的规律和特点,加强用药监测,以减少不良反应的发生。

  2. PTH(1-34) and zoledronic acid have differing longitudinal effects on juvenile mouse femur strength and morphology.

    Science.gov (United States)

    Bartlow, Christopher M; Oest, Megan E; Mann, Kenneth A; Zimmerman, Nicholas D; Butt, Bilal B; Damron, Timothy A

    2016-09-21

    Treatment of secondary pediatric osteoporosis-particularly that due to chronic diseases, immobilization, and necessary medical treatments-is currently limited by a poor understanding of the long-term efficacy and safety of skeletal metabolism modifying drugs. This study aimed to characterize longitudinal effects of representative anabolic (parathyroid hormone, PTH) and anti-catabolic (zoledronic acid, ZA) drugs on skeletal morphology, mechanical strength, and growth in juvenile mice. BALB/cJ mice aged 4 weeks were given PTH(1-34) or vehicle (control) daily for 8 weeks, or 4 weekly doses of ZA, and evaluated at time points 0-26 weeks after treatment initiation. There were no enduring differences in body length or mass between treatment groups. ZA increased femur size as early as week 0, including increased distal femur bone volume and diaphyseal cross-sectional area, persisting through week 26. PTH treatment only transiently increased bone size, including distal femur volume at weeks 4-12. ZA decreased diaphyseal cortical tissue mineral density (TMD) at 12-26 weeks versus controls; PTH decreased TMD only at 2 weeks (vs. controls). ZA increased bending strength at 0-12 weeks and flexural strength at week 4 (vs. controls), but decreased flexural strength and modulus at week 26. PTH treatment increased bending strength only at 4 weeks, and did not affect flexural strength. Overall, ZA rapidly and persistently increased femur strength and size, but compromised bone material quality long-term. In healthy juvenile mice, limited-duration PTH treatment did not exert a strong anabolic effect, and had no adverse effects on femur strength, morphology, or growth. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. Novel therapeutic intervention for osteoporosis prepared with strontium hydroxyapatite and zoledronic acid: In vitro and pharmacodynamic evaluation.

    Science.gov (United States)

    Khajuria, Deepak Kumar; Vasireddi, Ramakrishna; Trebbin, Martin; Karasik, David; Razdan, Rema

    2017-02-01

    Osteoporosis therapeutics has been monopolized mainly by bisphosphonates, which are potent anti-osteoporotic drugs, while they do not promote bone formation or replenish the already resorbed bone. Although strontium substituted hydroxyapatite (SrHA) has been proclaimed to improve bone properties in an osteoporotic animal model, there is no published data on direct delivery of SrHA nanoparticles by bisphosphonate-like zoledronic acid (ZOL) to the bone. Therefore, this study was designed to investigate the potential of using SrHA/ZOL nanoparticle-based drug formulation in an ovariectomized rat model of postmenopausal osteoporosis. SrHA and SrHA/ZOL nanoparticles were prepared and characterized by field-emission scanning electron microscopy (FESEM), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Twelve weeks after ovariectomy, rats were treated with either single intravenous dose of SrHA/ZOL (100, 50 or 25μg/kg); ZOL (100μg/kg); or SrHA (100μg/kg). Saline-treated OVX and SHAM-OVX groups served as controls. The energy-dispersive X-ray (EDX) microanalysis of bone specimen obtained from SrHA/ZOL groups yielded range between 64.3±6.7 to 66.9±6.8 of calcium weight (wt) % and 1.64±0.6 to 1.74±0.8 of calcium/phosphorus (Ca/P) ratio which was significantly higher when compared with 39.7±9.3 calcium and 1.30±0.2 Ca/P ratio for OVX group. Moreover, the strontium wt% in SrHA/ZOL group (between 3.1±0.5 and 6.8±0.4) was significantly higher than SrHA group (1.8±0.9). These results confirmed targeted delivery of SrHA nanoparticles by ZOL to the bone. Therapy with SrHA/ZOL showed significant improvements in trabecular bone microarchitecture and mechanical strength as compared to ZOL or SrHA (posteoporosis.

  9. 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.

  10. Zoledronic acid treatment for cancerous bone metastases: a phase IV study in Taiwan

    Directory of Open Access Journals (Sweden)

    Po-Hui Chiang

    2013-01-01

    Full Text Available Aim of study: To investigate the features, adverse effects, bone marker changes in patients with breast cancer, prostate cancer, and multiple myeloma with bone metastases under Zometa® therapy. Materials and Methods: This post-marketing study included 414 Taiwanese patients with bone metastases secondary to breast cancer, prostate cancer, or multiple myeloma who received Zometa® for 48 weeks. The patients′ characteristics, medication and adverse events were recorded, meanwhile changes in four serum bone metabolic markers and pain reduction were assessed every three months for one year. Results: A total of 3,711 doses of Zometa® were infused, accounting for 294.5 patient-years. Adverse events occurred in 9.4% of patients, with bone pain, insomnia, constipation, and pyrexia as the most frequently reported. There was no osteonecrosis of the jaw. The incidence of skeletal-related events decreased significantly from 44.9% to 18.8%. Serum NTx, BAP, and TRACP5b steadily decreased to nadir at six months, but serum OPG was persistently elevated until the end of one year. The average decrease in pain score was 14.1, 14.3, and 16.7 for prostate cancer, breast cancer, and multiple myeloma patients, respectively. Conclusion: Zometa® can be safely administered in Taiwanese patients with bone metastases secondary to breast cancer, prostate cancer, and multiple myeloma. There are concomitant decreases in skeletal-related events and bone pain.

  11. A multicenter phase Ⅱ trial of domestic product of zoledronic acid in the treatment of malignant hypercalcemia%国产唑来膦酸治疗肿瘤高钙血症多中心Ⅱ期临床观察

    Institute of Scientific and Technical Information of China (English)

    Lijun Di; Jun Ren; Ying Yan

    2007-01-01

    Objective: To evaluate the effect and safety of clinical use of zoledronic acid in the treatment of malignant hypercalcemia. Methods: A multi-center, open phase Ⅱ clinical trial was conducted in 15 cases with malignant hypercalcemia who received zoledronic acid intravenously for 15 min. The level of blood calcium and side effects were recorded regularly within 28 days after injection. Results: One case was dropped out due to bad compliance. The complete response rate (the corrected serum calcium was reduced to normal level) was 100.00% (14/14). The medium time of complete response rate was 5.07 days. The medium maintain time was 22.30 days. Slight, or moderate fever was observed. Conclusion: Zoledronic acid can effectively reduce the malignant hypercalcemia. The use of zoledronic acid appears to be safety and convenient.

  12. 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

  13. Efecto de una sola dosis de ácido zoledrónico en un caso de enfermedad de Paget ósea Effect of a single dose of zoledronic acid in a case of Paget bone disease

    Directory of Open Access Journals (Sweden)

    Melina Sabán

    2010-10-01

    . We administered intravenous zoledronic acid (4 mg in a single dose. After this treatment we observed clinical and biochemical remission during four years and a significantly improvement in the scintigraphy. We report a case of Paget´s disease, resistant to pamidronate treatment in whom a single dose of zoledronic acid produced clinical and biochemical remission during 4 years and a significant improvement in the scintigraphic scan.

  14. 唑来膦酸促进口腔种植体骨结合的研究现状%Zoledronic acid promotes osseointegration of dental implant

    Institute of Scientific and Technical Information of China (English)

    谢淑娟; 占柳

    2012-01-01

    种植体的骨整合是目前口腔学界种植义齿的研究热点.改善种植体的骨结合,增加种植体周围的骨量,可以较好的提高种植体的稳定性,从而提高种植体成功率和延长种植体使用寿命.双磷酸盐( bisphosphonate,BPs)类药物的新生力量——唑来膦酸( Zoledronic acid),以其在BPs类药物中具有最强效的抗骨质吸收能力吸引了众多关注,在临床成功应用后,口腔专家进一步研究其在种植体方面的良好效应,通过多项实验项目观察发现其具有改善种植体骨结合的效用,并且与其他药物联合应用时可以得到更好的效果,有望投入临床,应用前景不可小觑.%Osseointegration is now the focus of research on dental implant. It can improve the stability of the implant, and hence increase its success rate and prolong its life. Bisphosphonates-zoledronic acid, with its most powerful anti-bone resorption ability among bisphosphonates (BPs) , has attracted a lot of attention to the very success in its clinical application. Recently, dental experts have further studied its good effects in tooth implant by a number of pilot projects. Experiments show that it can improve osseointegration and produce better effect when combined with other drugs.

  15. Zoledronic Acid Injection

    Science.gov (United States)

    ... called bisphosphonates. It works by slowing bone breakdown, increasing bone density (thickness), and decreasing the amount of ... parts of the body); anemia (condition in which red blood cells cannot bring enough oxygen to other parts of ...

  16. Clinical trials progression of anti-cancer effects exerted by zoledronic acid%唑来膦酸抗肿瘤作用的临床研究进展

    Institute of Scientific and Technical Information of China (English)

    王增; 卢红阳; 翁琳

    2011-01-01

    Zoledronic acid, the third generation of nitrogen-containing bisphosphonate, is a potent inhibitor of osteoclastic bone resorption by inhibiting osteoclast activity and inducing os-teoclast apoptosis and is currently approved for the treatment of tumor-induced hypercalcemia and the reduction and delay of skeletal complications in advanced bone-related malignancies. Data from preclinical studies of zoledronic acid suggest its definite anti-tumor effect. Recently, as several zoledronic acid related clinical trials are carried out, the anti-tumor effect of zoledronic acid attracts people's attention. These clinical trials show that zoledronic acid may improvetreatment response of multiple myeloma, breast cancer, prostate cancer and lung cancer including prolonging the disease free survival (DFS) and overall survival (OS). However, some important questions remain, including optimal dosing, initiation and duration of therapy, to be studied in further investigations. Here, we summarized the potential role of zoledronic acid in cancer treatment.%唑来膦酸是第三代双膦酸盐类药物,主要通过抑制破骨细胞的活性和诱导破骨细胞凋亡来抑制骨吸收,目前用于治疗恶性高钙血症、控制恶性肿瘤骨转移等.多个临床前研究显示唑来膦酸具有明确的抗肿瘤作用.近年来,随着多项临床试验的开展,唑来膦酸潜在的抗肿瘤作用也越来越受到关注.多个临床研究结果表明,唑来膦酸能改善多发性骨髓瘤,乳腺癌、前列腺癌、肺癌等恶性肿瘤治疗的疗效,包括延长患者的总生存时间和无病生存期等.然而,对于唑来膦酸与其他抗肿瘤治疗合用的最佳方案和剂量、持续时间还需要进一步的研究.在此,本文就唑表膦酸抗肿瘤作用的临床研究进展作一综述.

  17. 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.

  18. Safety of zoledronic acid and incidence of osteonecrosis of the jaw (ONJ) during adjuvant therapy in a randomised phase III trial (AZURE: BIG 01-04) for women with stage II/III breast cancer.

    Science.gov (United States)

    Coleman, R; Woodward, E; Brown, J; Cameron, D; Bell, R; Dodwell, D; Keane, M; Gil, M; Davies, C; Burkinshaw, R; Houston, S J; Grieve, R J; Barrett-Lee, P J; Thorpe, H

    2011-06-01

    The AZURE trial is an ongoing phase III, academic, multi-centre, randomised trial designed to evaluate the role of zoledronic acid (ZOL) in the adjuvant therapy of women with stage II/III breast cancer. Here, we report the safety and tolerability profile of ZOL in this setting. Eligible patients received (neo)adjuvant chemotherapy and/or endocrine therapy and were randomised to receive neither additional treatment nor intravenous ZOL 4 mg. ZOL was administered after each chemotherapy cycle to exploit potential sequence-dependent synergy. ZOL was continued for 60 months post-randomisation (six doses in the first 6 months, eight doses in the following 24 months and five doses in the final 30 months). Serious (SAE) and non-serious adverse event (AE) data generated during the first 36 months on study were analysed for the safety population. 3,360 patients were recruited to the AZURE trial. The safety population comprised 3,340 patients (ZOL 1,665; control 1,675). The addition of ZOL to standard treatment did not significantly impact on chemotherapy delivery. SAE were similar in both treatment arms. No significant safety differences were seen apart from the occurrence of osteonecrosis of the jaw (ONJ) in the ZOL group (11 confirmed cases; 0.7%; 95% confidence interval 0.3-1.1%). ZOL in the adjuvant setting is well tolerated, and can be safely administered in addition to adjuvant therapy including chemotherapy. The adverse events were consistent with the known safety profile of ZOL, with a low incidence of ONJ.

  19. 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.

  20. 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.

  1. Combined zoledronic acid and meloxicam reduced bone loss and tumour growth in an orthotopic mouse model of bone-invasive oral squamous cell carcinoma.

    Science.gov (United States)

    Martin, C K; Dirksen, W P; Carlton, M M; Lanigan, L G; Pillai, S P; Werbeck, J L; Simmons, J K; Hildreth, B E; London, C A; Toribio, R E; Rosol, T J

    2015-09-01

    Oral squamous cell carcinoma (OSCC) is common in cats and humans and invades oral bone. We hypothesized that the cyclooxygenase (COX)-2 inhibitor, meloxicam, with the bisphosphonate, zoledronic acid (ZOL), would inhibit tumour growth, osteolysis and invasion in feline OSCC xenografts in mice. Human and feline OSCC cell lines expressed COX-1 and COX-2 and the SCCF2 cells had increased COX-2 mRNA expression with bone conditioned medium. Luciferase-expressing feline SCCF2Luc cells were injected beneath the perimaxillary gingiva and mice were treated with 0.1 mg kg(-1) ZOL twice weekly, 0.3 mg kg(-1) meloxicam daily, combined ZOL and meloxicam, or vehicle. ZOL inhibited osteoclastic bone resorption at the tumour-bone interface. Meloxicam was more effective than ZOL at reducing xenograft growth but did not affect osteoclastic bone resorption. Although a synergistic effect of combined ZOL and meloxicam was not observed, combination therapy was well-tolerated and may be useful in the clinical management of bone-invasive feline OSCC.

  2. 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.

  3. Maximizing bone formation in posterior spine fusion using rhBMP-2 and zoledronic acid in wild type and NF1 deficient mice.

    Science.gov (United States)

    Bobyn, Justin; Rasch, Anton; Kathy, Mikulec; Little, David G; Schindeler, Aaron

    2014-08-01

    Spinal pseudarthrosis is a well described complication of spine fusion surgery in NF1 patients. Reduced bone formation and excessive resorption have been described in NF1 and anti-resorptive agents may be advantageous in these individuals. In this study, 16 wild type and 16 Nf1(+/-) mice were subjected to posterolateral fusion using collagen sponges containing 5 µg rhBMP-2 introduced bilaterally. Mice were dosed twice weekly with 0.02 mg/kg zoledronic acid (ZA) or sterile saline. The fusion mass was assessed for bone volume (BV) and bone mineral density (BMD) by microCT. Co-treatment using rhBMP-2 and ZA produced a significant increase (p Nf1(+/-) mice (+174%). Co-treatment also produced a significantly higher total BMD of the fusion mass compared to rhBMP-2 alone in both groups (p Nf1(+/-) deficient mice still generated less bone than wild type controls. TRAP staining on histological sections indicated an increased osteoclast surface/bone surface (Oc.S/BS) in Nf1(+/-) mice relative to wild type mice, and this was reduced with ZA treatment.

  4. Clinical study on zoledronic acid combined with calcium carbonate D3 in treatment of osteoporosis%唑来膦酸联合碳酸钙D3治疗骨质疏松症的临床研究

    Institute of Scientific and Technical Information of China (English)

    郭丙杰; 张东洋; 李少华

    2015-01-01

    Objective To evaluate the clinical efficacy of zoledronic acid combined with calcium carbonate D3 in treatment of osteoporosis. Methods The patients with osteoporosis (120 cases) of Ninth People’s Hospital of Zhengzhou City from January 2010 to September 2013 were randomly divided into control and treatment groups, and each group had 60 cases. The patients in the control group were po administered with Calcium Carbonate D3 Tablets, 1 tablet/time, twice daily. The patients in the control group were iv administered with Zoledronic Acid Injection (5 mg diluted with 100 mL physiological saline) more than 15 min, 1 time/year. The patients in two groups were treated for one year. After the treatment, the efficacy was evaluated, and the changes of BMD, VAS score, blood calcium, phosphorus and AKP were compared in two groups. Results The efficacies in the control and treatment groups were 65.0% and 96.7%, respectively, and there were differences between two groups (P< 0.05). After treatment, BMD of L1 - 4 and blood calcium in treatment group were significantly elevated, while the AKP and VAS score was significantly reduced, and the differences were statistically significant in the same group (P < 0.05, 0.01). Degree of the improvement in the treatment group was better than that in the control group, with significant difference between two groups (P<0.05). Conclusion Zoledronic acid combined with calcium carbonate D3 has the good clinical effect in treatment of osteoporosis, and can relieve patients’ pain, while can improve and maintain the BMD level with high safety, which is worth clinical promotion.%目的:探讨唑来膦酸联合碳酸钙D3治疗骨质疏松症的临床疗效。方法2010年1月-2013年9月郑州市第九人民医院收治的骨质疏松症患者120例,随机分为对照组和治疗组,每组60例。对照组口服碳酸钙D3片,1片/次,2次/d。治疗组在对照组基础上静脉滴注唑来膦酸注射液(5 mg以100 mL生理盐水

  5. 唑来膦酸注射液治疗老年骨质疏松症患者的药物经济学分析%Pharmacoeconomic Analysis of Zoledronic Acid Injection Treatment in Elderly Patients with Osteoporosis

    Institute of Scientific and Technical Information of China (English)

    范洪春

    2015-01-01

    目的 探讨鲑鱼降钙素鼻喷剂与唑来膦酸注射液治疗老年骨质疏松症患者的成本-效果药物经济学.方法 选取2013年6月至2014年8月200例老年骨质疏松症患者,将患者分为试验组(100例)和对照组(100例),分别应用唑来膦酸注射液、鲑鱼降钙素鼻喷剂治疗,比较其疗效,并进行成本-效果分析.结果 试验组患者治疗总有效率、成本-效果比优于对照组,差异均有统计学意义(均P<0.05).结论 唑来膦酸注射液治疗老年骨质疏松症疗效佳,成本-效果优.%Objective To explore the effect of Calcitonin Salmon calcitonin nasal spray and actual Zoledronic Acid Injection treatment in elderly patients with osteoporosis,and pharmacoeconomic analysis.Methods From 2013 June to 2014 August 200 cases of elderly patients with osteoporosis,the patients were divided into test group and control group of 100 cases and 100 cases,respectively,the application of Zoledronic Acid Injection,Salmon Calcitonin Nasal Spray treatment,compared the efficacy and cost-effectiveness analysis.Results Results in the test group,the total efficiency of treatment cost is better than the control group,the difference was statisticaly significant(P<0.05). Conclusion Zoledronic Acid Injection treatment of senile osteoporosis effect of good,cost-effective advantages.

  6. Clinical safety observation of zoledronic acid treatment for senile primary osteoporosis%唑来膦酸治疗老年原发性骨质疏松症的临床安全性观察

    Institute of Scientific and Technical Information of China (English)

    郝杰; 胡侦明; 张晓军; 江维; 沈皆亮

    2013-01-01

    目的 探讨临床应用唑来膦酸静脉滴注治疗老年原发性骨质疏松症的安全性和依从性.方法 观察首次静脉滴注唑来膦酸治疗50例原发性骨质疏松症患者的一般情况和副反应,询问患者是否愿意接受第二次治疗.结果 所有患者在滴注过程中均无严重不良反应发生,但24%患者在输注后3d内出现了急性一过性不良反应,包括发热、关节痛、肌痛、流感样症状、头痛等,绝大多数患者同意继续使用.结论 唑来膦酸治疗原发性骨质疏松症安全性较高,依从性好,是一种较理想的治疗新选择,其疗效有待于长期随访.%Objective To investigate the safety and compliance of zoledronic acid, which was clinically used through intravenous injection, for the treatment of senile primary osteoporosis. Methods A total of 50 patients with primary osteoporosis who were treated with zoledronic acid intravenously for the first-time were enrolled. General condition and adverse reaction of all the patients were observed. Their willing about whether to receive the 2nd treatment or not was inquired. Results None of 50 patients had severe adverse reaction during the process of intravenous injection. Whereas 24% patients had acute and temporary adverse reaction, including fever, joint pain, myosalgia, influenza-like symptom, and headache in the first 3 days after intravenously injection. Most patients agreed to use zoledronic acid for the treatment continually. Conclusion The safety of zoledronic acid for the treatment of primary osteoporosis is high, and the compliance is good. The treatment is a new ideal choice, but the clinical effect needs long-term follow-up.

  7. Gamma-delta T lymphocytes and 25-hydroxy vitamin D levels as key factors in autoimmunity and inflammation: the case of zoledronic acid-induced acute phase reaction.

    Science.gov (United States)

    De Santis, M; Cavaciocchi, F; Ceribelli, A; Crotti, C; Generali, E; Fabbriciani, G; Selmi, C; Massarotti, M

    2015-04-01

    Zoledronic acid (ZA) infusion for osteoporosis is frequently associated with the onset of an acute phase reaction (APR) secondary to the activation of γδ T cell receptor (TCR) lymphocytes (γδ T cells) and to low vitamin D levels, similar to what is observed in chronic inflammation and autoimmunity. In this study we investigated whether the phenotype of γδ T cells is associated with APR and 25-OH vitamin D (25-OHvD) levels. For flow-cytometry analysis, peripheral blood samples were obtained from 52 osteoporotic women prior to 5 mg ZA intravenous infusion and from nine women (five with APR) one week later. Twenty-six/52 (50%) patients reported APR and APR+ cases had a higher percentage of central memory Th1-like γδ T cells. One week after ZA infusion, APR was associated with a decreased percentage of central memory Th1-like γδ T cells, an increase in the percentage and activation of effector memory Th1-like γδ T cells, and an increase in Th17-like γδ T cells. Lower 25-OHvD levels were significantly associated with APR, but no correlation was found between 25-OHvD level and γδ T cell percentage or subsets. In conclusion, patients experiencing APR related to ZA infusion have lower 25-OHvD levels and we suggest that the higher percentage of central memory Th1-like γδ T cells and the expansion of effector memory Th1-like and Th17-like γδ T cells are associated with the occurrence of APR.

  8. 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.

  9. 唑来膦酸治疗女性绝经后骨质疏松所致急性发热临床分析%Analysis of acute fever reaction in postmenopausal women with zoledronic acid treatment for osteoporosis

    Institute of Scientific and Technical Information of China (English)

    杨毅; 刘丽梅; 李蓬秋; 鲜杨; 张学军; 包明晶; 张磊; 杨艳; 朱显军; 曹旭

    2013-01-01

    Objective To analyze the incidence of acute fever reaction after the treatment of intravenous zoledronic acid in postmenopausal women with osteoporosis, and to identify the related factors. Methods Clinical data of 63 postmenopausal women with osteoporosis, who were treated with intravenous infusion of 5mg zoledronic acid from June 2010 to April 2012, were analyzed retrospectively. The incidence of acute fever reaction in these patients was observed. All the patients were divided into fever group and non-fever group according to whether having fever symptoms or not. The age, severity of osteoporosis before zoledronic acid treatment, variations of parathyroid hormone and serum calcium, and the use of anti-osteoporosis drugs before the treatment were compared between the 2 groups. Results Twenty-one patients had acute fever reaction ( 33.3% ). Among these 21 patients, 71% patients ( 15/21 ) had fever on the day of zoledronic acid treatment, and the other patients had fever on the first day after the treatment. The fever lasted for 1 day in 66. 7% of the patients ( 14/21 ), and for 2 days in 5 patients. The average temperature was 38. 8 ±0.5 C. The patients with fever had higher parathyroid hormone level before treatment than those without fever ( P <0.05 ). Serum calcium and bone mineral density showed no significant difference between the 2 groups. Conclusion Acute fever reaction is not rare in postmenopausal patients receiving intravenous zoledronic acid for the treatment of osteoporosis, but it is transient. Parathyroid hormone level before the treatment is associated with the fever.%目的 分析静脉用唑来膦酸治疗女性绝经后骨质疏松患者引起的急性发热反应及其相关因素.方法 回顾性分析我科2010年6月至2012年4月使用静脉用唑来膦酸5mg治疗的绝经后骨质疏松患者共63人.观察急性期发热出现比例.按是否出现发热症状分为发热组与无发热组.比较两组患者年龄、静脉用唑来膦

  10. 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

  11. Research Progress on Antitumor Effects of Zoledronic Acid%唑来膦酸抗肿瘤作用的研究进展

    Institute of Scientific and Technical Information of China (English)

    刘俊彦

    2012-01-01

    唑来膦酸作为第三代双膦酸盐药物已广泛用于恶性实体瘤骨转移相关事件的防治.进一步研究发现,唑来膦酸可通过抑制甲羟戊酸途径中焦磷酸合酶的活性,使异戊烯焦磷酸大量蓄积,同时异戊烯焦磷酸与细胞内一磷酸腺苷结合形成三磷酸腺苷分解类似物蓄积于细胞中,从而改变细胞周期蛋白和凋亡蛋白水平,抑制肿瘤细胞生长并促进其凋亡,具有一定的直接和/或间接抗肿瘤作用.有关肺癌、乳腺癌、前列腺癌及肝癌等前期临床试验提示唑来膦酸与细胞毒药物、内分泌药物及靶向药物联合具有一定程度的协同抗肿瘤作用,并且在抗肿瘤药物之后序贯应用效果更好.一些相关的临床试验正在进行中.%Zoledronic acid (ZOL), a third-generation bisphosphonate, has been widely used for the treatment of skeletal-related events in malignant solid tumors. Previous studies have demonstrated that ZOL can induce direct and indirect antitumor activities through py-rophosphate synthase inhibition, which blocks the mevalonate pathway and causes isopentenyl pyrophosphate ( IPP ) accumulation. IPP becomes conjugated to AMP to form a novel ATP analog. The amount of IPP and ATP analog is correlated with cyclin and apoptotic protein levels, which are associated with cell line growth and apoptosis. Preclinical studies on lung cancer, breast cancer, prostate cancer, liver cancer, and so on, confirmed a synergistic effect between ZOL and cytotoxic, endocrine, and targeted drugs. The observed improvement in antitumor effects by using combination therapy with ZOL is currently being verified through additional clinical trials.

  12. Synthesis, crystal structure and antitumor effect of a novel copper(II) complex bearing zoledronic acid derivative.

    Science.gov (United States)

    Qiu, Ling; Lv, Gaochao; Guo, Liubin; Chen, Liping; Luo, Shineng; Zou, Meifen; Lin, Jianguo

    2015-01-07

    A great majority of Cu(II) complexes currently studied in the anticancer research field exert their antiproliferative activities through ligand exchange. In this work, we present the synthesis and structural characterization of two novel Cu(II) complexes, {[Cu3(ZL)2(H2O)6]·6H2O}n (1) (ZL = 1-hydroxy-2-(1H-imidazol-1-yl)ethane-1,1-diyldiphosphonic acid) and [Cu(IPrDP)2]·3H2O (2) (IPrDP = 1-hydroxy-3-(1H-imidazol-1-yl)propane-1,1-diyldiphosphonic acid). Due to the insolubility of polymer 1 in common solvents, only the biological activities of complex 2 were investigated. The antitumor activity of complex 2 was evaluated against a panel of human cancer cell lines, including U2OS, A549, HCT116, MDA-MB-231 and HepG2. Complex 2 exhibited comparable cytotoxic effect to cisplatin (CDDP) against the human colon carcinoma cells HCT116, and superior selectivity for inhibiting human hepatocarcinoma cells rather than normal liver cells. The cell cycle distribution analysis indicates that complex 2 inhibits human carcinoma cells by inducing the cell cycle arrest at the G2/M phase, showing a similar mechanism of action to that of CDDP. The binding interaction of complex 2 with calf thymus DNA (CT-DNA) has been explored by UV-vis absorption and circular dichroism (CD), demonstrating complex 2 has a moderate binding affinity for DNA through intercalation.

  13. 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.

  14. 1型糖尿病模型大鼠股骨骨代谢紊乱及唑来膦酸的影响%Effects of zoledronic acid on bone metabolism disturbance in the femur of type 1 diabetic rat models

    Institute of Scientific and Technical Information of China (English)

    曹鲁宁; 崔敏; 于灵芝; 张娜; 赵旭

    2015-01-01

    BACKGROUND:Osteoporosis caused by diabetes melitus as common secondary osteoporosis has been paid more and more attention recently. Zoledronic acid serves as a novel drug for osteoporosis, and its effect on osteoblasts in vivo remains unclear. OBJECTIVE:To investigate the changes of the expression of bone morphogenetic protein 2 andNoggin in the femur of type 1 diabetes melitus rats and the effect of zoledronic acid on them. METHODS:Models of type 1 diabetes melitus were established by intraperitoneal injection of streptozotocin in 130 Wistar rats. 3 days later, rats with blood sugar > 16.7 mmol/L for three consecutive times were considered as successful models, 120 in total. These models were randomly divided into model, prevention and treatment groups. Rats in the prevention and treatment groups were intravenously administered zoledronic acid (0.1 mg/kg) on the day of modeling and 2 weeks after model establishment. An additional 40 rats were injected with citrate buffer solution as control group. RESULTS AND CONCLUSION: Compared with the control group, femur bone mineral density, serum alkaline phosphatase levels, and femur bone morphogenetic protein 2 mRNA expression levels were significantly lower in the model group (P 16.7 mmol/L鼠为造模成功鼠,共120只,随机等分为模型组、预防组和治疗组。后2组大鼠分别在造模后当天和2周后一次性静脉给予唑来膦酸(0.1 mg/kg)。另取40只大鼠注射柠檬酸缓冲液作为对照组。结果与结论:与对照组相比,模型组大鼠股骨骨密度、血清碱性磷酸酶水平、股骨骨形态发生蛋白2 mRNA表达水平明显降低(P <0.05),Noggin mRNA表达水平显著升高(P <0.05)。与模型组相比,预防组和治疗组大鼠骨密度和骨形态发生蛋白2 mRNA表达水平显著升高(P <0.05),Noggin mRNA表达水平显著降低(P <0.05),血清骨碱性磷酸酶水平也逐渐恢复。提示1型糖尿病大鼠骨代谢紊乱在病程早期即出现,

  15. Effect of zoledronic acid on bone mass in osteoporotic patients%唑来膦酸对骨质疏松骨含量的影响

    Institute of Scientific and Technical Information of China (English)

    高雷; 任艳; 高华增

    2015-01-01

    Objective To explore the influence of bisphosphonates in bone mass in osteoporosis. Methods Fifty⁃nine patients with postmenopausal osteoporosis were selected and were randomly divided into treatment group ( n=30 ) and control group ( n=29). In treatment group, patients received intravenous 5mg zoledronic acid (Aclasta) injection once, and continued with 0�9%normal saline 100ml and calcium gluconate 10 ml (1g) once a day for 3-5 days. They also took calcium carbonate 600mg/d and active vitamin D3 400 iu/d. In control group, patients were given oral calcium 600 mg/d and active vitamin D3 400 iu/d. The efficacy was evaluated after 6 months. Results After the treatment, BMD of patients increased in varying degree. Bone mineral content was elevated significantly. The pain decreased significantly. The difference was statistically significant ( P < 0�05 ) compared with that before treatment. No osteoporotic fractures occurred during the follow⁃up. Conclusion Bisphosphonates combining with calcium can significantly relieve the pain symptom, improve and maintain the BMD level, increase bone mass and reduce the incidence of osteoporotic fractures in the treatment of postmenopausal osteoporosis. It is a safe and effective method for treatment of postmenopausal osteoporosis.%目的:探讨双膦酸盐对骨质疏松骨量的影响。方法选绝经后骨质疏松症患者59例,随机分为治疗组和对照组,其中治疗组(30例),一次性静脉滴注唑来膦酸注射液5 mg,后次日始日一次静点0�9%生理盐水100 ml+葡萄糖酸钙10 ml(1g)3~5天,同时碳酸钙600 mg/d,活性维生素D3400IU/d口服;对照组(29例),给予同剂量的碳酸钙及活性维生素D3口服,6个月后复查评价疗效。结果患者临床疗效比较,治疗后患者BMD值有不同程度增高,其中骨含量一项升高明显,疼痛感明显下降,与治疗前比较,差异有统计学意义(P<0�05),随访期间

  16. 唑来膦酸在骨质疏松患者中的应用及疗效%Efficacy and application of zoledronic acid in the treatment of osteoporosis

    Institute of Scientific and Technical Information of China (English)

    段鹏; 涂萍; 吴和平; 丁浔; 肖魏华; 邓波

    2014-01-01

    Objective To observe the safety and efficacy of intravenous infusion of zoledronic acid ( 5 mg/100 ml ) in the treatment of primary osteoporosis and type 2 diabetes combined with osteoporosis.Methods Forty-six patients with osteoporosis, who were treated in our hospital, were selected.Among all the patients, 25 patients were divided into primary osteoporosis group, and 21 patients were divided into type 2 diabetes combined with osteoporosis group.Physical examination was performed, and the body mass index ( BMI ) was calculated.Serum glucose was detected using glucose oxidase method.The bone mineral density ( BMD) of the lumbar vertebrae ( L2-L4 ) and the left femoral neck was detected using dual energy X-ray absorptiometry ( DXA) . All the patients were treated with intravenous infusion of zoledronic acid.The adverse effect was monitored.One year later, BMD was re-detected, and the change of BMD after the treatment was also observed.Results No significant difference of age, BMI, and BMD of the lumbar vertebrae and the left femoral neck between the two groups was observed (P>0.05).After the intravenous infusion of zoledronic acid, the adverse effect including fever, acratia, headache, arthralgia, and nausea was observed in both groups.Seven patients in type 2 diabetes combined with osteoporosis group showed a transient increase of blood glucose, but all the symptoms disappeared and blood glucose returned to normal in 3 days.After 1-year treatment with zoledronic acid, BMD of the lumbar vertebrae and the left femoral neck in primary osteoporosis group increased by 4.27% and 4.11%, respectively, which increased by 3.42% and 3.26% in type 2 diabetes combined with osteoporosis group, respectively.BMD in both groups was significant higher than that before the treatment (P0.05).Conclusion Zoledronic acid can increase BMD in patients with osteoporosis.And it has a good efficacy for the patients with primary osteoporosis or type 2 diabetes combined with osteoporosis.%

  17. Efeito do ácido zoledrônico em tíbias de ratas ooforectomizadas: estudo prospectivo e randomizado Effects of zoledronic acid on ooforectomized rats' tibiae: a prospective and randomized study

    Directory of Open Access Journals (Sweden)

