Zoledronic acid and alendronate sodium and the implications in orthodontic movement.

Science.gov (United States)

Franzoni, J S; Soares, F M P; Zaniboni, E; Vedovello Filho, M; Santamaria, M P; Dos Santos, G M T; Esquisatto, M A M; Felonato, M; Mendonca, F A S; Franzini, C M; Santamaria, M

2017-08-01

To evaluate orthodontic tooth movement (OTM) in rats treated with two types of bisphosphonates (BPs), alendronate sodium (A) and zoledronic acid (Z). In all, 15 male Wistar rats were randomly divided into three groups. Group OTM+A: orthodontic tooth movement and subcutaneous administration of alendronate sodium (2.5 mg/kg); Group OTM+Z: orthodontic tooth movement and subcutaneous administration of zoledronic acid (0.02 mg/kg), and Group OTM: orthodontic tooth movement and subcutaneous injection of saline. The BPs were administered once a day during 25 days before OTM started and during 10 days of OTM. The left upper first molar was moved with a stainless-steel closed coil spring which delivered an initial force of 0.4N. OTM was measured with a digital caliper comparing the moved and the contralateral side. The histomorphometric analysis counted the number of osteoclasts, inflammatory cells, blood vessels and fibroblasts (n/10 4  m 2 ) in periodontal ligament (PDL) of the distobuccal root. A reduction of 58.3% of OTM was found in Group OTM+A and 99.6% in Group OTM+Z, when compared with Group OTM. There was a significant decrease of osteoclasts and inflammatory cells in BP-treated groups. Blood vessels and fibroblastic cells decreased mainly in Group OTM+Z. Alendronate sodium and zoledronic acid have similar effects on the periodontal tissue during orthodontic treatment in rats. Especially, zoledronic acid can affect orthodontic tooth movement. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Association between timing of zoledronic acid infusion and hip fracture healing

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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...

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...

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

analysis, 101 of 1054 patients in the zoledronic acid group (9.6%) and 141 of 1057 patients in the placebo group (13.3%) died, a reduction of 28% in deaths from any cause in the zoledronic-acid group (P = 0.01). The most frequent adverse events in patients 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 in the two groups. CONCLUSIONS: An annual...

Evidences of safety and tolerability of the zoledronic acid 5 mg yearly in the post-menopausal osteoporosis: the HORIZON project

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F. Bertoldo

2011-06-01

Full Text Available Bisphosphonates are the most commonly prescribed medications for the treatment of osteoporosis. Despite evidence supporting the anti-fracture efficacy of aminobisphosphonates approximately 50% of patients do not follow their prescribed treatment regimen and/or discontinue treatment within the first year. Poor compliance is associated with negative outcomes, including increased fracture risk. Tolerability and safety are among the causes of poor compliance. Intravenous bisphosphonates avoids the gastrointestinal intolerance and the complex dosing instruction of the oral route ensuring full compliance which may provide improved efficacy. However, there are some concerns regarding potent intravenous bisphosphonates as zoledronic acid with respect to tolerability, mainly the acute phase response and to safety, mainly a theoretical risk of over suppression of bone turnover, renal toxicity and osteonecrosis of the jaw. In the HORIZON study, 152 patients on active treatment (82 or placebo (70 underwent to a bone biopsy after double tetracycline labeling. Bone biopsies (iliac crest were obtained at the final visit at month 36, 1 year after the last infusion. The biopsies were analyzed by histomorphometry on bone sections and by micro-CT (μCT analysis. 143 biopsies (76 zoledronic acid, 67 placebo had at least one μCT parameter measured and 111 were available for quantitative histomorphometry (59 zoledronic acid, 52 placebo. Micro-CT analysis of bone structure revealed higher trabecular bone volume (BV/TV, decreased trabecular separation (Tb.Sp, and a strong trend towards improvement in connectivity density in biopsies obtained from patients treated with zoledronic acid, indicating preservation of trabecular bone structure with respect to placebo. Histomorphometric analysis obtained from patients treated with zoledronic acid exhibited reduction of bone turnover, as suggested by decreased activation frequency (Ac.F by 63%, mineralizing surface (MS

Zoledronic acid overcomes chemoresistance and immunosuppression of malignant mesothelioma

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Kopecka, Joanna; Gazzano, Elena; Sara, Orecchia; Ghigo, Dario; Riganti, Chiara

2015-01-01

The human malignant mesothelioma (HMM) is characterized by a chemoresistant and immunosuppressive phenotype. An effective strategy to restore chemosensitivity and immune reactivity against HMM is lacking. We investigated whether the use of zoledronic acid is an effective chemo-immunosensitizing strategy. We compared primary HMM samples with non-transformed mesothelial cells. HMM cells had higher rate of cholesterol and isoprenoid synthesis, constitutive activation of Ras/extracellular signal-regulated kinase1/2 (ERK1/2)/hypoxia inducible factor-1α (HIF-1α) pathway and up-regulation of the drug efflux transporter P-glycoprotein (Pgp). By decreasing the isoprenoid supply, zoledronic acid down-regulated the Ras/ERK1/2/HIF-1α/Pgp axis and chemosensitized the HMM cells to Pgp substrates. The HMM cells also produced higher amounts of kynurenine, decreased the proliferation of T-lymphocytes and expanded the number of T-regulatory (Treg) cells. Kynurenine synthesis was due to the transcription of the indoleamine 1,2 dioxygenase (IDO) enzyme, consequent to the activation of the signal transducer and activator of transcription-3 (STAT3). By reducing the activity of the Ras/ERK1/2/STAT3/IDO axis, zoledronic acid lowered the kyurenine synthesis and the expansion of Treg cells, and increased the proliferation of T-lymphocytes. Thanks to its ability to decrease Ras/ERK1/2 activity, which is responsible for both Pgp-mediated chemoresistance and IDO-mediated immunosuppression, zoledronic acid is an effective chemo-immunosensitizing agent in HMM cells. PMID:25544757

Fracture risk and zoledronic acid therapy in men with osteoporosis

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

2012-01-01

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

Short-term intravenous zoledronic acid in severe osteogenesis imperfecta : A report of three siblings of children

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Hadyanto Lim

2008-06-01

Full Text Available This report documented the clinical and biochemical side effects on the first dose of intravenous zoledronic acid therapy in three siblings with severe osteogenesis imperfecta. Zoledronic acid was administered in 50 ml 0.9% saline solution over a period of 30 minutes. All patients had fever during the first 6 to 48 hours after the first infusion. There were no renal side effects, apart from asymptomatic hypocalcemia and hypophosphatemia at 48 and 72 hours after zoledronic acid infusion. The minimal clinical side effects were easily manageable. (Med J Indones 2008; 17: 127-30Keywords: zoledronic acid, osteogenesis imperfecta, side effects

Acute bilateral uveitis and right macular edema induced by a single infusion of zoledronic acid for the treatment of postmenopausal osteoporosis as a substitution for oral alendronate: a case report.

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Tian, Yiming; Wang, Rui; Liu, Lianyuan; Ma, Chunming; Lu, Qiang; Yin, Fuzai

2016-02-11

Zoledronic acid-induced uveitis (ZAIU) is rare but severe, and has been recently considered part of an acute phase reaction. Only 15 cases have been reported since 2005. Here we describe a case with macular edema, which is the first reported case observed after long-term alendronate tolerance. A 63-year-old Asian woman received her first intravenous zoledronic acid treatment for the management of postmenopausal osteoporosis as a more convenient substitute for oral alendronate. Twenty-four hours later, bilateral eye irritations, periorbital swelling, blurred vision, and diplopia presented. The complete blood count and transaminase levels were normal, but the erythrocytic sedimentation, C-reactive protein, and serum C4 levels were elevated. On detailed ophthalmological examination, a diagnosis of bilateral acute uveitis and macular edema in the right eye was made. The ocular symptoms were not improved until administration of topical and oral steroids. Complete resolution was achieved. There was no rechallenge of bisphosphonates, and no recurrence at 6 months follow-up. Based on an extensive review, abnormal fundus is rarely reported, especially in cases of macular edema. Rechallenge with zoledronic acid in five cases induced no additional uveitis, and changing the medication to pamidronate in another patient was also tolerated. Interestingly, our patient suffered from uveitis soon after intravenous zoledronate exposure after a two-year tolerance to oral alendronate. This is the first report of zoledronic acid induced uveitis with macular edema after long-term alendronate tolerance. Prior oral alendronate may not entirely prevent ZAIU. Steroids are usually necessary in the treatment of ZAIU. Bisphosphonate rechallenge is not fully contraindicated, and prior steroid administration may be a more reasonable treatment choice according to the available evidence.

Cost-effectiveness of denosumab versus zoledronic acid for preventing skeletal-related events in the Czech Republic.

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Cristino, Joaquim; Finek, Jíndřich; Jandova, Petra; Kolek, Martin; Pásztor, Bálint; Giannopoulou, Christina; Qian, Yi; Brezina, Tomas; Lothgren, Mickael

2017-08-01

This study assessed the cost-effectiveness of the subcutaneous RANKL inhibitor, denosumab, vs the intravenous bisphosphonate, zoledronic acid, for the prevention of skeletal-related events (SREs) in patients with prostate cancer, breast cancer, and other solid tumors (OST) in the Czech Republic. A lifetime Markov model was developed to compare the effects of denosumab and zoledronic acid on costs (including drug costs and administration, patient management, SREs, and adverse events), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios from a national payer perspective. Different discount rates, time horizons, SRE rates, distributions, and nature (asymptomatic vs all SREs), and the inclusion of treatment discontinuation were considered in scenario analyses. The robustness of the model was tested using deterministic and probabilistic sensitivity analyses. Across tumor types, denosumab was associated with fewer SREs, improved QALYs, and higher total costs over a lifetime. The incremental cost per QALY gained for denosumab vs zoledronic acid was 382,673 CZK for prostate cancer, 408,450 CZK for breast cancer, and 608,133 CZK for OST. Incremental costs per SRE avoided for the same tumor type were 54,007 CZK, 51,765 CZK, and 94,426 CZK, respectively. In scenario analyses, the results remained similar to baseline, when different discount rates and time horizons were considered. At a non-official willingness-to-pay threshold of 1.2 million CZK, the probabilities of denosumab being cost-effective vs zoledronic acid were 0.64, 0.67, and 0.49 for prostate cancer, breast cancer, and OST, respectively. The SRE rates used were obtained from clinical trials; studies suggest rates may be higher in clinical practice. Additional evidence on real-world SRE rates could further improve the accuracy of the modeling. Compared with zoledronic acid, denosumab provides a cost-effective treatment option for the prevention of SREs in patients with prostate cancer

Monitoring changes in quality of life in patients with lung cancer under treatment with chemotherapy and co administration of zoledronic acid by using specialized questionnaires.

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Tremmas, Ioannis; Petsatodis, George; Potoupnis, Michael; Laskou, Stella; Giannakidis, Dimitrios; Mantalovas, Stylianos; Koulouris, Charilaos; Katsaounis, Athanasios; Pavlidis, Efstathios; Amaniti, Aikaterini; Huang, Haidong; Bai, Chong; Shi, Dongchen; Dardas, Athanasios; Zarogoulidis, Paul; Sardeli, Chrisanthi; Konstantinou, Fotis; Katsikogiannis, Nikolaos; Zarogoulidis, Konstantinos; Karapantzos, Ilias; Karapantzou, Chrysanthi; Shen, Xiaping; Kesisoglou, Isaak; Sapalidis, Konstantinos

2018-01-01

Background: Due to the severity of the primary disease in patients with lung cancer, quality of life (QoL) is often overlooked. Factors that form QoL should be taken in consideration when planning the appropriate treatment and determining therapy targets, because of the increasing frequency of bone metastasis leading to high levels of pain. Purpose of this study is to assess quality of life in patients with lung cancer, before and after treatment combined with zoledronic acid. Methods and materials: QoL was assessed in 80 patients (49 males-31 females), of which 45 developed bone metastasis. Prior and post treatment (with co administration of zoledronic acid) seven reliable scales: Pittsburgh Sleep Quality index (PSQI), Epworth Sleeping Scale (ess), Dyspnea Scale (ds), Fatigue Severity Scale (FSS), Brief Pain Inventory (BPI), Fact-G scale for sleep quality and EQ-5D for general health condition. Results: Statistically positive correlations were verified between PSQI-DS, PSQI-FSS, BPI-ESS, DS-FSS, DS-BPI and BPI-FSS (pbetterment in quality of life was marked (p<0,001). Although significant decrease in fatigue levels was observed (p<0,001) there has been an increase in dyspnea symptoms (p<0,001). Conclusions: Significant improvement was apparent when zoledronic acid was co administered in any treatment in patients with lung cancer. Sleep quality, fatigue and pain parameters also improved, with no positive impact on the symptoms of dyspnea.

Addition of docetaxel and/or zoledronic acid to standard of care for hormone-naive prostate cancer: a cost-effectiveness analysis.

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Zhang, Pengfei; Wen, Feng; Fu, Ping; Yang, Yu; Li, Qiu

2017-07-31

The effectiveness of the addition of docetaxel and/or zoledronic acid to the standard of care (SOC) for hormone-naive prostate cancer has been evaluated in the STAMPEDE trial. The object of the present analysis was to evaluate the cost-effectiveness of these treatment options in the treatment of advanced hormone-naive prostate cancer in China. A cost-effectiveness analysis using a Markov model was carried out from the Chinese societal perspective. The efficacy data were obtained from the STAMPEDE trial and health utilities were derived from previous studies. Transition probabilities were calculated based on the survival in each group. The primary endpoint in the analysis was the incremental cost-effectiveness ratio (ICER), and model uncertainties were explored by 1-way sensitivity analysis and probabilistic sensitivity analysis. SOC alone generated an effectiveness of 2.65 quality-adjusted life years (QALYs) at a lifetime cost of $20,969.23. At a cost of $25,001.34, SOC plus zoledronic acid was associated with 2.69 QALYs, resulting in an ICER of $100,802.75/QALY compared with SOC alone. SOC plus docetaxel gained an effectiveness of 2.85 QALYs at a cost of $28,764.66, while the effectiveness and cost data in the SOC plus zoledronic acid/docetaxel group were 2.78 QALYs and $32,640.95. Based on the results of the analysis, SOC plus zoledronic acid, SOC plus docetaxel, and SOC plus zoledronic acid/docetaxel are unlikely to be cost-effective options in patients with advanced hormone-naive prostate cancer compared with SOC alone.

Zoledronic acid enhances the effect of radiotherapy for bone metastases from renal cell carcinomas. More than a 24-month median follow-up

International Nuclear Information System (INIS)

Takeda, Naoki; Isu, Kazuo; Hiraga, Hiroaki; Shinohara, Nobuo; Minami, Akio; Kamata, Hajime

2012-01-01

Renal cell carcinoma (RCC) is thought to respond unreliably to radiotherapy (RT). Zoledronic acid significantly reduces the risk of skeletal complications. This study investigated whether RT with zoledronic acid prolonged the time to bone-lesion progression in comparison with RT alone. Twenty-seven patients (34 lesions) with bone metastases secondary to RCC undergoing treatment with RT with or without zoledronic acid were retrospectively evaluated at two institutions between 1999 and 2009. Twelve patients were treated with RT alone from 1999 to 2008 (RT group). Fifteen patients were treated with RT and zoledronic acid from 2006 to 2009 (RT+Z group). The time to skeletal-related events and pain progression were assessed from patients' medical records. The median (range) follow-up was 26 (3-75) and 24 (3-55) months in the RT and RT+Z groups, respectively. Three patients (three lesions) in the RT+Z group had skeletal-related events (SREs). In contrast, six patients (eight lesions) in the RT group had SREs. SREs comprised pathological fractures in five, additional surgeries in three, spinal cord or cauda equine compression in two, and repeat RT in one. There was a significant difference in SRE-free survival time and duration of site-specific pain response between groups. RT combined with zoledronic acid significantly prolonged SRE-free survival and duration of pain response compared with RT alone in the treatment of osseous metastases from RCC. (author)

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

report a case of a young woman with CF, lung transplantation and low bone mass developing long-term leukopenia after treatment with zoledronic acid. The leukopenia, with a strong affection of the neutrocytes, lasted for 4 months and the condition only went into remission after granulocyte-colony...

Enhancing cytotoxic and apoptotic effect in OVCAR-3 and MDAH-2774 cells with all-trans retinoic acid and zoledronic acid: a paradigm of synergistic molecular targeting treatment for ovarian cancer

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Kısım Aslı

2010-07-01

Full Text Available Abstract Background Ovarian cancer is the most fatal gynecologic malignancies in the world. Although, platinum based treatments are widely used, the disease becomes treatment refractory within two years, and novel treatment options should be searched. All- trans retinoic acid (ATRA induces growth arrest, differentiation and cell death in some types of cancer cells and its combination with various anticancer agents results in enhanced cytotoxicity. Zoledronic acid is a common bisphosphonate known for its anticancer effects beyond its current use in the treatment of cancer-induced bone disease. We aimed to investigate the possible additive/synergistic effect of both agents in OVCAR-3 and MDAH-2774 ovarian cancer cell lines, since both agents show superiority to conventional cytotoxics in terms of adverse events. Methods XTT cell proliferation assay was used for showing cytotoxicity. For verifying apoptosis, both DNA Fragmentation by ELISA assay and caspase 3/7 activity measurement were used. OligoGeArray® which consists of 112 apoptosis related genes was used to elucidate the genetic changes within cancer cells. To validate our oligoarray results, quantitative real-time PCR was performed on four selected genes that were maximally effected by the combination treatment: lymphotoxin beta receptor (LTBR, myeloid cell leukemia-1 (MCL-1, tumor necrosis factor receptor superfamily, member 1A (TNFRSF1A, TNFRSF1A-associated death domain protein (TRADD. Results We demonstrated that a novel combination of ATRA and zoledronic acid is a strong inducer of apoptotic related cell death in both ovarian cancer cells. While the combination therapy significantly induced proapoptotic genes such as tumor necrosis factor receptor superfamily (TNFRSF, TRADD and caspase 4, some of the antiapoptotic genes such as members of MCL-1, LTBR, BAG3 and Bcl-2 family members were inhibited. Conclusions These are the preliminary molecular results of a novel combination treatment of

Incidence of osteonecrosis of the jaw in women with postmenopausal osteoporosis in the health outcomes and reduced incidence with zoledronic acid once yearly pivotal fracture trial.

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Grbic, John T; Landesberg, Regina; Lin, Shou-Qing; Mesenbrink, Peter; Reid, Ian R; Leung, Ping-Chung; Casas, Noemi; Recknor, Christopher P; Hua, Ye; Delmas, Pierre D; Eriksen, Erik F

2008-01-01

The authors determined incidence of osteonecrosis of the jaw (ONJ) in a large, prospective three-year clinical trial of zoledronic acid in women with postmenopausal osteoporosis (PMO). A total of 7,714 women with PMO received intravenous zoledronic acid 5 mg or a placebo. No spontaneous reports of ONJ were received. An independent, blinded adjudication committee searched the trial's adverse event database by using 60 terms. On an ongoing basis, the committee reviewed the identified events, and it defined ONJ as exposed bone in the maxillofacial area with delayed healing for more than six weeks despite appropriate care. One participant who received a placebo and one participant who received zoledronic acid experienced delayed healing associated with infection. Both conditions resolved after antibiotic therapy, débridement or both. The occurrence of ONJ is rare in a PMO population, and delayed healing of lesions can occur with and without bisphosphonate use over three years. The low incidence of ONJ must be assessed in the context of the clinical benefit of zoledronic acid therapy in reducing hip, vertebral and nonvertebral fractures in this at-risk population. There is no evidence to suggest that healthy patients with osteoporosis who are receiving bisphosphonates require any special treatment beyond routine dental care or to support altering standard treatment practices.

Once-Yearly Zoledronic Acid and Days of Disability, Bed Rest, and Back Pain: Randomized, Controlled HORIZON Pivotal Fracture Trial

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Cauley, Jane A.; Black, Dennis; Boonen, Steven; Cummings, Steven R.; Mesenbrink, Peter; Palermo, Lisa; Man, Zulema; Hadji, Peyman; Reid, Ian R.

2016-01-01

The objective of this study was to determine the effect of once-yearly zoledronic acid on the number of days of back pain and the number of days of disability (ie, limited activity and bed rest) owing to back pain or fracture in postmenopausal women with osteoporosis. This was a multicenter, randomized, double-blind, placebo-controlled trial in 240 clinical centers in 27 countries. Participants included 7736 postmenopausal women with osteoporosis. Patients were randomized to receive either a single 15-minute intravenous infusion of zoledronic acid (5 mg) or placebo at baseline, 12 months, and 24 months. The main outcome measures were self-reported number of days with back pain and the number of days of limited activity and bed rest owing to back pain or a fracture, and this was assessed every 3 months over a 3-year period. Our results show that although the incidence of back pain was high in both randomized groups, women randomized to zoledronic acid experienced, on average, 18 fewer days of back pain compared with placebo over the course of the trial (p = .0092). The back pain among women randomized to zoledronic acid versus placebo resulted in 11 fewer days of limited activity (p = .0017). In Cox proportional-hazards models, women randomized to zoledronic acid were about 6% less likely to experience 7 or more days of back pain [relative risk (RR) = 0.94, 95% confidence interval (CI) 0.90–0.99] or limited activity owing to back pain (RR = 0.94, 95% CI 0.87–1.00). Women randomized to zoledronic acid were significantly less likely to experience 7 or more bed-rest days owing to a fracture (RR = 0.58, 95% CI 0.47–0.72) and 7 or more limited-activity days owing to a fracture (RR = 0.67, 95% CI 0.58–0.78). Reductions in back pain with zoledronic acid were independent of incident fracture. Our conclusion is that in women with postmenopausal osteoporosis, a once-yearly infusion with zoledronic acid over a 3-year period significantly reduced the number of days that

The effect of a single infusion of zoledronic acid on early implant migration in total hip arthroplasty. A randomized, double-blind, controlled trial.

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Friedl, Gerald; Radl, Roman; Stihsen, Christoph; Rehak, Peter; Aigner, Reingard; Windhager, Reinhard

2009-02-01

Aseptic loosening is the most frequent cause of implant failure in total hip arthroplasty. While a direct link between aseptic loosening and periprosthetic bone loss remains elusive, there is plentiful evidence for a close association with early implant migration. The present trial was primarily designed to evaluate whether a single infusion of 4 mg of zoledronic acid prevented early implant migration in patients with osteonecrosis of the femoral head. Fifty patients were consecutively enrolled to receive either zoledronic acid or saline solution after cementless total hip arthroplasty. Radiographs, biochemical parameters of bone turnover, and the Harris hip-rating score were determined preoperatively and at each follow-up examination at seven weeks, six months, one year, and yearly thereafter. The median follow-up period was 2.8 years. We found a significant subsidence of the stem of up to a mean (and standard deviation) of -1.2 +/- 0.6 mm at two years within the control group, and the cups had a mean medialization of 0.6 +/- 1.0 mm and a mean cranialization of 0.6 +/- 0.8 mm (p < 0.001). Treatment with zoledronic acid effectively minimized the migration of the cups in both the transverse and the vertical direction (mean, 0.15 +/- 0.6 mm and 0.06 +/- 0.6 mm, respectively; p < 0.05), while only a trend to decreased subsidence of the stem was detected. Finally, the Harris hip score rapidly increased over time in both treatment groups, although this increase was significantly more pronounced in the zoledronate-treated group than in the control group (analysis of variance, p = 0.008). A single infusion of zoledronic acid shows promise in improving initial fixation of a cementless implant, which may improve the clinical outcome of total hip arthroplasty in patients with osteonecrosis of the femoral head.

PRGF exerts a cytoprotective role in zoledronic acid-treated oral cells.

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Anitua, Eduardo; Zalduendo, Mar; Troya, María; Orive, Gorka

2016-04-01

Bisphosphonates-related osteonecrosis of the jaw (BRONJ) is a common problem in patients undergoing long-term administration of highly potent nitrogen-containing bisphosphonates (N-BPs). This pathology occurs via bone and soft tissue mechanism. Zoledronic acid (ZA) is the most potent intravenous N-BP used to prevent bone loss in patients with bone dysfunction. The objective of this in vitro study was to evaluate the role of different ZA concentrations on the cells from human oral cavity, as well as the potential of plasma rich in growth factors (PRGF) to overcome the negative effects of this BP. Primary human gingival fibroblasts and primary human alveolar osteoblasts were used. Cell proliferation was evaluated by means of a fluorescence-based method. A colorimetric assay to detect DNA fragmentation undergoing apoptosis was used to determine cell death, and the expression of both NF-κB and pNF-κB were quantified by Western blot analysis. ZA had a cytotoxic effect on both human gingival fibroblasts and human alveolar osteoblasts. This BP inhibits cell proliferation, stimulates apoptosis, and induces inflammation. However, the addition of PRGF suppresses all these negative effects of the ZA. PRGF shows a cytoprotective role against the negative effects of ZA on primary oral cells. At present, there is no definitive treatment for bisphosphonates-related osteonecrosis of the jaw (BRONJ), being mainly palliatives. Our results revealed that PRGF has a cytoprotective role in cells exposed to zoledronic acid, thus providing a reliable adjunctive therapy for the treatment of BRONJ pathology.

Reproductive hormone analyses and effects of adjuvant zoledronic acid in early breast cancer – An AZURE (BIG 01/04 sub-study

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Caroline Wilson

2017-11-01

Full Text Available Purpose: Adjuvant bisphosphonates have been shown to improve disease outcomes in early breast cancer in women who are postmenopausal at the start of treatment. We explored the influence of pretreatment serum levels of reproductive hormones in the hypothalamic-pituitary-gonadal (HPG axis from a subset of patients included in the AZURE trial to investigate their impact on disease recurrence and whether reproductive hormone measurements are of value in selecting patients for treatment with adjuvant zoledronic acid.Patients and methods; The AZURE trial is an academic, multi-centre, international phase III trial that randomised patients to standard adjuvant therapy (chemotherapy and/or endocrine therapy±intravenous zoledronic acid, 4 mg for 5 years. Serum from 865 patients taken at randomisation was stored at −80 °C prior to central batch analysis for inhibin A, oestradiol and follicle stimulating hormone (FSH. We assessed the clinical value of pretreatment hormone levels for predicting invasive disease free survival (IDFS, skeletal recurrence and distant recurrence and response to treatment with zoledronic acid. Results: Oestradiol in the postmenopausal range (26 IU/l was associated with a longer time to bone as first recurrence (HR 0.66 95%CI: 0.41–1.04 p=0.072 compared to an FSH ≤26 IU/l. When all 3 hormone levels were within the assay specified postmenopausal range, a trend to improved IDFS was seen with addition of zoledronic acid in biochemically postmenopausal women only (postmenopausal HR=0.81; 95%CI: 0.54–1.22, non-postmenopausal HR=0.99; 95%CI: 0.69–1.39 with risk reductions that mirrored the results of the main AZURE study, although the interaction between menopausal status and treatment effect was not statistically significant (p=0.47. Conclusion: Oestradiol and FSH may influence the pattern of disease recurrence with postmenopausal levels possibly creating a less conducive environment for the

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

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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.

Zoledronic acid enhances antitumor efficacy of liposomal doxorubicin.

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Hattori, Yoshiyuki; Shibuya, Kazuhiko; Kojima, Kaori; Miatmoko, Andang; Kawano, Kumi; Ozaki, Kei-Ichi; Yonemochi, Etsuo

2015-07-01

Previously, we found that the injection of zoledronic acid (ZOL) into mice bearing tumor induced changes of the vascular structure in the tumor. In this study, we examined whether ZOL treatment could decrease interstitial fluid pressure (IFP) via change of tumor vasculature, and enhance the antitumor efficacy of liposomal doxorubicin (Doxil®). When ZOL solution was injected at 40 µg/mouse per day for three consecutive days into mice bearing murine Lewis lung carcinoma LLC tumor, depletion of macrophages in tumor tissue and decreased density of tumor vasculature were observed. Furthermore, ZOL treatments induced inflammatory cytokines such as interleukin (IL)-10 and -12, granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor (TNF)-α in serum of LLC tumor-bearing mice, but not in normal mice, indicating that ZOL treatments might induce an inflammatory response in tumor tissue. Furthermore, ZOL treatments increased antitumor activity by Doxil in mice bearing a subcutaneous LLC tumor, although they did not significantly increase the tumor accumulation of doxorubicin (DXR). These results suggest that ZOL treatments might increase the therapeutic efficacy of Doxil via improvement of DXR distribution in a tumor by changing the tumor vasculature. ZOL treatment can be an alternative approach to increase the antitumor effect of liposomal drugs.

Percutaneous kyphoplasty combined with zoledronic acid infusion in the treatment of osteoporotic thoracolumbar fractures in the elderly

OpenAIRE

Shi,Chen; Zhang,Mi; Cheng,An-Yuan; Huang,Zi-Feng

2018-01-01

Chen Shi,1,* Mi Zhang,2,* An-Yuan Cheng,1 Zi-Feng Huang1 1Department of Trauma Surgery, Wuhan No 1 Hospital, Wuhan, China; 2Department of Orthopedics, Wuhan No 5 Hospital, Wuhan, China *These authors contributed equally to this work Objective: We studied the efficacy of zoledronic acid (ZOL) infusion on radiographic and clinical outcomes after percutaneous kyphoplasty (PKP) for elderly patients with osteoporotic thoracolumbar fractures (osteoporotic vertebral compression fractures...

Percutaneous kyphoplasty combined with zoledronic acid infusion in the treatment of osteoporotic thoracolumbar fractures in the elderly

OpenAIRE

Shi C; Zhang M; Cheng AY; Huang ZF

2018-01-01

Chen Shi,1,* Mi Zhang,2,* An-Yuan Cheng,1 Zi-Feng Huang1 1Department of Trauma Surgery, Wuhan No 1 Hospital, Wuhan, China; 2Department of Orthopedics, Wuhan No 5 Hospital, Wuhan, China *These authors contributed equally to this work Objective: We studied the efficacy of zoledronic acid (ZOL) infusion on radiographic and clinical outcomes after percutaneous kyphoplasty (PKP) for elderly patients with osteoporotic thoracolumbar fractures (osteoporotic vertebral compression fractures [OV...

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

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

DEFF Research Database (Denmark)

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

2009-01-01

undergone surgical repair of hip fracture. In this analysis, we examined whether timing of the first infusion of zoledronic acid study drug after hip fracture repair influenced the antifracture efficacy and mortality benefit observed in the study. A total of 2127 patients (1065 on active treatment and 1062...... was approximately 6 wk. Posthoc analyses were performed by dividing the study population into 2-wk intervals (calculated from time of first infusion in relation to surgical repair) to examine effects on BMD, fracture, and mortality. Analysis by 2-wk intervals showed a significant total hip BMD response......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...

Bone effect of adjuvant tamoxifen, letrozole or letrozole plus zoledronic acid in early-stage breast cancer: the randomized phase 3 HOBOE study.

Science.gov (United States)

Nuzzo, F; Gallo, C; Lastoria, S; Di Maio, M; Piccirillo, M C; Gravina, A; Landi, G; Rossi, E; Pacilio, C; Labonia, V; Di Rella, F; Bartiromo, A; Buonfanti, G; De Feo, G; Esposito, G; D'Aniello, R; Maiolino, P; Signoriello, S; De Maio, E; Tinessa, V; Colantuoni, G; De Laurentiis, M; D'Aiuto, M; Di Bonito, M; Botti, G; Giordano, P; Daniele, G; Morabito, A; Normanno, N; de Matteis, A; Perrone, F

2012-08-01

To measure bone mineral density (BMD) reduction produced by letrozole as compared with tamoxifen and the benefit of the addition of zoledronic acid. A phase 3 trial comparing tamoxifen, letrozole or letrozole+zoledronic acid in patients with hormone receptor-positive early breast cancer was conducted; triptorelin was given to premenopausal patients. Two comparisons were planned: letrozole versus tamoxifen and letrozole+zoledronic acid versus letrozole. Primary end point was the difference in 1-year change of T-score at lumbar spine (LTS) measured by dual energy X-ray absorptiometry scan. Out of 483 patients enrolled, 459 were available for primary analyses. Median age was 50 (range 28-80). The estimated mean difference (95% confidence interval [CI]) in 1-year change of LTS was equal to -0.30 (95% CI -0.44 to -0.17) in the letrozole versus tamoxifen comparison (P<0.0001) and to +0.60 (95% CI +0.46 to +0.77) in the letrozole+zoledronic acid versus letrozole comparison (P<0.0001). Bone damage by letrozole decreased with increasing baseline body mass index in premenopausal, but not postmenopausal, patients (interaction test P=0.004 and 0.47, respectively). In the HOBOE (HOrmonal BOne Effects) trial, the positive effect of zoledronic acid on BMD largely counteracts damage produced by letrozole as compared with tamoxifen. Letrozole effect is lower among overweight/obese premenopausal patients.

Local effect of zoledronic acid on new bone formation in posterolateral spinal fusion with demineralized bone matrix in a murine model.

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Zwolak, Pawel; Farei-Campagna, Jan; Jentzsch, Thorsten; von Rechenberg, Brigitte; Werner, Clément M

2018-01-01

Posterolateral spinal fusion is a common orthopaedic surgery performed to treat degenerative and traumatic deformities of the spinal column. In posteriolateral spinal fusion, different osteoinductive demineralized bone matrix products have been previously investigated. We evaluated the effect of locally applied zoledronic acid in combination with commercially available demineralized bone matrix putty on new bone formation in posterolateral spinal fusion in a murine in vivo model. A posterolateral sacral spine fusion in murine model was used to evaluate the new bone formation. We used the sacral spine fusion model to model the clinical situation in which a bone graft or demineralized bone matrix is applied after dorsal instrumentation of the spine. In our study, group 1 received decortications only (n = 10), group 2 received decortication, and absorbable collagen sponge carrier, group 3 received decortication and absorbable collagen sponge carrier with zoledronic acid in dose 10 µg, group 4 received demineralized bone matrix putty (DBM putty) plus decortication (n = 10), and group 5 received DBM putty, decortication and locally applied zoledronic acid in dose 10 µg. Imaging was performed using MicroCT for new bone formation assessment. Also, murine spines were harvested for histopathological analysis 10 weeks after surgery. The surgery performed through midline posterior approach was reproducible. In group with decortication alone there was no new bone formation. Application of demineralized bone matrix putty alone produced new bone formation which bridged the S1-S4 laminae. Local application of zoledronic acid to demineralized bone matrix putty resulted in significant increase of new bone formation as compared to demineralized bone matrix putty group alone. A single local application of zoledronic acid with DBM putty during posterolateral fusion in sacral murine spine model increased significantly new bone formation in situ in our model. Therefore, our

A simple RP-HPLC method for related substances of zoledronic acid in pharmaceutical products

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L. Maheswara Reddy

2017-02-01

Full Text Available A novel, selective and sensitive reverse phase-high performance liquid chromatography (RP-HPLC method has been developed for the validated estimation of imidazol-1-yl-acetic acid in zoledronic acid formulations. The separation was achieved on a 5 μ C18 column (250 × 4.6 mm using a mobile phase that consists of the buffer (4.5 g of di-potassium hydrogen phosphate anhydrous and 2.0 g of tetra butyl ammonium hydrogen sulphate (TBAHS in 1000 mL of water and methanol in the ratio of 900:100 v/v. The flow rate was maintained at 1.0 mL min−1. The detection of the constituents was done at 215 nm using a UV detector. The retention times of imidazol-1-yl-acetic acid and zoledronic acid were 7.2 and 10.2 min respectively. Recovery studies were satisfactory and the correlation coefficient, 0.999 indicates linearity of the method within the limits. The developed method can be applicable for regular qualitative analysis.

Combination sclerostin antibody and zoledronic acid treatment outperforms either treatment alone in a mouse model of osteogenesis imperfecta.

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Little, David G; Peacock, Lauren; Mikulec, Kathy; Kneissel, Michaela; Kramer, Ina; Cheng, Tegan L; Schindeler, Aaron; Munns, Craig

2017-08-01

In this study, we examined the therapeutic potential of anti-Sclerostin Antibody (Scl-Ab) and bisphosphonate treatments for the bone fragility disorder Osteogenesis Imperfecta (OI). Mice with the Amish OI mutation (Col1a2 G610C mice) and control wild type littermates (WT) were treated from week 5 to week 9 of life with (1) saline (control), (2) zoledronic acid given 0.025mg/kg s.c. weekly (ZA), (3) Scl-Ab given 50mg/kg IV weekly (Scl-Ab), or (4) a combination of both (Scl-Ab/ZA). Functional outcomes were prioritized and included bone mineral density (BMD), bone microarchitecture, long bone bending strength, and vertebral compression strength. By dual-energy absorptiometry, Scl-Ab treatment alone had no effect on tibial BMD, while ZA and Scl-Ab/ZA significantly enhanced BMD by week 4 (+16% and +27% respectively, P<0.05). Scl-Ab/ZA treatment also led to increases in cortical thickness and tissue mineral density, and restored the tibial 4-point bending strength to that of control WT mice. In the spine, all treatments increased compression strength over controls, but only the combined group reached the strength of WT controls. Scl-Ab showed greater anabolic effects in the trabecular bone than in cortical bone. In summary, the Scl-Ab/ZA intervention was superior to either treatment alone in this OI mouse model, however further studies are required to establish its efficacy in other preclinical and clinical scenarios. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Pregnancy and Lactation-Associated Osteoporosis: Bone Histomorphometric Analysis and Response to Treatment with Zoledronic Acid.

Science.gov (United States)

Grizzo, Felipe Merchan Ferraz; da Silva Martins, Janaina; Pinheiro, Marcelo M; Jorgetti, Vanda; Carvalho, Maria Dalva Barros; Pelloso, Sandra Marisa

2015-10-01

Pregnancy and lactation-associated osteoporosis (PAO) is a rare condition with little known pathophysiology. Most cases are diagnosed in the third trimester of pregnancy or in the first weeks postpartum, particularly in first pregnancies. Vertebral fractures are most commonly observed and characterised by prolonged severe pain, functional limitations and a loss of height. Measurements of bone mineral density and biochemical markers of bone remodelling are the clinical methods most commonly used for the management of these patients. However, a bone biopsy with histomorphometric analysis has been considered to be the gold-standard. Few studies have evaluated the histomorphometry in patients with this clinical condition and none of them performed the procedure at the beginning of the clinical assessment. In this study, we report a case of PAO in a 31-year-old postpartum patient who had undergone a twin pregnancy. We describe the clinical, laboratory tests and imaging features. Bone histomorphometry showed a high resorption rate and excellent evolution after 1 year of treatment with intravenous zoledronic acid. Our data suggest that osteoclastogenesis plays a central role in the pathophysiological processes of this disease.

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

DEFF Research Database (Denmark)

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

2011-01-01

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

Multicompartment vectors as novel drug delivery systems: selective activation of Tγδ lymphocytes after zoledronic acid delivery.

Science.gov (United States)

Agrati, Chiara; Marianecci, Carlotta; Sennato, Simona; Carafa, Maria; Bordoni, Veronica; Cimini, Eleonora; Tempestilli, Massimo; Pucillo, Leopoldo P; Turchi, Federica; Martini, Federico; Borioni, Giorgio; Bordi, Federico

2011-04-01

Multicompartment nanoscopic carriers can be easily assembled by inducing the aggregation of anionic "hybrid" niosomes by means of cationic biocompatible polyelectrolytes. The resulting vesicle clusters, whose size and overall net charge can be easily controlled by varying the polyelectrolyte-to-particle charge ratio, show an interesting potential for multidrug delivery. In this article we provide strong evidence for their effective use in vitro as multicompartment vectors selectively directed toward monocyte/macrophage cells, showing that the monocyte/macrophage-mediated activation of Tγδ lymphocytes induced by zoledronic acid is enhanced by a factor 10(3) when the zoledronic acid is intracellularly delivered through these carriers. Furthermore, the multicompartment ɛ-polylysine niosome clusters, with their intrinsic selectivity toward macrophages, appear particularly suitable for implementing therapeutic strategies against chronically infected macrophages. ɛ-polylysine niosome clusters, with their intrinsic selectivity toward macrophages, offer the potential for multidrug delivery. The effectiveness of aminobisphosphonate zoledronate is demonstrated to enhance the recruitment of Tγδ lymphocytes by macrophages by 2 orders of magnitude, suggesting a new therapeutic strategy for addressing pathologies featuring chronically infected macrophages. Copyright © 2011 Elsevier Inc. All rights reserved.

Combined Use of Zoledronic Acid Augments Ursolic Acid-Induced Apoptosis in Human Osteosarcoma Cells through Enhanced Oxidative Stress and Autophagy

Directory of Open Access Journals (Sweden)

Chia-Chieh Wu

2016-11-01

Full Text Available Ursolic acid (UA, a naturally occurring pentacyclic triterpene acid found in many medicinal herbs and edible plants, triggers apoptosis in several tumor cell lines but not in human bone cancer cells. Most recently, we have demonstrated that UA exposure reduces the viability of human osteosarcoma MG-63 cells through enhanced oxidative stress and apoptosis. Interestingly, an inhibitor of osteoclast-mediated bone resorption, zoledronic acid (ZOL, also a third-generation nitrogen-containing bisphosphonate, is effective in the treatment of bone metastases in patients with various solid tumors. In this present study, we found that UA combined with ZOL to significantly suppress cell viability, colony formation, and induce apoptosis in two lines of human osteosarcoma cells. The pre-treatment of the antioxidant had reversed the oxidative stress and cell viability inhibition in the combined treatment, indicating that oxidative stress is important in the combined anti-tumor effects. Moreover, we demonstrated that ZOL combined with UA significantly induced autophagy and co-administration of autophagy inhibitor reduces the growth inhibitory effect of combined treatment. Collectively, these data shed light on the pathways involved in the combined effects of ZOL and UA that might serve as a potential therapy against osteosarcoma.

Zoledronic acid as compared with observation in multiple myeloma patients at biochemical relapse: results of the randomized AZABACHE Spanish trial

Science.gov (United States)

García-Sanz, Ramón; Oriol, Albert; Moreno, María J.; de la Rubia, Javier; Payer, Angel R.; Hernández, Miguel T.; Palomera, Luis; Teruel, Ana I.; Blanchard, María J.; Gironella, Mercedes; Ribas, Paz; Bargay, Joan; Abellá, Eugenia; Granell, Miquel; Ocio, Enrique M.; Ribera, Josep M.; San Miguel, Jesús F.; Mateos, María V.

2015-01-01

This study analyzed the anti-myeloma effect of zoledronic acid monotherapy by investigating patients at the time of asymptomatic biochemical relapse. One hundred patients were randomized to receive either zoledronic acid (4 mg iv/4 weeks, 12 doses) (n=51) or not (n=49). Experimental and control groups were well balanced for disease and prognostic features. Zoledronic acid did not show an antitumor effect according to changes in M-component. However, there were fewer symptomatic progressions in the experimental group than in the control group (34 versus 41, respectively; P=0.05) resulting in a median time to symptoms of 16 versus 10 months (P=0.161). The median time to next therapy was also slightly longer for the treated group than the untreated, control group (13.4 versus 10.1 months), although the difference was not statistically significant (P=0.360). The pattern of relapses was different for treated versus control patients: progressive bone disease (8 versus 20), anemia (24 versus 18), renal dysfunction (1 versus 2), and plasmacytomas (1 versus 1, respectively). This concurred with fewer skeletal-related events in the treated group than in the control group (2 versus 14), with a projected 4-year event proportion of 6% versus 40% (P<0.001). In summary, zoledronic acid monotherapy does not show an antitumor effect on biochemical relapses in multiple myeloma, but does reduce the risk of progression with symptomatic bone disease and skeletal complications. This trial was registered in the ClinicalTrials.gov database with code NCT01087008 PMID:26069291

Farnesyl diphosphate synthase is involved in the resistance to zoledronic acid of osteosarcoma cells. : resistance of osteosarcoma to nitrogen bisphosphonates

OpenAIRE

Ory , Benjamin; Moriceau , Gatien; Trichet , Valérie; Blanchard , Frédéric; Berreur , Martine; Rédini , Françoise; Rogers , Michael; Heymann , Dominique

2008-01-01

International audience; We recently demonstrated original anti-tumor effects of zoledronic acid (Zol) on osteosarcoma cell lines independently of their p53 and Rb status. The present study investigated the potential Zol-resistance acquired by osteosarcoma cells after prolonged treatment. After 12 weeks of culture in the presence of 1 microm Zol, the effects of high doses of Zol (10-100 microm) were compared between the untreated rat (OSRGA, ROS) and human (MG63, SAOS2) osteosarcoma cells and ...

Once-yearly zoledronic acid in hip fracture prevention

Science.gov (United States)

Demontiero, Oddom; Duque, Gustavo

2009-01-01

Osteoporosis is an escalating global problem. Hip fractures, the most catastrophic complication of osteoporosis, continue to cause significant mortality and morbidity despite increasing availability of effective preventative agents. Among these agents, oral bisphosphonates have been the first choice for the treatment and prevention of osteoporotic fractures. However, the use of oral bisphosphonates, especially in the older population, has been limited by their side effects and method of administration thus compromising their persistent use. The resultant low adherence by patients has undermined their full potential and has been associated with an increase in the incidence of fragility fractures. Recently, annual intravenous zoledronic acid (ZOL) has been approved for osteoporosis. Randomized controlled trials have demonstrated ZOL to be safe, have good tolerability and produce significant effect on bone mass and microarchitecture. Adherence has also been shown to be better with ZOL. Furthermore two large trials firmly demonstrated significant anti-osteoporotic effect (∼59% relative risk reduction of hip fractures) and mortality benefit (28% reduction in mortality) of ZOL in older persons with recent hip fractures. In this review, we report the current evidence on the use of ZOL for the prevention of hip fractures in the elderly. We also report the pharmacological characteristics and the advantages and disadvantages of ZOL in this particular group. PMID:19503777

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

DEFF Research Database (Denmark)

Raina, Deepak Bushan; Isaksson, Hanna; Hettwer, Werner

2016-01-01

-the-shelf osteoinductive bone substitutes that can replace bone grafts are required. We tested the carrier properties of a biphasic, calcium sulphate and hydroxyapatite ceramic material, containing a combination of recombinant human bone morphogenic protein-2 (rhBMP-2) to induce bone, and zoledronic acid (ZA) to delay...

Zoledronic acid in children with osteogenesis imperfecta and Bruck syndrome: a 2-year prospective observational study.

Science.gov (United States)

Otaify, G A; Aglan, M S; Ibrahim, M M; Elnashar, M; El Banna, R A S; Temtamy, S A

2016-01-01

Treatment with zoledronic acid (ZA) over 2 years, among 33 children with osteogenesis imperfecta (OI) and five Bruck syndrome cases, showed reduction in fracture rates, pain, and improvement in bone mineral density (BMD) and motor milestones of development. This is the first study reporting the use of bisphosphonates in patients with Bruck syndrome (BS). OI and BS are genetic disorders that result in bone fragility and reduced BMD. There is little literature describing the efficacy and safety of ZA in this population. In this study, we assess the response to treatment with ZA at six monthly intervals in Egyptian children with OI and BS for a period of 2 years. Thirty-three patients with OI and five patients with BS were treated with 0.1 mg/kg ZA intravenously every 6 months for 2 years during which they were followed up using different parameters. A clinical severity score (CSS) was applied to the patients before and 2 years after the start of therapy. Comparison of disease severity and response to ZA treatment between autosomal-dominant (AD) and autosomal-recessive (AR) OI patients was also done. After 6 months of treatment, OI and BS patients showed a significant increase in BMD Z-scores (P < 0.003 in the spine and P < 0.004 in the hip), together with a significant drop in fracture rate (P < 0.001), relief of pain (P < 0.001), and improvement in ambulation (P < 0.001). CSS was significantly reduced after 2 years of treatment in both OI and BS patients. AR-OI patients were more severely affected than AD-OI patients and showed more significant improvement. Zoledronic acid proved to be safe and effective in the treatment of OI and BS. The biannual infusion protocol was convenient to patients. There was a positive correlation between disease severity and benefits of the treatment. The use of the CSS proved to be of value in the assessment of the degree of severity in OI, and with some modifications, it was a valuable tool for the assessment of

Determination of rat vertebral bone compressive fatigue properties in untreated intact rats and zoledronic-acid-treated, ovariectomized rats

NARCIS (Netherlands)

Brouwers, J.E.M.; Ruchselman, M.; Rietbergen, van B.; Bouxsein, M.L.

2009-01-01

Summary Compressive fatigue properties of whole vertebrae, which may be clinically relevant for osteoporotic vertebral fractures, were determined in untreated, intact rats and zoledronic-acid-treated, ovariectomized rats. Typical fatigue behavior was found and was similar to that seen in other

The Effect of 3 Versus 6 Years of Zoledronic Acid Treatment of Osteoporosis: A Randomized Extension to the HORIZON-Pivotal Fracture Trial (PFT)

Science.gov (United States)

Black, Dennis M; Reid, Ian R; Boonen, Steven; Bucci-Rechtweg, Christina; Cauley, Jane A; Cosman, Felicia; Cummings, Steven R; Hue, Trisha F; Lippuner, Kurt; Lakatos, Peter; Leung, Ping Chung; Man, Zulema; Martinez, Ruvie Lou Maria; Tan, Monique; Ruzycky, Mary Ellen; Su, Guoqin; Eastell, Richard

2012-01-01

Zoledronic acid 5 mg (ZOL) annually for 3 years reduces fracture risk in postmenopausal women with osteoporosis. To investigate long-term effects of ZOL on bone mineral density (BMD) and fracture risk, the Health Outcomes and Reduced Incidence with Zoledronic acid Once Yearly–Pivotal Fracture Trial (HORIZON-PFT) was extended to 6 years. In this international, multicenter, double-blind, placebo-controlled extension trial, 1233 postmenopausal women who received ZOL for 3 years in the core study were randomized to 3 additional years of ZOL (Z6, n = 616) or placebo (Z3P3, n = 617). The primary endpoint was femoral neck (FN) BMD percentage change from year 3 to 6 in the intent-to-treat (ITT) population. Secondary endpoints included other BMD sites, fractures, biochemical bone turnover markers, and safety. In years 3 to 6, FN-BMD remained constant in Z6 and dropped slightly in Z3P3 (between-treatment difference = 1.04%; 95% confidence interval 0.4 to 1.7; p = 0.0009) but remained above pretreatment levels. Other BMD sites showed similar differences. Biochemical markers remained constant in Z6 but rose slightly in Z3P3, remaining well below pretreatment levels in both. New morphometric vertebral fractures were lower in the Z6 (n = 14) versus Z3P3 (n = 30) group (odds ratio = 0.51; p = 0.035), whereas other fractures were not different. Significantly more Z6 patients had a transient increase in serum creatinine >0.5 mg/dL (0.65% versus 2.94% in Z3P3). Nonsignificant increases in Z6 of atrial fibrillation serious adverse events (2.0% versus 1.1% in Z3P3; p = 0.26) and stroke (3.1% versus 1.5% in Z3P3; p = 0.06) were seen. Postdose symptoms were similar in both groups. Reports of hypertension were significantly lower in Z6 versus Z3P3 (7.8% versus 15.1%, p < 0.001). Small differences in bone density and markers in those who continued versus those who stopped treatment suggest residual effects, and therefore, after 3 years of annual ZOL, many patients may discontinue

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

International Nuclear Information System (INIS)

Banys, Malgorzata; Wackwitz, Birgit; Hirnle, Peter; Wallwiener, Diethelm; Fehm, Tanja; Solomayer, Erich-Franz; Gebauer, Gerhard; Janni, Wolfgang; Krawczyk, Natalia; Lueck, Hans-Joachim; Becker, Sven; Huober, Jens; Kraemer, Bernhard

2013-01-01

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

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.

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.

Modulation of Tumor Cell Metabolism by Laser Photochemotherapy with Cisplatin or Zoledronic Acid In Vitro.

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Heymann, Paul Günther Baptist; Henkenius, Katharina Sabine Elisabeth; Ziebart, Thomas; Braun, Andreas; Hirthammer, Klara; Halling, Frank; Neff, Andreas; Mandic, Robert

2018-03-01

Laser photochemotherapy is a new approach in cancer treatment using low-level laser therapy (LLLT) to enhance the effect of chemotherapy. In order to evaluate the effect of LLLT on tumor cells, HeLa cells were treated with cisplatin or zoledronic acid (ZA) followed by LLLT. Cell viability was evaluated with 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide assay. Oxidative phosphorylation and glycolysis were measured using extracellular flux analysis. Immunocytochemistry of heat-shock protein 70 (HSP70) and western blot analysis were performed. LLLT alone increased viability and was associated with lower oxidative phosphorylation but higher glycolysis rates. Cisplatin and ZA alone lowered cell viability, glycolysis and oxidative phosphorylation. This effect was significantly enhanced in conjunction with LLLT and was accompanied by reduced oxidative phosphorylation and collapse of glycolysis. Our observations indicate that LLLT may raise the cytotoxicity of cisplatin and ZA by modulating cellular metabolism, pointing to a possible application in cancer treatment. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

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

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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.

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

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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

Short-term effect of zoledronic acid upon fracture resistance of the mandibular condyle and femoral head in an animal model.

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Camacho-Alonso, Fabio; López-Jornet, Pía; Vicente-Hernández, Ascensión

2013-05-01

The aim of this study was to compare the effects in terms of resistance to fracture of the mandibular condyle and femoral head following different doses of zoledronic acid in an animal model. A total of 80 adult male Sprague-Dawley rats were included in a prospective randomized study. The animals were randomly divided into four groups of 20 rats each. Group 1 (control) received sterile saline solution, while groups 2, 3 and 4 received a accumulated dose of 0.2 mg, 0.4 mg and 0.6 mg of zoledronic acid, respectively. The animals were sacrificed 28 days after the last dose, and the right hemimandible and the right femur were removed. The fracture strength was measured (in Newtons) with a universal test machine using a 1 kN load connected to a metal rod with one end angled at 30 degrees. The cross-head speed was 1 mm/min. Later, the specimens were observed under a scanning electron microscope with backscattered electron imaging (SEM-BSE). At last, chemical analysis and elemental mapping of the mineral bone composition were generated using a microanalytical system based on energy-dispersive and X-ray spectrometry (EDX). A total of 160 fracture tests were performed. The fracture resistance increased in mandible and femur with a higher accumulated dose of zoledronic acid. Statistically significant differences were recorded versus the controls with all the studies groups. The chemical analysis in mandible showed a significantly increased of calcium and phosphorous to compare the control with all of the study groups; however, in femur no statistically significant differences between the four study groups were observed. The administration of bisphosphonates increases the fracture resistance in mandible and femur.

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

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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 (Phealing in conditions at risk for MRONJ development.

Zoledronic acid use in patients with bone metastases from renal cell carcinoma or bladder cancer.

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Saad, Fred; Eastham, James A

2010-06-01

Approximately 30% of patients with renal cell carcinoma (RCC) and 40% of patients with bladder cancer develop bone metastases that can disrupt normal bone homeostasis and place patients at risk for potentially life-limiting skeletal-related events (SREs). In the absence of bone-directed therapies, patients with RCC may experience up to four SREs per year. In patients with bone metastases from RCC or bladder cancer, zoledronic acid (ZOL) significantly reduced the risk of SREs compared with placebo. In addition to its bone-protective effects, preclinical and early clinical evidence indicates that ZOL prevents tumor progression. For example, retrospective subset analysis in patients with RCC indicated that ZOL extended time to disease progression and demonstrated a trend toward improved overall survival compared with placebo. Additionally, a study in patients with bone metastases from bladder cancer demonstrated that ZOL improved 1-year overall survival compared with placebo. Bone metastases place a heavy burden on patients with RCC or bladder cancer, and early, continuous treatment with ZOL may provide anticancer benefits in addition to important patient quality of life. 2010. Published by Elsevier Inc.

Is Administration of Trastuzumab an Independent Risk Factor for Developing Osteonecrosis of the Jaw Among Metastatic Breast Cancer Patients Under Zoledronic Acid Treatment?

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Pilanci, Kezban Nur; Alco, Gul; Ordu, Cetin; Sarsenov, Dauren; Celebi, Filiz; Erdogan, Zeynep; Agacayak, Filiz; Ilgun, Serkan; Tecimer, Coskun; Demir, Gokhan; Eralp, Yesim; Okkan, Sait; Ozmen, Vahit

2015-01-01

Abstract One of the most important adverse effects of zoledronic acid (ZA) is osteonecrosis of the jaw (ONJ). In previous literature, several risk factors have been identified in the development of ONJ. In this study, we aimed to determine the role of trastuzumab, an antiangiogenic agent, as an independent risk factor for the development of this serious side effect. Our study included 97 patients (mean age: 54 ± 10 years) with breast cancer, recorded in the archives of the Istanbul Florence Nightingale Breast Study Group, who received ZA therapy due to bone metastases between March 2006 and December 2013. We recorded the patients’ ages, weights, duration of treatment with ZA, number of ZA infusions, dental procedures, anticancer treatments (chemotherapy, aromatase inhibitor, trastuzumab), the presence of diabetes mellitus or renal dysfunction, and smoking habits. Thirteen patients (13.40%) had developed ONJ. Among the patients with ONJ, the mean time of exposure to ZA was 41 months (range: 13–82) and the mean number of ZA infusions was 38 (range: 15–56). The duration of treatment with ZA and the use of trastuzumab were observed to be 2 factors that influenced the development of ONJ (P = 0.049 and P = 0.028, respectively). The development of ONJ under ZA treatment may be associated solely with the duration of ZA treatment and the concurrent administration of trastuzumab. These findings show that patients who are administered trastuzumab for metastatic breast cancer while undergoing ZA treatment are prone to developing ONJ. Therefore, we recommend intense clinical observation to avoid this particular condition in patients receiving ZA and trastuzumab. PMID:25950681

Toxicity of a dental adhesive compared with ionizing radiation and zoledronic acid.

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Alcaraz, Miguel; Olivares, Amparo; Achel, Daniel-Giyngiri; García-Cruz, Emilio; Fondevilla-Soler, Adriana; Canteras-Jordana, Manuel

2015-07-01

To determine the toxicity of aqueous dilutions of a universal self-priming dental adhesive (DA) and comparing these with those elicited by exposure to ionizing radiation (IR), Zoledronic acid (Z) treatment and the synergic effects of the combined treatment with IR+Z. The genotoxic effect of DA was determined by the increase in the frequency of micronuclei in cytokinesis-blocked in cultured human lymphocytes before and after exposure to 2Gy of X-rays. The cytotoxic effect was studied by using the MTT cell viability test in normal prostate cell lines (PNT2) after exposure to different X-ray doses (0Gy-20Gy). The cell lines divided into different groups and treated with different test substances: DA in presence of O2, DA in absence of O2, Z-treated and control. An in vitro dose-dependent and time-dependent cytotoxic effect of DA, Z and IR on PNT2 cells (p>0.001) was demonstrated. DA without-O2, following the recommendations of manufacturers, had a more pronounced effect of increasing cell death than DA with-O2 (p<0.001). In the genotoxicity assay, DA at 25% of its original concentration significantly increased chromosome damage (p<0.001). The samples studied were found to be toxic, and the samples photo-polymerized in absence of O2 showed a bigger cytotoxic effect comparable to the additive toxic effect showed by the combined treatment of IR+Z. Additional effort should be carried out to develop adhesives, which would reduce the release of hazardous substances; since toxic effects are similar to that reported by other agents whose clinical use is controlled by the health authorities.

Sclerostin Blockade and Zoledronic Acid Improve Bone Mass and Strength in Male Mice With Exogenous Hyperthyroidism.

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Tsourdi, Elena; Lademann, Franziska; Ominsky, Michael S; Rijntjes, Eddy; Köhrle, Josef; Misof, Barbara M; Roschger, Paul; Klaushofer, Klaus; Hofbauer, Lorenz C; Rauner, Martina

2017-11-01

Hyperthyroidism in mice is associated with low bone mass, high bone turnover, and high concentrations of sclerostin, a potent Wnt inhibitor. Here, we explored the effects of either increasing bone formation with sclerostin antibodies (Scl-Ab) or reducing bone turnover with bisphosphonates on bone mass and strength in hyperthyroid mice. Twelve-week-old C57BL/6 male mice were rendered hyperthyroid using l-thyroxine (T4; 1.2 µg/mL added to the drinking water) and treated with 20 mg/kg Scl-Ab twice weekly or 100 µg/kg zoledronic acid (ZOL) once weekly or phosphate-buffered saline for 4 weeks. Hyperthyroid mice displayed a lower trabecular bone volume at the spine (-42%, P hyperthyroid mice increased trabecular bone volume at the spine by threefold and twofold, respectively. Serum bone formation and resorption markers were increased in hyperthyroid mice and suppressed by treatment with ZOL but not Scl-Ab. Trabecular bone stiffness at the lumbar vertebra was 63% lower in hyperthyroid mice (P hyperthyroidism, was increased by Scl-Ab by 71% and ZOL by 22% (both P hyperthyroid mice was restored by treatment with Scl-Ab and ZOL. Thus, bone-forming and antiresorptive drugs prevent bone loss in hyperthyroid mice via different mechanisms. Copyright © 2017 Endocrine Society.

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

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Johannesen, Jesper; Briody, Julie; McQuade, Mary

2009-01-01

Background: Intravenous bisphosphonate therapy is associated with preservation of femoral head sphericity and congruence in 77% of children with traumatic avascular necrosis. The aim was to describe the systemic effects of intravenous zoledronic acid (ZA) on bone and mineral metabolism in otherwise...... normal children and adolescents with femoral head AVN. Material and methods: 37 children (age 10.8+/-2.76 years) diagnosed with avascular necrosis AVN (Slipped Capital Femoral Epiphysis (SCFE), N=20 or Legg-Calve-Perthes disease (LCPD), N=17) were treated with at least 12 months of ZA. Bone mineral...

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

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Fehm, Tanja; Zwirner, Manfred; Wallwiener, Diethelm; Seeger, Harald; Neubauer, Hans

2012-01-01

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). 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. 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 < 0.05). The median IC50 value for Zol (8.03% TDC) was significantly lower than the IC50 values for FEC (33.5% TDC) and TAC (19.3% TDC) treatment (p < 0.05). However, the median IC90 value for Zol (152.5% TDC) was significantly higher than the IC90 value obtained with TAC (49.5% TDC; p < 0.05), but similar to the IC90 value for FEC (180.9% TDC). In addition a significant positive correlation was observed for the IndexSum of Zol and the ER status

Self-assembling nanoparticles encapsulating zoledronic acid inhibit mesenchymal stromal cells differentiation, migration and secretion of proangiogenic factors and their interactions with prostate cancer cells

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Borghese, C.; Casagrande, N.; Pivetta, E.; Colombatti, A.; Boccellino, M.; Amler, Evžen; Normanno, N.; Caraglia, M.; de Rosa, G.; Aldinucci, D.

2017-01-01

Roč. 8, č. 26 (2017), s. 42926-42938 ISSN 1949-2553 Institutional support: RVO:68378041 Keywords : zoledronic acid * self-assembling nanoparticles * mesenchymal stromal cells * prostate cancer * tumor microenvironment Subject RIV: FP - Other Medical Disciplines OBOR OECD: Technologies involving the manipulation of cells, tissues, organs or the whole organism (assisted reproduction) Impact factor: 5.168, year: 2016

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

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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

Zoledronate induces apoptosis in cells from fibro-cellular membrane of unicameral bone cyst (UBC).

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Yu, John; Chang, Seong-Sil; Suratwala, Sanjeev; Chung, Woo-Sik; Abdelmessieh, Peter; Lee, Hahn-Jun; Yang, Jay; Lee, Francis Young-In

2005-09-01

Unicameral bone cyst (UBC) is a benign cystic lesion in children which is prone to fracture. Various treatments are available, but recurrence after different types of percutaneous injection therapy can cause bone destruction and pathologic fracture. The potential therapeutic effects of anti-resorptive agents, such as bisphosphonates, have not been investigated for UBC. The objective of this study was to characterize the cells from the fibro-cellular membrane of unicameral bone cyst (UBC cells) and to determine whether zoledronate, a nitrogen-containing bisphosphonate, could induce apoptosis in UBC cells. Flow cytometry and immunoblotting were performed in order to determine whether zoledronate induced apoptosis. Cells derived from normal human trabecular bones were used as controls against UBC cells to compare the effect of zoledronate in inducing apoptosis. Immunohisto/cytochemistry (IHC/ICC) and mini-array analyses were performed on tissues and cultured cells. Isolated peripheral blood mononuclear cells were incubated with conditioned media from the UBC cells to determine whether they are capable of inducing osteoclastogenesis. UBC membrane is composed of cells staining positively with CD68, SDF-1, STRO-1 and RANKL, but in vitro cells showed no staining with antibodies to CD68 and STRO-1, suggesting that there was a clonal selection of stromal cells during cell culture. UBC cells also express RUNX2 (runt-related transcription factor-2, core binding factor-1), a key transcription factor for osteoblastic differentiation. In addition, media collected from UBC cells induced a generation of multi-nucleated osteoclast-like cells of peripheral blood mononuclear cells. Zoledronate induced apoptosis of UBC cells in a dose-dependent manner. Apoptosis was evidenced by induction of the active cleaved form of caspase-3. The baseline apoptotic fractions were similar in UBC cells and trabecular bone cells. However, in the overall apoptotic fractions in this study, trabecular

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

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Richhariya A

2012-02-01

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

Early, middle, or late administration of zoledronate alleviates spontaneous nociceptive behavior and restores functional outcomes in a mouse model of CFA-induced arthritis.

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Morado-Urbina, Carlos Eduardo; Alvarado-Vázquez, Perla Abigail; Montiel-Ruiz, Rosa Mariana; Acosta-González, Rosa Issel; Castañeda-Corral, Gabriela; Jiménez-Andrade, Juan Miguel

2014-11-01

This study was performed to evaluate whether early, middle, or late treatment of zoledronate, an approved bisphosphonate that blocks bone resorption, can reduce nociceptive behaviors in a mouse arthritis model. Arthritis was produced by repeated intra-articular knee injections of complete Freund's adjuvant (CFA). A dose-response curve with zoledronate (3, 30, 100, and 300 μg/kg, i.p., day 4 to day 25, twice weekly for 3 weeks) was performed, and the most effective dose of zoledronate (100 μg/kg, i.p.) was initially administered at different times of disease progression: day 4 (early), day 15 (middle), or day 21 (late) and continued until day 25 after the first CFA injection. Flinching of the injected extremity (spontaneous nociceptive behavior), vertical rearings and horizontal activity (functional outcomes), and knee edema were assessed. Zoledronate improved both functional outcomes and reduced flinching behavior. At day 25, the effect of zoledronate on flinching behavior and vertical rearings was greater in magnitude when it was given early or middle rather than late in the treatment regimen. Chronic zoledronate did not reduce knee edema in CFA-injected mice nor functional outcomes in naïve mice by itself. These results suggest that zoledronate may have a positive effect on arthritis-induced nociception and functional disabilities. © 2014 Wiley Periodicals, Inc.

Optimal Timing of Bisphosphonate Administration in Combination with Samarium-153 Oxabifore in the Treatment of Painful Metastatic Bone Disease

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Rasulova, Nigora; Lyubshin, Vladimir; Arybzhanov, Dauranbek; Sagdullaev, Sh.; Krylov, Valery; Khodjibekov, Marat

2013-01-01

While bisphosphonates are indicated for prevention of skeletal-related events, radionuclide therapy is widely used for treatment of painful bone metastases. Combined radionuclide therapy with bisphosphonates has demonstrated improved effectiveness in achieving bone pain palliation in comparison to mono therapy with radionuclides or bisphosphonates alone. However, there are conflicting reports as to whether bisphosphonates adversely influence skeletal uptake of the bone-seeking radiotracers used for therapy. Recent studies analyzing influence of Zoledronic acid on total bone uptake of Samarium-153 EDTMP (Sm-153 EDTMP) by measuring cumulative urinary activity of Sm-153 on baseline study, as well as in combination with bisphosphonates (administrated 48 hours prior to Sm-153) did not provide any statistically significant difference in urinary excretion of Sm-153 between the two groups. It may be noted that the exact temporal sequence of bisphosphonate administration vis a vis radionuclide therapy has not yet been studied. One of the side effects of bisphosphonates is transient flare effect on bone pain. Radionuclide therapy may also have similar side effect. Keeping in view the above the current study was designed with the main objective of determining the exact timing of bisphosphonate administration in patients receiving combined therapy so as to achieve optimal efficacy of bone pain palliation. Ninety-three patients suffering from metastatic bone pain who received combination therapy with Sm-153 oxabifore (an analog of Sm-153 EDTMP) and Zoledronic acid were divided into three groups according to the timing of Zoledronic acid administration: Group I: 39 patients who received Zoledronic acid 7 or more days prior to Sm-153 oxabifore treatment; Group II: 32 patients who received Zoledronic acid 48-72 hours prior to Sm-153 oxabifore treatment and Group III: 22 patients who received Zoledronic acid 7 days after Sm-153 oxabifore treatment. Sm-153 oxabifore was administered

[gammadelta T cells stimulated by zoledronate kill osteosarcoma cells].

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Jiang, Hui; Xu, Qiang; Yang, Chao; Cao, Zhen-Guo; Li, Zhao-Xu; Ye, Zhao-Ming

2010-12-01

To investigate the cytotoxicity of human γδT cells from PBMCs stimulated by zoledronate against osteosarcoma cell line HOS in vitro and in vivo and evaluate the relavent pathways. The peripheral blood mononuclear cells (PBMCs)of healthy donors were stimulated by single dose zoledronate and cultured in the present of IL-2 for two weeks, analysising the percentage of γδT cells on a FACSCalibur cytometer.Study the cytotoxicity of γδT cells against the osteosarcoma line HOS using LDH release assay kit. Pre-treatment of γδT cells with anti-human γδTCR antibody, anti-human NKG2D antibody and concanamycin A to bolck the relavent pathways for evaluating the mechenisms of its cytotoxicity. In vivo, BALB/c mice were inoculated subcutaneously osteosarcoma cell HOS for developing hypodermal tumors. And they were randomized into two groups: unteated group, γδT cell therapy group. Tumor volume and weight of the two groups were compared. After two weeks of culture, γδT cells from zoledronate-stimulated PBMCs could reach (95±3)%. When the E:T as 6:1, 12:1, 25:1, 50:1, the percentage of osteosarcoma cell HOS killed by γδT cells was 26.8%, 31.5%, 37.8%, 40.9%, respectively.When anti-huma γδTCR antibody, anti-human NKG2D antibody and concanamycin A blocked the relavent pathways, the percentage was 32.3%, 4.7%, 16.7% ( E:T as 25:1), respectively. In vivo, the tumor inhibition rate of the group of γδT cell therapy was 42.78%. γδT cells derived from PBMCs stimulated by zoledronate can acquired pure γδT cells. And they show strong cytoxicity against osteosarcoma cell line HOS in vitro and in vivo.

The impact of zoledronic acid on regenerate and native bone after consolidation and removal of the external fixator: an animal model study.

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Saghieh, Said; Khoury, Nabil J; Tawil, Ayman; Masrouha, Karim Z; Musallam, Khaled M; Khalaf, Kinda; Dosh, Laura; Jaouhari, Rosemarie Reich; Birjawi, Ghina; El-Hajj-Fuleihan, Ghada

2010-02-01

We investigated the role of zoledronic acid on the regenerate and native bone after consolidation and removal of the external fixator in a rabbit model of distraction osteogenesis using 28 New Zealand white rabbits. The rabbits were randomly distributed into two groups. The first group received three doses of zoledronic acid (ZA) 0.1 mg/kg subcutaneously at weekly intervals while the second group received injections of sterile saline. Distraction started on day 7 at a rate of 0.8 mm/day for 12 days. At week 3 the average lengthening, regenerate density, and regenerate continuity were comparable between the two groups. At week 11 the regenerate in the treated group had a significant increase in Bone Mineral Density (BMD) and Bone Mineral Content (BMC) compared to the placebo group. On axial compression, the regenerate showed an increase in the peak load and a higher modulus of elasticity in the treated group. At 6 months, radiographs demonstrated signs of osteopenia of the proximal metaphysis in the control group, and failure of new bone formation around the pin sites in the treated group. BMC and BMD value differences between the two groups were not statistically significant. Histologically, there was persistence of more bone trabeculae in the medullary canal of the regenerate with the persistence of the pin-holes in the treated group. Mechanically, the regenerates in the treated group remain stronger in resisting the axial compression. The proximal fragment in the treated group exhibited a statistically significant decrease in the peak load, toughness and efail %. In conclusion, bisphosphonate-treated rabbits have a stronger regenerate during distraction, and directly after removal of the fixator. They do not develop disuse osteopenia in their lengthened tibia. This treatment may shorten the time in the external fixator and prevent fragility fractures in the treated extremity. However, its long-term safety has not yet been established. (c) 2009 Elsevier Inc. All

Zoledronic acid inhibits vasculogenic mimicry in murine osteosarcoma cell line in vitro.

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Fu, Dehao; He, Xianfeng; Yang, Shuhua; Xu, Weihua; Lin, Tao; Feng, Xiaobo

2011-06-30

To study the effects of zoledronic acid (ZA) on the vasculogenic mimicry of osteosarcoma cells in vitro. A Three-dimensional culture of LM8 osteosarcoma cells on a type I collagen matrix was used to investigate whether osteosarcoma cells can develop vasculogenic mimicry, and to determine the effects of ZA on this process. In addition, the cellular ultrastructural changes were observed using scanning electron microscopy and laser confocal microscopy. The effects of ZA on the translocation of RhoA protein from the cytosol to the membrane in LM8 cells were measured via immunoblotting. ZA inhibited the development of vasculogenic mimicry by the LM8 osteosarcoma cells, decreased microvilli formation on the cell surface, and disrupted the F-actin cytoskeleton. ZA prevented translocation of RhoA protein from the cytosol to the membrane in LM8 cells. ZA can impair RhoA membrane localization in LM8 cells, causing obvious changes in the ultrastructure of osteosarcoma cells and induce cell apoptosis, which may be one of the underlying mechanisms by which the agent inhibits the development of vasculogenic mimicry by the LM8 cells.

Zoledronic acid inhibits vasculogenic mimicry in murine osteosarcoma cell line in vitro

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Lin Tao

2011-06-01

Full Text Available Abstract Background To study the effects of zoledronic acid (ZA on the vasculogenic mimicry of osteosarcoma cells in vitro. Methods A Three-dimensional culture of LM8 osteosarcoma cells on a type I collagen matrix was used to investigate whether osteosarcoma cells can develop vasculogenic mimicry, and to determine the effects of ZA on this process. In addition, the cellular ultrastructural changes were observed using scanning electron microscopy and laser confocal microscopy. The effects of ZA on the translocation of RhoA protein from the cytosol to the membrane in LM8 cells were measured via immunoblotting. Results ZA inhibited the development of vasculogenic mimicry by the LM8 osteosarcoma cells, decreased microvilli formation on the cell surface, and disrupted the F-actin cytoskeleton. ZA prevented translocation of RhoA protein from the cytosol to the membrane in LM8 cells. Conclusions ZA can impair RhoA membrane localization in LM8 cells, causing obvious changes in the ultrastructure of osteosarcoma cells and induce cell apoptosis, which may be one of the underlying mechanisms by which the agent inhibits the development of vasculogenic mimicry by the LM8 cells.

Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athymic Rats.

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Curtis, Ryan C; Custis, James T; Ehrhart, Nicole P; Ehrhart, E J; Condon, Keith W; Gookin, Sara E; Donahue, Seth W

2016-01-01

Clinical studies using definitive-intent stereotactic radiation therapy (SRT) for the local treatment of canine osteosarcoma (OSA) have shown canine patients achieving similar median survival times as the current standard of care (amputation and adjuvant chemotherapy). Despite this, there remains an unacceptable high risk of pathologic fracture following radiation treatment. Zoledronic acid (ZA) and parathyroid hormone (PTH) are therapeutic candidates for decreasing this fracture risk post-irradiation. Due to differing mechanisms, we hypothesized that the combined treatment with ZA and PTH would significantly improve bone healing more than ZA or PTH treatment alone. Using an orthotopic model of canine osteosarcoma in athymic rats, we evaluated bone healing following clinically-relevant doses of radiation therapy (12 Gy x 3 fractions, 36 Gy total). Groups included 36 Gy SRT only, 36 Gy SRT plus ZA, 36 Gy SRT plus ZA and PTH, 36 Gy SRT plus PTH, and 36 Gy SRT plus localized PTH treatment. Our study showed significant increases in bone volume and increased polar moments of inertia (in the distal femoral metaphysis) 8 weeks after radiation in the combined (ZA/PTH) treatment group as compared to radiation treatment alone. Histomorphometric analysis revealed evidence of active mineralization at the study endpoint as well as successful tumor-cell kill across all treatment groups. This work provides further evidence for the expanding potential indications for ZA and PTH therapy, including post-irradiated bone disease due to osteosarcoma.

Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athymic Rats.

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Ryan C Curtis

Full Text Available Clinical studies using definitive-intent stereotactic radiation therapy (SRT for the local treatment of canine osteosarcoma (OSA have shown canine patients achieving similar median survival times as the current standard of care (amputation and adjuvant chemotherapy. Despite this, there remains an unacceptable high risk of pathologic fracture following radiation treatment. Zoledronic acid (ZA and parathyroid hormone (PTH are therapeutic candidates for decreasing this fracture risk post-irradiation. Due to differing mechanisms, we hypothesized that the combined treatment with ZA and PTH would significantly improve bone healing more than ZA or PTH treatment alone. Using an orthotopic model of canine osteosarcoma in athymic rats, we evaluated bone healing following clinically-relevant doses of radiation therapy (12 Gy x 3 fractions, 36 Gy total. Groups included 36 Gy SRT only, 36 Gy SRT plus ZA, 36 Gy SRT plus ZA and PTH, 36 Gy SRT plus PTH, and 36 Gy SRT plus localized PTH treatment. Our study showed significant increases in bone volume and increased polar moments of inertia (in the distal femoral metaphysis 8 weeks after radiation in the combined (ZA/PTH treatment group as compared to radiation treatment alone. Histomorphometric analysis revealed evidence of active mineralization at the study endpoint as well as successful tumor-cell kill across all treatment groups. This work provides further evidence for the expanding potential indications for ZA and PTH therapy, including post-irradiated bone disease due to osteosarcoma.

Effect of low-level laser therapy on tissue repair after dental extraction in rats administered zoledronic acid and dexamethasone

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Weber, João Batista Blessmann; Camilotti, Renata Stifelman; Jasper, Juliana; Casagrande, Liliane Cristina Onofre; Maito, Fábio Luiz Dal Moro

2017-05-01

Bisphosphonates (BPs) are being increasingly used for the treatment of metabolic and oncological pathologies involving the skeletal system. Because of the severity of the BP associated osteonecrosis of the jaws, the difficulties of treatment, and patient discomfort, additional support methods for their management are needed. Laser therapy has an easy handling, photobiostimulator effect on tissues healing, so it can be considered a preferred therapy. The aim of this study was to evaluate the influence of low-level laser therapy in the 685- and 830-nm wavelength in the healing process of the bone and soft tissues in rats under BP therapy [zoledronic acid (ZA)] and dexamethasone concomitantly that underwent a surgery for the extraction of upper molars. There were statistically significant differences in the clinical evaluation of the wound and the weight of the animals. Regarding the histological evaluation, it was possible to observe the different maturations of the healing stage between groups. The effect of drug therapy with ZA and dexamethasone in the bone tissue repair process induces osteonecrosis of the jaw in rats and slows down the healing process. In the laser groups, at the stipulated dosimetry, a positive influence on the bone and soft tissue repair process was observed.

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

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Khajuria, Deepak Kumar, E-mail: deepak_kumarkhajuria@yahoo.co.in [The Musculoskeletal Genetics Laboratory, Faculty of Medicine in the Galilee, Bar-Ilan University, Safed (Israel); Department of Pharmacology, Al-Ameen College of Pharmacy, Bangalore (India); Vasireddi, Ramakrishna; Trebbin, Martin [Hamburg Center for Ultrafast Imaging, University of Hamburg, Hamburg (Germany); Karasik, David [The Musculoskeletal Genetics Laboratory, Faculty of Medicine in the Galilee, Bar-Ilan University, Safed (Israel); Razdan, Rema [Department of Pharmacology, Al-Ameen College of Pharmacy, Bangalore (India)

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 25 μg/kg); ZOL (100 μg/kg); or SrHA (100 μg/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 (p < 0.05). Moreover, treatment with SrHA/ZOL significantly precluded an increase in serum bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase than either ZOL or SrHA (p < 0.05). These results strongly implicate

Diminished Progression of Periapical Lesions with Zoledronic Acid in Ovariectomized Rats.

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Wayama, Marcelo Tadahiro; Yoshimura, Hitoshi; Ohba, Seigo; Yoshida, Hisato; Matsuda, Shinpei; Kobayashi, Junichi; Kobayashi, Motohiro; Gomes Filho, João Eduardo; Sano, Kazuo

2015-12-01

The aim of this study was to investigate the effects of systemically administered zoledronic acid (ZOL) on the progression of periapical lesions in estrogen-deficient rats. Female Wistar rats were divided into the following groups: SHAM-veh, sham surgery treated with vehicle (physiological saline); OVX-veh, ovariectomy treated with vehicle; SHAM-ZOL, sham surgery treated with ZOL; and OVX-ZOL, ovariectomy treated with ZOL. Vehicle or ZOL was administered intravenously once a week for 4 weeks. The pulp of the mandibular first molar of all rats was exposed to the oral environment to induce a periapical lesion, and the lesions were analyzed after 7 and 30 days. The mandibles were examined by micro-computed tomographic imaging and histopathologic, histometric, and immunohistochemical analyses. Histopathologically, the OVX-veh group had more severe inflammation and bone loss and a larger number of cells that were positive for tartrate-resistant acid phosphatase compared with the SHAM-veh and OVX-ZOL groups; the SHAM-veh and OVX-ZOL groups were similar to each other. The SHAM-ZOL group had the lowest magnitude of these conditions. Tomographically, the OVX-veh group had greater bone loss than the other groups at both time points. The SHAM-veh, SHAM-ZOL, and OVX-ZOL groups had similar bone loss at both time points. In the sagittal section on day 30, the SHAM-ZOL group had lower bone loss compared with the SHAM-veh and OVX-ZOL groups. The hypoestrogenic condition aggravates the progression of periapical lesions. ZOL therapy may help contain bone destruction of periapical lesions. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

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

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Schindeler, Aaron; Little, David G.

2005-01-01

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

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

International Nuclear Information System (INIS)

Asikoglu, Makbule; Gamze Durak, Funda

2009-01-01

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

Inhibition of Zoledronic Acid on Cell Proliferation and Invasion of Lung Cancer Cell Line 95D

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Mingming LI

2009-03-01

Full Text Available Background and objective Abnormal proliferation and metastasis is the basic characteristic of malignant tumors. The aim of this work is to explore the effects of zoledronic acid on cell proliferation and invasion in lung cancer cell line 95D. Methods The effect of zoledrnic acid (ZOL on proliferation of lung cancer cell line 95D was detected by MTT. The expression of proliferation and invasion-relation genes and proteins were detected by Western blot, RT-PCR and immunofluorescence. Changes of invasion of lung cancer cell numbers were measured by polycarbonates coated with Matrigel. Results ZOL could inhibit the proliferation of lung cancer cell line 95D in vitro in a time-dependant and a dose-dependant manner. With time extending after ZOL treated, the mRNA expresion of VEGF, MMP9, MMP2 and protein expression of VEGF, MMP9, ERK1/ ERK2 were decreased. The results of Tanswell invasion showed the numbers of invasive cells were significantly reduced in 95D cells treated with ZOL 4 d and 6 d later. Conclusion ZOL could inhibit cell proliferation and invasion of lung cancer cell line 95D.

Administration of zoledronic acid enhances the effects of docetaxel on growth of prostate cancer in the bone environment

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Vessella Robert L

2006-01-01

Full Text Available Abstract Background After development of hormone-refractory metastatic disease, prostate cancer is incurable. The recent history of chemotherapy has shown that with difficult disease targets, combinatorial therapy frequently offers the best chance of a cure. In this study we have examined the effects of a combination of zoledronic acid (ZOL, a new-generation bisphosphonate, and docetaxel on LuCaP 23.1, a prostate cancer xenograft that stimulates the osteoblastic reaction when grown in the bone environment. Methods Intra-tibial injections of LuCaP 23.1 cells were used to generate tumors in the bone environment, and animals were treated with ZOL, docetaxel, or a combination of these. Effects on bone and tumor were evaluated by measurements of bone mineral density and histomorphometrical analysis. Results ZOL decreased proliferation of LuCaP 23.1 in the bone environment, while docetaxel at a dose that effectively inhibited growth of subcutaneous tumors did not show any effects in the bone environment. The combination of the drugs significantly inhibited the growth of LuCaP 23.1 tumors in the bone. Conclusion In conclusion, the use of the osteolysis-inhibitory agent ZOL in combination with docetaxel inhibits growth of prostate tumors in bone and represents a potential treatment option.

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

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

2013-01-01

Zoledronic acid (Zol) is used to treat bone disease in both multiple myeloma (MM) and breast cancer patients with bone metastasis (BC). However, bones of MM and BC patients show a difference in retention of the bisphosphonate used for bone scintigraphy. Therefore, we hypothesized that disease...... of Zol correlated with bone-specific alkaline phosphatase (bALP) levels in BC (p = 0.001), and with CTX/bALP in Zol naive MM patients (p = 0.012). Especially in BC patients, WBrt correlated with age (p = 0.014) independently of kidney function. In MM patients WBrt was found to primarily correlate...... with the extent of bone disease (p = 0.028). Multivariate linear regression analyses of the entire cohort pointed out that WBrt of Zol was best predicted by age (p ...

Effects of intravenous zoledronate and ibandronate on carotid intima-media thickness, lipids and FGF-23 in postmenopausal osteoporotic women.

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Gonnelli, S; Caffarelli, C; Tanzilli, L; Pondrelli, C; Lucani, B; Franci, B M; Nuti, R

2014-04-01

Osteoporosis and atherosclerosis are interconnected entities and share also some pathophysiological mechanisms. Moreover, recent literature data have supported the hypothesis that bisphosphonates (BPs) may have some antiatherogenic actions. This study aimed to evaluate the effects of one year with zoledronate or ibandronate given intravenously on lipid profile and on carotid artery intima-media thickness (CA-IMT). Sixty postmenopausal osteoporotic women (mean age: 66.6±7.8years) were randomly assigned to 1-year treatment with zoledronate 5mg i.v. annually or ibandronate 3mg i.v. every 3 months. In all patients at baseline and after 12months we measured CA-IMT, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), 25-hydroxyvitamin D (25OHD), bone alkaline phosphatase (B-ALP), type I collagen β carboxy telopeptide (βCTX), osteocalcin (OC), fibroblast growth factor 23 (FGF-23) and sclerostin. The osteoporotic women treated with zoledronate showed a greater reduction in CA-IMT than those treated with ibandronate. HDL-C and HDL-C/LDL-C ratio showed a significant (pwomen treated with zoledronate and in those treated with ibandronate. At the end of the study period sclerostin serum levels showed a higher increase in the patients treated with zoledronate than in those treated with ibandronate. In osteoporotic women both zoledronate and ibandronate given intravenously resulted in an increase in HDL-C/LDL-C ratio and a reduction of CA-IMT which was significant only for zoledronate. Further prospective studies are needed to clarify whether the change in FGF-23 and sclerostin levels is a marker or a potential mechanism of the action of BPs at a vascular level. Copyright © 2014 Elsevier Inc. All rights reserved.

Zoledronic acid produces combinatory anti-tumor effects with cisplatin on mesothelioma by increasing p53 expression levels.

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Shinya Okamoto

Full Text Available We examined anti-tumor effects of zoledronic acid (ZOL, one of the bisphosphonates agents clinically used for preventing loss of bone mass, on human mesothelioma cells bearing the wild-type p53 gene. ZOL-treated cells showed activation of caspase-3/7, -8 and -9, and increased sub-G1 phase fractions. A combinatory use of ZOL and cisplatin (CDDP, one of the first-line anti-cancer agents for mesothelioma, synergistically or additively produced the cytotoxicity on mesothelioma cells. Moreover, the combination achieved greater anti-tumor effects on mesothelioma developed in the pleural cavity than administration of either ZOL or CDDP alone. ZOL-treated cells as well as CDDP-treated cells induced p53 phosphorylation at Ser 15, a marker of p53 activation, and up-regulated p53 protein expression levels. Down-regulation of p53 levels with siRNA however did not influence the ZOL-mediated cytotoxicity but negated the combinatory effects by ZOL and CDDP. In addition, ZOL treatments augmented cytotoxicity of adenoviruses expressing the p53 gene on mesothelioma. These data demonstrated that ZOL-mediated augmentation of p53, which was not linked with ZOL-induced cytotoxicity, played a role in the combinatory effects with a p53 up-regulating agent, and suggests a possible clinical use of ZOL to mesothelioma with anti-cancer agents.

Zoledronic acid at subtoxic dose extends osteoblastic stage span of primary human osteoblasts.

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Zara, Susi; De Colli, Marianna; di Giacomo, Viviana; Zizzari, Vincenzo Luca; Di Nisio, Chiara; Di Tore, Umberto; Salini, Vincenzo; Gallorini, Marialucia; Tetè, Stefano; Cataldi, Amelia

2015-04-01

This study aimed to check the effect of zoledronic acid (ZA) at subtoxic dose on human osteoblasts (HOs) in terms of cell viability, apoptosis occurrence, and differentiation induction. ZA belongs to the family of bisphosphonates (BPs), largely used in the clinical practice for the treatment of bone diseases, often associated with jaw osteonecrosis onset. Their pharmacological action consists in the direct block of the osteoclast-mediated bone resorption along with indirect action on osteoblasts. HOs were treated choosing the highest limit concentration (10(-5) M) which does not induce toxic effects. Live/dead staining, flow cytometry, mitochondrial membrane potential assay, osteocalcin western blotting, gp38 RT-PCR, collagen type I, PGE2, and IL-6 ELISA assays were performed. Similar viability level between control and ZA-treated samples is found along with no significant increase of apoptotic and necrotic cells in ZA-treated sample. To establish if an early apoptotic pathway was triggered, Bax expression and mitochondrial membrane potential were evaluated finding a higher protein expression in control sample and a good integrity of mitochondrial membrane in both experimental points. Type I collagen secretion and alkaline phosphatase (ALP) activity appear increased in ZA-treated sample, osteocalcin expression level is reduced in ZA-treated cells, whereas no modifications of gp38 mRNA level are evidenced. No statistical differences are identified in PGE2 secretion level whereas IL-6 secretion is lower in ZA-treated HOs with respect to control ones. These results highlight that ZA, delaying the osteoblastic differentiation process versus the osteocytic lineage, strengthens its pharmacological activity enhancing bone density. The knowledge of ZA effects on osteoblasts at subtoxic dose allows to improve therapeutic protocols in order to strengthen drug pharmacological activity through a combined action on both osteoclastic and osteoblastic cells.

Systematic review and meta-analysis of the efficacy and safety of alendronate and zoledronate for the treatment of postmenopausal osteoporosis.

Science.gov (United States)

Serrano, Ana Julissa; Begoña, Leire; Anitua, Eduardo; Cobos, Raquel; Orive, Gorka

2013-12-01

The aim of this meta-analysis was to evaluate the efficacy and safety of two bisphosphonates (alendronate and zoledronate) in the treatment of postmenopausal osteoporosis. The incidence of fractures was considered as primary endpoint. Only randomized trials with a follow-up period of 1 year or more were included in this systematic review and meta-analysis. We excluded studies that included patients with secondary osteoporosis especially in relation to therapy with corticosteroids or other drugs or diseases known to affect bone mineral density. Studies published as subgroup analysis, extension studies, economic evaluations, and comparisons with active control were excluded. The methodological quality of controlled clinical trials that met these inclusion criteria was evaluated. No studies were excluded from analysis due to lack of quality. The risk ratio of hip, vertebral and wrist fractures for alendronate were 0.61 [95% confidence interval (CI) 0.40-0.93], 0.54 (95% CI 0.44-0.66) and 0.65 (95% CI 0.33-1.25), respectively. Zoledronate risk ratio was 0.62 (95% CI 0.46-0.82) and 0.38 (95% CI 0.22-0.67) for hip and vertebral fractures, respectively.

Effect of zoledronic acid on reducing femoral bone mineral density loss following total hip arthroplasty: A meta-analysis from randomized controlled trails.

Science.gov (United States)

Gao, Jian; Gao, Chong; Li, Hui; Wang, Guo-Sheng; Xu, Chang; Ran, Jian

2017-11-01

This meta-analysis aimed to assess the efficiency of intravenous administration of zoledronic acid on reducing femoral periprosthetic bone mineral density loss in patients undergoing primary total hip arthroplasty (THA). A systematic search was performed in Medline (1966-2017.07.31), PubMed (1966-2017.07.31), Embase (1980-2017.07.31), ScienceDirect (1985-2017.07.31) and the Cochrane Library (1966-2017.07.31). Fixed/random effect model was used according to the heterogeneity tested by I 2 statistic. Sensitivity analysis was conducted and publication bias was assessed. Meta-analysis was performed using Stata 11.0 software. Four studies including 185 patients met the inclusion criteria. The present meta-analysis indicated that there were significant differences between groups in terms of periprosthetic bone mineral density in Gruen zone 1 (SMD = 0.752, 95% CI: 0.454 to 1.051, P = 0.000), 2 (SMD = 0.524, 95% CI: 0.230 to 0.819, P = 0.000), 4 (SMD = 0.400, 95% CI: 0.107 to 0.693, P = 0.008), 6 (SMD = 0.893, 95% CI: 0.588 to 1.198, P = 0.000) and 7 (SMD = 0.988, 95% CI: 0.677 to 1.300, P = 0.000). Intravenous administration of zoledronic acid could significantly reduce periprosthetic bone mineral density loss (Gruen zone 1, 2, 4, 6 and 7) after THA. In addition, no severe adverse events were identified. High-quality RCTs with large sample size were still required. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

5-year follow-up of a randomized controlled trial of immediate versus delayed zoledronic acid for the prevention of bone loss in postmenopausal women with breast cancer starting letrozole after tamoxifen: N03CC (Alliance) trial.

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Wagner-Johnston, Nina D; Sloan, Jeff A; Liu, Heshan; Kearns, Ann E; Hines, Stephanie L; Puttabasavaiah, Suneetha; Dakhil, Shaker R; Lafky, Jacqueline M; Perez, Edith A; Loprinzi, Charles L

2015-08-01

Postmenopausal women with breast cancer receiving aromatase inhibitors are at an increased risk of bone loss. The current study was undertaken to determine whether upfront versus delayed treatment with zoledronic acid (ZA) impacted bone loss. This report described the 5-year follow-up results. A total of 551 postmenopausal women with breast cancer who completed tamoxifen treatment and were undergoing daily letrozole treatment were randomized to either upfront (274 patients) or delayed (277 patients) ZA at a dose of 4 mg intravenously every 6 months. In the patients on the delayed treatment arm, ZA was initiated for a postbaseline bone mineral density T-score of prevented bone loss compared with delayed treatment in postmenopausal women receiving letrozole and these differences were maintained at 5 years. The incidence of osteoporosis or fractures was not found to be significantly different between treatment arms. © 2015 American Cancer Society.

High-Dose Hypofractionated Radiation Therapy for Noncompressive Vertebral Metastases in Combination With Zoledronate: A Phase 1 Study

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Pichon, Baptiste [Department of Radiation Oncology, ICO Cancer Center, Saint-Herblain (France); Campion, Loïc [Department of Biostatistics, ICO Cancer Center, Saint-Herblain (France); Delpon, Grégory [Department of Medical Physics, ICO Cancer Center, Saint-Herblain (France); CRCNA, Inserm U892, CNRS UMR 6299, Nantes (France); Thillays, François [Department of Radiation Oncology, ICO Cancer Center, Saint-Herblain (France); Carrie, Christian [Department of Radiation Oncology, Léon Bérard Center, Lyon (France); Cellier, Patrice [Department of Radiation Oncology, ICO Cancer Center, Angers (France); Pommier, Pascal; Laude, Cécile [Department of Radiation Oncology, Léon Bérard Center, Lyon (France); Mervoyer, Augustin [Department of Radiation Oncology, ICO Cancer Center, Saint-Herblain (France); Hamidou, Hadji [Department of Radiation Oncology, ICO Cancer Center, Angers (France); Mahé, Marc-André [Department of Radiation Oncology, ICO Cancer Center, Saint-Herblain (France); Supiot, Stéphane, E-mail: stephane.supiot@ico.unicancer.fr [Department of Radiation Oncology, ICO Cancer Center, Saint-Herblain (France); CRCNA, Inserm U892, CNRS UMR 6299, Nantes (France)

2016-11-15

Introduction: Hypofractionated stereotactic radiation therapy (HSRT) for vertebral metastases gives good results in terms of local control but increases the risk of fracture in the treated volume. Preclinical and clinical studies have shown that zoledronate not only reduces the risk of fracture and stimulates osteoclastic remodeling but also increases the immune response and radiosensitivity. This study aimed to evaluate the tolerability and effectiveness of zoledronate in association with radiation therapy. Patients and Methods: We conducted a multicenter phase 1 study that combined HSRT (3 × 9 Gy) and zoledronate in patients with vertebral metastasis ( (NCT01219790)). The principal objective was the absence of spinal cord adverse reactions at 1 year. The secondary objectives were acute tolerability, the presentation of a bone event, local tumor control, pain control, progression-free survival, and overall survival. Results: Thirty patients (25 male, 5 female), median age 66 years, who were followed up for a median period of 19.2 months, received treatment for 49 vertebral metastases. A grade 3 acute mucosal adverse event occurred in 1 patient during the treatment and in 2 more at 1 month. No late neurologic adverse events were reported at 1 year. The mean pain scores diminished significantly at 1 month (1.35; P=.0125) and 3 months (0.77; P<.0001) compared with pain scores at study entry (2.49). Vertebral collapse in the irradiated zone occurred in 1 (2%) treated vertebra. Control of local disease was achieved in 94% of irradiated patients (3 local recurrences). Conclusion: The combination of zoledronate and HSRT in the treatment of vertebral metastasis is well tolerated and seems to reduce the rate of vertebral collapse, effectively relieve pain, and achieve good local tumor control with no late neurologic adverse effects.

Zoledronic acid preserves bone structure and increases survival but does not limit tumour incidence in a prostate cancer bone metastasis model.

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Tzong-Tyng Hung

Full Text Available BACKGROUND: The bisphosphonate, zoledronic acid (ZOL, can inhibit osteoclasts leading to decreased osteoclastogenesis and osteoclast activity in bone. Here, we used a mixed osteolytic/osteoblastic murine model of bone-metastatic prostate cancer, RM1(BM, to determine how inhibiting osteolysis with ZOL affects the ability of these cells to establish metastases in bone, the integrity of the tumour-bearing bones and the survival of the tumour-bearing mice. METHODS: The model involves intracardiac injection for arterial dissemination of the RM1(BM cells in C57BL/6 mice. ZOL treatment was given via subcutaneous injections on days 0, 4, 8 and 12, at 20 and 100 µg/kg doses. Bone integrity was assessed by micro-computed tomography and histology with comparison to untreated mice. The osteoclast and osteoblast activity was determined by measuring serum tartrate-resistant acid phosphatase 5b (TRAP 5b and osteocalcin, respectively. Mice were euthanased according to predetermined criteria and survival was assessed using Kaplan Meier plots. FINDINGS: Micro-CT and histological analysis showed that treatment of mice with ZOL from the day of intracardiac injection of RM1(BM cells inhibited tumour-induced bone lysis, maintained bone volume and reduced the calcification of tumour-induced endochondral osteoid material. ZOL treatment also led to a decreased serum osteocalcin and TRAP 5b levels. Additionally, treated mice showed increased survival compared to vehicle treated controls. However, ZOL treatment did not inhibit the cells ability to metastasise to bone as the number of bone-metastases was similar in both treated and untreated mice. CONCLUSIONS: ZOL treatment provided significant benefits for maintaining the integrity of tumour-bearing bones and increased the survival of tumour bearing mice, though it did not prevent establishment of bone-metastases in this model. From the mechanistic view, these observations confirm that tumour-induced bone lysis is not a

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

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

2013-01-01

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. (paper)

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

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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.

Early effects of zoledronic acid and teriparatide on bone microarchitecture, remodeling and collagen crosslinks: comparison between iliac crest and lumbar vertebra in ewes.

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Portero-Muzy, N R; Chavassieux, P M; Bouxsein, M L; Gineyts, E; Garnero, P; Chapurlat, R D

2012-10-01

Iliac crest bone biopsies are used to assess the mechanism of action of drug treatments, yet there are little data comparing this site to sites prone to fracture. The purpose of this study was to compare the delay and the amplitude of responses to treatment in two different bone sites. The short-term effects of zoledronic acid and teriparatide on microarchitecture, collagen crosslinks and bone remodeling were evaluated in iliac crest and lumbar vertebrae. Aged ewes (n=8/gr) received either vehicle (CTRL) or a single injection of zoledronic acid (ZOL, 10mg) or daily injections of teriparatide (TPTD, 20 μg/d) for 3 months. Blood samples were collected monthly for assessing bone turnover markers. At the end of the study, a transiliac bone biopsy (IC) and L1 lumbar vertebrae (LV1) were collected to assess bone microarchitecture; pyridinoline (PYD), deoxypyridinoline (DPD), pentosidine (PEN) content, static and dynamic parameters of bone remodeling. In CTRL, Tb-BV/TV was significantly higher in LV1 than IC (psALP (p<0.001) and sCTX (p<0.001) were observed in the ZOL-group whereas in TPTD-group, after transient increases, they returned to baseline values. When compared to their respective CTRL, ZOL induced significant increases in Tb.BV/TV, Conn.D, Tb.N and Tb.Sp, in IC but not in LV1. Regardless of the site, ZOL markedly depressed the bone turnover: The static parameters of bone formation significantly decreased and the diminution of MS/BS, BFR/BS and Ac.f varied from -94 to -98% vs CTRL (p<0.01 to 0.001). It was associated with a diminution of the DPD content and the PYD/DPD ratio mainly in IC cortices. In contrast, after 3 months, TPTD did not modify the 3D structure and microarchitecture in IC and LV1, except a trend of higher Conn.D in IC, compared to IC-CTRL. TPTD treatment induced a significant increase in cortical porosity in LV1 (p<0.05) when compared to LV1-CTRL. Static parameters of bone formation and resorption were augmented in both sites, significantly

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

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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.

Downregulation of CXCR4 Expression and Functionality After Zoledronate Exposure in Canine Osteosarcoma.

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Byrum, M L; Pondenis, H C; Fredrickson, R L; Wycislo, K L; Fan, T M

2016-07-01

The establishment and progression of metastases remains the life-limiting factor for dogs diagnosed with osteosarcoma (OS). The pattern of metastases is likely regulated through interactions between chemokine receptors and chemokines, and perturbations in these signaling cascades responsible for cytoskeletal organization and directional migration have the potential to alter metastatic cell trafficking behaviors. Zoledronate will impair directional migration of OS cells through downregulation of chemokine (C-X-C motif) receptor 4 (CXCR4) expression and functionality. Nineteen archived tumor specimens and plasma from 20 dogs with OS. Prospectively, the expressions of CXCR4 were studied in OS cell lines and spontaneous tumor samples. The effect of zoledronate on CXCR4 expression and functionality was investigated by characterizing responses in 3 OS cell lines. In 19 OS specimens and 20 dogs with OS, changes in CXCR4 expression and circulating CXCR4 concentrations were characterized in response to zoledronate therapy respectively. All canine OS cells express CXCR4, and zoledronate reduces CXCR4 expression and functionality by 27.7% (P < .0001), through augmented proteasome degradation and reduced prenylation of heterotrimeric G-proteins in 33% of tumor cell lines evaluated. In OS-bearing dogs, zoledronate reduces CXCR4 expressions by 40% within the primary tumor compared to untreated controls (P = .03) and also decreases the circulating concentrations of CXCR4 in 18 of 20 dogs with OS. Zoledronate can alter CXCR4 expression and functionality in OS cells, and consequent perturbations in CXCR4 intracellular signaling cascades might influence patterns of metastases. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

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

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Glatt M.

2001-01-01

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

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

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

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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. Copyright © 2015 Elsevier B.V. All rights reserved.

Effective combination treatment of GD2-expressing neuroblastoma and Ewing's sarcoma using anti-GD2 ch14.18/CHO antibody with Vγ9Vδ2+ γδT cells.

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Fisher, Jonathan P H; Flutter, Barry; Wesemann, Florian; Frosch, Jennifer; Rossig, Claudia; Gustafsson, Kenth; Anderson, John

Gamma delta T lymphocytes (γδT cells) have pleiotropic properties including innate cytotoxicity, which make them attractive effectors for cancer immunotherapy. Combination treatment with zoledronic acid and IL-2 can activate and expand the most common subset of blood γδT, which express the Vγ9Vδ2 T cell receptor (TCR) (Vδ2 T cells). Vγ9Vδ2 T cells are equipped for antibody-dependent cell-mediated cytotoxicity (ADCC) through expression of the low-affinity FcγR CD16. GD2 is a highly ranked tumor associated antigen for immunotherapy due to bright expression on the cell surface, absent expression on normal tissues and availability of therapeutic antibodies with known efficacy in neuroblastoma. To explore the hypothesis that zoledronic acid, IL-2 and anti-GD2 antibodies will synergize in a therapeutic combination, we evaluated in vitro cytotoxicity and tumor growth inhibition in the GD2 expressing cancers neuroblastoma and Ewing's sarcoma. Vδ2 T cells exert ADCC against GD2-expressing Ewing's sarcoma and neuroblastoma cell lines, an effect which correlates with the brightness of GD2 expression. In an immunodeficient mouse model of small established GD2-expressing Ewing's sarcoma or neuroblastoma tumors, the combination of adoptively transferred Vδ2+ T cells, expanded in vitro with zoledronic acid and IL-2, with anti-GD2 antibody ch14.18/CHO, and with systemic zoledronic acid, significantly suppressed tumor growth compared to antibody or γδT cell-free controls. Combination treatment using ch14.18/CHO, zoledronic acid and IL-2 is more effective than their use in isolation. The already-established safety profiles of these agents make testing of the combination in GD2 positive cancers such as neuroblastoma or Ewing's sarcoma both rational and feasible.

In vitro comparison of new bisphosphonic acids and zoledronate effects on human gingival fibroblasts viability, inflammation and matrix turnover.

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De Colli, Marianna; Tortorella, Paolo; Marconi, Guya Diletta; Agamennone, Mariangela; Campestre, Cristina; Tauro, Marilena; Cataldi, Amelia; Zara, Susi

2016-11-01

Bisphosphonates (BPs) are drugs clinically used in resorptive diseases. It was already proved that some clinically relevant BPs can inhibit a class of enzymes called matrix metalloproteinases (MMPs), required during tissue remodelling. Combining the arylsulfonamide function with the bisphosphonic group, several compounds were synthesized to obtain selective inhibitors of MMPs. The aim of the present study was to compare the effect of zoledronic acid (ZA), the most potent bisphosphonate available as therapy, with new sulfonamide containing BPs in an in vitro model of human gingival fibroblasts (HGFs). Western blot was used to measure procollagen I, β1 integrin MMP-8 and MMP-9, phase contrast and MTT for cell viability; L-lactate-dehydrogenase (LDH) measurement was performed for toxicity evaluation and ELISA for prostaglandin E 2 (PGE 2 ) secretion assessment. When compared with ZA, the treatment with the newly synthesized compounds shows increasing viability, procollagen I expression and decreased expression of β1 integrin in HGFs. Higher levels of released LDH, PGE 2 and MMP-9 expression are recorded in ZA-treated HGFs. Increased levels of MMP-8 are recorded in newly synthesized compounds-treated samples. These findings allowed to conclude that new tested BPs did not affect HGFs viability and adhesion, did not induce cellular toxicity, were not responsible for inflammatory event induction and could preserve the physiological matrix turnover. It could be hypothesized that the new molecules were better tolerated by soft tissues, resulting in lesser side effects.