    Fernando Roberto Alves Pereira

    2009-02-01

    Full Text Available OBJETIVO: Investigar as repercussões clínicas, biomecânicas e histomorfométricas do ácido zoledrônico em tíbias de ratas osteoporóticas, após ooforectomia bilateral. MÉTODOS: Foram estudadas, prospectivamente, 40 ratas da linhagem Wistar (Rattus novergicus albinus. Com 60 dias de vida, os animais foram aleatorizados em dois grupos de acordo com o procedimento cirúrgico: ooforectomia bilateral (O (n=20 e pseudo-cirurgia ("sham" (P (n=20. Após 30 dias, os animais foram divididos em quatro subgrupos, de acordo com a administração de 0,1mg/kg de ácido zoledrônico (AZ ou água destilada (AD: OAZ (n=10, OAD (n=10, PAZ (n=10 e PAD (n=10. Após 12 meses, os animais foram eutanasiados e suas tíbias analisadas. No estudo clínico foi considerado o peso dos animais; no estudo biomecânico foram realizados ensaios compressivos e na análise histomorfométrica foi determinada a área trabecular óssea. RESULTADOS: Os grupos "O" tiveram aumento de peso significativamente maior que os grupos "P" (p=0,005. Os grupos OAZ e PAZ tiveram aumento, não significativo, de peso quando comparados aos grupos OAD (p=0,47 e PAD (p=0,68. Os grupos com ácido zoledrônico e com água destilada suportaram carga máxima, semelhante (p=0,2, no momento em que ocorreu fratura. Nos grupos com ácido zoledrônico verificou-se o aumento não significante da área trabecular óssea quando comparados aos grupos com água destilada (p=0,21. Houve correlação positiva entre a área trabecular e a carga máxima (p=0,04; r=0,95. CONCLUSÃO: O ácido zoledrônico não influiu significativamente no peso dos animais. Os resultados mostraram aumento, não significante, tanto da resistência óssea diafisária tibial, como da área trabecular óssea.OBJECTIVE: To investigate clinical, biomechanic and histomorphometric effects of zoledronic acid on osteoporotic rats'tibiae after bilateral ooforectomy. METHODS: 40 female Wistar (Rattus novergicus albinus rats were prospectively

  18. Effect of Zoledronic Acid on the Healing of Distal Radial Fracture%唑来膦酸对老年桡骨远端骨折术后疗效观察

    Institute of Scientific and Technical Information of China (English)

    尹自龙; 石磊; 王林; 刘驰; 郑念野; 纪泉; 张华俦; 良元; 薛庆云

    2014-01-01

    目的:观察唑来膦酸对老年桡骨远端骨折的术后疗效。方法分析自2012年1月1日至2012年12月31日行桡骨远端骨折手术患者136例接受手术治疗并纳入研究,118例获得随访(87%),分成唑来膦酸组(A 组,59例)和对照组(B 组,59例)。唑来膦酸组平均年龄(73.09±5.04)岁,男12例,女47例,术后2~7 d 使用唑来膦酸抗骨质疏松治疗,并常规补充钙剂和骨化三醇;对照组平均年龄(73.25±6.96)岁,男14例,女45例,术后2~7 d 使用针剂密盖息抗骨质疏松治疗,出院后继续使用密盖息鼻喷剂至术后3个月,常规补充钙剂和骨化三醇,术后4周、3个月随访骨折愈合的情况及术后1年复查骨密度的情况。结果老年桡骨远端骨折患者使用唑来膦酸抗骨质疏松药物后骨折愈合无明显影响且腕关节功能改善,术后1年骨密度较前增加。结论发生桡骨远端骨折的老年骨质疏松患者使用唑来膦酸药物后骨质疏松治疗效果好,同时对骨质疏松性桡骨远端愈合无明显不利影响。%Objective To observe the effect of zoledronic acid on distal radius fractures in elderly patients after operation. Methods Analysis of 136 cases of distal radius fractures underwent operation in our hospital from January 1,2012 to Decem-ber 31,2012,118 patients were followed up(87% ),Patients were divided into zoledronic acid group(group A,59 patients) and control group(group B,59 patients),group A with an average age of 73. 09 ± 5. 04,12 male patients,47 female patients, postoperative second to seventh day with anti osteoporosis treatment of zoledronic acid,and a conventional calcium and calcitri-ol supplement,B group with an average age of 73. 25 ± 6. 96,male 14 patients,female patient 45,postoperative second to sev-enth day with anti osteoporosis treatment of Injection of Miacalcic,continue using of Miacalcic nasal spray from discharge to postoperative 3 months

  19. Observation of the Effect for Elderly Women's Osteoporosis Using Zoledronic Acid Combination%唑来膦酸联合用药治疗老年女性骨质疏松患者的疗效观察

    Institute of Scientific and Technical Information of China (English)

    郑彬彬; 叶曼; 李晓静

    2013-01-01

    OBJECTIVE To investigate the effect of zoledronic acid combinated salmon calcitonin see calcimar,Caltrate D,alfacalcidol and bone-peptide injection cure old osteoporosis.METHODS Forty cases of thoracolumbar pain of osteoporosis patients were randomly divided into two groups:The control group received salmon calcitonin see calcimar,Caltrate D,alfacalcidol,the therapeutic group received zoledronic acid and bone-peptide injection besides salmon calcitonin see calcimar,Caltrate D,calcitonin.The two groups received six months therapia.Observe the BMD and pain before and after the therapy.RESULTS The BMD of two groups both rised(P<0.05).The BMD of therapeutic group is higher than the control (P<0.05).The VAS score of two groups both descend(P<0.05).The VAS score of therapeutic group is lower than the control (P<0.05).CONCLUSION Zoledronic acid combinated salmon calcitonin see calcimar,Caltrate D,alfacalcidol and bone-peptide injection is a safe curation for old osteoporosis,and more effective than the curation used salmon calcitonin see calcimar,Caltrate D and alfacalcidol together.%目的 探讨唑来膦酸及鲑鱼降钙素联合钙尔奇D、阿法骨化醇、复方骨肽注射液治疗老年女性骨质疏松症的疗效.方法 选取40例老年女性骨质疏松性胸腰椎疼痛患者随机分为两组,对照组服用钙尔奇D片(钙尔奇D600)、阿法骨化醇,鲑鱼降钙素注射液、治疗组在对照组的基础上加用唑来磷酸注射液和复方骨肽注射液,两组均连续治疗半年,观察治疗前后的骨密度和疼痛变化.结果 两组治疗后骨密度均明显上升.与治疗前比较差异有统计学意义(P<0.05).治疗后治疗组骨密度明显高于对照组,差异有统计学意义(P<0.05).治疗后两组VAS评分均明显下降,与治疗前比较差异有统计学意义(P<0.05),治疗后治疗组VAS评分下降程度高于对照组,差异有统计学意义(P<0.05).结论 唑来膦酸及鲑鱼降钙素注射液联合

  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. 唑来膦酸盐治疗重度绝经后骨质疏松及腰背痛的临床观察%Clinical Efficacy of Zoledronic Acid on Osteoporosis and Back Pain of Postmenopausal Women

    Institute of Scientific and Technical Information of China (English)

    于斌; 夏英鹏; 杜文军; 李辉南; 高军伟

    2015-01-01

    Objective To evaluate the clinical efficacy of 5mg of zoledronic acid in the treatment of osteoporosis and back pain of postmenopausal women.Methods Randomized comparative study was taken.From April 2012 to April 2013, a total of 84 patients with osteoporosis and back pain were randomly divided into experimental group and control group, with 42 cases in each group.All the patients were continually treated with 600mg of calcium, Vitamin D 124 IU/d and calcitriol 0.25 μg/d for one year.Patients of ex-perimental group received 5mg zoledronic acid once.The lumbar spine (LS) and total hip (TP) bone mineral density (BMD), blood calcium, X-ray examination of thoracolumbar spine, VAS pain sore and ODI were carried out before treatment and after treatment for 12 months.Results 39 patients in experimental group and 40 patients in control group were followed up for more than 12 months.In experimental group, BMD of LS increased by 5.8%, TP by 3.5%, with significant difference.In control group, BMD of LS and TP increased by 2.0% and 1.4% with significant difference.The increases of MBD (both LS and TP) of experimental group were greater than those in control group, and the difference was statistically significant.After 12 months, VAS scores, ODI scores, the increase of VAS and ODI in experimental group were greater than those in control group, and the difference was statistically significant.There were no new clinical vertebral fractures in both groups and no serious adverse reactions in experimental group.Conclusion A once-yearly use of zoledronic acid (5 mg) can significantly increase the BMD of lumbar spine and hip, and released back pain prominently. With the good compliance and tolerance of patients, zoledronic acid (5 mg) is an important means of treating osteoporosis.%目的:分析应用唑来膦酸盐5 mg 治疗重度绝经后骨质疏松及腰背痛的临床疗效。方法采用随机对照研究,选取2012年4月至2013年4月以腰背痛就诊的

  2. 补肾健骨胶囊联合唑来膦酸注射液和碳酸钙 D3治疗老年骨质疏松症的临床研究%Clinical study of Bushen Jiangu Capsules combined with Zoledronic Acid Injection and calcium carbonate D3 in treatment of aged osteoporosis

    Institute of Scientific and Technical Information of China (English)

    都海; 肖波; 易泽洪; 杨国齐; 刘光勇; 马俊; 刘建伟; 康兵文; 赵明; 彭德全

    2016-01-01

    and Calcium Carbonate D3 Tablets in treatment of aged osteoporosis. Methods Patients (114 cases) with aged osteoporosis in the Department of Orthopedics of Pixian County People’s Hospital from May 2012 to January 2015 were enrolled in this study. According to the different treatment plans, patients were divided into control group (57 cases) and treatment group (57 cases). All patients were po administrated with Calcium Carbonate D3 Tablets, 1 tablet/time, once daily. The patients in the control group were iv administered with Zoledronic Acid Injection, 5 mg Zoledronic Acid Injection added into normal saline 250 mL, once monthly, and the infusion times were not less than 15 min. The patients in the treatment group were po administered with Bushen Jiangu Capsules on the basis of the control group, 4 capsules/time, three times daily. The patients in two groups were treated for 12 months. After treatment, the efficacy was observed, and bone metabolic markers, BMD, BGP, BMP-2, and VAS scores in two groups before and after treatment were compared. Results After treatment, the efficacies in the control and treatment groups were 82.46% and 94.74%, respectively, and there were differences between two groups (P < 0.05). After treatment, S-P and S-Ca in two groups were significantly increased, but ALP was obviously decreased, and the differences were statistically significant in the same group (P < 0.05). After treatment, the observational indexes in the treatment group were significantly better than those in the control group, with significant difference between two groups (P < 0.05). After treatment, L2-L4 BMD, femoral neck BMD, BGP, and BMP-2 in two groups were significantly increased, but VAS scores were obviously decreased, and the differences were statistically significant in the same group (P < 0.05). After treatment, the observational indexes in the treatment group were significantly better than those in the control group, with significant difference between two groups

  3. 唑来膦酸联合化疗治疗恶性肿瘤骨转移32例临床分析%Clinical efficacy of zoledronic acid combined with chemotherapy in the treatment of malignant tumor with bone metastases

    Institute of Scientific and Technical Information of China (English)

    李学超

    2014-01-01

    目的:观察唑来膦酸联合化疗对恶性肿瘤骨转移的临床疗效及不良反应。方法:将64例恶性肿瘤骨转移患者随机分为2组,其中对照组32例单用化疗;治疗组32例接受唑来膦酸联合化疗,2组化疗方案相同。结果:治疗组疼痛总有效率81.3%,对照组为46.9%。治疗组骨病灶控制总有效率62.5%,对照组为28.1%;治疗组均优于对照组(P<0.01)。2组无严重不良反应发生。结论:唑来膦酸联合化疗治疗恶性肿瘤骨转移疗效确切,优于单用化疗,且不良反应少,患者依从性好。%Objective:To investigate the effects and adverse reactions of zoledronic acid combined with chemotherapy in the treatment of malignant tumor with bone metastases. Methods:Sixty-four malignant tumor patients with bone metastases were randomly divided into the control group and trial group(32 cases each group). The control group and trial group were treated with single chemotherapy and zoledronic acid combined with chemotherapy,respectively. The chemotherapy regimens of two groups were the same. Results:The totally effective rates of curing pain in trial group and control group were 81. 3% and 46. 9%, respectively. The totally effective rates of controlling bone metastases in trial group and control group were 62. 5% and 28. 1%,respectively. The treatment effect in trial group was better than that in control group(P<0. 01),no serious adverse reaction in two groups was found. Conclusions:The therapeutic effect of zoledronic acid combined with chemotherapy is better than that of single chemotherapy. The adverse reaction of zoledronic acid combined with chemotherapy is slight,and the patient is well-tolerated.

  4. Hemato-biochemical responses to packing in donkeys administered ascorbic acid during the harmattan season.

    Science.gov (United States)

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

    2015-02-01

    Experiments were performed to investigate the effect of ascorbic acid (AA) in reducing hemato-biochemical changes in pack donkeys during the cold-dry (harmattan) season. Six experimental donkeys administered orally AA (200 mg/kg) and six control donkeys not administered ascorbic acid were subjected to packing. Blood samples were collected from all donkeys for hematological and biochemical analyses. In the control donkeys, packed cell volume (PCV), erythrocyte count and hemoglobin concentration (Hb) decreased significantly (Ppacking. In the experimental donkeys, there was no significant difference between the pre- and post-packing values of PCV, erythrocyte count and Hb. In the control donkeys, the neutrophil and neutrophil:lymphocyte ratio increased significantly (Ppacking, but in the experimental donkeys, the pre- and post-packing values were not significantly different. The eosinophil count increased significantly (Ppacking. In conclusion, packing exerted significant adverse effects on the hematological parameters ameliorated by AA administration. AA may modulate neutrophilia and induce a considerable alteration of erythroid markers in donkeys subjected to packing during the harmattan season.

  5. 唑来膦酸联合钙尔奇D治疗原发性骨质疏松症的研究%Clinical study of Zoledronic acid injection combined with Caltrate D on treatment for primary osteoporosis

    Institute of Scientific and Technical Information of China (English)

    刘国强; 姜世平; 徐谦

    2012-01-01

    目的 探讨唑来膦酸联合钙尔奇D治疗原发性骨质疏松症患者的临床疗效.方法 选择2010年10月-2011年12月收治的原发性骨质疏松症患者31例,分为研究组16例,年龄(67±4.8)岁,对照组15例,年龄(66.4±4.3)岁.所有患者均初次诊断为骨质疏松症,且未进行系统抗骨质疏松症治疗,排除患有骨代谢性疾病或服用影响骨代谢药物情况.两组患者均给予钙尔奇D片口服,600 mg 1次/d;研究组患者则于治疗初期滴注唑来膦酸注射液5mg1次/d.比较两组患者治疗后药物不良反应、随访6个月后骨密度(BMD)改善程度、疼痛缓解程度、有否合并骨折等情况.结果 研究组患者BMD平均增长率为10.67%,且较对照组增长明显,疼痛及活动改善优良率为75%,无骨坏死、新发骨折.用药后不良反应:恶心54%、低热38%、全身骨关节疼痛加重23%、无症状低钙血症16%,且上述症状均于药物输注3d后明显缓解,随访未见反复;对照组患者BMD平均增长率为2.48%,疼痛及活动改善优良率为26.7%,新发骨折2例,未见药物不良反应,两组比较,研究组优于对照组,差异有统计学意义(P<0.05).结论 唑来膦酸注射液联合钙尔奇D口服是治疗原发性骨质疏松症患者安全有效的方法.%Objective To observe the clinical effect of Zoledronic acid injection combined with Caltrate D on treatment for primary osteoporosis. Methods Choose 31 cases of primary osteoporosis patients since October 2010 to December 2011, who were diagnosed for the first time without any systemic treatment. 31 patients were divided into two groups, there were 16 cases in the research group, aged (67 ?.8) years and 15 cases in the control group, aged (66.4 ?.3) years. Two groups were equally given Caltrate 600mg once a day, while the research group received the treatment of the Zoledronic acid injection 5mg early. After that, we compared the different situations such as adverse drug

  6. 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.

  7. Urinary excretion of orally administered oxalic acid in saccharin and o-phenylphenol-fed NMRI mice.

    Science.gov (United States)

    Salminen, E; Salminen, S

    1986-01-01

    Both saccharin and o-phenylphenol have been suggested to be carcinogenic to the urinary bladder in experimental animals, but the mechanism has remained unclear. The aim of this study was to investigate the effects of dietary saccharin and o-phenylphenol on the urinary excretion of dietary oxalic acid. Male NMRI mice were gradually adapted to either 3% o-phenylphenol or 5% saccharin in their diet. Having being adapted to these diets for 1 week or after consuming them for 3 months, the animals were fasted for 6 h and given a 2.5-microCi oral dose of U-14C-oxalic acid. Dosed animals were kept in metabolism cages for 48 h to monitor urinary and fecal excretion of the label. Adaptation to dietary o-phenylphenol appeared to increase the urinary excretion of orally administered U-14C-oxalic acid when food and water were available during urinary and fecal collections. Adaptation to dietary saccharin had little effect on urinary oxalate levels when compared to control animals. These results indicate that changes in urinary oxalate levels should be more carefully studied in connection with potential urinary bladder carcinogens to avoid the possibility of bladder irritation by increased urinary oxalate excretion.

  8. 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

  9. 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.

  10. Capric acid and hydroxypropylmethylcellulose increase the immunogenicity of nasally administered peptide vaccines.

    Science.gov (United States)

    Nordone, Sushila K; Peacock, James W; Kirwan, Shaun M; Staats, Herman F

    2006-06-01

    Immunization by the nasal route is an established method for the induction of mucosal and systemic humoral and cell-mediated antigen-specific responses. However, the effectiveness of nasal immunization is often hampered by the need for increased doses of antigen. Bioadhesives and absorption enhancers were investigated for their ability to enhance immune responses in mice after nasal immunization with model HIV-1 peptide and protein immunogens. Two additives, hydroxypropylmethylcellulose (HPMC) and capric acid, consistently enhanced antigen-specific serum IgG endpoint titers under conditions in which antigen dose was limiting. Nasal immunization of mice with 20 microg of an HIV-1 peptide immunogen plus cholera toxin (CT) as adjuvant induced serum antipeptide IgG titers of 1:9.5log2 after four immunizations while the addition of CA or HPMC to the vaccine formulation increased serum antipeptide IgG titers to 1:15.4log2 and 1:17.6log2, respectively. When 5 microg recombinant HIV-1 gp41 was used as the immunogen, the addition of CA or HPMC to the vaccine formulation increased serum anti-gp41 IgG titers to 1:11.6log2 and 1:8.8log2, respectively, compared to 1:5.2log2 after three nasal immunizations with 5 microg gp41 + CT alone. Thus, HPMC and capric acid may be useful additives that increase the immunogenicity of nasally administered vaccines and permit less antigen to be used with each immunization.

  11. 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.

  12. 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

  13. 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.

  14. Observation and nursing of the transient adverse effect of zoledronic acid in the treatment of postmenopausal osteoporosis%唑来膦酸治疗绝经后骨质疏松症的一过性反应的观察与护理

    Institute of Scientific and Technical Information of China (English)

    庞雪; 刘英; 曹积弘; 王莉; 郭岩; 王立恒

    2013-01-01

    目的:观察唑来膦酸治疗绝经后骨质疏松症的一过性药物反应并探讨护理措施。方法22例患者均为绝经后骨质疏松症患者。均给予唑来膦酸5 mg/100 ml静脉滴注15 min以上输完。给药结束后记录治疗效果及不良反应。所有患者给予心理护理,用药护理及治疗后不良反应的处理。结果唑来膦酸静脉滴注后主要的一过性不良反应为发热(>37.5℃),本科用药患者均出现发热(22例),其次症状为肌痛16例,流感样症状15例,关节痛10例,头痛5例。以上症状均为一过性,不超过48小时,并且给予非甾体类抗炎镇痛类药物后症状可缓解。2例第二次用药患者均未出现任何不良反应。血细胞分析及肝肾功检查均未出现异常。结论唑来膦酸给药后会出现发热、肌痛等反应,但均为一过性,通过采用积极的用药后护理措施可以提高用药的安全性避免药物反应带来的不良影响。%Objective To observe the transient drug reaction of zoledronic acid in the treatment of postmenopausal osteoporosis , and to explore the nursing intervention method .Methods In this study, 22 patients were diagnosed with postmenopausal osteoporosis .All the patients were treated with an intravenous drip of 5mg/100ml zoledronic acid for more than 15 minutes.Therapeutic effect and adverse reaction were recorded after the administration .All patients received psychological care , medication care , and treatment of adverse reaction after the administration .Results The main adverse reaction was fever ( >37.5℃) after the intravenous drip of zoledronic acid .All the 22 patients in our department had fever .The other symptoms were myalgia ( 16 cases ) , influenza-like symptoms (15 cases), joint pain (10 cases), and headache (5 cases).All these symptoms were transient, lasting less than 48 hours, and relieved after treated with non-steroidal anti-inflammatory drugs.Two patients had no

  15. Zoledronate and Ion-releasing Resins Impair Dentin Collagen Degradation

    Science.gov (United States)

    Tezvergil-Mutluay, A.; Seseogullari-Dirihan, R.; Feitosa, V.P.; Tay, F.R.; Watson, T.F.; Pashley, D.H.; Sauro, S.

    2014-01-01

    This study analyzed the amounts of solubilized telopeptides cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and C-terminal crosslinked telopeptide of type I collagen (CTX) derived from matrix-metalloproteinases (MMPs) and cysteine cathepsins (CTPs) subsequent to application of a filler-free (Res.A) or an ion-releasing resin (Res.B) to ethylenediaminetetraacetic acid (EDTA)-demineralized dentin with or without zoledronate-containing primer (Zol-primer) pre-treatment. The chemical modification induced following treatments and artificial saliva (AS) storage was also analyzed through attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). Totally EDTA-demineralized specimens were infiltrated with Res.A or Res.B with or without Zol-primer pre-treatment, light-cured, and immersed in AS for up to 4 wk. ICTP release was reduced following infiltration with Res.B and further reduced when Res.B was used with Zol-primer; remarkable phosphate mineral uptake was attained after AS storage. CTX release was increased in Res.A- and Res.B-treated dentin. However, when Zol-primer was used with Res.A, the CTX release fell significantly compared to the other tested resin-infiltration methods. In conclusion, zoledronate offers an additional inhibitory effect to the ion-releasing resins in MMP-mediated collagen degradation. However, Zol-primer induces a modest reduction in CTX release only when used with resin-based systems containing no ion-releasing fillers. PMID:25074494

  16. 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

  17. Dental extraction following zoledronate, induces osteonecrosis in rat´s jaw

    Science.gov (United States)

    Gómez-Clavel, José-Francisco; Gaitán-Cepeda, Luis-Alberto

    2017-01-01

    Background Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) is clinically characterized by the presence of exposed bone in the oral cavity that persists for more than eight weeks. Previous attempts to establish an animal model have not sufficiently considered disease features. Our aim was to establish an inexpensive and replicable animal model that develops BRONJ in a short time. Material and Methods Thirty-two male Wistar rats were randomly divided into two groups: control and experimental. In the experimental group, we administered 0.06mg/kg intraperitoneal dose of zoledronic acid (ZA) 7 and 14 days prior to maxillary second molar extraction. At two, four and six weeks after tooth extraction, the animals were euthanized, and we dissected the maxilla following histological procedures. We stained serial slides with hematoxylin and eosin and Masson’s trichrome. The samples were harvested for macroscopic, radiologic and histological evaluation of bone changes. Results At two weeks postextraction, we observed exposed necrotic bone in dental socket areas in experimental groups. Radiological analysis revealed osteolytic lesions accompanied by extensive destruction and sequestrum formation in the same group. Histological examination confirmed the absence of necrotic bone in control groups in contrast with the experimental groups. The percentage of empty lacunae and the number of osteoclasts and the necrotic bone area were significantly increased (p<0.05) in the experimental groups. Conclusions The animal model using ZA administration to prior dental extraction successfully mimicked human BRONJ lesions. Also, the model was easily replicated, inexpensive and showed different features than other previous BRONJ models. Key words:Bisphosphonates, osteonecrosis, dental extractions, animal model, BRONJ. PMID:28160593

  18. Fate of orally administered radioactive fatty acids in the late-pregnant rat.

    Science.gov (United States)

    López-Luna, Pilar; Ortega-Senovilla, Henar; López-Soldado, Iliana; Herrera, Emilio

    2016-03-01

    To investigate the biodisponibility of placental transfer of fatty acids, rats pregnant for 20 days were given tracer amounts of [(14)C]palmitic (PA), oleic (OA), linoleic (LA), α-linolenic (LNA), or docosahexaenoic acid (DHA) orally and euthanized at 0.5, 1.0, 2.0, or 8.0 h thereafter. Maternal plasma radioactivity in lipids initially increased only to decline at later times. Most of the label appeared first as triacylglycerols (TAG); later, the proportion in phospholipids (PhL) increased. The percentage of label in placental lipids was also always highest shortly after administration and declined later; again, PhL increased with time. Fetal plasma radioactivity increased with time, with its highest value at 8.0 h after DHA or LNA administration. DHA initially appeared primarily in the nonesterified fatty acids (NEFA) and PA, OA, LA, and LNA as TAG followed by NEFA; in all cases, there was an increase in PhL at later times. Measurement of fatty acid concentrations allowed calculation of specific (radio)activities, and the ratio (fetal/maternal) of these in the plasmas gave an index of placental transfer activity, which was LNA > LA > DHA = OA > PA. It is proposed that a considerable proportion of most fatty acids transferred through the placenta are released into the fetal circulation in the form of TAG.

  19. 唑来膦酸局部治疗对骨质疏松时自体髂骨移植内种植体骨结合的影响%Effect of Local Treatment with Zoledronate Acid on Osseointegration of Dental Implants in Autologous lllac Graft in Os teoporotic Rabbits.

    Institute of Scientific and Technical Information of China (English)

    李剑平; 戚孟春; 石燕萍; 于静; 胡静

    2011-01-01

    Objective: To investigate the effect of local treatment with zoledronate acid on osseointegration of dental implants in autologous lilac graft in osteoporotic rabbits. Methods: Thirty female rabbits were randomly divided into three groups: A, B and C. Animals in group B and C received bilatreal ovariectomy and group A underwent sham operation. 12 weeks after surgery, femoral bones of rabbits were examined for bone mineral density to verify osteoporosis status. Then bone defects were made at the proximal metaphyses of tibiae and autologous iliac bone graft with simultaneous placement of HA coated titanium implants (group A and B) or zoledronate acid immobilized HA -implants (group C) were performed. Animals were killed at 2 and 12 weeks after bone graft surgery and undecalcified sections were prepared and examined histologically and histomorphometrically. Results: Osteoporotic status was verified in ovariectomized rabbits by significantly decreased BMD when compared to sham-operated animals.At 2 weeks after implantation surgery, thickness of cortical bone, bone volume in cancellous area and implant-bone contact rate in group B and C were similar, but all were significantly lower than those in group A. At 12weeks,TCB, IBCR and BVC were highest in group A, followed by group C, and lowest in group B. Compared with 2 weeks, no significant changes for TCB were found at 12 weeks both in group A and in group C, while TCB in group B was slightly decreased. IBCR and BVC at 12 weeks were significantly increased in all groups when compared with those at 2 weeks, except BVC in group B, which was significantly decreased. Conclusion: Experimental osteoporosis can accelerate resorption of bone grafts and decrease cancellous bone volume and implant-bone contact rate, while local treatment with zoledronate acid may resist the negative influence of osteoporosis and increase osseointagration of dental implants.%目的:研究唑来膦酸局部治疗对骨质疏松时自体髂骨移植

  20. The effect of intravenous zoledronic acid on glucocorticoid-induced multiple vertebral fractures in juvenile systemic lupus erythematosus Efeito do ácido zoledrônico nas múltiplas fraturas vertebrais induzidas por glicocorticóide no lúpus eritematoso juvenil

    Directory of Open Access Journals (Sweden)

    Sonia Cristina de Magalhães Souza

    2004-01-01

    Full Text Available Glucocorticoids are widely used in the treatment of lupus patients, and adverse effects, which include osteoporosis and associated fractures, are frequent. Treatment of osteoporosis of young patients should be effective and not harmful to bone growth and remodeling. Bisphosphonates are drugs that decrease the incidence of bone fractures, but their use in juvenile patients is still controversial because of their possible side effects on the growing skeleton. However, recently published studies showed that linear growth continued normally after treatment with these drugs, and there was no excessive suppression of bone remodeling or mineralization defects. Zoledronic acid is a new intravenous bisphosphonate that has been approved by the US FDA for use with hypercalcemia of malignancies and might be an effective treatment for postmenopausal osteoporosis. The authors report a case of a young girl with systemic lupus who developed multiple vertebral collapses due to glucocorticoid therapy, and zoledronic acid was used producing significant clinical and densitometric improvement.Glicocorticóides são fármacos comumente usados no tratamento de pacientes lúpicos, porém apresentam efeitos adversos importantes, principalmente a osteoporose e fraturas. O tratamento da osteoporose em pacientes jovens deve ser eficaz e não prejudicial ao crescimento e remodelamento ósseo. Os bisfosfonatos são drogas que reduzem a incidência de fraturas, mas seu uso em crianças e adolescentes ainda é controverso, devido a seus possíveis efeitos adversos no esqueleto em crescimento. Estudos recentemente publicados demonstraram que o crescimento linear se manteve normal com o uso de bisfosfonatos, não havendo supressão excessiva do remodelamento ósseo ou defeitos de mineralização. O ácido zoledrônico é um novo bisfosfonato endovenoso aprovado pelo FDA para o uso na hipercalcemia das neoplasias e parece ser um tratamento eficaz para a osteoporose p

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. Effect of dietary n-3 fatty acids supplementation on fatty acid metabolism in atorvastatin-administered SHR.Cg-Lepr(cp)/NDmcr rats, a metabolic syndrome model.

    Science.gov (United States)

    Al Mamun, Abdullah; Hashimoto, Michio; Katakura, Masanori; Tanabe, Yoko; Tsuchikura, Satoru; Hossain, Shahdat; Shido, Osamu

    2017-01-01

    The effects of cholesterol-lowering statins, which substantially benefit future cardiovascular events, on fatty acid metabolism have remained largely obscured. In this study, we investigated the effects of atorvastatin on fatty acid metabolism together with the effects of TAK-085 containing highly purified eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) ethyl ester on atorvastatin-induced n-3 polyunsaturated fatty acid lowering in SHR.Cg-Lepr(cp)/NDmcr (SHRcp) rats, as a metabolic syndrome model. Supplementation with 10mg/kg body weight/day of atorvastatin for 17 weeks significantly decreased plasma total cholesterol and very low density lipoprotein cholesterol. Atorvastatin alone caused a subtle change in fatty acid composition particularly of EPA and DHA in the plasma, liver or erythrocyte membranes. However, the TAK-085 consistently increased both the levels of EPA and DHA in the plasma, liver and erythrocyte membranes. After confirming the reduction of plasma total cholesterol, 300mg/kg body weight/day of TAK-085 was continuously administered for another 6 weeks. Supplementation with TAK-085 did not decrease plasma total cholesterol but significantly increased the EPA and DHA levels in both the plasma and liver compared with rats administered atorvastatin only. Supplementation with atorvastatin alone significantly decreased sterol regulatory element-binding protein-1c, Δ5- and Δ6-desaturases, elongase-5, and stearoyl-coenzyme A (CoA) desaturase-2 levels and increased 3-hydroxy-3-methylglutaryl-CoA reductase mRNA expression in the liver compared with control rats. TAK-085 supplementation significantly increased stearoyl-CoA desaturase-2 mRNA expression. These results suggest that long-term supplementation with atorvastatin decreases the EPA and DHA levels by inhibiting the desaturation and elongation of n-3 fatty acid metabolism, while TAK-085 supplementation effectively replenishes this effect in SHRcp rat liver.

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. 鲑鱼降钙素联合唑来膦酸注射液治疗老年原发性骨质疏松症的疗效观察%Efficacy of salmon calcitonin combined with zoledronic acid in treatment of senile primary osteoporosis

    Institute of Scientific and Technical Information of China (English)

    沈小明; 黄成龙; 陈刚; 龚遂良

    2016-01-01

    One hundred and twenty patients with senile primary osteoporosis were enrolled in the study from January 2012 to April 2013,including 41 males and 79 females.Patients were randomly assigned to two groups:60 patients in study group were treated with salmon calcitonin combined with zoledronic acid (salmon calcitonin 50 IU i.m,q.d for 7 d,then 100 IU q.i.d for 7 d,followed by zoledronic acid 5 mg i.v gtt/y);60 cases in control group were treated with alendronate (70 mg p.o/wk).Both groups received the same doses of calcium.Visual analogue scale (VAS) scores were assessed before,and 1,6 and 12 months after treatment,12-Item Short-Form Health Survey (SF-12) and bone mineral density (BMD) were assessed before and 12 months after treatment.There were no significant differences in all baseline parameters between two groups (P > 0.05).After 1 month of treatment,the VAS scores of study group was lower than that of the control group (2.1 ± 3.0 vs.4.2 ± 3.1,P < 0.05),however,both groups had similar improvements in VAS scores in 6 and 12 months after the treatment (P >0.05).Compared to those before treatment,physical component summary and mental component summary of SF-12 scores after 1 year of treatment were improved significantly in both groups (P < 0.05).Also,BMD was significantly improved after 1 year of treatment in both groups (P < 0.05).The incidence of side effect in study group was lower than that in control group (16% vs.20%,P <0.05).The results indicate that salmon calcitonin combined with zoledronic acid is an effective,safe,reliable and well tolerated therapy for senile primary osteoporosis.The long-term outcomes remain to be determined.%对2012年1月至2013年4月在我院接受诊治的120例老年原发性骨质疏松症患者(男41例,女性79例),除常规补充钙剂外,60例采用鲑鱼降钙素联合唑来膦酸注射液治疗(观察组),60例采用阿仑膦酸钠治疗(对照组).药物剂量为肌肉注射鲑鱼降钙素50 U/次、1

  11. 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...

  12. 尿N-乙酰-β-D氨基葡萄糖酶、丙氨酸氨肽酶和α1-微球蛋白检测在唑来膦酸致肾损伤早期诊断作用%Effects of detecting of N-acety-beta-D-glucosaminidase,Alanine aminopeptidase andα1-microglobulin in urine on early diag-nosis of kidney injury induced by zoledronic acid

    Institute of Scientific and Technical Information of China (English)

    刘星; 刘大为; 谢晓冬; 郭占文; 郑振东; 张丽辉; 张娇蕊; 刘永叶

    2016-01-01

    目的 探讨尿N-乙酰-β-D氨基葡萄糖酶(NAG)、丙氨酸氨肽酶(AAP)和α1-微球蛋白(α1-MG)检测在唑来膦酸致肾损伤早期诊断中的作用.方法 选取2012年2月至2014年7月沈阳军区总医院收治的100例应用唑来膦酸治疗的恶性肿瘤骨转移患者为研究对象.其中,男性48例,女性52例,年龄25~82岁,平均(60±11)岁.患者接受唑来膦酸注射液4 mg静脉滴注,1次/25~35 d,30 min滴完,连续应用3次.每次用药前和用药次日,留取患者清晨尿液及静脉血,检测并比较尿NAG、AAP、α1-MG和血肌酐(Scr)、尿素氮(BUN)水平.结果 每次用药前、后比较尿NAG水平,差异均有统计学意义(P0.05);而第2次和第3次用药前后,尿α1-MG水平比较,差异有统计学意义(P0.05).每次用药前后,Scr、BUN水平比较,差异均无统计学意义(P>0.05).3次用药后,尿NAG、α1-MG水平组间比较,差异均有统计学意义(P0.05).结论 唑来膦酸致肾损伤患者尿NAG、AAP和α1-MG水平变化早于血肌酐.尿NAG、AAP和α1-MG联合检测可作为肾损伤的早期诊断指标.%Objective To explore the effects of detecting of N-acety-beta-D-glucosaminidase( NAG) ,Alanine aminopeptidase( AAP) andα1-microglobulin(α1-MG) in urine on early diagnosis of kidney injury induced by zoledronic acid. Methods A total of 100 pa-tients comprised 48 males and 52 females with a mean age of (60 ± 11)years were enrolled into the study. The patients with malignant tumor bone metastasis and received zoledronic acid from February 2012 to July 2014 in the General Hospital of Shenyang Military Command. They received IV infusion of zoledronic acid 4 mg,once for 25 to 35 days,finished within 30 minutes. The therapy was ap-plied 3 times continuously. The patients′urine and venous blood samples were taken before and after each medication′s morning. The level of NAG,AAP and α1-MG in urine and serum creatinine,blood urea nitrogen were detected and compared. Results The differ

  13. DELAYED PREPUTIAL SEPARATION (PPS) AND SP22 MEASUREMENT IN RATS ADMINISTERED BROMOCHLOROACETIC ACID (BCA) IN DRINKING WATER

    Science.gov (United States)

    Reproductive effects of BCA were determined in a dose range finding study (DRFS) and definitive two-generational study. Adult male and female CD� (SD) rats were administered BCA in drinking water for two weeks in the DRFS (10/sex/group) and ten weeks in the definitive study (25/s...