Activity of mevalonate pathway inhibitors against breast and ovarian cancers in the ATP-based tumour chemosensitivity assay

International Nuclear Information System (INIS)

Knight, Louise A; Kurbacher, Christian M; Glaysher, Sharon; Fernando, Augusta; Reichelt, Ralf; Dexel, Susanne; Reinhold, Uwe; Cree, Ian A

2009-01-01

Previous data suggest that lipophilic statins such as fluvastatin and N-bisphosphonates such as zoledronic acid, both inhibitors of the mevalonate metabolic pathway, have anti-cancer effects in vitro and in patients. We have examined the effect of fluvastatin alone and in combination with zoledronic acid in the ATP-based tumour chemosensitivity assay (ATP-TCA) for effects on breast and ovarian cancer tumour-derived cells. Both zoledronic acid and fluvastatin showed activity in the ATP-TCA against breast and ovarian cancer, though fluvastatin alone was less active, particularly against breast cancer. The combination of zoledronic acid and fluvastatin was more active than either single agent in the ATP-TCA with some synergy against breast and ovarian cancer tumour-derived cells. Sequential drug experiments showed that pre-treatment of ovarian tumour cells with fluvastatin resulted in decreased sensitivity to zoledronic acid. Addition of mevalonate pathway components with zoledronic acid with or without fluvastatin showed little effect, while mevalonate did reduced inhibition due to fluvastatin. These data suggest that the combination of zoledronic acid and fluvastatin may have activity against breast and ovarian cancer based on direct anti-cancer cell effects. A clinical trial to test this is in preparation

Dgroup: DG00787 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available DG00787 Chemical ... DGroup Zoledronic acid ... D08689 ... Zoledronic acid (INN) D01968 ... Zoledron...ic acid (USAN); Zoledronic acid hydrate (JAN) ... D06378 ... Zoledronate disodium (USAN) D06379 ... Zoledron...ate trisodium (USAN) D10515 ... Zoledronic acid hemipentahydrate (JAN) Other ... DG01600 ... Bisphosphonate ATC code: M05BA08 Bisphosphonates FDPS [HSA:2224] [KO:K00787] ...

Effect of local injection of Zolena, zoledronic acid made in Iran, on orthodontic tooth movement and root and bone resorption in rats.

Science.gov (United States)

Seifi, Massoud; Asefi, Sohrab; Hatamifard, Ghazal; Lotfi, Ali

2017-01-01

Background. Anchorage control is an essential part of orthodontic treatment planning, especially in adult patients who demand a more convenient treatment. Zoledronic acid (ZA) is an effective choice to address this problem. It is the most potent member of the bisphosphonates family that has an inhibitory effect on bone resorption by suppressing osteoclast function. Therefore, ZA might be a good option for orthodontic anchorage control. The current study evaluated the effect of local administration of Zolena (ZA made in Iran) on orthodontic tooth movement (OTM) and root and bone resorption. Methods. The experimental group consisted of 30 rats in 3 subgroups (n=10). Anesthesia was induced, and one closed NiTi coil spring was installed between the first molar and central incisor unilaterally, except for the negative control group. The positive control group received vestibular injection of 0.01 mL of saline next to the maxillary first molar, and 0.01 mL of the solution was injected at the same site in the ZA group. After 21 days, the rats were sacrificed and the distance between the first and second molars was measured with a leaf gauge. Histological analysis was conducted by a blind pathologist for the number of Howship's lacunae, blood vessels, osteoclast-like cells and root resorption lacunae. Data were analyzed with ANOVA, Tukey test and t-test. Results. There were no significant differences in OTM between the force-applied groups. ZA significantly inhibited bone/root resorption and angiogenesis compared to the positive control group. Conclusion. Zolena did not decrease OTM but significantly inhibited bone and root resorption. Zolena might be less potent than its foreign counterparts.

Local application of zoledronate for maximum anchorage during space closure.

Science.gov (United States)

Ortega, Adam J A J; Campbell, Phillip M; Hinton, Robert; Naidu, Aparna; Buschang, Peter H

2012-12-01

Orthodontists have used various compliance-dependent physical means such as headgears and intraoral appliances to prevent anchorage loss. The aim of this study was to determine whether 1 local application of the bisphosphonate zoledronate could be used to prevent anchorage loss during extraction space closure in rats. Thirty rats had their maxillary left first molars extracted and their maxillary left second molars protracted into the extraction space with a 10-g nickel-titanium closing coil for 21 days. Fifteen control rats received a local injection of phosphate-buffered saline solution, and 15 experimental rats received 16 μg of the bisphosphonate zoledronate. Bisphosphonate was also delivered directly into the extraction site and left undisturbed for 5 minutes. Cephalograms and incremental thickness gauges were used to measure tooth movements. Tissues were analyzed by microcomputed tomography and histology. The control group demonstrated significant (P <0.05) tooth movements throughout the 21-day period. They showed significantly greater tooth movements than the experimental group beginning in the second week. The experimental group showed no significant tooth movement after the first week. The microcomputed tomography and histologic observations showed significant bone loss in the extraction sites and around the second molars of the controls. In contrast, the experimental group had bone preservation and bone fill. There was no evidence of bisphosphonate-associated osteonecrosis in any sample. A single small, locally applied dose of zoledronate provided maximum anchorage and prevented significant bone loss. Copyright © 2012 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Zoledronic acid inhibits pulmonary metastasis dissemination in a preclinical model of Ewing’s sarcoma via inhibition of cell migration

International Nuclear Information System (INIS)

Odri, Guillaume; Kim, Pui-Pui; Lamoureux, François; Charrier, Céline; Battaglia, Séverine; Amiaud, Jérôme; Heymann, Dominique; Gouin, François; Redini, Françoise

2014-01-01

Ewing’s sarcoma (ES) is the second most frequent primitive malignant bone tumor in adolescents with a very poor prognosis for high risk patients, mainly when lung metastases are detected (overall survival <15% at 5 years). Zoledronic acid (ZA) is a potent inhibitor of bone resorption which induces osteoclast apoptosis. Our previous studies showed a strong therapeutic potential of ZA as it inhibits ES cell growth in vitro and ES primary tumor growth in vivo in a mouse model developed in bone site. However, no data are available on lung metastasis. Therefore, the aim of this study was to determine the effect of ZA on ES cell invasion and metastatic properties. Invasion assays were performed in vitro in Boyden’s chambers covered with Matrigel. Matrix Metalloproteinase (MMP) activity was analyzed by zymography in ES cell culture supernatant. In vivo, a relevant model of spontaneous lung metastases which disseminate from primary ES tumor was induced by the orthotopic injection of 10 6 human ES cells in the tibia medullar cavity of nude mice. The effect of ZA (50 μg/kg, 3x/week) was studied over a 4-week period. Lung metastases were observed macroscopically at autopsy and analysed by histology. ZA induced a strong inhibition of ES cell invasion, probably due to down regulation of MMP-2 and −9 activities as analyzed by zymography. In vivo, ZA inhibits the dissemination of spontaneous lung metastases from a primary ES tumor but had no effect on the growth of established lung metastases. These results suggest that ZA could be used early in the treatment of ES to inhibit bone tumor growth but also to prevent the early metastatic events to the lungs

Bone targeting compounds for radiotherapy and imaging: *Me(III)-DOTA conjugates of bisphosphonic acid, pamidronic acid and zoledronic acid.

Science.gov (United States)

Meckel, M; Bergmann, R; Miederer, M; Roesch, F

2017-01-01

Bisphosphonates have a high adsorption on calcified tissues and are commonly used in the treatment of bone disorder diseases. Conjugates of bisphosphonates with macrocyclic chelators open new possibilities in bone targeted radionuclide imaging and therapy. Subsequent to positron emission tomography (PET) examinations utilizing 68 Ga-labelled analogues, endoradiotheraphy with 177 Lu-labelled macrocyclic bisphosphonates may have a great potential in the treatment of painful skeletal metastases. Based on the established pharmaceuticals pamidronate and zoledronate two new DOTA-α-OH-bisphosphonates, DOTA PAM and DOTA ZOL (MM1.MZ) were successfully synthesized. The ligands were labelled with the positron emitting nuclide 68 Ga and the β - emitting nuclide 177 Lu and compared in in vitro studies and in ex vivo biodistribution studies together with small animal PET and single photon emission computed tomography (SPECT) studies against [ 18 F]NaF and a known DOTA-α-H-bisphosphonate conjugate (BPAPD) in healthy Wistar rats. The new DOTA-bisphosphonates can be labelled in high yield of 80 to 95 % in 15 min with post-processed 68 Ga and >98 % with 177 Lu. The tracers showed very low uptake in soft tissue, a fast renal clearance and a high accumulation on bone. The best compound was [ 68 Ga]DOTA ZOL (SUV Femur  = 5.4 ± 0.6) followed by [ 18 F]NaF (SUV Femur  = 4.8 ± 0.2), [ 68 Ga]DOTA PAM (SUV Femur  = 4.5 ± 0.2) and [ 68 Ga]BPAPD (SUV Femur  = 3.2 ± 0.3). [ 177 Lu]DOTA ZOL showed a similar distribution as the diagnostic 68 Ga complex. The 68 Ga labelled compounds showed a promising pharmacokinetics, with similar uptake profile and distribution kinetics. Bone accumulation was highest for [ 68 Ga]DOTA ZOL , which makes this compound probably an interesting bone targeting agent for a therapeutic approach with 177 Lu. The therapeutic compound [ 177 Lu]DOTA ZOL showed a high target-to-background ratio. SPECT experiments showed concordance

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

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Clive, Amelia O; Hooper, Clare E; Edey, Anthony J; Morley, Anna J; Zahan-Evans, Natalie; Hall, David; Lyburn, Iain; White, Paul; Braybrooke, Jeremy P; Sequeiros, Iara; Lyen, Stephen M; Milton, Tim; Kahan, Brennan C; Maskell, Nick A

2015-01-01

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.

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

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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.

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

International Nuclear Information System (INIS)

Lin Jianguo; Qiu Ling; Cheng Wen; Luo Shineng; Ye Wanzhong

2011-01-01

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

The IL-6 receptor super-antagonist Sant7 enhances antiproliferative and apoptotic effects induced by dexamethasone and zoledronic acid on multiple myeloma cells.

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Tassone, Pierfrancesco; Galea, Eulalia; Forciniti, Samantha; Tagliaferri, Pierosandro; Venuta, Salvatore

2002-10-01

Interleukin-6 (IL-6) is the major growth and survival factor for multiple myeloma (MM), and has been shown to protect MM cells from apoptosis induced by a variety of agents. IL-6 receptor antagonists, which prevent the assembly of functional IL-6 receptor complexes, inhibit cell proliferation and induce apoptosis in MM cells. We have investigated whether the IL-6 receptor super-antagonist Sant7 might enhance the antiproliferative and apoptotic effects induced by the combination of dexamethasone (Dex) and zoledronic acid (Zln) on human MM cell lines and primary cells from MM patients. Here we show that each of these compounds individually induced detectable antiproliferative effects on MM cells. Sant7 significantly enhanced growth inhibition and apoptosis induced by Dex and Zln on both MM cell lines and primary MM cells. These results indicate that overcoming IL-6 mediated cell resistance by Sant7 potentiates the effect of glucocorticoides and bisphosphonates on MM cell growth and survival, providing a rationale for therapies including IL-6 antagonists in MM.

Home-based zoledronic acid infusion therapy in patients with solid tumours: compliance and patient-nurse satisfaction.

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Lebret, Thierry; Mouysset, Jean-Loup; Lortholary, Alain; El Kouri, Claude; Bastit, Laurent; Ktiouet, Meryem; Slimane, Khemaies; Murraciole, Xavier; Guérif, Stéphane

2013-06-01

This study aimed to explore patient and nurse satisfaction, compliance with best practice, technical feasibility and safety of home infusion of the bisphosphonate zoledronic acid (ZOL). This was a prospective 1-year survey of home ZOL therapy (4 mg Zometa, 15-min i.v., every 3-4 weeks) in patients with bone metastases secondary to a solid malignancy. A physician questionnaire, nurse satisfaction/feasibility questionnaire and patient satisfaction questionnaire were administered at several time-points. Physician participation rate was 56.5% (87/154). Physicians enrolled 818 patients visited by 381 predominantly community nurses. Of the 788 case report forms received, 763 met inclusion criteria. Patient characteristics were as follows: median age, 68 years (30-95); M/F, 40/60; ECOG-PS 0 or 1, 78.6%; and primary tumour site, breast (55.2%), prostate (28.4%), lung (7.2%) or other (9.4%). Nurse satisfaction rates were high: organisation of home ZOL therapy, 90.9%; ease of infusion, 96.7%; patient-nurse relationship, 97.5%; and relationship with hospital staff, 73%. Patient satisfaction was also very high (95.3%). The main reasons were quality of the nurse-patient relationship (57.6%), less travel/waiting (68.8%), home environment (52.9%) and less disruption to daily routine (36.6%). ZOL therapy was well tolerated, the discontinuation rate due to adverse events (including deaths whether related to diseases progression or not) was 33.6%. The incidence of osteonecrosis of the jaw was 0.6% and of fractures, 0.2%. Practitioner compliance with best practice was 76.7-83.7% for recommended and/or tolerated dosage, 73% for dental hygiene checks at inclusion and 48-56% thereafter, 66% for pre-infusion hydration, and often undocumented for calcium/vitamin D supplementation. Home ZOL therapy was well tolerated. Both patient and nurse satisfaction were very high. However, better compliance with best practice should be encouraged.

Zoledronic Acid improves clinical outcomes when administered before onset of bone pain in patients with prostate cancer.

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Saad, Fred; Eastham, James

2010-11-01

To evaluate, in an exploratory analysis, the effect of zoledronic acid (ZOL) on skeletal-related event (SRE) incidence as determined by the bone pain levels at study entry. Bone metastases can undermine skeletal integrity long before the onset of symptoms. Treating patients before symptom onset might be more effective in preventing SREs and improving patients' quality of life. ZOL has shown significant reductions in SREs and pain compared with placebo in patients with bone metastases from advanced prostate cancer in a randomized placebo-controlled trial. Patients from a placebo-controlled, Phase III trial of men with castration-resistant prostate cancer, randomized to receive ZOL 4 mg (n = 214) or placebo (n = 208) for ≤ 24 months, were stratified by pain or no pain at baseline. Bone pain was assessed at baseline, week 3, and week 6 and at 6-week intervals thereafter. The primary endpoint was the proportion of patients with ≥ 1 SRE. ZOL significantly reduced the mean pain scores compared with placebo at 3, 9, 21, and 24 months (P ≤ .03 for each point) and reduced the annual incidence of SREs. Among patients without baseline pain, ZOL decreased the percentage of patients with ≥ 1 SRE by 39% and reduced the annual incidence of SREs by 49% compared with placebo. ZOL delayed the onset of bone pain in those patients without pain at baseline compared with placebo. ZOL reduced bone pain and SREs compared with placebo in patients with bone metastases from castration-resistant prostate cancer, irrespective of the baseline pain status, and appeared more efficacious when initiated before the onset of pain. Copyright © 2010 Elsevier Inc. All rights reserved.

Advantages and Disadvantages of Bone Protective Agents in Metastatic Prostate Cancer: Lessons Learned

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Christian Thomas

2016-08-01

Full Text Available Nine out of ten metastatic prostate cancer (PCa patients will develop osseous metastases. Of these, every second will suffer from skeletal-related events (SRE. SRE are associated with an increased risk for death, which is markedly increased in the presence of pathological fracture. Moreover, health insurance costs nearly double in the presence of SRE. Zoledronic acid and denosumab are both approved drugs for the prevention or delay of SRE in castration-resistant prostate cancer (CRPC patients with osseous metastases. However, long-term treatment with one of these two drugs is associated with the development of medication-related osteonecrosis of the jaw (MRONJ. Routine inspections of the oral cavity before and during treatment are mandatory in these patients. Regarding imaging techniques, bone scintigraphy seems to be a promising tool to detect early stage MRONJ. Zoledronic acid does not reduce the incidence of SRE in hormone-sensitive PCa. First data shows 3-monthly application of zoledronic acid to be equi-effective to monthly application.

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

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

2016-01-01

ZOL not modulating trabecular thickness in CL + NAHU mice. In summary, our integrated model simulates the combination of weightlessness, exercise-induced mechanical strain, and anti-resorptive treatment that astronauts experience during space missions. Based on these results, we conclude that, at the structural and stiffness level, zoledronate treatment during simulated spaceflight does not impede the skeletal response to axial compression. In contrast to our hypothesis, our data show that zoledronate confers no additional mechanical or structural benefit beyond those gained from cyclical loading.

Osteogenesis imperfecta type V: Genetic and clinical findings in eleven Chinese patients.

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Liu, Yi; Wang, Jiawei; Ma, Doudou; Lv, Fang; Xu, Xiaojie; Xia, Weibo; Jiang, Yan; Wang, Ou; Xing, Xiaoping; Zhou, Peiran; Wang, Jianyi; Yu, Wei; Li, Mei

2016-11-01

Osteogenesis imperfecta (OI) type V is a rare inherited disease characterized by multiple fractures, intraosseous membrane calcification, and hypercallus formation. We investigate the causative gene, phenotype and also observe the effects of zoledronic acid in Chinese OI type V patients. The clinical phenotype and causative gene mutation was investigated in eleven patients with type V OI. Patients were given a dose of zoledronic acid 5mg intravenously. Fracture incidence and Z-score of bone mineral density (BMD) were evaluated. Serum levels of biomarkers such as cross linked C-telopeptide of type I collagen (β-CTX) and safety parameters were assessed. The c.-14C>T mutation in the 5' untranslated region of IFITM5 was detected in all patients. The phenotype was largely variable, and no significant correlation of genotype and phenotype was found. After one dose of zoledronic acid infusion, fracture incidence significantly dropped from 2fractures/year before treatment to 0fracture/year after treatment (P=0.01). Z score of lumbar spine BMD elevated from -2.6 to -1.3 (P<0.001). Serum β-CTX level decreased by 50% (P<0.05). No serious adverse event was found. No obvious correlation was found between the genotype and phenotype. Zoledronic acid had significantly skeletal protective effects in OI of type V. Copyright © 2016 Elsevier B.V. All rights reserved.

Zoledronate complexes. III. Two zoledronate complexes with alkaline earth metals: [Mg(C(5)H(9)N(2)O(7)P(2))(2)(H(2)O)(2)] and [Ca(C(5)H(8)N(2)O(7)P(2))(H(2)O)](n).

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Freire, Eleonora; Vega, Daniel R; Baggio, Ricardo

2010-06-01

Diaquabis[dihydrogen 1-hydroxy-2-(imidazol-3-ium-1-yl)ethylidene-1,1-diphosphonato-kappa(2)O,O']magnesium(II), [Mg(C(5)H(9)N(2)O(7)P(2))(2)(H(2)O)(2)], consists of isolated dimeric units built up around an inversion centre and tightly interconnected by hydrogen bonding. The Mg(II) cation resides at the symmetry centre, surrounded in a rather regular octahedral geometry by two chelating zwitterionic zoledronate(1-) [or dihydrogen 1-hydroxy-2-(imidazol-3-ium-1-yl)ethylidene-1,1-diphosphonate] anions and two water molecules, in a pattern already found in a few reported isologues where the anion is bound to transition metals (Co, Zn and Ni). catena-Poly[[aquacalcium(II)]-mu(3)-[hydrogen 1-hydroxy-2-(imidazol-3-ium-1-yl)ethylidene-1,1-diphosphonato]-kappa(5)O:O,O':O',O''], [Ca(C(5)H(8)N(2)O(7)P(2))(H(2)O)](n), consists instead of a Ca(II) cation in a general position, a zwitterionic zoledronate(2-) anion and a coordinated water molecule. The geometry around the Ca(II) atom, provided by six bisphosphonate O atoms and one water ligand, is that of a pentagonal bipyramid with the Ca(II) atom displaced by 0.19 A out of the equatorial plane. These Ca(II) coordination polyhedra are ;threaded' by the 2(1) axis so that successive polyhedra share edges of their pentagonal basal planes. This results in a strongly coupled rhomboidal Ca(2)-O(2) chain which runs along [010]. These chains are in turn linked by an apical O atom from a -PO(3) group in a neighbouring chain. This O-atom, shared between chains, generates strong covalently bonded planar arrays parallel to (100). Finally, these sheets are linked by hydrogen bonds into a three-dimensional structure. Owing to the extreme affinity of zoledronic acid for bone tissue, in general, and with calcium as one of the major constituents of bone, it is expected that this structure will be useful in modelling some of the biologically interesting processes in which the drug takes part.

Early inhibitory effects of zoledronic acid in tooth extraction sockets in dogs are negated by recombinant human bone morphogenetic protein.

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Gerard, David A; Carlson, Eric R; Gotcher, Jack E; Pickett, David O

2014-01-01

This study was conducted with 2 purposes. The first was to determine the effect of a single dose of zoledronic acid (ZA) on the healing of a tooth extraction socket in dogs. The second was to determine if placement of recombinant human bone morphogenetic protein-2 (rhBMP-2)/absorbable collagen sponge (ACS) - INFUSE, (Medtronic, Memphis, TN) into these extraction sockets would inhibit the inhibition on bone healing and remodeling by ZA. Nine adult female beagle dogs (2 to 3 yr old) were placed into 3 groups of 3 dogs each. Group I received 15 mL of sterile saline intravenously; group II received 2.5 mg of ZA intravenously; and group III received 5 mg of ZA intravenously. Forty-five days after treatment, all dogs underwent extraction of noncontiguous right and left mandibular first molars and second premolars. In group I, the right mandibular extraction sockets had nothing placed in them, whereas the left mandibular sockets had only ACS placed in them. In groups II and III, the right mandibular sockets had rhBMP-2/ACS placed in them, whereas the left mandibular sockets had only ACS placed. All extraction sockets were surgically closed. Tetracycline was given intravenously 5 and 12 days later, and all animals were euthanized 15 days after tooth extraction. The extraction sockets and rib and femur samples were harvested immediately after euthanasia, processed, and studied microscopically. A single dose of ZA significantly inhibited healing and bone remodeling in the area of the tooth extractions. The combination of rhBMP-2/ACS appeared to over-ride some of the bone remodeling inhibition of the ZA and increased bone fill in the extraction sites, and remodeling activity in the area was noted. The effects of rhBMP-2/ACS were confined to the area of the extraction sockets because bone activity at distant sites was not influenced. A single dose of ZA administered intravenously inhibits early healing of tooth extraction sockets and bone remodeling in this animal model. The

Exploring methods for comparing the real-world effectiveness of treatments for osteoporosis: adjusted direct comparisons versus using patients as their own control.

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Karlsson, Linda; Mesterton, Johan; Tepie, Maurille Feudjo; Intorcia, Michele; Overbeek, Jetty; Ström, Oskar

2017-09-21

Using Swedish and Dutch registry data for women initiating bisphosphonates, we evaluated two methods of comparing the real-world effectiveness of osteoporosis treatments that attempt to adjust for differences in patient baseline characteristics. Each method has advantages and disadvantages; both are potential complements to clinical trial analyses. We evaluated methods of comparing the real-world effectiveness of osteoporosis treatments that attempt to adjust for both observed and unobserved confounding. Swedish and Dutch registry data for women initiating zoledronate or oral bisphosphonates (OBPs; alendronate/risedronate) were used; the primary outcome was fracture. In adjusted direct comparisons (ADCs), regression and matching techniques were used to account for baseline differences in known risk factors for fracture (e.g., age, previous fracture, comorbidities). In an own-control analysis (OCA), for each treatment, fracture incidence in the first 90 days following treatment initiation (the baseline risk period) was compared with fracture incidence in the 1-year period starting 91 days after treatment initiation (the treatment exposure period). In total, 1196 and 149 women initiating zoledronate and 14,764 and 25,058 initiating OBPs were eligible in the Swedish and Dutch registries, respectively. Owing to the small Dutch zoledronate sample, only the Swedish data were used to compare fracture incidences between treatment groups. ADCs showed a numerically higher fracture incidence in the zoledronate than in the OBPs group (hazard ratio 1.09-1.21; not statistically significant, p > 0.05). For both treatment groups, OCA showed a higher fracture incidence in the baseline risk period than in the treatment exposure period, indicating a treatment effect. OCA showed a similar or greater effect in the zoledronate group compared with the OBPs group. ADC and OCA each possesses advantages and disadvantages. Combining both methods may provide an estimate of real

The role of vitamin E in the prevention of zoledronic acid-induced nephrotoxicity in rats: a light and electron microscopy study.

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Sert, İbrahim Unal; Kilic, Ozcan; Akand, Murat; Saglik, Lutfi; Avunduk, Mustafa Cihat; Erdemli, Esra

2018-03-01

Bisphosphonates are widely used in metastatic cancer such as prostate and breast cancer, and their nephrotoxic effects have been established previously. In this study we aimed to evaluate both the nephrotoxic effects of zoledronic acid (ZA) and the protective effects of vitamin E (Vit-E) on this process under light and electron microscopy. A total of 30 male Sprague-Dawley rats were divided into 3 groups. The first group constituted the control group. The second group was given i.v. ZA of 3 mg/kg once every 3 weeks for 12 weeks from the tail vein. The third group received the same dosage of ZA with an additional i.m . injection of 15 mg Vit-E every week for 12 weeks. Tissues were taken 4 days after the last dose of ZA for histopathological and ultrastructural evaluation. Paller score, tubular epithelial thickness and basal membrane thickness were calculated for each group. For group 2, the p -values are all < 0.001 for Paller score, epitelial thickness, and basal membrane thickness. For group 3 (ZA + Vit. E), the p -values are < 0.001 for Paller score, 0.996 for epitelial thickness, and < 0.001 basal membrane thickness. Significant differences were also observed in ultrastructural changes for group 2. However, adding Vit-E to ZA administration reversed all the histopathological changes to some degree, with statistical significance. Administration of ZA had nephrotoxic effects on rat kidney observed under both light and electron microscopy. Concomitant administration of Vit-E significantly reduces toxic histopathological effects of ZA.

Expression of Dlx-5 and Msx-1 in Craniofacial Skeletons and Ilia of Rats Treated With Zoledronate.

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Xuan, Bin; Yang, Pan; Wu, Shichao; Li, Lin; Zhang, Jian; Zhang, Wenyi

2017-05-01

Because of the different embryologic origins of the craniofacial skeleton and ilium, differences in gene expression patterns have been observed between the jaw bones and ilium. Distal-less homeobox (Dlx) genes and Msh homeobox genes, particularly Dlx-5 and Msx-1, play major roles in cell differentiation and osteogenesis. The purpose of this study was to investigate the effects of zoledronate (ZOL) on the craniofacial skeleton and ilium by detecting changes in Dlx-5 and Msx-1 expression at both the protein and messenger RNA levels. A total of 24 female Sprague-Dawley rats were randomly divided into 2 groups: ZOL group (n = 12), in which the rats were injected intraperitoneally with zoledronic acid for 12 weeks, and control group (n = 12), in which the rats were injected with saline solution for 12 weeks. By use of immunohistochemistry, Western blotting, and real-time reverse transcription polymerase chain reaction, the expression levels of Dlx-5 and Msx-1 in the craniofacial skeleton (including the maxilla, mandible, and parietal bone) and ilium were examined. Dlx-5 expression in the maxilla and mandible was increased at the protein and messenger RNA levels in the ZOL group compared with the control group (P Msx-1 expression in the maxilla and mandible was decreased in the ZOL group (P Msx-1 expression in the ilium was decreased in the ZOL group (P Msx-1 expression in the parietal bone was observed between the 2 groups (P > .05). Site-specific differences in the effects of ZOL on the craniofacial skeleton and ilium could be explained by differently altered tendencies in Dlx-5 and Msx-1 expression. The jaw bones were more susceptible to the effects of ZOL than the parietal bone and ilium. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Effect of Zoledronic Acid and Denosumab in Patients With Low Back Pain and Modic Change: A Proof-of-Principle Trial.

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Cai, Guoqi; Laslett, Laura L; Aitken, Dawn; Halliday, Andrew; Pan, Feng; Otahal, Petr; Speden, Deborah; Winzenberg, Tania M; Jones, Graeme

2018-05-01

The aim of this study was to evaluate the effect of zoledronic acid (ZA) and denosumab on low back pain (LBP) and Modic change (MC) over 6 months. Adults aged ≥40 years with significant LBP for at least 6 months duration and MC (type 1, 2, or mixed) were randomized to receive ZA (5 mg/100 mL), denosumab (60 mg), or placebo. LBP was measured monthly by visual analogue scale (VAS) and the LBP Rating Scale (RS). MC was measured from MRIs of T 12 -S 1 vertebrae at screening and 6 months. A total of 103 participants with moderate/severe LBP (mean VAS = 57 mm; mean RS = 18) and median total MC area 538 mm 2 were enrolled. Compared to placebo, LBP reduced significantly at 6 months in the ZA group for RS (-3.3; 95% CI, -5.9 to -0.7) but not VAS (-8.2; 95% CI, -18.8 to +2.4) with similar findings for denosumab (RS, -3.0; 95% CI, -5.7 to -0.3; VAS, -10.7; 95% CI, -21.7 to +0.2). There was little change in areal MC size overall and no difference between groups with the exception of denosumab in those with type 1 Modic change (-22.1 mm 2 ; 95% CI, -41.5 to -2.7). In post hoc analyses, both medications significantly reduced VAS LBP in participants with milder disc degeneration and non-neuropathic pain, and denosumab reduced VAS LBP in those with type 1 MC over 6 months, compared to placebo. Adverse events were more frequent in the ZA group. These results suggests a potential therapeutic role for ZA and denosumab in MC-associated LBP. © 2018 American Society for Bone and Mineral Research. © 2018 American Society for Bone and Mineral Research.

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

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Vidal-Gutiérrez, X; Gómez-Clavel, J-F; Gaitán-Cepeda, L-A

2017-03-01

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. 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. 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. 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.

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.

Risk factors influencing the duration of treatment with bisphosphonates until occurrence of an osteonecrosis of the jaw in 963 cancer patients.

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Gabbert, Tatjana I; Hoffmeister, Bodo; Felsenberg, Dieter

2015-04-01

Osteonecrosis of the jaw (ONJ) is an adverse effect that is associated with bisphosphonate (BP) use. Little data are available on risk factors influencing the time of treatment until an osteonecrosis occurs. From 1 Dec 2004 until 21 Sep 2012, the German Register collected all patients with validated diagnoses of ONJ (N = 1,229) that were reported to the national pharmaco-vigilance system or to the Register directly. We analysed 963 patients with cancerous disease and an ONJ during i.v. BP treatment. Duration of BP treatment until first diagnosis of ONJ and Kaplan-Meier curves of ONJ-free survival were analysed stratified by gender, type of BP and type of cancer. Main indications for BP treatment were breast cancer (36%), multiple myeloma (24%), prostate cancer (16%) and kidney cancer (4%). Men suffered from their ONJ earlier than women. A total of 780 patients (81%) had their ONJ during zoledronate treatment, 93 (10%) under pamidronate and 90 (9%) under ibandronate treatment. ONJ-free survival in single BP users was significantly longer in pamidronate-treated patients than in zoledronate or ibandronate users. Ibandronate users had the shortest median duration of treatment (17 months), similar to that of zoledronate users (21.5 months). Sequential prescription of two different BPs prolonged the period of overall BP treatment until an ONJ occurred. Time of BP treatment was shortest in patients with kidney cancer. Age or a concomitant osteoporosis did not influence the time to event of an ONJ. Systemic risk factors such as gender play a significant role in certain subgroups only. Comparative analysis of different cancer patients helps the treating oncologist/dentist to identify patients with a more imminent risk to develop an ONJ (i.e. kidney cancer, ibandronate/zoledronate use).

Prostate-specific antigen kinetics and outcomes in patients with bone metastases from castration-resistant prostate cancer treated with or without zoledronic acid.

Science.gov (United States)

Saad, Fred; Segal, Scott; Eastham, James

2014-01-01

Zoledronic acid (ZOL) is a standard therapy for the prevention of skeletal-related events (SREs) in patients with castration-resistant prostate cancer (CRPC). Although prostate-specific antigen (PSA) is an established marker for monitoring prostate cancer patients, correlations between PSA and disease outcomes during ZOL therapy are unclear. To evaluate the relationships among PSA kinetics, bone-directed therapy with ZOL, and clinical outcomes in men with bone metastases from CRPC using a ZOL phase 3 trial database. Exploratory analyses from a phase 3 trial in men with bone metastases from CRPC (n=643) randomized to ZOL or placebo every 3 wk. PSA levels during the first 3 mo of the study were evaluated in linear and logarithmic (log) models stratified using prognostic factors established in a ZOL phase 3 trial and a CRPC nomogram. Relative risks of SREs, bone disease progression (BDP), and death were calculated per 1 log (nanograms per milliliter) PSA increase. Baseline PSA models used the study median (PSA: 77.3 ng/ml) as the high/low cut-off point. A total of 202 placebo- and 434 ZOL-treated patients were assessable. In both groups, PSA increases correlated with significantly increased risks of death, BDP, and first SRE. In the placebo and ZOL groups, associated increases in risk per 1 log (nanograms per milliliter) PSA increase were 29% (p<0.0001) and 10% (p<0.0074), respectively, for BDP, and 24% (p=0.0010) and 13% (p=0.0079), respectively, for first SRE. Limitations include the retrospective nature of these analyses and the potential confounding effects of concurrent antineoplastic therapies. PSA is an important prognostic tool for survival in patients with bone metastases from CRPC, and these analyses show that PSA is also prognostic for BDP and SREs regardless of bone-targeted therapy. Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Osteoporosebehandling kan pauseres efter individuel vurdering

DEFF Research Database (Denmark)

Eiken, Pia Agnete; Abrahamsen, Bo

2017-01-01

In most patients, treatment of osteoporosis is a long-term challenge. Because alendronate and zoledronic acid accumulate in bone with some persistent antifracture efficacy after therapy, it is reasonable to consider a "drug holiday" for low-risk patients. It is recommended that the duration...

Treatment of Fatty Acid Oxidation Disorders

Science.gov (United States)

... Treatment of fatty acid oxidation disorders Treatment of fatty acid oxidation disorders E-mail to a friend Please ... this page It's been added to your dashboard . Fatty acid oxidation disorders are rare health conditions that affect ...

Design and methods for a Scandinavian pharmacovigilance study of osteonecrosis of the jaw and serious infections among cancer patients treated with antiresorptive agents for the prevention of skeletal-related events

DEFF Research Database (Denmark)

Acquavella, John; Ehrenstein, Vera; Schiødt, Morten

2016-01-01

OBJECTIVE: Osteonecrosis of the jaw (ONJ) is a recognized complication of potent antiresorptive therapies, especially at the doses indicated to prevent skeletal complications for cancer patients with bone metastases. This paper describes the rationale and methods for a prospective, post-authoriza......OBJECTIVE: Osteonecrosis of the jaw (ONJ) is a recognized complication of potent antiresorptive therapies, especially at the doses indicated to prevent skeletal complications for cancer patients with bone metastases. This paper describes the rationale and methods for a prospective, post...... (120 mg subcutaneously) or zoledronic acid (4 mg intravenously, adjusted for renal function). Patients will be identified using routinely collected data combined with medical chart review in Denmark, Sweden, and Norway. Followup will extend from the first administration of antiresorptive treatment...... to the earliest of death, loss-to-follow-up, or 5 years after therapy initiation. Results will be reported for three treatment cohorts: denosumab-naïve patients, zoledronic acid-naïve patients, and patients who switch from bisphosphonate treatment to denosumab. ONJ cases will be identified in three newly...

Treatment of acid mine wastewaters

International Nuclear Information System (INIS)

Hayward, D.; Barnard, R.

1993-01-01

Acid mine drainage often results from the oxidation sulfide minerals to form sulfuric acid. As a consequence, high concentrations of metals in the both the suspended and dissolved state result from the low pH water. This paper discusses several of the more common treatment methods for acid mine drainage including the use of chemical precipitation agents, pH correction agents, filtration methods, and biodegradation methods. Advanced treatment technologies are also briefly described and include microfiltration, reverse osmosis, ion exchange, and electrodialysis

The long-term effects of switching from active intravenous bisphosphonate treatment to low-dose maintenance therapy in children with osteogenesis imperfecta.

Science.gov (United States)

Biggin, Andrew; Zheng, Linda; Briody, Julie N; Coorey, Craig P; Munns, Craig F

2015-01-01

Intravenous bisphosphonate therapy is the first-line treatment in moderate-to-severe osteogenesis imperfecta (OI), but there are varied treatment protocols with little data on long-term efficacy. This study evaluates the clinical outcomes when transitioning from active bisphosphonate treatment to maintenance therapy. A retrospective review was conducted on 17 patients before treatment, following active treatment (zoledronate 0.05 mg/kg 6-monthly or pamidronate 6-9 mg/kg/year) and after establishment on maintenance treatment for more than 2 years (zoledronate 0.025 mg/kg 6-monthly or pamidronate lean tissue mass increased during active treatment. These improvements were maintained during the period of maintenance treatment. Vertebral height improved in fractured thoracic vertebrae from pre-treatment to active therapy and improved further during maintenance treatment. Metacarpal cortical thickness and relative cortical area also increased over the treatment periods. Maintenance intravenous bisphosphonate therapy preserved the beneficial effects of active treatment at the doses stated above. Further studies are required to determine the optimal bisphosphonate treatment regimen in the management of children with OI. © 2015 S. Karger AG, Basel.

Where Do Bone-Targeted Agents RANK in Breast Cancer Treatment?

Directory of Open Access Journals (Sweden)

Roger von Moos

2013-08-01

Full Text Available Breast cancer cells preferentially metastasise to the skeleton, owing, in part, to the fertile environment provided by bone. Increased bone turnover releases growth factors that promote tumour cell growth. In turn, tumour cells release factors that stimulate further bone turnover, resulting in a vicious cycle of metastasis growth and bone destruction. The RANK-RANK ligand (RANKL pathway plays a key role in this cycle, and inhibition of RANKL using the fully-human monoclonal antibody denosumab, has demonstrated efficacy in delaying skeletal complications associated with bone metastases in three phase 3 trials. Preclinical studies suggest that the RANKL pathway also plays a role in breast cancer tumourigenesis and migration to bone. In a subgroup analysis of the negative Adjuvant Zoledronic Acid to Reduce Recurrence (AZURE trial, the bisphosphonate zoledronic acid showed potential for improving survival in patients who were postmenopausal; however, a prospective study in this patient population is required to validate this observation. Ongoing trials are examining whether adjuvant blockade of the RANKL pathway using denosumab can prevent disease recurrence in patients with high-risk breast cancer. These are building on analogous studies that have shown that denosumab improves bone metastasis-free survival in prostate cancer and suggested that it confers an overall survival benefit in non-small-cell lung cancer.

Comparative pharmacoeconomic analysis of the use of Bonviva® (ibandronat to prevent fractures in postmenopausal osteoporosis

Directory of Open Access Journals (Sweden)

E A Pyadushkina

2012-01-01

Full Text Available Objective: to make a pharmacoeconomic analysis of the use of oral (a 150-mg tablet once a month and injectable (a solution for intravenous bolus injection of 3 mg in 3 ml once every 3 months ibandronate in patients with postmenopausal osteoporosis (OP. Material and methods. The cost minimization method was used to calculate differences in the cost of using oral ibandronate, alendronate, and strontium ranelate in patients with postmenopausal OP for a year. The budgetary impact of administration of intravenous bisphosphonates (ibandronate and zoledronic acid was analyzed in patients with OP in a hospital context. A model calculator based on the Microsoft Excel software was applied to estimate how the expenditures of a health care facility were changing when different shares of drugs (ibandronate and zoledronic acid were used in purchase patterns. The cost of therapy with bisphosphonates (ibandronate and zoledronic acid, concomitant therapy (calcium and vitamin D, expendable materials, and therapy for adverse reactions (ARs due to the use of bisphophonates was considered in terms of the incidence of these ARs. Results. Among the oral drugs, ibandronate is more economically sound than alendronate: the difference in annual treatment costs was 7090.02 and 7334.31 rubles per patient, respectively, in favor of ibandronate. The inpatient use of only intravenous ibandronate versus the real administration practice determined on the basis of the data of the Farmekspert Marketing Researches Center on purchases in the hospital segment (30% for ibandronate and 70% for zoledronic acid considerably reduces the expenditures of a hospital, the saving will be 185416.06 rubles per year (if injections will be made in 20 patients. With 100% use of ibandronate, one can additionally provide 39 inpatients with bisphosphonate injections without additional expenditures.

In vitro and in vivo investigation of bisphosphonate-loaded hydroxyapatite particles for peri-implant bone augmentation.

Science.gov (United States)

Kettenberger, Ulrike; Luginbuehl, Vera; Procter, Philip; Pioletti, Dominique P

2017-07-01

Locally applied bisphosphonates, such as zoledronate, have been shown in several studies to inhibit peri-implant bone resorption and recently to enhance peri-implant bone formation. Studies have also demonstrated positive effects of hydroxyapatite (HA) particles on peri-implant bone regeneration and an enhancement of the anti-resorptive effect of bisphosphonates in the presence of calcium. In the present study, both hydroxyapatite nanoparticles (nHA) and zoledronate were combined to achieve a strong reinforcing effect on peri-implant bone. The nHA-zoledronate combination was first investigated in vitro with a pre-osteoclastic cell assay (RAW 264.7) and then in vivo in a rat model of postmenopausal osteoporosis. The in vitro study confirmed that the inhibitory effect of zoledronate on murine osteoclast precursor cells was enhanced by loading the drug on nHA. For the in vivo investigation, either zoledronate-loaded or pure nHA were integrated in hyaluronic acid hydrogel. The gels were injected in screw holes that had been predrilled in rat femoral condyles before the insertion of miniature screws. Micro-CT-based dynamic histomorphometry and histology revealed an unexpected rapid mineralization of the hydrogel in vivo through formation of granules, which served as scaffold for new bone formation. The delivery of zoledronate-loaded nHA further inhibited a degradation of the mineralized hydrogel as well as a resorption of the peri-implant bone as effectively as unbound zoledronate. Hyaluronic acid with zoledronate-loaded nHA, thanks to its dual effect on inducing a rapid mineralization and preventing resorption, is a promising versatile material for bone repair and augmentation. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Treatment of menorrhagia during menstruation: randomised controlled trial of ethamsylate, mefenamic acid, and tranexamic acid.

Science.gov (United States)

Bonnar, J; Sheppard, B L

1996-09-07

To compare the efficacy and acceptability of ethamsylate, mefenamic acid, and tranexamic acid for treating menorrhagia. Randomised controlled trial. A university department of obstetrics and gynaecology. 76 women with dysfunctional uterine bleeding. Treatment for five days from day 1 of menses during three consecutive menstrual periods. 27 patients were randomised to take ethamsylate 500 mg six hourly, 23 patients to take mefenamic acid 500 mg eight hourly, and 26 patients to take tranexamic acid 1 g six hourly. Menstrual loss measured by the alkaline haematin method in three control menstrual periods and three menstrual periods during treatment; duration of bleeding; patient's estimation of blood loss; sanitary towel usage; the occurrence of dysmenorrhoea; and unwanted events. Ethamsylate did not reduce mean menstrual blood loss whereas mefenamic acid reduced blood loss by 20% (mean blood loss 186 ml before treatment, 148 ml during treatment) and tranexamic acid reduced blood loss by 54% (mean blood loss 164 ml before treatment, 75 ml during treatment). Sanitary towel usage was significantly reduced in patients treated with mefenamic acid and tranexamic acid. Tranexamic acid given during menstruation is a safe and highly effective treatment for excessive bleeding. Patients with dysfunctional uterine bleeding should be offered medical treatment with tranexamic acid before a decision is made about surgery.

Bile acids in treatment of ocular disease

OpenAIRE

Boatright, Jeffrey H.; Nickerson, John M.; Moring, Anisha G.; Pardue, Machelle T.

2009-01-01

Bear bile has been included in Asian pharmacopeias for thousands of years in treatment of several diseases, ranging from sore throat to hemorrhoids. The hydrophilic bile acids tauroursodeoxycholic acid (TUDCA) and ursodeoxycholic acid (UDCA) are the major bile acids of bear bile. Both of these are available as synthetic formulations and are approved by the health administrations of several countries for treatment of cirrhosis and gallstones. This review briefly covers the use of bear bile in ...

Endocrine effects of adjuvant letrozole compared with tamoxifen in hormone-responsive postmenopausal patients with early breast cancer: the HOBOE trial.

Science.gov (United States)

Rossi, Emanuela; Morabito, Alessandro; Di Rella, Francesca; Esposito, Giuseppe; Gravina, Adriano; Labonia, Vincenzo; Landi, Gabriella; Nuzzo, Francesco; Pacilio, Carmen; De Maio, Ermelinda; Di Maio, Massimo; Piccirillo, Maria Carmela; De Feo, Gianfranco; D'Aiuto, Giuseppe; Botti, Gerardo; Chiodini, Paolo; Gallo, Ciro; Perrone, Francesco; de Matteis, Andrea

2009-07-01

PURPOSE We compared the endocrine effects of 6 and 12 months of adjuvant letrozole versus tamoxifen in postmenopausal patients with hormone-responsive early breast cancer within an ongoing phase III trial. PATIENTS AND METHODS Patients were randomly assigned to receive tamoxifen, letrozole, or letrozole plus zoledronic acid. Serum values of estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, dehydroepiandrosterone-sulphate (DHEA-S), progesterone, and cortisol were measured at baseline and after 6 and 12 months of treatment. For each hormone, changes from baseline at 6 and 12 months were compared between treatment groups, and differences over time for each group were analyzed. Results Hormonal data were available for 139 postmenopausal patients with a median age of 62 years, with 43 patients assigned to tamoxifen and 96 patients assigned to letrozole alone or combined with zoledronic acid. Baseline values were similar between the two groups for all hormones. Many significant changes were observed between drugs and for each drug over time. Namely, three hormones seemed significantly affected by one drug only: estradiol that decreased and progesterone that increased with letrozole and cortisol that increased with tamoxifen. Both drugs affected FSH (decreasing with tamoxifen and slightly increasing with letrozole), LH (decreasing more with tamoxifen than with letrozole), testosterone (slightly increasing with letrozole but not enough to differ from tamoxifen), and DHEA-S (increasing with both drugs but not differently between them). Zoledronic acid did not have significant impact on hormonal levels. CONCLUSION Adjuvant letrozole and tamoxifen result in significantly distinct endocrine effects. Such differences can explain the higher efficacy of letrozole as compared with tamoxifen.

Acid Mine Drainage Treatment

National Research Council Canada - National Science Library

Fripp, Jon

2000-01-01

.... Acid mine drainage (AMD) can have severe impacts to aquatic resources, can stunt terrestrial plant growth and harm wetlands, contaminate groundwater, raise water treatment costs, and damage concrete and metal structures...

Fractures and mortality in relation to different osteoporosis treatments.

Science.gov (United States)

Yun, Huifeng; Delzell, Elizabeth; Saag, Kenneth G; Kilgore, Meredith L; Morrisey, Michael A; Muntner, Paul; Matthews, Robert; Guo, Lingli; Wright, Nicole; Smith, Wilson; Colón-Emeric, Cathleen; O'Connor, Christopher M; Lyles, Kenneth W; Curtis, Jeffrey R

2015-01-01

Few studies have assessed the effectiveness of different drugs for osteoporosis (OP). We aimed to determine if fracture and mortality rates vary among patients initiating different OP medications. We used the Medicare 5% sample to identify new users of intravenous (IV) zoledronic acid (n=1.674), oral bisphosphonates (n=32.626), IV ibandronate (n=492), calcitonin (n=2.606), raloxifene (n=1.950), or parathyroid hormone (n=549). We included beneficiaries who were ≥65 years of age, were continuously enrolled in fee-for-service Medicare and initiated therapy during 2007-2009. Outcomes were hip fracture, clinical vertebral fracture, and all-cause mortality, identified using inpatient and physician diagnosis codes for fracture, procedure codes for fracture repair, and vital status information. Cox regression models compared users of each medication to users of IV zoledronic acid, adjusting for multiple confounders. During follow-up (median, 0.8-1.5 years depending on the drug), 787 subjects had hip fractures, 986 had clinical vertebral fractures, and 2.999 died. Positive associations included IV ibandronate with hip fracture (adjusted hazard ratio (HR), 2.37; 95% confidence interval (CI) 1.25-4.51), calcitonin with vertebral fracture (HR=1.59, 95%CI 1.04-2.43), and calcitonin with mortality (HR=1.31; 95%CI 1.02-1.68). Adjusted HRs for other drug-outcome comparisons were not statistically significant. IV ibandronate and calcitonin were associated with higher rates of some types of fracture when compared to IV zolendronic acid. The relatively high mortality associated with use of calcitonin may reflect the poorer health of users of this agent.

Prevention and treatment of glucocorticoid-induced osteoporosis in International and Italian scenarios

Directory of Open Access Journals (Sweden)

A. Delle Sedie

2011-09-01

Full Text Available Osteoporosis (OP and increased risk of fracture (Fx associated with chronic glucocorticoid treatment pushed panels of experts and scientific societies to produce recommendations for both prevention and treatment of glucocorticoid-induced OP (GIO. Recently the American College of Rheumatology developed and/or endorsed their updated guidelines and recommendations for the prevention and treatment of GIO. In these recommendations the use of FRAX tool, for the 10-year probability of a major osteoporotic Fx, was integrated with other clinical risk factors to define low-, medium-, and high-risk patients. Updated approaches are delineated for post-menopausal women and men >50 years, pre-menopausal women not of childbearing potential, men 50 years, receiving >5 mg/day prednisone equivalent for >3 months; more recently teriparatide has also been included, only for those patients presenting ≥1 prevalent fragility Fx and receiving >5 mg/day prednisone equivalent for >12 months. Also zoledronic acid has been approved by Italian Agency of the Drug (AIFA, 30/08/10 for “… post-menopausal women and men chronically treated with GC ad high risk of Fx”, but the drug is dispensed exclusively at the hospital.

Optimizing dosing frequencies for bisphosphonates in the management of postmenopausal osteoporosis: patient considerations

Directory of Open Access Journals (Sweden)

John Sunyecz

2008-12-01

Full Text Available John SunyeczMenopauseRx, Inc., Hopwood, PA, USAAbstract: Postmenopausal osteoporosis is common and underrecognized among elderly women. Osteoporotic fractures cause disability and disfigurement and threaten patients’ mobility, independence, and survival. Care for incident fractures in this age group must go beyond orthopedic repair, to assessment and treatment of the underlying bone fragility. Fracture risk can be reduced by vitamin D and calcium supplementation along with antiresorptive drug treatment. First-line osteoporosis pharmacotherapy employs nitrogen-containing bisphosphonates. The inconvenience of daily oral treatment has motivated development of weekly, monthly, and intermittent oral regimens, as well as quarterly and yearly intravenous (iv regimens. Ibandronate is the first bisphosphonate to have shown direct anti-fracture efficacy with a non-daily regimen; it was approved for once-monthly oral dosing in 2005 and for quarterly iv dosing in 2006. Intermittent oral risedronate and yearly iv zoledronic acid were approved in 2007. Newly available regimens with extended dosing intervals reduce the inconvenience of bisphosphonate therapy and provide patients with a range of options from which to select a maximally sustainable course of treatment. This review discusses the development, efficacy, safety, and tolerability of extended-interval bisphosphonate regimens and examines their potential to improve patient acceptance and long-term success of osteoporosis treatment.Keywords: ibandronate, alendronate, risedronate, zoledronic acid, adherence, persistence

Effects of alkali or acid treatment on the isomerization of amino acids.

Science.gov (United States)

Ohmori, Taketo; Mutaguchi, Yuta; Doi, Katsumi; Ohshima, Toshihisa

2012-10-01

The effect of alkali treatment on the isomerization of amino acids was investigated. The 100×D/(D+L) values of amino acids from peptide increased with increase in the number of constituent amino acid residues. Furthermore, the N-terminal amino acid of a dipeptide was isomerized to a greater extent than the C-terminal residue. Copyright © 2012. Published by Elsevier B.V.

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.

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

Science.gov (United States)

Miszczyk, Patrycja; Wieczorek, Dorota; Gałęzowska, Joanna; Dziuk, Błażej; Wietrzyk, Joanna; Chmielewska, Ewa

2017-02-08

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 (aminomethylene)bisphosphonates. 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.

Design and methods for a Scandinavian pharmacovigilance study of osteonecrosis of the jaw and serious infections among cancer patients treated with antiresorptive agents for the prevention of skeletal-related events

Directory of Open Access Journals (Sweden)

Acquavella J

2016-07-01

. Patients will be identified using routinely collected data combined with medical chart review in Denmark, Sweden, and Norway. Follow-up will extend from the first administration of antiresorptive treatment to the earliest of death, loss-to-follow-up, or 5 years after therapy initiation. Results will be reported for three treatment cohorts: denosumab-naïve patients, zoledronic acid-naïve patients, and patients who switch from bisphosphonate treatment to denosumab. ONJ cases will be identified in three newly established national ONJ databases and adjudicated by the committee that functioned during the XGEVA® clinical trials program. Conclusion: This study will provide a real world counterpart to the clinical trial-estimated risks for ONJ and serious infections for cancer patients initiating denosumab or zoledronic acid. The establishment of ONJ databases in the three Scandinavian countries will have potential benefits outside this study for the elucidation of ONJ risk factors and the evaluation of ONJ treatment strategies. Keywords: cohort study, osteonecrosis of the jaw, pharmacovigilance, postmarketing drug surveillance, denosumab, zoledronic acid

Vγ9Vδ2 T cells and zoledronate mediate antitumor activity in an orthotopic mouse model of human chondrosarcoma.

Science.gov (United States)

Sun, L; Li, Y; Jiang, Z; Zhang, J; Li, H; Li, B; Ye, Z

2016-06-01

Chondrosarcoma (CS) is a cartilaginous malignant neoplasm characterized by resistance to conventional adjuvant therapy. The prognosis of unresectable or metastatic CS is poor. Therefore, it is imperative to explore novel therapeutic approaches to improve the treatment efficacy for those CS patients. Emerging data has implicated the synergistic antitumor activity of zoledronate (ZOL) and Vγ9Vδ2 T cells. However, whether ZOL-stimulated Vγ9Vδ2 T cells could infiltrate bone sarcoma and inhibit tumor growth has not been thoroughly answered yet. In this study, Vγ9Vδ2 T cells from healthy donors and CS patients were expanded in the presence of ZOL (1 μM) and IL-2 (400 IU/ml). The antitumor activity of Vγ9Vδ2 T cells to ZOL-pretreated human CS was examined both in vitro and in vivo. ZOL pretreatment substantially enhanced the cytotoxicity of Vγ9Vδ2 T cells to SW1353 and primary CS cells. ZOL potentiated the migration and cytotoxicity of Vγ9Vδ2 T cells to SW1353 in dose- and time-dependent manner. Moreover, weekly intravenous ZOL followed by Vγ9Vδ2 T cells inhibited subcutaneous xenograft growth. Thus, Vγ9Vδ2 T cells were able to infiltrate bone tumor and significantly suppressed the development of orthotopic SW1353 xenografts. Altogether, the study raises the possibility of combining ZOL with Vγ9Vδ2 T cells for CS treatment.

300 Area waste acid treatment system closure plan

International Nuclear Information System (INIS)

LUKE, S.N.

1999-01-01

The Hanford Facility Dangerous Waste Permit Application is considered to be a single application organized into a General Information Portion (document number DOERL-91-28) and a Unit-Specific Portion. The scope of the Unit-Specific Portion includes closure plan documentation submitted for individual, treatment, storage, and/or disposal units undergoing closure, such as the 300 Area Waste Acid Treatment System. Documentation contained in the General Information Portion is broader in nature and could be used by multiple treatment, storage, and/or disposal units (e.g., the glossary provided in the General Information Portion). Whenever appropriate, 300 Area Waste Acid Treatment System documentation makes cross-reference to the General Information Portion, rather than duplicating text. This 300 Area Waste Acid Treatment System Closure Plan (Revision 2) includes a Hanford Facility Dangerous Waste Permit Application, Part A, Form 3. Information provided in this closure plan is current as of April 1999

300 Area waste acid treatment system closure plan

Energy Technology Data Exchange (ETDEWEB)

LUKE, S.N.

1999-05-17

The Hanford Facility Dangerous Waste Permit Application is considered to be a single application organized into a General Information Portion (document number DOERL-91-28) and a Unit-Specific Portion. The scope of the Unit-Specific Portion includes closure plan documentation submitted for individual, treatment, storage, and/or disposal units undergoing closure, such as the 300 Area Waste Acid Treatment System. Documentation contained in the General Information Portion is broader in nature and could be used by multiple treatment, storage, and/or disposal units (e.g., the glossary provided in the General Information Portion). Whenever appropriate, 300 Area Waste Acid Treatment System documentation makes cross-reference to the General Information Portion, rather than duplicating text. This 300 Area Waste Acid Treatment System Closure Plan (Revision 2) includes a Hanford Facility Dangerous Waste Permit Application, Part A, Form 3. Information provided in this closure plan is current as of April 1999.

Osteonecrosis of the jaw: effect of bisphosphonate type, local concentration, and acidic milieu on the pathomechanism.

Science.gov (United States)

Otto, Sven; Pautke, Christoph; Opelz, Christine; Westphal, Ines; Drosse, Inga; Schwager, Joanna; Bauss, Frieder; Ehrenfeld, Michael; Schieker, Matthias

2010-11-01

Osteonecrosis of the jaw has been reported in patients receiving high doses of intravenous nitrogen-containing bisphosphonates (N-BPs) because of malignant disease. The exact pathomechanisms have been elusive and questions of paramount importance remain unanswered. Recent studies have indicated toxic effects of bisphosphonates on different cell types, apart from osteoclast inhibition. Multipotent stem cells play an important role in the processes of wound healing and bone regeneration, which seem to be especially impaired in the jaws of patients receiving high doses of N-BPs. Therefore, the aim of the present study was to investigate the effects of different bisphosphonate derivatives and dose levels combined with varying pH levels on the mesenchymal stem cells in vitro. The effect of 2 N-BPs (zoledronate and ibandronate) and 1 non-N-BP (clodronate) on immortalized mesenchymal stem cells was tested at different concentrations, reflecting 1, 3, and 6 months and 1, 3, 5, and 10 years of exposure to standard oncology doses of the 2 N-BPs and equimolar concentrations of clodronate at different pH values (7.4, 7.0, 6.7, and 6.3). Cell viability and activity were analyzed using a WST assay. Cell motility was investigated using scratch wound assays and visualized using time-lapse microscopy. Both types of bisphosphonates revealed remarkable differences. Zoledronate and ibandronate showed a dose- and pH-dependent cellular toxicity. Increasing concentrations of both N-BPs and an acidic milieu led to a significant decrease in cell viability and activity (P key role in the pathogenesis of osteonecrosis of the jaw in patients receiving high doses of N-BPs for malignant diseases. Also the potency of N-BPs might be different, suggesting a greater risk of osteonecrosis of the jaw with zoledronate. Copyright © 2010 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Comparison the effectiveness of pyruvic acid 50% and salicylic acid 30% in the treatment of acne.

Science.gov (United States)

Jaffary, Fariba; Faghihi, Gita; Saraeian, Sara; Hosseini, Sayed Mohsen

2016-01-01

Acne vulgaris is a chronic inflammatory disease of the pilosebaceous follicles and one of the most common skin diseases. The peeling method has been recently found to be effective for acne treatment. This study aimed to compare the efficacy of pyruvic acid 50% and salicylic acid 30% peeling in the treatment of mild to moderate acne. In a prospective single-blinded clinical trial, 86 patients with acne were randomly assigned into two groups. In both groups, the routine treatment of acne (topical solution of erythromycin 4%, triclorocarban soap, and sunscreen) were used twice a day for 8 weeks. In addition, salicylic acid 30% for the control group and pyruvic acid 50% for the case group were used. In both groups, acne severity index (ASI) was calculated before and at week 2, 4, 6, and 8 of the treatment. Patient satisfaction was assessed at the end of the treatment. Side effects were recorded using a checklist. In both groups, the reduction in the number of comedones, papules, and ASI were statistically significant ( P < 0.001) in the course of treatment. However, it was not significant regarding the number of pustules ( P = 0.09). None of the number of comedone, papules, pustules, and ASI was statistically different between study groups. Both treatment groups had similar side effects except for scaling in the fifth session, which was significantly lower in salicylic acid - treated patients ( P = 0.015). Both pyruvic acid 50% and salicylic acid 30% are effective in the improvement of mild to moderate acne with no significant difference in efficacy and side effects.

Use of bis phosphonates in prostate cancer

International Nuclear Information System (INIS)

Della Valle, A.

2004-01-01

Prostate cancer is the second leading cause of cancer death in men in the world, meaning a real public health problem. The prevalence of Bone metastases may reach 100% of those who die from this disease printing a serious decline in the quality of life especially in the occurrence of skeletal-related events. Since three decades we try to find an inhibitor bone resorption which might prevent or treat bone metastases develop bisphosphonates (BF). These can not only inhibit the recruitment and differentiation osteoclast but decrease its half-life leading to early apoptosis. All BF have similar physicochemical properties and pharmacokinetics, but they differ in their anti-resorptive potency, ibandronate and zoledronic acid are BF generation that have been successful in the treatment of pain and decreased bone events in several works, however only one study randomized was conducted to show significant therapeutic advantages bone metastasis of prostate cancer. Although most authors indicate a therapeutic benefit, the evidence is weak and higher costs. Urges the implementation of new studies assessing both ibandronate and zoledronic acid in order to assert its virtues

Comparison the effectiveness of pyruvic acid 50% and salicylic acid 30% in the treatment of acne

Directory of Open Access Journals (Sweden)

Fariba Jaffary

2016-01-01

Full Text Available Background: Acne vulgaris is a chronic inflammatory disease of the pilosebaceous follicles and one of the most common skin diseases. The peeling method has been recently found to be effective for acne treatment. This study aimed to compare the efficacy of pyruvic acid 50% and salicylic acid 30% peeling in the treatment of mild to moderate acne. Materials and Methods: In a prospective single-blinded clinical trial, 86 patients with acne were randomly assigned into two groups. In both groups, the routine treatment of acne (topical solution of erythromycin 4%, triclorocarban soap, and sunscreen were used twice a day for 8 weeks. In addition, salicylic acid 30% for the control group and pyruvic acid 50% for the case group were used. In both groups, acne severity index (ASI was calculated before and at week 2, 4, 6, and 8 of the treatment. Patient satisfaction was assessed at the end of the treatment. Side effects were recorded using a checklist. Results: In both groups, the reduction in the number of comedones, papules, and ASI were statistically significant (P < 0.001 in the course of treatment. However, it was not significant regarding the number of pustules (P = 0.09. None of the number of comedone, papules, pustules, and ASI was statistically different between study groups. Both treatment groups had similar side effects except for scaling in the fifth session, which was significantly lower in salicylic acid - treated patients (P = 0.015. Conclusion: Both pyruvic acid 50% and salicylic acid 30% are effective in the improvement of mild to moderate acne with no significant difference in efficacy and side effects.

Role of the nurse in preserving patients' independence.

Science.gov (United States)

Maxwell, Cathy

2007-01-01

Patients with metastatic bone disease may be treated with bisphosphonates to reduce or delay skeletal complications including pathologic fracture, radiotherapy to bone, and hypercalcemia of malignancy. Nurses can provide important education to patients and support or encourage the use of bisphosphonates throughout therapy. Literature and congress reports were reviewed for relevant efficacy information on bisphosphonates and adverse events that may occur during bisphosphonate therapy. Bisphosphonates can provide meaningful benefits to patients, and zoledronic acid is now approved for the treatment of bone metastases secondary to any solid tumor. To optimize care, nurses can monitor pain scores, changes in mobility, adverse events, and serum creatinine levels. A useful tool for recording these parameters is a patient diary. The nurse should fill out the diary at each patient visit and compare it with baseline information before treatment is administered. Patients should also be counseled on the importance of adequate hydration, good dental hygiene, the need for calcium and vitamin D supplements, and how to best manage potential side effects. Bisphosphonates are effective in reducing and delaying skeletal complications, and zoledronic acid has demonstrated significant efficacy in preventing skeletal complications across a wide range of solid tumors and multiple myeloma. Nurses play an important role in enabling patients to optimize bisphosphonate therapy and in supporting patients to continue treatment to preserve their functional independence.

Theobromine inhibits uric acid crystallization. A potential application in the treatment of uric acid nephrolithiasis.

Science.gov (United States)

Grases, Felix; Rodriguez, Adrian; Costa-Bauza, Antonia

2014-01-01

To assess the capacity of methylxanthines (caffeine, theophylline, theobromine and paraxanthine) to inhibit uric acid crystallization, and to evaluate their potential application in the treatment of uric acid nephrolithiasis. The ability of methylxathines to inhibit uric acid nucleation was assayed turbidimetrically. Crystal morphology and its modification due to the effect of theobromine were evaluated by scanning electron microscopy (SEM). The ability of theobromine to inhibit uric acid crystal growth on calculi fragments resulting from extracorporeal shock wave lithotripsy (ESWL) was evaluated using a flow system. The turbidimetric assay showed that among the studied methylxanthines, theobromine could markedly inhibit uric acid nucleation. SEM images showed that the presence of theobromine resulted in thinner uric acid crystals. Furthermore, in a flow system theobromine blocked the regrowth of post-ESWL uric acid calculi fragments. Theobromine, a natural dimethylxanthine present in high amounts in cocoa, acts as an inhibitor of nucleation and crystal growth of uric acid. Therefore, theobromine may be clinically useful in the treatment of uric acid nephrolithiasis.

Characterization of selectively etched halloysite nanotubes by acid treatment

Science.gov (United States)

Garcia-Garcia, Daniel; Ferri, Jose M.; Ripoll, Laura; Hidalgo, Montserrat; Lopez-Martinez, Juan; Balart, Rafael

2017-11-01

Halloysite nanotubes (HNTs) are a type of naturally occurring inorganic nanotubes that are characterized by a different composition between their external and internal walls. The internal walls are mainly composed of alumina whilst external walls are composed of silica. This particular structure offers a dual surface chemistry that allows different selective surface treatments which can be focused on increasing the lumen, increasing porosity, etc. In this work, HNTs were chemically treated with different acids (sulphuric, acetic and acrylic acid), for 72 h at a constant temperature of 50 °C. As per the obtained results, the treatment with sulphuric acid is highly aggressive and the particular shape of HNTs is almost lost, with a remarkable increase in porosity. The BET surface area increases from 52.9 (untreated HNTs) up to 132.4 m2 g-1 with sulphuric acid treatment, thus showing an interesting potential in the field of catalysis. On the other hand, the treatment with acetic acid led to milder effects with a noticeable increase in the lumen diameter that changed from 13.8 nm (untreated HNTs) up to 18.4 nm which the subsequent increase in the loading capacity by 77.8%. The aluminium content was measured by X-ray fluorescence (XRF) and laser induced breakdown spectroscopy (LIBS). The final results using two systems, suggest a good correlation between the acid strength and the aluminium reduction. Consequently, is possible to conclude that new applications for HNTs can be derived from selective etching with acids. Sulphuric acid widens the potential of HNTs in the field of catalysis while weak acids such as acetic and acrylic acids give a controlled and homogeneous lumen increase with the corresponding increase in the loading capacity.

Osteoporosebehandling kan pauseres efter individuel vurdering

DEFF Research Database (Denmark)

Eiken, Pia A; Abrahamsen, Bo

2017-01-01

In most patients, treatment of osteoporosis is a long-term challenge. Because alendronate and zoledronic acid accumulate in bone with some persistent antifracture efficacy after therapy, it is reasonable to consider a "drug holiday" for low-risk patients. It is recommended that the duration...... and length of drug holiday should be individualized for each patient. For all other bisphosphonates data are limited. For other antiresorptive and anabolic agents "drug holiday" is not recommended....

Theobromine inhibits uric acid crystallization. A potential application in the treatment of uric acid nephrolithiasis.

Directory of Open Access Journals (Sweden)

Felix Grases

Full Text Available To assess the capacity of methylxanthines (caffeine, theophylline, theobromine and paraxanthine to inhibit uric acid crystallization, and to evaluate their potential application in the treatment of uric acid nephrolithiasis.The ability of methylxathines to inhibit uric acid nucleation was assayed turbidimetrically. Crystal morphology and its modification due to the effect of theobromine were evaluated by scanning electron microscopy (SEM. The ability of theobromine to inhibit uric acid crystal growth on calculi fragments resulting from extracorporeal shock wave lithotripsy (ESWL was evaluated using a flow system.The turbidimetric assay showed that among the studied methylxanthines, theobromine could markedly inhibit uric acid nucleation. SEM images showed that the presence of theobromine resulted in thinner uric acid crystals. Furthermore, in a flow system theobromine blocked the regrowth of post-ESWL uric acid calculi fragments.Theobromine, a natural dimethylxanthine present in high amounts in cocoa, acts as an inhibitor of nucleation and crystal growth of uric acid. Therefore, theobromine may be clinically useful in the treatment of uric acid nephrolithiasis.

Microscopic Evaluation of the Effect of Oral Microbiota on the Development of Bisphosphonate-Related Osteonecrosis of the Jaws in Rats

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Felipe M. Silveira

2017-01-01

Full Text Available Objectives: Osteonecrosis of the jaws is a side effect associated with the use of bisphosphonates. Using histologic analysis, this study aimed to evaluate the influence of microbial colonies in the development of osteonecrosis in the jaws of rats subjected to nitrogenous and non-nitrogenous bisphosphonates, undergoing surgical procedures. Material and Methods: Thirty-four rats (Rattus norvegicus, Wistar strain were allocated randomly into three groups: 12 animals treated with zoledronic acid; 12 animals treated with clodronate; and 10 animals treated with saline. Sixty days after the start of treatment, the animals underwent three extractions of the upper right molars. After 120 days of drug administration, the rats were killed. Histologic analysis was performed on specimens stained with hematoxylin and eosin by the technique of manual counting points using Image-Pro Plus software on images of the right hemimaxilla. Results: Osteonecrosis was induced in the test groups. There was no statistically significant association between the presence of microbial colonies and the presence of non-vital bone (Kruskal-Wallis, P > 0.05. Conclusions: Use of zoledronic acid was associated with non-vital bone and the results suggested that the presence of microbial colonies does not lead to osteonecrosis.

Bile acid changes after high-dose ursodeoxycholic acid treatment in primary sclerosing cholangitis: relation to disease progression

Science.gov (United States)

Sinakos, Emmanouil; Marschall, Hanns-Ulrich; Kowdley, Kris V.; Befeler, Alex; Keach, Jill; Lindor, Keith

2010-01-01

High-dose (28-30mg/kg/day) ursodeoxycholic acid (UDCA) treatment improves serum liver tests in patients with primary sclerosing cholangitis (PSC) but does not improve survival and is associated with increased rates of serious adverse events. The mechanism for the latter undesired effect remains unclear. High-dose UDCA could result in the production of hepatotoxic bile acids, such as lithocholic acid (LCA), due to limited small bowel absorption of UDCA and conversion of UDCA by bacteria in the colon. We determined the serum bile acid composition in 56 patients with PSC previously enrolled in a randomized, double-blind controlled trial of high dose UDCA versus placebo. Samples for analysis were obtained at baseline and at the end of treatment. The mean changes in UDCA (16.86 vs 0.05 μmol/L) and total bile acid (17.21 vs −0.55 μmol/L) levels were significantly higher in the UDCA group (n=29) compared to placebo (n=27) when pretreatment levels were compared (pacid (CA), deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA). Patients (n=9) in the UDCA group who reached clinical endpoints of disease progression (development of cirrhosis, varices, liver transplantation or death) tend to have greater increase in their post-treatment total bile acid levels (34.99 vs 9.21 μmol/L) (pacid pool including lithocholic acid. PMID:20564380

The Comparison of Hydrochloric Acid and Phosphoric Acid Treatments in the Preparation of Montmorillonite Catalysts for RNA Synthesis

Science.gov (United States)

Aldersley, Michael Frank; Joshi, Prakash C.; Huang, Yixing

2017-09-01

The treatment of clay minerals with a preliminary acid wash and titration to pH 7 has proven to generate catalysts for the most interesting of oligomerization reactions in which activated RNA-nucleotides generate oligomers up to 40-mers. Significantly, not all clay minerals become catalytic following this treatment and none are catalytic in the absence of such treatment. The washing procedure has been modified and explored further using phosphoric acid and the outcomes are compared to those obtained when clay samples are prepared following a hydrochloric acid wash.

Influencing factors on microbubble ozonation treatment of acid red 3R wastewater

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Yurong YA

2017-08-01

Full Text Available The microbubble ozonation was used to treat acid red 3R wastewater in order to investigate the influencing factors on its performance. The effects of ozone dose, initial acid red 3R concentration and activated carbon on the performance of microbubble ozonation treatment of acid red 3R wastewater are investigated. The decolorization rate, TOC removal rate, pH variation and ozone utilization efficiency in the microbubble ozonation treatment are compared under different treatment conditions. The results indicate that when increasing ozone dose or decreasing initial acid red 3R concentration, both decolorization rate and TOC removal rate of acid red 3R wastewater increase, but ozone utilization efficiency decreases. The coal-based activated carbon shows strong catalytic activity for microbubble ozonation, which could enhance the decolorization rate and TOC removal rate of acid red 3R wastewater. The better performance of microbubble ozonation treatment is achieved when the ozone dose is 48.3 mg/min and the initial acid red 3R mass concentration is 100 mg/L. Under these conditions, the decolorization efficiency reaches to 100% after treatment for 30 min, the TOC removal efficiency reaches to 78.0% after treatment for 120 min, the reaction rate constant of TOC removal is 0.015 min^-1 and the ozone utilization efficiency is higher than 99%. With addition of the coal-based activated carbon of 5 g/L, the decolorization efficiency reaches to 100% after treatment for 15 min, the TOC removal efficiency reaches to 91.2% after treatment for 120 min and the reaction rate constant of TOC removal increases to 0037 min^-1.The accumulation and following degradation of intermediate products of small molecule organic acid happens during treatment process, and as a result, the solution pH decreases initially and then increases. Therefore, the optimization of influencing factors for microbubble ozonation could increase both contaminant removal

Production of Valuables Organic Acids from Organic Wastes with Hydrothermal Treatment Process

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Muhammad Faisal

2009-06-01

Full Text Available This article reports production of valuables organic acids from the hydrothermal treatment of representative organic wastes and compounds (i. e. domestic sludge, proteinaceous, cellulosic and plastic wastes with or without oxidant (H2O2. Organic acids such as acetic, formic, propionic, succinic and lactic acids were obtained in significant amounts. At 623 K (16.5 MPa, acetic acid of about 26 mg/g-dry waste fish entrails was obtained. This increased to 42 mg/g dry waste fish entrails in the presence of H2O2. Experiments on glucose to represent cellulosic wastes were also carried out, getting acetic acid of about 29 mg/g-glucose. The study was extended to terephthalic acid and glyceraldehyde, reaction intermediates of hydrothermal treatment of PET plastic wastes and glucose, respectively. Studies on temperature dependence of formation of organic acids showed thermal stability of acetic acid, whereas, formic acid decomposed readily under hydrothermal conditions. In general, results demonstrated that the presence of oxidants favored formation of organic acids with acetic acid being the major product. Keywords: hydrothermal treatment, organic acids, organic wastes, oxidant, supercritical water oxidation

Promotion of Crystal Growth on Biomass-based Carbon using Phosphoric Acid Treatments

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Liwei Yu

2015-02-01

Full Text Available The effect of phosphoric acid treatments on graphitic microcrystal growth of biomass-based carbons was investigated using X-ray diffraction, infrared spectroscopy, and Raman spectroscopy. Although biomass-based carbons are believed to be hard to graphitize even after heat treatments well beyond 2000 °C, we found that graphitic microcrystals of biomass-based carbons were significantly promoted by phosphoric acid treatments above 800 °C. Moreover, twisted spindle-like whiskers were formed on the surface of the carbons. This suggests that phosphorus-containing groups turn graphitic microcrystalline domains into graphite during phosphoric acid treatments. In addition, the porous texture of the phosphoric acid-treated carbon has the advantage of micropore development.

Gibberellic acid promoting phytic acid degradation in germinating soybean under calcium lactate treatment.

Science.gov (United States)

Hui, Qianru; Wang, Mian; Wang, Pei; Ma, Ya; Gu, Zhenxin; Yang, Runqiang

2018-01-01

Phytic acid as a phosphorus storage vault provides phosphorus for plant development. It is an anti-nutritional factor for humans and some animals. However, its degradation products lower inositol phosphates have positive effects on human health. In this study, the effect of gibberellic acid (GA) on phytic acid degradation under calcium lactate (Ca) existence was investigated. The results showed that Ca + GA treatment promoted the growth status, hormone metabolism and phytic acid degradation in germinating soybean. At the same time, the availability of phosphorus, the activity of phytic acid degradation-associated enzyme and phosphoinositide-specific phospholipase C (PI-PLC) increased. However, the relative genes expression of phytic acid degradation-associated enzymes did not vary in accordance with their enzymes activity. The results revealed that GA could mediate the transport and function of calcium and a series of physiological and biochemical changes to regulate phytic acid degradation of soybean sprouts. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

BONE TURNOVER IN OSTEOPOROTIC WOMEN DURING LONG-TERM ORAL BISPHOSPHONATES TREATMENT: IMPLICATIONS FOR TREATMENT FAILURE AND "DRUG HOLIDAY" IN THE REAL WORLD.

Science.gov (United States)

Liel, Yair; Plakht, Ygal; Tailakh, Muhammad Abu

2017-07-01

Little data exist to support concerns over bone turnover suppression during prolonged oral bisphosphonate treatment and on consequences of the recommended "drug holiday." This study was performed to assess bone resorption rates in postmenopausal osteoporotic women on prolonged oral bisphosphonate treatment and in response to switching to "drug holiday" intravenous bisphosphonate, or continuation of oral bisphosphonates. The frequency distribution of the bone resorption marker urinary deoxypyridinoline crosslinks (uDPD), was obtained retrospectively from 211 osteoporotic women attended at an academic hospital endocrine clinic, treated for >2 years with oral bisphosphonates. In some patients, uDPD was re-assessed following modification or continuation of treatment. The mean duration of oral bisphosphonates treatment was 7.2 ± 3.1 years. uDPD was within reference range for premenopausal women in 61.6% of the patients, below in 7.6% of the patients, and above upper limit in 30.8%. uDPD decreased significantly following intravenous zoledronic acid, increased significantly during "drug holiday," and slightly decreased in those continued on oral bisphosphonate treatment. In this real-world study, the majority of women on prolonged oral bisphosphonates maintained bone resorption rates within the normal reference range for premenopausal women. The likelihood for inadequate suppression was considerably greater than that of over-suppression. Implementing a "drug holiday" resulted in a marked increase in bone resorption rates. Additional studies should explore the potential role of bone turnover markers in the evaluation of patients on prolonged oral bisphosphonates and during "drug holiday" in different settings and using additional markers. BMD = bone mineral density; IQR = interquartile range; uDPD = urinary deoxypyridinoline crosslinks.

Amorphous, Smart, and Bioinspired Polyphosphate Nano/Microparticles: A Biomaterial for Regeneration and Repair of Osteo-Articular Impairments In-Situ

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Werner E. G. Müller

2018-01-01

Full Text Available Using femur explants from mice as an in vitro model, we investigated the effect of the physiological polymer, inorganic polyphosphate (polyP, on differentiation of the cells of the bone marrow in their natural microenvironment into the osteogenic and chondrogenic lineages. In the form of amorphous Ca-polyP nano/microparticles, polyP retains its function to act as both an intra- and extracellular metabolic fuel and a stimulus eliciting morphogenetic signals. The method for synthesis of the nano/microparticles with the polyanionic polyP also allowed the fabrication of hybrid particles with the bisphosphonate zoledronic acid, a drug used in therapy of bone metastases in cancer patients. The results revealed that the amorphous Ca-polyP particles promote the growth/viability of mesenchymal stem cells, as well as the osteogenic and chondrogenic differentiation of the bone marrow cells in rat femur explants, as revealed by an upregulation of the expression of the transcription factors SOX9 (differentiation towards osteoblasts and RUNX2 (chondrocyte differentiation. In parallel to this bone anabolic effect, incubation of the femur explants with these particles significantly reduced the expression of the gene encoding the osteoclast bone-catabolic enzyme, cathepsin-K, while the expression of the tartrate-resistant acid phosphatase remained unaffected. The gene expression data were supported by the finding of an increased mineralization of the cells in the femur explants in response to the Ca-polyP particles. Finally, we show that the hybrid particles of polyP complexed with zoledronic acid exhibit both the cytotoxic effect of the bisphosphonate and the morphogenetic and mineralization inducing activity of polyP. Our results suggest that the Ca-polyP nano/microparticles are not only a promising scaffold material for repairing long bone osteo-articular damages but can also be applied, as a hybrid with zoledronic acid, as a drug delivery system for

Biomimetic Deposition of Hydroxyapatite by Mixed Acid Treatment of Titanium Surfaces.

Science.gov (United States)

Zhao, J M; Park, W U; Hwang, K H; Lee, J K; Yoon, S Y

2015-03-01

A simple chemical method was established for inducing bioactivity of Ti metal. In the present study, two kinds of mixed acid solutions were used to treat Ti specimens to induce Ca-P formation. Following a strong mixed acid activation process, Ca-P coatings successfully formed on the Ti surfaces in the simulated body fluid. Strong mixed acid etching was used to increase the roughness of the metal surface, because the porous and rough surfaces allow better adhesion between Ca-P coatings and substrate. Nano-scale modification of titanium surfaces can alter cellular and tissue responses, which may benefit osseointegration and dental implant therapy. Some specimens were treated with a 5 M NaOH aqueous solution, and then heat treated at 600 °C in order to form an amorphous sodium titanate layer on their surface. This treated titanium metal is believed to form a dense and uniform bone-like apatite layer on its surface in a simulated body fluid (SBF). This study proved that mixed acid treatment is not only important for surface passivation but is also another bioactive treatment for titanium surfaces, an alternative to alkali treatment. In addition, mixed acid treatment uses a lower temperature and shorter time period than alkali treatment.

FES-Rowing versus Zoledronic Acid to Improve BoneHealth in SCI

Science.gov (United States)

2016-12-01

Army position, policy or decision unless so designated by other documentation. REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704-0188 Public...no established treatment to prevent bone loss or to induce new bone formation following SCI. The goal of this clinical trial -- FES-Rowing versus...infusion at the VA Boston Healthcare-Jamaica Plain Campus. The nurse practitioner that administered the infusion made follow-up phone calls within 24

Oxidative acid treatment and characterization of new biocarbon from sustainable Miscanthus biomass

International Nuclear Information System (INIS)

Anstey, Andrew; Vivekanandhan, Singaravelu; Rodriguez-Uribe, Arturo; Misra, Manjusri; Mohanty, Amar Kumar

2016-01-01

Oxidative acid treatments of biochar produced from Miscanthus were performed in this study using nitric acid, sulfuric acid, and a mixture of both. The structural and morphological changes of the acid-treated biochar were investigated using Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), Raman spectroscopy, organic elemental analysis and energy-dispersive X-ray spectroscopy (EDS). Improved surface functionality of the treated biochars was observed in their respective FT-IR spectra through the presence of nitro and carboxylic acid functional groups. SEM–EDS and elemental analysis revealed a large increase in the oxygen to carbon ratio in the biochar, which was evidence of chemical oxidation from the acid treatment. Further, TGA study showed the reduced thermal stability of acid-treated biochar over 200 °C due to the increased oxygen content. Acid treatments also influenced the graphitic structure of the biochar, as observed in the Raman spectra. The results suggest that biochar can be successfully functionalized for composite applications and provide a sustainable alternative to petroleum-based carbon additives. - Highlights: • Biochar was investigated as a candidate for renewable functionalized carbon. • Oxidative acid treatment was used to modify the carbon structure. • The chemical and morphological properties of the treated biochar were examined. • Successful chemical modification of biochar was verified through characterization. • Biochar shows potential as a sustainable carbon additive for polymer composites.

Oxidative acid treatment and characterization of new biocarbon from sustainable Miscanthus biomass

Energy Technology Data Exchange (ETDEWEB)

Anstey, Andrew [Bioproducts Discovery and Development Centre (BDDC), Department of Plant Agriculture, Crop Science Building, University of Guelph, Guelph, ON N1G 2W1 (Canada); School of Engineering, Thornbrough Building, University of Guelph, Guelph, ON N1G 2W1 (Canada); Vivekanandhan, Singaravelu [Bioproducts Discovery and Development Centre (BDDC), Department of Plant Agriculture, Crop Science Building, University of Guelph, Guelph, ON N1G 2W1 (Canada); Sustainable Materials and Nanotechnology Lab, Department of Physics, VHNSN College, Virudhunagar 626 001, Tamilnadu (India); Rodriguez-Uribe, Arturo [Bioproducts Discovery and Development Centre (BDDC), Department of Plant Agriculture, Crop Science Building, University of Guelph, Guelph, ON N1G 2W1 (Canada); Misra, Manjusri [Bioproducts Discovery and Development Centre (BDDC), Department of Plant Agriculture, Crop Science Building, University of Guelph, Guelph, ON N1G 2W1 (Canada); School of Engineering, Thornbrough Building, University of Guelph, Guelph, ON N1G 2W1 (Canada); Mohanty, Amar Kumar, E-mail: mohanty@uoguelph.ca [Bioproducts Discovery and Development Centre (BDDC), Department of Plant Agriculture, Crop Science Building, University of Guelph, Guelph, ON N1G 2W1 (Canada); School of Engineering, Thornbrough Building, University of Guelph, Guelph, ON N1G 2W1 (Canada)

2016-04-15

Oxidative acid treatments of biochar produced from Miscanthus were performed in this study using nitric acid, sulfuric acid, and a mixture of both. The structural and morphological changes of the acid-treated biochar were investigated using Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), Raman spectroscopy, organic elemental analysis and energy-dispersive X-ray spectroscopy (EDS). Improved surface functionality of the treated biochars was observed in their respective FT-IR spectra through the presence of nitro and carboxylic acid functional groups. SEM–EDS and elemental analysis revealed a large increase in the oxygen to carbon ratio in the biochar, which was evidence of chemical oxidation from the acid treatment. Further, TGA study showed the reduced thermal stability of acid-treated biochar over 200 °C due to the increased oxygen content. Acid treatments also influenced the graphitic structure of the biochar, as observed in the Raman spectra. The results suggest that biochar can be successfully functionalized for composite applications and provide a sustainable alternative to petroleum-based carbon additives. - Highlights: • Biochar was investigated as a candidate for renewable functionalized carbon. • Oxidative acid treatment was used to modify the carbon structure. • The chemical and morphological properties of the treated biochar were examined. • Successful chemical modification of biochar was verified through characterization. • Biochar shows potential as a sustainable carbon additive for polymer composites.

Effects of Organic Acids Treatments with or without Ultra-Sonic Treatment on Increasing the Shelf Life of Fresh Cut Kiwifruit

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A. Mansoory

2016-02-01

Full Text Available The market sales of ready to use fresh cut fruits have grown rapidly in recent decades. Kiwi fruit is an important fruit that its marketing as fresh cut has increased in recent years. The main limiting factors in shelf life of fresh cut fruits are microbial spoilage, drastic softening and browning. In this study, the effects of oxalic and citric acids, both at 0, 2, 4 and 6 mM concentrations, with or without ultra-sonic treatment were investigated on the increasing the shelf life of fresh cut kiwi fruit. After treatments, the fresh slices were stored at 2°C for 7 or 14 days and assessed for several traits and analyzed. Results showed that, oxalic and citric acid treated slices, in comparison to the control, had greater marketability, as well as higher flesh firmness, titrable acidity, ascorbic acid content, total phenol content and antioxidant capacity and smaller bacterial forming colony unit (CFU. Among the treatments, 2, 4 and 6 mM oxalic acid and 6 mM citric acid treatments were found more appropriate than the reaming treatments. Application of ultra-sonic treatment, despite the reduction of microbial load and maintaining antioxidant capacity, had no effects on marketability of fresh cut kiwi fruit. Hence, application of organic acid treatments as dipping can be used to increase the shelf life of fresh cut kiwi fruit.

The Comparison of Hydrochloric Acid and Phosphoric Acid Treatments in the Preparation of Montmorillonite Catalysts for RNA Synthesis.

Science.gov (United States)

Aldersley, Michael Frank; Joshi, Prakash C; Huang, Yixing

2017-09-01

The treatment of clay minerals with a preliminary acid wash and titration to pH 7 has proven to generate catalysts for the most interesting of oligomerization reactions in which activated RNA-nucleotides generate oligomers up to 40-mers. Significantly, not all clay minerals become catalytic following this treatment and none are catalytic in the absence of such treatment. The washing procedure has been modified and explored further using phosphoric acid and the outcomes are compared to those obtained when clay samples are prepared following a hydrochloric acid wash.

Treatment and prevention systems for acid mine drainage and halogenated contaminants

Science.gov (United States)

Jin, Song [Fort Collins, CO; Fallgren, Paul H [Laramie, WY; Morris, Jeffrey M [Laramie, WY

2012-01-31

Embodiments include treatments for acid mine drainage generation sources (10 perhaps by injection of at least one substrate (11) and biologically constructing a protective biofilm (13) on acid mine drainage generation source materials (14). Further embodiments include treatments for degradation of contaminated water environments (17) with substrates such as returned milk and the like.

Soil microbial community responses to acid exposure and neutralization treatment.

Science.gov (United States)

Shin, Doyun; Lee, Yunho; Park, Jeonghyun; Moon, Hee Sun; Hyun, Sung Pil

2017-12-15

Changes in microbial community induced by acid shock were studied in the context of potential release of acids to the environment due to chemical accidents. The responses of microbial communities in three different soils to the exposure to sulfuric or hydrofluoric acid and to the subsequent neutralization treatment were investigated as functions of acid concentration and exposure time by using 16S-rRNA gene based pyrosequencing and DGGE (Denaturing Gradient Gel Electrophoresis). Measurements of soil pH and dissolved ion concentrations revealed that the added acids were neutralized to different degrees, depending on the mineral composition and soil texture. Hydrofluoric acid was more effectively neutralized by the soils, compared with sulfuric acid at the same normality. Gram-negative ß-Proteobacteria were shown to be the most acid-sensitive bacterial strains, while spore-forming Gram-positive Bacilli were the most acid-tolerant. The results of this study suggest that the Gram-positive to Gram-negative bacterial ratio may serve as an effective bio-indicator in assessing the impact of the acid shock on the microbial community. Neutralization treatments helped recover the ratio closer to their original values. The findings of this study show that microbial community changes as well as geochemical changes such as pH and dissolved ion concentrations need to be considered in estimating the impact of an acid spill, in selecting an optimal remediation strategy, and in deciding when to end remedial actions at the acid spill impacted site. Copyright © 2017 Elsevier Ltd. All rights reserved.

Higher Serum Uric Acid Levels in Multiple Sclerosis Patients After Longterm Interferon Beta Treatment

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Toncev Gordana

2017-10-01

Full Text Available Interferon beta is a safe and efficacious treatment for relapsing multiple sclerosis (MS. However, there is some evidence that uric acid, a scavenger of peroxynitrite, is involved in MS pathology and that increasing serum uric acid levels might have beneficial therapeutic effects. The aim of this study is to investigate serum uric acid levels in MS patients before and after long-term interferon beta treatment. Blood samples from 101 MS patients (53 receiving interferon beta 1a treatment and 48 receiving interferon beta 1b treatment; 28 male and 73 female; mean age at treatment onset 32,4±7,3 years; mean duration of disease at treatment onset 5,1±3,2 years; mean EDSS 2±1,3 before and after interferon beta treatment (mean treatment duration 3±2 years were analysed. Serum uric acid levels were measured using a quantitative enzymatic assay (Elitech Diagnostic, Sees, France. MS patients had significantly increased serum uric acid levels after treatment compared with those at the beginning of treatment (272,31±78,21 μmol/l vs. 210,17±53,65 μmol/l; p=0,019, Wilcoxon Mann-Whitney U-test. We did not find significant differences in serum uric acid levels between the interferon beta 1a and interferon beta 1b groups (p=0.98. These results indicate that one of the beneficial effects of interferon beta in MS might be based on the elevation of serum uric acid levels as a natural scavenger of peroxynitrite.

Tranexamic acid-associated seizures: Causes and treatment.

Science.gov (United States)

Lecker, Irene; Wang, Dian-Shi; Whissell, Paul D; Avramescu, Sinziana; Mazer, C David; Orser, Beverley A

2016-01-01

Antifibrinolytic drugs are routinely used worldwide to reduce the bleeding that results from a wide range of hemorrhagic conditions. The most commonly used antifibrinolytic drug, tranexamic acid, is associated with an increased incidence of postoperative seizures. The reported increase in the frequency of seizures is alarming, as these events are associated with adverse neurological outcomes, longer hospital stays, and increased in-hospital mortality. However, many clinicians are unaware that tranexamic acid causes seizures. The goal of this review is to summarize the incidence, risk factors, and clinical features of these seizures. This review also highlights several clinical and preclinical studies that offer mechanistic insights into the potential causes of and treatments for tranexamic acid-associated seizures. This review will aid the medical community by increasing awareness about tranexamic acid-associated seizures and by translating scientific findings into therapeutic interventions for patients. © 2015 The Authors Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.

Retinoic acid for treatment of systemic sclerosis and morphea: A literature review.

Science.gov (United States)

Thomas, Renee M; Worswick, Scott; Aleshin, Maria

2017-03-01

Systemic sclerosis and morphea are connective tissue diseases characterized by tightening, thickening, and hardening of the skin, leading to significant morbidity. Unfortunately, current treatment options have limited efficacy for many patients. Cutaneous manifestations of these diseases arise from excess collagen deposition and fibrosis in the skin, through pathogenic mechanisms which have yet to be extensively detailed at the causal immune and cellular levels. Research elucidating the mechanism of action of retinoic acid on collagen production in the skin and case series highlighting the success of retinoic acid on the skin manifestations of systemic sclerosis and on morphea demonstrate its promise as a treatment. Herein they will briefly review the treatment options for both systemic sclerosis and morphea, and will discuss the potential of retinoic acid as a therapy and the supporting evidence from the literature, highlighting the previously published basic science and clinical studies investigating the role of retinoic acid in the treatment of sclerotic skin diseases. © 2016 Wiley Periodicals, Inc.

Folic acid treatment increases homocysteine remethylation and methionine transmethylation in healthy subjects

NARCIS (Netherlands)

Stam, F.; Smulders, Y.M.; van Guldener, C.; Jakobs, C.A.J.M.; Stehouwer, C.D.A.; van der Meer, K.

2005-01-01

Folic acid treatment decreases plasma total homocysteine concentrations in healthy subjects, but the effects on homocysteine metabolism are unknown. In the present study, we investigated the effect of 3 weeks of oral treatment with 5 mg of folic acid on one-carbon flux rates in 12 healthy subjects,

Recent advances in delivery of drug-nucleic acid combinations for cancer treatment.

Science.gov (United States)

Li, Jing; Wang, Yan; Zhu, Yu; Oupický, David

2013-12-10

Cancer treatment that uses a combination of approaches with the ability to affect multiple disease pathways has been proven highly effective in the treatment of many cancers. Combination therapy can include multiple chemotherapeutics or combinations of chemotherapeutics with other treatment modalities like surgery or radiation. However, despite the widespread clinical use of combination therapies, relatively little attention has been given to the potential of modern nanocarrier delivery methods, like liposomes, micelles, and nanoparticles, to enhance the efficacy of combination treatments. This lack of knowledge is particularly notable in the limited success of vectors for the delivery of combinations of nucleic acids with traditional small molecule drugs. The delivery of drug-nucleic acid combinations is particularly challenging due to differences in the physicochemical properties of the two types of agents. This review discusses recent advances in the development of delivery methods using combinations of small molecule drugs and nucleic acid therapeutics to treat cancer. This review primarily focuses on the rationale used for selecting appropriate drug-nucleic acid combinations as well as progress in the development of nanocarriers suitable for simultaneous delivery of drug-nucleic acid combinations. Copyright © 2013 Elsevier B.V. All rights reserved.

Drug Repositioning for Effective Prostate Cancer Treatment.

Science.gov (United States)

Turanli, Beste; Grøtli, Morten; Boren, Jan; Nielsen, Jens; Uhlen, Mathias; Arga, Kazim Y; Mardinoglu, Adil

2018-01-01

Drug repositioning has gained attention from both academia and pharmaceutical companies as an auxiliary process to conventional drug discovery. Chemotherapeutic agents have notorious adverse effects that drastically reduce the life quality of cancer patients so drug repositioning is a promising strategy to identify non-cancer drugs which have anti-cancer activity as well as tolerable adverse effects for human health. There are various strategies for discovery and validation of repurposed drugs. In this review, 25 repurposed drug candidates are presented as result of different strategies, 15 of which are already under clinical investigation for treatment of prostate cancer (PCa). To date, zoledronic acid is the only repurposed, clinically used, and approved non-cancer drug for PCa. Anti-cancer activities of existing drugs presented in this review cover diverse and also known mechanisms such as inhibition of mTOR and VEGFR2 signaling, inhibition of PI3K/Akt signaling, COX and selective COX-2 inhibition, NF-κB inhibition, Wnt/β-Catenin pathway inhibition, DNMT1 inhibition, and GSK-3β inhibition. In addition to monotherapy option, combination therapy with current anti-cancer drugs may also increase drug efficacy and reduce adverse effects. Thus, drug repositioning may become a key approach for drug discovery in terms of time- and cost-efficiency comparing to conventional drug discovery and development process.

Tracking acidic pharmaceuticals, caffeine, and triclosan through the wastewater treatment process.

Science.gov (United States)

Thomas, Paul M; Foster, Gregory D

2005-01-01

Pharmaceuticals are a class of emerging contaminants whose fate in the wastewater treatment process has received increasing attention in past years. Acidic pharmaceuticals (ibuprofen, naproxen, mefenamic acid, ketoprofen, and diclofenac), caffeine, and the antibacterial triclosan were quantified at four different steps of wastewater treatment from three urban wastewater treatment plants. The compounds were extracted from wastewater samples on Waters Oasis hydrophilic-lipophilic balance solid-phase extraction columns, silylated, and analyzed by gas chromatography-mass spectrometry. For the chemicals studied, it was found that the majority of the influent load was removed during secondary treatment (51-99%), yielding expected surface water concentrations of 13 to 56 ng/L.

Acid Water Neutralization Using Microbial Fuel Cells: An Alternative for Acid Mine Drainage Treatment

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Eduardo Leiva

2016-11-01

Full Text Available Acid mine drainage (AMD is a complex environmental problem, which has adverse effects on surface and ground waters due to low pH, high toxic metals, and dissolved salts. New bioremediation approach based on microbial fuel cells (MFC can be a novel and sustainable alternative for AMD treatment. We studied the potential of MFC for acidic synthetic water treatment through pH neutralization in batch-mode and continuous-flow operation. We observed a marked pH increase, from ~3.7 to ~7.9 under batch conditions and to ~5.8 under continuous-flow operation. Likewise, batch reactors (non-MFC inoculated with different MFC-enriched biofilms showed a very similar pH increase, suggesting that the neutralization observed for batch operation was due to a synergistic influence of these communities. These preliminary results support the idea of using MFC technologies for AMD remediation, which could help to reduce costs associated with conventional technologies. Advances in this configuration could even be extrapolated to the recovery of heavy metals by precipitation or adsorption processes due to the acid neutralization.

Effect of acidic treatment on carbon nano tubes for immobilization of cellulase enzyme

International Nuclear Information System (INIS)

Al-Khatib, M.F.R.; Mohd Zahangir Alam; Rasha Mohammed

2009-01-01

Full text: The effect of acidic treatment on MWCNTs functionalization was studied by mixing different ratios (1:1, 1:2, and 1:3 v/v %) of nitric acid and sulphuric acid, respectively. The effect of these treatments on the structure of MWCNTs was characterized by Fourier transform infrared spectroscopy (FTIR) and Filed emission scanning electron microscopy (FESEM). Results showed that the optimum ratio 1:3 (v/v %) is best suitable in imparting carboxylic acid and hydroxyl groups which are required for immobilization of cellulase enzyme on functionalized CNTs. (author)

Treatment of alpha-bearing combustible wastes using acid digestion

International Nuclear Information System (INIS)

Lerch, R.E.; Allen, C.R.; Blasewitz, A.G.

1978-01-01

Acid digestion has been developed at the Hanford Engineering Development Laboratory (HEDL) in Richland, Washington to reduce the volume of combustible nuclear waste materials, while converting them to an inert, noncombustible residue. A 100 kg/day test unit has recently been constructed to demonstrate the process using radioactively contaminated combustible wastes. The unit, called the Radioactive Acid Digestion Test Unit (RADTU) was completed in September 1977 and is currently undergoing cold shakedown tests. Hot operation is expected in May 1978. Features of RADTU include: storage and transfer station for incoming wastes, a feed preparation station, an extrusion feed mechanism for transfer of the waste to the acid digester, the acid digester a residue recovery system, and an off-gas treatment system

Treatment of alpha-bearing combustible wastes using acid digestion

International Nuclear Information System (INIS)

Lerch, R.E.; Allen, C.R.; Blasewitz, A.G.

1977-11-01

Acid digestion has been developed at the Hanford Engineering Development Laboratory (HEDL) in Richland, Washington to reduce the volume of combustible nuclear waste materials, while converting them to an inert, noncombustible residue. A 100 kg/day test unit has recently been constructed to demonstrate the process using radioactively contaminated combustible wastes. The unit, called the Radioactive Acid Digestion Test Unit (RADTU) was completed in September 1977 and is currently undergoing cold shakedown tests. Hot operation is expected in May 1978. Features of RADTU include: storage and transfer station for incoming wastes, a feed preparation station, an extrusion feed mechanism for transfer of the waste to the acid digester, the acid digester, a residue recovery system, and an off-gas treatment system

Hyper-thermal acid hydrolysis and adsorption treatment of red seaweed, Gelidium amansii for butyric acid production with pH control.

Science.gov (United States)

Ra, Chae Hun; Jeong, Gwi-Taek; Kim, Sung-Koo

2017-03-01

Optimal hyper-thermal (HT) acid hydrolysis conditions for Gelidium amansii were determined to be 12% (w/v) seaweed slurry content and 144 mM H 2 SO 4 at 150 °C for 10 min. HT acid hydrolysis-treated G. amansii hydrolysates produced low concentrations of inhibitory compounds and adsorption treatment using 3% activated carbon. An adsorption time of 5 min was subsequently used to remove the inhibitory 5-hydroxymethylfurfural from the medium. A final maximum monosaccharide concentration of 44.6 g/L and 79.1% conversion from 56.4 g/L total fermentable monosaccharides with 120 g dw/L G. amansii slurry was obtained from HT acid hydrolysis, enzymatic saccharification, and adsorption treatment. This study demonstrates the potential for butyric acid production from G. amansii hydrolysates under non-pH-controlled as well as pH-controlled fermentation using Clostridium acetobutylicum KCTC 1790. The activated carbon treatment and pH-controlled fermentation showed synergistic effects and produced butyric acid at a concentration of 11.2 g/L after 9 days of fermentation.

The importance of γ-linolenic acid in the prevention and treatment

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Małgorzata Białek

2015-07-01

Full Text Available The etiology of diet-related disorders is closely associated with dietary factors. A special role is attributed to intake of fat and fatty acid profile, both quantitative and qualitative. For prevention and treatment of the abovementioned diseases a proper supply of unsaturated fatty acids plays a significant role, because of their particular importance to health. γ-Linolenic acid (GLA, with three double bonds in the carbon chain, also known as all-cis 6,9,12-octadecatrienoic acid, belongs to the n-6 family of fatty acids. It plays biologically important functions in the human body, such as being a substrate for eicosanoids synthesis, involvement in the transport and oxidation of cholesterol, and being one of the components of lipid membrane. Its inadequate dietary intake or impaired formation is the cause of many inflammatory and degenerative diseases. A rich source of this fatty acid is vegetable oils, until recently used mainly in folk medicine. Nowadays, studies conducted both in animal models and in humans suggest its health-promoting properties in the prevention and treatment of atopic dermatitis, cardiovascular diseases, diabetes, cancers and rheumatoid arthritis.

Modeling and optimizing the design of matrix treatments in carbonate reservoirs with self-diverting acid systems

International Nuclear Information System (INIS)

Bulgakova, G T; Kharisov, R Ya; Sharifullin, A R; Pestrikov, A V

2015-01-01

Application of a self-diverting-acid based on viscoelastic surfactant (SDVA) is a promising technology for improving the efficacy of acid treatment in oil and gas-bearing carbonate reservoirs. In this study, we present a mathematical model for assessing SDVA flow and reaction with carbonate rock using the SDVA rheological characteristics. The model calculates the technological parameters for acidizing operations and the prediction of well productivity after acid treatment, in addition to technical and economic optimization of the acidizing process by modeling different acid treatment options with varying volumes, injection rates, process fluids stages and initial economic scenarios

Effect of Ultrasonic Treatment Combined with Peracetic Acid Treatment Reduces Decay and Maintains Quality in Loquat Fruit

Directory of Open Access Journals (Sweden)

Chen Ling

2018-01-01

Full Text Available The effects of ultrasonic treatment (UT, 400 watts for 6 min combined with peracetic acid (PA, 0.4% (W/W treatment on fruit decay, browning, and quality and physiological changes in loquat fruit stored at 20°C were investigated. The results showed that treatment with UT or PA alone significantly reduced both decay and browning index in loquat fruit compared with the control. The combined treatment was more effective in decreasing decay and browning index and maintaining higher quality parameters than UT or PA treatment alone. Loquat fruits treated with the combined treatment maintained higher activities of polyphenol oxidase (PPO and peroxidase (POD than those treated with other treatments. In addition, UT combined with PA treatment significantly reduced the increase of firmness and increased fruit extractable juice, total soluble solid (TSS, and ascorbic acid content in loquat fruit. Moreover, the contents of total phenolics and total flavonoids were enhanced by the combination of UT and PA treatment. The combination of UT and PA treatment could be a useful method to reduce decay and browning in loquat fruit stored at room temperature, which has potential for application in the loquat industry.

Tranexamic acid for the treatment of heavy menstrual bleeding: efficacy and safety

Science.gov (United States)

Leminen, Henri; Hurskainen, Ritva

2012-01-01

Tranexamic acid has proven to be an effective treatment for heavy menstrual bleeding (HMB). It reduces menstrual blood loss (MBL) by 26%–60% and is significantly more effective than placebo, nonsteroidal anti-inflammatory drugs, oral cyclical luteal phase progestins, or oral etamsylate, while the levonorgestrel-releasing intrauterine system reduces MBL more than tranexamic acid. Other treatments used for HMB are oral contraceptives, danazol, and surgical interventions (endometrial ablation and hysterectomy). Medical therapy is usually considered a first-line treatment for idiopathic HMB. Tranexamic acid significantly improves the quality of life of women treated for HMB. The recommended oral dosage is 3.9–4 g/day for 4–5 days starting from the first day of the menstrual cycle. Adverse effects are few and mainly mild. No evidence exists of an increase in the incidence of thrombotic events associated with its use. An active thromboembolic disease is a contraindication. In the US, a history of thrombosis or thromboembolism, or an intrinsic risk for thrombosis or thromboembolism are considered contraindications as well. This review focuses on the efficacy and safety of tranexamic acid in the treatment of idiopathic HMB. We searched for medical literature published in English on tranexamic acid from Ovid Medline, PubMed, and Cinahl. Additional references were identified from the reference lists of articles. Ovid Medline, PubMed, and Cinahl search terms were “tranexamic acid” and “menorrhagia” or “heavy menstrual bleeding.” Searches were last updated on March 25, 2012. Studies with women receiving tranexamic acid for HMB were included; randomized controlled studies with a description of appropriate statistical methodology were preferred. Relevant data on the physiology of menstruation and the pharmacodynamics and pharmacokinetics of tranexamic acid are also included. PMID:22956886

Fracture during intravenous bisphosphonate treatment in a child with osteogenesis imperfecta: an argument for a more frequent, low-dose treatment regimen.