  14. Orally administered glycidol and its fatty acid esters as well as 3-MCPD fatty acid esters are metabolized to 3-MCPD in the F344 rat.

    Science.gov (United States)

    Onami, Saeko; Cho, Young-Man; Toyoda, Takeshi; Akagi, Jun-ichi; Fujiwara, Satoshi; Ochiai, Ryosuke; Tsujino, Kazushige; Nishikawa, Akiyoshi; Ogawa, Kumiko

    2015-12-01

    IARC has classified glycidol and 3-monochloropropane-1,2-diol (3-MCPD) as group 2A and 2B, respectively. Their esters are generated in foodstuffs during processing and there are concerns that they may be hydrolyzed to the carcinogenic forms in vivo. Thus, we conducted two studies. In the first, we administered glycidol and 3-MCPD and associated esters (glycidol oleate: GO, glycidol linoleate: GL, 3-MCPD dipalmitate: CDP, 3-MCPD monopalmitate: CMP, 3-MCPD dioleate: CDO) to male F344 rats by single oral gavage. After 30 min, 3-MCPD was detected in serum from all groups. Glycidol was detected in serum from the rats given glycidol or GL and CDP and CDO in serum from rats given these compounds. In the second, we examined if metabolism occurs on simple reaction with rat intestinal contents (gastric, duodenal and cecal contents) from male F344 gpt delta rats. Newly produced 3-MCPD was detected in all gut contents incubated with the three 3-MCPD fatty acid esters and in gastric and duodenal contents incubated with glycidol and in duodenal and cecal contents incubated with GO. Although our observation was performed at 1 time point, the results showed that not only 3-MCPD esters but also glycidol and glycidol esters are metabolized into 3-MCPD in the rat.

  15. 鲑鱼降钙素和唑来膦酸治疗绝经后骨质疏松症的成本-效果分析%Cost-effectiveness Analysis of Salmon Calcitonin and Zoledronic Acid in Treating Postmenopausal Osteoporosis

    Institute of Scientific and Technical Information of China (English)

    白瑶; 周学琴; 刘玉琴

    2015-01-01

    Objective To study the cost-effectiveness of calcitonin salmon and zoledronic acid in treating postmenopausal osteoporo-sis.Methods 126casesofpostmenopausalosteoporosiswerecollectedandrandomlydividedintotwogroups:groupAandgroupB.Data was evaluated using the cost-effectiveness analysis of pharmacoeconomics.Results The costs of group A and group B were 2 279.42 and 3 316.79 yuan respectively.The total effective rates of group A and group B were 57.14%and 79.37%respectively.Group B was higher than those in group A,and the difference was statistically significant in two groups (P<0.05).The cost-effectiveness ratios (C/E) of group A and group B were 39.89 and 41.78 respectively.Conclusion Group B has better compliance and is more reasonable as compared with group A.%目的:比较鲑鱼降钙素和唑来膦酸治疗绝经后骨质疏松症( PMOP)的成本与效果。方法将126例PMOP患者分为A组和B组,运用药物经济学原理进行成本-效果分析。结果 A组和B组的治疗成本分别为2279.43元和3316.79元;总有效率分别为57.14%和79.37%,B组明显高于A组,有统计学差异( P<0.05);经济学方面A组和B组的成本-效果比分别是39.89和41.79。结论应用唑来膦酸治疗绝经后骨质疏松症比鲑鱼降钙素更为合理。

  16. 唑来膦酸注射液+钙制剂+ VD 对骨质疏松患者症状缓解情况的对照研究%A case - control study of Zoledronic acid injection + calcium preparations + VD in symptoms miti-gation patients with osteoporosis

    Institute of Scientific and Technical Information of China (English)

    亢鸿儒

    2016-01-01

    目的:探讨骨质疏松患者采用唑来膦酸注射液+钙制剂+维生素 D(VD)对症状缓解的效果。方法选取灵宝市第一人民医院2013年2月至2015年2月收治的骨质疏松患者60例,随机分为钙制剂+ VD 治疗组(对照组)与联用唑来膦酸注射治疗组(观察组),每组30例。比较两组患者的临床效果。结果两组患者治疗前左股骨大粗隆骨密度、第1~4腰椎骨密度、降钙素、甲状旁腺激素、骨钙素、肌酐、血清磷、血清钙差异未见统计学意义(P >0.05),治疗后观察组左股骨大粗隆骨密度、腰椎 L1-4骨密度明显升高、甲状旁腺激素有所降低,与治疗前及对照组比较差异有统计学意义(P 0. 05). After treatment in the observation group,left femoral trochanter BMD L1 - 4 lumbar spine BMD increased sig-nificantly,parathyroid hormone decreased,there were significant differences compared with before treat-ment and control group(P < 0. 05). There were no significant changes in other indicators. There were no serious adverse reactions. Conclusions Osteoporosis,calcium and vitamin D preparations conventional therapy,taking zoledronic acid plus can significantly improve patients’body and prevent adverse events. This path has important meaning in the protection of the quality of life.

  17. Administering different levels of parenteral phosphate and amino acids did not influence growth in extremely preterm infants

    DEFF Research Database (Denmark)

    Thomsen, Katrine Moe; Beck-Nielsen, Signe Sparre; Lando, Ane

    2015-01-01

    AIM: When a new high amino acid parenteral nutrition (PN) solution was introduced to our hospital, a design error led to decreased phosphate levels. This prompted us to examine the effect of three different PN solutions on plasma phosphate, plasma calcium and weight increases on extremely preterm...

  18. 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.

  19. 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

    The objective of this study was to examine the effects of triacylglycerol (TAG) structure and level of n-3 fatty acids on fatty acid profile of brain phospholipids (PL) of dams and offspring, and the memory and learning ability of the offspring, when administered during initial development...... and 22:6n-3 adding up to a total of 2 mol% n-3 fatty acids. The effects of the experimental diets were compared to the effect of a chow diet. Results: The amount of 22:6n-3 in brain phosphatidyl ethanolamine (PE) and phosphatidyl serine (PS) of dams and offspring (3 and 13 weeks of age) was not affected...... 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...

  20. Efficacy observation and safety analysis of Zoledronic acid on osteoporosis of postoperative gynaecological manligancies%唑来膦酸对妇科恶性肿瘤术后骨质疏松的疗效观察及安全性分析

    Institute of Scientific and Technical Information of China (English)

    张玉会; 李正英

    2016-01-01

    目的:观察唑来膦酸对妇科恶性肿瘤术后骨质疏松患者的疗效并进行不良反应监测与分析。方法选择2010年2月至2014年2月辽河油田总医院与海原县中医医院收治的120例妇科恶性肿瘤术后骨质疏松患者,采用随机双盲对照的研究设计将患者分为观察组与对照组,各60例。观察组予5mg唑来膦酸并服用钙尔奇D片,对照组给予5mg安慰剂并服用钙尔奇D片,比较两组治疗前后视觉模拟评分法( visual analogue scale/score,VAS)评分、腰椎与股骨颈骨密度以及急性期不良反应等情况。结果观察组VAS评分、腰椎与股骨颈骨密度均有显著改善(P<0.05),且效果明显优于对照组(P<0.05);观察组急性期不良反应发生率高达31.79%,但症状较轻且能较快缓解,并无严重不良反应。结论唑来膦酸对妇科恶性肿瘤术后骨质疏松的患者疗效明显,具有一定的安全性。%Objective To observe the curative effect as well as to monitor and analysis adverse reaction of osteoporosis treatment in patients with gynecological malignant tumor. Method 120 cases of patients who had come to the General Hospital of Liaohe Oil Field and Haiyuan County Hospital of Traditional Chinese Medicine from February 2010 to February 2014 were selected. Using randomized, double-blind and placebo-controlled study design, selected 120 cases after of gynecologic malignant tumor operation with osteoporosis. The observation group were given 5 mg of zoledronic acid with Caltrate D, the control group were given 5 mg placebo Caltrate D,Observe the two groups before and after treatment by VAS score, lumbar vertebra ,femoral neck bone mineral density and acute adverse reactions. Results After treatment,VAS score, lumbar spine and femoral neck bone mineral density were significantly improved (P<0. 05)in the observation group and were better than the control group (P<0. 05);acute stage adverse reaction rate in the observation group is as high

  1. Zoledronic Acid in Aromatase Inhibitor Induced Musculoskeletal Symptoms

    Science.gov (United States)

    2016-11-10

    Ductal Carcinoma in Situ; Estrogen Receptor-positive Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage I Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  2. Zoledronate inhibits ischemia-induced neovascularization by impairing the mobilization and function of endothelial progenitor cells.

    Directory of Open Access Journals (Sweden)

    Shih-Hung Tsai

    Full Text Available BACKGROUND: Bisphosphonates are a class of pharmacologic compounds that are commonly used to treat postmenopausal osteoporosis and malignant osteolytic processes. Studies have shown that bone marrow-derived endothelial progenitor cells (EPCs play a significant role in postnatal neovascularization. Whether the nitrogen-containing bisphosphonate zoledronate inhibits ischemia-induced neovascularization by modulating EPC functions remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: Unilateral hindlimb ischemia was surgically induced in wild-type mice after 2 weeks of treatment with vehicle or zoledronate (low-dose: 30 μg/kg; high-dose: 100 μg/kg. Doppler perfusion imaging demonstrated that the ischemic limb/normal side blood perfusion ratio was significantly lower in wild-type mice treated with low-dose zoledronate and in mice treated with high-dose zoledronate than in controls 4 weeks after ischemic surgery (control vs. low-dose vs. high-dose: 87±7% vs. *61±18% vs. **49±17%, *p<0.01, **p<0.005 compared to control. Capillary densities were also significantly lower in mice treated with low-dose zoledronate and in mice treated with high-dose zoledronate than in control mice. Flow cytometry analysis showed impaired mobilization of EPC-like cells (Sca-1(+/Flk-1(+ after surgical induction of ischemia in mice treated with zoledronate but normal levels of mobilization in mice treated with vehicle. In addition, ischemic tissue from mice that received zoledronate treatment exhibited significantly lower levels of the active form of MMP-9, lower levels of VEGF, and lower levels of phosphorylated eNOS and phosphorylated Akt than ischemic tissue from mice that received vehicle. Results of the in vitro studies showed that incubation with zoledronate inhibited the viability, migration, and tube-forming capacities of EPC. CONCLUSIONS/SIGNIFICANCE: Zoledronate inhibited ischemia-induced neovascularization by impairing EPC mobilization and angiogenic functions

  3. 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.

  4. Chronically administered retinoic acid has trophic effects in the rat small intestine and promotes adaptation in a resection model of short bowel syndrome.

    Science.gov (United States)

    Wang, Lihua; Tang, Yuzhu; Rubin, Deborah C; Levin, Marc S

    2007-06-01

    Following the loss of functional small bowel surface area, the intestine undergoes a compensatory adaptive response. The observation that adaptation is inhibited in vitamin A-deficient rats following submassive intestinal resection suggested that vitamin A is required for this response and raised the possibility that exogenous vitamin A could augment adaptation. Therefore, to directly assess whether chronically administered retinoic acid could stimulate gut adaptation in a model of short bowel syndrome and to address the mechanisms of any such effects, Sprague-Dawley rats were implanted with controlled release retinoic acid or control pellets and then subjected to mid-small bowel or sham resections. At 2 wk postoperation, changes in gut morphology, crypt cell proliferation and apoptosis, enterocyte migration, the extracellular matrix, and gene expression were assessed. Retinoic acid had significant trophic effects in resected and sham-resected rats. Retinoic acid markedly inhibited apoptosis and stimulated crypt cell proliferation and enterocyte migration postresection. Data presented indicate that these proadaptive effects of retinoic acid may be mediated via changes in the extracellular matrix (e.g., by increasing collagen IV synthesis, decreasing E-cadherin expression, and reducing integrin beta(3) levels), via affects on Hedgehog signaling (e.g., by reducing expression of the Hedgehog receptors Ptch and Ptch2 and the Gli1 transcription factor), by increasing expression of Reg1 and Pap1, and by modulation of retinoid and peroxisome proliferator-activated receptor signaling pathways. These studies are the first to demonstrate that retinoic acid can significantly enhance intestinal adaptation and suggest it may be beneficial in patients with short bowel syndrome.

  5. Cis-urocanic acid increases immunotoxicity and lethality of dermally administered permethrin in C57BL/6N mice.

    Science.gov (United States)

    Prater, M R; Gogal, R M; Blaylock, B L; Holladay, S D

    2003-01-01

    Immunomodulatory effects of a single topical permethrin exposure, 5-day exposure to cis-urocanic acid (cUCA), or a combination of the two chemicals were evaluated in 4- to 5-week-old female C57BL/6N mice. Permethrin alone decreased thymic weight and cellularity. Although cUCA alone did not affect thymic end points, coexposure to topical permethrin and cUCA exacerbated the thymolytic effects of permethrin. The single topical dose of permethrin also depressed several immune responses in isolated splenic leukocytes. This included splenic T-cell proliferative response to mitogen, splenic macrophage hydrogen peroxide production, and splenic B lymphocyte-specific antibody production. Unlike the effect of coexposure to these agents on thymic end points, cUCA did not exacerbate permethrin's adverse effect on any of the splenic end points examined. These results appear to suggest divergent mechanisms by which these compounds affect precursor and functionally mature T cells. At the doses used in this study, permethrin caused neurotoxic effects, including lethality, in a portion of the mice. For undetermined reasons, cUCA significantly increased the rate of lethality caused by permethrin. Although the permethrin doses used in this study exceed that typically used in human medicine, these results raise some concerns about the possibility that sunlight, via cUCA, may increase the risk of adverse central nervous system and immune effects caused by permethrin alone.

  6. 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.

  7. 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.

  8. 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 packing and may be of value in the amelioration of adverse effects of heat stress associated with work in donkeys.

  9. Periodontal disease level-butyric acid amounts locally administered in the rat gingival mucosa induce ER stress in the systemic blood.

    Science.gov (United States)

    Cueno, Marni E; Saito, Yuko; Ochiai, Kuniyasu

    2016-05-01

    Periodontal diseases have long been postulated to contribute to systemic diseases and, likewise, it has been proposed that periodontal disease treatment may ameliorate certain systemic diseases. Short-chain fatty acids (SCFA) are major secondary metabolites produced by oral anaerobic bacteria and, among the SCFAs, butyric acid (BA) in high amounts contribute to periodontal disease development. Periodontal disease level-butyric acid (PDL-BA) is found among patients suffering from periodontal disease and has previously shown to induce oxidative stress, whereas, oxidative stress is correlated to endoplasmic reticulum (ER) stress. This would imply that PDL-BA may likewise stimulate ER stress, however, this was never elucidated. A better understanding of the correlation between PDL-BA and systemic ER stress stimulation could shed light on the possible systemic effects of PDL-BA-related periodontal diseases. Here, PDL-BA was injected into the gingival mucosa and the systemic blood obtained from the rat jugular was collected at 0, 15, 60, and 180 min post-injection. Collected blood samples were purified and only the blood cytosol was used throughout this study. Subsequently, we measured blood cytosolic GADD153, Ca(2+), representative apoptotic and inflammatory caspases, and NF-κB amounts. We found that PDL-BA presence increased blood cytosolic GADD153 and Ca(2+) amounts. Moreover, we observed that blood cytosolic caspases and NF-κB were activated only at 60 and 180 min post-injection in the rat gingival mucosa. This suggests that PDL-BA administered through the gingival mucosa may influence the systemic blood via ER stress stimulation and, moreover, prolonged PDL-BA retention in the gingival mucosa may play a significant role in ER stress-related caspase and NF-κB activation. In a periodontal disease scenario, we propose that PDL-BA-related ER stress stimulation leading to the simultaneous activation of apoptosis and inflammation may contribute to periodontal disease

  10. 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.

  11. 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...

  12. 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.

  13. The Regulation of Matrix Metalloproteinase Expression and the Role of Discoidin Domain Receptor 1/2 Signalling in Zoledronate-treated PC3 Cells.

    Science.gov (United States)

    Reel, Buket; Korkmaz, Ceren Gonen; Arun, Mehmet Zuhuri; Yildirim, Gokce; Ogut, Deniz; Kaymak, Aysegul; Micili, Serap Cilaker; Ergur, Bekir Ugur

    2015-01-01

    Discoidin Domain Receptors (DDR1/DDR2) are tyrosine kinase receptors which are activated by collagen. DDR signalling regulates cell migration, proliferation, apoptosis and matrix metalloproteinase (MMP) production. MMPs degrade extracellular matrix (ECM) and play essential role in tumor growth, invasion and metastasis. Nitrogen-containing bisphosphonates (N-BPs) which strongly inhibit osteoclastic activity are commonly used for osteoporosis treatment. They also have MMP inhibitory effect. In this study, we aimed to investigate the effects of zoledronate in PC3 cells and the possible role of DDR signalling and downstream pathways in these inhibitory effects. We studied messenger RNA (mRNA) and protein expressions of MMP-2,-9,-8, DDR1/DDR2 type I procollagen (TIP) and mRNA levels of PCA-1, MMP-13 and DDR-initiated signalling pathway players including K-Ras oncogene, ERK1, JNK1, p38, AKT-1 and BCLX in PC3 cells in the presence or absence of zoledronate (10-100 μM) for 2-3 days. Zoledronate (100 μM) down-regulated DDR1/ DDR2, TIP mRNAs but did not change MMP-13 (collagenase-3) mRNA. However, zoledronate up-regulated MMP-8 (collagenase-2) mRNA. Zoledronate also inhibited mRNA expressions of K-Ras, ERK1, AKT-1, BCLX and PCA-1; but did not change JNK1, p38 mRNA levels. Zoledronate (100 μM) supressed DDR1/DDR2, TIP expressions; and gelatinase (MMP-2/MMP-9) expressions/activities. Conversely, zoledronate up-regulated MMP-8 expression in PC3 cells. Zoledronate down-regulates MMP-2/-9 expressions in PC3 prostate cancer cells. DDR1/DDR2 signalling and DDR-initiated downstream Ras/Raf/ERK and PI3K/AKT pathways may at least partially responsible for MMP inhibitory effect of zoledronate.

  14. 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

  15. 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

  16. Observation of the efficacy and safety of zoledronic and in postmenopausal osteoporosis%唑来膦酸治疗绝经后骨质疏松症的有效性和安全性

    Institute of Scientific and Technical Information of China (English)

    黄淑纾; 王军; 林华

    2016-01-01

    Objective:To investigate whether there is an effective attenuation of osteoporosis treatments on BMD in-crease and whether they are safe with increasing ages and increasing uses of zoledronic acid. To investigate whether there ’s any improvement of health-related quality of life (HRQL) as zoledronic acid improves BMD. Methods: In this self-control, prospective trial, 220 postmenopausal women with osteoporosis (mean age 67 years) received a single infusion of ZOL 5 mg at baseline in the 12th month. BMD and HRQL were measured at baseline, in the 12th and 24th month (before each use of zoledronic acid). The main outcome measures were the changes in lumbar spine and hip BMD and the changes in HRQL by the Short Form-36 questionaire (SF-36). The ANOVA and LSD multiple comparison was used for statistical comparison. Safety evaluation was conducted at the same time. Results: The patients with postmenopausal osteoporosis had significantly higher L1-4 (0.841 ±0.134), total hip (0.730 ±0.096), femoral neck (0.695 ±0.073), Ward’s triangle (0.498 ±0.036) and trochanter (0.559±0.056) BMD (P<0.05) and improved BP, GH and PCS in HRQL (P<0.05) over 2-year treatment of once-yearly ZOL 5mg. No serious adverse events directly related occurred. Conclusions: Zoledronic acid is safe and effective, increases bone mineral density substantially, and increases health-related quality of life, especially in the physical aspects, over 2 years of treatment in women with postmenopausal osteoporosis.%目的:探讨唑来膦酸(ZOL)治疗绝经后骨质疏松症的疗效和安全性。方法:采用自身对比前瞻性研究,220例绝经后骨质疏松症妇女在基线、12个月时接受单次静脉输注ZOL 5mg,在基线、12个月和24个月时使用双能X线(DXA)测定骨密度(BMD)、SF-36问卷表评估健康相关生活质量(HRQL),同时进行安全性观察。结果:经过2年ZOL治疗,患者L1-L4(0.841±0.134)、全髋(0.730±0.096

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    , and bone and musculoskeletal pain. No cases of osteonecrosis of the jaw were reported, and no adverse effects on the healing of fractures were noted. The rates of renal and cardiovascular adverse events, including atrial fibrillation and stroke, were similar in the two groups. CONCLUSIONS: An annual...

  18. Atypical Subtrochanteric Femur Fracture in Patient with Metastatic Breast Cancer Treated with Zoledronic Acid

    OpenAIRE

    2012-01-01

    Several case series have suggested an association exists between atypical femoral subtrochanteric fractures and long-term use of bisphosphonates. It is thought that prolonged use of bisphosphonates may lead to adynamic, fragile bone. The radiologic features of atypical fractures include diffuse cortical thickening, transverse fracture, and beaking at the lateral subtrochanteric area. Atypical subtrochanteric femur fractures have been reported after use of alendronate, but there have been rare...

  19. Severe resistant hypocalcemia in multiple myeloma after zoledronic acid administration: a case report

    OpenAIRE

    Noriega Aldave, Adrian P; Jaiswal, Shikha

    2014-01-01

    Introduction Hypercalcemia is one of the most common metabolic abnormalities encountered in any form of malignancy. Hypocalcemia, however, is a rare manifestation, especially in cancers with bone involvement. Here we present a case of hypocalcemia in a patient with multiple myeloma that was refractory to treatment. Case presentation A 73-year-old African American woman recently diagnosed with multiple myeloma, presented with a 2-day history of fever, vomiting and hypocalcemia. Ten days prior ...

  20. 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

  1. FES-Rowing versus Zoledronic Acid to Improve Bone Health in SCI

    Science.gov (United States)

    2015-10-01

    Leslie R. Morse, DO Betty Diamond 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail: lmorse4@partners.org 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION...bone strength of the lower extremity in a dose dependent fashion. Reportable Outcomes Publications Taylor JA, Picard G, Porter A, Morse LR

  2. Palkanlaskennan perehdytysopas Case: Administer Oy

    OpenAIRE

    Vänttinen, Sakari

    2016-01-01

    Opinnäytetyössä tehtiin palkanlaskennan perehdytysopas sähköisen taloushallinnon palveluntarjoajalle Administer Oy:lle. Työn päätavoitteena oli luoda palkanlaskennan perehdytysopas Administer Oy:n sisäiseen käyttöön. Perehdytysoppaan on tarkoitus tukea ja selkeyttää uusien palkanlaskijoiden työn aloittamista ja työtehtävien omaksumista. Perehdytysoppaan tavoitteena on lisäksi nopeuttaa ja helpottaa perehdyttäjien työtä perehdytysprosessin aikana. Työ keskittyy vain palkanlaskentapalveluun...

  3. Synthesis and antiproliferative activity of aromatic and aliphatic bis[aminomethylidene(bisphosphonic)] acids.

    Science.gov (United States)

    Goldeman, Waldemar; Nasulewicz-Goldeman, Anna

    2014-08-01

    A series of aromatic and aliphatic bis[aminomethylidene(bisphosphonic)] acids was synthesized in the reaction of triethylphosphite with isonitriles followed by hydrolysis or dealkylation. The in vitro anti-proliferative effect of all synthesized tetraphosphonic acids against MCF-7 breast cancer cells, J774E macrophages and HL-60 promyelocytic leukemia cells was determined. Three aromatic derivatives (5a, 5f and 5j) showed a similar or higher anti-proliferative activity than zoledronic acid.

  4. 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.

  5. 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.

  6. 22 CFR 196.4 - Administering office.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Administering office. 196.4 Section 196.4... AFFAIRS/GRADUATE FOREIGN AFFAIRS FELLOWSHIP PROGRAM § 196.4 Administering office. The Department of State's Bureau of Human Resources, Office of Recruitment is responsible for administering the Thomas...

  7. 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....

  8. Protective role of caffeic acid phenethyl ester and erdosteine on activities of purine-catabolizing enzymes and level of nitric oxide in red blood cells of isoniazid-administered rats.

    Science.gov (United States)

    Yilmaz, H R; Uz, E; Gökalp, O; Ozçelik, N; Ciçek, E; Ozer, M K

    2008-09-01

    The aim of this experimental study was to investigate the possible role of nitric oxide (NO) and the activities of adenosine deaminase (ADA) and xanthine oxidase (XO) in the pathogenesis of isoniazid (INH)-induced oxidative damage in red blood cells (RBCs), and also to show the effect of caffeic acid phenethyl ester (CAPE) and erdosteine, antioxidants, in decreasing this toxicity. A total of 25 adult male rats were divided into four experimental groups as follows: control group (n = 7), INH-treated group (n = 6), INH + CAPE-treated group (n = 6), and INH + erdosteine-treated group (n = 6). INH, INH-CAPE, and INH-erdosteine-treated groups were treated orally with INH 50 mg/kg daily and with the tap water for 15 days. Control group was given only tap water. CAPE was intraperitoneally injected for 15 days at a dose of 10 micromol/kg. Erdosteine was treated orally for 15 days at a dose of 10 mg/kg/day. The injection of INH led to a significant increase in the activities of ADA, XO, and NO levels in RBCs of rats. Co-treatment with CAPE caused a significant decrease in the activities of ADA and XO and the levels of NO in RBCs. In addition, co-treatment with erdosteine caused a significant decrease in the activities of ADA and XO and the levels of NO in RBCs. The results of this study showed that ADA, XO, and NO may play an important role in the pathogenesis of INH-induced oxidative stress in RBCs. CAPE and erdosteine may have protective potential in this process and they may become a promising drug in the prevention of this undesired side effect of INH.

  9. Skeletal Site-specific Effects of Zoledronate on in vivo Bone Remodeling and in vitro BMSCs Osteogenic Activity

    Science.gov (United States)

    Gong, Xue; Yu, Wanlu; Zhao, Hang; Su, Jiansheng; Sheng, Qing

    2017-01-01

    Bisphosphonate-related osteonecrosis of the jaw (BRONJ) has been associated with long-term oral or intravenous administration of nitrogen-containing bisphosphonates (BPs). However, the pathogenesis of BRONJ remains unknown, and definitively effective treatment has not yet been established. Bisphosphonate-related osteonecrosis (BRON) tends to occur in maxillofacial bones. Why this occurs is still unclear. Here we show that zoledronate (Zol) treatment suppresses alveolar bone remodeling after tooth typical clinical and radiographic hallmarks of the human BRONJ, whereas enhances peripheral bone quantity in bone remodeling following injury in the same individuals, shown as increased cortical bone thickness, increased trabecular bone formation and accelerated bone defect repair. We find that the RANKL/OPG ratio and Wnt-3a expression are suppressed at the extracted alveolar sites in Zol-treated rats compared with those at the injured sites of peripheral bones. We also show that Zol-treated bone marrow stromal cell (BMSCs) derived from jaw and peripheral bones exhibit differences in cell proliferation, alkaline phosphatase (ALP) activity, expression of osteogenic and chondrogenic related marker genes, and in vivo bone formation capacity. Hopefully, this study will help us better understand the pathogenesis of BRONJ, and deepen the theoretical research. PMID:28139685

  10. 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.

  11. 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

    SD at 12 months follow-up. Biochemical markers of bone turnover were decreased and PTH increased during the first 12 months of treatment and bone modeling was reduced. All markers stabilised over the next 6 months. There were no incidences of fracture, spondylolisthesis or osteonecrosis of the jaw...

  12. 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...

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    -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...

  14. On the Interchangeability of Individually Administered and Group Administered Ability Tests

    Science.gov (United States)

    Nevo, Baruch; Sela, Roni

    2003-01-01

    This research studied the interchangeability of individually administered and group administered cognitive tests. Seventy undergraduate students took the Hebrew version of the WAIS-R (Wechsler Adult Intelligence Scale-Revised), and their IQs were measured. They also took the IPET (Israeli Psychometric Entrance Test) and their IPET scores were…

  15. Influence of zoledronate on osteoclast differentiation and gene expression of calmodulin and calmodulin-dependent protein kinase Ⅱ%唑来膦酸对破骨细胞分化中钙调蛋白和钙调蛋白依赖性激酶Ⅱ基因表达的影响

    Institute of Scientific and Technical Information of China (English)

    李鹏; 林珏杉; 张鹏; 董伟; 李金源; 戚孟春

    2013-01-01

    目的 研究唑来膦酸对破骨细胞分化及信号分子钙调蛋白、钙调蛋白依赖性激酶(calmodulin-dependent protein kinase,CAMK)Ⅱ基因表达的影响.方法 应用核因子κB受体激活蛋白配体(receptor activatior of nuclear factor κB ligand,RANKL)诱导小鼠单核巨噬细胞株RAW264.7向破骨细胞分化.细胞分为两组:A组用RANKL诱导5 d;B组在RANKL诱导3d后加用唑来膦酸处理2d.检测破骨细胞生成及钙调蛋白、CAMKⅡ基因表达情况.结果 B组新生多核破骨细胞、吸收陷窝数目及面积分别为(23±3)、(19±2)和(4951±223) μm2,均显著低于A组的(44±3)、(46±1)和(13 331±248) μm2 (P <0.01).与A组比较,B组钙调蛋白、CAMKⅡ基因表达也显著下降(P<0.01),mRNA及蛋白水平钙调蛋白分别下降了26.7%和37.2%;CAMKⅡ分别下降了57.0%和76.1%.结论 唑来膦酸可显著抑制破骨细胞生成和骨吸收功能,并下调钙调蛋白、CAMKⅡ基因表达;信号分子钙调蛋白、CAMKⅡ可能参与了唑来膦酸对破骨细胞的抑制作用.%Objective To investigate the effect of zoledronate acid on osteoclast differentiation and gene expression of calmodulin (CAM) and calmodulin-dependent protein kinase (CAMK) Ⅱ.Methods Receptor activatior of nuclear factor κB ligand (RANKL) was used to induce differentiation of RAW264.7cells into osteoclasts in vitro.The cells were divided into two groups,group A and group B.Both groups were treated with RANKL for 5 days,whereas group B was also treated with zoledronate for the last 2 days.Osteoclastogenesis and gene expression of CAM and CAMK Ⅱ were examined.Results In group B,the number of new-generated osteoclasts (≥ 3 nuclei),number and size of dentin resorption lacunaes were (23 ±3),(19 ±2) and (4951 ±223) μm2 respevtively,which were significantly lower than those [(44 ±3),(46±1) and (13 331 ±248) μ m2]in group A (P<0.01).mRNA and protein level of CAM and CAMK Ⅱ were also significantly

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    Peiqi Li

    2015-10-01

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

  2. 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

  3. A Computer-Administered Examination in Professional Ethics.

    Science.gov (United States)

    White, Michael J.

    1988-01-01

    Presents rationale and procedure for a computer-administered examination in professional ethics. Discusses advantages and implications of computer-administered testing in professional ethics, noting benefits for instructors and students of professional ethics in counseling and counseling psychology. (Author/NB)

  4. 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.

  5. 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

    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...

  6. 唑来膦酸影响骨密度效果的系统评价%Effectiveness of Zoledronic Acid Increasing Bone Mineral Density : A Systematic Review

    Institute of Scientific and Technical Information of China (English)

    赵奇; 刘世清; 张春; 廖琦; 黄涛; 杨越

    2014-01-01

    目的 系统评价唑来膦酸影响骨密度的临床效果.方法 计算机检索Cochrane Ce4ntral Register of Controlled Trials,OTA,AAOS,High Wire Press,Springer Link,MEDLINE,EMBASE,CINAHL,ISI Web of Science,CNKI,VIP,万方数据库和中国生物医学文献数据库(CBM)并辅以手工检索关于唑来膦酸影响骨密度的随机对照试验(RCT).结果 共纳入7个RCT.3个RCT显示唑来膦酸可增加腰椎骨密度增加率,3个RCT显示唑来膦酸可增加股骨颈骨密度增加率,4个RCT显示唑来膦酸可增加腰椎骨密度.结论 唑来膦酸对增加全身多处骨密度有一定效果.

  7. Zoledronic acid increases docetaxel cytotoxicity through pMEK and Mcl-1 inhibition in a hormone-sensitive prostate carcinoma cell line

    OpenAIRE

    Silvestrini Rosella; Tesei Anna; Vannini Ivan; Ulivi Paola; Carloni Silvia; Brigliadori Giovanni; Fabbri Francesco; Amadori Dino; Zoli Wainer

    2008-01-01

    Abstract Background In prostate cancer, the identification of drug combinations that could reduce the tumor cell population and rapidly eradicate hormone-resistant cells potentially present would be a remarkable breakthrough in the treatment of this disease. Methods The study was performed on a hormone-sensitive prostate cancer cell line (LNCaP) grown in normal or hormone-deprived charcoal-stripped (c.s.) medium. Cell viability and apoptosis were assessed by SRB assay and Annexin-V/TUNEL assa...

  8. 40 CFR 282.68 - Louisiana State-Administered Program.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Louisiana State-Administered Program. 282.68 Section 282.68 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.68...

  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. 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......, these results demonstrated different lymphatic absorption patterns of fat from dairy products differing in physiochemical properties. Because the fatty acid composition of the dairy products differed only slightly, other factors such as viscosity, type of emulsion, particle size, and likely also protein content...

  11. 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.

  12. Reaction of 3-Amino-1,2,4-Triazole with Diethyl Phosphite and Triethyl Orthoformate: Acid-Base Properties and Antiosteoporotic Activities of the Products

    Directory of Open Access Journals (Sweden)

    Patrycja Miszczyk

    2017-02-01

    Full Text Available The reaction of diethyl phosphite with triethyl orthoformate and a primary amine followed by hydrolysis is presented, and the reaction was suitable for the preparation of (aminomethylenebisphosphonates. 3-Amino-1,2,4-triazole was chosen as an interesting substrate for this reaction because it possesses multiple groups that can serve as the amino component in the reaction—namely, the side-chain and triazole amines. This substrate readily forms 1,2,4-triazolyl-3-yl-aminomethylenebisphosphonic acid (compound 1 as a major product, along with N-ethylated bisphosphonates as side products. The in vitro antiproliferative effects of the synthesized aminomethylenebisphosphonic acids against J774E macrophages were determined. These compounds exhibit similar activity to zoledronic acid and higher activity than incadronic acid.