Science.gov (United States)

Biggin, Andrew; Briody, Julie N; Ormshaw, Elizabeth; Wong, Karen K Y; Bennetts, Bruce H; Munns, Craig F

2014-01-01

Intravenous bisphosphonate therapy is the mainstay of medical treatment in osteogenesis imperfecta (OI) and has been shown to increase bone mass, decrease bone pain, improve mobility, and reduce the incidence of fractures. Sclerotic metaphyseal lines parallel to the growth plate are seen on long bone radiographs following cyclical intravenous therapy. These areas create stress risers within the bone that may act as foci for subsequent fractures as exemplified in this clinical case. An 8-year-old girl with OI sustained a distal radial fracture following 3 years of treatment with 6-monthly intravenous zoledronate. Her diagnosis, response to treatment, and subsequent fracture at a sclerotic metaphyseal line is described. Peripheral quantitative computer tomography was used to characterise the presence of multiple stress risers at the distal forearm. Trabecular bone mineral density fluctuated from 34 to 126% compared to neighbouring 2-mm regions. There remain many unanswered questions about optimal bisphosphonate treatment regimens in children with OI. The formation of stress risers following intravenous bisphosphonate treatment raises the hypothesis that a more frequent and low-dose bisphosphonate regimen would provide more uniform dosing of bone in the growing child and reduce the likelihood of fractures compared to current treatment practices.

Essential fatty acids in the treatment of dry eye syndrome: A myth or reality?

OpenAIRE

Al Mahmood, Ammar M.; Al-Swailem, Samar A.

2014-01-01

Dry eye is a common condition that can severely impair the quality of life. Systemic and topical omega-3 fatty acids and omega-6 fatty acids have been used as treatment for patients with dry eye disease and showed promising results. Further multicenter randomized controlled trials are required in order to establish a standardized protocol for the treatment of dry eye syndrome with those essential fatty acids.

Effect of postharvest methyl jasmonate treatment on fatty acid composition and phenolic acid content in olive fruits during storage.

Science.gov (United States)

Flores, Gema; Blanch, Gracia Patricia; Del Castillo, María Luisa Ruiz

2017-07-01

The nutritional effects of both table olives and olive oil are attributed not only to their fatty acids but also to antioxidant phenolics such as phenolic acids. Delays in oil processing usually result in undesirable oxidation and hydrolysis processes leading to formation of free fatty acids. These alterations create the need to process oil immediately after olive harvest. However, phenolic content decreases drastically during olive storage resulting in lower quality oil. In the present study we propose postharvest methyl jasmonate treatment as a mean to avoid changes in fatty acid composition and losses of phenolic acids during olive storage. Contents of fatty acids and phenolic acids were estimated in methyl jasmonate treated olives throughout 30-day storage, as compared with those of untreated olives. Significant decreases of saturated fatty acids were observed in treated samples whereas increases of oleic, linoleic and linolenic acids were respectively measured (i.e. from 50.8% to 64.5%, from 7.2% to 9.1% and from 1.5% to 9.3%). Also, phenolic acid contents increased significantly in treated olives. Particularly, increases of gallic acid from 1.35 to 6.29 mg kg -1 , chlorogenic acid from 9.18 to 16.21 mg kg -1 , vanillic acid from 9.61 to 16.99 mg kg -1 , caffeic acid from 5.12 to 12.55 mg kg -1 , p-coumaric acid from 0.96 to 5.31 mg kg -1 and ferulic acid from 4.05 to 10.43 mg kg -1 were obtained. Methyl jasmonate treatment is proposed as an alternative postharvest technique to traditional methods to guarantee olive oil quality when oil processing is delayed and olive fruits have to necessarily to be stored. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Influence of pH-control in phosphoric acid treatment of zinc oxide

Energy Technology Data Exchange (ETDEWEB)

Onoda, H., E-mail: onoda@kpu.ac.jp [Department of Informatics and Environmental Sciences, Kyoto Prefectural University (Japan); Chemel, M. [Ecole de Biologie Industrielle, CERGY Cedex (France)

2017-04-15

Zinc oxide is often used as a white pigment for cosmetics; however, it shows photocatalytic activity that causes decomposition of sebum on the skin when exposed to the ultraviolet radiation in sunlight. In this work, zinc oxide was reacted with phosphoric acid at various pH values to synthesize a novel white pigment for cosmetics. The chemical composition, powder properties, photocatalytic activities, colors, and smoothness of these pigments were studied. The obtained materials exhibited X-ray diffraction peaks relating to zinc oxide and phosphate after phosphoric acid treatment. The ratio of zinc phosphate to zinc oxide was estimated from inductively coupled plasma - atomic emission spectroscopy results. Samples treated at pH 4-7 yielded small particles with sub-micrometer sizes. The photocatalytic activity of zinc oxide became lower after phosphoric acid treatment. Samples treated at pH 4-7 showed the same reflectance as zinc oxide in both the ultraviolet and visible ranges. Adjustment of the pH was found to be important in the phosphoric acid treatment of zinc oxide. (author)

[Amplification of γδ T cells in PBMCs of healthy donors and osteosarcoma patients stimulated by zoledronate].

Science.gov (United States)

Li, Zhao-xu; Sun, Ling-ling; Cheng, Rui-lin; Sun, Zheng-wang; Ye, Zhao-ming

2012-08-01

To investigate the amplification and cytotoxicity of γδ T cells in peripheral blood mononuclear cells (PBMCs) of healthy donors and osteosarcoma patients stimulated by zoledronate (Zol) and IL-2. PBMCs from healthy donors and osteosarcoma patients were stimulated with IL-2 and Zol+IL-2, respectively. After 14-day culture, the purity of γδ T cells was assessed by flow cytometry. The cytotoxicity of γδ T cells against target cells was analyzed using a standard lactate dehydrogenase release assay with γδ T lymphocyte-sensitive Daudi cells, γδ T lymphocyte-resistant Raji cells and human osteoblast cell line, hFOB, as the target cells. After 2-week culture ex vivo of PBMCs from healthy donors and osteosarcoma patients, compared with stimulation of IL-2, Zol+IL-2 significantly promoted the amplification of γδ T cells. In addition, γδ T cells showed the higher cytotoxicity against Daudi cells, but no cytotoxic effect on normal cells like hFOB. γδ T cells of high purity and high cytotoxicity can be obtained by the stimulation of Zol combined with IL-2 on PBMCs from healthy donors and osteosarcoma patients.

Azelaic acid in dermatological treatment – current state of knowledge

Directory of Open Access Journals (Sweden)

Radomir Reszke

2016-09-01

Full Text Available Azelaic acid (AZA is a naturally occurring substance produced by Malassezia furfur which exerts various effects on the skin. Azelaic acid has antibacterial, anti-inflammatory, keratolytic, comedolytic, sebostatic and tyrosinase-inhibiting properties. Topical application of AZA as 20% cream or 15% gel is a well-established therapeutic method in various common dermatoses, mainly acne vulgaris, rosacea and disorders associated with hyperpigmentation. Azelaic acid is used as a component of chemical peels as well. The paper summarizes the most relevant issues concerning AZA application in dermatological treatment based on current knowledge.

Cost-effectiveness of zoledronic acid in the prevention of skeletal-related events in patients with bone metastases secondary to advanced renal cell carcinoma: application to France, Germany, and the United Kingdom.

Science.gov (United States)

Botteman, M F; Meijboom, M; Foley, I; Stephens, J M; Chen, Y M; Kaura, S

2011-12-01

The use of zoledronic acid (ZOL) has recently been shown to significantly reduce the risk of new skeletal-related events (SREs) in renal cell carcinoma (RCC) patients with bone metastases. The present exploratory study assessed the cost-effectiveness of ZOL in this population, adopting a French, German, and United Kingdom (UK) government payer perspective. This cost-effectiveness model was based on a post hoc retrospective analysis of a subset of patients with RCC who were included in a larger randomized clinical trial of patients with bone metastases secondary to a variety of cancers. In the trial, patients were randomized to receive ZOL (n = 27) or placebo (n = 19) with concomitant antineoplastic therapy every 3 weeks for 9 months (core study) plus 12 months during a study extension. Since the trial did not collect costs or data on the quality-adjusted life years (QALYs) of the patients, these outcomes had to be assumed via modeling exercises. The costs of SREs were estimated using hospital DRG tariffs. These estimates were supplemented with literature-based costs where possible. Drug, administration, and supply costs were obtained from published and internet sources. Consistent with similar economic analyses, patients were assumed to experience quality of life decrements lasting 1 month for each SRE. Uncertainty surrounding outcomes was addressed via multivariate sensitivity analyses. Patients receiving ZOL experienced 1.07 fewer SREs than patients on placebo. Patients on ZOL experienced a gain in discounted QALYs of approximately 0.1563 in France and Germany and 0.1575 in the UK. Discounted SRE-related costs were substantially lower among ZOL than placebo patients (-€ 4,196 in France, - € 3,880 in Germany, and -€ 3,355 in the UK). After taking into consideration the drug therapy costs, ZOL saved € 1,358, € 1,223, and € 719 in France, Germany, and the UK, respectively. In the multivariate sensitivity analyses, therapy with ZOL saved costs in 67

Treatment of Arctic wastewater by chemical coagulation, UV and peracetic acid disinfection.

Science.gov (United States)

Chhetri, Ravi Kumar; Klupsch, Ewa; Andersen, Henrik Rasmus; Jensen, Pernille Erland

2017-02-16

Conventional wastewater treatment is challenging in the Arctic region due to the cold climate and scattered population. Thus, no wastewater treatment plant exists in Greenland, and raw wastewater is discharged directly to nearby waterbodies without treatment. We investigated the efficiency of physicochemical wastewater treatment, in Kangerlussuaq, Greenland. Raw wastewater from Kangerlussuaq was treated by chemical coagulation and UV disinfection. By applying 7.5 mg Al/L polyaluminium chloride (PAX XL100), 73% of turbidity and 28% phosphate was removed from raw wastewater. E. coli and Enterococcus were removed by 4 and 2.5 log, respectively, when UV irradiation of 0.70 kWh/m 3 was applied to coagulated wastewater. Furthermore, coagulated raw wastewater in Denmark, which has a chemical quality similar to Greenlandic wastewater, was disinfected by peracetic acid or UV irradiation. Removal of heterotrophic bacteria by applying 6 and 12 mg/L peracetic acid was 2.8 and 3.1 log, respectively. Similarly, removal of heterotrophic bacteria by applying 0.21 and 2.10 kWh/m 3 for UV irradiation was 2.1 and greater than 4 log, respectively. Physicochemical treatment of raw wastewater followed by UV irradiation and/or peracetic acid disinfection showed the potential for treatment of arctic wastewater.

A systematic review and economic evaluation of bisphosphonates for the prevention of fragility fractures.

OpenAIRE

Davis, S.; Martyn-St James, M.; Sanderson, J.; Stevens, J.; Goka, E.; Rawdin, A.; Sadler, S.; Wong, R.; Campbell, F.; Stevenson, M.; Strong, M.; Selby, P.; Gittoes, N.

2016-01-01

BACKGROUND: Fragility fractures are fractures that result from mechanical forces that would not ordinarily result in fracture. OBJECTIVES: To evaluate the clinical effectiveness and safety of bisphosphonates [alendronic acid (Fosamax(®) and Fosamax(®) Once Weekly, Merck Sharp & Dohme Ltd), risedronic acid (Actonel(®) and Actonel Once a Week(®), Warner Chilcott UK Ltd), ibandronic acid (Bonviva(®), Roche Products Ltd) and zoledronic acid (Aclasta(®), Novartis Pharmaceuticals UK Ltd)] for the p...

Sialic acid changes in Dalton's lymphoma-bearing mice after cyclophosphamide and cisplatin treatment

Directory of Open Access Journals (Sweden)

Nicol B.M.

2002-01-01

Full Text Available Sialic acid changes in Dalton's lymphoma cells and other tissues of 10-12-week-old Swiss albino mice were investigated in relation to tumour growth in vivo and following cyclophosphamide (ip, 200 mg/kg body weight or cisplatin (ip, 8 mg/kg body weight treatment. Three to four animals of both sexes were used in each experimental group. The sialic acid level of tumour cells (0.88 µmol/g increased with tumour progression (1.44-1.59 µmol/g; P<=0.05 in mice. Sialic acid concentration in other tissues (liver, kidney, testes and brain also increased (~40, 10, 30 and 58%, respectively in the tumour-bearing hosts as compared with that in the respective tissues of normal mice. In vivo cyclophosphamide or cisplatin treatment resulted in an overall decrease of sialic acid contents in the tissues. Cyclophosphamide was more efficient in lowering tissue sialic acid than cisplatin (P<=0.01, ANOVA. It is suggested that sialic acid residues could be an important factor contributing to the manifestation of malignant properties in cancer cells in general and Dalton's lymphoma cells in particular. A significant decrease in the sialic acid content of Dalton's lymphoma cells after cisplatin or cyclophosphamide treatment may bring about specific changes in tumour cells which could be associated with tumour regression.

Hydrolysis of Miscanthus for bioethanol production using dilute acid presoaking combined with wet explosion pre-treatment and enzymatic treatment

DEFF Research Database (Denmark)

Sørensen, Annette; Teller, Philip Johan; Hilstrøm, Troels

2008-01-01

xylose prior to wet explosion. The acid presoaking extracted 63.2% xylose and 5.2% glucose. Direct enzymatic hydrolysis of the presoaked biomass was found to give only low sugar yields of 24-26% glucose. Wet explosion is a pre-treatment method that combines wet-oxidation and steam explosion. The effect...... of wet explosion on non-presoaked and presoaked Miscanthus was investigated using both atmospheric air and hydrogen peroxide as the oxidizing agent. All wet explosion pre-treatments showed to have a disrupting effect on the lignocellulosic biomass, making the sugars accessible for enzymatic hydrolysis......Miscanthus is a high yielding bioenergy crop. In this study we used acid presoaking, wet explosion, and enzymatic hydrolysis to evaluate the combination of the different pre-treatment methods for bioethanol production with Miscanthus. Acid presoaking is primarily carried out in order to remove...

Current perspectives on bisphosphonate treatment in Paget’s disease of bone

Directory of Open Access Journals (Sweden)

Wat WZM

2014-11-01

Full Text Available Winnie Zee Man Wat Department of Medicine, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong Abstract: Paget’s disease of bone is a chronic metabolic bone disease with focal increase in bone turnover. The exact etiology of the disease is uncertain, although genetic and environmental factors are believed to be important. Bisphosphonate is the main class of medication being used to control disease activity via its antiresorptive effect. This review discusses the controversies concerning the use of bisphosphonates in the treatment of Paget’s disease of bone, the efficacy of different bisphosphonates in controlling disease activity, and the possible rare side effects of bisphosphonates. Symptoms are the main indication for treatment in Paget’s disease of bone. As treatment benefits in asymptomatic individuals remain controversial and nonevidence based, the decision to treat these patients should be individualized to their risk and benefit profiles. There are several trials conducted to evaluate and compare the efficacy of different regimes of bisphosphonates for treating Paget’s disease of bone. Most trials used biochemical markers rather than clinical symptoms or outcomes as parameters for comparison. Zoledronate is an attractive option as it can achieve high rates of biochemical remission and sustain long duration of suppression by a single dose. Atypical femoral fracture and osteonecrosis of the jaw are two rare and severe side effects reported, possibly related to the use of bisphosphonates in patients with osteoporosis and malignancy-induced hypercalcemia. As the regimes of bisphosphonates used for treating Paget’s disease of bone are different from those two diseases, the risks of developing these two possible side effects are expected to be very low, although this remains unknown. Vitamin D and calcium supplement should be given to patients at risk of vitamin D insufficiency when given zoledronate, as symptomatic

Osseointegration of biochemically modified implants in an osteoporosis rodent model

Directory of Open Access Journals (Sweden)

B Stadlinger

2013-07-01

Full Text Available The present study examined the impact of implant surface modifications on osseointegration in an osteoporotic rodent model. Sandblasted, acid-etched titanium implants were either used directly (control or were further modified by surface conditioning with NaOH or by coating with one of the following active agents: collagen/chondroitin sulphate, simvastatin, or zoledronic acid. Control and modified implants were inserted into the proximal tibia of aged ovariectomised (OVX osteoporotic rats (n = 32/group. In addition, aged oestrogen competent animals received either control or NaOH conditioned implants. Animals were sacrificed 2 and 4 weeks post-implantation. The excised tibiae were utilised for biomechanical and morphometric readouts (n = 8/group/readout. Biomechanical testing revealed at both time points dramatically reduced osseointegration in the tibia of oestrogen deprived osteoporotic animals compared to intact controls irrespective of NaOH exposure. Consistently, histomorphometric and microCT analyses demonstrated diminished bone-implant contact (BIC, peri-implant bone area (BA, bone volume/tissue volume (BV/TV and bone-mineral density (BMD in OVX animals. Surface coating with collagen/chondroitin sulphate had no detectable impact on osseointegration. Interestingly, statin coating resulted in a transient increase in BIC 2 weeks post-implantation; which, however, did not correspond to improvement of biomechanical readouts. Local exposure to zoledronic acid increased BIC, BA, BV/TV and BMD at 4 weeks. Yet this translated only into a non-significant improvement of biomechanical properties. In conclusion, this study presents a rodent model mimicking severely osteoporotic bone. Contrary to the other bioactive agents, locally released zoledronic acid had a positive impact on osseointegration albeit to a lesser extent than reported in less challenging models.

[Use of alpha-lipoic acid and omega-3 in postpartum pain treatment].

Science.gov (United States)

Costantino, D; Guaraldi, C; Costantino, M; Bounous, V E

2015-10-01

Postpartum pain is a frequent condition that negatively affects women's quality of life, interferring with everyday life. Analgesic drugs and surgery are often contraindicated in pregnancy and during breast feeding. This review of the literature aims to evaluate the rational of the association of lipoic acid and omega-3 employ in the management of postpartum pain. Lipoic acid is a cofactor essential in mitochondrial metabolism with antioxidant and anti-inflammatory activity. Lipoic acid has been shown to be effective in neuropatic pain treatment in patients with sciatica, carpal tunnel syndrome and diabetic neuropathy. Omega-3 are known for their anti-inflammatory and neurotrophic activity. The peripheral and central activity of both substances allows to act on neuroinflammation mechanisms thus reducing cronicization of pain and also determining a potential improvement of women's emotional status. The preliminary data here presented confirm the positive effect of this association on the treatment of postpartum perineal pain. The supplementation of lipoic acid in association with omega-3 seems effective and safe for the treatment of chronic postpartum pain, allowing a pathogenetic approach to neuroinflammation, thus reducing the consumption of analgesic drugs, often contraindicated during breast-feeding.

Application of citric acid in acid stimulation treatments

Energy Technology Data Exchange (ETDEWEB)

Alkhaldi, M.H.; Sarma, H.K. [Adelaide Univ., Adelaide (Australia); Nasr-el-Din, H.A. [Texas A and M Univ., College Station, TX (United States)

2009-07-01

A rotating disk apparatus was used to investigate mass transfer during the reaction of citric acid with calcite. The study evaluated the effects of initial acid concentrations, temperature, and disk rotational speed on the effective diffusion coefficient of citric acid. The diffusion coefficient was calculated at 25, 40, and 50 degrees C using various citric acid concentrations. The study indicated that the coefficient was a function of the interactions between calcium citrate precipitation and counter calcium ions. At high acid concentrations, the effects of calcium citrate precipitation and counter calcium ions were significant. The calculated citric acid diffusion coefficients were not comparable with measured effective diffusion coefficients using the rotating disk. At lower initial citric acid concentrations, the effects of both calcium citrate precipitation and counter calcium ions on citric acid diffusivity were minimal. It was concluded that temperature effects on the diffusion coefficient followed Arrhenius law. Activation energy was equal to 37.9 kJ/mol. 34 refs., 4 tabs., 13 figs.

Solution of Azelaic Acid (20%), Resorcinol (10%) and Phytic Acid (6%) Versus Glycolic Acid (50%) Peeling Agent in the Treatment of Female Patients with Facial Melasma.

Science.gov (United States)

Faghihi, Gita; Taheri, Azam; Shahmoradi, Zabihollah; Nilforoushzadeh, Mohammad Ali

2017-01-01

Melasma, a common acquired disorder of hyperpigmentation, especially in women, is often resistant to therapy. This study was aimed to evaluate the efficacy and safety of azelaic acid, resorcinol and phytic acid solution in chemical peeling of melasma in comparison to 50% glycolic acid. This clinical trial was performed, on 42 female patients with bilateral melasma. Severity of melasma was assessed by melasma area and severity index (MASI). Combination of (20% azelaic acid + 10% resorcinol + 6% phytic acid) was used as a new peeling agent on the right side of the face and 50% glycolic acid on the left side every 2 weeks for 6 times. Follow-up was carried out for 3 months after the last session. Any decrease in MASI score and unwanted complications following peeling were evaluated and compared during the trial. Patients showed marked improvement as calculated with MASI score before and after treatment in both sides of the face. The efficacy of combination formula (azelaic acid, resorcinol and phytic acid) was similar to glycolic acid, but with fewer complications. There was no statistically difference in improvement between two groups ( P > 0.05). However, the patient's discomfort following procedures was significantly lower with azelaic acid, resorcinol and phytic compared with the glycolic acid peels ( P < 0.05) and there was the same duration in the beginning of the therapeutic response in both groups. Results showed that triple-combination was found to be an effective and safe peeling agent in the treatment of melasma and it was as effective as 50% glycolic acid peel.

Treatment of periorbital dark circles: Comparative study of chemical peeling with a combination of trichloroacetic acid and lactic acid versus carboxytherapy

Directory of Open Access Journals (Sweden)

Arwa Mohammad Hassan

2016-07-01

Full Text Available Periorbital dark circles (PODC are a common worldwide cosmetic problem. It is difficult to treat due to complications in its pathogenesis and aetiology. Available lines of treatment for PODC include whitening creams, topical retinoid acid, chemical peeling, laser therapy, carboxytherapy, autologous fat transplantation, injectable fillers and surgery (blepharoplasty.The aim of this study isto evaluate and compare the efficacy of chemical peels using trichloroacetic acid (3.75% and lactic acid (15% in a gel formula with that of carboxytherapy, in the treatment of periorbital hyperpigmentation.Two groups of patients with PODC were included in the study, named Group A and B in which each group consisted of 15 patients. Group A was assigned for patients who received treatment with chemical peeling with a combination of trichloroacetic acid (3.75% and lactic acid (15% in a gel formula, once a week for four weeks. Group B was assigned for patients who received carboxytherapy that was performed by subcutaneous and intradermal injection of CO2 once a week for four weeks. All patients were assessed by digital photographs, before and after treatment, by observing the improvement in the grade of PODC. Reports of patient satisfaction and global tolerance were evaluated by three medical observers. There was a significant improvement in the grade of PODC in both groups. The degree of improvement of PODC in group A was excellent, with good grade in 93.4% of the treated patients while fair grade in 6.6% of them. There was a statistically significant improvement in the pigmented type. The degree of improvement of PODC in group B was excellent, with good grade in 86.7% of the treated patients while fair grade in 13.3% of them. However, no statistically significant difference between the two groups was observed. Minimal and transient side effects were noticed; however, it did not require further treatment. In conclusion, the two methods of treatment were effective

Integrated treatment of acid mine drainage using cryptocrystalline magnesite and barium chloride

CSIR Research Space (South Africa)

Masindi, Vhahangwele

2017-08-01

Full Text Available This study endeavours to report the efficiency of a hybrid approach in the treatment of acid mine drainage. Cryptocrystalline magnesite was used to pre-treat acid mine drainage and barium chloride was used to remove the residual sulphate through...

Reduced Bacterial Wilt in Tomato Plants by Bactericidal Peroxyacetic Acid Mixture Treatment

Directory of Open Access Journals (Sweden)

Jeum Kyu Hong

2018-02-01

Full Text Available Peroxyacetic acid mixture Perosan, composed of peroxyacetic acid, hydrogen peroxide and acetic acid, was evaluated for eco-friendly management of tomato bacterial wilt by Ralstonia pseudosolanacearum. Perosan drastically suppressed in vitro growth of R. pseudosolanacearum in liquid cultures in dose- and incubation time-dependent manners. Higher perosan doses (0.1 and 1% caused lowered pH and phytotoxicity to detached leaves of two tomato cultivars Cupirang and Benekia 220 in aqueous solution. Treatment with 0.01% of Perosan delayed wilting symptom significantly in the detached leaves of two cultivars inoculated with R. pseudosolanacearum (10⁷ cfu/ml. Soil drenching of 5% Perosan solution in pots caused severe tissue collapse of tomato seedlings at the four-week-old stage of two tomato cultivars. Treatment with 1% Perosan by soil-drenching significantly reduced bacterial wilt in the tomato seedlings of two cultivars. These findings suggest that Perosan treatment can be applied to suppress bacterial wilt during tomato production.

Mobile Clinical Decision Support System for Acid-base Balance Diagnosis and Treatment Recommendation.

Science.gov (United States)

Mandzuka, Mensur; Begic, Edin; Boskovic, Dusanka; Begic, Zijo; Masic, Izet

2017-06-01

This paper presents mobile application implementing a decision support system for acid-base disorder diagnosis and treatment recommendation. The application was developed using the official integrated development environment for the Android platform (to maximize availability and minimize investments in specialized hardware) called Android Studio. The application identifies disorder, based on the blood gas analysis, evaluates whether the disorder has been compensated, and based on additional input related to electrolyte imbalance, provides recommendations for treatment. The application is a tool in the hands of the user, which provides assistance during acid-base disorders treatment. The application will assist the physician in clinical practice and is focused on the treatment in intensive care.

Optimisation of dilute acid pre-treatment of artisan rice hulls for ethanol production

International Nuclear Information System (INIS)

Lopez, Yoney; Martin, Carlos; Gullon, Beatriz; Parajo, Juan Carlos

2011-01-01

Rice hulls are potential low-cost feedstocks for fuel ethanol production in many countries. In this work, the dilute-acid pre-treatment of artisan rice hulls was investigated using a central composite rotatable experimental design. The experimental variables were temperature (140-210 C), biomass load (5-20%) and sulphuric acid concentration (0.5-1.5 g per 100 g of reaction mixture). A total of 16 experimental runs, including a 23-plan, two replicates at the central point and six star points, were carried out. Low temperatures were found to be favourable for the hydrolysis of xylan and of the easily hydrolyzable glucan fraction. High glucose formation (up to 15.3 g/100 g), attributable to starch hydrolysis, was detected in the hydrolysates obtained under the least severe pre-treatment conditions. Using the experimental results, several models for predicting the effect of the operational conditions on the yield of pretreated solids, xylan and glucan conversion upon pre-treatment, and on enzymatic convertibility of cellulose were developed. Optimum results were predicted for the conversion of easily-hydrolyzable glucan in the material pretreated at 140.7 C, and for the enzymatic saccharification of cellulose in the material pretreated at 169 C. These results suggested the use of two-step acid hydrolysis as future pre-treatment strategy for artisan rice hulls. Key words: Dilute acid hydrolysis, enzymatic hydrolysis, pre-treatment, rice hulls. (author)

A review of minodronic acid hydrate for the treatment of osteoporosis

Directory of Open Access Journals (Sweden)

Tanishima S

2013-02-01

Full Text Available Shinji Tanishima, Yasuo MorioDepartment of Orthopedic Surgery, Misasa Onsen Hospital, Misasa, Tottori, JapanAbstract: Minodronic acid hydrate was the first bisphosphonate developed and approved for osteoporosis treatment in Japan. With regard to inhibition of bone resorption, minodronic acid hydrate is 1000 times more effective than etidronic acid and 10–100 times more effective than alendronic acid. Clinical trials conducted to date have focused on postmenopausal female patients suffering from primary osteoporosis. In these trials, 1 mg of oral minodronic acid hydrate was administrated once daily, and a significant increase was observed in lumbar-spine and hip-joint bone density 1–2 years after administration. All markers of bone metabolism urinary collagen type 1 cross-linked N-telopeptide, urinary free deoxypyridinoline, serum bone alkaline phosphatase, and serum osteocalcin were decreased. The incidence rate of new vertebral and nonvertebral fractures was also decreased. Therefore, effectiveness in fracture prevention was confirmed. A form of minodronic acid (50 mg requiring once-monthly administration has been developed and is currently being used clinically. A comparative study between this new formulation and once-daily minodronic acid (1 mg showed no significant differences between the two formulations in terms of improvement rates in lumbar-spine and hip-joint bone density, changes in bone metabolism markers, or incidence of side effects. This indicates the noninferiority of the monthly formulation. Side effects such as osteonecrosis of the jaw or atypical femoral fractures were not reported with other bisphosphonates, although it is believed that these side effects may emerge as future studies continue to be conducted. On the basis of studies conducted to date, minodronic acid hydrate is considered effective for improving bone density and preventing fractures. We anticipate further investigations in the future

Solution of Azelaic Acid (20%, Resorcinol (10% and Phytic Acid (6% Versus Glycolic Acid (50% Peeling Agent in the Treatment of Female Patients with Facial Melasma

Directory of Open Access Journals (Sweden)

Gita Faghihi

2017-01-01

Full Text Available Background: Melasma, a common acquired disorder of hyperpigmentation, especially in women, is often resistant to therapy. This study was aimed to evaluate the efficacy and safety of azelaic acid, resorcinol and phytic acid solution in chemical peeling of melasma in comparison to 50% glycolic acid. Materials and Methods: This clinical trial was performed, on 42 female patients with bilateral melasma. Severity of melasma was assessed by melasma area and severity index (MASI. Combination of (20% azelaic acid + 10% resorcinol + 6% phytic acid was used as a new peeling agent on the right side of the face and 50% glycolic acid on the left side every 2 weeks for 6 times. Follow-up was carried out for 3 months after the last session. Any decrease in MASI score and unwanted complications following peeling were evaluated and compared during the trial. Results: Patients showed marked improvement as calculated with MASI score before and after treatment in both sides of the face. The efficacy of combination formula (azelaic acid, resorcinol and phytic acid was similar to glycolic acid, but with fewer complications. There was no statistically difference in improvement between two groups (P > 0.05. However, the patient's discomfort following procedures was significantly lower with azelaic acid, resorcinol and phytic compared with the glycolic acid peels (P < 0.05 and there was the same duration in the beginning of the therapeutic response in both groups. Conclusion: Results showed that triple-combination was found to be an effective and safe peeling agent in the treatment of melasma and it was as effective as 50% glycolic acid peel.

300 Area waste acid treatment system closure plan. Revision 1

International Nuclear Information System (INIS)

1996-03-01

This section provides a description of the Hanford Site, identifies the proposed method of 300 Area Waste Acid Treatment System (WATS) closure, and briefly summarizes the contents of each chapter of this plan

300 Area waste acid treatment system closure plan. Revision 1

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-03-01

This section provides a description of the Hanford Site, identifies the proposed method of 300 Area Waste Acid Treatment System (WATS) closure, and briefly summarizes the contents of each chapter of this plan.

Reducing Heavy Metal Element from Coal Bottom Ash by Using Citric Acid Leaching Treatment

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Yahya Ahmad Asyari

2017-01-01

Full Text Available Coal ash is the residue that is produced during coal combustion for instance fly ash, bottom ash or boiler slag which was primarily produced from the combustion of coal. With growth in coal burning power station, huge amount of coal bottom ash (CBA considered as hazardous material which are normally disposed in an on-site disposal system without any commercialization purpose. Previous researchers have studied the extraction of silica from agricultural wastes such as palm ash and rice husk ash (RHA and CBA by using leaching treatment method. In this study, the weaker acid, citric acid solution was used to replace the strong acid in leaching treatment process. Result showed that the heavy metal content such as Copper (Cu, Zinc (Zn and Lead (Pb can be decrease. Meanwhile the silica can be extracted up to 44% from coal bottom ash using citric acid leaching treatment under the optimum reaction time of 60 minutes with solution temperature of 60°C and concentration of citric acid more than 2%.

Application of 5-Aminosalicylic Acid Preparations in the Treatment of Inflammatory Bowel Diseases

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Yu.M. Stepanov

2016-09-01

Full Text Available The article is devoted to the comparative characterization of different derivatives of 5-aminosalicylic acid. Researches of the past decades have changed the presentation of the potential use of aminosalicylates in the therapy of various inflammatory bowel diseases. In connection with unknown etiology of Crohn’s disease and ulcerative colitis, there is no causal treatment of these diseases. The essence of treatment is reduced to inhibition of inflammatory activity during exacerbations and a course of preventive treatment. Numerous studies over the past 20 years have shown that the basis of basic treatment for nonspecific chronic inflammatory bowel diseases is 5-aminosalicylic acid drugs, or salicylates. When choosing the dosage form, you should take into account the differences between mesalazine preparations depending on the type of the coat. It is shown that in terms of pharmacokinetics, the most effective mesalazine dosage forms for the treatment of ulcerative colitis and Crohn’s disease with lesions of the colon are enteric coated tablets that provides a pH-dependent gradual release of 5-aminosalicylic acid throughout the entire colon. 5-aminosalicylic acid drugs available today on the pharmaceutical market are able to control the course of ulcerative colitis and Crohn’s disease with lesions of the colon in the majority of patients. The use of 5-aminosalicylic acid preparations is not limited to the treatment of ulcerative colitis and Crohn’s disease. The drug is widely used in other diseases of the bowel, such as diverticular disease of the colon, colitis banal, radiation damages of the colon, as well as to treat common diseases, such as irritable bowel syndrome. The study, which was conducted in the department bowel disease of the State Institution «Institute of Gastroenterology» for 2 years, showed a positive effect of 20-day treatment with Mesacol in uncomplicated diverticular disease. The use of Mesacol at a dose of 1,600 mg

Kinetics of salivary pH after acidic beverage intake by patients undergoing orthodontic treatment.

Science.gov (United States)

Turssi, Cecilia P; Silva, Carolina S; Bridi, Enrico C; Amaral, Flavia Lb; Franca, Fabiana Mg; Basting, Roberta T

2015-01-01

The saliva of patients undergoing orthodontic treatment with fixed appliances can potentially present a delay in the diluting, clearing, and buffering of dietary acids due to an increased number of retention areas. The aim of this clinical trial was to compare salivary pH kinetics of patients with and without orthodontic treatment, following the intake of an acidic beverage. Twenty participants undergoing orthodontic treatment and 20 control counterparts had their saliva assessed for flow rate, pH, and buffering capacity. There was no significant difference between salivary parameters in participants with or without an orthodontic appliance. Salivary pH recovery following acidic beverage intake was slower in the orthodontic subjects compared to controls. Patients with fixed orthodontic appliances, therefore, seem to be at higher risk of dental erosion, suggesting that dietary advice and preventive care need to be implemented during orthodontic treatment.

Evidence for the prevention of bone loss in elderly and old early non-metastatic breast cancer patients treated with aromatase inhibitors

DEFF Research Database (Denmark)

Gunmalm, V.; Jørgensen, N. R.; Abrahamsen, B.

2017-01-01

Breast cancer (BC) is the most common cancer amongst women worldwide. Bone health is emerging as an important issue for BC survivors. In this literature study, we focus on agents for preventing bone loss in early non-metastatic estrogen receptor positive BC in treatment with aromatase inhibitors...... (AI) and to assess the evidence for antiresorptive treatment of bone loss in early non-metastatic breast cancer. We included randomized controlled trials (RCT's) comparing: (a) bisphosphonates and control; (b) different bisphosphonates; (c) denosumab and control and (d) bisphosphonates vs. denosumab...... in early non-metastatic BC women in AI treatment. Among antiresorptives, zoledronic acid currently has the highest evidence for prevention of AI associated bone loss in early non-metastatic BC. Data on fracture prevention among all patients, elderly and old is sparse. More randomized controlled studies...

Effects of Acid treatment on the compression and mechanical ...

African Journals Online (AJOL)

This study investigated the effect of acid treatment on the compression and mechanical properties of the cellulosic fibrous residue obtained after a high proportion of starch has been removed from the peeled and rasped tuberous root of Xanthosoma sagittifolium (Family: Araceae). Powdered fibrous residues were subjected ...

Efficacy of combination of glycolic acid peeling with topical regimen in treatment of melasma.

Science.gov (United States)

Chaudhary, Savita; Dayal, Surabhi

2013-10-01

Various treatment modalities are available for management of melasma, ranging from topical and oral to chemical peeling, but none is promising alone. Very few studies are available regarding efficacy of combination of topical treatment with chemical peeling. Combination of chemical peeling and topical regimen can be a good treatment modality in the management of this recalcitrant disorder. To assess the efficacy of combination of topical regimen (2% hydroquinone, 1% hydrocortisone and 0.05% tretinoin) with serial glycolic acid peeling in the treatment of melasma in Indian patients. Forty Indian patients of moderate to severe epidermal variety melasma were divided into two groups of 20 each. One Group i.e. peel group received topical regimen (2% hydroquinone, 1% hydrocortisone and 0.05% tretinoin) with serial glycolic acid peeling and other group i.e. control group received topical regimen (2% hydroquinone, 1% hydrocortisone, 0.05% tretinoin). There was an overall decrease in MASI from baseline in 24 weeks of therapy in both the groups (P value peel with topical regimen showed early and greater improvement than the group which was receiving topical regimen only. This study concluded that combining topical regimen (2% hydroquinone, 1% hydrocortisone and 0.05% tretinoin) with serial glycolic acid peeling significantly enhances the therapeutic efficacy of glycolic acid peeling. The combination of glycolic acid peeling with the topical regimen is a highly effective, safe and promising therapeutic option in treatment of melasma.

Treatment of infectious skin defects or ulcers with electrolyzed strong acid aqueous solution.

Science.gov (United States)

Sekiya, S; Ohmori, K; Harii, K

1997-01-01

A chronic ulcer with an infection such as methicillin-resistant Staphylococcus aureus is hard to heal. Plastic and reconstructive surgeons often encounter such chronic ulcers that are resistant to surgical or various conservative treatments. We applied conservative treatment using an electrolyzed strong acid aqueous solution and obtained satisfactory results. The lesion was washed with the solution or soaked in a bowl of the solution for approximately 20 min twice a day. Fresh electrolyzed strong acid aqueous solution is unstable and should be stored in a cool, dark site in a sealed bottle. It should be used within a week after it has been produced. Here we report on 15 cases of infectious ulcers that were treated by electrolyzed strong acid aqueous solution. Of these cases, 7 patients were healed, 3 were granulated, and in 5, infection subsided. In most cases the lesion became less reddish and less edematous. Discharge or foul odor from the lesion was decreased. Electrolyzed strong acid aqueous solution was especially effective for treating a chronic refractory ulcer combined with diabetes melitus or peripheral circulatory insufficiency. This clinically applied therapy of electrolyzed strong acid aqueous solution was found to be effective so that this new therapeutic technique for ulcer treatment can now be conveniently utilized.

Toxic corneal epitheliopathy after intravitreal methotrexate and its treatment with oral folic acid.

Science.gov (United States)

Gorovoy, Ian; Prechanond, Tidarat; Abia, Maravillas; Afshar, Armin R; Stewart, Jay M

2013-08-01

To determine whether oral folic acid can ameliorate an iatrogenic, visually significant corneal epitheliopathy, which commonly occurs with intravitreal injections of methotrexate for the treatment of intraocular lymphoma. We report 2 cases of visually significant corneal epitheliopathy occurring after intravitreal injections of methotrexate for intraocular lymphoma. The first patient did not receive any treatment for the corneal disease, and the second patient with bilateral intraocular lymphoma received 1 mg of oral folic acid daily, a commonly used dosage for patients on systemic methotrexate. In the first patient without treatment, there was a complete regression of the corneal epithelial disease only when the frequency of intravitreal methotrexate was reduced from weekly to monthly as per a commonly used dosage regimen for methotrexate. In the second patient, the corneal disease improved 80% within 1 week of initiating oral folic acid for her eye already experiencing severe epitheliopathy during her weekly dosing regimen of methotrexate and also had significantly decreased epithelial disease in her second eye that started weekly intravitreal methotrexate several weeks after beginning oral folic acid. Currently, oral folic acid supplements are recommended for patients using systemic methotrexate to minimize drug toxicity. We suggest a similar use in patients undergoing intravitreal methotrexate injections to decrease toxic effects on the corneal epithelium.

Comparison of trichostatin A and valproic acid treatment regimens in a mouse model of kidney fibrosis

Energy Technology Data Exchange (ETDEWEB)

Van Beneden, Katrien, E-mail: kvbenede@vub.ac.be [Department of Human Anatomy, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Geers, Caroline [Department of Pathology, Universitair Ziekenhuis Brussel, Brussels (Belgium); Pauwels, Marina [Department of Human Anatomy, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Mannaerts, Inge [Department of Cell Biology, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Wissing, Karl M. [Department of Nephrology, Universitair Ziekenhuis Brussel, Brussels (Belgium); Van den Branden, Christiane [Department of Human Anatomy, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Grunsven, Leo A. van, E-mail: lvgrunsv@vub.ac.be [Department of Cell Biology, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium)

2013-09-01

Histone deacetylase (HDAC) inhibitors are promising new compounds for the therapy of fibrotic diseases. In this study we compared the effect of two HDAC inhibitors, trichostatin A and valproic acid, in an experimental model of kidney fibrosis. In mice, doxorubicin (adriamycin) can cause nephropathy characterized by chronic proteinuria, glomerular damage and interstitial inflammation and fibrosis, as seen in human focal segmental glomerulosclerosis. Two treatment regimens were applied, treatment was either started prior to the doxorubicin insult or delayed until a significant degree of proteinuria and fibrosis was present. Pre-treatment of trichostatin A significantly hampered glomerulosclerosis and tubulointerstitial fibrosis, as did the pre-treatment with valproic acid. In contrast, the development of proteinuria was only completely inhibited in the pre-treated valproic acid group, and not in the pre-treated trichostatin A animals. In the postponed treatment with valproic acid, a complete resolution of established doxorubicin-induced proteinuria was achieved within three days, whereas trichostatin A could not correct proteinuria in such a treatment regimen. However, both postponed regimens have comparable efficacy in maintaining the kidney fibrosis to the level reached at the start of the treatments. Moreover, not only the process of fibrosis, but also renal inflammation was attenuated by both HDAC inhibitors. Our data confirm a role for HDACs in renal fibrogenesis and point towards a therapeutic potential for HDAC inhibitors. The effect on renal disease progression and manifestation can however be different for individual HDAC inhibitors. - Highlights: • Valproic acid is a potent antiproteinuric drug, whereas trichostatin A is not. • Trichostatin A and valproic acid reduce kidney fibrosis in doxorubicin nephropathy. • Both valproic acid and trichostatin A attenuate renal inflammation.

Comparison of trichostatin A and valproic acid treatment regimens in a mouse model of kidney fibrosis

International Nuclear Information System (INIS)

Van Beneden, Katrien; Geers, Caroline; Pauwels, Marina; Mannaerts, Inge; Wissing, Karl M.; Van den Branden, Christiane; Grunsven, Leo A. van

2013-01-01

Histone deacetylase (HDAC) inhibitors are promising new compounds for the therapy of fibrotic diseases. In this study we compared the effect of two HDAC inhibitors, trichostatin A and valproic acid, in an experimental model of kidney fibrosis. In mice, doxorubicin (adriamycin) can cause nephropathy characterized by chronic proteinuria, glomerular damage and interstitial inflammation and fibrosis, as seen in human focal segmental glomerulosclerosis. Two treatment regimens were applied, treatment was either started prior to the doxorubicin insult or delayed until a significant degree of proteinuria and fibrosis was present. Pre-treatment of trichostatin A significantly hampered glomerulosclerosis and tubulointerstitial fibrosis, as did the pre-treatment with valproic acid. In contrast, the development of proteinuria was only completely inhibited in the pre-treated valproic acid group, and not in the pre-treated trichostatin A animals. In the postponed treatment with valproic acid, a complete resolution of established doxorubicin-induced proteinuria was achieved within three days, whereas trichostatin A could not correct proteinuria in such a treatment regimen. However, both postponed regimens have comparable efficacy in maintaining the kidney fibrosis to the level reached at the start of the treatments. Moreover, not only the process of fibrosis, but also renal inflammation was attenuated by both HDAC inhibitors. Our data confirm a role for HDACs in renal fibrogenesis and point towards a therapeutic potential for HDAC inhibitors. The effect on renal disease progression and manifestation can however be different for individual HDAC inhibitors. - Highlights: • Valproic acid is a potent antiproteinuric drug, whereas trichostatin A is not. • Trichostatin A and valproic acid reduce kidney fibrosis in doxorubicin nephropathy. • Both valproic acid and trichostatin A attenuate renal inflammation

Mechanical, thermal and morphological properties of glutaraldehyde crosslinked bovine pericardium followed by glutamic acid treatment

Directory of Open Access Journals (Sweden)

Gilberto Goissis

2009-03-01

Full Text Available Major problems with valve bioprostheses are associated with progressive structural deterioration and calcification, directly associated with the use of glutaraldehyde (GA. This work describes the effects of GA processing and borate/glutamic acid buffer treatment on the mechanical, thermal and morphological properties of 0.5% GA crosslinked bovine pericardium (BP. The results showed that while the treatment of 0.5% GA crosslinked BP with borate/glutamic acid significantly improves the mechanical properties, it had no visible effect on surface morphology. Better surface preservation was only achieved for BP pre-treated with a lower GA concentration followed by the conventional treatment (0.5% GA. Improvements in mechanical properties probably arises from structural changes probably involving the depolymerization of polymeric GA crosslinks and an increase electrostatic interaction due to covalent binding of glutamic acid to free carbonyl groups (Schiff base.The results indicate that the treatment GA crosslinked BP with borate/glutamic acid buffer may be an attractive procedure for the manufacture of heart valve bioprostheses.

Undecylenic acid in the treatment of psoriasis and neurodermatitis.

Science.gov (United States)

NELSON, L M

1951-01-01

Undecylenic acid in a dosage tolerated by most patients is of doubtful value in the treatment of psoriasis and neurodermatitis.Thirty-one patients were given the drug. Exudative dermatitis developed in one case, generalized pruritus in another. One patient may have had a cardiac accident attributable to the drug.

The Sonodegradation of Caffeic Acid under Ultrasound Treatment: Relation to Stability

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Yujing Sun

2013-01-01

Full Text Available The degradation of caffeic acid under ultrasound treatment in a model system was investigated. The type of solvent and temperature were important factors in determining the outcome of the degradation reactions. Liquid height, ultrasonic intensity and duty cycle only affected degradation rate, but did not change the nature of the degradation. The degradation rate of caffeic acid decreased with increasing temperature. Degradation kinetics of caffeic acid under ultrasound fitted a zero-order reaction from −5 to 25 °C. Caffeic acid underwent decomposition and oligomerization reactions under ultrasound. The degradation products were tentatively identified by FT-IR and HPLC-UV-ESIMS to include the corresponding decarboxylation products and their dimers.

Eradication of breast cancer with bone metastasis by autologous formalin-fixed tumor vaccine (AFTV) combined with palliative radiation therapy and adjuvant chemotherapy: a case report.

Science.gov (United States)

Kuranishi, Fumito; Ohno, Tadao

2013-06-04

Skeletal metastasis of breast carcinoma is refractory to intensive chemo-radiation therapy and therefore is assumed impossible to cure. Here, we report an advanced case of breast cancer with vertebra-Th7 metastasis that showed complete response to combined treatments with formalin-fixed autologous tumor vaccine (AFTV), palliative radiation therapy with 36 Gy, and adjuvant chemotherapy with standardized CEF (cyclophosphamide, epirubicin, and 5FU), zoledronic acid, and aromatase inhibitors following mastectomy for the breast tumor. The patient has been disease-free for more than 4 years after the mammary surgery and remains well with no evidence of metastasis or local recurrence. Thus, a combination of AFTV, palliative radiation therapy, and adjuvant chemotherapy may be an effective treatment for this devastating disease.

Optimizing the productivity of acid-fracture treatments in horizontal wells

Energy Technology Data Exchange (ETDEWEB)

Allen, E.

1995-12-31

Existing prediction methods are inadequate for unstable radial displacement, with prediction errors of up to 500%. This work provides a new theoretical basis for understanding unstable displacements in both Newtonian and non-Newtonian fluids, based on a detailed analysis of the fingering morphology and a new derivation using fractional flow theory for radial flow. Design guidelines are given to assist in optimizing the design of fingered acid-fracture treatments for horizontal wells in carbonate formations. Unstable radial displacement creates power-law (fractal) displacement patterns, for a wide range of mobility ratios, and the displacement efficiency can be expressed as a function of the mobility ratio M. The finger wavelength is a function of the Peclet number and the fracture aperture, and the detailed morphology can be understood in terms of the fluid theology. The size of the fingering zone can be predicted from the mobility ratio and Peclet number. A productivity index factor PIF can be used to compare different treatment scenarios, and thus optimise the productivity of acid-fracture treatments.

Gastrointestinal events and association with initiation of treatment for osteoporosis

Directory of Open Access Journals (Sweden)

Modi A

2015-11-01

Full Text Available Ankita Modi,1 Ethel S Siris,2 Jackson Tang,3 Shiva Sajjan,1 Shuvayu S Sen1 1Center for Observational and Real-World Evidence, Merck & Co., Inc, Kenilworth, NJ, 2Toni Stabile Osteoporosis Center, Columbia University Medical Center, NY Presbyterian Hospital, New York, NY, 3Asclepius Analytics Ltd, Brooklyn, NY, USA Background: Preexisting gastrointestinal (GI events may deter the use of pharmacologic treatment in patients diagnosed with osteoporosis (OP. The objective of this study was to examine the association between preexisting GI events and OP pharmacotherapy initiation among women diagnosed with OP. Methods: The study utilized claims data from a large US managed care database to identify women aged ≥55 years with a diagnosis code for OP (index date during 2002–2009. Patients with a claim for pharmacologic OP treatment in the 12-month pre-index period (baseline were excluded. OP treatment initiation in the post-index period was defined as a claim for bisphosphonates (alendronate, ibandronate, risedronate, zoledronic acid, calcitonin, raloxifene, or teriparatide. During the post-index period (up to 12 months, GI events were identified before treatment initiation. A time-dependent Cox regression model was used to investigate the likelihood of initiating any OP treatment. Among patients initiating OP treatment, a discrete choice model was utilized to assess the relationship between post-index GI events and likelihood of initiating with a bisphosphonate versus a non-bisphosphonate. Results: In total, 65,344 patients (mean age 66 years were included; 23.7% had a GI event post diagnosis and before treatment initiation. Post-index GI events were associated with a 75% lower likelihood of any treatment initiation (hazard ratio 0.25; 95% confidence interval 0.24–0.26. Among treated patients (n=23,311, those with post-index GI events were 39% less likely to receive a bisphosphonate versus a non-bisphosphonate (odds ratio 0.61; 95% confidence

Improvement of Haramay Fiber by Pre-treatment of Retting Process withPhosphoric Acid

International Nuclear Information System (INIS)

Kuntari-Sasas; Neni-Rustini Eriawati

2000-01-01

Haramay as bast fiber contains of cellulose fiber as the main part, mixedwith hemi cellulose, pectin, and lignin as binding material for cellulosefiber to keep it together in the bundle form. For textile material, this bastfiber has to be freed from its binding material, called as retting process,before subjecting to scouring, dyeing and finishing process in textileindustry. In the retting process the dissolve of binding material can be doneeither by using enzyme in bio technology or extraction with strong alkalinecondition in common technology. Using sodium hydroxide for dissolving thebinding material can be carried out easily with good dissolving ability, butcan render the strength retention of the cellulose fiber. Pre-treatment ofthe bast fiber with phosphoric acid (H 3 PO 4 ), is expected to hydrolyze someof the binding materials that can not be dissolved in alkaline condition,including natural pigment that colored the fiber with creamy white. In thisstudy, the pre-treatment process before retting with phosphoric acid wascarried out in various condition, such as concentration of phosphoric acid (5ml/l- 25 ml/l), time and temperature of pre-treatment (1-3 hours at 50 o C or12-24 hours at room temperature), followed by neutralization in dilutealkaline. The retting process was carried out by means of scouring in variousconcentration of sodium hydroxide (NaOH 38 o Be, 10 ml/l-30 m/l), and then wascontinued with bleaching process in hydrogen peroxide solution. Aftercarrying out those experiment, the bast fiber that called haramay wassubjected to testing for weight reduction, strength retention and degree ofwhiteness. From the testing results it is concluded that pre-treatment withphosphoric acid can increase the weight reduction, strength retention ortenacity and degree of whiteness of haramay fiber compared to the oneswithout pre-treatment with phosphoric acid. The best result was obtained bypre-treatment with 5 ml/l H 3 PO 4 at 50 o C for 2 hours, continued by

Palovarotene, a novel retinoic acid receptor gamma agonist for the treatment of emphysema.