  13. Hemodynamic effects of calcium gluconate administered to conscious horses.

    Science.gov (United States)

    Grubb, T L; Foreman, J H; Benson, G J; Thurmon, J C; Tranquilli, W J; Constable, P D; Olson, W O; Davis, L E

    1996-01-01

    Calcium gluconate was administered to conscious horses at 3 different rates (0.1, 0.2, and 0.4 mg/kg/min for 15 minutes each). Serum calcium concentrations and parameters of cardiovascular function were evaluated. All 3 calcium administration rates caused marked increases in both ionized and total calcium concentrations, cardiac index, stroke index, and cardiac contractility (dP/dtmax). Mean arterial pressure and right atrial pressure were unchanged; heart rate decreased markedly during calcium administration. Ionized calcium concentration remained between 54% and 57% of total calcium concentration throughout the study. We conclude that calcium gluconate can safely be administered to conscious horses at 0.1 to 0.4 mg/kg/min and that administration will result in improved cardiac function.

  14. 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...... patients (1.3%) and hypotension observed in 71 patients (3.0%). CONCLUSION: Intravenous fentanyl caused clinically meaningful pain reduction in most patients and was safe in the hands of ambulance personnel. Many patients had moderate to severe pain at hospital arrival. As the protocol allowed higher doses...

  15. 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.

  16. 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.

  17. A self administered reliable questionnaire to assess lower bowel symptoms

    Directory of Open Access Journals (Sweden)

    Katelaris Peter H

    2008-03-01

    Full Text Available Abstract Background Bowel symptoms are considered indicators of the presence of colorectal cancer and other bowel diseases. Self administered questionnaires that elicit information about lower bowel symptoms have not been assessed for reliability, although this has been done for upper bowel symptoms. Our aim was to develop a self administered questionnaire for eliciting the presence, nature and severity of lower bowel symptoms potentially related to colorectal cancer, and assess its reliability. Methods Immediately before consulting a gastroenterologist or colorectal surgeon, 263 patients likely to have a colonoscopy completed the questionnaire. Reliability was assessed in two ways: by assessing agreement between patient responses and (a responses given by the doctor at the consultation; and (b responses given by patients two weeks later. Results There was more than 75% agreement for 78% of the questions for the patient-doctor comparison and for 92% of the questions for the patient-patient comparison. Agreement for the length of time a symptom was present, its severity, duration, frequency of occurrence and whether or not medical consultation had been sought, all had agreement of greater than 70%. Over all questions, the chance corrected agreement for the patient-doctor comparison had a median kappa of 65% (which represents substantial agreement, interquartile range 57–72%. The patient-patient comparison also showed substantial agreement with a median kappa of 75%, interquartile range 68–81%. Conclusion This self administered questionnaire about lower bowel symptoms is a useful way of eliciting details of bowel symptoms. It is a reliable instrument that is acceptable to patients and easily completed. Its use could guide the clinical consultation, allowing a more efficient, comprehensive and useful interaction, ensuring that all symptoms are assessed. It will also be a useful tool in research studies on bowel symptoms and their predictive

  18. Administering an epoch initiated for remote memory access

    Science.gov (United States)

    Blocksome, Michael A.; Miller, Douglas R.

    2013-01-01

    Methods, systems, and products are disclosed for administering an epoch initiated for remote memory access that include: initiating, by an origin application messaging module on an origin compute node, one or more data transfers to a target compute node for the epoch; initiating, by the origin application messaging module after initiating the data transfers, a closing stage for the epoch, including rejecting any new data transfers after initiating the closing stage for the epoch; determining, by the origin application messaging module, whether the data transfers have completed; and closing, by the origin application messaging module, the epoch if the data transfers have completed.

  19. 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.

  20. Urinary metabolites of daidzin orally administered in rats.

    Science.gov (United States)

    Yasuda, T; Ohsawa, K

    1998-09-01

    In a study on the metabolism of flavonoids, the isoflavone glycoside daidzin was orally administered to rats. Urine samples were collected and treated with beta-glucuronidase and arylsulfatase. Aglycone daidzein (M3) and other three metabolites, 3',4',7-trihydroxyisoflavone (M1), 4',7-dihydroxyisoflavanone (M2) and 4',7-dihydroxyisoflavan (M4) were isolated from the urine following treatment with enzymes. The structures of M1, M2 and M4 were determined on the basis of chemical and spectral data.

  1. 45 CFR 400.66 - Eligibility and payment levels in a publicly-administered RCA program.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 2 2010-10-01 2010-10-01 false Eligibility and payment levels in a publicly-administered RCA program. 400.66 Section 400.66 Public Welfare Regulations Relating to Public Welfare OFFICE OF...-administered RCA program. (a) In administering a publicly-administered refugee cash assistance program,...

  2. A Controlled Study to Assess the Clinical Efficacy of Totally Self-Administered Systematic Desensitization

    Science.gov (United States)

    Rosen, Gerald M.; And Others

    1976-01-01

    Highly anxious self-referred snake phobics received either (a) therapist-administered desensitization, (b) self-administered desensitization with weekly therapist phone calls, (c) totally self-administered desensitization, (d) self-administered double-blind placebo control, or (e) no treatment. Pretreatment to posttreatment measures revealed…

  3. Taurine ameliorated thyroid function in rats co-administered with chlorpyrifos and lead.

    Science.gov (United States)

    Akande, Motunrayo Ganiyat; Shittu, Muftau; Uchendu, Chidiebere; Yaqub, Lukuman Surakat

    2016-12-01

    Chlorpyrifos is a widely used organophosphate insecticide for domestic, agricultural and industrial purposes. Lead is a toxic heavy metal and it is used for domestic and industrial purposes. Taurine is a semi essential amino acid with bioprotective properties. The aim of this study was to investigate the effects of taurine on thyroid function in Wistar rats co-administered with chlorpyrifos and lead. The rats were divided into 5 groups of 10 rats each. The first two groups were administered with distilled water and soya oil (1 ml/kg) respectively. The other groups received taurine (50 mg/kg), chlorpyrifos + lead [chlorpyrifos (4.25 mg/kg, 1/20 median lethal dose] and lead (233.25 mg/kg, 1/20 median lethal dose) and taurine + chlorpyrifos + lead respectively. The treatments were administered once daily by oral gavage for 16 weeks. The rats were euthanized after the completion of the study and the thyroid function and thyroid histoarchitecture were evaluated. The results revealed that co-administration of chlorpyrifos and lead to the rats induced perturbations in thyroid function and this was manifested by reductions in the concentrations of triiodothyronine and thyroxine, increased thyroid stimulating hormone concentration and degeneration of the follicular epithelia of the thyroid gland. Taurine alleviated the perturbations in thyroid function and improved thyroid gland histoarchitecture. The beneficial effects of taurine may be attributed to its ability to protect the body from toxicity and oxidative stress. Taurine may be useful for prophylaxis against disruptions in thyroid function in animals that are exposed to environmental chlorpyrifos and lead.

  4. 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.

  5. Metabolism of exogenously administered natural surfactant in the newborn lamb

    Energy Technology Data Exchange (ETDEWEB)

    Glatz, T.; Ikegami, M.; Jobe, A.

    1982-09-01

    (/sup 3/H)-Palmitate labeled natural lamb surfactant and free (/sup 14/C)-choline were mixed with the lung fluid of 11 term lambs at cesarean section, before the first breath. After receiving the isotope, the lambs were delivered, allowed to breathe spontaneously, and were subsequently sacrificed from 5 min to 96 h of age. Alveolar washes, lung homogenates, microsomal and lamellar body fractions of lungs, and pulmonary alveolar macrophages were examined for the presence of labeled phosphatidylcholine. Analysis of the labeled natural surfactant kinetic data revealed an apparent t 1/2 of phosphatidylcholine in the whole lung of 6.0 days. This half-life can be interpreted only as a rough estimate. Appearance of considerable (/sup 3/H) labeled phosphatidylcholine in the lung homogenates demonstrated uptake of phosphatidylcholine from alveoli into lung tissue. The surfactant-associated label in homogenates was localized preferentially to lamellar body fractions. Some of the administered (/sup 14/C)-choline appeared in phosphatidylcholine. Almost all of this labeled phosphatidylcholine was associated with the homogenate. Extremely small % of administered (3H) and (14C) were found in pulmonary alveolar macrophages.

  6. 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.

  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...... 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...

  8. Administering truncated receive functions in a parallel messaging interface

    Science.gov (United States)

    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.

  9. 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.

  10. Peripherally administered orexin improves survival of mice with endotoxin shock

    Science.gov (United States)

    Ogawa, Yasuhiro; Irukayama-Tomobe, Yoko; Murakoshi, Nobuyuki; Kiyama, Maiko; Ishikawa, Yui; Hosokawa, Naoto; Tominaga, Hiromu; Uchida, Shuntaro; Kimura, Saki; Kanuka, Mika; Morita, Miho; Hamada, Michito; Takahashi, Satoru; Hayashi, Yu; Yanagisawa, Masashi

    2016-01-01

    Sepsis is a systemic inflammatory response to infection, accounting for the most common cause of death in intensive care units. Here, we report that peripheral administration of the hypothalamic neuropeptide orexin improves the survival of mice with lipopolysaccharide (LPS) induced endotoxin shock, a well-studied septic shock model. The effect is accompanied by a suppression of excessive cytokine production and an increase of catecholamines and corticosterone. We found that peripherally administered orexin penetrates the blood-brain barrier under endotoxin shock, and that central administration of orexin also suppresses the cytokine production and improves the survival, indicating orexin’s direct action in the central nervous system (CNS). Orexin helps restore body temperature and potentiates cardiovascular function in LPS-injected mice. Pleiotropic modulation of inflammatory response by orexin through the CNS may constitute a novel therapeutic approach for septic shock. DOI: http://dx.doi.org/10.7554/eLife.21055.001 PMID:28035899

  11. 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.

  12. Safety of florfenicol administered in feed to tilapia (Oreochromis sp.)

    Science.gov (United States)

    Gaikowski, Mark P.; Wolf, Jeffrey C.; Schleis, Susan M.; Tuomari, Darrell; Endris, Richard G.

    2013-01-01

    The safety of Aquaflor® (50% w/w florfenicol [FFC]) incorporated in feed then administered to tilapia for 20 days (2x the recommended duration) at 0, 15, 45, or 75 mg/kg body weight/day (0, 1, 3, or 5x the recommended dose of 15 mg FFC/kg BW/d) was investigated. Mortality, behavioral change, feed consumption, body size, and gross and microscopic lesions were determined. Estimated delivered doses were >96.9% of target. Three unscheduled mortalities occurred but were considered incidental since FFC-related findings were not identified. Feed consumption was only affected during the last 10 dosing days when the 45 and 75 mg/kg groups consumed only 62.5% and 55.3% of the feed offered, respectively. There were significant, dose-dependent reductions in body size in the FFC-dose groups relative to the controls. Treatment-related histopathological findings included increased severity of lamellar epithelial hyperplasia, increased incidence of lamellar adhesions, decreased incidence of lamellar telangiectasis in the gills, increased glycogen-type and lipid-type hepatocellular vacuolation in the liver, decreased lymphocytes, increased blast cells, and increased individual cell necrosis in the anterior kidney, and tubular epithelial degeneration and mineralization in the posterior kidney. These changes are likely to be of minimal clinical relevance, given the lack of mortality or morbidity observed. This study has shown that FFC, when administered in feed to tilapia at the recommended dose (15 mg FFC/kg BW/day) for 10 days would be well tolerated.

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

    Science.gov (United States)

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

    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. PMID:21987624

  14. 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.

  15. Multi-omic profiles of hepatic metabolism in TPN-fed preterm pigs administered new generation lipid emulsions.

    Science.gov (United States)

    Guthrie, Gregory; Kulkarni, Madhulika; Vlaardingerbroek, Hester; Stoll, Barbara; Ng, Kenneth; Martin, Camilia; Belmont, John; Hadsell, Darryl; Heird, William; Newgard, Christopher B; Olutoye, Oluyinka; van Goudoever, Johannes; Lauridsen, Charlotte; He, Xingxuan; Schuchman, Edward H; Burrin, Douglas

    2016-09-01

    We aimed to characterize the lipidomic, metabolomic, and transcriptomic profiles in preterm piglets administered enteral (ENT) formula or three parenteral lipid emulsions [parenteral nutrition (PN)], Intralipid (IL), Omegaven (OV), or SMOFlipid (SL), for 14 days. Piglets in all parenteral lipid groups showed differential organ growth versus ENT piglets; whole body growth rate was lowest in IL piglets, yet there were no differences in either energy expenditure or (13)C-palmitate oxidation. Plasma homeostatic model assessment of insulin resistance demonstrated insulin resistance in IL, but not OV or SL, compared with ENT. The fatty acid and acyl-CoA content of the liver, muscle, brain, and plasma fatty acids reflected the composition of the dietary lipids administered. Free carnitine and acylcarnitine (ACT) levels were markedly reduced in the PN groups compared with ENT piglets. Genes associated with oxidative stress and inflammation were increased, whereas those associated with alternative pathways of fatty acid oxidation were decreased in all PN groups. Our results show that new generation lipid emulsions directly enrich tissue fatty acids, especially in the brain, and lead to improved growth and insulin sensitivity compared with a soybean lipid emulsion. In all total PN groups, carnitine levels are limiting to the formation of ACTs and gene expression reflects the stress of excess lipid on liver function.

  16. Pharmacokinetics and pharmacodynamics of midazolam administered as a concentrated intranasal spray. A study in healthy volunteers.

    NARCIS (Netherlands)

    Knoester, P.D.; Jonker, D.M.; Hoeven, R.T. van der; Vermeij, T.A.; Edelbroek, P.M.; Brekelmans, G.J.; Haan, G.J. de

    2002-01-01

    AIMS: To investigate the pharmacokinetic and pharmacodynamic profile of midazolam administered as a concentrated intranasal spray, compared with intravenous midazolam, in healthy adult subjects. METHODS: Subjects were administered single doses of 5 mg midazolam intranasally and intravenously in a cr

  17. 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.

  18. Cardioprotective effect of Volvariella volvacea in streptozotocin administered rats

    Directory of Open Access Journals (Sweden)

    Soosaimanickam Carmel Punitha

    2016-12-01

    Full Text Available The present study examined the cardioprotective role of methanol extract of the edible mushroom Volvariella volvacea against oxidative stress in hyperglycemic rats. Rats divided into 6 groups were administered with nicotinamide and streptozotocin intraperitoneally, except Group I (control. Group II served as diabetic control. Group III was given glibenclamide. Two groups (IV and V of rats received (200 and 400 mg/kg mushroom extracts orally for 30 days and Group VI received vitamin E (40 mg/kg. After the treatment period, lipid peroxides, carbonyl end products, advanced glycation end products, reduced glutathione, glutathione peroxidase, glutathione-S transferase, catalase, superoxide dismutase and non-enzymatic anti-oxidants (vitamin C and E were assessed in the heart tissues of experimental animals. Glycosylated hemoglobin was estimated in blood. Electrocardiography recordings of the treated groups were also done. The results showed that mushroom extract treatment reduced the lipid peroxides, advanced glycation end products and protein carbonyls significantly and reversed the altered anti-oxidant enzymes, and the vitamins.

  19. 45 CFR 400.65 - Continuation of a publicly-administered RCA program.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 2 2010-10-01 2010-10-01 false Continuation of a publicly-administered RCA... RESETTLEMENT PROGRAM Refugee Cash Assistance § 400.65 Continuation of a publicly-administered RCA program. Sections 400.65 through 400.69 apply to publicly-administered RCA programs. If a State chooses to operate...

  20. 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...

  1. Pharmacokinetics of oral gabapentin alone or co-administered with meloxicam in ruminant beef calves.

    Science.gov (United States)

    Coetzee, Johann F; Mosher, Ruby A; Kohake, Laura E; Cull, Charley A; Kelly, Lindsey L; Mueting, Stacy L; KuKanich, Butch

    2011-10-01

    Gabapentin is a γ-aminobutyric acid (GABA) analogue indicated for treatment of neuropathic pain. This study determined the pharmacokinetics of oral (PO) gabapentin alone or in combination with meloxicam in ruminant calves. Gabapentin capsules at 10mg/kg or gabapentin powder (from capsules at 15mg/kg) and meloxicam tablets (0.5mg/kg) were administered PO to six beef calves. Plasma drug concentrations were determined over 48h post-administration by liquid chromatography/mass spectrometry followed by non-compartmental pharmacokinetic analysis. The mean (± standard deviation, SD) C(max), T(max) and elimination half-life (t(½)λz) for gabapentin (10mg/kg) alone was 2.97 ± 0.40μg/mL, 9.33 ± 2.73h and 11.02 ± 3.68h, respectively. The mean (± SD) C(max), T(max) and t(½)λz for gabapentin (15mg/kg) co-administered with meloxicam was 3.57±1.04μg/mL, 7.33 ± 1.63h and 8.12±2.11h, respectively. The mean (±SD) C(max), T(max) and t(½)λz for meloxicam was 2.11± 0.19μg/mL, 11.67 ± 3.44h and 20.47 ± 9.22h, respectively. Plasma gabapentin concentrations >2μg/mL were maintained for up to 15h and meloxicam concentrations >0.2μg/mL for up to 48h. The pharmacokinetic profile of oral gabapentin and meloxicam supported clinical evaluation of these compounds for management of neuropathic pain in cattle.

  2. Bioequivalence in dogs of a meloxicam formulation administered as a transmucosal oral mist with an orally administered pioneer suspension product.

    Science.gov (United States)

    Lees, P; Cheng, Z; Keefe, T J; Weich, E; Bryd, J; Cedergren, R; Cozzi, E

    2013-02-01

    A mucosal mist formulation of meloxicam, administered as a spray into the mouth (test article), was compared for bioequivalence to a pioneer meloxicam suspension for oral administration (reference article). Pharmacokinetic profiles and average bioequivalence were investigated in 20 dogs. The study design comprised a two-period, two-sequence, two-treatment cross-over design, with maximum concentration (C(max)) and area under plasma concentration-time curve to last sampling time (AUC(last)) used as pivotal bioequivalence variables. Bioequivalence of the products was confirmed, based on relative ratios of geometric mean concentrations (and 90% confidence intervals within the range 0.80-1.25) for C(max) of 101.9 (97.99-106.0) and for AUC(last) of 97.24 (94.44-100.1). The initial absorption of meloxicam was more rapid for the test article, despite virtually identical C(max) values for the two products. Mean elimination half-lives were 29.6 h (test article) and 30.0 h (reference article). The meloxicam plasma concentration-time profiles were considered in relation to published data on the inhibition of the cyclooxygenase-1 (COX-1) and COX-2 isoenzymes by meloxicam.

  3. Amphiphilic γ-PGA nanoparticles administered on rat middle ear mucosa produce adjuvant-like immunostimulation in vivo

    DEFF Research Database (Denmark)

    Nilsson, Johan; Broos, Sissela; Akagi, Takami;

    2014-01-01

    CONCLUSION: Amphiphilic biodegradable nanoparticles (NPs) composed of poly(γ-glutamic acid) conjugated with L-phenylalanine ethylester (γ-PGA-Phe NPs) applied on the rat middle ear mucosa produce an inflammatory type 1 response. The observation is of relevance for the use of γ-PGA-Phe NPs...... as a concomitant antigen delivery system and adjuvant measure in the context of vaccinations. OBJECTIVES: To examine effects of topical mucosal administration of γ-PGA-Phe NPs as a potentially combined antigen delivery system and adjuvant. METHODS: γ-PGA-Phe NPs were administered on rat middle ear mucosa in a sham...

  4. Therapeutic effect of orally administered microencapsulated oxaliplatin for colorectal cancer.

    Science.gov (United States)

    Urbanska, Aleksandra M; Karagiannis, Emmanouil D; Guajardo, Gonzalo; Langer, Robert S; Anderson, Daniel G

    2012-06-01

    Colorectal cancer is a significant source of morbidity and mortality in the United States and other Western countries. Oral delivery of therapeutics remains the most patient accepted form of medication. The development of an oral delivery formulation for local delivery of chemotherapeutics in the gastrointestinal tract can potentially alleviate the adverse side effects including systemic cytotoxicity, as well as focus therapy to the lesions. Here we develop an oral formulation of the chemotherapeutic drug oxaliplatin for the treatment of colorectal cancer. Oxaliplatin was encapsulated in pH sensitive, mucoadhesive chitosan-coated alginate microspheres. The microparticles were formulated to release the chemotherapeutics after passing through the acidic gastric environment thus targeting the intestinal tract. In vivo, these particles substantially reduced the tumor burden in an orthotopic mouse model of colorectal cancer, and reduced mortality.

  5. 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

  6. 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

  7. 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.

  8. Action of peripherally administered cholecystokinin on monoaminergic and GABAergic neurons in the rat brain.

    Directory of Open Access Journals (Sweden)

    Kaneyuki,Takao

    1989-06-01

    Full Text Available In an acute study, cholecystokinin octapeptide sulfate (CCK in doses of 1, 10 or 100 micrograms/kg body weight was injected intraperitoneally into rats just prior to the dark cycle. Rats were sacrificed two hours following the CCK injection. Norepinephrine levels were elevated in the dorsal amygdala of rats injected with 10 micrograms of CCK as well as in the septum of rats injected with 1 and 10 micrograms of CCK. The dopamine level in the septum of rats injected with 1 microgram of CCK as well as the gamma-aminobutyric acid (GABA level in the lateral hypothalamus of rats injected with 10 micrograms of CCK were also elevated. In a chronic study, CCK (1 microgram/kg body weight/h was subcutaneously infused into rats with Alzet osmotic minipump for seven consecutive days. The daily food consumption did not change during the 7 days of CCK infusion. The dopamine turnover in the striatum accelerated and the GABA level increased. On the contrary, dopamine metabolism in the substantia nigra and locus coeruleus decreased. Furthermore, the serotonin level in the substantia nigra decreased. Norepinephrine levels decreased in the nucleus paraventricularis, the locus coeruleus and the substantia nigra. The results suggest that peripherally administered CCK may act on the monoaminergic neurons and GABAergic neurons in the brain.

  9. Electrocardiographic ( EKG ) Observation in 30 Volunteers Administered Gossypol

    Institute of Scientific and Technical Information of China (English)

    胡承阅; 蒋婵华

    1996-01-01

    To investigate the safety of gossypol in small doses, electrocardiograms (EKG) of 30 healthy male voluteers were traced at the 4th, 12th, 36th and 52th weeks after administration of the drug. The dosage regimen was gossypol acetic acid, 15 mg per day, for the first 12 weeks (induction phase), followed by 10 mg or 7. 5 mg for the rest 40 weeks (effective phase ). Twelve voluteers were withdrawn due to hypokalemia, normal spermatogenesis in the effective phase or others before the 52thweek. Wave form of all EKGs (96 groups obtained in the period) .was normal. However, compared with EKG made before gossypol administration, in most cases the average of PR interval became longer and the average of QRS duration shorter. Subjects with PR interval prolongation, in the whole observation period, were more than those with PR interval reduction. Thea lteration of PR interval at the 4th and 12th week was statistically significant (P<0. 05). The results were difficult to be explained with effect of gossypol on potassium metabolism. More extensive research is necessary to use gossypol, as a polyphenolie aldehyde compound for any clinical object.

  10. 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.

  11. Aspartic acid

    Science.gov (United States)

    Aspartic acid is a nonessential amino acids . Amino acids are building blocks of proteins. "Nonessential" means that our ... this amino acid from the food we eat. Aspartic acid is also called asparaginic acid. Aspartic acid helps ...

  12. Oral Administration of a Retinoic Acid Receptor Antagonist Reversibly Inhibits Spermatogenesis in Mice

    OpenAIRE

    Chung, Sanny S. W.; Wang, Xiangyuan; Roberts, Shelby S.; Stephen M Griffey; Reczek, Peter R.; Wolgemuth, Debra J.

    2011-01-01

    Meeting men's contraceptive needs, orally administered retinoic acid receptor antagonists represent new lead molecules in developing non-hormonal, reversible male contraceptives without adverse side effects.

  13. 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…

  14. 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"....

  15. 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...

  16. 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,...

  17. 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)...

  18. 20 CFR 664.610 - How is the summer employment opportunities element administered?

    Science.gov (United States)

    2010-04-01

    ... element administered? 664.610 Section 664.610 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION... Opportunities § 664.610 How is the summer employment opportunities element administered? Chief elected officials... recipient or fiscal agent under WIA section 117(d)(3)(B). If, in the administration of the summer...

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

    Science.gov (United States)

    2010-07-01

    ... State of California, except those on Indian lands, is the program administered by the California... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class II wells. 147.250 Section 147.250 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY...

  20. Proinflammatory effects of exogenously administered IL-10 in experimental autoimmune orchitis

    DEFF Research Database (Denmark)

    Kaneko, Tetsushi; Itoh, Masahiro; Nakamura, Yoichi;

    2003-01-01

    We studied the effects of exogenously administered recombinant murine interleukin (IL)-10 on the development of experimental autoimmune orchitis (EAO) in C3H/He mice. IL-10 significantly augments histological signs of EAO when administered for 6 consecutive days from days 15 to 20 after primary...

  1. 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

  2. Effect of orally administered L. fermentum NCIMB 5221 on markers of metabolic syndrome: an in vivo analysis using ZDF rats.

    Science.gov (United States)

    Tomaro-Duchesneau, Catherine; Saha, Shyamali; Malhotra, Meenakshi; Jones, Mitchell L; Labbé, Alain; Rodes, Laetitia; Kahouli, Imen; Prakash, Satya

    2014-01-01

    Metabolic syndrome, encompassing type 2 diabetes mellitus and cardiovascular disease, is a growing health concern of industrialized countries. Ferulic acid (FA) is a phenolic acid found in foods normally consumed by humans that has demonstrated antioxidant activity, cholesterol-lowering capabilities, and anti-tumorigenic properties. Select probiotic bacteria, including Lactobacillus fermentum NCIMB 5221, produce FA due to intrinsic ferulic acid esterase activity. The aim of the present research was to investigate a FA-producing probiotic, L. fermentum NCIMB 5221, as a biotherapeutic for metabolic syndrome. The probiotic formulation was administered daily for 8 weeks to Zucker diabetic fatty (ZDF) rats, a model of hyperlipidemia and hyperglycemia. Results show that the probiotic formulation reduced fasting insulin levels and insulin resistance, significantly reduced serum triglycerides (p = 0.016), lowered serum low-density lipoprotein cholesterol levels (p = 0.008), and significantly reduced the atherogenic (p = 0.016) and atherosclerosis (p = 0.012) index as compared to the control animals. In addition, the probiotic formulation significantly increased high-density lipoprotein cholesterol levels (p = 0.041) as compared to the control animals. This research indicates that administration of the FA-producing L. fermentum NCIMB 5221 has the potential to reduce insulin resistance, hyperinsulinemia, hypercholesterolemia, and other markers involved in the pathogenesis of metabolic syndrome. Further studies are required to investigate the human clinical potential of the probiotic formulation in affecting the markers and pathogenesis of metabolic syndrome.

  3. Genetic algorithm guided population pharmacokinetic model development for simvastatin, concurrently or non-concurrently co-administered with amlodipine.

    Science.gov (United States)

    Chaturvedula, Ayyappa; Sale, Mark E; Lee, Howard

    2014-02-01

    An automated model development was performed for simvastatin, co-administered with amlodipine concurrently or non-concurrently (i.e., 4 hours later) in 17 patients with coexisting hyperlipidemia and hypertension. The single objective hybrid genetic algorithm (SOHGA) was implemented in the NONMEM software by defining the search space for structural, statistical and covariate models. Candidate models obtained from the SOHGA runs were further assessed for biological plausibility and the precision of parameter estimates, followed by traditional backward elimination process for model refinement. The final population pharmacokinetic model shows that the elimination rate constant for simvastatin acid, the active form by hydrolysis of its lactone prodrug (i.e., simvastatin), is only 44% in the concurrent amlodipine administration group compared with the non-concurrent group. The application of SOHGA for automated model selection, combined with traditional model selection strategies, appears to save time for model development, which also can generate new hypotheses that are biologically more plausible.

  4. 26 CFR 20.2053-3 - Deduction for expenses of administering estate.

    Science.gov (United States)

    2010-04-01

    ..., the law and practice in the jurisdiction in which the estate is being administered, and the skill and... expenses include such expenses as court costs, surrogates' fees, accountants' fees, appraisers' fees,...

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

    DEFF Research Database (Denmark)

    Aberer, W; Maurer, M; Reshef, A

    2014-01-01

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

  6. Enhanced brain targeting efficiency of intranasally administered plasmid DNA: an alternative route for brain gene therapy.

    Science.gov (United States)

    Han, In-Kwon; Kim, Mi Young; Byun, Hyang-Min; Hwang, Tae Sun; Kim, Jung Mogg; Hwang, Kwang Woo; Park, Tae Gwan; Jung, Woon-Won; Chun, Taehoon; Jeong, Gil-Jae; Oh, Yu-Kyoung

    2007-01-01

    Recently, nasal administration has been studied as a noninvasive route for delivery of plasmid DNA encoding therapeutic or antigenic genes. Here, we examined the brain targeting efficiency and transport pathways of intranasally administered plasmid DNA. Quantitative polymerase chain reaction (PCR) measurements of plasmid DNA in blood and brain tissues revealed that intranasally administered pCMVbeta (7.2 kb) and pN2/CMVbeta (14.1 kb) showed systemic absorption and brain distribution. Following intranasal administration, the beta-galactosidase protein encoded by these plasmids was significantly expressed in brain tissues. Kinetic studies showed that intranasally administered plasmid DNA reached the brain with a 2,595-fold higher efficiency than intravenously administered plasmid DNA did, 10 min post-dose. Over 1 h post-dose, the brain targeting efficiencies were consistently higher for intranasally administered plasmid DNA than for intravenously administered DNA. To examine how plasmid DNA enters the brain and moves to the various regions, we examined tissues from nine brain regions, at 5 and 10 min after intranasal or intravenous administration of plasmid DNA. Intravenously administered plasmid DNA displayed similar levels of plasmid DNA in the nine different regions, whereas, intranasally administered plasmid DNA exhibited different levels of distribution among the regions, with the highest plasmid DNA levels in the olfactory bulb. Moreover, plasmid DNA was mainly detected in the endothelial cells, but not in glial cells. Our results suggest that intranasally applied plasmid DNA may reach the brain through a direct route, possibly via the olfactory bulb, and that the nasal route might be an alternative method for efficiently delivering plasmid DNA to the brain.

  7. Evaluation of administered dose using portal images in craniospinal irradiation of pediatric patients.

    Science.gov (United States)

    Coelho, Carina Marques; Calçada, Raquel; Rodrigues, Sofia; Barragán, Juan Antonio; Sá, Ana Cravo; Macedo, Ana Paula; de Fátima Monsanto, Maria

    2017-03-21

    This study aimed to assess the administered dose based on portal imaging in craniospinal pediatric irradiation by evaluating cases in which portal images did or did not account for the total administered dose. We also intended to calculate the mean increase in total administered dose. Data were collected from General University Hospital Gregorio Marañón; we evaluated the total dose administered, total dose planned, number of portal images per treatment and corresponding monitor units of two different groups: one in which the dose from portal images is deducted from the total administered dose (D), and another in which it was not (N). We used descriptive statistics to analyze the collected data, including the mean and respective standard deviation. We used the Shapiro-Wilk and Spearman rank correlation coefficient tests and estimated the linear regression coefficients. Patients in group D received a mean dose of 29.00 ± 10.28 cGy based on the verification portal images, a quantity that was deducted from the planned dose to match the total administered dose. Patients in group N received a mean dose of 41.50 ± 30.53 cGy, which was not deducted from the planned dose, evidencing a mean increase of 41.50 ± 30.55 cGy over the total administered dose. The acquisition of the set-up verification portal images, without their inclusion in the total administered dose, reflects an average increase in total dose for craniospinal irradiation of pediatric patients. Subtraction of the monitor units used to acquire the verification images is recommended.

  8. 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.

  9. 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.

  10. 高血钙症治疗药唑来膦酸的合成方法改进%An improved synthesis of zoledronic acid as a new treating hypercalcemia drug

    Institute of Scientific and Technical Information of China (English)

    李家明; 童元峰; 张永

    2002-01-01

    以咪唑为起始原料,与溴乙酸乙酯反应再经水解制得咪唑-1-基乙酸,最后与三氯化磷和亚磷酸反应经精制得到唑来膦酸,总收率为27.0%.在合成中使用TEBA替代BBDE Cl作为相转移催化剂、以咪唑乙酸替代咪唑乙酸盐酸盐进行反应,可以方便地得到纯度、收率均较好的产品.

  11. 34 CFR 692.80 - How does a State administer its community service work-study program?

    Science.gov (United States)

    2010-07-01

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

  12. 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...

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

    Science.gov (United States)

    Nozawa, Akio; Takei, Yuya

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

  14. Mercury excretion and intravenous ascorbic acid.

    Science.gov (United States)

    Dirks, M J; Davis, D R; Cheraskin, E; Jackson, J A

    1994-01-01

    We tested the hypothesis that intravenous ascorbic acid increases urinary excretion of mercury in subjects with low mercury levels from dental amalgam, food, and other sources. From 89 adult volunteers we selected 28 subjects with the highest mercury excretions (2 to 14 micrograms/24 h). We administered intravenous infusions of 500 ml lactated Ringer's solution with and without addition of 750 mg of ascorbic acid/kg body weight, up to 60 g ascorbic acid. Average mercury excretion during the 24 h after infusion of ascorbic acid was 4.0 +/- 0.5 micrograms (mean +/- SEM), which was not significantly more than after infusion of Ringer's solution alone (3.7 +/- 0.5 micrograms). Lead excretion was similarly unaffected. If ascorbic acid administered intravenously benefits some persons with suspected adverse reactions to mercury, the benefit in subjects similar to ours appears unrelated to short-term enhanced excretion of mercury or lead.

  15. TECHNOLOGY FOR ADMINISTERING OF THE ACCESS TO INFORMATION RESOURCES IN MANAGEMENT SYSTEM ON THE AVIATION ENTERPRISE

    Directory of Open Access Journals (Sweden)

    Andrey V. Degtyarev

    2015-01-01

    Full Text Available The task of administering software-information complex occurs duringthe development of application systems for managing business-processes and is connected with the organization of access forusers to information resources in conditions of multi-user information systems for management. For solution of this problem proposed theapproach, which is based on a hierarchical system of access rightsto information resources on the levels: tool, object and procedural.Keywords: software-information complex, information resources,administering, permissions, separation of powers, access model.

  16. Effects of peripherally administered urocortin 3 on feeding behavior and gastric emptying in mice

    OpenAIRE

    2011-01-01

    Human and mouse urocortin 3 (Ucn3) were first identified in 2001. Ucn3 binds selectively to corticotropin-releasing factor receptor type 2 (CRF-R2). Previous studies have shown that centrally administered Ucn3 decreases food intake in rats. However, the role of Ucn3 in the regulation of gut motility remains to be determined. In the present study, we investigated the effects of peripherally administered Ucn3 on food intake and gastric emptying in mice. After intraperitoneal (i.p.) administrati...

  17. 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...

  18. 40 CFR 147.52 - State-administered program-Hydraulic Fracturing of Coal Beds.

    Science.gov (United States)

    2010-07-01

    ... Fracturing of Coal Beds. 147.52 Section 147.52 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... PROGRAMS Alabama § 147.52 State-administered program—Hydraulic Fracturing of Coal Beds. The UIC program for hydraulic fracturing of coal beds in the State of Alabama, except those on Indian lands, is the...

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  20. 9 CFR 103.2 - Disposition of animals administered experimental biological products or live organisms.

    Science.gov (United States)

    2010-01-01

    ... 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 BIOLOGICAL PRODUCTS PRIOR TO LICENSING § 103.2 Disposition of animals administered experimental biological products...

  1. 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...

  2. 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...

  3. 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.…

  4. 30 CFR 250.1508 - What must I do when MMS administers written or oral tests?

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What must I do when MMS administers written or oral tests? 250.1508 Section 250.1508 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Well Control...

  5. 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

    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...

  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. 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…

  8. 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

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

    Science.gov (United States)

    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. PMID:6439234

  10. 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

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

    DEFF Research Database (Denmark)

    Plenge, P; Amin, M; Agarwal, A K

    1999-01-01

    OBJECTIVES: To study the prophylactic efficacy of lithium administered every second day to patients with bipolar disorder or recurrent unipolar depressive disorder. METHODS: The study was carried out as a WHO multicentre study in five different psychiatric clinics: Russia (Moscow), Canada (Montreal...

  12. 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....

  13. 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...

  14. The National Council for Geographic Education Standards-Based Geography Test. Intermediate Level. Directions for Administering.

    Science.gov (United States)

    National Council for Geographic Education.

    This document contains a test designed by the National Council for Geographic Education for middle school students to determine what knowledge, skills, and understandings students have developed in geography. The document also contains directions for administering the test, test performance data from a sample of 468 middle school students in 18…

  15. 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…

  16. 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…

  17. 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...

  18. 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)

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    . The existing literature on capnography for endoscopy patients sedated with nurse-administered propofol sedation (NAPS) is limited. Can the addition of capnography to standard monitoring during endoscopy with NAPS reduce the number, duration, and level of hypoxia. Materials and methods. This study...

  20. Safety evaluation of orally administered afoxolaner and milbemycin oxime in eight-week-old dogs.

    Science.gov (United States)

    Drag, M; Saik, J; Harriman, J; Letendre, L; Yoon, S; Larsen, D

    2016-11-27

    The safety profile of afoxolaner (an isoxazoline molecule) when combined with milbemycin oxime (a macrocyclic lactone) was evaluated according to the regulatory requirements when administered six times orally in a soft chewable formulation at a dose of at least 1×, 3×, or 5× the maximum exposure dose in 8-week-old Beagle dogs. Thirty-two healthy puppies (16 males and 16 females) were enrolled and allocated randomly to one of four treatment groups. Three doses were administered at 28-day intervals (Days 0, 28, and 56), followed by three additional doses administered with 14-day intervals (Days 84, 98, and 112). The study ended on Day 126. Treatment groups were as follows: Group 1: untreated, sham-dosed control; Group 2: afoxolaner/milbemycin oxime chews administered at a dose of at least 5 and 1 mg/kg, respectively (1×); Group 3: afoxolaner/milbemycin oxime chews administered at a dose of at least 15 and 3 mg/kg, respectively (3); and Group 4: afoxolaner/milbemycin oxime chews administered at a dose of at least 25 and 5 mg/kg, respectively (5×). All dogs were examined for general health twice a day beginning on Day -14. Physical examinations, and blood collections for clinical pathology analysis and afoxolaner and milbemycin oxime plasma concentrations, were performed throughout the study. No afoxolaner/milbemycin oxime treatment-related changes were observed in growth, physical variables, clinical pathology variables, or tissues examined histologically. No clinically relevant or statistically significant health abnormalities related to the administration of afoxolaner/milbemycin oxime were observed. No signs of macrocyclic lactone sensitivity were observed at any time during the study. Vomiting and diarrhea were observed sporadically across all groups including the controls. Based upon the results of this study, afoxolaner/milbemycin oxime soft chewables were shown to be safe when administered repeatedly at up to 5× the maximum exposure dose in dogs as

  1. Ghrelin and gastric acid secretion

    OpenAIRE

    Yakabi, Koji; Kawashima, Junichi; Kato, Shingo

    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 in-vivo experiment. In t...

  2. Safety evaluation of orally administered afoxolaner in 8-week-old dogs.

    Science.gov (United States)

    Drag, Marlene; Saik, Judith; Harriman, Jay; Larsen, Diane

    2014-04-02

    The safety profile of afoxolaner, a new isoxazoline molecule, was evaluated following the regulatory requirements when administered six times orally in a soft chewable formulation at a dose of at least 1×, 3× or 5× the maximum exposure dose (6.3mg/kg) in 8-week-old Beagle dogs. Thirty-two healthy puppies (16 males and 16 females) were enrolled and allocated randomly to one of four treatment groups. Treatments were administered at three, one-month dose intervals (Days 0, 28 and 56) followed by three, 2-week dose intervals (Days 84, 98 and 112). The study ended at Day 126. The groups were: Group 1: non-treated control; Group 2: afoxolaner chews administered at a dosage of at least 6.3mg/kg (1×); Group 3: afoxolaner chews administered at a dosage of at least 18.9 mg/kg (3×); and Group 4: afoxolaner chews administered at a dosage of at least 31.5mg/kg (5×). All dogs were examined for general health twice a day beginning on at least Day-14. Physical examinations, and blood collections for clinical pathology analysis and afoxolaner plasma concentrations, were performed throughout the study. On Day 126, 2 weeks following the last treatment, all dogs were humanely euthanized prior to the conduction of a full necropsy with tissue collection. No afoxolaner-related changes were observed in growth, physical variables, clinical pathology variables, or tissues examined histologically. No clinically or statistically significant health abnormalities related to the administration of afoxolaner were observed. Vomiting and diarrhea were observed sporadically across all groups including the controls. The kinetics of afoxolaner plasma concentrations was linear following 6 doses of 6.3, 18.9 and 31.5mg/kg and dose proportionality was demonstrated. There were no statistical differences (pafoxolaner was shown to be safe when administered repeatedly in a soft chewable formulation at up to 5× the maximum exposure dose in dogs as young as 8 weeks of age.

  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. Characterization of acute biliary hyperplasia in Fisher 344 rats administered the indole-3-carbinol analog, NSC-743380.

    Science.gov (United States)

    Eldridge, Sandy R; Covey, Joseph; Morris, Joel; Fang, Bingliang; Horn, Thomas L; Elsass, Karen E; Hamre, John R; McCormick, David L; Davis, Myrtle A

    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 100mg/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 100mg/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.

  5. Survival and digestibility of orally-administered immunoglobulin preparations containing IgG through the gastrointestinal tract in humans.

    Science.gov (United States)

    Jasion, Victoria S; Burnett, Bruce P

    2015-03-07

    Oral immunoglobulin (Ig) preparations are prime examples of medicinal nutrition from natural sources. Plasma products containing Ig have been used for decades in animal feed for intestinal disorders to mitigate the damaging effects of early weaning. These preparations reduce overall mortality and increase feed utilization in various animal species leading to improved growth. Oral administration of Ig preparations from human serum as well as bovine colostrum and serum have been tested and proven to be safe as well as effective in human clinical trials for a variety of enteric microbial infections and other conditions which cause diarrhea. In infants, children, and adults, the amount of intact IgG recovered in stool ranges from trace amounts up to 25% of the original amount ingested. It is generally understood that IgG can only bind to antigens within the GI tract if the Fab structure is intact and has not been completely denatured through acidic pH or digestive proteolytic enzymes. This is a comprehensive review of human studies regarding the survivability of orally-administered Ig preparations, with a focus on IgG. This review also highlights various biochemical studies on IgG which potentially explain which structural elements are responsible for increased stability against digestion.

  6. Ursodeoxycholic acid for primary biliary cirrhosis

    DEFF Research Database (Denmark)

    Rudic, Jelena S; Poropat, Goran; Krstic, Miodrag N;

    2012-01-01

    Ursodeoxycholic acid is administered to patients with primary biliary cirrhosis, a chronic progressive inflammatory autoimmune-mediated liver disease with unknown aetiology. Despite its controversial effects, the U.S. Food and Drug Administration has approved its usage for primary biliary cirrhosis....

  7. Centrally administered urocortin 3 inhibits food intake and gastric emptying in mice.

    Science.gov (United States)

    Ushikai, Miharu; Asakawa, Akihiro; Sakoguchi, Takeo; Tanaka, Chie; Inui, Akio

    2011-04-01

    Urocortin 3 (Ucn3) is recognized as a member of the corticotropin-releasing factor (CRF) family, which plays an important role in regulating food intake. We investigated the effects of centrally administered Ucn3 on food intake and gastric emptying in mice. Intracerebroventricular (ICV)administration of Ucn3 (0.1–1 nmol per mouse) decreased food intake in a dose-dependent manner. The inhibitory effect of Ucn3 on food intake was less potent than that of centrally administered CRF and Urocortin 1. ICV administration of Ucn3 (0.1–1 nmol per mouse) decreased the gastric emptying rate in a dose-dependent manner. Ucn3 decreased food intake in high-fat diet-fed obese mice as well as in lean mice. These results indicated that Ucn3 influences feeding behavior and gut motility, and may be a promising therapeutic target in the treatment of eating and functional gastrointestinal disorders.

  8. 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.

  9. 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.

  10. 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.

  11. [Side effects analyses in consideration of renal function for S-1-administered patients].

    Science.gov (United States)

    Iwai, Mina; Kimura, Michio; Yoshimura, Tomoaki; Yasuda, Tadashi

    2011-06-01

    Although many analyses of S-1 side effects are reported, there are no reports where the analyses of side effects were performed in consideration of renal function, which is an important index of medication dose. Therefore, we investigated side effects in consideration of renal function. The subjects were 163 patients administered S-1 at the Department of Surgery of Ogaki Municipal Hospital, between October 2008 and December 2009. The frequency and severity of side effects were high and serious in the groupwhose creatinine clearance was low. A significant difference was observed among 3 groups with regard to thrombocytopenia and dehydration. In conclusion, we think that pharmacists must take renal function into consideration when administering medication, to keepclose medicinal guidance, and to actively observe progress.

  12. Folic acid

    Science.gov (United States)

    ... taking folic acid by itself, or with L-carnitine a compound similar to an amino acid from ... levels. It is not clear if folic acid supplementation reduces hearing loss in people with normal folate ...

  13. 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.

  14. Justification of administered dose level in brain perfusion imaging with 99mTc-HMPAO

    Science.gov (United States)

    Stefanoyiannis, A. P.; Gerogiannis, I.; Geronikola-Trapali, X.; Armeniakos, I.; Prentakis, A.; Soultanis, S.; Chatziioannou, S. N.

    2011-09-01

    Brain perfusion imaging by means of 99mTc-HMPAO is widely used in the diagnosis of Alzheimer's disease. The administered dose range recommended by the manufacturer and reported in bibliography is rather wide (~ 9.5 - 27 mCi), necessitating further quantitative analysis. In the framework of this study, a quantitative evaluation of the radiopharmaceutical performance for different values of administered dose was carried out, based on image quality indicators. Evaluation of image quality was based on wavelet-generated contrast, noise, and contrast-to-noise ratio indicators, denoted as CI, NI and CNR respectively. Subsequently, a generic image quality index was correlated with the administered dose, to produce an overall performance indicator (denoted as PI). Application of appropriate statistical tests (analysis of variance for normal and Kruskal-Wallis test for non-normal distributions) showed that there is a statistically significant difference in CI (p 0.05) values. Application of Tukey test for CI and NI normal distributions demonstrated that CI (10 mCi) = CI (20 mCi) NI (20 mCi), while NI (15 mCi) could not be characterised. Finally, application of non-parametric multiple comparisons showed that CNR (20 mCi) < CNR (10 mCi), while CNR (15 mCi) could not be characterised. Consequently, brain perfusion imaging, by means of 99mTc-HMPAO utilising an administered dose of 20 mCi, results in improved image quality on the basis of the estimated indicators. Additionally, this image quality improvement is sufficient to justify the increased patient radiation burden.

  15. Pain in adolescent girls receiving human papillomavirus vaccine with concomitantly administered vaccines.

    Science.gov (United States)

    Walter, Emmanuel B; Kemper, Alex R; Dolor, Rowena J; Dunne, Eileen F

    2015-02-01

    Using the Faces Pain Scale - Revised, we assessed injection site pain 10 minutes after vaccination in young females randomized to receive either quadrivalent human papillomavirus vaccine (HPV4) before or after concomitantly administered vaccines. Although pain was modestly more after HPV4 injection than after other vaccines, the pain intensity after HPV4 injection was significantly less in those who received HPV4 before receiving other concomitant vaccines.

  16. Influence of emotional stress on pharmacokinetics of isosorbide dinitrate intraperitoneally administered to rats.

    Directory of Open Access Journals (Sweden)

    Gomita,Yutaka

    1990-02-01

    Full Text Available The plasma level of isosorbide dinitrate intraperitoneally administered to rats stressed by foot-shock was almost the same as that in non-stressed control rats. However, levels of its metabolites, 5-isosorbide mononitrate and 2-isosorbide mononitrate, were lower in stressed rats than in non-stressed rats, suggesting that stress may influence the metabolism and/or excretion of the metabolites.

  17. 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

  18. 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 administr....... This led to establishment of an in vitro/in vivo correlation for this particular formulation....

  19. Dissociable neural activity to self- vs. externally administered thermal hyperalgesia: a parametric fMRI study.

    Science.gov (United States)

    Mohr, C; Leyendecker, S; Helmchen, C

    2008-02-01

    Little is known regarding how cognitive strategies help to modulate neural responses of the human brain in ongoing pain syndromes to alleviate pain. Under pathological pain conditions, any self-elicited contact with usually non-painful stimuli may become painful. We examined whether the human brain is capable of dissociating self-controlled from externally administered thermal hyperalgesia in the experimental capsaicin model. Using functional magnetic resonance imaging, 17 male subjects were investigated in a parametric design with heat stimuli at topically capsaicin-sensitized skin. In contrast to external stimulation, self-administered pain was controllable. For both conditions application trials without noticeable thermal stimulation were introduced and used as high-level baseline (HLB) to account for the capsaicin-induced ongoing pain and other covariables. Following subtraction of the HLB, the anterior insula and the anterior cingulate cortex (ACC) but not the somatosensory cortices maintained parametric neural responses to thermal hyperalgesia. A stronger pain-related activity increase during self-administered stimuli was observed in the posterior insula. In contrast, prefrontal cortex showed stronger increases to uncontrollable external heat stimuli. In the state of ongoing pain (capsaicin), pain-intensity-encoding regions (anterior insula, ACC) but not those with sensory discriminative functions (SI, SII) showed graded, pain-intensity-related neural responses in thermal hyperalgesia. Some areas were able to dissociate between self- and externally administered stimuli in thermal hyperalgesia, which might be related to differences in perceived controllability. Thus, neural mechanisms maintain the ability to dissociate external from self-generated states of injury in thermal hyperalgesia. This may help to understand how cognitive strategies potentially alleviate chronic pain syndromes.

  20. Orally administered melatonin prevents lipopolysaccharide-induced neural tube defects in mice.

    Directory of Open Access Journals (Sweden)

    Lin Fu

    Full Text Available Lipopolysaccharide (LPS has been associated with adverse pregnant outcomes, including fetal demise, intra-uterine growth restriction (IUGR, neural tube defects (NTDs and preterm delivery in rodent animals. Previous studies demonstrated that melatonin protected against LPS-induced fetal demise, IUGR and preterm delivery. The aim of the present study was to investigate the effects of melatonin on LPS-induced NTDs. All pregnant mice except controls were intraperitoneally injected with LPS (25 µg/kg daily from gestational day (GD8 to GD12. Some pregnant mice were orally administered with melatonin (MT, 50 mg/kg before each LPS injection. A five-day LPS injection resulted in 27.5% of fetuses with anencephaly, exencephaly or encephalomeningocele. Additional experiment showed that maternal LPS exposure significantly down-regulated placental proton-coupled folate transporter (pcft and disturbed folate transport from maternal circulation through the placentas into the fetus. Interestingly, melatonin significantly attenuated LPS-induced down-regulation of placental pcft. Moreover, melatonin markedly improved the transport of folate from maternal circulation through the placentas into the fetus. Correspondingly, orally administered melatonin reduced the incidence of LPS-induced anencephaly, exencephaly or encephalomeningocele. Taken together, these results suggest that orally administered melatonin prevents LPS-induced NTDs through alleviating LPS-induced disturbance of folate transport from maternal circulation through the placenta into the fetus.

  1. Recommended administered activities for {sup 68}Ga-labelled peptides in paediatric nuclear medicine

    Energy Technology Data Exchange (ETDEWEB)

    Machado, J.S.; Beykan, S.; Lassmann, M. [University Hospital Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Herrmann, K. [University Hospital Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); David Geffen School of Medicine at UCLA, Department of Molecular and Medical Pharmacology, Los Angeles, CA (United States)

    2016-10-15

    The aim of this study was to establish a method for determining administered activities for {sup 68}Ga-labelled peptides. Dose calculations were based on the weight-independent effective dose model proposed by the EANM paediatric dosage card for use in paediatric nuclear medicine. Previously published time-integrated activity coefficients for {sup 68}Ga-DOTATATE, {sup 68}Ga-DOTATOC and {sup 68}Ga-pentixafor were used to calculate age-independent effective doses. Consequently, the corresponding weight-dependent effective dose coefficients were rescaled according to the formalism of the EANM dosage card to determine the radiopharmaceutical class of {sup 68}Ga-labelled peptides (''multiples'') and to calculate the baseline activities based on an upper limit for administered activity (185 MBq) in an adult. All calculated normalization factors suggest that the {sup 68}Ga-labelled peptides are class ''B'' radiopharmaceuticals. The baseline activity for all compounds is 12.8 MBq. In analogy to {sup 18}F-fluoride, we recommend a minimum activity of 14 MBq. For paediatric nuclear medicine applications involving {sup 68}Ga-labelled peptides, we suggest determining administered activities based on the formalism proposed in this work. The corresponding effective doses from these procedures will remain age-independent. (orig.)

  2. 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.

  3. An Experimental Study on Blood according to the administered dosage of Carthami Flos

    Directory of Open Access Journals (Sweden)

    Cho, Hoo-Lee

    2006-12-01

    Full Text Available Objectives : The purpose of this study is to examine what are the effect of Carthami Flos on Blood according to the administered dosage. Methods : thrity Sprague-Dawleys rats of starved during 3 days were used and divided 3 groups ; Normal group ; Experimental group that were administered Carthmi Flos 117mg/200g(Sample1 ; Experimental group that were administered Carthmi Flos 936mg/200g(Sample2. and the observerd blood(RBC, Hct, Hb, MCV, MCH, MCHC, PLT, WBC NEUT, LYM, MONO, EOSIN. Results : the result were obtained as follows ; 1. RBC, Hb, MCHC were significantly increased, and MCV were decreased in Sample1.(p<0.05 2. PLT, MCHC, LYM were significantly increased, and Hct, MCV were decreased in Sample2.(p<0.05 Conclusions : According th the above result, it was consided that a small quantity dosage of Carthami Flos was nourished the blood, and a large quantity of that was curative for thrombosis and elevated blood viscosity and it is suggested that more interest and study in the mechanism and clinical use were needed

  4. 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.

  5. Intravenous tranexamic acid for hyperacute primary intracerebral hemorrhage

    DEFF Research Database (Denmark)

    Sprigg, Nikola; Robson, Katie; Bath, Philip

    2016-01-01

    RATIONALE: Outcome after intracerebral hemorrhage remains poor. Tranexamic acid is easy to administer, readily available, inexpensive, and effective in other hemorrhagic conditions. AIM: This randomized trial aims to test the hypothesis that intravenous tranexamic acid given within 8 h of spontan...

  6. 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…

  7. 40 CFR 147.1601 - State-administered program-Class I, III, IV and V wells.

    Science.gov (United States)

    2010-07-01

    ... lands, is the program administered by the New Mexico Water Quality Control Commission, the Environmental...). (c)(1) The Memorandum of Agreement between EPA Region VI and the New Mexico Water Quality Control... CONTROL PROGRAMS New Mexico § 147.1601 State-administered program—Class I, III, IV and V wells. The...

  8. 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...

  9. 40 CFR 147.1250 - State-administered program-Class I, III, IV, and V wells.

    Science.gov (United States)

    2010-07-01

    ... CONTROL PROGRAMS Mississippi § 147.1250 State-administered program—Class I, III, IV, and V wells. The UIC program for Class I, III, IV and V wells in the State of Mississippi, except those on Indian lands, is the... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class...

  10. 40 CFR 147.200 - State-administered program-Class I, III, IV, and V wells.

    Science.gov (United States)

    2010-07-01

    ... CONTROL PROGRAMS Arkansas § 147.200 State-administered program—Class I, III, IV, and V wells. The UIC program for Class I, III, IV and V wells in the State of Arkansas, except those wells on Indian lands, is... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class...

  11. 40 CFR 147.500 - State-administered program-Class I, III, IV, and V wells.

    Science.gov (United States)

    2010-07-01

    ... CONTROL PROGRAMS Florida § 147.500 State-administered program—Class I, III, IV, and V wells. The UIC program for Class I, III, IV, and V wells in the State of Florida, except for those on Indian lands is... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class...

  12. 40 CFR 147.700 - State-administered program-Class I, III, IV, and V wells.

    Science.gov (United States)

    2010-07-01

    ... CONTROL PROGRAMS Illinois § 147.700 State-administered program—Class I, III, IV, and V wells. The UIC program for Class I, III, IV and V wells in the State of Illinois, except those on Indian lands, is the... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class...

  13. 40 CFR 147.850 - State-administered program-Class I, III, IV and V wells.

    Science.gov (United States)

    2010-07-01

    ... PROGRAMS Kansas § 147.850 State-administered program—Class I, III, IV and V wells. The UIC program for Class I, III, IV and V wells in the State of Kansas, except those on Indian lands as described in § 147... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class...

  14. 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

  15. Ghrelin and gastric acid secretion.

    Science.gov (United States)

    Yakabi, Koji; Kawashima, Junichi; Kato, Shingo

    2008-11-07

    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 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-induced 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 acid 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.

  16. Exposure control practices for administering nitrous oxide: a survey of dentists, dental hygienists and dental assistants.

    Science.gov (United States)

    Boiano, James M; Steege, Andrea L; Sweeney, Marie H

    2016-12-12

    Engineering, administrative, and work practice controls have been recommended for many years to minimize exposure to nitrous oxide during dental procedures. To better understand the extent to which these exposure controls are used, the NIOSH Health and Safety Practices Survey of Healthcare Workers was conducted among members of professional practice organizations representing dentists, dental hygienists and dental assistants. The anonymous, modular, web-based survey was completed by 284 dental professionals in private practice who administered nitrous oxide to adult and/or pediatric patients in the seven days prior to the survey. Use of primary engineering controls [i.e., nasal scavenging mask and/or local exhaust ventilation (LEV) near the patient's mouth] was nearly universal, reported by 93% and 96% of respondents who administered to adult (A) and pediatric (P) patients, respectively. However, adherence to other recommended precautionary practices were lacking to varying degrees, and were essentially no different among those administering nitrous oxide to adult or pediatric patients. Examples of work practices which increase exposure risk, expressed as percent of respondents, included: not checking nitrous oxide equipment for leaks (41% A; 48% P); starting nitrous oxide gas flow before delivery mask or airway mask was applied to patient (13% A; 12% P); and not turning off nitrous oxide gas flow before turning off oxygen flow to the patient (8% A; 7% P). Absence of standard procedures to minimize worker exposure to nitrous oxide (13% of all respondents) and not being trained on safe handling and administration of nitrous oxide (3%) were examples of breaches of administrative controls which may also increase exposure risk. Successful management of nitrous oxide emissions should include properly fitted nasal scavenging masks, supplemental LEV (when nitrous oxide levels cannot be adequately controlled using nasal masks alone), adequate general ventilation, regular

  17. 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

    2016-10-02

    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

  18. 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

  19. The relationship between administered radiopharmaceutical activity in myocardial perfusion scintigraphy and imaging outcome

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, C.N.; Aswegen, A. van; Tout, D.A. [Royal Brompton and Harefield NHS Trust, London (United Kingdom); Julious, S.A. [University of Sheffield, Sheffield (United Kingdom); Nunan, T.O. [Guy' s and St Thomas' Hospital NHS Trust, London (United Kingdom); Thomson, W.H. [Sandwell and West Birmingham Hospitals NHS Trust, Birmingham (United Kingdom); Tindale, W.B. [Sheffield Teaching Hospitals, Sheffield (United Kingdom); Underwood, S.R. [Royal Brompton and Harefield NHS Trust, London (United Kingdom); Imperial College London, London (United Kingdom); Royal Brompton Hospital, London (United Kingdom)

    2008-02-15

    Lower radiopharmaceutical activities are used for myocardial perfusion scintigraphy (MPS) in the UK than in other countries. There is no evidence to suggest that higher activities improve imaging or clinical outcome. We undertook a multicentre study of the relationship between radiopharmaceutical activity and imaging outcome. Fifty-one patients with clinical referrals for MPS followed a 2-day protocol with an injection of 1,000 MBq {sup 99m}Tc-tetrofosmin for each of the stress and rest images. ECG-gated acquisition was performed in three rotations occupying 25, 35 and 40% of a standard acquisition, and rotations were summed to simulate administered activities of 250, 400, 750 and 1,000 MBq. Each set of images was reported by an experienced physician who was blinded to all clinical information and to the simulated activity. Scores were assigned for image quality, low count, attenuation and reconstruction artefact, segmental tracer uptake, segmental and global defect classification, and confidence in the global classification. The images were reported twice to assess intra-observer variability. Positive relationships were found between administered activity and overall image quality, observer confidence and intra-observer agreement of uptake score, and a negative relationship was found with low-count artefact. For the majority of comparisons, there was no additional improvement with increasing activity from 750 to 1,000 MBq. Intra-observer agreement was found to be better in female patients and in those below average body mass index. We conclude that higher administered radiopharmaceutical activities lead to better quality images and improved surrogate parameters for clinical outcome, but that activities above 750 MBq may be unnecessary in average patients. (orig.)

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

    Directory of Open Access Journals (Sweden)

    Ackatz Lori E

    2011-05-01

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

  2. Relative bioavailability in man of noscapine administered in lozenges and mixture

    DEFF Research Database (Denmark)

    Jensen, L.N.; Christrup, Lona Louring; Jacobsen, L.

    1992-01-01

    The bioavailability of noscapine base administered in lozenges in a dose of 100 mg to twelve healthy volunteers, in a study using an open balanced cross-over design, was compared with that of 100 mg of noscapine hydrochloride given perorally as a mixture. The bioavailability of noscapine after...... administration in lozenges was significantly higher than that after administration of the drug as a mixture. It is concluded that the lozenges containing noscapine base may be a valuable alternative to the conventional noscapine hydrochloride mixture....

  3. A Review of "Challenging Situations When Administering Palliative 
Chemotherapy--A Nursing Perspective".

    Science.gov (United States)

    Houlihan, Nancy G

    2015-05-01

    The December 2014 issue of the European Journal of Oncology Nursing published an article by Näppä, Rasmussen, Axelsson, and Lindqvist that reported on a qualitative study of the challenges experienced by Swedish nurses when administering palliative cancer treatment at the end of life. The study identified the various clinical scenarios that create dilemmas among nurses. The authors described why chemotherapy at the end of life has become so prevalent and offered strategies to minimize or prevent the moral distress that can occur. Research from the United States identified similar trends in end-of-life treatment and supportive recommendations for multidisciplinary palliative care team collaboration as a solution.

  4. Knee Injury and Osteoarthritis Outcome Score (KOOS)--development of a self-administered outcome measure

    DEFF Research Database (Denmark)

    1998-01-01

    and recreation function, and knee-related quality of life. In this clinical study, the KOOS proved reliable, responsive to surgery and physical therapy, and valid for patients undergoing anterior cruciate ligament reconstruction. The KOOS meets basic criteria of outcome measures and can be used to evaluate......-term patient-relevant outcomes following knee injury, based on the WOMAC Osteoarthritis Index, a literature review, an expert panel, and a pilot study. The Knee injury and Osteoarthritis Outcome Score (KOOS) is self-administered and assesses five outcomes: pain, symptoms, activities of daily living, sport...

  5. 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.

  6. Comparing portable computers with bedside computers when administering medications using bedside medication verification.

    Science.gov (United States)

    Ludwig-Beymer, Patti; Williams, Phillip; Stimac, Ellen

    2012-01-01

    This research examined bedside medication verification administration in 2 adult critical care units, using portable computers and permanent bedside computers. There were no differences in the number of near-miss errors, the time to administer the medications, or nurse perception of ease of medication administration, care of patients, or reliability of technology. The percentage of medications scanned was significantly higher with the use of permanent bedside computers, and nurses using permanent bedside computers were more likely to agree that the computer was always available.

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

    DEFF Research Database (Denmark)

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

    1990-01-01

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

  8. 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. Studies on the metabolism of beta-hydroxy- aspartic acid

    Directory of Open Access Journals (Sweden)

    Ikegami,Takuma

    1975-08-01

    Full Text Available The content of beta-hydroxyaspartic acid was measured in the urine of man and several species of animals. The configuration of urinary beta-hydroxyaspartic acid was deduced to be L-erythro in form by chromatographic comparisons with authentic samples. An increased excretion of urinary beta-hydroxyaspartic acid was observed in cats when serine or thiamine was administered with glycine. Glycine-1-14C administered to rats was incorporated into the urinary beta-hydroxyaspartic acid. The formation of beta-hydroxyaspartic acid in pig-liver homogenate increased in the presence of glutamate and thiamine pyrophosphate. These results were discussed in relation to the author's working hypothesis on the biosynthesis of beta-hydroxyaspartic acid.

  10. 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.

  11. 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.

  12. 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.

  13. Results of long-term carcinogenicity bioassays on Coca-Cola administered to Sprague-Dawley rats.

    Science.gov (United States)

    Belpoggi, Fiorella; Soffritti, Morando; Tibaldi, Eva; Falcioni, Laura; Bua, Luciano; Trabucco, Francesca

    2006-09-01

    Coca-Cola was invented in May 1886 in Atlanta, Georgia by a pharmacist who, by accident or design, mixed carbonated water with the syrup of sugar, phosphoric acid, caffeine, and other natural flavors to create what is known as "the world's favorite soft drink." Coca-Cola is currently sold in more than 200 countries and in early 2000, the company sold its 10 billionth unit case of Coca-Cola branded products. Given the worldwide consumption of Coca-Cola, a project of experimental bioassays to study its long-term effects when administered as substitute for drinking water on male and female Sprague-Dawley rats was planned and executed. The objective of the project was to study whether and how long-term consumption of Coca-Cola affects the basic tumorigram of test animals. The bioassays were performed on rats beginning at different ages, namely: (a) on males and females exposed since embryonic life or from 7 weeks of age; and (b) on males and females exposed from 30, 39, or 55 weeks of age. Overall, the project included 1999 rats. During the biophase, data were collected on fluid and feed consumption, body weight, and survival. Animals were kept under observation until spontaneous death and underwent complete necropsy. The results indicate: (a) an increase in body weight in all treated animals; (b) a statistically significant increase of the incidence in females, both breeders and offspring, bearing malignant mammary tumors; (c) a statistically significant increase in the incidence of exocrine ademonas of the pancreas in both male and female breeders and offspring; and (d) an increased incidence, albeit not statistically significant, of pancreatic islet cell carcinomas in females, a malignant tumor which occurs very rarely in our historical controls. On the basis of the results of this study, excessive consumption of regular soft-drinks should be generally discouraged, in particular for children and adolescents.

  14. 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)

  15. Effects of peripherally administered urocortin 3 on feeding behavior and gastric emptying in mice.

    Science.gov (United States)

    Terashi, Mutsumi; Asakawa, Akihiro; Cheng, Kai-Chun; Koyama, Ken-Ichiro; Chaolu, Huke; Ushikai, Miharu; Inui, Akio

    2011-03-01

    Human and mouse urocortin 3 (Ucn3) were first identified in 2001. Ucn3 binds selectively to corticotropin-releasing factor receptor type 2 (CRF-R2). Previous studies have shown that centrally administered Ucn3 decreases food intake in rats. However, the role of Ucn3 in the regulation of gut motility remains to be determined. In the present study, we investigated the effects of peripherally administered Ucn3 on food intake and gastric emptying in mice. After intraperitoneal (i.p.) administration of Ucn3, food intake was measured in the light and dark phases, and the rate of gastric emptying was determined. We found that i.p. administration of Ucn3 significantly inhibited feeding behavior in mice, and significantly delayed gastric emptying 1-2 h after administration in a dose-dependent manner. These results suggest that Ucn3 contributes to the modulation of feeding behavior and gut motility. Thus, Ucn3 and CRF-R2 may be involved in the pathogenesis of functional gastrointestinal and eating disorders.

  16. 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

    2014-12-17

    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.

  17. 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.

  18. Effect of self-administered stretching on NIRS-measured oxygenation dynamics.

    Science.gov (United States)

    Kruse, Nicholas T; Scheuermann, Barry W

    2016-03-01

    This study determined human skeletal muscle oxygenation dynamics during and after a single bout of self-administered stretching (SAS) of the plantar flexors. Nine healthy recreationally fit men (n = 7; age = 25·7 years) and women (n = 2; age = 23·5 years) performed two protocols: (i) one bout of SAS for 4 min and (ii) one bout of moderate intensity cycling for 4 min. We used near infrared spectroscopy to measure changes in muscle deoxygenated haemoglobin-myoglobin ([HHb]) and blood volume ([Hbtot ]) of gastrocnemius medialis muscle before, during and after stretching. The SAS caused an increase (Pstretching between 60 and 240 s relative to baseline, but not at 30 s. No significant difference was found for [Hbtot ] at any time interval during SAS. Furthermore, the increase in local blood flow (suggested by [Hbtot ] changes) was found to be significantly increased relative to baseline at 1, 5 and 10 min after SAS, thus providing novel evidence for a poststretch hyperaemia. No significant interaction for [HHb] was found between stretching and cycling conditions, suggesting that the metabolic disturbance during stretching closely resembles moderate intensity exercise. These findings suggest that a single self-administered stretch for 60 s can produce a substantial microcirculatory event and that blood flow may be enhanced for up to 10 min after stretching.

  19. 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)

  20. Increased toxicity when fibrates and statins are administered in combination--a metabolomics approach with rats.

    Science.gov (United States)

    Strauss, V; Mellert, W; Wiemer, J; Leibold, E; Kamp, H; Walk, T; Looser, R; Prokoudine, A; Fabian, E; Krennrich, G; Herold, M; van Ravenzwaay, B

    2012-06-01

    Combination therapies with fibrates and statins are used to treat cardiovascular diseases, because of their synergistic effect on lowering plasma lipids. However, fatal side-effects like rhabdomyolysis followed by acute renal necrosis sometimes occur. To elucidate biochemical changes resulting from the interaction of fibrates and statins, doses of 100 mg/kg fenofibrate, 50mg/kg clofibrate, 70 mg/kg atorvastatin and 200 mg/kg pravastatin as well as combinations thereof were administered to Crl:Wi(Han) rats for 4 weeks. Plasma metabolome profile was measured on study days 7, 14 and 28. Upon study termination, clinical pathology parameters were measured. In a separate experiment plasmakinetic data were measured in male rats after 1 week of drug administration in monotherapy as well as in combinations. Lowering of blood lipid levels as well as toxicological effects, like liver cell degradation (statins) and anemia (fibrates) and distinct blood metabolite level alterations were observed in monotherapy. When fibrates and statins were co-administered metabolite profile interactions were generally underadditive or at the utmost additive according to the linear mixed effect model. However, more metabolite levels were significantly altered during combination therapy. New effects on the antioxidant status and the cardiovascular system were found which may be related to a development of rhabdomyolysis. Accumulation of drugs during the combination therapy was not observed.