Science.gov (United States)

Hind, Matthew; Stinchcombe, Sian

2009-11-01

Emphysema is characterized by the destruction of alveoli and alveolar ducts within the lungs. Retinoid signaling is believed to play a role in alveologenesis, with the retinoic acid receptor gamma thought to be required for alveolar formation. Based on this hypothesis, Roche Holding AG is developing palovarotene (R-667, RO-3300074), a selective retinoic acid receptor gamma agonist for the treatment of emphysema. In small animal studies, palovarotene was claimed to reverse the structural, functional and inflammatory features of cigarette smoke-induced emphysema. Phase I clinical trials of palovarotene in patients with emphysema demonstrated that the drug is well tolerated, with improvements observed in markers of emphysema progression. Unlike all-trans retinoic acid, the pharmacokinetic profile of palovarotene appears to be dose-proportional. At the time of publication, a phase II, placebo-controlled trial was ongoing, and was expected to report prospective measurements of exercise, gas transfer and lung densitometry endpoints. The development of a selective retinoic acid receptor gamma agonist for the treatment of emphysema represents the first of a new class of small-molecule regenerative therapies that may prove useful for the treatment of destructive or age-related lung disease.

The Efficacy and Safety of Azelaic Acid 15% Foam in the Treatment of Facial Acne Vulgaris.

Science.gov (United States)

Hashim, Peter W; Chen, Tinley; Harper, Julie C; Kircik, Leon H

2018-06-01

Azelaic acid demonstrates anti-inflammatory, anti-oxidative, anti-comedogenic, and anti-microbial effects. Azelaic acid 20% cream is currently approved for the treatment of acne vulgaris, and azelaic acid 15% foam has recently been approved for rosacea. Given the favorable tolerability profile of foam preparations, it is reasonable to assume that azelaic acid 15% foam could serve as a viable treatment option for facial acne. To examine the efficacy and safety of azelaic acid 15% foam in the treatment of moderate-to-severe facial acne Methods: Twenty subjects with moderate-to-severe facial acne vulgaris were enrolled in this two-center, open-label pilot study. All study subjects were treated with azelaic acid 15% foam for 16 weeks. Efficacy analyses were based on the change in facial investigator global assessment (FIGA) and changes in total, inflammatory, non-inflammatory lesion counts between baseline and week 16. There was a significant reduction in FIGA scores from baseline to week 16 (p = .0004), with 84% of subjects experiencing at least a 1 grade improvement, and 63% of subjects achieving a final grade of Clear or Almost Clear. All subjects experienced reductions in inflammatory and total lesion counts by week 16, and 89% of subjects experienced reductions in non-inflammatory lesions. Azelaic acid 15% foam was well tolerated, with almost all instances of erythema, dryness, peeling, oiliness, pruritus, and burning being of mild or trace degree, and most adverse effects resolving by the end of the study. Azelaic acid 15% foam is effective and safe in the treatment of facial acne vulgaris. Given the convenience of foam vehicles, azelaic acid 15% foam should be considered as a viable treatment option for this condition. J Drugs Dermatol. 2018;17(6):641-645.

Improved Lignin Polyurethane Properties with Lewis Acid Treatment

OpenAIRE

Chung, Hoyong; Washburn, Newell R.

2012-01-01

Chemical modification strategies to improve the mechanical properties of lignin-based polyurethanes are presented. We hypothesized that treatment of lignin with Lewis acids would increase the concentration of hydroxyl groups available to react with diisocyanate monomers. Under the conditions used, hydrogen bromide-catalyzed modification resulted in a 28% increase in hydroxyl group content. Associated increases in hydrophilicity of solvent-cast thin films were also recorded as evidenced by ...

Ursodeoxycholic acid for treatment of cholestasis in patients with hepatic amyloidosis

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Faust Dominik

2009-01-01

Full Text Available Background. Amyloidosis represents a group of different diseases characterized by extracellular accumulation of pathologic fibrillar proteins in various tissues and organs. Severe amyloid deposition in the liver parenchyma has extrahepatic involvement predominantly in the kidney or heart. We evaluated the effect of ursodeoxycholic acid, in four patients with severe hepatic amyloidosis of different etiologies, who presented with increased alkaline phosphatase and γ-glutamyl transferase. Case report. The study included four patients who presented with amyloidosis-associated intrahepatic cholestasis. Three of them had renal amyloidosis which developed 1-3 years before cholestasis occurred, the remaining one having intrahepatic cholestasis as the primary sign of the disease. Amyloidosis was identified from liver biopsies in all patients by its specific binding to Congo red and green birefringence in polarized light. The biochemical nature and the class of amyloid deposits were identified immunohistochemically. In addition to their regular treatment, the patients received 750 mg ursodeoxycholic acid per day. After 2-4 weeks all patients had a significant decrease of serum alkaline phosphatase and γ-glutamyl transferase, and their general status significantly improved. Conclusion. Treatment with ursodeoxycholic acid may be beneficial in patients with hepatic amyloidosis, and do extend indications for the use of ursodeoxycholic acid in amyloidotic cholestatic liver disease.

Role of acidic chemistries in steam treatment of aluminium alloys

DEFF Research Database (Denmark)

Din, Rameez Ud; Jellesen, Morten Stendahl; Ambat, Rajan

2015-01-01

The effect of acidic chemistry on the accelerated growth of oxide on aluminium alloys Peraluman 706TM and AA6060 under exposure to high temperature steam was investigated. Studied chemistries were based on citrates and phosphates. Results showed that the presence of citrate and phosphate anions...... initiate doxide growth at the intermetallic particles while growth and corrosion performance of oxide was found tobe a function of anions type and their concentration. Further, steam treatment with phosphates exhibited better performance under acetic acid salt spray and filiform corrosion test whereas...

Efficacy of hyaluronic acid in the treatment of chronic gingivitis in children

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Igić Marija

2011-01-01

Full Text Available Introduction/Aim. Gingivitis is a common occurrence in children and may well be thought as a risk factor for the appearance and progression of the diseases of parodontal tissues. It is thus necessary to react in a timely and adequate fashion to prevent the disease to become serious and produce parodontopathy. The aim of the study was to establish the efficacy of hyaluronic acid in the treatment of chronic gingivitis in children. Methods. The study enrolled 130 children with permanent dentition. All of the examinees were divided into three groups: group I - 50 patients with chronic gingivitis in which only the basic treatment was applied; group II - 50 patients with chronic gingivitis in which hyaluronic acid was applied in addition to basic treatment; group III - 30 examinees with healthy gingiva (control group. Assessment of oral hygiene and status of the gingiva and parodontium was done using the appropriate indexes before and after the treatment. Inflammation of the gingiva was monitored by way of cytomorphometric studies. Results. The pretreatment values of the plaque index (PI were high: in the group I PI was 1.94; in the group II PI was 1.68. After the treatment, the PI value was reduced to null in both groups (PI = 0. In the group III PI was 0.17. The bleeding index (BI in the group I was 2.02 before and 0.32 after the treatment; the BI value in the group II was 1.74 before and 0.16 after the treatment. In the group III BI was 0. In the group I, the Community Periodontal Index of Treatment Needs (CPITN was 1.66 before and 0.32 after the treatment; in the group II, the CPITN value was 1.5 before and 0.24 after the treatment. In the group III, the CPITN value was 0. In the group I, the size of the nuclei of the stratified squamous epithelium of the gingiva was reduced, although not so much as the nuclear size in the group II of examinees. Conclusion. Basic treatment is able to successfully treat chronic gingivitis in children. The use of

Optimizing the Treatment of Atopic Dermatitis in Infants Using Ursodeoxycholic Acid

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O.H. Shadrin

2016-08-01

Full Text Available We have determined the advisability of including a suspension of ursodeoxycholic acid into the treatment of atopic dermatitis in infants. It is proved that taking a suspension of ursodeoxycholic acid in 25 infants with atopic dermatitis leads to a positive clinical dynamics of both skin and gastrointestinal manifestations that resulted in a decrease in the area of skin lesions, intensity of itching, sleep normalization and regression of abdominal pain syndrome, possetings.

Effect of ursodeoxycholic acid treatment on the altered progesterone and bile acid homeostasis in the mother-placenta-foetus trio during cholestasis of pregnancy.

Science.gov (United States)

Estiú, Maria C; Monte, Maria J; Rivas, Laura; Moirón, Maria; Gomez-Rodriguez, Laura; Rodriguez-Bravo, Tomas; Marin, Jose J G; Macias, Rocio I R

2015-02-01

Intrahepatic cholestasis of pregnancy (ICP) is characterized by pruritus and elevated bile acid concentrations in maternal serum. This is accompanied by an enhanced risk of intra-uterine and perinatal complications. High concentrations of sulphated progesterone metabolites (PMS) have been suggested to be involved in the multifactorial aetiopathogenesis of ICP. The aim of this study was to investigate further the mechanism accounting for the beneficial effect of oral administration of ursodeoxycholic acid (UDCA), which is the standard treatment, regarding bile acid and PMS homeostasis in the mother-placenta-foetus trio. Using HPLC-MS/MS bile acids and PMS were determined in maternal and foetal serum and placenta. The expression of ABC proteins in placenta was determined by real time quantitative PCR (RT-QPCR) and immunofluorescence. In ICP, markedly increased concentrations of bile acids (tauroconjugates > glycoconjugates > unconjugated), progesterone and PMS in placenta and maternal serum were accompanied by enhanced concentrations in foetal serum of bile acids, but not of PMS. UDCA treatment reduced bile acid accumulation in the mother-placenta-foetus trio, but had no significant effect on progesterone and PMS concentrations. ABCG2 mRNA abundance was increased in placentas from ICP patients vs. controls and remained stable following UDCA treatment, despite an apparent further increase in ABCG2. UDCA administration partially reduces ICP-induced bile acid accumulation in mothers and foetuses despite the lack of effect on concentrations of progesterone and PMS in maternal serum. Up-regulation of placental ABCG2 may play an important role in protecting the foetus from high concentrations of bile acids and PMS during ICP. © 2014 The British Pharmacological Society.

Organising pneumonia associated with fumaric acid ester treatment for psoriasis.

LENUS (Irish Health Repository)

Deegan, Alexander Paul

2012-02-01

INTRODUCTION: We present the case of a 49-year old male who presented with dyspnoea, cough, weight loss, night sweats and general malaise. He had been on treatment with oral fumaric acid esters (FAE, Fumaderm(R); Biogen Idec GmbH, Ismaning, Germany) for 6 months. METHODS: Report of a case. RESULTS: His chest X-ray showed patchy infiltrates in the left upper lobe which failed to resolve under empiric antibiotic therapy. A computed tomography of thorax revealed bilateral, mostly peripheral foci of consolidation with air bronchograms. Transbronchial biopsies showed a pattern of organising pneumonia (OP). CONCLUSIONS: Therapy with oral prednisolone (40 mg\\/day) resulted in a rapid clinical and radiological improvement. An association of FAE and OP has not previously been reported. Please cite this paper as: Deegan AP, Kirby B, Rogers S, Crotty TB and McDonnell TJ. Organising pneumonia associated with fumaric acid ester treatment for psoriasis.

Impact of Surface Potential on Apatite Formation in Ti Alloys Subjected to Acid and Heat Treatments.

Science.gov (United States)

Yamaguchi, Seiji; Hashimoto, Hideki; Nakai, Ryusuke; Takadama, Hiroaki

2017-09-24

Titanium metal (Ti) and its alloys are widely used in orthopedic and dental fields. We have previously shown that acid and heat treatment was effective to introduce bone bonding, osteoconduction and osteoinduction on pure Ti. In the present study, acid and heat treatment with or without initial NaOH treatment was performed on typical Ti-based alloys used in orthopedic and dental fields. Dynamic movements of alloying elements were developed, which depended on the kind of treatment and type of alloy. It was found that the simple acid and heat treatment enriched/remained the alloying elements on Ti-6Al-4V, Ti-15Mo-5Zr-3Al and Ti-15Zr-4Nb-4Ta, resulting in neutral surface charges. Thus, the treated alloys did not form apatite in a simulated body fluid (SBF) within 3 days. In contrast, when the alloys were subjected to a NaOH treatment prior to an acid and heat treatment, alloying elements were selectively removed from the alloy surfaces. As a result, the treated alloys became positively charged, and formed apatite in SBF within 3 days. Thus, the treated alloys would be useful in orthopedic and dental fields since they form apatite even in a living body and bond to bone.

Case Report: Valproic Acid and Risperidone Treatment Leading to Development of Hyperammonemia and Mania

Science.gov (United States)

Carlson, Teri; Reynolds, Charles A.; Caplan, Rochelle

2007-01-01

This case report describes two children who developed hyperammonemia together with frank manic behavior during treatment with a combination of valproic acid and risperidone. One child had been maintained on valproic acid for years and risperidone was added. In the second case, valproic acid was introduced to a child who had been treated with…

Combination cancer treatment through photothermally controlled release of selenous acid from gold nanocages.

Science.gov (United States)

Cheng, Haoyan; Huo, Da; Zhu, Chunlei; Shen, Song; Wang, Wenxia; Li, Haoxuan; Zhu, Zhihong; Xia, Younan

2018-04-03

Selenite, one of the inorganic forms of selenium, is emerging as an attractive chemotherapeutic agent owing to its selectivity in eradicating cancer cells. Here we demonstrate a new formulation of nanomedicine based on selenous acid, which is mixed with lauric acid (a phase-change material with a melting point around 43 °C) and then loaded into the cavities of Au nanocages. The Au nanocages can serve as a carrier during cell endocytosis and then as a photothermal agent to melt the lauric acid upon the irradiation with a near-infrared laser, triggering the swift release of selenous acid. The photothermal and chemo therapies can also work synergistically, leading to enhanced destruction of cancer cells relative to normal cells. Our systematic study suggests that the impaired mitochondrial function arising from the ROS generated through combination treatment is responsible for the cell death. This study offers an appealing candidate that holds great promise for synergistic cancer treatment. Published by Elsevier Ltd.

The treatments of soil Rirang by floatation and Acid leaching

International Nuclear Information System (INIS)

Kosim-Affandi; Umar-Sarip; Alwi, Guswita; Sri-Sudaryanto

2000-01-01

The treatments of soil Rirang by floatation and acid leaching has been carried out to increase high uranium concentrates of materials, separating associated economical minerals and to reduce the gangue minerals which bothering at chemical processing. The physical treatment has been done by ore preparation and floatation using oleic acid and p ine oil , 20 % of pulp at pH 9, condition time at 5 minutes and collections of float fraction was 10 minutes. The chemical processing has been done by dynamic leaching using H 2 SO 4 100 kg/ton, MnO 2 20 kg/ton, 50 % of solid with ore size - 65 mesh, temperature at 80 o C and time of leaching was 8 hours. The result of experiments is as follows : Physical treatment by floatation shown that the concentrates of U increased at sink fraction by (1.5 - 2) times against feed sample for all the samples, and in the float fraction the recovery of molybdenite separation is 58 - 81 % and rare earths is 57 - 80 %. The result of dynamic leaching is 76 - 91 %, and recovery uranium increasing from 81.02 % (mixture samples soil before floatation) to 91.16 % ( mixture samples of float fraction)

COMPOST-FREE BIOREACTOR TREATMENT OF ACID ROCK DRAINAGE - TECHNOLOGY CAPSULE

Science.gov (United States)

As part of the Superfund Innovative Technology Evaluation (SITE) program, an evaluation of the compost-free bioreactor treatment of acid rock drainage (ARD) from the Aspen Seep was conducted at the Leviathan Mine Superfund site located in a remote, high altitude area of Alpine Co...

Where to from here? The treatment of impetigo in children as resistance to fusidic acid emerges.

Science.gov (United States)

Vogel, Alison; Lennon, Diana; Best, Emma; Leversha, Alison

2016-10-14

Admissions for skin and soft-tissue infections have been increasing steadily in children and in the general population. Concerns have been raised recently about the increasing widespread use of topical fusidic acid and concurrent increase of fusidic acid-resistant Staphylococcus aureus. Fusidic acid resistance and methicillin resistant Staphylococcus aureus (MRSA) are both more prevalent in youngest age group (<5 year-olds) and particularly in the North island. In New Zealand, fusidic acid is recommended for treatment of minor impetigo and is the only fully-funded topical antibiotic. The evidence base for alternative treatment strategies for mild impetigo is limited. Most children with impetigo in the current Counties Manukau skin and sore throat schools programme received care with wound management with only a few requiring escalation. An upcoming randomised controlled trial comparing topical hydrogen peroxide cream, topical fusidic acid and wound management only (clean and cover) will help provide evidence about the effectiveness of alternative treatments in the New Zealand setting.

The effect of dilute acid pre-treatment process in bioethanol production from durian (Durio zibethinus) seeds waste

Science.gov (United States)

Ghazali, K. A.; Salleh, S. F.; Riayatsyah, T. M. I.; Aditiya, H. B.; Mahlia, T. M. I.

2016-03-01

Lignocellulosic biomass is one of the promising feedstocks for bioethanol production. The process starts from pre-treatment, hydrolysis, fermentation, distillation and finally obtaining the final product, ethanol. The efficiency of enzymatic hydrolysis of cellulosic biomass depends heavily on the effectiveness of the pre-treatment step which main function is to break the lignin structure of the biomass. This work aims to investigate the effects of dilute acid pre-treatment on the enzymatic hydrolysis of durian seeds waste to glucose and the subsequent bioethanol fermentation process. The yield of glucose from dilute acid pre-treated sample using 0.6% H2SO4 and 5% substrate concentration shows significant value of 23.4951 g/L. Combination of dilute acid pre-treatment and enzymatic hydrolysis using 150U of enzyme able to yield 50.0944 g/L of glucose content higher compared to normal pre-treated sample of 8.1093 g/L. Dilute acid pre-treatment sample also shows stable and efficient yeast activity during fermentation process with lowest glucose content at 2.9636 g/L compared to 14.7583g/L for normal pre-treated sample. Based on the result, it can be concluded that dilute acid pre-treatment increase the yield of ethanol from bioethanol production process.

Citric acid treatment of chronic nonhealing ulcerated tophaceous gout with bursitis.

Science.gov (United States)

Nagoba, Basavaraj S; Punpale, Ajay; Poddar, Ashok; Suryawanshi, Namdev M; Swami, Ganesh A; Selkar, Sohan P

2013-12-01

The ulceration associated with gout tophi is very difficult to treat because of impaired and halted local inflammatory response resulting from the gout treatment regimen. We report chronic nonhealing tophaceous gout with bursitis in an 80-year-old male, not responding to conventional treatment modality for months together. This nonhealing ulcer was treated successfully with local application of 3% citric acid ointment for 22 days.

Dystrophic Cutaneous Calcification and Metaplastic Bone Formation due to Long Term Bisphosphonate Use in Breast Cancer

Directory of Open Access Journals (Sweden)

Ali Murat Tatlı

2013-01-01

Full Text Available Bisphosphonates are widely used in the treatment of breast cancer with bone metastases. We report a case of a female with breast cancer presented with a rash around a previous mastectomy site and a discharge lesion on her right chest wall in August 2010. Biopsy of the lesion showed dystrophic calcification and metaplastic bone formation. The patient’s history revealed a long term use of zoledronic acid for the treatment of breast cancer with bone metastasis. We stopped the treatment since we believed that the cutaneous dystrophic calcification could be associated with her long term bisphosphonate therapy. Adverse cutaneous events with bisphosphonates are very rare, and dystrophic calcification has not been reported previously. The dystrophic calcification and metaplastic bone formation in this patient are thought to be due to long term bisphosphonate usage.

Folinic acid treatment for schizophrenia associated with folate receptor autoantibodies.

Science.gov (United States)

Ramaekers, V T; Thöny, B; Sequeira, J M; Ansseau, M; Philippe, P; Boemer, F; Bours, V; Quadros, E V

2014-12-01

Auto-antibodies against folate receptor alpha (FRα) at the choroid plexus that block N(5)-methyltetrahydrofolate (MTHF) transfer to the brain were identified in catatonic schizophrenia. Acoustic hallucinations disappeared following folinic acid treatment. Folate transport to the CNS prevents homocysteine accumulation and delivers one-carbon units for methyl-transfer reactions and synthesis of purines. The guanosine derivative tetrahydrobiopterin acts as common co-factor for the enzymes producing dopamine, serotonin and nitric oxide. Our study selected patients with schizophrenia unresponsive to conventional treatment. Serum from these patients with normal plasma homocysteine, folate and vitamin B12 was tested for FR autoantibodies of the blocking type on serial samples each week. Spinal fluid was analyzed for MTHF and the metabolites of pterins, dopamine and serotonin. The clinical response to folinic acid treatment was evaluated. Fifteen of 18 patients (83.3%) had positive serum FR auto-antibodies compared to only 1 in 30 controls (3.3%) (χ(2)=21.6; pfolate flux to the CNS, which explained low CSF folate values in 6 and normal values in 7 patients. The mean±SD for CSF MTHF was diminished compared to previously established controls (t-test: 3.90; p=0.0002). A positive linear correlation existed between CSF MTHF and biopterin levels. CSF dopamine and serotonin metabolites were low or in the lower normal range. Administration of folinic acid (0.3-1mg/kg/day) to 7 participating patients during at least six months resulted in clinical improvement. Assessment of FR auto-antibodies in serum is recommended for schizophrenic patients. Clinical negative or positive symptoms are speculated to be influenced by the level and evolution of FRα antibody titers which determine folate flux to the brain with up- or down-regulation of brain folate intermediates linked to metabolic processes affecting homocysteine levels, synthesis of tetrahydrobiopterin and neurotransmitters

Organising pneumonia associated with fumaric acid ester treatment for psoriasis.

Science.gov (United States)

Deegan, Alexander Paul; Kirby, Brian; Rogers, Sarah; Crotty, Tom Bernard; McDonnell, Timonthy John

2010-10-01

  We present the case of a 49-year old male who presented with dyspnoea, cough, weight loss, night sweats and general malaise. He had been on treatment with oral fumaric acid esters (FAE, Fumaderm®; Biogen Idec GmbH, Ismaning, Germany) for 6 months.   Report of a case.   His chest X-ray showed patchy infiltrates in the left upper lobe which failed to resolve under empiric antibiotic therapy. A computed tomography of thorax revealed bilateral, mostly peripheral foci of consolidation with air bronchograms. Transbronchial biopsies showed a pattern of organising pneumonia (OP).   Therapy with oral prednisolone (40 mg/day) resulted in a rapid clinical and radiological improvement. An association of FAE and OP has not previously been reported. Please cite this paper as: Deegan AP, Kirby B, Rogers S, Crotty TB and McDonnell TJ. Organising pneumonia associated with fumaric acid ester treatment for psoriasis. © 2010 Blackwell Publishing Ltd.

Ethanol addition enhances acid treatment to eliminate Lactobacillus fermentum from the fermentation process for fuel ethanol production.

Science.gov (United States)

Costa, M A S; Cerri, B C; Ceccato-Antonini, S R

2018-01-01

Fermentation is one of the most critical steps of the fuel ethanol production and it is directly influenced by the fermentation system, selected yeast, and bacterial contamination, especially from the genus Lactobacillus. To control the contamination, the industry applies antibiotics and biocides; however, these substances can result in an increased cost and environmental problems. The use of the acid treatment of cells (water-diluted sulphuric acid, adjusted to pH 2·0-2·5) between the fermentation cycles is not always effective to combat the bacterial contamination. In this context, this study aimed to evaluate the effect of ethanol addition to the acid treatment to control the bacterial growth in a fed-batch system with cell recycling, using the industrial yeast strain Saccharomyces cerevisiae PE-2. When only the acid treatment was used, the population of Lactobacillus fermentum had a 3-log reduction at the end of the sixth fermentation cycle; however, when 5% of ethanol was added to the acid solution, the viability of the bacterium was completely lost even after the first round of cell treatment. The acid treatment +5% ethanol was able to kill L. fermentum cells without affecting the ethanol yield and with a low residual sugar concentration in the fermented must. In Brazilian ethanol-producing industry, water-diluted sulphuric acid is used to treat the cell mass at low pH (2·0) between the fermentative cycles. This procedure reduces the number of Lactobacillus fermentum from 10 7 to 10 4  CFU per ml. However, the addition of 5% ethanol to the acid treatment causes the complete loss of bacterial cell viability in fed-batch fermentation with six cell recycles. The ethanol yield and yeast cell viability are not affected. These data indicate the feasibility of adding ethanol to the acid solution replacing the antibiotic use, offering a low cost and a low amount of residue in the biomass. © 2017 The Society for Applied Microbiology.

Antioxidative Peptides Derived from Enzyme Hydrolysis of Bone Collagen after Microwave Assisted Acid Pre-Treatment and Nitrogen Protection

Directory of Open Access Journals (Sweden)

Jin Sun

2010-11-01

Full Text Available This study focused on the preparation method of antioxidant peptides by enzymatic hydrolysis of bone collagen after microwave assisted acid pre-treatment and nitrogen protection. Phosphoric acid showed the highest ability of hydrolysis among the four other acids tested (hydrochloric acid, sulfuric acid and/or citric acid. The highest degree of hydrolysis (DH was 9.5% using 4 mol/L phosphoric acid with a ratio of 1:6 under a microwave intensity of 510 W for 240 s. Neutral proteinase gave higher DH among the four protease tested (Acid protease, neutral protease, Alcalase and papain, with an optimum condition of: (1 ratio of enzyme and substrate, 4760 U/g; (2 concentration of substrate, 4%; (3 reaction temperature, 55 °C and (4 pH 7.0. At 4 h, DH increased significantly (P < 0.01 under nitrogen protection compared with normal microwave assisted acid pre-treatment hydrolysis conditions. The antioxidant ability of the hydrolysate increased and reached its maximum value at 3 h; however DH decreased dramatically after 3 h. Microwave assisted acid pre-treatment and nitrogen protection could be a quick preparatory method for hydrolyzing bone collagen.

Citric acid facilitated thermal treatment: An innovative method for the remediation of mercury contaminated soil

International Nuclear Information System (INIS)

Ma, Fujun; Peng, Changsheng; Hou, Deyi; Wu, Bin; Zhang, Qian; Li, Fasheng; Gu, Qingbao

2015-01-01

Highlights: • Hg content was reduced to <1.5 mg/kg when treated at 400 °C with citric acid. • The treated soil retained most of its original soil physicochemical properties. • Proton provided by citric acid facilitates thermal removal of mercury. • This thermal treatment method is expected to reduce energy input by 35%. - Abstract: Thermal treatment is a promising technology for the remediation of mercury contaminated soils, but it often requires high energy input at heating temperatures above 600 °C, and the treated soil is not suitable for agricultural reuse. The present study developed a novel method for the thermal treatment of mercury contaminated soils with the facilitation of citric acid (CA). A CA/Hg molar ratio of 15 was adopted as the optimum dosage. The mercury concentration in soils was successfully reduced from 134 mg/kg to 1.1 mg/kg when treated at 400 °C for 60 min and the treated soil retained most of its original soil physiochemical properties. During the treatment process, CA was found to provide an acidic environment which enhanced the volatilization of mercury. This method is expected to reduce energy input by 35% comparing to the traditional thermal treatment method, and lead to agricultural soil reuse, thus providing a greener and more sustainable remediation method for treating mercury contaminated soil in future engineering applications.

Citric acid facilitated thermal treatment: An innovative method for the remediation of mercury contaminated soil

Energy Technology Data Exchange (ETDEWEB)

Ma, Fujun [State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); Peng, Changsheng [The Key Lab of Marine Environmental Science and Ecology, Ministry of Education, Ocean University of China, Qingdao 266100 (China); Hou, Deyi [Geotechnical and Environmental Research Group, Department of Engineering, University of Cambridge, Cambridge CB2 1PZ (United Kingdom); Wu, Bin; Zhang, Qian; Li, Fasheng [State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); Gu, Qingbao, E-mail: guqb@craes.org.cn [State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012 (China)

2015-12-30

Highlights: • Hg content was reduced to <1.5 mg/kg when treated at 400 °C with citric acid. • The treated soil retained most of its original soil physicochemical properties. • Proton provided by citric acid facilitates thermal removal of mercury. • This thermal treatment method is expected to reduce energy input by 35%. - Abstract: Thermal treatment is a promising technology for the remediation of mercury contaminated soils, but it often requires high energy input at heating temperatures above 600 °C, and the treated soil is not suitable for agricultural reuse. The present study developed a novel method for the thermal treatment of mercury contaminated soils with the facilitation of citric acid (CA). A CA/Hg molar ratio of 15 was adopted as the optimum dosage. The mercury concentration in soils was successfully reduced from 134 mg/kg to 1.1 mg/kg when treated at 400 °C for 60 min and the treated soil retained most of its original soil physiochemical properties. During the treatment process, CA was found to provide an acidic environment which enhanced the volatilization of mercury. This method is expected to reduce energy input by 35% comparing to the traditional thermal treatment method, and lead to agricultural soil reuse, thus providing a greener and more sustainable remediation method for treating mercury contaminated soil in future engineering applications.

The Efficacy and Safety of Azelaic Acid 15% Foam in the Treatment of Truncal Acne Vulgaris.

Science.gov (United States)

Hoffman, Lauren K; Del Rosso, James Q; Kircik, Leon H

2017-06-01

INTRODUCTION: Truncal acne is often associated with facial acne, but there are fewer options for an effective topical treatment on the trunk. Given the advent of foam formulations with enhanced percutaneous absorption and convenient application due to easy spreadability on skin, the previously held idea that effective treatment of truncal acne requires oral treatment is challenged. Azelaic acid cream has been previously approved for acne vulgaris, thus azelaic acid foam may be a viable treatment option for truncal acne. STUDY DESIGN: A single-center, open label pilot study was conducted to investigate the efficacy and safety of azelaic acid 15% foam as a treatment modality for moderate truncal acne. Use for facial acne was also allowed and monitored during the study. RESULTS: Twice-daily application of azelaic acid 15% foam to affected areas resulted in a 1-grade reduction in truncal investigator global assessment (IGA) scores in nearly all patients (16/18). Eight out of 18 patients (44%) were rated as Clear or Almost Clear in the trunk by the end of the study. There were also improvements in facial IGA scores; 9 of 18 patients (50%) exhibited a 1-grade improvement in IGA scores and 11 of 18 were Clear or Almost Clear by the end of the study. A significant reduction in lesion counts was found throughout the study and the medication was well tolerated. CONCUSION: Azelaic acid 15% foam was effective in treating moderate truncal acne and facial acne in this pilot study. Given the efficacy and convenience of the foam vehicle, azelaic acid may be considered as a viable option for treatment of acne vulgaris, including on the trunk. Further studies are suggested in a larger population of patients, including adult females with acne. J Drugs Dermatol. 2017;16(6):534-538..

[Tranexamic acid as first-line emergency treatment for episodes of bradykinin-mediated angioedema induced by ACE inhibitors].

Science.gov (United States)

Beauchêne, C; Martins-Héricher, J; Denis, D; Martin, L; Maillard, H

2018-05-04

Episodes of acquired bradykinin-mediated angioedema due to angiotensin-converting enzyme (ACE) inhibitors may result in fatal outcomes. There is no consensus regarding emergency pharmacological management of these episodes. Treatment options include icatibant and C1INH concentrate. Tranexamic acid is administered for moderate episodes. Its efficacy in the treatment of ACE inhibitor-induced episodes of angioedema is not established. The aim of this retrospective study is to assess the benefits of emergency tranexamic acid administration in the management of ACE inhibitor-induced episodes of angioedema. Retrospective analysis of the medical files of patients who consulted between 2010 and 2016 in two French tertiary care hospitals for a bradykinic angioedema attributed to an ACE treatment. All of them had received tranexamic acid as a first line treatment. Thirty three patients who had experienced severe episode of angioedema were included. Twenty seven patients showed significant improvement when treated with tranexamic acid alone. The six remaining patients were treated with icatibant (5/33) or C1INH concentrate (1/33), due to partial improvement after tranexamic acid therapy. None of the patients were intubated, no fatalities were recorded and no side effects were reported. Tranexamic acid is an easily accessible and affordable therapy that may provide effective treatment for ACE inhibitor-induced episodes of angioedema. It may help while waiting for a more specific treatment (icatibant and C1INH concentrate) that is at times unavailable in emergency departments. Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Removal of cyanobacterial amino acids in water treatment by activated carbon adsorption

Czech Academy of Sciences Publication Activity Database

Čermáková, Lenka; Kopecká, Ivana; Pivokonský, Martin; Pivokonská, Lenka; Janda, V.

2017-01-01

Roč. 173, č. 1 (2017), s. 330-338 ISSN 1383-5866 Institutional support: RVO:67985874 Keywords : amino acids * activated carbon * adsorption * algal organic matter * water treatment * coagulation * microcystis aeruginosa * peptides/proteins * permanganate pre-oxidation * water treatment Subject RIV: DJ - Water Pollution ; Quality OBOR OECD: Environmental sciences (social aspects to be 5.7) Impact factor: 3.359, year: 2016

Relation between Omega 3 Fatty Acid, Iron, Zinc and Treatment of ADHD

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Maryam Shalileh

2014-10-01

Full Text Available In some studies, it is suggested that a number of dietary factors including essential fatty acid, iron and zinc deficiency, may be linked to attention-deficit/hyperactivity-disorder (ADHD. However, the exact mechanism of this relationship is yet unclear. The purpose of this study is to investigate the relationship between omega-3 fatty acids, zinc, and iron in etiopathology and management of ADHD. For the purpose of this study, Science Direct, PubMed, and Medline databases were explored and thirty-four relevant articles in english language were collected. Eighteen out of twenty-two studies confirmed the relationship between omega-3 fatty acid and ADHD. In addition, the role of insufficient store of iron in developing ADHD symptoms and the positive effect of iron supplement in improvement of ADHD behavioral symptoms have been shown. Also, plasma zinc concentration in children with ADHD was lower than the normal population, and the effect of zinc supplement on reducing on attentive-deficit symptoms was contradictory. Although polyunsaturated fatty acids (PUFA and iron supplements are not suggested as main treatment for ADHD, but if future studies confirm the positive results of that, use of these supplements as complementary treatment will affect ADHD symptoms. Considering the little amount of studies on zinc, more research is necessary.

Combined treatment with caffeic and ferulic acid from Baccharis uncinella C. DC. (Asteraceae) protects against metabolic syndrome in mice.

Science.gov (United States)

Bocco, B M; Fernandes, G W; Lorena, F B; Cysneiros, R M; Christoffolete, M A; Grecco, S S; Lancellotti, C L; Romoff, P; Lago, J H G; Bianco, A C; Ribeiro, M O

2016-03-01

Fractionation of the EtOH extract from aerial parts of Baccharis uncinella C. DC. (Asteraceae) led to isolation of caffeic and ferulic acids, which were identified from spectroscopic and spectrometric evidence. These compounds exhibit antioxidant and anti-inflammatory properties and have been shown to be effective in the prevention/treatment of metabolic syndrome. This study investigated whether the combined treatment of caffeic and ferulic acids exhibits a more significant beneficial effect in a mouse model with metabolic syndrome. The combination treatment with caffeic and ferulic acids was tested for 60 days in C57 mice kept on a high-fat (40%) diet. The data obtained indicated that treatment with caffeic and ferulic acids prevented gain in body weight induced by the high-fat diet and improved hyperglycemia, hypercholesterolemia and hypertriglyceridemia. The expression of a number of metabolically relevant genes was affected in the liver of these animals, showing that caffeic and ferulic acid treatment results in increased cholesterol uptake and reduced hepatic triglyceride synthesis in the liver, which is a likely explanation for the prevention of hepatic steatosis. In conclusion, the combined treatment of caffeic and ferulic acids displayed major positive effects towards prevention of multiple aspects of the metabolic syndrome and liver steatosis in an obese mouse model.

Nucleic acid labeling with [3H]orotic acid and nucleotide profile in rats in protein deprivation, enteral and parenteral essential amino acid administration, and 5-fluorouracil treatment

International Nuclear Information System (INIS)

Jakobsson, B.; el Hag, I.A.; Andersson, M.; Christensson, P.I.; Stenram, U.

1990-01-01

Rats were fed a 0% casein diet for 1 week, with or without enteral or parenteral administration of essential amino acids, or a 25% casein diet, in one group supplemented with 5-fluorouracil treatment. Ninety minutes before sacrifice the rats were given a tracer of [3H]orotic acid. Incorporation into the acid soluble fraction, RNA, and DNA was determined in liver, small intestine, bone marrow, and kidney. Nucleotide profile was examined in liver and intestine. Protein deficiency caused inter alia a decrease in body weight; a decrease in RNA/DNA ratio and an increase in the specific RNA labeling in liver and kidney; an altered nucleotide profile in the liver; an increase in the nucleotide/DNA and RNA/DNA ratios and a decrease in the specific labeling of the acid soluble fraction, RNA, and DNA in the bone marrow. These changes were prevented to the same extent by giving essential amino acids, either orally or intravenously. The minor changes in intestinal nucleotide profile in protein deprivation were prevented to a slightly larger extent by amino acids orally than parenterally. 5-Fluorouracil treatment gave a decrease in the RNA/DNA ratio in the liver and kidney but an increase in the nucleotide/DNA and RNA/DNA ratios in the bone marrow. Nucleotide profiles were unaltered. The amount of DNA per gram of tissue decreased in bone marrow and increased in kidney. Parenteral administration per se resulted in almost no changes

Efficacy of salicylic acid in the treatment of digital dermatitis in dairy cattle

DEFF Research Database (Denmark)

Schultz, N.; Capion, N.

2013-01-01

Digital dermatitis (DD) is one of the most important causes of lameness in dairy cattle worldwide. The objective of this study was to evaluate the efficacy of salicylic acid in the treatment of the disease. A total of 201 DD lesions from 173 cows from four commercial dairy herds were evaluated...... at day 0 during routine hoof trimming and were allocated into two groups, namely, a control group given chlortetracycline spray, and a treatment group given 10 g of salicylic acid powder applied topically within a bandage. Pain, lesion size and clinical appearance (scored MO to M4) were evaluated on days...... the control group were 2.2 times more likely (P = 0.09) to have a pain score equal to 2 by day 14. The proportion of lesions getting smaller by days 14 and 34 was 2.5 times higher (P salicylic acid should be considered as an alternative...

In-situ treatment of acid mine waters using fluidized bed ash: Field study

International Nuclear Information System (INIS)

Everett, J.W.; Canty, G.A.

1999-01-01

A slurry of mine water and fluidized bed ash (FBA) was injected into an abandoned coal mine in eastern Oklahoma in July 1997. Oil-field technology was used to inject 1.8 Gg (418 tons) of FBA through five wells in 15 hours. Prior to injection the seep water had a pH of 4.4, was net acidic (acidity over 400 mg/L as CaCO 3 ), and had relatively high metal concentrations (in mg/L: Fe-200; Mn-7; and Al-6). After injection, during the period of effective treatment, the seep water had a pH above 6.0, less net acidity, and had lower metals concentrations (in mg/L: Fe-120; Mn-5; and Al-< PQL). When the treated seep water exited the mine, the dissolved metals oxidized and hydrolyzed. As the metals precipitated, the alkalinity introduced by the FBA was consumed and the pH dropped. However, the seep water characteristics upon entering the receiving stream were improved, compared to pre-injection. The resulting seep water quality is such that it is more amenable to further treatment by passive treatment methods, such as anoxic limestone drains or wetlands. Alkaline injection is a finite treatment process. Eventually, the added alkalinity is exhausted, at which time the seep returns to pre-injection conditions, necessitating another injection of ash. For the study discussed in this paper, the treatment lasted approximately 15 months. While the amount of alkalinity added to the mine could have potentially treated much more than a year's volume of seep water, it is believed that much of the injected alkalinity was unavailable in backwater areas in the mine. This alkalinity contributed little, if any, to the treatment of water flowing through the mine. Mine hydrology, especially during injection are crucial to treatment longevity

Tranexamic acid treatment of hemothorax in two patients with malignant mesothelioma

NARCIS (Netherlands)

de Boer, W. A.; Koolen, M. G.; Roos, C. M.; ten Cate, J. W.

1991-01-01

Patients with malignant mesothelioma may present with hemothorax. We used a combination of oral and intrapleural tranexamic acid to treat two patients with this severe complication. Initiation of treatment with this potent anti-fibrinolytic drug resulted in rapid reduction of bleeding and of

Treatment with Docosahexaenoic Acid, but Not Eicosapentaenoic Acid, Delays Ca2+-Induced Mitochondria Permeability Transition in Normal and Hypertrophied Myocardium

OpenAIRE

Khairallah, Ramzi J.; O'Shea, Karen M.; Brown, Bethany H.; Khanna, Nishanth; Des Rosiers, Christine; Stanley, William C.

2010-01-01

Intake of fish oil containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) prevents heart failure; however, the mechanisms are unclear. Mitochondrial permeability transition pore (MPTP) opening contributes to myocardial pathology in cardiac hypertrophy and heart failure, and treatment with DHA + EPA delays MPTP opening. Here, we assessed: 1) whether supplementation with both DHA and EPA is needed for optimal prevention of MPTP opening, and 2) whether this benefit occurs in hyper...

Effects of sulphuric acid and hot water treatments on seed ...

African Journals Online (AJOL)

A study was carried out to investigate the effects of sulphuric acid and hot water treatments on the germination of Tamarind (Tamarindus indica L). Seeds were placed on moistened filter papers in 28 cm diameter Petri dishes under laboratory condition for germination. 330 seeds of T. indica (10 seeds per Petri dish) with ...

Zonun’s regime (35% glycolic acid peel with microneedling followed by tretinoin 0.05% plus glycolic acid 12% application followed by salicylic acid 30% peeling for treatment of acne scars: a pilot study

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Zonunsanga

2015-01-01

Full Text Available Introduction: Acne scars are the result of inflammation within the dermis brought on by acne. The scar is created by the wound trying to heal itself resulting in too much collagen in one spot. Current treatment available are not much satisfactory. Microneedling injure the dermis, thereby stimulating collagen formation. Glycolic acid acts as vehicle for delivery of drugs to dermis: in addition to that, it also has a role in collagen induction. Tretinoin helps in collagen formation. Salicylic acid remodel the superficial skin after the treatment. Material and Methods: A total of 4 patients in which 3 out of 4 patient, grade 3 acne scars and 1 out of 4 had grade 2 scar were treated with the regime. After taking consent 35% Glycolic acid peeling was done followed by microneedling. From the next day 12% Glycolic acid plus 0.05% Tretinoin is applied once a day for 2 months. After 2 months 30% Salicylic acid peeling is done. Photographs were taken before treatment, after 1 month and after 2 months of completion of the therapy and compared. Objective assessment was done according to Global Acne Scarring Classification. Result: subjectively 2 patients reported excellent response and 2 patients reported good response. Objectively, all patients showed good to excellent response. Conclusion: Zonun’s regime may be effective for treatment of acne scars.

Assessment of clinical practice guideline methodology for the treatment of knee osteoarthritis with intra-articular hyaluronic acid.

Science.gov (United States)

Altman, Roy D; Schemitsch, Emil; Bedi, Asheesh

2015-10-01

Clinical practice guidelines are of increasing importance in the decision making for the treatment of knee osteoarthritis. Inconsistent recommendations regarding the use of intra-articular hyaluronic acid for the treatment of knee osteoarthritis have led to confusion among treating physicians. Literature search to identify clinical practice guidelines that provide recommendations regarding the use of intra-articular hyaluronic acid treatment for knee osteoarthritis was conducted. Included guidelines were appraised using the AGREE II instrument. Guideline development methodologies, how the results were assessed, the recommendation formation, and work group composition were summarized. Overall, 10 clinical practice guidelines were identified that met our inclusion criteria. AGREE II domain scores were variable across the included guidelines. The methodology utilized across the guidelines was heterogeneous regarding the evidence inclusion criteria, analysis of evidence results, formulation of clinical practice recommendations, and work group composition. The recommendations provided by the guidelines for intra-articular hyaluronic acid treatment for knee osteoarthritis are highly inconsistent as a result of the variability in guideline methodology. Overall, 30% of the included guidelines recommended against the use of intra-articular hyaluronic acid in the treatment of knee osteoarthritis, while 30% deemed the treatment an appropriate intervention under certain scenarios. The remaining 40% of the guidelines provided either an uncertain recommendation or no recommendation at all, based on the high variability in reviewed evidence regarding efficacy and trial quality. There is a need for a standard "appropriate methodology" that is agreed upon for osteoarthritis clinical practice guidelines in order to prevent the development of conflicting recommendations for intra-articular hyaluronic acid treatment for knee osteoarthritis, and to assure that treating physicians who

Gambogic acid-loaded biomimetic nanoparticles in colorectal cancer treatment

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Zhang Z

2017-02-01

Full Text Available Zhen Zhang,1 Hanqing Qian,2 Mi Yang,2 Rutian Li,2 Jing Hu,1 Li Li,1 Lixia Yu,2 Baorui Liu,1,2 Xiaoping Qian1,2 1Comprehensive Cancer Center, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Traditional Chinese Medicine, 2Comprehensive Cancer Center, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute, Nanjing University, Nanjing, China Abstract: Gambogic acid (GA is expected to be a potential new antitumor drug, but its poor aqueous solubility and inevitable side effects limit its clinical application. Despite these inhe­rent defects, various nanocarriers can be used to promote the solubility and tumor targeting of GA, improving antitumor efficiency. In addition, a cell membrane-coated nanoparticle platform that was reported recently, unites the customizability and flexibility of a synthetic copolymer, as well as the functionality and complexity of natural membrane, and is a new synthetic biomimetic nanocarrier with improved stability and biocompatibility. Here, we combined poly(lactic-co-glycolic acid (PLGA with red blood-cell membrane (RBCm, and evaluated whether GA-loaded RBCm nanoparticles can retain and improve the antitumor efficacy of GA with relatively lower toxicity in colorectal cancer treatment compared with free GA. We also confirmed the stability, biocompatibility, passive targeting, and few side effects of RBCm-GA/PLGA nanoparticles. We expect to provide a new drug carrier in the treatment of colorectal cancer, which has strong clinical application prospects. In addition, the potential antitumor drug GA and other similar drugs could achieve broader clinical applications via this biomimetic nanocarrier. Keywords: gambogic acid, nanocarriers, RBCm-GA/PLGA nanoparticles, colorectal cancer

Ursodeoxycholic Acid and Atorvastatin in the Treatment of Nonalcoholic Steatohepatitis

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Murat Kiyici

2003-01-01

Full Text Available BACKGROUND/AIMS: Nonalcoholic steatohepatitis (NASH is a serious disorder with the potential to gradually progress to cirrhosis. It is generally associated with obesity, diabetes and hyperlipidemia. Currently, there is no established therapy for NASH. The aim of the present study was to evaluate the effectiveness of atorvastatin and ursodeoxycholic acid (UDCA in the treatment of NASH.

COMPOST-FREE BIOLOGICAL TREATMENT OF ACID ROCK DRAINAGE, TECHNICAL EVALUATION BULLETIN

Science.gov (United States)

As part of the Superfund Innovative Technology Evaluation (SITE) program, an evaluation of the compost-free bioreactor treatment of acid rock drainage (ARD) from the Aspen Seep was conducted at the Leviathan Mine Superfund site located in a remote, high altitude area of Alpine Co...

A clinical and histopathological comparison of the effectiveness of salicylic acid to a compound of inorganic acids for the treatment of digital dermatitis in cattle

DEFF Research Database (Denmark)

Capion, N.; Larsson, E. K.; Nielsen, O. L.

2018-01-01

; however, the demand for effective nonantibiotic alternatives is increasing. The objective was to evaluate the performance of 3 nonantibiotic topical treatments (salicylic acid and a compound of inorganic acids in a 20% solution and in a dry form) on DD in a commercial dairy herd. Within the 30-d test...... of spirochetes present in the epidermis), 2 (moderate number of spirochetes present and reaching an intermediary level in the epidermis), and 3 (large number of spirochetes present and reaching the deepest part of the epidermis or the superficial dermis). The improvement rate was 10/14 (71%) for salicylic acid......, 11/15 (73%) for the inorganic acid solution, and 8/13 (62%) for the inorganic acid powder. The analysis showed no difference among treatments. The association between clinical score and histopathological score was determined by an odds ratio. The odds ratio of a healed lesion having spirochetes...

Method of improving the decontaminating efficiency of ruthenium in evaporating treatment of nitric acid

International Nuclear Information System (INIS)

Kubota, Kanya; Yamana, Hajime; Takeda, Seiichiro.

1984-01-01

Purpose: To significantly improve the ruthenium removing efficiency in a nitric acid solution in an acid recovery system for the recovery of nitric acid from nitric acid liquid wastes through evaporating condensation. Method: Upon evaporating treatment of nitric acid solution containing ruthenium by supplying and heating the solution to a nitric acid evaporating device, hydrazine is previously added to the nitric acid solution. Hydrazine and intermediate reaction product of hydrazine such as azide causes a reduction reaction with intermediate reaction product of ruthenium tetraoxide to suppress the oxidation of ruthenium and thereby improve the decontaminating efficiency of ruthenium. The amount of hydrazine to be added is preferably between 20 - 500 mg/l and most suitably between 200 - 2000 mg/l per one liter of the liquid in the evaporating device. (Seki, T.)

PERIODS OF VERTEBRAL COLUMN SENSITIVITY TO BORIC ACID TREATMENT IN CD-1 MICE IN UTERO

Science.gov (United States)

Periods of vertebral column sensitivity to boric acid treatment in CD-1 mice in utero.Cherrington JW, Chernoff N.Department of Toxicology, North Carolina State University, Raleigh, NC 27695, USA. jana_cherrington@hotmail.comBoric acid (BA) has many uses as...

Effect of Omega-3 Fatty Acids Treatment on Insulin Resistance

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Mogoş Tiberius

2014-12-01

Full Text Available Background and aims: Insulin resistance (IR is a common pathogenic factor of several diseases: diabetes mellitus, the metabolic syndrome, arterial hypertension, atherosclerosis, dyslipidemia, etc. There are many therapeutic factors involved in decreasing IR. Among them we mention metformin, pioglitazone, physical activity, weight loss, diet, etc. In the last decade, there are more observations of the influence of polyunsaturated fatty acids on IR. The most powerful seem to be omega-3 fatty acids. In our study, we wanted to asses if the administration of omega-3 fatty acids is involved in modifying IR. Materials and methods: We evaluated 126 diabetic patients with IR from January 2011 until July 2014. The study was open-label and non-randomized. For the determination of IR we used the HOMA-IR method. Results: For both males and females there was a regression of HOMA-IR during the 4 weeks of treatment with omega-3 and also after 2 weeks after stopping the administration of these fatty acids. The decrease of HOMA-IR was statistically significant (p<0.05. The statistic result observed in the next 2 weeks after stopping administration of omega-3 was also significant (p<0.05.

Glycyrrhizic Acid in the Treatment of Liver Diseases: Literature Review

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Jian-yuan Li

2014-01-01

Full Text Available Glycyrrhizic acid (GA is a triterpene glycoside found in the roots of licorice plants (Glycyrrhiza glabra. GA is the most important active ingredient in the licorice root, and possesses a wide range of pharmacological and biological activities. GA coupled with glycyrrhetinic acid and 18-beta-glycyrrhetic acid was developed in China or Japan as an anti-inflammatory, antiviral, and antiallergic drug for liver disease. This review summarizes the current biological activities of GA and its medical applications in liver diseases. The pharmacological actions of GA include inhibition of hepatic apoptosis and necrosis; anti-inflammatory and immune regulatory actions; antiviral effects; and antitumor effects. This paper will be a useful reference for physicians and biologists researching GA and will open the door to novel agents in drug discovery and development from Chinese herbs. With additional research, GA may be more widely used in the treatment of liver diseases or other conditions.

Study of immobilization of waste from treatment of acid waters of a uranium mining facility

International Nuclear Information System (INIS)

Goda, R.T.; Oliveira, A.P. de; Silva, N.C. da; Villegas, R.A.S.; Ferreira, A.M.

2017-01-01

This study aimed to produce scientific and technical knowledge aiming at the development of techniques to immobilize the waste generated in the treatment of acid waters in the UTM-INB Caldas uranium mining and processing facility using Portland cement. This residue (calcium diuranate - DUCA) contains uranium compounds and metal hydroxides in a matrix of calcium sulfate. It is observed that this material, in contact with the lake of acid waters of the mine's own pit, undergoes resolubilization and, therefore, changes the quality of the acidic water contained therein, changing the treatment parameters. For the study of immobilization of this residue, the mass of water contained in both the residue deposited in the pit of the mine and in the pulp resulting from the treatment of the acid waters was determined. In addition, different DUCA / CEMENT / WATER ratios were used for immobilization and subsequent mechanical strength and leaching tests. The results showed that in the immobilized samples with 50% cement mass condition, no uranium was detected in the leaching tests, and the mechanical strength at compression was 9.4 MPa, which indicates that more studies are needed, but indicate a good capacity to immobilize uranium in cement

Effects of gamma irradiation and ozone treatment on microbial decontamination and fatty acid compositions of aloe and pollen powders

International Nuclear Information System (INIS)

Yook, H.S.; Chung, Y.J.; Kim, J.O.; Kwon, O.J.; Byun, M.W.

1997-01-01

The comparative effects of gamma irradiation and ozone treatment on the microbial inactivation and fatty acid composition were investigated for improving hygienic quality of aloe and pollen powders. Gamma irradiation at 10 kGy resulted in sterilizing total aerobic bacteria, molds and coliforms below detective levels, while ozone treatment for 8 hours up to 18 ppm did not sufficiently eliminate the microorganisms of aloe and pollen powders. The compositions of fatty acid were not significantly changed by gamma irradiation up to 10 kGy. However, ozone treatment markedly decreased unsaturated fatty acids by approximately 20-80% in contents, whereas it significantly increased saturated fatty acids (p<0.05)

Tomato type and post-treatment water rinse affect efficacy of acid washes against Salmonella enterica inoculated on stem scars of tomatoes and product quality.