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

    Science.gov (United States)

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

    2015-08-10

    Complex and lengthy endoscopic examinations like endoscopic ultrasonography and/or endoscopic retrograde cholangiopancreatography benefit from deep sedation, due to an enhanced quality of examinations, reduced discomfort and anxiety of patients, as well as increased satisfaction for both the patients and medical personnel. Current guidelines support the use of propofol sedation, which has the same rate of adverse effects as traditional sedation with benzodiazepines and/or opioids, but decreases the procedural and recovery time. Non-anesthesiologist administered propofol sedation has become an option in most of the countries, due to limited anesthesiology resources and the increasing evidence from prospective studies and meta-analyses that the procedure is safe with a similar rate of adverse events with traditional sedation. The advantages include a high quality of endoscopic examination, improved satisfaction for patients and doctors, as well as decreased recovery and discharge time. Despite the advantages of non-anesthesiologist administered propofol, there is still a continuous debate related to the successful generalization of the procedures.

  2. Tolerability assessment of a lectin fraction from Tepary bean seeds (Phaseolus acutifolius orally administered to rats

    Directory of Open Access Journals (Sweden)

    Roberto Ferriz-Martínez

    2015-01-01

    Full Text Available Our previous studies have shown that a lectin rich fraction (TBLF extracted from Tepary bean seeds differentially inhibits cancer cells proliferation in vitro. Before testing the in vivo anticancer effect, the acute and subchronic toxicological assays in rats were conducted, where an oral dose of 50 mg/body weight kg was determined as the NOAEL. This study evaluated the resistance to digestion and complete blood count (CBC after 24 h of the orally administered 50 mg/kg TBLF. The digestion resistance test showed lectins activity retention after 72 h and the CBC study showed a high level of eosinophils, suggesting an allergic-like response. Tolerability was assayed after 6 weeks of treatment by dosing with an intragastric cannula every third day per week. It was observed a transient reduction in food intake and body weight in the first weeks, resulting in body weight gain reduction of 10% respect to the control group at the end of the study. Additionally, organs weight, histopathological analysis and blood markers for nutritional status and for liver, pancreas and renal function were not affected. Our results suggest that 50 mg/kg TBLF administered by oral route, exhibit no toxicity in rats and it was well tolerated. Further studies will focus on long-term studies.

  3. Assessing smoking status in disadvantaged populations: is computer administered self report an accurate and acceptable measure?

    Directory of Open Access Journals (Sweden)

    Bryant Jamie

    2011-11-01

    Full Text Available Abstract Background Self report of smoking status is potentially unreliable in certain situations and in high-risk populations. This study aimed to determine the accuracy and acceptability of computer administered self-report of smoking status among a low socioeconomic (SES population. Methods Clients attending a community service organisation for welfare support were invited to complete a cross-sectional touch screen computer health survey. Following survey completion, participants were invited to provide a breath sample to measure exposure to tobacco smoke in expired air. Sensitivity, specificity, positive predictive value and negative predictive value were calculated. Results Three hundred and eighty three participants completed the health survey, and 330 (86% provided a breath sample. Of participants included in the validation analysis, 59% reported being a daily or occasional smoker. Sensitivity was 94.4% and specificity 92.8%. The positive and negative predictive values were 94.9% and 92.0% respectively. The majority of participants reported that the touch screen survey was both enjoyable (79% and easy (88% to complete. Conclusions Computer administered self report is both acceptable and accurate as a method of assessing smoking status among low SES smokers in a community setting. Routine collection of health information using touch-screen computer has the potential to identify smokers and increase provision of support and referral in the community setting.

  4. 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

  5. Pharmacokinetics of the Antiviral Lectin Griffithsin Administered by Different Routes Indicates Multiple Potential Uses

    Directory of Open Access Journals (Sweden)

    Christopher Barton

    2016-12-01

    Full Text Available Griffithsin (GRFT is a red alga-derived lectin with demonstrated broad spectrum antiviral activity against enveloped viruses, including severe acute respiratory syndrome–Coronavirus (SARS-CoV, Japanese encephalitis virus (JEV, hepatitis C virus (HCV, and herpes simplex virus-2 (HSV-2. However, its pharmacokinetic profile remains largely undefined. Here, Sprague Dawley rats were administered a single dose of GRFT at 10 or 20 mg/kg by intravenous, oral, and subcutaneous routes, respectively, and serum GRFT levels were measured at select time points. In addition, the potential for systemic accumulation after oral dosing was assessed in rats after 10 daily treatments with GRFT (20 or 40 mg/kg. We found that parenterally-administered GRFT in rats displayed a complex elimination profile, which varied according to administration routes. However, GRFT was not orally bioavailable, even after chronic treatment. Nonetheless, active GRFT capable of neutralizing HIV-Env pseudoviruses was detected in rat fecal extracts after chronic oral dosing. These findings support further evaluation of GRFT for pre-exposure prophylaxis against emerging epidemics for which specific therapeutics are not available, including systemic and enteric infections caused by susceptible enveloped viruses. In addition, GRFT should be considered for antiviral therapy and the prevention of rectal transmission of HIV-1 and other susceptible viruses.

  6. 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...

  7. [Clinical study of astromicin administered by intravenous drip infusion against chronic complicated urinary tract infections].

    Science.gov (United States)

    Suzuki, K; Takanashi, K; Nagakubo, I; Kiyosaki, H; Naide, Y

    1987-07-01

    Astromicin (ASTM) was administered by intravenous drip infusion (i.v.d.) to 22 patients with chronic complicated urinary tract infections and the clinical efficacy and safety of this drug were evaluated. The overall clinical efficacy rate obtained was 71.4% (excellent 6; moderate 9) of 21 evaluable cases by the UTI committee's criteria. Concerning the response on clinical isolates, the drug was highly effective especially against strains of Escherichia coli, indole positive Proteus and Serratia marcescens. It was not effective, however, against 2 strains of Pseudomonas aeruginosa. As for adverse reactions, there was one case which complained of headache on the 3rd day after starting treatment. In this case the drug administration was discontinued at the 5th day. The symptom disappeared within 24 hours without any treatment. No any other adverse reactions were noted. With regard to clinical test values for peripheral blood, liver and renal functions, no abnormality was observed in any of the cases treated with the drug. In conclusion, ASTM was found to be a highly effective and safe drug when administered by intravenous drip infusion in the treatment of chronic complicated urinary tract infections.

  8. Biorelevant in vitro performance testing of orally administered dosage forms-workshop report.

    Science.gov (United States)

    Reppas, Christos; Friedel, Horst-Dieter; Barker, Amy R; Buhse, Lucinda F; Cecil, Todd L; Keitel, Susanne; Kraemer, Johannes; Morris, J Michael; Shah, Vinod P; Stickelmeyer, Mary P; Yomota, Chikako; Brown, Cynthia K

    2014-07-01

    Biorelevant in vitro performance testing of orally administered dosage forms has become an important tool for the assessment of drug product in vivo behavior. An in vitro performance test which mimics the intraluminal performance of an oral dosage form is termed biorelevant. Biorelevant tests have been utilized to decrease the number of in vivo studies required during the drug development process and to mitigate the risk related to in vivo bioequivalence studies. This report reviews the ability of current in vitro performance tests to predict in vivo performance and generate successful in vitro and in vivo correlations for oral dosage forms. It also summarizes efforts to improve the predictability of biorelevant tests. The report is based on the presentations at the 2013 workshop, Biorelevant In Vitro Performance Testing of Orally Administered Dosage Forms, in Washington, DC, sponsored by the FIP Dissolution/Drug Release Focus Group in partnership with the American Association of Pharmaceutical Scientists (AAPS) and a symposium at the AAPS 2012 Annual meeting on the same topic.

  9. InfuShield: a shielded enclosure for administering therapeutic radioisotope treatments using standard syringe pumps.

    Science.gov (United States)

    Rushforth, Dominic P; Pratt, Brenda E; Chittenden, Sarah J; Murray, Iain S; Causer, Louise; Grey, Matthew J; Gear, Jonathan I; Du, Yong; Flux, Glenn D

    2017-03-01

    The administration of radionuclide therapies presents significant radiation protection challenges. The aim of this work was to develop a delivery system for intravenous radioisotope therapies to substantially moderate radiation exposures to staff and operators. A novel device (InfuShield) was designed and tested before being used clinically. The device consists of a shielded enclosure which contains the therapeutic activity and, through the hydraulic action of back-to-back syringes, allows the activity to be administered using a syringe pump external to the enclosure. This enables full access to the pump controls while simultaneously reducing dose to the operator. The system is suitable for use with all commercially available syringe pumps and does not require specific consumables, maximising both the flexibility and economy of the system. Dose rate measurements showed that at key stages in an I mIBG treatment procedure, InfuShield can reduce dose to operators by several orders of magnitude. Tests using typical syringes and infusion speeds show no significant alteration in administered flow rates (maximum of 1.2%). The InfuShield system provides a simple, safe and low cost method of radioisotope administration.

  10. 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.

  11. Orally administered misoprostol for induction of labor with prelabor rupture of membranes at term.

    Science.gov (United States)

    Radoff, Kari A

    2014-01-01

    Prelabor rupture of membranes (PROM) occurs in approximately 8% to 10% of women with term pregnancies. The management of PROM continues to be controversial. Approaches include expectant management and immediate induction of labor. The use of orally administered misoprostol for the management of women with PROM may provide significant advantages when they choose immediate induction of labor. This literature review presents current evidence that supports the use of oral misoprostol for women with PROM, including the benefits of a decreased interval time from PROM to vaginal birth, good safety profile, and reductions in the use of oxytocin augmentation and epidural anesthesia. In addition to clinically proven benefits to women of oral misoprostol for PROM, it also has the potential to reduce chorioamnionitis by reducing the number of sterile vaginal examinations performed thereby reducing the risk of ascending bacteria. Women have also reported acceptability and satisfaction when using oral misoprostol for immediate induction of labor. This review of literature discusses what is known about the use of orally administered misoprostol for the management of term PROM and makes recommendations for clinical use.

  12. Valproic Acid

    Science.gov (United States)

    ... acid is in a class of medications called anticonvulsants. It works by increasing the amount of a ... older (about 1 in 500 people) who took anticonvulsants such as valproic acid to treat various conditions ...

  13. Ascorbic Acid

    Science.gov (United States)

    Ascorbic acid is used to prevent and treat scurvy, a disease caused by a lack of vitamin C ... Ascorbic acid comes in extended-release (long-acting) capsules and tablets, lozenges, syrup, chewable tablets, and liquid drops ...

  14. Amino acids

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002222.htm Amino acids To use the sharing features on this page, please enable JavaScript. Amino acids are organic compounds that combine to form proteins . ...

  15. 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.

  16. 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

  17. 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

  18. 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

  19. Therapeutic time window for the neuroprotective effects of NGF when administered after focal cerebral ischemia.

    Science.gov (United States)

    Yang, Ji-Ping; Liu, Huai-Jun; Yang, Hua; Feng, Ping-Yong

    2011-06-01

    In the present study, we evaluated the neuroprotection time window for nerve growth factor (NGF) after ischemia/reperfusion brain injury in rabbits as related to this anti-apoptosis mechanism. Male New Zealand rabbits were subjected to 2 h of middle cerebral artery occlusion (MCAO), followed by 70 h of reperfusion. NGF was administered after injury to evaluate the time window. Neurological deficits, infarct volume, neural cell apoptosis and expressions of caspase-3 and Bcl-2 were measured. Compared to saline-treated control, NGF treatment at 2, 3 and 5 h after MCAO significantly reduced infarct volume, neural cell apoptosis and expression of caspase-3 (P NGF provides an extended time window of up to 5 h after ischemia/reperfusion brain injury, in part by attenuating the apoptosis.

  20. 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 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...... 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....

  1. Sähköisen taloushallintojärjestelmän kirjanpidon opas - Case Administer Oy

    OpenAIRE

    Hänninen, Eeva-Maria

    2013-01-01

    Opinnäytetyön toimeksiantajana toimii Administer Oy, joka on sähköisiin taloushallintopalveluihin erikoistunut tilitoimisto. Yrityksellä on käytössään sen itse kehittämä taloushallintojärjestelmä eFina. Järjestelmälle ei ole ollut saatavissa käyttöohjeita, minkä vuoksi yrityksellä oli tarve oppaalle. Opas rajattiin koskemaan järjestelmän kirjanpidon osiota jättäen maksuliikenne, osto- ja myyntireskontra sekä muut järjestelmän osat työn ulkopuolelle. Tällä vältettiin opinnäytetyön liiallinen l...

  2. 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.

  3. Effect of subcutaneously administered diclazuril on the output of Eimeria species oocysts by experimentally infected rabbits.

    Science.gov (United States)

    Pan, B L; Zhang, Y F; Suo, X; Xue, Y

    2008-02-02

    The effect of subcutaneously injected diclazuril on the output of Eimeria species oocysts was studied in experimentally infected rabbits. Diclazuril was administered either prophylactically at 0.5, 1 or 2 mg/kg bodyweight two days before each rabbit was inoculated with 20,000 oocysts of a mixed-species field isolate of Eimeria or therapeutically at 1, 2 or 4 mg/kg bodyweight five days after they were inoculated. The prophylactic treatments significantly reduced (PEimeria stiedae, Eimeria magna, Eimeria irresidua, Eimeria flavescens, Eimeria piriformis and Eimeria intestinalis was significantly reduced (P<0.05) in all the treated groups. The burden of oocysts in the livers of the therapeutic groups (4000 to 9000) were significantly lower (P<0.05) than in the inoculated but untreated control group (23,000), but higher than in the prophylactic groups (around 1000).

  4. Actions of salbutamol, disodium cromoglycate, and placebo administered as aerosols in acute asthma.

    Science.gov (United States)

    Hasham, F; Kennedy, J D; Jones, R S

    1981-01-01

    The effects on the peak expiratory flow rate of the drug sequences, placebo-salbutamol-disodium cromoglycate and placebo-disodium cromoglycate-salbutamol administered via a nebuliser were examined in 35 children with asthma. Twenty children were each examined once within 4 hours of admission to hospital with an acute attack of asthma, and the remaining 15 children were examined later in the attack on two occasions. The placebo effect of sterile water accounted for about half of the total bronchodilator action both early and late in the attack. It is suggested that this effect is due to the action of water on the surface film of surfactant, causing collapse of bubbles and strands or webs of mucoid material, thus decreasing airways resistance. At this time salbutamol is significantly more potent than disodium cromoglycate as a bronchodilator agent. PMID:6794462

  5. Exposure variability of fosfomycin administered to pigs in food or water: impact of social rank.

    Science.gov (United States)

    Soraci, Alejandro L; Amanto, Fabián; Tapia, María O; de la Torre, Eulalia; Toutain, Pierre-Louis

    2014-02-01

    The objective of this study was to document the effect of social ranking on the internal exposure of pigs to an antibiotic (fosfomycin) administered either in food or in drinking water. Signs of aggression were recorded at the feeder and drinker. The interindividual variability explained by the social rank was even greater when the test antibiotic was given in food despite the fact that the water consumption was less variable than the food intake. The range of plasma concentrations after administration of fosfomycin either in food or drinking water leads to a number of pigs in the treated group being exposed to rather low and highly variable concentrations of fosfomycin and not able to maintain adequate plasma concentrations above the typical minimum inhibitory concentration (MIC). Social rank clearly influences the level of exposure of pigs to fosfomycin both in food and drinking. However, its administration in drinking water is likely to be the best option to optimize antibiotic efficacy.

  6. 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.

  7. Influenza vaccine concurrently administered with a combination measles, mumps, and rubella vaccine to young children.

    Science.gov (United States)

    Lum, Lucy Chai See; Borja-Tabora, Charissa Fay; Breiman, Robert F; Vesikari, Timo; Sablan, Benjamin P; Chay, Oh Moh; Tantracheewathorn, Taweewong; Schmitt, Heinz-Josef; Lau, Yu-Lung; Bowonkiratikachorn, Piyaporn; Tam, John S; Lee, Bee Wah; Tan, Kah Kee; Pejcz, Jerzy; Cha, Sungho; Gutierrez-Brito, Maricruz; Kaltenis, Petras; Vertruyen, Andre; Czajka, Hanna; Bojarskas, Jurgis; Brooks, W Abdullah; Cheng, Sheau-Mei; Rappaport, Ruth; Baker, Sherryl; Gruber, William C; Forrest, Bruce D

    2010-02-10

    Children aged 11 to vaccine (LAIV) or placebo, 35+/-7 days apart. Dose 1 was administered concomitantly with a combined measles, mumps, and rubella vaccine (Priorix). Seroresponses to measles and mumps were similar between groups. Compared with placebo, response rates to rubella in LAIV+Priorix recipients were statistically lower at a 15 IU/mL threshold (83.9% vs 78.0%) and the prespecified noninferiority criteria were not met. In a post hoc analysis using an alternate widely accepted threshold of 10 IU/mL, the noninferiority criteria were met (93.4% vs 89.8%). Concomitant administration with Priorix did not affect the overall influenza protection rate of LAIV (78.4% and 63.8% against antigenically similar influenza strains and any strain, respectively).

  8. User requirements for a practice-integrated nurse-administered online communication service for cancer patients.

    Science.gov (United States)

    Ruland, Cornelia M; Borosund, Elin; Varsi, Cecilie

    2009-01-01

    This paper describes the use of participatory design methods in the development of a nurse-administered online patient-provider communication (OPPC) service that is designed to be integrated into routine clinical practice. The OPPC service let patients stay connected with expert nurses and other health care providers to ask questions and receive advice from home. Through focus groups, workshops, heuristic evaluations and usability testing, we identified patients' and clinicians' (nurses' and physicians') user requirements, factors important for successful adoption, implementation and maintenance of the OPPC service, and usability. This paper shares important insights from these participatory design processes that may be helpful for other researchers who wish to implement clinical applications into routine practice.

  9. 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.

  10. [Inhibition of Candida mycelia growth by a medium chain fatty acids, capric acid in vitro and its therapeutic efficacy in murine oral candidiasis].

    Science.gov (United States)

    Takahashi, Miki; Inoue, Shigeharu; Hayama, Kazumi; Ninomiya, Kentaro; Abe, Shigeru

    2012-01-01

    We assessed anti-C. albicans activities of the 4 fatty acids : caproic acid, caprylic acid, capric acid and lauric acid in vitro. All four inhibited not only the mycelial but also the yeast-form growth of Candida albicans. In particular, capric acid and caprylic acid inhibited Candida mycelia growth at very low concentrations. The effects of treatment of these two fatty acids on oral candidiasis were examined using a murine model. When 50 µl of capric acid (more than 48.8 µM) was administered three times into the oral cavity of Candida-infected mice, symptom scores of tongues of the mice were significantly improved. Histological studies of the capric acid-treated animals indicated that the fatty acid suppressed mycelial growth of the fungus on the tongue surface. These results suggest that all four fatty acids, and especially capric acid, have potential as substances supporting anti-Candida treatment.

  11. 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.

  12. 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.

  13. Muscle protein metabolism in neonatal alloxan-administered rats: effects of continuous and intermittent swimming training

    Directory of Open Access Journals (Sweden)

    Ribeiro Carla

    2012-02-01

    Full Text Available Abstract Background This study aimed to examine the effects of intermittent and continuous swimming training on muscle protein metabolism in neonatal alloxan-administered rats. Methods Wistar rats were used and divided into six groups: sedentary alloxan (SA, sedentary control (SC, continuous trained alloxan (CA, intermittent trained alloxan (IA, continuous trained control (CC and intermittent trained control (IC. Alloxan (250 mg/kg body weight was injected into newborn rats at 6 days of age. The continuous training protocol consisted of 12 weeks of swimming training in individual cylinder tanks while supporting a load that was 5% of body weight; uninterrupted swimming for 1 h/day, five days a week. The intermittent training protocol consisted of 12 weeks of swimming training in individual cylinder tanks while supporting a load that was 15% of body weight; 30 s of activity interrupted by 30 s of rest for a total of 20 min/day, five days a week. Results At 28 days, the alloxan animals displayed higher glycemia after glucose overload than the control animals. No differences in insulinemia among the groups were detected. At 120 days, no differences in serum albumin and total protein among the groups were observed. Compared to the other groups, DNA concentrations were higher in the alloxan animals that were subjected to continuous training, whereas the DNA/protein ratio was higher in the alloxan animals that were subjected to intermittent training. Conclusion It was concluded that continuous and intermittent training sessions were effective in altering muscle growth by hyperplasia and hypertrophy, respectively, in alloxan-administered animals.

  14. 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.

  15. 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.

  16. Adherence to safe handling guidelines by health care workers who administer antineoplastic drugs.

    Science.gov (United States)

    Boiano, James M; Steege, Andrea L; Sweeney, Marie H

    2014-01-01

    The toxicity of antineoplastic drugs is well documented. Many are known or suspected human carcinogens where no safe exposure level exists. Authoritative guidelines developed by professional practice organizations and federal agencies for the safe handling of these hazardous drugs have been available for nearly three decades. As a means of evaluating the extent of use of primary prevention practices such as engineering, administrative and work practice controls, personal protective equipment (PPE), and barriers to using PPE, the National Institute for Safety and Health (NIOSH) conducted a web survey of health care workers in 2011. The study population primarily included members of professional practice organizations representing health care occupations which routinely use or come in contact with selected chemical agents. All respondents who indicated that they administered antineoplastic drugs in the past week were eligible to complete a hazard module addressing self-reported health and safety practices on this topic. Most (98%) of the 2069 respondents of this module were nurses. Working primarily in hospitals, outpatient care centers, and physician offices, respondents reported that they had collectively administered over 90 specific antineoplastic drugs in the past week, with carboplatin, cyclophosphamide, and paclitaxel the most common. Examples of activities which increase exposure risk, expressed as percent of respondents, included: failure to wear nonabsorbent gown with closed front and tight cuffs (42%); intravenous (I.V.) tubing primed with antineoplastic drug by respondent (6%) or by pharmacy (12%); potentially contaminated clothing taken home (12%); spill or leak of antineoplastic drug during administration (12%); failure to wear chemotherapy gloves (12%); and lack of hazard awareness training (4%). The most common reason for not wearing gloves or gowns was "skin exposure was minimal"; 4% of respondents, however, reported skin contact during handling and

  17. Development of macrolide-resistant Campylobacter in broilers administered subtherapeutic or therapeutic concentrations of tylosin.

    Science.gov (United States)

    Ladely, Scott R; Harrison, Mark A; Fedorka-Cray, Paula J; Berrang, Mark E; Englen, Mark D; Meinersmann, Richard J

    2007-08-01

    The use of antimicrobials in food animal production, particularly those commonly used to treat infections in humans, has become a source of debate in recent years. However, limited data are available regarding the development of resistance following the subtherapeutic or therapeutic administration of antimicrobials in animal production. The objective of this study was to evaluate the effect of the administration of therapeutic and subtherapeutic concentrations of tylosin on the erythromycin susceptibility of Campylobacter jejuni and Campylobacter coli isolated from the ceca of treated broilers. In three replicated studies, day-of-hatch chicks were exposed to macrolide-susceptible C. jejuni or C. coli. At 2 weeks of age, tylosin was administered at subtherapeutic (22 ppm, continuously in the diet) or therapeutic concentrations (529 ppm, in the drinking water for 5 days). Broilers were sacrificed weekly. Total and erythromycin-resistant Campylobacter spp. were enumerated from individual ceca plus cecal contents. Overall erythromycin resistance was observed at a higher frequency (P tylosin administration. Across Campylobacter species, erythromycin resistance was observed at a higher frequency (P tylosin was administered at subtherapeutic (62.7%) than at therapeutic (11.4%) concentrations. Subtherapeutic administration resulted in the recovery of 83.3 and 56.1% erythromycin-resistant isolates compared with only 33.3 and 7.9% of the isolates expressing erythromycin resistance following the administration of therapeutic concentrations for C. coli and C. jejuni, respectively. Further studies are needed to determine the factors involved in the apparent difference in the acquisition of macrolide resistance in C. coli compared with C. jejuni.

  18. Chronic effects of the novel glucocorticosteroid RPR 106541 administered to beagle dogs by inhalation.

    Science.gov (United States)

    Miller, G K; Valerio, M G; Pino, M V; Larson, J L; Viau, A; Hamelin, N; Labbé, R; Banks, C M

    2000-01-01

    The preclinical safety of RPR 106541, a novel 17-thiosteroid, was evaluated in young adult and mature dogs by inhalation exposure for 26 weeks and 52 weeks, respectively. A dry powder formulation of RPR 106541 in lactose was administered to young adult dogs (approximately 6 months of age at initiation) at doses of 0 (air and placebo controls), 10, 100, or 1,000 microg/kg/d for 26 weeks. A solution-based aerosol formulation was administered to mature dogs (approximately 10 months at initiation) from a pressurized metered dose inhaler at 0 (air and placebo controls), 10, 50, and 150 microg/kg/d for 52 weeks. Clinical evidence of glucocorticosteroid-induced immunosuppression was observed by weeks 20-26 following relatively high dose exposures (100 microg/kg/d and 1,000 microg/kg/d) in young dogs receiving the dry powder formulation for 26 weeks. Classic glucocorticosteroid effects were observed, including adrenocortical atrophy, reduced bone mass with retention of epiphyseal growth plates in long bones, prominence of stromal adipose tissue in bone marrow, and atrophy of lymphoid tissues. Inhalation administration of RPR 106541 to sexually mature dogs facilitated more definitive characterization of endocrine affects of RPR 106541 as compared with administration in younger, sexually immature animals. Significant effects in female reproductive organs included absence of corpora lutea in association with atresia of vesicular follicles within the ovaries, endometrial hyperplasia, and lobular development of mammary tissue. Discordant development of mammary tissue, accumulation of secretory material within hyperplastic endometrial glands, and hypertrophy of uterine lining epithelium in absence of ovulation were consistent with a secondary progestin effect by a potent glucocorticosteroid.

  19. 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.

  20. Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles

    Science.gov (United States)

    Davis, Mark E.; Zuckerman, Jonathan E.; Choi, Chung Hang J.; Seligson, David; Tolcher, Anthony; Alabi, Christopher A.; Yen, Yun; Heidel, Jeremy D.; Ribas, Antoni

    2010-01-01

    Therapeutics that are designed to engage RNA interference (RNAi) pathways have the potential to provide new, major ways of imparting therapy to patients.1,2 Fire et al. first demonstrated that long, double stranded RNAs mediate RNAi in Caenorhabditis elegans,3 and Elbashir et al. opened the pathway to the use of RNAi for human therapy by showing that small interfering RNAs (siRNAs: ca. 21 base pair double stranded RNA) can elicit RNAi in mammalian cells without producing an interferon response.4 We are currently conducting the first-in-human Phase I clinical trial involving the systemic administration of siRNA to patients with solid cancers using a targeted, nanoparticle delivery system. Here we provide evidence of inducing an RNAi mechanism of action in a human from the delivered siRNA. Tumor biopsies from melanoma patients obtained after treatment reveal: (i) the presence of intracellularly-localized nanoparticles in amounts that correlate with dose levels of the nanoparticles administered (this is a first for systemically delivered nanoparticles of any kind), and (ii) reduction in both the specific mRNA (M2 subunit of ribonucleotide reductase (RRM2)) and the protein (RRM2) when compared to pre-dosing tissue. Most importantly, we detect the presence of an mRNA fragment that demonstrates siRNA mediated mRNA cleavage occurs specifically at the site predicted for an RNAi mechanism from a patient who received the highest dose of the nanoparticles. These data when taken in total demonstrate that siRNA administered systemically to a human can produce a specific gene inhibition (reduction in mRNA and protein) by an RNAi mechanism of action. PMID:20305636

  1. Developmental toxicity of orally administered sildenafil citrate (Viagra) in SWR/J mice.

    Science.gov (United States)

    Abou-Tarboush, Faisal Mohamed; Abdel-Samad, Mohamed Fathy; Al-Meteri, Mokhlid Hamed

    2011-04-01

    Normal adult inbred SWR/J mice were used to investigate the teratogenic and other possible toxic effects of various dose levels of sildenafil citrate (Viagra) on fetuses. Multiple dose levels of 6.5, 13.0, 19.5, 26.0, 32.5 or 40.0 mg of sildenafil citrate/kg body weight (which correspond to the multiples of 1, 2, 3, 4, 5 or 6 of human 50 mg Viagra, respectively) were orally administered into pregnant mice on days 7-9, 10-12 or 13-15 of gestation. On day 17 of pregnancy, all fetuses were removed and examined for toxic phenomena (embryo-fetal toxicity) and for external, internal and skeletal malformations. A total of 285 pregnant mice were used in the present study. None of the dams treated with sildenafil citrate at any of the oral dose levels used in the present study died during the experimental period and all dams treated with the drug failed to reveal overt signs of maternal toxicity. Moreover, the results of the present study clearly demonstrate that none of the multiple oral dose levels of the drug at any time interval used has induced any external, internal or skeletal malformations in the fetuses obtained from treated females. However, the dose level of 40 mg/kg body weight of sildenafil citrate has a growth suppressing effect on alive fetuses when it was administered at all the time intervals used in the present study. Furthermore, the dose levels 26.0, 32.5 and 40 mg/kg of the drug have embryo-fetal toxicity when the drug is applied on days 13-15 of gestation. The possible mechanisms involved in the embryo-fetal toxicity and fetal growth suppressing effects of sildenafil citrate were discussed. The results of this study have important implications for the widespread use of this drug.

  2. 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.

  3. 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

  4. 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

  5. Fatty acids - trans fatty acids

    Science.gov (United States)

    The data supporting a negative effect of dietary trans fatty acids on cardiovascular disease risk is consistent. The primary dietary sources of trans fatty acids include partially hydrogenated fat and rudiment fat. The adverse effect of trans fatty acids on plasma lipoprotein profiles is consisten...

  6. Successful treatment of acute hereditary angioedema attacks with self-administered icatibant in patients with venous access problems.

    Science.gov (United States)

    Wiednig, Michaela

    2013-04-25

    Hereditary angioedema is a rare and potentially fatal autosomal dominant disorder characterised by unpredictable skin, gastrointestinal tract or respiratory tract oedema. Plasma-derived C1-esterase inhibitors are effective in the prophylaxis or treatment of hereditary angioedema type I and II attacks, but must be administered intravenously. This may be problematic in patients with venous access difficulties. Icatibant, a bradykinin B2-receptor antagonist, is administered subcutaneously. In July 2008 icatibant received approval for healthcare professional-administered treatment of hereditary angioedema attacks in adults. In 2011 it received European Medicines Agency and US Food and Drug Administration licences for patient-administered treatment of hereditary angioedema attacks. Given these approvals, and with the appropriate training, icatibant could provide the opportunity for patients to self-administer treatment. This is one of the first long-term follow-up reports of patients with hereditary angioedema using self-administered icatibant. During follow-up, icatibant remained effective and patient satisfaction was high.

  7. 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...

  8. 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

  9. 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

  10. Effect of Mesalamine and Prednisolone on TNBS Experimental Colitis, following Various Doses of Orally Administered Iron

    Directory of Open Access Journals (Sweden)

    John K. Triantafillidis

    2014-01-01

    Full Text Available Background. Experimental data suggest that oral iron (I. supplementation can worsen colitis in animals. Aim. To investigate the influence of various concentrations of orally administered I. in normal gut mucosa and mucosa of animals with TNBS colitis, as well as the influence of Mesalamine (M. and Prednisolone (P. on the severity of TNBS colitis following orally administered I. Methods and Materials. 156 Wistar rats were allocated into 10 groups. Colitis was induced by TNBS. On the 8th day, all animals were euthanatized. Activity of colitis and extent of tissue damage were assessed histologically. The levels of tissue tumor necrosis factor-α (t-TNF-α and tissue malondialdehyde (t-MDA were estimated in all animal groups. Results. Moderate and high I. supplementation induced inflammation in the healthy colon and increased the activity of the experimentally induced TNBS colitis. Administration of M. on TNBS colitis following moderate iron supplementation (0.3 g/Kg diet resulted in a significant improvement in the overall histological score as well as in two individual histological parameters. M. administration, however, did not significantly reduce the t-TNF-α levels (17.67±4.92 versus 14.58±5.71, P=0.102, although it significantly reduced the t-MDA levels (5.79±1.55 versus 3.67±1.39, P=0.000. Administration of M. on TNBS colitis following high iron supplementation (3.0 g/Kg diet did not improve the overall histological score and the individual histological parameters, neither reduced the levels of t-TNF-α (16.57 ± 5.61 versus 14.65±3.88, P=0.296. However, M. significantly reduced the t-MDA levels (5.99±1.37 versus 4.04±1.41, P=0.000. Administration of P. on TNBS colitis after moderate iron supplementation resulted in a significant improvement in the overall histological score as well as in three individual histological parameters. P. also resulted in a significant reduction in the t-TNF-α levels (17.67±4.92 versus 12.64±3

  11. Okadaic acid

    DEFF Research Database (Denmark)

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

    2014-01-01

    Okadaic acid (OA) is a polyether fatty acid produced by marine dinoflagellates and the causative agent of diarrhetic shellfish poisoning. The effect of OA on apical endocytosis in the small intestine was studied in organ cultured porcine mucosal explants. Within 0.5-1 h of culture, the toxin caused...... 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....

  12. 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.

  13. Subchronic dispositional and toxicological effects of arsenate administered in drinking water to mice.

    Science.gov (United States)

    Hughes, M F; Thompson, D J

    1996-10-11

    Exposure to the drinking water contaminant arsenate is a daily occurrence and there are concerns that this exposure may lead to cancer. Although the acute dispositional effects of arsenate have been studied in detail, there is minimal information on the disposition and toxicological effects of it after continuous exposure. The objective of this study was to examine in mice the effect of a 4-wk treatment with arsenate administered in drinking water. Female B6C3F1 mice (3/cage) were housed in metabolism cages and given water and food ad libitum. Two groups (A, B) of mice were treated (4 cages/treatment/group) with distilled water (control, C) or water containing 0.025 mg/L (L) or 2.5 mg/L (H) arsenate. Group A was sacrificed on d 28 and plasma and urine samples were taken for determination of clinical chemistry parameters. Liver and kidney tissue samples were taken for histopathological analysis. The reduced nonprotein sulfhydryl (NPSH) content in several tissues was determined. Group B was gavaged with [73As]arsenate on d 28 and continued the arsenate drinking water exposure for 48 h. Excreta and tissues were collected and analyzed for 73As. Urine was further analyzed for arsenate and its metabolites. There were no effects on the mean daily amount of water and food consumed, whereas the mean daily urine volume excreted was significantly elevated by 10% in the H-treated animals compared to C and L. A dose-related hepatic vacuolar degeneration in the liver was observed, but no histological changes were evident in the kidney. Only clinical chemistry parameters in plasma were altered by the arsenate treatment. Glucose was significantly lower at the H dose compared to C and L, triglycerides were significantly greater in C than L and H, and creatinine was significantly greater in H than C. Hepatic NPSH content in the H animals was significantly lower than C and L animals, whereas no effects in lung and kidney were detected. The weights of liver, lung, and kidney, as well

  14. Brachytherapy Application With In Situ Dose Painting Administered by Gold Nanoparticle Eluters

    Energy Technology Data Exchange (ETDEWEB)

    Sinha, Neeharika [Department of Sciences, Wentworth Institute of Technology, Boston, Massachusetts (United States); Cifter, Gizem [Department of Physics and Applied Physics, University of Massachusetts, Lowell, Massachusetts (United States); Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women' s Hospital and Harvard Medical School, Boston, Massachusetts (United States); Sajo, Erno [Department of Physics and Applied Physics, University of Massachusetts, Lowell, Massachusetts (United States); Kumar, Rajiv; Sridhar, Srinivas [Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women' s Hospital and Harvard Medical School, Boston, Massachusetts (United States); Electronic Materials Research Institute and Department of Physics, Northeastern University, Boston, Massachusetts (United States); Nguyen, Paul L.; Cormack, Robert A.; Makrigiorgos, G. Mike [Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women' s Hospital and Harvard Medical School, Boston, Massachusetts (United States); Ngwa, Wilfred, E-mail: wngwa@lroc.harvard.edu [Department of Physics and Applied Physics, University of Massachusetts, Lowell, Massachusetts (United States); Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women' s Hospital and Harvard Medical School, Boston, Massachusetts (United States)

    2015-02-01

    Purpose: Recent studies show promise that administering gold nanoparticles (GNP) to tumor cells during brachytherapy could significantly enhance radiation damage to the tumor. A new strategy proposed for sustained administration of the GNP in prostate tumors is to load them into routinely used brachytherapy spacers for customizable in situ release after implantation. This in silico study investigated the intratumor biodistribution and corresponding dose enhancement over time due to GNP released from such GNP-loaded brachytherapy spacers (GBS). Method and Materials: An experimentally determined intratumoral diffusion coefficient (D) for 10-nm nanoparticles was used to estimate D for other sizes by using the Stokes-Einstein equation. GNP concentration profiles, obtained using D, were then used to calculate the corresponding dose enhancement factor (DEF) for each tumor voxel, using dose painting-by-numbers approach, for times relevant to the considered brachytherapy sources' lifetimes. The investigation was carried out as a function of GNP size for the clinically applicable low-dose-rate brachytherapy sources iodine-125 (I-125), palladium-103 (Pd-103), and cesium-131 (Cs-131). Results: Results showed that dose enhancement to tumor voxels and subvolumes during brachytherapy can be customized by varying the size of GNP released or eluted from the GBS. For example, using a concentration of 7 mg/g GNP, significant DEF (>20%) could be achieved 5 mm from a GBS after 5, 12, 25, 46, 72, 120, and 195 days, respectively, for GNP sizes of 2, 5, 10, 20, 30, and 50 nm and for 80 nm when treating with I-125. Conclusions: Analyses showed that using Cs-131 provides the highest dose enhancement to tumor voxels. However, given its relatively longer half-life, I-125 presents the most flexibility for customizing the dose enhancement as a function of GNP size. These findings provide a useful reference for further work toward development of potential new brachytherapy application

  15. An estimate of the cost of administering intravenous biological agents in Spanish day hospitals

    Science.gov (United States)

    Nolla, Joan Miquel; Martín, Esperanza; Llamas, Pilar; Manero, Javier; Rodríguez de la Serna, Arturo; Fernández-Miera, Manuel Francisco; Rodríguez, Mercedes; López, José Manuel; Ivanova, Alexandra; Aragón, Belén

    2017-01-01

    Objective To estimate the unit costs of administering intravenous (IV) biological agents in day hospitals (DHs) in the Spanish National Health System. Patients and methods Data were obtained from 188 patients with rheumatoid arthritis, collected from nine DHs, receiving one of the following IV therapies: infliximab (n=48), rituximab (n=38), abatacept (n=41), or tocilizumab (n=61). The fieldwork was carried out between March 2013 and March 2014. The following three groups of costs were considered: 1) structural costs, 2) material costs, and 3) staff costs. Staff costs were considered a fixed cost and were estimated according to the DH theoretical level of activity, which includes, as well as personal care of each patient, the DH general activities (complete imputation method, CIM). In addition, an alternative calculation was performed, in which the staff costs were considered a variable cost imputed according to the time spent on direct care (partial imputation method, PIM). All costs were expressed in euros for the reference year 2014. Results The average total cost was €146.12 per infusion (standard deviation [SD] ±87.11; CIM) and €29.70 per infusion (SD ±11.42; PIM). The structure-related costs per infusion varied between €2.23 and €62.35 per patient and DH; the cost of consumables oscillated between €3.48 and €20.34 per patient and DH. In terms of the care process, the average difference between the shortest and the longest time taken by different hospitals to administer an IV biological therapy was 113 minutes. Conclusion The average total cost of infusion was less than that normally used in models of economic evaluation coming from secondary sources. This cost is even less when the staff costs are imputed according to the PIM. A high degree of variability was observed between different DHs in the cost of the consumables, in the structure-related costs, and in those of the care process. PMID:28356746

  16. 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

  17. 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

  18. Enhanced Wound Healing Using Topically Administered Nanoparticle Encapsulated siRNA

    Science.gov (United States)

    2013-11-01

    metal soaps, metal soaps, amine soaps, sulphurated and sulphonated compounds, invert soaps, higher fatty alcohols, partial fatty acid esters of...optimization (size distribution and cationic properties ) This quarter, optimization studies on the siRNA nanoparticle delivery platform progressed along...either neutral or anionic nanoparticles. Our strategy for inducing cationic properties into our platform entailed doping our initial and standard

  19. Antiviral Biologic Produced in DNA Vaccine/Goose Platform Protects Hamsters Against Hantavirus Pulmonary Syndrome When Administered Post-exposure.

    Directory of Open Access Journals (Sweden)

    Nicole Haese

    Full Text Available Andes virus (ANDV and ANDV-like viruses are responsible for most hantavirus pulmonary syndrome (HPS cases in South America. Recent studies in Chile indicate that passive transfer of convalescent human plasma shows promise as a possible treatment for HPS. Unfortunately, availability of convalescent plasma from survivors of this lethal disease is very limited. We are interested in exploring the concept of using DNA vaccine technology to produce antiviral biologics, including polyclonal neutralizing antibodies for use in humans. Geese produce IgY and an alternatively spliced form, IgYΔFc, that can be purified at high concentrations from egg yolks. IgY lacks the properties of mammalian Fc that make antibodies produced in horses, sheep, and rabbits reactogenic in humans. Geese were vaccinated with an ANDV DNA vaccine encoding the virus envelope glycoproteins. All geese developed high-titer neutralizing antibodies after the second vaccination, and maintained high-levels of neutralizing antibodies as measured by a pseudovirion neutralization assay (PsVNA for over 1 year. A booster vaccination resulted in extraordinarily high levels of neutralizing antibodies (i.e., PsVNA80 titers >100,000. Analysis of IgY and IgYΔFc by epitope mapping show these antibodies to be highly reactive to specific amino acid sequences of ANDV envelope glycoproteins. We examined the protective efficacy of the goose-derived antibody in the hamster model of lethal HPS. α-ANDV immune sera, or IgY/IgYΔFc purified from eggs, were passively transferred to hamsters subcutaneously starting 5 days after an IM challenge with ANDV (25 LD50. Both immune sera, and egg-derived purified IgY/IgYΔFc, protected 8 of 8 and 7 of 8 hamsters, respectively. In contrast, all hamsters receiving IgY/IgYΔFc purified from normal geese (n=8, or no-treatment (n=8, developed lethal HPS. These findings demonstrate that the DNA vaccine/goose platform can be used to produce a candidate antiviral

  20. 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.

  1. Advax, a Delta Inulin Microparticle, Potentiates In-built Adjuvant Property of Co-administered Vaccines

    Directory of Open Access Journals (Sweden)

    Masayuki Hayashi

    2017-02-01

    Full Text Available Advax, a delta inulin-derived microparticle, has been developed as an adjuvant for several vaccines. However, its immunological characteristics and potential mechanism of action are yet to be elucidated. Here, we show that Advax behaves as a type-2 adjuvant when combined with influenza split vaccine, a T helper (Th2-type antigen, but behaves as a type-1 adjuvant when combined with influenza inactivated whole virion (WV, a Th1-type antigen. In addition, an adjuvant effect was not observed when Advax-adjuvanted WV vaccine was used to immunize toll-like receptor (TLR 7 knockout mice which are unable to respond to RNA contained in WV antigen. Similarly, no adjuvant effect was seen when Advax was combined with endotoxin-free ovalbumin, a neutral Th0-type antigen. An adjuvant effect was also not seen in tumor necrosis factor (TNF-α knockout mice, and the adjuvant effect required the presences of dendritic cells (DCs and phagocytic macrophages. Therefore, unlike other adjuvants, Advax potentiates the intrinsic or in-built adjuvant property of co-administered antigens. Hence, Advax is a unique class of adjuvant which can potentiate the intrinsic adjuvant feature of the vaccine antigens through a yet to be determined mechanism.

  2. Expanding the scope of practice--should dental nurses be permitted to administer local analgesia?

    Science.gov (United States)

    Noble, Rowan

    2014-01-01

    Dumbing down the profession or meeting the need of more patients by the optimum management of resources? Unequivocally, patient safety and non-maleficence are central to this issue. Restrictions must be imposed to ensure this. Without doubt, continuing competence would have to be demonstrated by the registrant and they would only administer local analgesia after a written prescription by a dentist. Restrictions to infiltration analgesia would also seem prudent. if all involved, including patient representatives, consider this of merit, several issues would have to be resolved such as who wouldnd be responsible for training, the content of the programme a funding for training. This is fundamental for the conception and implementation of such a qualification. Recently, the issue of direct access has been opened. The profession has changed in recent years with more focus being placed on dentists to meet the need of patients burdened by dental disease, particularly the disenfranchised, by utilising the whole dental team. Notwithstanding this and it may seem counter intuitive, but if this role was extended to dental nurses, it may be most adopted in services where time is not so important such as the salaried and other secondary services.

  3. 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.

  4. 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).

  5. 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.

  6. Aminothiol Receptors for Decorporation of Intravenously Administered 60Co in the Rat

    Energy Technology Data Exchange (ETDEWEB)

    Levitskaia, Tatiana G.; Morris, James E.; Creim, Jeffrey A.; Woodstock, Angela D.; Luders, Teresa; Curry, Terry L.; Thrall, Karla D.

    2010-01-01

    The reported investigation provides a comparison of the oral decorporation efficacy of L-glutathione (GSH), L-cysteine (Cys), and a liposomal GSH formulation (ReadiSorb) toward systemic cobalt-60 (60Co) to that observed following intravenous administration of GSH and Cys in F344 rats. L-histidine (His) was tested intravenously to compare in vivo efficacy of the aminothiol GSH and Cys chelators with that of aminoimidazole (His) chelator. 60Co was administered to animals by intravenous injection, followed by intravenous or oral gavage doses of a chelator repeated at 24 hour intervals for a total of 5 doses. The results suggest that GSH and Cys are potent decorporation agents for 60Co in the rat model, although the efficacy of treatment depends largely on systemic availability of a chelator. The intravenous GSH or Cys were most effective in reducing tissue 60Co levels and in increasing excretion of radioactivity compared to control animals. Liposomal encapsulation was found to markedly enhance the oral bioavailability of GSH compared to non-formulated GSH. Oral administration of ReadiSorb reduced 60Co levels in nearly all tissues by 12-43% compared to that observed for non-formulated GSH. Efficacy of oral Cys was only slightly reduced in comparison with intravenous Cys. Further studies to optimize the dosing regimen in order to maximize decorporation efficiency are warranted.

  7. 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.

  8. Disposition kinetics of tylosin tartrate administered intravenously and intramuscularly to normal and water-deprived camels.

    Science.gov (United States)

    Ziv, G; Creveld, C V; Ben-Zvi, Z; Glickman, A; Yagil, R

    1995-08-01

    The disposition kinetics of tylosin tartrate administered intravenously (i.v.) at 10 mg/kg and intramuscularly (i.m.) at 20 mg/kg were studied in normal camels and in the same camels at the end of a 14 day water-deprivation period. After i.v. treatment, serum tylosin concentrations in the water-deprived camels were significantly higher, rate of drug elimination was slower, the volume of distribution was significantly smaller, and total body clearance was significantly slower than in the normal camels. On the other hand, serum drug concentrations were lower in the water deprived camels after i.m. dosing, the mean absorption time was significantly shorter and the i.m. availability was significantly smaller than in the normal camels. Water-deprivation was thought to cause reduced rate of tylosin elimination by the liver, as was shown for antipyrine--a drug which is eliminated from the body exclusively by the liver. Redistribution of tylosin in tissues concomitant with a greater proportion of drug in blood and extracellular fluid of water-deprived camels was suggested as a partial explanation for the higher serum drug levels seen after i.v. dosing. The low i.m. availability observed in the water-deprived camels implies that i.v. is the route of choice for tylosin administration to ill, dehydrated camels.

  9. Evaluation of ATC as an Orally Administered Drug in Treatment of Cadmium Toxicity of Rat Organs

    Directory of Open Access Journals (Sweden)

    S. Nabilaldine Fatemi

    2009-01-01

    Full Text Available The effect of N-tetramethylene dithiocarbamate (ATC as a chelating agent on the excretion of cadmium was evaluated in cadmium-poisoned Wistar rats following administration through food and drink. The present research aimed to characterize the potential efficiency of ATC as an orally administered chelator drug after cadmium administration for 60 days. This chelator significantly enhanced the urinary and biliary excretion of cadmium and restored the altered levels of iron. Cadmium and iron concentrations in different tissues were determined by graphite furnace and flame atomic absorption spectrometry (GF AAS and F AAS methods, respectively. The chelation therapy results show that ATC is able to remove cadmium ions from different tissues while iron concentration returned to the normal level and the clinical symptoms were also reduced. In summary, we conclude that ATC is able to mobilize and promote the excretion of cadmium in rat organs and reduce the side effects and general symptoms of toxicity caused by cadmium and might be useful for preliminary testing of the efficacy of chelating agents in human body. However, these results should be confirmed in different experimental models before extrapolation to other systems. This testing procedure of course does not provide all the relevant answers for evaluating the efficiency of chelating agents in cadmium toxicity.

  10. 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.

  11. Lethal poisoning with theophylline in the form of rectally administered tablets

    Directory of Open Access Journals (Sweden)

    Paweł Kopacz

    2015-02-01

    Full Text Available The paper discusses the case of death of a 56-year-old man who died in a municipal hospital from which his body was taken to the Chair and Department of Forensic Medicine, Jagiellonian University Medical College, Krakow. The man was said to have been found unconscious by accidental passers-by. While being transported to the hospital’s emergency department, he suffered an attack of convulsions and went into cardiac arrest. He was subsequently successfully resuscitated. A physical examination performed at the hospital revealed the presence of multiple, only slightly dissolved tablets in the man’s rectum. The patient died on the 25th day of hospitalization. A toxicological analysis showed a toxic concentration of theophylline (25 mg/l in the man’s blood. Theophylline was identified as the main ingredient of the tablets. The cause of death was thus given as theophylline poisoning. The reported case is unusual in that the poisoning occurred as a result of overdosing on an oral drug which was administered by the victim rectally, and in that the chosen substance currently is not very commonly used in medicine, and does not cause symptoms of intoxication.

  12. Developmental toxicity study of sodium molybdate dihydrate administered in the diet to Sprague Dawley rats.

    Science.gov (United States)

    Jay Murray, F; Tyl, Rochelle W; Sullivan, Frank M; Tiwary, Asheesh K; Carey, Sandra

    2014-11-01

    Molybdenum is an essential nutrient for humans and animals and is a constituent of several important oxidase enzymes. It is normally absorbed from the diet and to a lesser extent from drinking water and the typical human intake is around 2μg/kg bodyweight per day. No developmental toxicity studies to contemporary standards have been published and regulatory decisions have been based primarily on older studies where the nature of the test material, or the actual dose levels consumed is uncertain. In the current study the developmental toxicity of sodium molybdate dihydrate as a representative of a broad class of soluble molybdenum(VI) compounds, was given in the diet to Sprague Dawley rats in accordance with OECD Test Guideline 414. Dose levels of 0, 3, 10, 20 and 40mgMo/kgbw/day were administered from GD6 to GD20. No adverse effects were observed at any dose level on the dams, or on embryofetal survival, fetal bodyweight, or development, with no increase in malformations or variations. Significant increases in serum and tissue copper levels were observed but no toxicity related to these was observed. The NOAEL observed in this study was 40mgMo/kgbw/day, the highest dose tested.

  13. 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.

  14. Advax, a Delta Inulin Microparticle, Potentiates In-built Adjuvant Property of Co-administered Vaccines.

    Science.gov (United States)

    Hayashi, Masayuki; Aoshi, Taiki; Haseda, Yasunari; Kobiyama, Kouji; Wijaya, Edward; Nakatsu, Noriyuki; Igarashi, Yoshinobu; Standley, Daron M; Yamada, Hiroshi; Honda-Okubo, Yoshikazu; Hara, Hiromitsu; Saito, Takashi; Takai, Toshiyuki; Coban, Cevayir; Petrovsky, Nikolai; Ishii, Ken J

    2017-02-01

    Advax, a delta inulin-derived microparticle, has been developed as an adjuvant for several vaccines. However, its immunological characteristics and potential mechanism of action are yet to be elucidated. Here, we show that Advax behaves as a type-2 adjuvant when combined with influenza split vaccine, a T helper (Th)2-type antigen, but behaves as a type-1 adjuvant when combined with influenza inactivated whole virion (WV), a Th1-type antigen. In addition, an adjuvant effect was not observed when Advax-adjuvanted WV vaccine was used to immunize toll-like receptor (TLR) 7 knockout mice which are unable to respond to RNA contained in WV antigen. Similarly, no adjuvant effect was seen when Advax was combined with endotoxin-free ovalbumin, a neutral Th0-type antigen. An adjuvant effect was also not seen in tumor necrosis factor (TNF)-α knockout mice, and the adjuvant effect required the presences of dendritic cells (DCs) and phagocytic macrophages. Therefore, unlike other adjuvants, Advax potentiates the intrinsic or in-built adjuvant property of co-administered antigens. Hence, Advax is a unique class of adjuvant which can potentiate the intrinsic adjuvant feature of the vaccine antigens through a yet to be determined mechanism.

  15. 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.

  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. 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.

  18. The influence of dexamethasone administered prenatally on cartilage of newborn spiny mouse (Acomys cahirinus) offspring.

    Science.gov (United States)

    Iwaniak, P; Dobrowolski, P; Tomaszewska, E; Hułas-Stasiak, M; Tomczyk, A; Gawron, A

    2015-11-17

    Considering the negative effects of glucocorticoid treatment, especially during fetal development it is important to investigate effectors decreasing such disadvantages. The aim of this study was to investigate the effect of prenatally administered dexamethasone (Dex), a synthetic glucocorticoid, on the histomorphometry of the femur in the offspring of spiny mice. The study was performed on 24 pregnant spiny mice. The time of the experiment included the prenatal period between the 20th day of gestation until birth (pregnancy lasts on average of 36-38 days). The mice from the experimental group received dexamethasone per os in a dose of 125 mg/kg birth weight daily. At the end, the newborns from the experimental and control group were weighted and euthanized. Maternal Dex treatment resulted in a 17% decrease in birth weight in newborns. Dex administration significantly reduced the thickness of the hypertrophy zone of the growth plate by 34% and total thickness by 8,7%. In addition, Dex decreased the number of cells in the articular cartilage by 27% and significantly decreased their diameter by 5%. Dex also affected the structure and spatial distribution of thick and thin collagen fibers, lowering the proportion of thin fibers compared with the control group. Moreover, Dex treatment considerably lowered the amount of proteoglycans in articular and growth cartilages. Exposure to glucocorticoids in pregnant spiny mice affects cartilage development by accelerating maturity of collagen fibers and growth plate, presumably along with further disruption of longitudinal growth of long bones.

  19. Neuroprotective activity of peripherally administered liver growth factor in a rat model of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Rafael Gonzalo-Gobernado

    Full Text Available Liver growth factor (LGF is a hepatic mitogen purified some years ago that promotes proliferation of different cell types and the regeneration of damaged tissues, including brain tissue. Considering the possibility that LGF could be used as a therapeutic agent in Parkinson's disease, we analyzed its potential neuroregenerative and/or neuroprotective activity when peripherally administered to unilaterally 6-hydroxydopamine (6-OHDA-lesioned rats. For these studies, rats subjected to nigrostriatal lesions were treated intraperitoneally twice a week with LGF (5 microg/rat for 3 weeks. Animals were sacrificed 4 weeks after the last LGF treatment. The results show that LGF stimulates sprouting of tyrosine hydroxylase-positive terminals and increases tyrosine hydroxylase and dopamine transporter expression, as well as dopamine levels in the denervated striatum of 6-OHDA-lesioned rats. In this structure, LGF activates microglia and raises tumor necrosis factor-alpha protein levels, which have been reported to have a role in neuroregeneration and neuroprotection. Besides, LGF stimulates the phosphorylation of MAPK/ERK1/2 and CREB, and regulates the expression of proteins which are critical for cell survival such as Bcl2 and Akt. Because LGF partially protects dopamine neurons from 6-OHDA neurotoxicity in the substantia nigra, and reduces motor deficits in these animals, we propose LGF as a novel factor that may be useful in the treatment of Parkinson's disease.

  20. The role of capnography in endoscopy patients undergoing nurse-administered propofol sedation: a randomized study.

    Science.gov (United States)

    Slagelse, Charlotte; Vilmann, Peter; Hornslet, Pernille; Jørgensen, Henrik L; Horsted, Tina I

    2013-10-01

    OBJECTIVE. Standard benzodiazepine/opioid cocktail has proven inferior to propofol sedation during complicated endoscopic procedures and in low-tolerance patients. Propofol is a short-acting hypnotic with a potential risk of respiratory depression at levels of moderate to deep sedation. The existing literature on capnography for endoscopy patients sedated with nurse-administered propofol sedation (NAPS) is limited. Can the addition of capnography to standard monitoring during endoscopy with NAPS reduce the number, duration, and level of hypoxia. MATERIALS AND METHODS. This study was a randomized controlled trial with an intervention group (capnography) and a control group (without capnography). Eligible subjects were consecutive patients for endoscopy at Gentofte Hospital compliant with the criteria of NAPS. RESULTS. Five hundred and forty patients, 263 with capnography and 277 without capnography, were included in the analysis. The number and total duration of hypoxia was reduced by 39.3% and 21.1% in the intervention group compared to the control group (p > 0.05). No differences in actions taken against insufficient respiration were found. Changes in end-tidal carbon dioxide (R = 0.177, p-value 0.05). Capnography is able to detect insufficient respiration that may lead to hypoxia prior to changes in pulse oximetry. However, due to a limited clinical benefit and additional costs associated with capnography, we do not find capnography necessary during the use of NAPS.

  1. Pharmacodynamic comparison of prostaglandin E1 administered by different routes to rats.

    Science.gov (United States)

    Gu, Fu-gen; Cui, Fu-de; Gao, Yong-liang

    2007-07-01

    The pharmacodynamics of prostaglandin E1 (PGE1) administered by different routes to rats was investigated in this paper. The hypotensive effect of PGE, was used as an index of drug efficacy, pharmacodynamic parameters such as time to reach peak effect (Tmax), maximal percentage of blood pressure decrease (Emax, %), duration of effect (Td), and the area under the blood pressure decrease percent-time curves (AUC, % x min) were determined after PGE1 given to rats intranasally, sublingually, intraperitoneally (ip), and intramuscularly (im), separately, and compared with those obtained from intravenous (iv) administration. Similar to iv route, the pharmacodynamic parameters of PGE1 from the other administration routes, Emax, Td and in particular AUC values were all increased with increasing doses, showing dose-efficacy relationship. Tmax was found to be approximately 3-4 min for nasal route, 3-8 min for im, 6-8 min for ip and 12-30 min for sublingual route, separately. Thus, the order of magnitude of absorption rate of the drug was as follows: nasal approximately = im > ip > sublingual. If the pharmacological bioavailability (PF) for each administration route was used as a tentative measure of drug absorption extent, the order of magnitude of absolute bioavailability appeared as follows: nasal > im approximately = ip > sublingual. Furthermore, the interindividual difference was found to be larger for im and ip route than that for nasal and sublingual route. These results indicate nasal and sublingual routes are two promising routes for the systemic delivery of PGE1 in clinical applications.

  2. Individually administered or co-prescribed thiopurines and mesalamines for inflammatory bowel disease.

    Science.gov (United States)

    Actis, Giovanni-C; Pellicano, Rinaldo; Rizzetto, Mario; Ayoubi, Muhammad; Leone, Nicola; Tappero, Gianfranco; Pazienza, Paola; Rosina, Floriano

    2009-03-28

    Data from both basic research and clinical experience continue to suggest that mesalamines and thiopurines are effective and efficient for the maintenance of remission of inflammatory bowel diseases. Several decades following the formalization of their indications, attention on these two drugs has been fostered by recent achievements. Demonstration of the ability of mesalamine to activate a colonocyte differentiation factor has shed light on its chemopreventive effects on colorectal cancer; in addition to their anti-proliferative efficacy, thiopurines have been shown to be specific regulators of apoptosis. The two drugs are often co-administered in clinical practice. Recent advancements have shown that mesalamines exert a positive synergism in this context, insofar as they can inhibit side-methylation of thiopurines and hasten the function of the main immunosuppressive pathways. Considering that up to 40% of patients cannot tolerate thiopurines, such renovated targets have stimulated efforts to improve compliance by research on the toxicity mechanisms. The definition of genetic polymorphisms in the enzymes of thiopurine metabolism, and the uncovering of synergistic drug interactions, such as that with allopurinol, are just two of the results of such efforts. Interaction between basic research and clinical practice has continued to inform indications and refine the prescriptions of mesalamines and thiopurines; these have not been restrained (they have been implemented in some cases) by the advent of the novel biological molecules with anti-cytokine activity.

  3. 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

  4. CHEERUP: A General Software-Environment for Building, Using and Administering Predictive Monitoring Portals

    Directory of Open Access Journals (Sweden)

    MUSSI, S.

    2011-11-01

    Full Text Available The intended meaning of the term predictive monitoring used in the paper is the following. A population of subjects (living beings, machines, works of art, etc. is monitored by a domain expert with regard to the possible occurrence of an undesired/desired event E. More precisely, an expert periodically (e.g. every two years, every week, etc. depending on the specific application examines the single subjects and, for each of them, enters examination outcomes in a database where statistical data are automatically processed in order to produce probabilistic inferences about the occurrence in the future of E for the subject under examination (individualized prediction. This allows the expert to take suitable measures in advance in order to prevent/favour the occurrence of E for the subject. Such an approach to predictive monitoring requires that the expert who monitors subjects has at his/her disposal a suitable software system provided with database and algorithms for both properly managing monitoring-processes and producing probabilistic predictions. The paper presents CHEERUP : a prototype product, usable via Internet, that consists in a general software-environment for building, using and administering specific predictive monitoring software-systems (in the paper called portals.

  5. 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.

  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. An Atypical Case of Methemoglobinemia due to Self-Administered Benzocaine

    Directory of Open Access Journals (Sweden)

    Thomas M. Nappe

    2015-01-01

    Full Text Available Acquired methemoglobinemia is an uncommon hemoglobinopathy that results from exposure to oxidizing agents, such as chemicals or medications. Although, as reported in the adult population, it happens most often due to prescribed medication or procedural anesthesia and not due to easily accessed over-the-counter medications, the authors will describe an otherwise healthy male adult with no known medical history and no prescribed medications, who presented to the emergency department reporting generalized weakness, shortness of breath, headache, dizziness, and pale gray skin. In addition, the patient reported that he also had a severe toothache for several days, which he had been self-treating with an over-the-counter oral benzocaine gel. Ultimately, the diagnosis of methemoglobinemia was made by clinical history, physical examination, and the appearance of chocolate-colored blood and arterial blood gas (ABG with cooximetry. After 2 mg/kg of intravenous methylene blue was administered, the patient had complete resolution of all signs and symptoms. This case illustrates that emergency physicians should be keenly aware of the potential of toxic hemoglobinopathy secondary to over-the-counter, nonprescribed medications. Discussion with patients regarding the dangers of inappropriate use of these medicines is imperative, as such warnings are typically not evident on product labels.

  8. An Atypical Case of Methemoglobinemia due to Self-Administered Benzocaine.

    Science.gov (United States)

    Nappe, Thomas M; Pacelli, Anthony M; Katz, Kenneth

    2015-01-01

    Acquired methemoglobinemia is an uncommon hemoglobinopathy that results from exposure to oxidizing agents, such as chemicals or medications. Although, as reported in the adult population, it happens most often due to prescribed medication or procedural anesthesia and not due to easily accessed over-the-counter medications, the authors will describe an otherwise healthy male adult with no known medical history and no prescribed medications, who presented to the emergency department reporting generalized weakness, shortness of breath, headache, dizziness, and pale gray skin. In addition, the patient reported that he also had a severe toothache for several days, which he had been self-treating with an over-the-counter oral benzocaine gel. Ultimately, the diagnosis of methemoglobinemia was made by clinical history, physical examination, and the appearance of chocolate-colored blood and arterial blood gas (ABG) with cooximetry. After 2 mg/kg of intravenous methylene blue was administered, the patient had complete resolution of all signs and symptoms. This case illustrates that emergency physicians should be keenly aware of the potential of toxic hemoglobinopathy secondary to over-the-counter, nonprescribed medications. Discussion with patients regarding the dangers of inappropriate use of these medicines is imperative, as such warnings are typically not evident on product labels.

  9. Curative and preventive efficacy of orally administered afoxolaner against Ctenocephalides canis infestation in dogs.

    Science.gov (United States)

    Dumont, Pascal; Gale, Boyd; Chester, Theodore S; Larsen, Diane L

    2014-04-02

    The efficacy of orally administered afoxolaner against adult dog fleas, Ctenocephalides canis, was evaluated in a controlled, blinded study. A total of 32 dogs were infested with 100 adult unfed fleas approximately 24h prior to treatment and then at weekly intervals for 5 weeks after treatment. Live fleas were counted upon removal at 12h (for 16 dogs) and 24h (for the remaining 16 dogs) after treatment (for counts performed the first week) or after infestation (for counts performed on subsequent weeks). In addition, flea eggs were collected from each pen and counted for the dogs with flea removal at 24h. Dosing of individual dogs was achieved using a combination of the chewable tablets to be as close as possible to the minimum effective dose of 2.5mg/kg. The percent efficacy of the afoxolaner treatment was ≥ 99.0% for all 24-h flea counts. For flea counts performed 12h after treatment or infestations, the percent efficacy was ≥ 94.1% up to Day 21. After Day 1, no flea eggs were recovered from the afoxolaner treated group, providing 100% reduction in numbers of flea eggs recovered versus untreated control group. This study confirmed that a single oral treatment with afoxolaner provided excellent efficacy against infestations by C. canis within 12-24h after treatment, prevented re-infestations, and completely prevented egg production from new flea infestations for up to 5 weeks.

  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. 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

  12. Identification and quantification of metabolites of orally administered naringenin chalcone in rats.

    Science.gov (United States)

    Yoshimura, Mineka; Sano, Atsushi; Kamei, Jun-Ichi; Obata, Akio

    2009-07-22

    Naringenin chalcone is the main active component of tomato skin extract, which has an antiallergic activity. In this study, naringenin chalcone was orally administered to rats, and the chemical structures and levels of the major metabolites in the plasma and urine of rats were determined. HPLC analysis indicated the presence of three major metabolites in the urine. LC-MS and NMR analyses tentatively identified these as naringenin chalcone-2'-O-beta-D-glucuronide, naringenin-7-O-beta-D-glucuronide, and naringenin-4'-O-beta-D-glucuronide. Naringenin chalcone-2'-O-beta-D-glucuronide was the only metabolite detected in the plasma, and its peak plasma level was observed 1 h after naringenin chalcone administration. Naringenin chalcone-2'-O-beta-D-glucuronide also inhibited histamine release from rat peritoneal mast cells stimulated with compound 48/80. This activity might contribute to the antiallergic activity of naringenin chalcone in vivo. To the best of the authors' knowledge, this study is the first to report determination of naringenin chalcone metabolites in rat plasma and urine.

  13. Should anesthesiologists have to confirm effective facemask ventilation before administering the muscle relaxant?

    Science.gov (United States)

    Priebe, Hans-Joachim

    2016-02-01

    There is ongoing controversy as to whether effective facemask ventilation (FMV) should be established following induction of anesthesia before a muscle relaxant is administered. The rationale for such practice is the belief that, should FMV be ineffective, non-paralyzed patients can be woken up, and subsequently an alternative airway management can be considered. However, the chances of successfully restoring adequate spontaneous respiration before severe hypoxemia develops in an anesthetized, apneic patient who is prone to anesthetic-induced respiratory depression and airway collapse are very small. On the other hand, the overall evidence shows that muscle relaxation is likely to improve or leave unchanged, but not to worsen, the quality of FMV. Furthermore, muscle relaxation will facilitate placement of a supraglottic airway device and endotracheal intubation, interventions which may become essential should the patient become hypoxemic during failed FMV. Thus, the earliest administration of a muscle relaxant following induction of anesthesia may well be the most effective and safest practice. Insistence on demonstration of adequate FMV before administration of a muscle relaxant is more of a ritual than an evidence-based practice. It should therefore be abandoned.

  14. Gene delivery to dendritic cells by orally administered recombinant Saccharomyces cerevisiae in mice.

    Science.gov (United States)

    Kiflmariam, Meron G; Yang, Hanjiang; Zhang, Zhiying

    2013-02-27

    DNA vaccination has caught the attention of many for triggering humoral as well as cellular immune responses. And delivering DNA into the antigen presenting cells (APCs) in order to induce efficient immunoresponse has become the backbone of this field. It has been confirmed that Saccharomyces cerevisiae, though non-pathogenic, is being engulfed by the dendritic cells and macrophages and delivers not only proteins, but also DNA materials (already confirmed in vitro). In this research, S. cerevisiae is used to deliver green fluorescent protein (GFP) reporter gene controlled under cytomegalovirus (CMV) promoter in living organism (mice). The recombinant yeast, transfected with the plasmid containing the GFP gene, was heat killed and orally administered to mice. After 60 h of yeast administration, mice were sacrificed and intestine was separated, washed and frozen in liquid nitrogen. Tissues were cut at the size of 10 μm using Cryostat machine, and GFP expression was successfully detected under a fluorescence microscope. After 45 days Western blot was able to detect GFP antibody in the blood of mice. These results imply that S. cerevisiae, being non-pathogenic, cheap, and easy to culture could be a good candidate to deliver DNA materials to the immune cells for vaccination.

  15. 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.

  16. 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.

  17. 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...

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    Patricia A. Kinser

    2016-01-01

    Full Text Available 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.

  20. Folic Acid

    Science.gov (United States)

    ... damage. 10 Do I need folic acid after menopause? Yes. Women who have gone through menopause still need 400 micrograms of folic acid every ... United States: 2003–2006 . American Journal of Clinical Nutrition; 91(1): 231–237. Hamner, H.C., Cogswell, ...

  1. Pharmacology of ketoprofen administered orally to pigs : an experimental and clinical study

    OpenAIRE

    2012-01-01

    Ketoprofen is a non-steroidal anti-inflammatory drug belonging to the 2-arylpropionic acid group. It has been widely used in domestic animals because of its anti-inflammatory, antipyretic and analgesic actions. Ketoprofen is a chiral compound existing in two enantiomeric forms, S (+) and R (-) ketoprofen. Each enantiomer has different pharmacodynamic and pharmacokinetic properties. The commercial products in veterinary medicine are 50:50 racemic mixtures of both enantiomers. Ketoprofen underg...

  2. Ascorbic acid supplementation does not improve efficacy of meso-dimercaptosuccinic acid treatment in lead-exposed suckling rats.