Science.gov (United States)

Fan, Xuetong; Gurtler, Joshua B; Sokorai, Kimberly J B

2018-09-02

A study was conducted to evaluate the effects of post-treatment rinsing with water on the inactivation efficacy of acid treatments against Salmonella inoculated onto stem scar areas of two types of tomatoes. In addition, impact on fruit quality was investigated during 21 days post-treatment storage at 10 °C. A four-strain cocktail of Salmonella enterica (S. Montevideo, S. Newport, S. Saintpaul, and S. Typhimurium) was inoculated onto stem scar areas of grape and large round tomatoes. The inoculated fruits were then treated for 2 min with the following solutions: water, 2% lactic acid +2% acetic acid +2% levulinic acid, 1.7% lactic acid +1.7% acetic acid +1.7% levulinic acid, and 3% lactic acid +3% acetic acid. After treatments, half of the fruits were rinsed with water while another half were not rinsed. Non-inoculated grape tomatoes for quality analysis were treated with the same solutions with and without subsequent water rinse. Results demonstrated that the acid combinations reduced populations of Salmonella enterica on the stem scar area of grape tomatoes by 1.52-1.90 log CFU/fruit, compared with the non-treated control while water wash and rinse removed the bacterium by only 0.23-0.30 log CFU/fruit. On the stem scar of large round tomatoes, the same acid treatments achieved 3.54 log CFU/fruit reduction of the pathogen. The varying response to the acid washes between grape and large round tomatoes seems to be related to the differences in surface characteristics of stem scar areas observed with SEM. Rinsing with water after acid combination treatments did not significantly affect the efficacy of the treatments in either grape or large round tomatoes. Acidic off-odor was detected on fruits treated with acid combination without water rinse 1 day after treatment while water rinse eliminated the off-odor. The acid treatments with and without water rinse did not consistently affect appearance, color, firmness, or lycopene or ascorbic acid contents of

Cyclosporine A and palmitic acid treatment synergistically induce cytotoxicity in HepG2 cells

Energy Technology Data Exchange (ETDEWEB)

Luo, Yi, E-mail: yi.luo@pfizer.com; Rana, Payal; Will, Yvonne

2012-06-01

Immunosuppressant cyclosporine A (CsA) treatment can cause severe side effects. Patients taking immunosuppressant after organ transplantation often display hyperlipidemia and obesity. Elevated levels of free fatty acids have been linked to the etiology of metabolic syndromes, nonalcoholic fatty liver and steatohepatitis. The contribution of free fatty acids to CsA-induced toxicity is not known. In this study we explored the effect of palmitic acid on CsA-induced toxicity in HepG2 cells. CsA by itself at therapeutic exposure levels did not induce detectible cytotoxicity in HepG2 cells. Co-treatment of palmitic acid and CsA resulted in a dose dependent increase in cytotoxicity, suggesting that fatty acid could sensitize cells to CsA-induced cytotoxicity at the therapeutic doses of CsA. A synergized induction of caspase-3/7 activity was also observed, indicating that apoptosis may contribute to the cytotoxicity. We demonstrated that CsA reduced cellular oxygen consumption which was further exacerbated by palmitic acid, implicating that impaired mitochondrial respiration might be an underlying mechanism for the enhanced toxicity. Inhibition of c-Jun N-terminal kinase (JNK) attenuated palmitic acid and CsA induced toxicity, suggesting that JNK activation plays an important role in mediating the enhanced palmitic acid/CsA-induced toxicity. Our data suggest that elevated FFA levels, especially saturated FFA such as palmitic acid, may be predisposing factors for CsA toxicity, and patients with underlying diseases that would elevate free fatty acids may be susceptible to CsA-induced toxicity. Furthermore, hyperlipidemia/obesity resulting from immunosuppressive therapy may aggravate CsA-induced toxicity and worsen the outcome in transplant patients. -- Highlights: ► Palmitic acid and cyclosporine (CsA) synergistically increased cytotoxicity. ► The impairment of mitochondrial functions may contribute to the enhanced toxicity. ► Inhibition of JNK activity attenuated

Hepatic arachidonic acid metabolism is disrupted after hexachlorobenzene treatment

International Nuclear Information System (INIS)

Billi de Catabbi, Silvia C.; Faletti, Alicia; Fuentes, Federico; San Martin de Viale, Leonor C.; Cochon, Adriana C.

2005-01-01

Hexaclorobenzene (HCB), one of the most persistent environmental pollutants, can cause a wide range of toxic effects including cancer in animals, and hepatotoxicity and porphyria both in humans and animals. In the present study, liver microsomal cytochrome P450 (CYP)-dependent arachidonic acid (AA) metabolism, hepatic PGE production, and cytosolic phospholipase A 2 (cPLA 2 ) activity were investigated in an experimental model of porphyria cutanea tarda induced by HCB. Female Wistar rats were treated with a single daily dose of HCB (100 mg kg -1 body weight) for 5 days and were sacrificed 3, 10, 17, and 52 days after the last dose. HCB treatment induced the accumulation of hepatic porhyrins from day 17 and increased the activities of liver ethoxyresorufin O-deethylase (EROD), methoxyresorufin O-demethylase (MROD), and aminopyrine N-demethylase (APND) from day 3 after the last dose. Liver microsomes from control and HCB-treated rats generated, in the presence of NADPH, hydroxyeicosatetraenoic acids (HETEs), epoxyeicosatrienoic acids (EETs), 11,12-Di HETE, and ω-OH/ω-1-OH AA. HCB treatment caused an increase in total NADPH CYP-dependent AA metabolism, with a higher response at 3 days after the last HCB dose than at the other time points studied. In addition, HCB treatment markedly enhanced PGE production and release in liver slices. This HCB effect was time dependent and reached its highest level after 10 days. At this time cPLA 2 activity was shown to be increased. Unexpectedly, HCB produced a significant decrease in cPLA 2 activity on the 17th and 52nd day. Our results demonstrated for the first time that HCB induces both the cyclooxygenase and CYP-dependent AA metabolism. The effects of HCB on AA metabolism were previous to the onset of a marked porphyria and might contribute to different aspects of HCB-induced liver toxicity such as alterations of membrane fluidity and membrane-bound protein function. Observations also suggested that a possible role of cPLA 2 in

Treatment of an adrenomyeloneuropathy patient with Lorenzo's oil and supplementation with docosahexaenoic acid-A case report

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Bergh Jacobus J

2011-08-01

Full Text Available Abstract This is a case report of adrenomyeloneuropathy (AMN, the adult variant of adrenoleukodystryphy (ALD. The diagnoses in the patient, aged 34, was confirmed via increased serum very long chain fatty acid concentration (VLCFA. Treatment started with the cholesterol lowering drug, atorvastatin, followed by add-on therapy with Lorenzo's oil (LO and finally supplementation with docosahexaenoic acid (DHA. The magnetic resonance imaging (MRI scan of the AMN patient before DHA treatment, already showed abnormal white matter in the brain. Although the MRI showed no neurological improvement after 6 months of DHA treatment, no selective progression of demyelination was detected in the AMN patient. Contrary to what was expected, LO failed to sustain or normalize the VLCFA levels or improve clinical symptoms. It was however, shown that DHA supplementation in addition to LO, increased DHA levels in both plasma and red blood cells (RBC. Additionally, the study showed evidence that the elongase activity in the elongation of eicosapentaenoic acid (EPA to docosapentaenoic acid (DPA might have been significantly compromised, due to the increased DHA levels.

Improving the Keeping Quality and Vase Life of Cut Alstroemeria Flowers by Pre and Post-harvest Salicylic Acid Treatments

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Elnaz SOLEIMANY-FARD

2013-08-01

Full Text Available Keeping quality and length of vase life are important factors for evaluation of cut flowers quality, for both domestic and export markets. Studding the effect of pre- and post-harvest salicylic acid applications on keeping quality and vase life of cut alstroemeria flowers during vase period is the approach taken. Aqueous solutions of salicylic acid at 0.0 (with distilled water, 1, 2 and 3 mM were sprayed to run-off (approximately 500 mL per plant, about two weeks before flowers harvest. The cut flowers were harvested in the early morning and both of cut flowers treated (sprayed and untreated were kept in vase solutions containing salicylic acid at 0.0 (with distilled water, 1, 2 and 3 mM. Sucrose at 4% was added to all treatments as a base solution. The changes in relative fresh weight, water uptake, water loss, water balance, total chlorophyll content and vase life were estimated during vase period. The results showed that the relative fresh weight, water uptake, water balance, total chlorophyll content and vase life decreased significantly while the water loss increased significantly during experiment for all treatments. A significant difference between salicylic acid and control treatments in all measured parameters is observed. During vase period, the salicylic acid treatments maintained significantly a more favourable relative fresh weight, water uptake, water balance, total chlorophyll content and supressed significantly water loss, as compared to control treatment. Also, the results showed that the using salicylic acid increased significantly the vase life cut alstroemeria flowers, over control. The highest values of measured parameters were found when plants were treated by pre + post-harvest application of salicylic acid at 3 mM. The result revealed that the quality attributes and vase life of cut alstroemeria flowers were improved by the use of salicylic acid treatment.

Cadmium Phytoavailability and Enzyme Activity under Humic Acid Treatment in Fluvo-aquic Soil

Science.gov (United States)

Liu, Borui; Huang, Qing; Su, Yuefeng

2018-01-01

A pot experiment was conducted to investigate the cadmium (Cd) availability to pakchois (Brassica chinensis L.) as well as the enzyme activities in fluvo-aquic soil under humic acid treatment. The results showed that the phytoavailability of Cd in soil decreased gradually as humic acid concentration rose (0 to 12 g·kg-1), while the activities of urease (UE), alkaline phosphatase (ALP) and catalase (CAT) kept increasing (P enzymes due to the Cd pollution. In conclusion, humic acid is effective for the reduction of both Cd phytoavailability and the damage to enzyme activities due to Cd pollution in fluvo-aquic soil

Ursodeoxycholic acid for treatment of primary sclerosing cholangitis: a placebo-controlled trial

NARCIS (Netherlands)

Beuers, U.; Spengler, U.; Kruis, W.; AYDEMIR, U.; WIEBECKE, B.; HELDWEIN, W.; WEINZIERL, M.; Pape, G. R.; Sauerbruch, T.; Paumgartner, G.

1992-01-01

The efficacy and safety of ursodeoxycholic acid for the treatment of primary sclerosing cholangitis were evaluated in a prospective, randomized, double-blind, placebo-controlled trial. Fourteen patients with primary sclerosing cholangitis documented by cholestatic serum enzyme pattern, liver

Treatment of periorbital dark circles: Comparative study of chemical peeling with a combination of trichloroacetic acid and lactic acid versus carboxytherapy

OpenAIRE

Arwa Mohammad Hassan; Ghada Fawzy Hassan; Hedaya Yousef Aldalies; Gamal Mohammad El Maghraby

2016-01-01

Periorbital dark circles (PODC) are a common worldwide cosmetic problem. It is difficult to treat due to complications in its pathogenesis and aetiology. Available lines of treatment for PODC include whitening creams, topical retinoid acid, chemical peeling, laser therapy, carboxytherapy, autologous fat transplantation, injectable fillers and surgery (blepharoplasty).The aim of this study isto evaluate and compare the efficacy of chemical peels using trichloroacetic acid (3.75%) and lactic ac...

Gene expression profiling in human precision-cut liver slices upon treatment with the FXR agonist obeticholic acid [human

NARCIS (Netherlands)

IJssennagger, Noortje; Janssen, Aafke; Mil, van Saskia; Kersten, Sander

2016-01-01

Background: The bile acid-activated farnesoid X receptor (FXR) is a nuclear receptor regulating bile acid, glucose and cholesterol homeostasis. Obeticholic acid (OCA; also known as INT-747 or 6α-ethyl-chenodeoxycholic acid), a promising drug for the treatment of non-alcoholic steatohepatitis (NASH)

Gene expression profiling in human precision-cut liver slices upon treatment with the FXR agonist obeticholic acid [mouse

NARCIS (Netherlands)

IJssennagger, Noortje; Janssen, Aafke; Kersten, Sander; Mil, van S.W.C.

2016-01-01

Background: The bile acid-activated farnesoid X receptor (FXR) is a nuclear receptor regulating bile acid, glucose and cholesterol homeostasis. Obeticholic acid (OCA; also known as INT-747 or 6α-ethyl-chenodeoxycholic acid), a promising drug for the treatment of non-alcoholic steatohepatitis (NASH)

Effect of acid treatment on thermal extraction yield in ashless coal production

Energy Technology Data Exchange (ETDEWEB)

Chunqi Li; Toshimasa Takanohashi; Takahiro Yoshida; Ikuo Saito; Hideki Aoki; Kiyoshi Mashimo [National Institute of Advanced Industrial Science and Technology, Tsukuba (Japan). Institute for Energy Utilization

2004-04-01

Coals of different ranks were acid-treated in aqueous methoxyethoxy acetic acid (MEAA), acetic acid (AA), and HCl. The acid-treated coals were extracted with polar N-methyl-2-pyrrolidinone (NMP) and nonpolar 1-methylnaphthalene (1MN) solvents at temperatures from 200 to 360{sup o}C for 10 60 min. The thermal extraction yields with NMP for some acid-treated low-rank coals increased greatly; for example, the extraction yield for Wyodak coal (%C; 75.0%) increased from 58.4% for the raw coal to 82.9% for coal treated in 1.0 M MEAA. Conversely, the extraction yields changed minimally for all the acid-treated coals extracted in 1-MN. The type and concentration of acid affected the extraction yield when NMP was used as the extraction solvent. With increasing MEAA concentration from 0.01 to 0.1 M, the extraction yield for Wyodak coal increased from 66.3 to 81.4%, and subsequently did not change clearly with concentration. Similar changes in the extraction yield with acid concentration were also observed with AA and HCl. The de-ashing ratio for coals acid-treated in MEAA, AA, and HCl also increased greatly with concentration from 0.01 to 0.1 M, which corresponded to the change in the thermal extraction yield in NMP. For the acid-treated coals, high extraction yields were obtained at lower extraction temperatures and shorter extraction times than for the raw coal. The mechanisms for the acid treatment and thermal extraction are discussed. 27 refs., 6 figs., 3 tabs.

New developments in the treatment of primary biliary cholangitis – role of obeticholic acid

Directory of Open Access Journals (Sweden)

Jhaveri MA

2017-08-01

Full Text Available Manan A Jhaveri, Kris V Kowdley Liver Care Network, Swedish Medical Center, Seattle, WA, USA Abstract: Primary biliary cholangitis (PBC is a chronic autoimmune cholestatic liver disease that predominantly affects women in early to middle age. It is typically associated with autoantibodies to mitochondrial antigens and results in immune-mediated destruction of small and medium-sized intrahepatic bile ducts leading to cholestasis, hepatic fibrosis and may progress to cirrhosis or hepatic failure and, in some cases, hepatocellular carcinoma. The clinical presentation and the natural history of PBC have improved over the years due to recognition of earlier widespread use of ursodeoxycholic acid (UDCA; about one-third of patients show suboptimal biochemical response to UDCA with poor prognosis. Until recently, UDCA was the only US Food and Drug Administration approved agent for this disease for more than two decades; obeticholic acid was approved in 2016 for treatment of patients with PBC with a suboptimal response or intolerance to UDCA. Currently, liver transplantation is the most effective treatment modality for PBC patients with end-stage liver disease. This review will focus on the recent advances in therapy of primary biliary cholangitis, with emphasis on obeticholic acid. Keywords: primary biliary cholangitis, obeticholic acid, ursodeoxycholic acid

Heavy metal extraction from PCB wastewater treatment sludge by sulfuric acid

International Nuclear Information System (INIS)

Kuan, Yu-Chung; Lee, I-Hsien; Chern, Jia-Ming

2010-01-01

Heavy metals contaminated wastewater sludge is classified as hazardous solid waste and needs to be properly treated to prevent releasing heavy metals to the environment. In this study, the wastewater treatment sludge from a printed circuit board manufacturing plant was treated in a batch reactor by sulfuric acid to remove the contained heavy metals. The effects of sulfuric acid concentration and solid to liquid ratio on the heavy metal removal efficiencies were investigated. The experimental results showed that the total and individual heavy metal removal efficiencies increased with increasing sulfuric acid concentration, but decreased with increasing solid to liquid ratio. A mathematical model was developed to predict the residual sludge weights at varying sulfuric concentrations and solid to liquid ratios. The trivalent heavy metal ions, iron and chromium were more difficult to be removed than the divalent ions, copper, zinc, nickel, and cadmium. For 5 g/L solid to liquid ratio, more than 99.9% of heavy metals can be removed from the sludge by treating with 0.5 M sulfuric acid in 2 h.

Novel passive co-treatment of acid mine drainage and municipal wastewater.

Science.gov (United States)

Strosnider, William H J; Winfrey, Brandon K; Nairn, Robert W

2011-01-01

A laboratory-scale, four-stage continuous-flow reactor system was constructed to test the viability of high-strength acid mine drainage (AMD) and municipal wastewater (MWW) passive co-treatment. Synthetic AMD of pH 2.6 and acidity of 1870 mg L(-1) as CaCO3 equivalent containing a mean 46, 0.25, 2.0, 290, 55, 1.2, and 390 mg L(-1) of Al, As, Cd, Fe, Mn, Pb, and Zn, respectively, was added at a 1:2 ratio with raw MWW from the City of Norman, OK, to the system which had a total residence time of 6.6 d. During the 135-d experiment, dissolved Al, As, Cd, Fe, Mn, Pb, and Zn concentrations were consistently decreased by 99.8, 87.8, 97.7, 99.8, 13.9, 87.9, and 73.4%, respectively, pH increased to 6.79, and net acidic influent was converted to net alkaline effluent. At a wasting rate of 0.69% of total influent flow, the system produced sludge with total Al, As, Cd, Cr, Cu, Fe, Pb, and Zn concentrations at least an order of magnitude greater than the influent mix, which presents a metal reclamation opportunity. Results indicate that AMD and MWW passive co-treatment is a viable approach to use wastes as resources to improve water quality with minimal use of fossil fuels and refined materials.

Critical appraisal of the use of alpha lipoic acid (thioctic acid in the treatment of symptomatic diabetic polyneuropathy

Directory of Open Access Journals (Sweden)

McIlduff CE

2011-09-01

Full Text Available Courtney E McIlduff, Seward B RutkoveDepartment of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USABackground: The most common of the neuropathies associated with diabetes mellitus, diabetic sensorimotor polyneuropathy (DSPN is a syndrome of diffuse, length-dependent, symmetric nerve dysfunction. The condition is linked with substantial morbidity, frequent healthcare utilization, and compromised quality of life due to related discomfort. Correspondingly, antidepressants, anticonvulsants, and opioids are regularly prescribed with the goal of pain control. However, the agents rarely provide complete pain relief and fail to address progression of the disorder. Whereas strict blood glucose control can slow the onset and worsening of DSPN, near-normoglycemia is not easily attainable. Evidence implicating oxidative processes in the pathogenesis of DSPN offers one potentially important therapeutic avenue. Due to its properties as a potent antioxidant, alpha lipoic acid (ALA could mitigate the development of DSPN and attenuate resultant symptoms and signs. Approved for treatment of DSPN in Germany, the agent is not more widely used due to uncertainty about its efficacy and reported adverse effects. Here we review the effectiveness and tolerability of ALA in the treatment of symptomatic DSPN.Methods: The MEDLINE, EMBASE, and Cochrane Library databases were searched for English-language literature on the topic. Randomized, blinded studies comparing parenteral and oral ALA with placebo in the treatment of peripheral neuropathy in diabetic adults were selected. Analysis included studies with a level of evidence of at least 2b.Results: The current appraisal summarizes data from 1160 participants in the ALADIN, SYDNEY, ORPIL, SYDNEY 2, and ALADIN III trials. In four of the studies, ALA provided significant improvement in manifestations of DSPN.Conclusion: Treatment with ALA 600 mg iv daily for 3 weeks represents a well-tolerated and effective

[Treatment of interstitial cystitis by intravesical instillation of hyaluronic acid: A prospective study on 31 patients].

Science.gov (United States)

Van Agt, S; Gobet, F; Sibert, L; Leroi, A-M; Grise, P

2011-03-01

We evaluate the efficacy of hyaluronate acid instillation for treatment of interstitial cystitis (IC). From March 2008 to May 2009, a prospective study included 31 patients. We used the new definition of IC established by the ICS in 2002. Patients have a urinalysis, a cystoscopy, a hydrodistension test and bladder biopsies. The urodynamic evaluation was not systematic. Patients received weekly six instillations of 40mg (50ml) intravesical hyaluronate acid. We evaluated the efficacy and safety of treatment with two specific questionnaires of interstitial cystitis filled before and after 6 weeks of treatment: the O'Leary-Sant and Pelvic pain and Urgency/Frequency (PUF). Four groups were defined: good response, partial response, poor response and no response. They were composed by 14 patients (45%), two (7%), seven (22%) and eight patients (26%). We obtained 52% positive response (good response and partial response) after 6 weeks of treatment. Patients with cystoscopy and histology abnormal had a response rate of 60%. No serious side effects were observed. Hyaluronate acid has a place in the treatment of interstitial cystitis with an efficiency comparable to other treatments and good tolerance. The response rate to treatment can be improved by better selection of patients, particularly those having a cystoscopy and histology abnormal. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Acid and low temperature treatments on Salmonella Enteritidis inoculated in pork and its subsequent survival in simulated gastric fluid

Directory of Open Access Journals (Sweden)

Simone Quintão Silva

2016-03-01

Full Text Available ABSTRACT: The objective of this study was to evaluate the acid resistance of Salmonella enterica serovar Enteritidis (S. Enteritidis in stored pork and in simulated gastric fluid (SGF. A culture of S. Enteritidis was subjected to acid treatment prior to inoculation into pork, stored under refrigeration at frozen temperatures and exposed to SGF. The S. Enteritidis CCS3 and ATCC 13076 strains previously subjected to acid treatment (at pH 4.0-5.0 were inoculated in pork and stored at 4°C and -18°C. Storage at 4ºC did not affect the populations of both S. Enteritidis strains. After 84 days at -18°C, the mean population of both CCS3 and ATCC strains were reduced by 0.8 and 1.5 log cycles, respectively. Prior acid treatment did not enhance the survival of both strains at low temperatures. After acid treatment and low temperature storage, S. Enteritidis ATCC 13076 lost culturability after being exposed to SGF for 10 minutes. In contrast, S. Enteritidis CCS3 was tolerant until three hours of SGF exposure. S. Enteritidis CCS3 submitted to pH 4.0 was more tolerant to SGF exposure than when submitted to pH 4.5, 5.0 and without acid treatment. Therefore, this study indicates that exposure to an acidic and cold environment during processing enhanced the ability of S. Enteritidis to survive in the gastric environment of the human stomach, possibly increasing the risk of a Salmonella infection after consumption of pork.

Comparative study of 15% TCA peel versus 35% glycolic acid peel for the treatment of melasma.

Science.gov (United States)

Puri, Neerja

2012-05-01

Chemical peels are the mainstay of a cosmetic practitioner's armamentarium because they can be used to treat some skin disorders and can provide aesthetic benefit. To compare 15% TCA peel and 35% glycolic acid peel for the treatment of melasma. We selected 30 participants of melasma aged between 20 and 50 years from the dermatology outpatient department and treated equal numbers with 15% TCA and 35% glycolic acid. Subjective response as graded by the patient showed good or very good response in 70% participants in the glycolic acid group and 64% in the TCA group. There was statistically insignificant difference in the efficacy between the two groups for the treatment of melasma.

Evolution of plasma homovanillic acid (HVA) levels during treatment in schizo-affective disorder.

Science.gov (United States)

Galinowski, A; Castelnau, C; Spreux-Varoquaux, O; Bourdel, M C; Olie, J P; Loo, H; Poirier, M F

2000-11-01

1. Plasma Homovanillic Acid (p HVA) levels were measured by HPLC (high performance liquid chromatography) in 5 schizo-affective depressed patients receiving a standardized treatment. (lithium, chlorpromazine and clomipramine) during 4 weeks. 2. Four patients were pretreated, without a washout period. 3. No significant difference was observed between patients and normal controls at baseline. Under treatment, pHVA levels increased (ppHVA levels that increase with clinical improvement, unlike schizophrenic patients whose increased pHVA concentrations decline with neuroleptic treatment.

Successful Treatment of Fibrosing Organising Pneumonia Causing Respiratory Failure with Mycophenolic Acid.

Science.gov (United States)

Paul, Christina; Lin-Shaw, Ammy; Joseph, Mariamma; Kwan, Keith; Sergiacomi, Gianluigi; Mura, Marco

2016-01-01

Organising pneumonia (OP) is usually promptly responsive to corticosteroid treatment. We describe a series of 3 cases of severe, progressive, biopsy-proven fibrosing OP causing respiratory failure. All cases presented with peribronchial and subpleural consolidations, had a fibro-inflammatory infiltrative component in the alveolar septa, and only had a partial and unsatisfactory response to corticosteroids. However, they responded to mycophenolic acid (MPA) treatment with resolution of respiratory failure as well as clinical and functional improvement. MPA as an additional treatment option for aggressive forms of fibrosing OP and interstitial lung disease needs to be further explored. © 2016 S. Karger AG, Basel.

Phospholipid fatty acid patterns of microbial communities in paddy soil under different fertilizer treatments

Institute of Scientific and Technical Information of China (English)

ZHANG Qi-chun; WANG Guang-huo; YAO Huai-ying

2007-01-01

The microbial communities under irrigated rice cropping with different fertilizer treatments, including control (CK), PK, NK, NP, NPK fertilization, were investigated using phospholipid fatty acid (PLFA) profile method. The results of this study revealed that the fertilizer practice had an impact on the community structure of specific microbial groups. The principal components analysis (PCA) showed that proportion of the actinomycete PLFAs (10Me 18:0 and 10Me 16:0) were the lowest in the PK treatment and the highest in the NPK treatment, which means that soil nitrogen status affected the diversity of actinomycetes, whereas nitrogen cycling was related to the actinomycets. Under CK treatment, the ratio of Gram-positive to Gram-negative bacteria was lower compared with that in fertilizer addition treatments, indicating that fertilizer application stimulated Gram-positive bacterial population in paddy soil. The fatty acid 18:2ω6, 9, which is considered to be predominantly of fungal origin, was at low level in all the treatments. The ratio of cy19:0 to 18:1ω7, which has been proposed as an indicator of stress conditions, decreased in PK treatment. Changes of soil microbial community under different fertilizer treatments of paddy soil were detected in this study; however, the causes that lead to changes in the microbial community still needs further study.

In vitro digestion and physicochemical characteristics of corn starch mixed with amino acid modified by low pressure treatment.

Science.gov (United States)

Ji, Ying

2018-03-01

The digestibility and molecular structure of corn starch mixed with amino acid modified by low-pressure treatment (LPT) was investigated. Amino acid induced a significant increase in the slowly digestible starch (SDS) and decrease in the rapidly digestible starch (RDS) after LPT. The reason is the formation of ester bond between the molecular chains of amino acid and starch. Low pressure treatment altered greatly the morphology of corn starch mixed with or without amino acid. After LPT, less ordered Maltese and more granule fragments were observed for starch-amino acid complex. An increase in size distribution was obvious after LPT and the size distribution curves provided from a new variety. We found that higher enthalpy and relative crystallinity of the starch-amino acid complex were associated with a higher SDS content. It can be inferred that LPT had a greater impact on the digestion and structural characterization of corn starch mixed with amino acids. Copyright © 2017 Elsevier Ltd. All rights reserved.

Maleic acid treatment of biologically detoxified corn stover liquor.

Science.gov (United States)

Kim, Daehwan; Ximenes, Eduardo A; Nichols, Nancy N; Cao, Guangli; Frazer, Sarah E; Ladisch, Michael R

2016-09-01

Elimination of microbial and enzyme inhibitors from pretreated lignocellulose is critical for effective cellulose conversion and yeast fermentation of liquid hot water (LHW) pretreated corn stover. In this study, xylan oligomers were hydrolyzed using either maleic acid or hemicellulases, and other soluble inhibitors were eliminated by biological detoxification. Corn stover at 20% (w/v) solids was LHW pretreated LHW (severity factor: 4.3). The 20% solids (w/v) pretreated corn stover derived liquor was recovered and biologically detoxified using the fungus Coniochaeta ligniaria NRRL30616. After maleic acid treatment, and using 5 filter paper units of cellulase/g glucan (8.3mg protein/g glucan), 73% higher cellulose conversion from corn stover was obtained for biodetoxified samples compared to undetoxified samples. This corresponded to 87% cellulose to glucose conversion. Ethanol production by yeast of pretreated corn stover solids hydrolysate was 1.4 times higher than undetoxified samples, with a reduction of 3h in the fermentation lag phase. Copyright © 2016 Elsevier Ltd. All rights reserved.

Lignite pre-treatment and its effect on bio-stimulative properties of respective lignite humic acids

Energy Technology Data Exchange (ETDEWEB)

Vlckova, Z.; Grasset, L.; Antosova, B.; Pekar, M.; Kucerik, J. [Brno University of Technology, Brno (Czech Republic). Faculty of Chemistry

2009-09-15

Humic acids originating from South-Moravian lignite were subjected to a comparative study with the aim to assess the alteration of their physico-chemical properties after various lignite pre-treatments. Physical modification was achieved with two organic acids, such as acetic acid and citric acid and chemical modification by nitric acid and hydrogene peroxide in various concentrations. Elemental analysis, solid-state NMR, GC-MS analysis of polyols and size exclusion chromatography were carried out for chemical-physical characterization of obtained humic acids. Their biological effect, in form of potassium and ammonium humates, was tested on maize (Zea mays) seedlings. In these tests, potassium humates achieved far better overall results than ammonium humates. Results were inter-correlated in order to appraise the influence of humic acids physical and chemical properties on biological activity. Surprisingly, fractions with the lowest molecular size (0-35 kDa) showed no correlation with bioactivity results (Pearson coefficient from 0.05 to -0.4). On the contrary, middle-sized fractions (35-175 kDa) showed highly significant positive correlation (Pearson coefficient up to 0.92) and the highest molecular-size-fractions (275-350 kDa) showed negative correlation (Pearson coefficient up to -0.75). These findings were identical for both potassium and ammonium humates. No connection was found between bioactivity of humates and polyols content which was remarkably high; it reached 150 mg per g of humic acids in the most extreme case of 5% hydrogene peroxide pre-treatment. In the final analysis, the preparation mode bore pivotal responsibility for the control of humic acids biological effect and showed the best results for potassium humates obtained from lignite pre-treated by acetic acid and by 2% hydrogen peroxide.

The Effect of Ascorbic Acid Treatment on Viability and Vigor Maize (Zea mays L. Seedling under Drought Stress

Directory of Open Access Journals (Sweden)

HAMIDAH HAMAMA

2010-09-01

Full Text Available This study was conducted in the laboratory and the field to examine the effects of ascorbic acid treatment on germination and seedling growth under drought stress. The laboratory works consisted of two experiments and were designed to determine the critical osmotic potential of maize and to determine the optimum ascorbic acid concentration. The field study was designed to examine the effects of soaking seed in ascorbic acid on seedling growth under drought stress. Drought condition was simulated by PEG-6000 and regulation of water treatment. During the first experiment, interactions of both osmotic potential and varieties were significant at all variables. Germination percentage and speed of germination were significantly decreased by increasing of osmotic potential. The second experiment showed that interactions of both factors were significant at all variables except vigor index, the length of shoot, primary, and seminal root. The results showed that the ascorbic acid treatment improved the germination percentage, the speed of germination and the vigor index compared with the control, besides the increase in length of shoot, primary and seminal root and number of seminal root. However, the best result was showed by 55 mM ascobic acid. The result of field experiment showed that interactions were not always significant and 55 mM ascorbic acid treatment increased the seedling height, the number of leaves and leaf area but it had no effect on the water deficit and the root length.

Effect of quarantine treatments on the carbohydrate and organic acid content of mangoes (cv. Tommy Atkins)

International Nuclear Information System (INIS)

Cruz, J.N.; Soares, C.A.; Fabbri, A.D.T.; Cordenunsi, B.R.; Sabato, S.F.

2012-01-01

Brazil is one of the largest mango producers and the third largest mango exporter worldwide. Irradiation treatment and its commercial feasibility have been studied in our country to make it possible to develop new markets and, consequently, to compete with the major exporters of mangoes, Mexico and India. This work was designed to compare irradiation treatment with the hot water dip treatment in mangoes cv. Tommy Atkins for export and to verify that the main attributes for acceptance, color and texture, as well as carbohydrate and organic acid contents, were maintained. In this study, the fruit was divided into groups: control, hot water dip-treated (46 °C for 90 min), and irradiation-treated at doses of 0.4 kGy and 1.0 kGy. The fruit was stored at low temperature (11 °C±2) for 14 days and then at room temperature (23 °C±2) until the end of the study. The results indicated that the fruit given a dose of 1.0 kGy remained in a less advanced stage of ripening (stage 3) throughout the storage period, but experienced a greater loss of texture in the beginning of the experiment. It was noted that only the control group had higher levels of citric acid and succinic acid on the last day of the experiment. There were no significant differences in the total sugar content between any treatment groups. Gamma radiation can be used as a quarantine treatment and does not interfere negatively with the quality attributes of mangoes. - Highlights: ► In Brazil, one of the largest producers and exporters of mangoes, tropical fruits are routinely treated with a hot water dip. ► Results from this study demonstrate that irradiation is a good alternative to this conventional quarantine treatment. ► Carbohydrate and organic acid results are presented for irradiation and hot water dip treatments. ► Texture measurements are shown as a function of storage time for each of these treatments.

Performance of a passive treatment system for net-acidic coal mine drainage over five years of operation.

Science.gov (United States)

Matthies, Romy; Aplin, Andrew C; Jarvis, Adam P

2010-09-15

A full-scale passive treatment system (PTS) was commissioned in 2003 to treat two net-acidic coal mine water discharges in the Durham coalfield, UK. The principal aim of the PTS was to decrease concentrations of iron (3.2) and alkalinity (> or =0 mg L(-1) CaCO(3) eq). Secondary objectives were to decrease zinc (treatment, water qualities were improved by 84% in the case of Fe, 87% Al, 83% acidity, 51% Zn, 23% Mn and 29% SO(4)(2)(-). Alkalinity (74%) and pH (95% as H(+)) were increased. Area adjusted removal rates (Fe=1.49+/-0.66 g d(-1) m(-2); acidity=6.7+/-4.9 g d(-1) m(-2)) were low compared to design criteria, mainly due to load limitation. Disregarding seasonality effects, acidity removal and effluent pH were stable over time. A substantial temporal decrease in calcium and alkalinity generation suggests that limestone is increasingly armoured. Once pH is no longer buffered by the carbonate system, metals could be remobilized, putting treatment efficiency at risk. Copyright 2010 Elsevier B.V. All rights reserved.

Treatment of Hallux Valgus with Hyaluronic Acid: A Pilot Study

Directory of Open Access Journals (Sweden)

Ižlhan Sezer

2017-05-01

Full Text Available Aim: Hallux valgus is the deformity of the first metatarsophalangeal (MTP joint with abduction and valgus rotation of the great toe, combined with a medially prominent first metatarsal head. Hyaluronic acid injection has been used in the treatment of degenerative disorders of several joints successfully. In this research, we aimed to investigate the effectiveness of hyaluronic acid injection in patients with hallux valgus. Material and Method: Eleven female and two male patients with hallux valgus were included in this pilot study. Only patients with mild and moderate hallux valgus were included in the study. 1 cc hyaluronic acid was injected into the affected MTF joint three times, at one-week intervals. Visual analogue scale(VAS score, walking time without pain, walking distance, and daily analgesic needs of the patients were recorded. All clinical outcomes were assessed before, and then one and three months after the first injection. Results:The mean VAS score was 83.08±4.58. One month after the first injection, VAS scores of patients had decreased significantly (30±4.38, P: 0.001. Also, increased walking time and distance and decreased daily analgesic need were observed at the first month of postinjection follow-up (P: 0.001. After 3 months, the positive outcomes remained significant compared to preinjection evaluations. Discussion: According to our preliminary results, we suggest thathyaluronic acid injectionsmay be effective in reducing pain and increasing walking time and distance in patients with hallux valgus.Future studies are needed to clarify the beneficial effects of hyaluronic acid injection in patients with hallux valgus.

Development and characterization of a hydrophobic treatment for jute fibres based on zinc oxide nanoparticles and a fatty acid

Energy Technology Data Exchange (ETDEWEB)

Arfaoui, M.A. [CTT Group, Saint-Hyacinthe (Canada); Department of Mechanical Engineering, Ecole de technologie supérieure, Montréal (Canada); Dolez, P.I., E-mail: pdolez@gcttg.com [CTT Group, Saint-Hyacinthe (Canada); Dubé, M.; David, É. [Department of Mechanical Engineering, Ecole de technologie supérieure, Montréal (Canada)

2017-03-01

Highlights: • A hydrophobic treatment based on zinc oxide nanoparticles and stearic acid was developed for recycled jute fibres. • The water contact angle was increased from 33° for the scoured fibre to 148° after the ZnO nanorod/stearic acid hydrothermal treatment. • The fibre thermal degradation temperature remained the same throughout the treatment at around 315 °C. • A reduction in the fibre breaking force of 32% was observed between the as-received and the ZnO nanorod/stearic acid treated fibres. - Abstract: This work aims at developing a hydrophobic treatment for jute fibres based on the grafting and growth of zinc oxide (ZnO) nanorods on the fibre surface. The first step consists in removing impurities from the fibre surface with a scouring treatment. In the second step, the jute fibres are coated with a layer of ZnO nanoseeds. A hydrothermal process is carried out as a third step to ensure a uniform growth of ZnO nanorods on the surface of the jute fibres. Finally, a hydrophobic treatment is performed on the ZnO nanorod-covered jute fibres using stearic acid (SA), i.e., a typical fatty acid. A large improvement in the fibre hydrophobicity was obtained without any negative effect on thermal stability and limited reduction in strength. Complementary measurements by scanning electron microscopy and X-ray diffraction were also performed and revealed a hexagonal system for the ZnO nanorods.

Cryotherapy versus salicylic acid for the treatment of plantar warts (verrucae): a randomised controlled trial

Science.gov (United States)

Hewitt, Catherine; Hicks, Kate; Jayakody, Shalmini; Kang’ombe, Arthur Ricky; Stamuli, Eugena; Turner, Gwen; Thomas, Kim; Curran, Mike; Denby, Gary; Hashmi, Farina; McIntosh, Caroline; McLarnon, Nichola; Torgerson, David; Watt, Ian

2011-01-01

Objective To compare the clinical effectiveness of cryotherapy versus salicylic acid for the treatment of plantar warts. Design A multicentre, open, two arm randomised controlled trial. Setting University podiatry school clinics, NHS podiatry clinics, and primary care in England, Scotland, and Ireland. Participants 240 patients aged 12 years and over, with a plantar wart that in the opinion of the healthcare professional was suitable for treatment with both cryotherapy and salicylic acid. Interventions Cryotherapy with liquid nitrogen delivered by a healthcare professional, up to four treatments two to three weeks apart. Patient self treatment with 50% salicylic acid (Verrugon) daily up to a maximum of eight weeks. Main outcome measures Complete clearance of all plantar warts at 12 weeks. Secondary outcomes were (a) complete clearance of all plantar warts at 12 weeks controlling for age, whether the wart had been treated previously, and type of wart, (b) patient self reported clearance of plantar warts at six months, (c) time to clearance of plantar wart, (d) number of plantar warts at 12 weeks, and (e) patient satisfaction with the treatment. Results There was no evidence of a difference between the salicylic acid and cryotherapy groups in the proportions of participants with complete clearance of all plantar warts at 12 weeks (17/119 (14%) v 15/110 (14%), difference 0.65% (95% CI –8.33 to 9.63), P=0.89). The results did not change when the analysis was repeated but with adjustment for age, whether the wart had been treated previously, and type of plantar wart or for patients’ preferences at baseline. There was no evidence of a difference between the salicylic acid and cryotherapy groups in self reported clearance of plantar warts at six months (29/95 (31%) v 33/98 (34%), difference –3.15% (–16.31 to 10.02), P=0.64) or in time to clearance (hazard ratio 0.80 (95% CI 0.51 to 1.25), P=0.33). There was also no evidence of a difference in the number of plantar

Ab initio design of drug carriers for zoledronate guest molecule using phosphonated and sulfonated calix[4]arene and calix[4]resorcinarene host molecules

Science.gov (United States)

Jang, Yong-Man; Yu, Chol-Jun; Kim, Jin-Song; Kim, Song-Un

2018-04-01

Monomolecular drug carriers based on calix[n]-arenes and -resorcinarenes containing the interior cavity can enhance the affinity and specificity of the osteoporosis inhibitor drug zoledronate (ZOD). In this work we investigate the suitability of nine different calix[4]-arenes and -resorcinarenes based macrocycles as hosts for the ZOD guest molecule by conducting {\\it ab initio} density functional theory calculations for structures and energetics of eighteen different host-guest complexes. For the optimized molecular structures of the free, phosphonated, sulfonated calix[4]-arenes and -resorcinarenes, the geometric sizes of their interior cavities are measured and compared with those of the host-guest complexes in order to check the appropriateness for host-guest complex formation. Our calculations of binding energies indicate that in gaseous states some of the complexes might be unstable but in aqueous states almost all of the complexes can be formed spontaneously. Of the two different docking ways, the insertion of ZOD with the \\ce{P-C-P} branch into the cavity of host is easier than that with the nitrogen containing heterocycle of ZOD. The work will open a way for developing effective drug delivering systems for the ZOD drug and promote experimentalists to synthesize them.

Tiagabine treatment in kainic acid induced cerebellar lesion of dystonia rat model

Science.gov (United States)

Wang, Tsui-chin; Ngampramuan, Sukonthar; Kotchabhakdi, Naiphinich

2016-01-01

Dystonia is a neurological disorder characterized by excessive involuntary muscle contractions that lead to twisting movements. The exaggerated movements have been studied and have implicated basal ganglia as the point of origin. In more recent studies, the cerebellum has also been identified as the possible target of dystonia, in the search for alternative treatments. Tiagabine is a selective GABA transporter inhibitor, which blocks the reuptake and recycling of GABA. The study of GABAergic drugs as an alternative treatment for cerebellar induced dystonia has not been reported. In our study, tiagabine was i.p. injected into kainic acid induced, cerebellar dystonic adult rats, and the effects were compared with non-tiagabine injected and sham-operated groups. Beam walking apparatus, telemetric electromyography (EMG) recording, and histological verification were performed to confirm dystonic symptoms in the rats on post-surgery treatment. Involuntary dystonic spasm was observed with repetitive rigidity, and twisting movements in the rats were also confirmed by a high score on the dystonic scoring and a high amplitude on the EMG data. The rats with tiagabine treatment were scored based on motor amelioration assessed via beam walking. The result of this study suggests and confirms that low dose of kainic acid microinjection is sufficient to induce dystonia from the cerebellar vermis. In addition, from the results of the EMG recording and the behavioral assessment through beam walking, tiagabine is demonstrated as being effective in reducing dystonic spasm and may be a possible alternative therapeutic drug in the treatment of dystonia. PMID:28337103

Treatment of postoperative bleeding after fondaparinux with rFVIIa and tranexamic acid.

NARCIS (Netherlands)

Huvers, F.C.; Slappendel, R.; Benraad, B.; Hellemondt, G. van; Kraaij, M.G.J. van

2005-01-01

Treatment of a haemorrhagic shock after just a single dose of fondaparinux in an orthopaedic patient with reduced renal clearance is presented. Since all routine haemostatic parameters were nearly normal, single doses of rFVIIa (90 microg/kg) and of tranexamic acid (15 mg/kg) were administered to

Efficacy of Lactic Acid, Lactic Acid-Acetic Acid Blends, and Peracetic Acid To Reduce Salmonella on Chicken Parts under Simulated Commercial Processing Conditions.

Science.gov (United States)

Ramirex-Hernandez, Alejandra; Brashears, Mindy M; Sanchez-Plata, Marcos X

2018-01-01

The poultry processing industry has been undergoing a series of changes as it modifies processing practices to comply with new performance standards for chicken parts and comminuted poultry products. The regulatory approach encourages the use of intervention strategies to prevent and control foodborne pathogens in poultry products and thus improve food safety and protect human health. The present studies were conducted to evaluate the efficacy of antimicrobial interventions for reducing Salmonella on inoculated chicken parts under simulated commercial processing conditions. Chicken pieces were inoculated by immersion in a five-strain Salmonella cocktail at 6 log CFU/mL and then treated with organic acids and oxidizing agents on a commercial rinsing conveyor belt. The efficacy of spraying with six different treatments (sterile water, lactic acid, acetic acid, buffered lactic acid, acetic acid in combination with lactic acid, and peracetic acid) at two concentrations was evaluated on skin-on and skin-off chicken thighs at three application temperatures. Skinless chicken breasts were used to evaluate the antimicrobial efficacy of lactic acid and peracetic acid. The color stability of treated and untreated chicken parts was assessed after the acid interventions. The lactic acid and buffered lactic acid treatments produced the greatest reductions in Salmonella counts. Significant differences between the control and water treatments were identified for 5.11% lactic acid and 5.85% buffered lactic acid in both skin-on and skin-off chicken thighs. No significant effect of treatment temperature for skin-on chicken thighs was found. Lactic acid and peracetic acid were effective agents for eluting Salmonella cells attached to chicken breasts.

A randomized clinical trial of high eicosapentaenoic acid omega-3 fatty acids and inositol as monotherapy and in combination in the treatment of pediatric bipolar spectrum disorders: a pilot study.

Science.gov (United States)

Wozniak, Janet; Faraone, Stephen V; Chan, James; Tarko, Laura; Hernandez, Mariely; Davis, Jacqueline; Woodworth, K Yvonne; Biederman, Joseph

2015-11-01

We conducted a 12-week, randomized, double-blind, controlled clinical trial to evaluate the effectiveness and tolerability of high eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) omega-3 fatty acids and inositol as monotherapy and in combination in children with bipolar spectrum disorders. Participants were children 5-12 years of age meeting DSM-IV diagnostic criteria for bipolar spectrum disorders (bipolar I or II disorder or bipolar disorder not otherwise specified [NOS]) and displaying mixed, manic, or hypomanic symptoms. Subjects with severe illness were excluded. Subjects were randomized to 1 of 3 treatment arms: inositol plus placebo, omega-3 fatty acids plus placebo, and the combined active treatment of omega-3 fatty acids plus inositol. Data were collected from February 2012 to November 2013. Twenty-four subjects were exposed to treatment (≥ 1 week of study completed) (inositol [n = 7], omega-3 fatty acids [n = 7], and omega-3 fatty acids plus inositol [n =10]). Fifty-four percent of the subjects completed the study. Subjects randomized to the omega-3 fatty acids plus inositol arm had the largest score decrease comparing improvement from baseline to end point with respect to the Young Mania Rating Scale (P < .05). Similar results were found for the Children's Depression Rating Scale (P < .05) and the Brief Psychiatric Rating Scale (P <.05). Results of this pilot randomized, double-blind, controlled trial suggest that the combined treatment of omega-3 fatty acids plus inositol reduced symptoms of mania and depression in prepubertal children with mild to moderate bipolar spectrum disorders. Results should be interpreted in light of limitations, which include exclusion of severely ill subjects, 54% completion rate, and small sample size. ClinicalTrials.gov identifier: NCT01396486. © Copyright 2015 Physicians Postgraduate Press, Inc.

Kinetic modeling of cement slurry synthesized with Henna extract in oil well acidizing treatments

Directory of Open Access Journals (Sweden)

Amir Hossein Aghajafari

2016-06-01

Full Text Available Acidizing treatment in petroleum reservoirs is a short-term and viable strategy to preserve the productivity of a well. There is a major concern for the degradation of cement sheath integrity, leading to poor zonal isolation and environmental issues. Therefore, it is essential to understand how the cement behaves when attacked by hydrochloric acid. In this study, a cement slurry by incorporation of the Henna extract, as an environmentally friendly cement additive, was synthesized as a potential solution to solve this problem. The characteristics of the treated cement slurry were compared with a reference slurry (w/c = 0.44 which is composed of only cement and water. A kinetic study was carried out to evaluate the adsorption behavior of the cement slurries exposed to an acid solution with 0.1 M HCl in a range of 25 to 55 °C conditions. The features of the cement slurries were evaluated by multiple analytical techniques such as XRD, FTIR, TG, and DSC analysis. From the experimental data, it is concluded that the second-order Lagergren kinetic model revealed to be the best in describing kinetic isotherms taken, because the margin between experimental and calculated values was minor for this model. The results of the characterization and HCl interaction kinetic studies underlined the prominent protective role of Henna extract-modified cement slurry in the enhancement of the cement resistance against acid attack and utilization in environmentally favorable oil well acidizing treatments.

Synthesis of PBAD-lipiodol nanoparticles for combination treatment with boric acid in boron neutron capture therapy for hepatoma in-vitro

International Nuclear Information System (INIS)

Chou, F.I.; Chung, H.P.; Liu, H.M.; Wen, H.W.; Chi, C.W.; Lin, Shanyang; Lui, W.Y.; Kai, J.J.

2006-01-01

This study attempted to increase BNCT efficiency for hepatoma by a combined treatment of phenylboric acid derivative entrapped lipiodol nanoparticles (PBAD-L nanoparticles) with boric acid. The size of PBAD-L nanoparticles were 400-750 nm at the boron concentrations of 0.3-2.7 mg/ml. After 24 hours the boron concentration in PBAD-L nanoparticles treated human hepatoma HepG2 cells was 112 ppm, while that in rat liver Clone 9 cells was 52 ppm. With the use of 25 μg B/ml boric acid, after 6 hours the boron concentration in HepG2 and Clone 9 cells were 75 ppm and 40 ppm, respectively. In a combined treatment, boron concentration in HepG2 cells which were treated with PBAD-L nanoparticles for 18 hours and then combined with boric acid for 6 hours was 158 ppm. After neutron irradiation, the surviving fraction of HepG2 cells treated with PBAD-L nanoparticles was 12.6%, while that in the ones with a combined treatment was 1.3%. In conclusion, the combined treatment provided a higher boron concentration in HepG2 cells than treatments with either PBAD-L nanoparticles or boric acid, resulting in a higher therapeutic efficacy of BNCT in hepatoma cells. (author)

Potential risks of effluent from acid mine drainage treatment plants at abandoned coal mines.

Science.gov (United States)

Seo, Jaehwan; Kang, Sung-Wook; Ji, Wonhyun; Jo, Hun-Je; Jung, Jinho

2012-06-01

The lethal and sublethal toxicity of effluent from three acid mine drainage treatment plants were monitored from August 2009 to April 2010 using Daphnia magna (reference species) and Moina macrocopa (indigenous species). Acute lethal toxicity was observed in Samma effluent due to incomplete neutralization of acid mine drainages by the successive alkalinity producing system (SAPS). Additionally, there was no significant difference in toxicity values (TU) between D. magna and M. macrocopa (p water bodies.

Ursodeoxycholic acid treatment in patients with cystic fibrosis at risk for liver disease.

Science.gov (United States)

Siano, Maria; De Gregorio, Fabiola; Boggia, Bartolo; Sepe, Angela; Ferri, Pasqualina; Buonpensiero, Paolo; Di Pasqua, Antonio; Raia, Valeria

2010-06-01

Meconium ileus has been detected as a risk factor for development of liver disease in cystic fibrosis, with influence on morbidity and mortality. To evaluate the effect of early treatment with ursodeoxycholic acid in patients with cystic fibrosis and meconium ileus to prevent chronic hepatic involvement and to explore the potential role of therapy on clinical outcomes. 26 cystic fibrosis patients with meconium ileus (16 M, mean age 8,4 years, range 3,5-9) were assigned to two groups: group 1 (14 patients) treated early with ursodeoxycholic acid (UDCAe); group 2 (12 patients) treated with ursodeoxycholic acid at the onset of cystic fibrosis liver disease (UDCAd). Anthropometric data, pulmonary function tests, pancreatic status, complications such as diabetes, hepatic involvement and Pseudomonas aeruginosa colonisation were compared among groups. A higher prevalence of cystic fibrosis chronic liver disease was observed in the UDCAd group with a statistically significant difference at 9 years of age (p<0.05). Chronic infection by P. aeruginosa was found in 7% of UDCAe and 33% of UDCAd (p<0.05). No differences were observed in nutritional status and other complications. Early treatment with ursodeoxycholic acid may be beneficial in patients at risk of developing cystic fibrosis chronic liver disease such as those with meconium ileus. Multicentre studies should be encouraged to confirm these data. Copyright 2009 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Compounds formed by treatment of corn (Zea mays) with nitrous acid.

Science.gov (United States)

Archer, M C; Hansen, T J; Tannenbaum, S R

1980-01-01

Nitrohexane has been identified as a major product formed following treatment of corn (Zea mays) with nitrous acid. Preliminary evidence suggests that another compound isolated from the nitrosated corn is an unsaturated nitrolic acid. As an aid to the analysis of N-nitro compounds, we have characterized the response of a chemiluminescence detector (Thermal Energy Analyzer) as a function of pyrolysis chamber temperature for several nitrosamines and for an aliphatic C-nitroso compound, an aromatic C-nitro compound, a nitramine and an alkyl nitrite. The response-temperature profiles are valuable in distinguishing among the various compounds and in optimizing the sensitivity of the detector for use in chromatography. Other tests, including photolysis and stability toward nitrite-scavenging reagents, further aid in distinguishing among the various compounds.