    Science.gov (United States)

    Varnai, Veda Marija; Piasek, Martina; Blanusa, Maja; Juresa, Dijana; Sarić, Marija; Kostial, Krista

    2003-10-01

    It was suggested that ascorbic acid as a natural chelating agent can influence lead toxicokinetics and improve chelating properties of dimercaptosuccinic acid (DMSA) in adult rats. In this paper potential benefits of ascorbic acid supplementation, alone or combined with DMSA, in decreasing lead retention in suckling rats were evaluated. Such data in young mammals are not available. L-Ascorbic acid (daily dose 650 mg/kg b.wt.) and/or DMSA (daily dose 91 mg/kg b.wt.) were administered orally to suckling Wistar rats either during ongoing 8-day oral lead exposure (as acetate; daily dose 2 mg lead/kg b.wt.) or after 3-day lead exposure (total dose 12 mg lead/kg b.wt.). Lead concentrations were analysed in the carcass (skeleton), liver, kidneys and brain by atomic absorption spectrometry. By ascorbic acid supplementation lead retention was not reduced under either lead exposure condition. Lead concentration was even increased in the carcass. Treatment with DMSA under both exposure conditions significantly reduced lead in all analysed tissues. Combined treatment with ascorbic acid and DMSA during ongoing lead exposure was substantially less effective than DMSA treatment alone, and did not affect DMSA efficacy when administered after lead exposure. It was concluded that ascorbic acid administered either during or after lead exposure in suckling rats has no beneficial effect on either lead retention or DMSA chelation effectiveness.

  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.

  4. 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)

  5. Application of the yeast-surface-display system for orally administered salmon calcitonin and safety assessment.

    Science.gov (United States)

    Sun, Ping-Nan; Zhang, Xue-Cheng; Chen, Yun-Song; Zang, Xiao-Nan

    2010-01-01

    High manufacturing costs and oral delivery are the constraints in clinical application of calcitonin. We selected surface-displayed Saccharomyces cerevisiae as a low-cost and safe carrier for oral delivery of salmon calcitonin (sCT). The sCT DNA fragment, optimized according to the codon preference of S. cerevisiae, was synthesized and cloned into the plasmid M-pYD1 to yield recombinant yAGA2-sCT, which was induced to express sCT by galactose for 0, 12, and 24 h. sCT expression was detected on the cell surface by indirect immunofluorescence and peaked at 12 h. About 65% recombinants expressed sCT on flow cytometry. The in vivo and in vitro activity of recombinant sCT was determined by detecting bioactivity of antiosteoclastic absorption on bone wafers and orally administering yAGA2-sCT to Wistar rats, respectively. For safety assessment of yAGA2-sCT, we observed abnormalities, morbidity, and mortality and determined body weight, serum chemistry parameters, hematological parameters, and organ weight. In vitro bioactivity of the recombinant sCT was similar to that of commercial sCT, Miacalcic; oral administration of 5 g/kg yAGA2-sCT induced a long-term hypocalcemic effect in Wistar rats and no adverse effects. This study demonstrates that yAGA2-sCT anchoring sCT protein on a S. cerevisiae surface has potential for low-cost and safe oral delivery of sCT.

  6. Orally administered tylosin for the control of pneumonia in neonatal calves.

    Science.gov (United States)

    Matsuoka, T; Muenster, O A; Ose, E E; Tonkinson, L

    1980-08-16

    The effectiveness of orally administered tylosin tartrate for the control of naturally occurring pneumonia was determined in 287 neonatal calves. Tylosin tartrate was mixed with reconstituted milk replacer at the time of feeding. Daily doses of 1.0 g (0.5 g BID), 2.0 g (1.0 g BID) and 4.0 g (2.0 g BID) were evaluated for periods ranging from seven to 28 days. Tylosin at the optimum dose of 2.0 g daily reduced mortality to 12 out of 95 (12.6 per cent) compared to 38 out of 89 (42.7 per cent) in the non-medicated control calves. The 1.0 g daily dose did not reduce mortality. The number of calves with moderate to severe lung lesions was also reduced by treatment at 2.0 g daily to 13 out of 95 (13.7 per cent) compared to 45 out of 89 (50.6 per cent) in the control group. All dose levels had a similar effect in reducing the severity of clinical signs indicative of respiratory disease. Tylosin treatment at all dose levels reduced the number of Pasteurella multocida isolations from lung tissue to 15/146 (10.3 per cent) compared to 61/141 (43.3 per cent) for the controls. However, there were no differences between treated and controls in the number of P haemolytica isolations. The frequency of mycoplasma isolations from lung tissue were reduced significantly by tylosin treatment at the 4.0 g and 2.0 g dose levels to 36/93 (38.7 per cent) compared to 61/86 (70.9 per cent) for the control calves.

  7. In vitro viability effects on apheresis and buffy-coat derived platelets administered through infusion pumps

    Directory of Open Access Journals (Sweden)

    Sandgren P

    2014-12-01

    Full Text Available Per Sandgren,1,2 Veronica Berggren,3 Carl Westling,1,2 Viveka Stiller1 1Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, 2Department of Laboratory Medicine, Karolinska Institutet, 3Department of Neonatology, Karolinska University Hospital, Stockholm, SwedenBackground: Different infusion pump systems as well as gravity infusion have been widely used in neonatal transfusion. However, the limited number of published studies describing the use of infusion pumps on platelets illustrates the necessity for more robust data.Methods: To evaluate the potential in vitro effects on the cellular, metabolic, functional and phenotypic properties of platelets, we set up a four-arm paired study simultaneously comparing the use of different infusion pumps (Alaris® CC/GP with unexposed platelets. The platelet units (n=8 were either produced by the apheresis technique and suspended in 100% plasma or derived from buffy coats to yield platelet units stored in approximately 30% plasma and 70% SSP+. Fresh and 5-day old platelets were tested.Results: Regardless of the production system or storage time used, no significant differences were observed in glucose and lactate concentration, pH, adenosine triphosphate levels, response to extent of shape change, hypotonic shock response reactivity, and CD62P expression. Similarly, no differences were observed in expression of the conformational epitope on glycoprotein IIb/IIIa, determined using procaspase-activating compound 1, or in the expression of CD42b and platelet-endothelial cell adhesion molecule-1 in a comparison between platelets administered through infusion pumps versus unexposed platelets.Conclusion: Using Alaris CC/GP infusion pumps had no influence on the cellular, functional, and phenotypic in vitro properties of platelets. This fact seems not to be affected by different production systems or storage time.Keywords: platelets, neonatal platelet transfusion

  8. 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.

  9. Diazepam promotes choice of abstinence in cocaine self-administering rats.

    Science.gov (United States)

    Augier, Eric; Vouillac, Caroline; Ahmed, Serge H

    2012-03-01

    When facing a choice between cocaine and a potent, albeit inessential, non-drug alternative (i.e. water sweetened with saccharin), most cocaine self-administering rats abstain from cocaine in favor of the non-drug pursuit, regardless of the dose available and even after extended drug use. Only a minority continues to take the drug despite the opportunity of making a different choice and increasing stakes. This pattern of individual variation could suggest that the majority of rats are resilient to addiction, taking cocaine by default of other options. Only a minority would be vulnerable to addiction. This study tested the hypothesis that rats choose to refrain from cocaine self-administration because cocaine would be conflictual, having both rewarding and anxiogenic properties. Contrary to this hypothesis, however, we report here that diazepam-a broad-spectrum benzodiazepine anxiolytic-did not decrease, but instead, further increased cocaine abstinence. Interestingly, although diazepam decreased locomotion, rats adapted to this effect by spending more time near the lever associated with the preferred reward, a behavior that minimized the need for locomotion at the moment of choice. When responding for cocaine or saccharin was analyzed separately, we found that diazepam decreased responding for cocaine without affecting responding for saccharin. Finally, the abstinence-promoting effects of diazepam were also induced in cocaine-preferring rats treated chronically with diazepam. Overall, this study demonstrates that abstinence from cocaine cannot be explained away by the anxiogenic effects of cocaine, thereby reinforcing the notion of resilience to addiction. It also supports the use of benzodiazepines in the treatment of cocaine addiction.

  10. The pharmacokinetics of orally administered ivermectin in African elephants (Loxodonta africana): implications for parasite elimination.

    Science.gov (United States)

    Gandolf, A Rae; Lifschitz, A; Stadler, C; Watson, B; Galvanek, L; Ballent, M; Lanusse, C

    2009-03-01

    Loxodonta africana are susceptible to a wide variety of parasites that are often treated with the broad spectrum antiparasitic ivermectin (IVM) based on empirical knowledge. The objectives of this study were to 1) measure plasma IVM levels following administration of 0.1 mg/kg IVM p.o., 2) compare plasma IVM levels following administration with regular versus restricted feed rations, 3) measure IVM excretion in feces, and 4) use these findings to generate dosing recommendations for this species. Using a crossover design, six African elephants were divided into two groups. Ivermectin was administered and typical grain rations were either provided or withheld for 2 hr. Blood and fecal samples were collected for 7 days following drug administration. After a 5-wk washout period, groups were switched and the procedure repeated. Plasma and fecal IVM were analyzed using high-performance liquid chromatography. There was no statistically significant difference detected in the pharmacokinetic data between the fed and fasted groups. Peak plasma concentration, area under the curve, and half-life for plasma ranged between 5.41-8.49 ng/ml, 17.1-20.3 ng x day/ml, and 3.12-4.47 day, respectively. High IVM concentrations were detected in feces. The peak concentration values in feces were between 264-311-fold higher than those obtained in plasma. The comparatively large area under the curve and short time to maximum concentration in feces indicate elimination prior to absorption of much of the drug. Plasma IVM concentrations were low when compared to other species. Based on these findings, administration of 0.2-0.4 mg/kg p.o. should be appropriate for eliminating many types of parasites in elephants, and could minimize development of parasite resistance.

  11. 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

  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. 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

  14. Anti-tumor effect of a novel soluble recombinant human endostatin: administered as a single agent or in combination with chemotherapy agents in mouse tumor models.

    Directory of Open Access Journals (Sweden)

    Zhihua Ren

    Full Text Available Angiogenesis has become an attractive target in cancer treatment. Endostatin is one of the potent anti-angiogenesis agents. Its recombinant form expressed in the yeast system is currently under clinical trials. Endostatin suppresses tumor formation through the inhibition of blood vessel growth. It is anticipated that combined therapy using endostatin and cytotoxic compounds may exert an additive effect. In the present study, we expressed and purified recombinant human endostatin (rhEndostatin that contained 3 additional amino acid residues (arginine, glycine, and serine at the amino-terminus and 6 histidine residues in its carboxyl terminus. The recombinant protein was expressed in E. Coli and refolded into a soluble form in a large scale purification process. The protein exhibited a potent anti-tumor activity in bioassays. Furthermore, rhEndostatin showed an additive effect with chemotherapy agents including cyclophosphamide (CTX and cisplatin (DDP.rhEndostatin cDNA was cloned into PQE vector and expressed in E. Coli. The protein was refolded through dialysis with an optimized protocol. To establish tumor models, nude mice were subcutaneously injected with human cancer cells (lung carcinoma A549, hepatocellular carcinoma QGY-7703, or breast cancer Bcap37. rhEndostatin and/or DDP was administered peritumorally to evaluate the rate of growth inhibition of A549 tumors. For the tumor metastasis model, mice were injected intravenously with mouse melanoma B16 cells. One day after tumor cell injection, a single dose of rhEndostatin, or in combination with CTX, was administered intravenously or at a site close to the tumor.rhEndostatin reduced the growth of A549, QGY-7703, and Bcap37 xenograft tumors in a dose dependent manner. When it was administered peritumorally, rhEndostatin exhibited a more potent inhibitory activity. Furthermore, rhEndostatin displayed an additive effect with CTX or DDP on the inhibition of metastasis of B16 tumors or growth of

  15. Development and validation of a theoretical test in non-anaesthesiologist-administered propofol sedation for gastrointestinal endoscopy

    DEFF Research Database (Denmark)

    Jensen, Jeppe Thue; Savran, Mona Meral; Møller, Ann Merete;

    2016-01-01

    OBJECTIVE: Safety with non-anaesthesiologist-administered propofol sedation (NAAP) during gastrointestinal (GI) endoscopy is related to theoretical knowledge. A summative testing of knowledge before attempting supervised nurse-administered propofol sedation (NAPS) in the clinic is advised. The aims...... 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...

  16. Measurement of intravenously administered γ-Fe2O3 particle amount in mice tissues using vibrating sample magnetometer.

    Science.gov (United States)

    Kishimoto, Mikio; Miyamoto, Ryoichi; Oda, Tatsuya; Ohara, Yusuke; Yanagihara, Hideto; Ohkohchi, Nobuhiro; Kita, Eiji

    2014-12-01

    Dispersions of platelet γ-Fe2O3 particles 30-50nm in size were intravenously administered to mice and the amount of particles accumulated in each tissue was obtained by magnetization measurement using a vibrating sample magnetometer. Background noise was greatly reduced by measuring dried tissues under a magnetic field of 500 Oe so that the effect of diamagnetism was slight. Remarkable particle accumulation was observed in the liver and spleen. Considerable particle accumulation was observed in the lung when a large quantity of γ-Fe2 O3 particles was administered. There was no significant particle accumulation in the kidney and heart.

  17. 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.

  18. 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.

  19. 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.…

  20. Chenodeoxycholic acid reduces intestinal permeability in newly weaned piglets

    NARCIS (Netherlands)

    Meer, van der Y.; Gerrits, W.J.J.; Bosch, van den M.; Holst, J.J.; Moreto, M.; Buurman, W.A.; Kulik, W.; Kempen, van T.A.T.G.

    2012-01-01

    Piglets are highly susceptible to gut health-related problems. Intravenously administered chenodeoxycholic acid (CDCA) affects gut health mediated through glucagon-like peptide 2 (GLP-2). To test whether CDCA is a suitable feed additive for improving gut health, a trial was performed with newly wean

  1. 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.

  2. 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.

  3. Targeting synaptic dysfunction in Alzheimer's disease by administering a specific nutrient combination.

    Science.gov (United States)

    van Wijk, Nick; Broersen, Laus M; de Wilde, Martijn C; Hageman, Robert J J; Groenendijk, Martine; Sijben, John W C; Kamphuis, Patrick J G H

    2014-01-01

    Synapse loss and synaptic dysfunction are pathological processes already involved in the early stages of Alzheimer's disease (AD). Synapses consist principally of neuronal membranes, and the neuronal and synaptic losses observed in AD have been linked to the degeneration and altered composition and structure of these membranes. Consequently, synapse loss and membrane-related pathology provide viable targets for intervention in AD. The specific nutrient combination Fortasyn Connect (FC) is designed to ameliorate synapse loss and synaptic dysfunction in AD by addressing distinct nutritional needs believed to be present in these patients. This nutrient combination comprises uridine, docosahexaenoic acid, eicosapentaenoic acid, choline, phospholipids, folic acid, vitamins B12, B6, C, and E, and selenium, and is present in Souvenaid, a medical food intended for use in early AD. It has been hypothesized that FC counteracts synaptic loss and reduces membrane-related pathology in AD by providing nutritional precursors and cofactors that act together to support neuronal membrane formation and function. Preclinical studies formed the basis of this hypothesis which is being validated in a broad clinical study program investigating the potential of this nutrient combination in AD. Memory dysfunction is one key early manifestation in AD and is associated with synapse loss. The clinical studies to date show that the FC-containing medical food improves memory function and preserves functional brain network organization in mild AD compared with controls, supporting the hypothesis that this intervention counteracts synaptic dysfunction. This review provides a comprehensive overview of basic scientific studies that led to the creation of FC and of its effects in various preclinical models.

  4. Mefenamic Acid

    Science.gov (United States)

    ... any of the inactive ingredients in mefenamic acid capsules. Ask your pharmacist for a list of the inactive ingredients.tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking ...

  5. 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...

  6. 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.

  7. Systemic and Mucosal Antibody Responses to Soluble and Nanoparticle-Conjugated Antigens Administered Intranasally

    Directory of Open Access Journals (Sweden)

    Savannah E. Howe

    2016-10-01

    Full Text Available Nanoparticles (NPs are increasingly being used for drug delivery, as well as antigen carriers and immunostimulants for the purpose of developing vaccines. In this work, we examined how intranasal (i.n. priming followed by i.n. or subcutaneous (s.c. boosting immunization affects the humoral immune response to chicken ovalbumin (Ova and Ova conjugated to 20 nm NPs (NP-Ova. We show that i.n. priming with 20 mg of soluble Ova, a dose known to trigger oral tolerance when administered via gastric gavage, induced substantial systemic IgG1 and IgG2c, as well as mucosal antibodies. These responses were further boosted following a s.c. immunization with Ova and complete Freund’s adjuvant (Ova+CFA. In contrast, 100 µg of Ova delivered via NPs induced an IgG1-dominated systemic response, and primed the intestinal mucosa for secretion of IgA. Following a secondary s.c. or i.n. immunization with Ova+CFA or NP-Ova, systemic IgG1 titers significantly increased, and serum IgG2c and intestinal antibodies were induced in mice primed nasally with NP-Ova. Only Ova- and NP-Ova-primed mice that were s.c.-boosted exhibited substantial systemic and mucosal titers for up to 6 months after priming, whereas the antibodies of i.n.-boosted mice declined over time. Our results indicate that although the amount of Ova delivered by NPs was 1000-fold less than Ova delivered in soluble form, the antigen-specific antibody responses, both systemic and mucosal, are essentially identical by 6 months following the initial priming immunization. Additionally, both i.n.- and s.c.-boosting strategies for NP-Ova-primed mice were capable of inducing a polarized Th1/Th2 immune response, as well as intestinal antibodies; however, it is only by using a heterogeneous prime-boost strategy that long-lasting antibody responses were initiated. These results provide valuable insight for future mucosal vaccine development, as well as furthering our understanding of mucosal antibody responses.

  8. 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

  9. Multiple-dose pharmacokinetics and tolerability of gemifloxacin administered orally to healthy volunteers.

    Science.gov (United States)

    Allen, A; Bygate, E; Vousden, M; Oliver, S; Johnson, M; Ward, C; Cheon, A; Choo, Y S; Kim, I

    2001-02-01

    Gemifloxacin mesylate (SB-265805-S, LB-20304a) is a potent, novel fluoroquinolone agent with a broad spectrum of antibacterial activity. The pharmacokinetics and tolerability of oral gemifloxacin were characterized in two parallel group studies in healthy male volunteers after doses of 160, 320, 480, and 640 mg once daily for 7 days. Multiple serum or plasma and urine samples were collected on days 1 and 7 and were analyzed for gemifloxacin by high-performance liquid chromatography (HPLC)-fluorescence (study 1) or HPLC-mass spectrometry (study 2). Safety assessments included vital signs, 12-lead electrocardiogram (ECG) readings, hematology, clinical chemistry, urinalysis, and adverse experience monitoring. Gemifloxacin was rapidly absorbed, with a time to maximum concentration of approximately 1 h after dosing followed by a biexponential decline in concentration. Generally, maximum concentration and area under the concentration-time curve (AUC) increased linearly with dose after either single or repeat doses. Mean +/- standard deviation values of AUC(0-tau) on day 7 were 4.92 +/- 1.08, 9.06 +/- 2.20, 12.2 +/- 3.69, and 20.1 +/- 3.67 microg x h/ml following 160-, 320-, 480-, and 640-mg doses, respectively. The terminal-phase half-life was approximately 7 to 8 h, independent of dose, and was similar following single and repeated administrations. There was minimal accumulation of gemifloxacin after multiple dosing. Approximately 20 to 30% of the administered dose was excreted unchanged in the urine. The renal clearance was 160 ml/min on average after single and multiple doses, which was slightly greater than the accepted glomerular filtration rate (approximately 120 ml/min). These data show that the pharmacokinetics of gemifloxacin are linear and independent of dose. Gemifloxacin was generally well tolerated, although one subject was withdrawn from the study after 6 days at 640 mg for mild, transient elevations of alanine aminotransferase and aspartate

  10. 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

  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. Pharmacokinetics of orally administered ibuprofen in African and Asian elephants (Loxodonta africana and Elephas maximus).

    Science.gov (United States)

    Bechert, Ursula; Christensen, J Mark

    2007-06-01

    The pharmacokinetic parameters of S(+) and R(-) ibuprofen were determined in 20 elephants after oral administration of preliminary 4-, 5-, and 6-mg/kg doses of racemic ibuprofen. Following administration of 4 mg/kg ibuprofen, serum concentrations of ibuprofen peaked at 5 hr at 3.9 +/- 2.07 microg/ml R(-) and 10.65 +/- 5.64 microg/ml S(+) (mean +/- SD) in African elephants (Loxodonta africana) and at 3 hr at 5.14 +/- 1.39 microg/ml R(-) and 13.77 +/- 3.75 microg/ml S(+) in Asian elephants (Elephas maximus), respectively. Six-milligram/kilogram dosages resulted in peak serum concentrations of 5.91 +/- 2.17 microg/ml R(-) and 14.82 +/- 9.71 microg/ml S(+) in African elephants, and 5.72 +/- 1.60 microg/ml R(-) and 18.32 +/- 10.35 microg/ml S(+) in Asian elephants. Ibuprofen was eliminated with first-order kinetics characteristic of a single-compartment model with a half-life of 2.2-2.4 hr R(-) and 4.5-5.1 hr S(+) in African elephants and 2.4-2.9 hr R(-) and 5.9-7.7 hr S(+) in Asian elephants. Serum concentrations of R(-) ibuprofen were undetectable at 24 hr, whereas S(+) ibuprofen decreased to below 5 microg/ml 24 hr postadministration in all elephants. The volume of distribution was estimated to be between 322 and 356 ml/kg R(-) and 133 and 173 ml/kg S(+) in Asian elephants and 360-431 ml/kg R(-) and 179-207 ml/kg S(+) in African elephants. Steady-state serum concentrations of ibuprofen ranged from 2.2 to 10.5 microg/ml R(-) and 5.5 to 32.0 microg/ml S(+) (mean: 5.17 +/- 0.7 R(-) and 13.95 +/- 0.9 S(+) microg/ml in African elephants and 5.0 +/- 1.09 microg/ml R(-) and 14.1 +/- 2.8 microg/ml S(+) in Asian elephants). Racemic ibuprofen administered at 6 mg/kg/12 hr for Asian elephants and at 7 mg/kg/12 hr for African elephants results in therapeutic serum concentrations of this antiinflammatory agent.

  13. Pharmacokinetics and safety study of posaconazole intravenous solution administered peripherally to healthy subjects.

    Science.gov (United States)

    Kersemaekers, Wendy M; van Iersel, Thijs; Nassander, Ulla; O'Mara, Edward; Waskin, Hetty; Caceres, Maria; van Iersel, Marlou L P S

    2015-02-01

    This study evaluated the safety, tolerability, and pharmacokinetics of a posaconazole i.v. (intravenous) solution. This was a single-center, 2-part, randomized, rising single- and multiple-dose study in healthy adults. In part 1, subjects received 0 (vehicle), 50, 100, 200, 250, or 300 mg posaconazole in a single dose i.v. by 30-min peripheral infusion (6 cohorts of 12 subjects each [9 active and 3 placebo], making a total of 72 subjects). Blood samples were collected until 168 h postdose. In part 2, subjects were to receive 2 peripheral infusions at a 12-h interval on day 1 followed by once-daily infusion for 9 days. However, part 2 was terminated early because of high rates of infusion site reactions with multiple dosing at the same infusion site. The pharmacokinetics results for part 1 (n=45 subjects) showed that the mean posaconazole exposure (area under the concentration-time curve from time zero to infinity [AUC0-∞]) ranged from 4,890 to 46,400 ng · h/ml (range of coefficient of variation values, 26 to 50). The dose-proportionality slope estimate (90% confidence interval) for AUC0-∞ was 1.30 (1.19 to 1.41), indicating a greater-than-dose-proportional increase. The data for safety in part 1 show that 29/72 subjects had ≥1 adverse event. Infusion site reactions were reported in 2/9 vehicle subjects, 0/18 placebo subjects, and 7/45 i.v. posaconazole subjects. The data for safety in part 2 show that infusion site reactions were reported in 1/4 (25%) placebo subjects, 3/9 (33%) vehicle control subjects, and 4/5 (80%) i.v. posaconazole (100 mg) subjects (3 posaconazole recipients subsequently developed thrombophlebitis and were discontinued from treatment). In conclusion, the posaconazole i.v. solution showed a greater-than-dose-proportional increase in exposure, primarily at doses below 200 mg. When administered peripherally at the same infusion site, multiple dosing of i.v. posaconazole led to unacceptably high rates of infusion site reactions. Intravenous

  14. Distribution and histologic effects of intravenously administered amorphous nanosilica particles in the testes of mice

    Energy Technology Data Exchange (ETDEWEB)

    Morishita, Yuki [Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Yoshioka, Yasuo, E-mail: yasuo@phs.osaka-u.ac.jp [Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Satoh, Hiroyoshi; Nojiri, Nao [Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Nagano, Kazuya [Laboratory of Biopharmaceutical Research, National Institute of Biomedical Innovation, 7-6-8 Saitoasagi, Ibaraki, Osaka 567-0085 (Japan); Abe, Yasuhiro [Cancer Biology Research Center, Sanford Research/USD, 2301 E. 60th Street N, Sioux Falls, SD 57104 (United States); Kamada, Haruhiko; Tsunoda, Shin-ichi [Laboratory of Biopharmaceutical Research, National Institute of Biomedical Innovation, 7-6-8 Saitoasagi, Ibaraki, Osaka 567-0085 (Japan); The Center for Advanced Medical Engineering and Informatics, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Nabeshi, Hiromi [Division of Foods, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya-ku, Tokyo 158-8501 (Japan); Yoshikawa, Tomoaki [Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Tsutsumi, Yasuo, E-mail: ytsutsumi@phs.osaka-u.ac.jp [Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Laboratory of Biopharmaceutical Research, National Institute of Biomedical Innovation, 7-6-8 Saitoasagi, Ibaraki, Osaka 567-0085 (Japan); The Center for Advanced Medical Engineering and Informatics, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan)

    2012-04-06

    Highlights: Black-Right-Pointing-Pointer There is rising concern regarding the potential health risks of nanomaterials. Black-Right-Pointing-Pointer Few studies have investigated the effect of nanomaterials on the reproductive system. Black-Right-Pointing-Pointer Here, we evaluated the intra-testicular distribution of nanosilica particles. Black-Right-Pointing-Pointer We showed that nanosilica particles can penetrate the blood-testis barrier. Black-Right-Pointing-Pointer These data provide basic information on ways to create safer nanomaterials. -- Abstract: Amorphous nanosilica particles (nSP) are being utilized in an increasing number of applications such as medicine, cosmetics, and foods. The reduction of the particle size to the nanoscale not only provides benefits to diverse scientific fields but also poses potential risks. Several reports have described the in vivo and in vitro toxicity of nSP, but few studies have examined their effects on the male reproductive system. The aim of this study was to evaluate the testicular distribution and histologic effects of systemically administered nSP. Mice were injected intravenously with nSP with diameters of 70 nm (nSP70) or conventional microsilica particles with diameters of 300 nm (nSP300) on two consecutive days. The intratesticular distribution of these particles 24 h after the second injection was analyzed by transmission electron microscopy. nSP70 were detected within sertoli cells and spermatocytes, including in the nuclei of spermatocytes. No nSP300 were observed in the testis. Next, mice were injected intravenously with 0.4 or 0.8 mg nSP70 every other day for a total of four administrations. Testes were harvested 48 h and 1 week after the last injection and stained with hematoxylin-eosin for histologic analysis. Histologic findings in the testes of nSP70-treated mice did not differ from those of control mice. Taken together, our results suggest that nSP70 can penetrate the blood-testis barrier and the

  15. 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...

  16. Vincristine, doxorubicin and dexamethasone (VAD) administered as rapid intravenous infusion for first-line treatment in untreated multiple myeloma

    NARCIS (Netherlands)

    Segeren, CM; Sonneveld, P; van der Holt, B; Baars, JW; Biesma, DH; Cornellissen, JJ; Croockewit, AJ; Dekker, AW; Fibbe, WE; Lowenberg, B; Kooy, MV; van Oers, MHJ; Richel, DJ; Vellenga, E; Verhoef, GEG; Wijermans, PW; Wittebol, S; Lokhorst, HM

    1999-01-01

    We examined the feasibility of achieving a rapid response in patients with previously untreated multiple myeloma by administering vincristine 0.4mg and doxorubicin 9 mg/m(2) as a rapid intravenous infusion for 4d together with intermittent high-dose dexamethasone 40 mg (VAD) for remission induction

  17. 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…

  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. NEUROMUSCULAR AND CARDIOVASCULAR EFFECTS OF NEOSTIGMINE AND METHYL-ATROPINE ADMINISTERED AT DIFFERENT DEGREES OF ROCURONIUM-INDUCED NEUROMUSCULAR BLOCK

    NARCIS (Netherlands)

    VANDENBROEK, L; PROOST, JH; WIERDA, JMKH; NJOO, MD; HENNIS, PJ

    1994-01-01

    The neuromuscular and cardiovascular effects of neostigmine, 40 mug kg-1, and methyl-atropine, 7 mug kg-1, administered at different degrees of rocuronium-induced (600 mug kg-1) neuromuscular block were evaluated. In one group of patients spontaneous recovery was awaited (Group A; n = 20). Neostigmi

  20. Investigating Administered Essay and Multiple-Choice Tests in the English Department of Islamic Azad University, Hamedan Branch

    Science.gov (United States)

    Karimi, Lotfollah; Mehrdad, Ali Gholami

    2012-01-01

    This study has attempted to investigate the administered written tests in the language department of Islamic Azad University of Hamedan, Iran from validity, practicality and reliability points of view. To this end two steps were taken. First, examining 112 tests, we knew that the face validity of 50 tests had been threatened, 9 tests lacked…

  1. 8 CFR 1337.2 - 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. 1337.2 Section 1337.2 Aliens and Nationality EXECUTIVE OFFICE FOR IMMIGRATION REVIEW, DEPARTMENT OF JUSTICE NATIONALITY REGULATIONS OATH OF ALLEGIANCE § 1337.2...

  2. 40 CFR 147.51 - State-administered program-Class I, III, IV, and V wells.

    Science.gov (United States)

    2010-07-01

    ... PROGRAMS Alabama § 147.51 State-administered program—Class I, III, IV, and V wells. The UIC program for Class I, III, IV and V wells in the State of Alabama, except those on Indian lands, is the program... for Class I, III, IV, and V UIC Program,” September 21, 1982; (3) Letter from Alabama Chief...

  3. 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...

  4. 10 CFR Appendix A to Part 5 - List of Federal Financial Assistance Administered by the Nuclear Regulatory Commission to Which...

    Science.gov (United States)

    2010-01-01

    ... the Nuclear Regulatory Commission to Which Title IX Applies Note: All recipients of Federal financial... 10 Energy 1 2010-01-01 2010-01-01 false List of Federal Financial Assistance Administered by the Nuclear Regulatory Commission to Which Title IX Applies A Appendix A to Part 5 Energy NUCLEAR...

  5. Equivalency of Computer-Assisted and Paper-and-Pencil Administered Versions of the Minnesota Multiphasic Personality Inventory-2.

    Science.gov (United States)

    Pinsoneault, Terry B.

    1996-01-01

    Computer-assisted and paper-and-pencil-administered formats for the Minnesota Multiphasic Personality Inventories were investigated. Subjects were 32 master's and doctoral-level counseling students. Findings indicated that the two formats were comparable and that students preferred the computer-assisted format. (AEF)

  6. 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…

  7. 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...

  8. Maintenance of increased coronary blood flow in excess of demand by nisoldipine administered as an intravenous infusion

    NARCIS (Netherlands)

    A.L. Soward; P.J. de Feyter (Pim); P.G. Hugenholtz (Paul); P.W.J.C. Serruys (Patrick)

    1986-01-01

    textabstractSystemic and hemodynamic effects of nisoldipine, administered as a 4.5-micrograms/kg intravenous bolus over 3 minutes followed immediately by an infusion of 0.2 microgram/kg/min over 30 minutes, were studied in 13 patients undergoing diagnostic catheterization for suspected coronary arte

  9. 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…

  10. Walk a Mile in My Shoes: Stakeholder Accounts of Testing Experience with a Computer-Administered Test

    Science.gov (United States)

    Fox, Janna; Cheng, Liying

    2015-01-01

    In keeping with the trend to elicit multiple stakeholder responses to operational tests as part of test validation, this exploratory mixed methods study examines test-taker accounts of an Internet-based (i.e., computer-administered) test in the high-stakes context of proficiency testing for university admission. In 2013, as language testing…

  11. 40 CFR 147.251 - EPA-administered program-Class I, III, IV and V wells and Indian lands.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program-Class I, III, IV and V wells and Indian lands. 147.251 Section 147.251 Protection of Environment ENVIRONMENTAL... Indian lands. (a) Contents. The UIC program in the State of California for Class I, III, IV and V...

  12. 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

  13. PHARMACOKINETICS OF PARENTERAL 13-CIS-RETINOIC ACID FORMULATIONS IN RATS

    NARCIS (Netherlands)

    GUCHELAAR, HJ; BEUKEVELD, GJJ; MULDER, NH; OOSTERHUIS, JW; Wouda, S.

    1992-01-01

    The pharmacokinetics of three 13-cis-retinoic acid formulations were studied after intraperitoneal (ip) administration to rats. Rats were given ip injections of 2.5 mg of 13-cis-retinoic acid per 360 g of body weight; the drug was administered as an alkaline solution, suspended in corn oil, or as a

  14. Thai Grade 11 Students' Alternative Conceptions for Acid-Base Chemistry

    Science.gov (United States)

    Artdej, Romklao; Ratanaroutai, Thasaneeya; Coll, Richard Kevin; Thongpanchang, Tienthong

    2010-01-01

    This study involved the development of a two-tier diagnostic instrument to assess Thai high school students' understanding of acid-base chemistry. The acid-base diagnostic test (ABDT) comprising 18 items was administered to 55 Grade 11 students in a science and mathematics programme during the second semester of the 2008 academic year. Analysis of…

  15. The osmotically and histamine-induced enhancement of the plasma vasopressin level is diminished by intracerebroventricularly administered orexin in rats.

    Science.gov (United States)

    Kis, Gyöngyi K; Molnár, Andor H; Daruka, Leila; Gardi, János; Rákosi, Kinga; László, Ferenc; László, Ferenc A; Varga, Csaba

    2012-04-01

    The effects of the centrally administered neuropeptides orexin-A on water intake and vasopressin (VP) secretion were studied in male Wistar rats (180-250 g). Different doses (10, 30, and 90 μg/10 μl) of the orexins and the specific orexin receptor-1 (OX(1)) antagonist SB 408124 (30 μg/10 μl) were administered intracerebroventricularly (i.c.v.) under anaesthesia, and the water consumption was measured during 6 h. A plasma VP level elevation was induced by histamine (10 mg/kg) or 2.5% NaCl (10 ml/kg) administered intraperitoneally (i.p.). The plasma VP levels were measured by radioimmunoassay. Increased water consumption was observed after the administration of 30 μg/10 μl orexin-A. There were no changes in basal VP secretion after the administration of different doses of the orexins. A significant increase in plasma VP concentration was detected following histamine administration. After 2.5% NaCl administration, there was a moderate VP level enhancement. Intracerebroventricularly administered orexin-A (30 μg/10 μl) blocked the VP level increase induced by either histamine or 2.5% NaCl administration. The inhibitory effects were prevented by the specific OX(1) receptor antagonist. In conclusion, the orexins increased water consumption. After 30 μg/10 μl orexin-A administration, the polydipsia was more pronounced. The OX(1) receptor antagonist significantly decreased the polydipsia. Histamine or hyperosmotic VP release enhancement was blocked by previously administered orexin. This inhibition was not observed following OX(1) receptor antagonist administration. Our results suggest that the effects of the orexins on water consumption or blockade of the histamine and osmosis-induced VP level increase are mediated by the OX(1) receptor.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.