Application of nanofiltration to the treatment of acid mine drainage waters

International Nuclear Information System (INIS)

Bastos, Edna T.R.; Barbosa, Celina C.R.; Oliveira, Elizabeth E.M.; Carvalho, Leonel M. de; Pedro Junior, Antonio; Queiroz, Vanessa B.C. de

2009-01-01

This study investigated the separation of uranium and other elements in high concentrations from acid mine waters at Caldas Uranium Mining, in the southeast of Brazil, using nanofiltration membranes. Nanofiltrarion is widely used in water treatment due to the lower energy requirements and higher yields than reverse osmosis. Separation characteristics are dependent on both the molecular size and charge of the dissolved species in the feed solution as well as membrane properties. In this investigation the potential of nanofiltration to removed dissolved species like uranium from acid mine water drainage was measured. Two composite aromatic polyamide commercially membranes of FilmTec/Dow were tested and it found that uranium rejections of greater than 90% and also showed potential for the separation of aluminum and manganese. (author)

Treatment alternatives of liquid radioactive waste containing uranium in phosphoric acid

International Nuclear Information System (INIS)

Bustamante Escobedo, Mauricio

2003-01-01

The UGDR, receives annually 100 [l] of liquid radioactive waste containing, highly acid (pH=0) uranium in phosphoric acid from the Laboratory of Chemical Analysis. This waste must be chemically and radiologically decontaminated before it can be discharged in accordance with local environmental standards. Chemical precipitation and evaporation test were carried out to define the operating conditions for the radiological decontamination of this radioactive waste and to obtain a solid waste that can be conditioned in a cement matrix. The evaporation process generates excellent rates of volume reduction, over 80%, but generates a pulp that is hard handle when submitted to a drying process. Chemical precipitation generates good results for decontaminating these solutions and reducing volume (above 50%) to obtain a uranium free effluent. The treatment with calcium carbonate generated an effluent with a low concentration of polluting agents. A preliminary test was carried out condition these solids in a cement matrix, using ratios of 0.45 waste/cement and 2 of water/cement. The mix prepared with waste from the sodium hydroxide treatment had low mechanical resistance resulting from the saline incrustations. The waste from the calcium carbonate treatment was very porous due to the water evaporation from the highly exothermic reaction between the waste and the cement. The mix of the calcium carbonate generated waste and the cement matrix needs to be optimized, since it generates favorable conditions for adhering with the cement matrix (au)

Electron beam treatment technology for exhaust gas for preventing acid rain

International Nuclear Information System (INIS)

Aoki, Shinji

1990-01-01

Recently, accompanying the increase of the use of fossil fuel, the damage due to acid rain such as withering of trees and extinction of fishes and shells has occurred worldwide, and it has become a serious problem. The sulfur oxides and nitrogen oxides contained in exhaust gas are oxidized by the action of sunbeam to become sulfuric acid and nitric acid mists, which fall in the form of rain. Acid rain is closely related to the use of the coal containing high sulfur, and it hinders the use of coal which is rich energy source. In order to simplify the processing system for boiler exhaust gas and to reduce waste water and wastes, Ebara Corp. developed the dry simultaneous desulfurizing and denitrating technology utilizing electron beam in cooperation with Japan Atomic Energy Research Institute. The flow chart of the system applied to the exhaust gas treatment in a coal-fired thermal power station is shown. The mechanism of desulfurization and denitration, and the features of this system are described. The demonstration plant was constructed in a coal-fired thermal power station in Indianapolis, Indiana, USA, and the trial operation was completed in July, 1987. The test results are reported. (K.I.)

Effect of a reduction in uric acid on renal outcomes during losartan treatment

DEFF Research Database (Denmark)

Miao, Yan; Ottenbros, Stefan A; Laverman, Goos D

2011-01-01

Emerging data show that increased serum uric acid (SUA) concentration is an independent risk factor for end-stage renal disease. Treatment with the antihypertensive drug losartan lowers SUA. Whether reductions in SUA during losartan therapy are associated with renoprotection is unclear. We...

Treatment of Arctic Wastewater by Chemical Coagulation, UV and Peracetic Acid Disinfection

DEFF Research Database (Denmark)

Chhetri, Ravi Kumar; Klupsch, Ewa; Andersen, Henrik Rasmus

2017-01-01

Conventional wastewater treatment is challenging in the Arctic region due to the cold climate and scattered population. Thus, no wastewater treatment plant exists in Greenland and raw wastewater is discharged directly to nearby waterbodies without treatment. We investigated the efficiency...... of physico-chemical wastewater treatment, in Kangerlussuaq, Greenland. Raw wastewater from Kangerlussuaq was treated by chemical coagulation and UV disinfection. By applying 7.5 mg Al/L polyaluminium chloride (PAX XL100), 73% of turbidity and 28% phosphate was removed from raw wastewater. E. coli...... of heterotrophic bacteria by applying 6 mg/L and 12 mg/L peracetic acid was 2.8 and 3.1 log, respectively. Similarly, removal of heterotrophic bacteria by applying 0.21 kWh/m3 and 2.10 kWh/m3 for UV irradiation was 2.1 and greater than 4 log, respectively. Physico-chemical treatment of raw wastewater followed...

Effectiveness of chlorine, organic acids and UV treatments in reducing Escherichia coli O157:H7 and Yersinia enterocolitica on apples.

Science.gov (United States)

Escudero, M E; Velázquez, L; Favier, G; de Guzmán, A M

2003-06-01

This study assessed the effectiveness of 200 and 500 ppm of chlorine and organic acids (0.5% lactic acid and 0.5% citric acid) in wash solutions, and UV radiation for reducing Escherichia coli O157:H7 and Yersinia enterocolitica on apples contaminated by two different methods. Residual levels of these pathogens after different treatments were compared. On dip inoculated apples, Y. enterocolitica reductions of 2.66 and 2.77 logs were obtained with 200 and 500 ppm chlorine combined with 0.5% lactic acid, respectively. The E. coli O157:H7 population decreased 3.35 log with 0.5% lactic acid wash solution, and 2.72 and 2.62 logs after 500 ppm chlorine and 500 ppm chlorine plus 0.5% lactic acid treatments, respectively. Similar reductions were obtained with UV radiation. On spot inoculated apples, significant (p acid treatment as compared with the control. In sectioned apples, microorganisms infiltrated in inner core region and pulp were not significantly (p apples. Reductions such as those obtained with 500 ppm chlorine plus 0.5% lactic acid solution were very proximal to the 5-log score required by FDA for apple disinfection.

The EVERT (effective verruca treatments trial protocol: a randomised controlled trial to evaluate cryotherapy versus salicylic acid for the treatment of verrucae

Directory of Open Access Journals (Sweden)

Cockayne E Sarah

2010-02-01

Full Text Available Abstract Background Verrucae are a common, infectious and sometimes painful problem. The optimal treatment for verrucae is unclear due to a lack of high quality randomised controlled trials. The primary objective of this study is to compare the clinical effectiveness of two common treatments for verrucae: cryotherapy using liquid nitrogen versus salicylic acid. Secondary objectives include a comparison of the cost-effectiveness of the treatments, and an investigation of time to clearance of verrucae, recurrence/clearance of verrucae at six months, patient satisfaction with treatment, pain associated with treatment, and use of painkillers for the treatments. Methods/Design This is an open, pragmatic, multicentre, randomised controlled trial with two parallel groups: cryotherapy using liquid nitrogen delivered by a healthcare professional for a maximum of 4 treatments (treatments 2-3 weeks apart or daily self-treatment with 50% salicylic acid for a maximum of 8 weeks. Two hundred and sixty-six patients aged 12 years and over with a verruca are being enrolled into the study. The primary outcome is complete clearance of all verrucae as observed on digital photographs taken at 12 weeks compared with baseline and assessed by an independent healthcare professional. Secondary outcomes include self-reported time to clearance of verrucae, self-reported clearance of verrucae at 6 months, cost-effectiveness of the treatments compared to one another, and patient acceptability of both treatments including possible side effects such as pain. The primary analysis will be intention to treat. It is planned that recruitment will be completed by December 2009 and results will be available by June 2010. Trial registration Current Controlled Trials ISRCTN18994246.

[Clinical study of treatment of epistaxis of little's area by microwave, anterior nasal packing and trichloroacetic acid cautery].

Science.gov (United States)

Zhi, T; Liu, Y; Liu, F

1999-11-01

To study the difference and quality of three different kind of treatment methods for epistaxis of Little's area, such as: microwave, anterior packing of nasal cavity and trichloroacetic acid cautery. The cases were divided into three group. The state of bleeding, reaction of after-treatment and recurrence were recorded and analysed. Comparing with the anterior nasal packing and trichloroacetic acid cautery, the microwave is characteristic by thorough stop-bleeding, light reaction, less recurrence. Microwave is an ideal way to treat epistaxis of Little's area. The patient's reaction is mild and less the clinical effects is obviously better than the anterior packing of nasal cavity and trichloroacetic acid cautery.

Synthesis of stable TiO2 nanotubes: effect of hydrothermal treatment, acid washing and annealing temperature.

Science.gov (United States)

López Zavala, Miguel Ángel; Lozano Morales, Samuel Alejandro; Ávila-Santos, Manuel

2017-11-01

Effect of hydrothermal treatment, acid washing and annealing temperature on the structure and morphology of TiO 2 nanotubes during the formation process was assessed. X-ray diffraction, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy analysis were conducted to describe the formation and characterization of the structure and morphology of nanotubes. Hydrothermal treatment of TiO 2 precursor nanoparticles and acid washing are fundamental to form and define the nanotubes structure. Hydrothermal treatment causes a change in the crystallinity of the precursor nanoparticles from anatase phase to a monoclinic phase, which characterizes the TiO 2 nanosheets structure. The acid washing promotes the formation of high purity nanotubes due to Na + is exchanged from the titanate structure to the hydrochloric acid (HCl) solution. The annealing temperature affects the dimensions, structure and the morphology of the nanotubes. Annealing temperatures in the range of 400 °C and 600 °C are optimum to maintain a highly stable tubular morphology of nanotubes. Additionally, nanotubes conserve the physicochemical properties of the precursor Degussa P25 nanoparticles. Temperatures greater than 600 °C alter the morphology of nanotubes from tubular to an irregular structure of nanoparticles, which are bigger than those of the precursor material, i.e., the crystallinity turn from anatase phase to rutile phase inducing the collapse of the nanotubes.

Pharmacoeconomics of bisphosphonates for skeletal-related event prevention in metastatic non-breast solid tumours.

Science.gov (United States)

Carter, John A; Joshi, Avani D; Kaura, Satyin; Botteman, Marc F

2012-05-01

disutility was modelled over time. While the field of cost-effectiveness analysis in solid tumours other than breast cancer is still evolving, outcomes will likely continue to be driven by drug cost and assumptions regarding treatment benefits. Although considerations such as adverse events and administration costs are important, they were not found to influence cost-effectiveness estimates greatly. As zoledronic acid will lose patent protection in 2013 and subsequently be greatly reduced in price, it is likely that the field of cost effectiveness will change with regard to SRE-limiting agents. Meanwhile, research should be conducted to improve our understanding of the impact on quality of life and medical costs of preventing SREs.

Salicylic Acid 6% in an ammonium lactate emollient foam vehicle in the treatment of mild-to-moderate scalp psoriasis.

Science.gov (United States)

Kircik, Leon

2011-03-01

Scalp psoriasis is a common life-altering skin condition causing a great deal of distress. It significantly affects quality of life and is difficult to manage. Treatment can provide variable results, often impacting patient compliance with therapy. Salicylic acid is used as adjunctive therapy to other topical treatments because of its marked keratolytic effect. Its effectiveness as a monotherapy is not fully understood. An emollient foam formulation of 6% salicylic acid (Salkera) in an ammonium lactate vehicle has recently become available. Efficacy, tolerability and patient acceptability of salicylic acid 6% emollient foam were assessed in an open-label pilot study of 10 subjects with scalp psoriasis. All psoriasis severity parameters were reduced with a significant decrease in Psoriasis Scalp Severity Index (PSSI) score from 15.3 to 3.0 after four weeks of monotherapy (Poiliness severity and patient-reported burning tolerability. Salicylic acid 6% emollient foam provides a useful option in the treatment of psoriasis that is highly effective, well tolerated and acceptable to patients.

Acid Etching as Surface Treatment Method for Luting of Glass-Ceramic Restorations, part 1: Acids, Application Protocol and Etching Effectiveness

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Emilija Barjaktarova-Valjakova

2018-03-01

CONCLUSION: Acid etching of the bonding surface of glass - ceramic restorations is considered as the most effective treatment method that provides a reliable bond with composite cement. Selective removing of the glassy matrix of silicate ceramics results in a micromorphological three-dimensional porous surface that allows micromechanical interlocking of the luting composite.

Biological properties of 99Tcm-HMIBP and its usefulness for bone scintigraphy by comparing with 99Tcm-MDP

International Nuclear Information System (INIS)

Luo Shineng; Ye Wanzhong; Xie Minhao; Yu Yanhua; Zhao Yan; Cao Guoxian; Guo Xuehua; Zhou Lian

2008-01-01

Objective: Zoledronate has been extensively used for the treatment of tumor-induced hypercalcaemia and osteolytic bone metastases. 1-hydroxy-2-(1-methylimidazol-2-yl) ethylidene-1,1-bisphos- phonic acid (HMIBP) with similar chemical structure as Zoledronate, was therefore considered to be useful as bone imaging agent. In this study the usefulness of 99 Tc m labeled HMIBP for bone imaging was evaluated and the results with the well-established 99 Tc m -methylene diphosphonic acid (MDP) imaging was compared. Methods: Labeled with 99 Tc m , the SnCl 2 ·2H 2 O quantity, radiochemical purity, pH value and stability at 4 degree C of 99 Tc m -HMIBP were measured. Besides, the partition coefficient, plasma protein binding rate, hemodynamic parameters of 99 Tc m -HMIBP and median lethal dose (LD 50 ) of HMIBP were determined. 99 Tc m -HMIBP bone imaging was performed in normal New Zealand rabbits and compared with 99 Tc m -MDP bone imaging. Results: The kit composed of 5 mg HMIBP and 0.05 mg SnCl 2 ·2H 2 O. The labeling rate was 96% after 180 d storage at 4 degree C. The radiochemical purity of 99 Tc m -HMIBP was 98% at pH 5 and the partition coefficients were 0.0125 and 0.0054 at pH 7.0 and 7.4 respectively. The plasma protein binding rate of 99 Tc m -HMIBP was 44.77%. The hemodynamic parameter C valued 3.0979 e -0.0721t +0.1250 e -0.0076t and LD 50 was 8.2 mg/kg. The bone images of 99 Tc m -HMIBP were fairly well 3 h after the injection, which was comparable to 99 Tc m -MDP bone imaging. Conclusions: 99 Tc m -HMIBP had good biological properties and comparable bone imaging quality with 99 Tc m -MDP. It might be a potential agent for both treatment and imaging. (authors)

Easy synthesis of graphene sheets from alfalfa plants by treatment of nitric acid

International Nuclear Information System (INIS)

Qu, Jiao; Luo, Chunqiu; Zhang, Qian; Cong, Qiao; Yuan, Xing

2013-01-01

Highlights: ► An easy method for synthesis of graphene sheets using alfalfa plants was introduced. ► An novelty formation mechanism of graphene sheets using alfalfa plants was proposed. ► This method exploits a new carbon source and provides a novel idea to synthesize graphene sheets. -- Abstract: This letter focuses on synthesis of graphene sheets from alfalfa plants by treatment of nitric acid. The transmission electron microscopy image (TEM) demonstrates that the graphene sheets are agglomerated and overlapped, the energy dispersive spectrum (EDS) indicates that the products are pure, and the Raman spectrum shows the graphene sheets are well graphitized. In addition, the formation mechanism of the graphene sheets from alfalfa plants by treatment nitric acid is discussed. These findings inspire the search for a new strategy for synthesis of graphene sheets from renewable natural products, and the lower cost of this new process and carbon source may facilitate industrial production

Easy synthesis of graphene sheets from alfalfa plants by treatment of nitric acid

Energy Technology Data Exchange (ETDEWEB)

Qu, Jiao, E-mail: qujiao@bhu.edu.cn [School of Chemistry and Chemical Engineering, Bohai University, Jinzhou 121013 (China); School of Urban and Environmental Sciences, Northeast Normal University, Changchun 130024 (China); Luo, Chunqiu, E-mail: fplj_lcq@163.com [School of Chemistry and Chemical Engineering, Bohai University, Jinzhou 121013 (China); Zhang, Qian; Cong, Qiao [School of Chemistry and Chemical Engineering, Bohai University, Jinzhou 121013 (China); Yuan, Xing [School of Urban and Environmental Sciences, Northeast Normal University, Changchun 130024 (China)

2013-04-01

Highlights: ► An easy method for synthesis of graphene sheets using alfalfa plants was introduced. ► An novelty formation mechanism of graphene sheets using alfalfa plants was proposed. ► This method exploits a new carbon source and provides a novel idea to synthesize graphene sheets. -- Abstract: This letter focuses on synthesis of graphene sheets from alfalfa plants by treatment of nitric acid. The transmission electron microscopy image (TEM) demonstrates that the graphene sheets are agglomerated and overlapped, the energy dispersive spectrum (EDS) indicates that the products are pure, and the Raman spectrum shows the graphene sheets are well graphitized. In addition, the formation mechanism of the graphene sheets from alfalfa plants by treatment nitric acid is discussed. These findings inspire the search for a new strategy for synthesis of graphene sheets from renewable natural products, and the lower cost of this new process and carbon source may facilitate industrial production.

Treatment of palmoplantar warts with a diphencyprone and salicylic acid ointment.

Science.gov (United States)

Armour, Katherine; Orchard, David

2006-08-01

We report on 50 consecutive suitable patients with one or more palmoplantar warts who were treated with a patient-applied ointment comprising 0.1% diphencyprone and 15% salicylic acid in white soft paraffin. All patients sensitized to diphencyprone were followed up clinically and assessed by patient questionnaire. The intention to treat success rate in this series was 88%. The time to wart clearance ranged from less than 4 weeks to 4 months. In our patient group, 90% rated their treatment as 'excellent' or 'good', whereas 10% stated that the reaction induced by diphencyprone was 'too severe'. Our results are compared with those previously published using diphencyprone in the treatment of palmoplantar warts.

Influence of fenofibrate treatment on triacylglycerides, diacylglycerides and fatty acids in fructose fed rats.

Science.gov (United States)

Kopf, Thomas; Schaefer, Hans-Ludwig; Troetzmueller, Martin; Koefeler, Harald; Broenstrup, Mark; Konovalova, Tatiana; Schmitz, Gerd

2014-01-01

Fenofibrate (FF) lowers plasma triglycerides via PPARα activation. Here, we analyzed lipidomic changes upon FF treatment of fructose fed rats. Three groups with 6 animals each were defined as control, fructose-fed and fructose-fed/FF treated. Male Wistar Unilever Rats were subjected to 10% fructose-feeding for 20 days. On day 14, fenofibrate treatment (100 mg/kg p.o.) was initiated and maintained for 7 days. Lipid species in serum were analyzed using mass spectrometry (ESI-MS/MS; LC-FT-MS, GC-MS) on days 0, 14 and 20 in all three groups. In addition, lipid levels in liver and intestine were determined. Short-chain TAGs increased in serum and liver upon fructose-feeding, while almost all TAG-species decreased under FF treatment. Long-chain unsaturated DAG-levels (36:1, 36:2, 36:4, 38:3, 38:4, 38:5) increased upon FF treatment in rat liver and decreased in rat serum. FAs, especially short-chain FAs (12:0, 14:0, 16:0) increased during fructose-challenge. VLDL secretion increased upon fructose-feeding and together with FA-levels decreased to control levels during FF treatment. Fructose challenge of de novo fatty acid synthesis through fatty acid synthase (FAS) may enhance the release of FAs ≤ 16:0 chain length, a process reversed by FF-mediated PPARα-activation.

Influence of fenofibrate treatment on triacylglycerides, diacylglycerides and fatty acids in fructose fed rats.

Directory of Open Access Journals (Sweden)

Thomas Kopf

Full Text Available Fenofibrate (FF lowers plasma triglycerides via PPARα activation. Here, we analyzed lipidomic changes upon FF treatment of fructose fed rats. Three groups with 6 animals each were defined as control, fructose-fed and fructose-fed/FF treated. Male Wistar Unilever Rats were subjected to 10% fructose-feeding for 20 days. On day 14, fenofibrate treatment (100 mg/kg p.o. was initiated and maintained for 7 days. Lipid species in serum were analyzed using mass spectrometry (ESI-MS/MS; LC-FT-MS, GC-MS on days 0, 14 and 20 in all three groups. In addition, lipid levels in liver and intestine were determined. Short-chain TAGs increased in serum and liver upon fructose-feeding, while almost all TAG-species decreased under FF treatment. Long-chain unsaturated DAG-levels (36:1, 36:2, 36:4, 38:3, 38:4, 38:5 increased upon FF treatment in rat liver and decreased in rat serum. FAs, especially short-chain FAs (12:0, 14:0, 16:0 increased during fructose-challenge. VLDL secretion increased upon fructose-feeding and together with FA-levels decreased to control levels during FF treatment. Fructose challenge of de novo fatty acid synthesis through fatty acid synthase (FAS may enhance the release of FAs ≤ 16:0 chain length, a process reversed by FF-mediated PPARα-activation.

Comparison of salicylic acid 30% peel and pneumatic broadband light in the treatment of mild to moderately severe facial acne vulgaris.

Science.gov (United States)

Thuangtong, Rattapon; Tangjaturonrusamee, Chinmanat; Rattanaumpawan, Pinyo; Ditre, Chérie M

2017-07-01

Acne patients experience not only a medical disease but also an aesthetic condition, and this latter complication greatly motivates patients to seek out the best treatment regimen to hasten improvement in their appearance. The available clinical procedures for acne treatment include salicylic acid 30% peel and pneumatic broadband light (PBBL). The objective of this study was to compare the efficacy of salicylic acid 30% peel and PBBL treatments in patients with mild to moderately severe facial acne vulgaris. Twelve patients were recruited for a 12-week prospective, single-blind, randomized, split-face study. Patients were treated with a salicylic acid 30% peel on one side of the face and PBBL treatment was administered on the opposite side of the face for 6 consecutive weeks without other acne treatments. At every visit, treatment evaluations were performed using a modified Global Acne Grading Score (mGAGS), acne quality of life (QOL) questionnaire, Wong-Baker FACES Pain Rating Scale (WBPRS) assessments, and clinical photography. Improvement in acne symptoms was observed for both treatment procedures without significant differences and with minimal side effects. Salicylic acid 30% peel and PBBL were well tolerated in our study, and both clinical procedures were efficacious and well-tolerated by the patients.

O2 electrocatalysis in acid media on iron naphthalocyanine impregnations. Effect of nitric acid treatment on different carbon black supports

NARCIS (Netherlands)

Coowar, F.; Contamin, O.; Savy, M.; Scarbeck, G.; van den Ham, D.; Riga, J.; Verbist, J.J.

1991-01-01

O2 electrocatalysis on (2,3)FeNPc impregnations on different carbon blacks was investigated in H2SO4 medium. The effect of nitric acid treatment on the carbon black support is to enhance both the activity and stability of the catalyst. Moreover, as seen by XPS, the dissolution of iron is impeded by

Treatment of Active Acne Vulgaris by Chemical Peeling Using 88% Lactic Acid

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Khalifa E. Sharquie

2014-10-01

Full Text Available Introduction: The etiopathogenesis of acne vulgaris is multifactorial, and its therapy is prolonged course that might be not accepted by many patients. Most recently TCA 35% one session peeling gave complete clearance and full remission for active acne vulgaris. Lactic acid has been used effectively as therapeutic topical agents for many skin diseases. Aim: To evaluate the efficacy and safety of chemical peeling using 88% lactic acid solution in the treatment of active acne vulgaris. Material and Methods: This clinical, interventional, therapeutic study was done at the Department of Dermatology, Baghdad Teaching Hospital, during the period from October 2012 to October 2013. Twenty five patients with active acne vulgaris were included, 15 (60% females and 10 (40% males and their ages ranged from 16-36 (21.5000± 5.46279 years. Fifteen patients were associated with acne scars. Three chemical peels using 88% lactic acid solution was carried out two weeks apart for patients with active acne vulgaris with or without scarring. Scoring for active acne vulgaris and acne scar was done for each case before and after operation to evaluate the severity of acne and the degree of scar before and after treatment. All patients were with Fitzpatrick’s skin types III and IV. Patients were followed up every two weeks during period of therapy and monthly for 3 months after stopping the treatment. Results: Twenty five patients with active acne vulgaris were treated with 3 sessions of lactic acid, fifteen patients had associated acne scar. Scoring for active acne vulgaris including papules and pustules showed highly statistically significant reduction after 2 weeks of therapy (p=0.0001, after 4 weeks (p=0.0001and after 6 weeks (p=0.0001, with percent reduction 87.2% for papules and 94% for pustules after end of sessions while after 3 months follow up the reduction rate for papules 93.8% and p-value (p=0.001 and for pustules 97.6% and (p=0.0001. While the scarring

Effects of irradiation and fumaric acid treatment on the inactivation of Listeria monocytogenes and Salmonella typhimurium inoculated on sliced ham

Energy Technology Data Exchange (ETDEWEB)

Song, Hyeon-Jeong; Lee, Ji-Hye [Department of Food Science and Technology, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Song, Kyung Bin, E-mail: kbsong@cnu.ac.kr [Department of Food Science and Technology, Chungnam National University, Daejeon 305-764 (Korea, Republic of)

2011-11-15

To examine the effects of fumaric acid and electron beam irradiation on the inactivation of foodborne pathogens in ready-to-eat meat products, sliced ham was inoculated with Listeria monocytogenes and Salmonella typhimurium. The inoculated ham slices were treated with 0.5% fumaric acid or electron beam irradiation at 2 kGy. Fumaric acid treatment reduced the populations of L. monocytogenes and S. typhimurium by approximately 1 log CFU/g compared to control populations. In contrast, electron beam irradiation decreased the populations of S. typhimurium and L. monocytogenes by 3.78 and 2.42 log CFU/g, respectively. These results suggest that electron beam irradiation is a better and appropriate technique for improving the microbial safety of sliced ham. - Highlights: > We compare irradiation and fumaric acid treatment on the inactivation of pathogens. > We examine changes in the populations of L. monocytogenes and S. typhimurium. > Irradiation at 2 kGy is more effective in sliced ham than fumaric acid treatment. > Low-dose irradiation can improve the microbial safety of sliced ham during storage.

Effects of irradiation and fumaric acid treatment on the inactivation of Listeria monocytogenes and Salmonella typhimurium inoculated on sliced ham

International Nuclear Information System (INIS)

Song, Hyeon-Jeong; Lee, Ji-Hye; Song, Kyung Bin

2011-01-01

To examine the effects of fumaric acid and electron beam irradiation on the inactivation of foodborne pathogens in ready-to-eat meat products, sliced ham was inoculated with Listeria monocytogenes and Salmonella typhimurium. The inoculated ham slices were treated with 0.5% fumaric acid or electron beam irradiation at 2 kGy. Fumaric acid treatment reduced the populations of L. monocytogenes and S. typhimurium by approximately 1 log CFU/g compared to control populations. In contrast, electron beam irradiation decreased the populations of S. typhimurium and L. monocytogenes by 3.78 and 2.42 log CFU/g, respectively. These results suggest that electron beam irradiation is a better and appropriate technique for improving the microbial safety of sliced ham. - Highlights: → We compare irradiation and fumaric acid treatment on the inactivation of pathogens. → We examine changes in the populations of L. monocytogenes and S. typhimurium. → Irradiation at 2 kGy is more effective in sliced ham than fumaric acid treatment. → Low-dose irradiation can improve the microbial safety of sliced ham during storage.

Controllable size reduction of CdSe nanowires through the intermediate formation of Se-coated CdSe nanowires using acid and thermal treatment

Energy Technology Data Exchange (ETDEWEB)

Lam, N S [Department of Physics, Chinese University of Hong Kong, Hong Kong (China); Wong, K W [Department of Physics, Chinese University of Hong Kong, Hong Kong (China); Li, Q [Department of Physics, Chinese University of Hong Kong, Hong Kong (China); Zheng, Z [Department of Physics, Chinese University of Hong Kong, Hong Kong (China); Lau, W M [Surface Science Western, University of Western Ontario, London, ON, N6A 5B7 (Canada)

2007-10-17

Thinning of CdSe nanowires (NWs) with controllable size was achieved by a simple acid treatment and subsequent annealing on thick CdSe NWs synthesized from vapour phase growth. During acid treatment, not only the undesired impurities such as native oxides of Cd and Se could be etched, but surface reactions of CdSe NWs were also observed, resulting in the formation of a layer of elemental Se around a thinner CdSe core. As a result, a heterostructure of Se - CdSe nanostructure formed after acid treatment of CdSe NWs. Upon thermal annealing, the Se shell was effectively removed and thinned stoichiometric single-crystalline CdSe NWs could be obtained. It was observed that NWs could be thinned by up to {approx}60% in diameter by acid treatment and subsequent Se thermal desorption. The degree of thinning was controllable by adjusting the duration of acid treatment. The success of the thinning of CdSe NWs by simple acid treatment and the annealing process reported here opens a new processing route for obtaining stoichiometric CdSe NWs with controllable size reduction and improved aspect ratio. This can undoubtedly broadly improve the range of applications of 1D CdSe nanostructures and allow more exploration of their uni-directional properties. A correction was made to the last paragraph of section 3 on 18 September 2007. The corrected electronic version is identical to the print version.

Controllable size reduction of CdSe nanowires through the intermediate formation of Se-coated CdSe nanowires using acid and thermal treatment

International Nuclear Information System (INIS)

Lam, N S; Wong, K W; Li, Q; Zheng, Z; Lau, W M

2007-01-01

Thinning of CdSe nanowires (NWs) with controllable size was achieved by a simple acid treatment and subsequent annealing on thick CdSe NWs synthesized from vapour phase growth. During acid treatment, not only the undesired impurities such as native oxides of Cd and Se could be etched, but surface reactions of CdSe NWs were also observed, resulting in the formation of a layer of elemental Se around a thinner CdSe core. As a result, a heterostructure of Se - CdSe nanostructure formed after acid treatment of CdSe NWs. Upon thermal annealing, the Se shell was effectively removed and thinned stoichiometric single-crystalline CdSe NWs could be obtained. It was observed that NWs could be thinned by up to ∼60% in diameter by acid treatment and subsequent Se thermal desorption. The degree of thinning was controllable by adjusting the duration of acid treatment. The success of the thinning of CdSe NWs by simple acid treatment and the annealing process reported here opens a new processing route for obtaining stoichiometric CdSe NWs with controllable size reduction and improved aspect ratio. This can undoubtedly broadly improve the range of applications of 1D CdSe nanostructures and allow more exploration of their uni-directional properties. A correction was made to the last paragraph of section 3 on 18 September 2007. The corrected electronic version is identical to the print version

Comparison between undecylenic acid and tolnaftate in the treatment of tinea pedis.

Science.gov (United States)

Fuerst, J F; Cox, G F; Weaver, S M; Duncan, W C

1980-05-01

A double-blind parallel study comparing tolnaftate cream with undecylenic acid ointment and a placebo ointment in the treatment of symptomatic tinea pedis was conducted on the warm, humid Texas Gulf Coast. In one hundred and three patients studied, both the clinical and mycological effects of the two antifungal agents were indistinguishable. Both were significantly more effective than the placebo.

Some biochemical reactions of strawberry plants to infection with Botrytis cinerea and salicylic acid treatment

Directory of Open Access Journals (Sweden)

Urszula Małolepsza

2013-12-01

Full Text Available The reactions of strawberry plants to infection with B. cinerea and treatment with salicylic acid has been studied. Infection of leaves with B. cinerea resulted in early increases in active oxygen species generation, superoxide dismutase and peroxidase activities and phenolic compounds content. Some increases of the above reactions were noticed in plants treated with salicylic acid but not in the plants treated with SA and then later infected with B. cinerea.

Endoscopic Treatment of Vesicoureteral Reflux with Dextranomer/Hyaluronic Acid in Children

Directory of Open Access Journals (Sweden)

Andrew J. Kirsch

2008-06-01

Full Text Available Purpose. The goal of this review is to present current indications, injectable agents, techniques, success rates, complications, and potential future applications of endoscopic treatment for vesicoureteral reflux (VUR in children. Materials and Methods. The endoscopic method currently achieving one of the highest success rates is the double hydrodistention-implantation technique (HIT. This method employs dextranomer/hyaluronic acid copolymer, which has been used in pediatric urology for over 10 years and may be at present the first choice injectable agent due to its safety and efficacy. Results. While most contemporary series report cure rates of greater than 85% for primary VUR, success rates of complicated cases of VUR may be, depending on the case, significantly lower. Endoscopic treatment offers major advantages to patients while avoiding potentially complicated open surgery. As the HIT method continues to be applied to complex cases of VUR and more outcome data become available, the indication for endoscopic treatment may exceed the scope of primary VUR. Conclusions. Endoscopic injection is emerging as the treatment of choice for VUR in children.

The effects of acid treatment and sample preparation on 40Ar/39Ar ages

Science.gov (United States)

Morgan, L. E.; Davidheiser, B.; Kuiper, K.; Wijbrans, J. R.

2011-12-01

Practitioners of K-Ar and 40Ar/39Ar geochronology regularly use dilute acids (typically 5-10% hydrofluoric acid (HF)) to clean mineral grains prior to irradiation (in the case of 40Ar/39Ar), and analysis (e.g. Evernden and Curtis, 1965; Dalrymple, 1967). This treatment has been shown to reduce contamination from atmospheric Ar, which consists largely of 40Ar and thus must be differentiated from radiogenic 40Ar* (Evernden and Curtis, 1965). Acid treatments can also remove fine grained material attached to mineral grains, such as glass shards or devitrified glass, which can affect analyses and is difficult to remove by other means (Evernden and Curtis, 1965). Such treatments were originally examined for their efficacy in reducing atmospheric argon contamination (Dalrymple, 1967) but were not assessed for the possibility of leaching Ar* or K differentially, which would affect both K-Ar and 40Ar/39Ar ages. Indeed, Evernden and Curtis (1965) state that they are simply removing the "outer portions of the crystals" and apparently do not account for the potential for leaching of 40Ar* or K from the mass of their host mineral. Moreover, the capabilities of the K-Ar system in the 1960s was limited to a precision of ca. 3-4% on samples of 1-3 Ma (Cox and Dalrymple, 1967). Effects of smaller magnitude could not have been detected at the time. As the developments of the 40Ar/39Ar system and modern mass spectrometer technology have allowed for precision to approach 0.1%, the potential effects of acid treatment during sample preparation warrant revisiting. Additionally, the use of Calgon for sample disintegration has not previously been quantitatively assessed but is used extensively in some laboratories. Here we present a series of experiments from co-irradiated Fish Canyon sanidine (FCs) and Mes-4 (Kuiper et al., 2008). FCs is used as the mineral standard following standard procedures. Mes-4 splits were treated with H2O (10 minutes, ultrasonic), Calgon (10%, overnight at 50�

Nonuremic calciphylaxis precipitated by teriparatide [rhPTH(1-34)] therapy in the setting of chronic warfarin and glucocorticoid treatment.

Science.gov (United States)

Spanakis, E K; Sellmeyer, D E

2014-04-01

Calciphylaxis occurs rarely in the absence of end stage renal disease. Predisposing factors for nonuremic calciphylaxis (NUC) include hyperparathyroidism, coagulopathies, connective tissue disease, liver disease, glucocorticoid use, and malignancy. Warfarin can facilitate vascular calcification by reducing vitamin K-dependent carboxylation of matrix-Gla proteins. An 86-year-old Caucasian woman with a history of polymyalgia rheumatica, two spontaneous deep venous thromboses (DVTs) and multiple fractures was treated with calcium, vitamin D, prednisone, and warfarin. The patient's low bone density was treated initially with estrogen, then oral bisphosphonate, which was discontinued due to upper gastrointestinal symptoms. Nasal calcitonin was initiated. After 10 years of calcitonin treatment, she was changed to teriparatide. Two months after initiating teriparatide, she developed lower extremity edema and painful erythematous nodular lesions on her calves bilaterally, that progressed to necrotic ulcers despite antibiotic therapy. Biopsy of the lesions showed calcification in the media of small blood vessels and subcutaneous fat with fat necrosis, consistent with calciphylaxis. Teriparatide was discontinued. Aggressive wound care, antibiotics, and intravenous zoledronic acid were initiated. With cessation of teriparatide therapy and intensive wound care, the patient's lesions resolved over 8 months. We report the first case of NUC precipitated by teriparatide therapy. Our patient had multiple underlying predisposing factors including a connective tissue disorder, glucocorticoid therapy, warfarin use, and possible underlying coagulopathy given her history of multiple DVTs. In such patients, alternative osteoporosis therapies may be preferred.

Slag Treatment Followed by Acid Leaching as a Route to Solar-Grade Silicon

NARCIS (Netherlands)

Meteleva-Fischer, Y.V.; Yang, Y.; Boom, R.; Kraaijveld, B.; Kuntzel, H.

2012-01-01

Refining of metallurgical-grade silicon was studied using a process sequence of slag treatment, controlled cooling, and acid leaching. A slag of the Na2O-CaO-SiO2 system was used. The microstructure of grain boundaries in the treated silicon showed enhanced segregation of impurities, and the

Effect of quarantine treatments on the carbohydrate and organic acid content of mangoes (cv. Tommy Atkins)

Science.gov (United States)

Cruz, J. N.; Soares, C. A.; Fabbri, A. D. T.; Cordenunsi, B. R.; Sabato, S. F.

2012-08-01

Brazil is one of the largest mango producers and the third largest mango exporter worldwide. Irradiation treatment and its commercial feasibility have been studied in our country to make it possible to develop new markets and, consequently, to compete with the major exporters of mangoes, Mexico and India. This work was designed to compare irradiation treatment with the hot water dip treatment in mangoes cv. Tommy Atkins for export and to verify that the main attributes for acceptance, color and texture, as well as carbohydrate and organic acid contents, were maintained. In this study, the fruit was divided into groups: control, hot water dip-treated (46 °C for 90 min), and irradiation-treated at doses of 0.4 kGy and 1.0 kGy. The fruit was stored at low temperature (11 °C±2) for 14 days and then at room temperature (23 °C±2) until the end of the study. The results indicated that the fruit given a dose of 1.0 kGy remained in a less advanced stage of ripening (stage 3) throughout the storage period, but experienced a greater loss of texture in the beginning of the experiment. It was noted that only the control group had higher levels of citric acid and succinic acid on the last day of the experiment. There were no significant differences in the total sugar content between any treatment groups. Gamma radiation can be used as a quarantine treatment and does not interfere negatively with the quality attributes of mangoes.

Copper-Sulfate Pentahydrate as a Product of the Waste Sulfuric Acid Solution Treatment

Science.gov (United States)

Marković, Radmila; Stevanović, Jasmina; Avramović, Ljiljana; Nedeljković, Dragutin; Jugović, Branimir; Stajić-Trošić, Jasna; Gvozdenović, Milica

2012-12-01

The aim of this study is synthesis of copper-sulfate pentahydrate from the waste sulfuric acid solution-mother liquor generated during the regeneration process of copper bleed solution. Copper is removed from the mother liquor solution in the process of the electrolytic treatment using the insoluble lead anodes alloyed with 6 mass pct of antimony on the industrial-scale equipment. As the result of the decopperization process, copper is removed in the form of the cathode sludge and is precipitated at the bottom of the electrolytic cell. By this procedure, the content of copper could be reduced to the 20 mass pct of the initial value. Chemical characterization of the sludge has shown that it contains about 90 mass pct of copper. During the decopperization process, the very strong poison, arsine, can be formed, and the process is in that case terminated. The copper leaching degree of 82 mass pct is obtained using H2SO4 aqueous solution with the oxygen addition during the cathode sludge chemical treatment at 80 °C ± 5 °C. Obtained copper salt satisfies the requirements of the Serbian Standard for Pesticide, SRPS H.P1. 058. Therefore, the treatment of waste sulfuric acid solutions is of great economic and environmental interest.

Combined Treatment with Hyaluronic Acid and Mesalamine Protects Rats from Inflammatory Bowel Disease Induced by Intracolonic Administration of Trinitrobenzenesulfonic Acid

Directory of Open Access Journals (Sweden)

Chih-Tung Chiu

2017-05-01

Full Text Available Drugs such as mesalamine (5-ASA are currently recommended for the treatment of inflammatory bowel disease (IBD. To reduce the frequency of their administration and improve their therapeutic effect, this study investigated the adhesion efficacy, wound healing promotion, and decrease in inflammation in ulcers in the colonic tissue of rats with colitis after combined treatment with hyaluronic acid (HA and 5-ASA (IBD98-M. HA-fluoresceinamine (FL conjugates successfully adhered to the mucosal layer and were conjugated in the vascular tissue. In addition, macroscopic and microscopic observations indicated that colonic injuries reduced significantly after treatment with IBD98-M. Compared with PBS and 5-ASA treatment alone, treatment with IBD98-M more effectively reduced bowel inflammation and promoted colonic mucosal healing in TNBS-induced colitis. IBD98-M treatment also reduced myeloperoxidase activity and the expression levels of cyclooxygenase 2 and tumor necrosis factor-αin the colitis tissue. In conclusion, IBD98-M treatment strongly promoted wound healing in colonic injuries and significantly inhibited MPO activity in the inflamed colon tissue of rats. Combined treatment with HA and 5-ASA can accelerate wound healing and reduce inflammatory reaction in rat colitis.

CITOGENETICS EFFECTS INDUCED BY THE ASCORBIC ACID TREATMENT OF LARIX DECIDUA MILL. SSP. CARPATICA AND PICEA ABIES (L. KARST

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Ioana Ieremia

2006-08-01

Full Text Available The paper present the influence of ascorbic acid upon the mitotic division of Larix decidua Mill ssp. carpatica and Picea abies (L. Karst. The treatment is applied of two variants, germinated seed in ascorbic acid (variantAand germinated seeds in disttilate water, than treated with ascorbic acid in 3 concentrations (variant B.

Functionalization of carbon nanotube yarn by acid treatment

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H.E. Misak

2014-01-01

Full Text Available Carbon nanotube (CNT yarn was functionalized using sulfuric and nitric acid solutions in 3:1 volumetric ratio. Successful functionalization of CNT yarn with carboxyl and hydroxyl groups (e.g., COOH, COO–, OH, etc. was confirmed by attenuated total reflectance spectroscopy. X-ray diffraction revealed no significant change to the atomic in-plane alignment in the CNTs; however, the coherent length along the diameter was significantly reduced during functionalization. A morphology change of wavy extensions protruding from the surface was observed after the functionalization treatment. The force required to fracture the yarn remained the same after the functionalization process; however, the linear density was increased (310%. The increase in linear density after functionalization reduced the tenacity. However, the resistivity density product of the CNT yarn was reduced significantly (234% after functionalization.

Treatment of the acid mine drainage residue for uranium recovery

International Nuclear Information System (INIS)

Dias, M.M.; Horta, D.G.; Fukuma, H.T.; Villegas, R.A.S.; Carvalho, C.H.T. de; Silva, A.C. da

2017-01-01

Acid mine drainage (AMD) is a process that occurs in many mining that have sulfide ores. With water and oxygen, several metals are oxidized, one example being uranium. At the mine pit of the Osamu Utsumi Mine located at INB - Caldas and in two other boot-wastes (mining waste pile), AMD is present and currently, without a technological solution. The acidic water present in the pit is treated with hydrated lime, generating water for disposal and an alkaline residue called calcium diuranate - DUCA. The DUCA has a concentration of approximately 0.32% U 3 O 8 , which makes interesting the development of a process for extracting that metal. One of the processes that can be used is leaching. For this study, it was decided to evaluate the alkaline leaching to extract the uranium present in the residue. It is necessary to optimize operational parameters for the process: percentage of solids, concentration of leaching agent in solution, temperature and reaction time. With these parameters, it is possible to improve the leaching so that the largest amount of uranium is extracted from the sample, to help solve the environmental impact caused by the wastewater from the treatment of acid waters and, in addition, to give an economical destination for this metal that is contained in the deposited DUCA

Enhanced Biocide Treatments with D-amino Acid Mixtures against a Biofilm Consortium from a Water Cooling Tower.

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Jia, Ru; Li, Yingchao; Al-Mahamedh, Hussain H; Gu, Tingyue

2017-01-01

Different species of microbes form mixed-culture biofilms in cooling water systems. They cause microbiologically influenced corrosion (MIC) and biofouling, leading to increased operational and maintenance costs. In this work, two D-amino acid mixtures were found to enhance two non-oxidizing biocides [tetrakis hydroxymethyl phosphonium sulfate (THPS) and NALCO 7330 (isothiazoline derivatives)] and one oxidizing biocide [bleach (NaClO)] against a biofilm consortium from a water cooling tower in lab tests. Fifty ppm (w/w) of an equimass mixture of D-methionine, D-leucine, D-tyrosine, D-tryptophan, D-serine, D-threonine, D-phenylalanine, and D-valine (D8) enhanced 15 ppm THPS and 15 ppm NALCO 7330 with similar efficacies achieved by the 30 ppm THPS alone treatment and the 30 ppm NALCO 7330 alone treatment, respectively in the single-batch 3-h biofilm removal test. A sequential treatment method was used to enhance bleach because D-amino acids react with bleach. After a 4-h biofilm removal test, the sequential treatment of 5 ppm bleach followed by 50 ppm D8 achieved extra 1-log reduction in sessile cell counts of acid producing bacteria, sulfate reducing bacteria, and general heterotrophic bacteria compared with the 5 ppm bleach alone treatment. The 10 ppm bleach alone treatment showed a similar efficacy with the sequential treatment of 5 ppm bleach followed by 50 ppm D8. The efficacy of D8 was found better than that of D4 (an equimass mixture of D-methionine, D-leucine, D-tyrosine, and D-tryptophan) in the enhancement of the three individual biocides against the biofilm consortium.

Enhanced Biocide Treatments with D-amino Acid Mixtures against a Biofilm Consortium from a Water Cooling Tower

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Ru Jia

2017-08-01

Full Text Available Different species of microbes form mixed-culture biofilms in cooling water systems. They cause microbiologically influenced corrosion (MIC and biofouling, leading to increased operational and maintenance costs. In this work, two D-amino acid mixtures were found to enhance two non-oxidizing biocides [tetrakis hydroxymethyl phosphonium sulfate (THPS and NALCO 7330 (isothiazoline derivatives] and one oxidizing biocide [bleach (NaClO] against a biofilm consortium from a water cooling tower in lab tests. Fifty ppm (w/w of an equimass mixture of D-methionine, D-leucine, D-tyrosine, D-tryptophan, D-serine, D-threonine, D-phenylalanine, and D-valine (D8 enhanced 15 ppm THPS and 15 ppm NALCO 7330 with similar efficacies achieved by the 30 ppm THPS alone treatment and the 30 ppm NALCO 7330 alone treatment, respectively in the single-batch 3-h biofilm removal test. A sequential treatment method was used to enhance bleach because D-amino acids react with bleach. After a 4-h biofilm removal test, the sequential treatment of 5 ppm bleach followed by 50 ppm D8 achieved extra 1-log reduction in sessile cell counts of acid producing bacteria, sulfate reducing bacteria, and general heterotrophic bacteria compared with the 5 ppm bleach alone treatment. The 10 ppm bleach alone treatment showed a similar efficacy with the sequential treatment of 5 ppm bleach followed by 50 ppm D8. The efficacy of D8 was found better than that of D4 (an equimass mixture of D-methionine, D-leucine, D-tyrosine, and D-tryptophan in the enhancement of the three individual biocides against the biofilm consortium.

A review of omeprazole use in the treatment of acid-related disorders in children.

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Zimmermann, A E; Walters, J K; Katona, B G; Souney, P E; Levine, D

2001-05-01

Acid peptic disease is a common problem, with a similar prevalence of gastroesophageal reflux disease (GERD) in adults and children. The presentation of GERD in infants and children varies from crying, irritability, or sleep disturbance to feeding difficulties, vomiting, or rumination. Helicobacter pylori (HP)-related diseases and gastric and duodenal ulcers are much more common in adults than in children, who are more likely to have gastritis or duodenitis. However, because HP infection is most likely acquired in childhood, treatment of children with endoscopically documented active HP disease may minimize the potential risk for peptic ulcer or gastric cancer in adulthood, although this is yet to be proved. Omeprazole has been shown to be effective in the treatment of acid-related diseases. This paper reviews the literature on the use and administration of omeprazole for the treatment of GERD, peptic ulcer disease, HP infection, and other acid-related conditions in children. Studies were identified through searches of MEDLINE and Science Citation Index for the period 1986 to November 2000, and from the reference lists of identified articles. The search terms used included omeprazole, proton pump inhibitor (PPI), children, pediatrics, routes of administration, GERD, HP infection, esophagitis, and administration. In addition, the manufacturer of omeprazole was asked for relevant unpublished information. Marketed and extemporaneous formulations of omeprazole have been administered to children aged 2 months to 18 years for the treatment of erosive esophagitis, gastric ulcer, duodenal ulcer, HP infection, and related conditions at dosages of 5 to 80 mg/d (0.2-3.5 mg/kg/d) for periods ranging from 14 days to 36 months with a low incidence of adverse effects. The initial dose most consistently reported to heal esophagitis and provide relief of symptoms of GERD appears to be 1 mg/kg per day. In uncontrolled clinical trials and case reports to date, omeprazole has been

Gorham-Stout syndrome of the pelvic girdle treated by radiation therapy. A case report

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Heyd, Reinhard; Tselis, Nikolaos; Zamboglou, Nikolaos; Rabeneck, Daniela; Universitaetsklinikum Frankfurt, Frankfurt am Main; Doernenburg, Oliver

2011-01-01

The Gorham-Stout syndrome (GSS) is a rare, benign idiopathic and progressive disorder causing massive osteolysis due to a vascular hyperproliferation replacing the bony structure. Clinical experience concerning the efficacy of radiation therapy (RT) is limited to about 50 of an overall 200 cases reported worldwide. Case Report: A 24-year-old bedridden woman had histologically proven GSS with destruction of the anterior pelvic girdle and received RT for a total dose of 45.0 Gy applied in 5 weekly fractions of 1.8 Gy. In addition, the patient received intravenously 4 mg zoledronic acid once a month. One year after the combined treatment, complete pain relief occurred, and the patient was able to walk without the use of appliances. Imaging studies revealed no progression of the osteolysis but only minimal signs of remineralization. Conclusion: Combined treatment with RT and bisphosphonate administration can prevent the progression of osteolysis in GSS. Total doses of 40-45 Gy are recommended. (orig.)

Gorham-Stout syndrome of the pelvic girdle treated by radiation therapy. A case report

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Heyd, Reinhard; Tselis, Nikolaos; Zamboglou, Nikolaos [Klinikum Offenbach, Offenbach am Main (Germany). Strahlenklinik; Rabeneck, Daniela [Klinikum Offenbach, Offenbach am Main (Germany). Strahlenklinik; Universitaetsklinikum Frankfurt, Frankfurt am Main (Germany). Klinik fuer Strahlentherapie und Onkologie; Doernenburg, Oliver [Klinikum Offenbach, Offenbach am Main (Germany). Inst. fuer Diagnostische und Interventionelle Radiologie

2011-02-15

The Gorham-Stout syndrome (GSS) is a rare, benign idiopathic and progressive disorder causing massive osteolysis due to a vascular hyperproliferation replacing the bony structure. Clinical experience concerning the efficacy of radiation therapy (RT) is limited to about 50 of an overall 200 cases reported worldwide. Case Report: A 24-year-old bedridden woman had histologically proven GSS with destruction of the anterior pelvic girdle and received RT for a total dose of 45.0 Gy applied in 5 weekly fractions of 1.8 Gy. In addition, the patient received intravenously 4 mg zoledronic acid once a month. One year after the combined treatment, complete pain relief occurred, and the patient was able to walk without the use of appliances. Imaging studies revealed no progression of the osteolysis but only minimal signs of remineralization. Conclusion: Combined treatment with RT and bisphosphonate administration can prevent the progression of osteolysis in GSS. Total doses of 40-45 Gy are recommended. (orig.)

Treatment of a traumatic atrophic depressed scar with hyaluronic acid fillers: a case report

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Hussain SN

2017-08-01

Full Text Available Syed Nazim Hussain,1 Greg J Goodman,2,3 Eqram Rahman4 1Royal Lush Skin Hair & Laser Clinic, Saket, New Delhi, India; 2Department of Primary Care, Monash University, Clayton, 3Skin and Cancer Foundation Inc, Carlton, VIC, Australia; 4Faculty of Medical Science, Postgraduate Medical Institute, Anglia Ruskin University, Chelmsford, UK Background: Hyaluronic acid filler has been documented in the treatment of atrophic depressed acne scars relatively frequently in the literature but rarely in chronic depressed traumatic atrophic facial scars.Methods: This case report discusses the use of hyaluronic acid fillers in the correction of a post-traumatic facial atrophic scar on the right cheek.Results: The right cheek scar was substantially corrected with one session of two different hyaluronic acids injected in a deep and superficial plane.Conclusion: Relatively accurate, simple and effective correction of this atrophic traumatic scar may suggest that fillers are a suitable alternative to surgery for such scars. Keywords: scarring, scar correction, filler, hyaluronic acid, facial scar

A review of treatment strategies for hydrofluoric acid burns: current status and future prospects.

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Wang, Xingang; Zhang, Yuanhai; Ni, Liangfang; You, Chuangang; Ye, Chunjiang; Jiang, Ruiming; Liu, Liping; Liu, Jia; Han, Chunmao

2014-12-01

Hydrofluoric acid (HF), a dangerous inorganic acid, can cause severe corrosive effects and systemic toxicity. HF enters the human body via where it contacts, such as skin and mucosa, alimentary and respiratory tracts, and ocular surfaces. In the recent years, the incidence of HF burn has tended to increase over time. The injury mechanism of HF is associated primarily with the massive absorption of HF and the release of hydrogen ions. Correct diagnosis and timely treatment are especially important for HF burns. The critical procedure to treat HF burn is to prevent on-going HF absorption, and block the progressive destruction caused by fluoride ions. Due to the distinct characteristics of HF burns, the topical treatment, as well as systemic support, has been emphasised. Whereas, management of patients with HF burns remains a great challenge in some situations. To date, there has been no widely accepted protocol for the rescue of HF burns, partly due to the diversity of HF burns. This paper overviews the current status and problems of treatment strategies for HF burns, for the purpose of promoting the future researches and improvement. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

Surface modification of polylactic acid films by atmospheric pressure plasma treatment

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Kudryavtseva, V. L.; Zhuravlev, M. V.; Tverdokhlebov, S. I.

2017-09-01

A new approach for the modification of polylactic acid (PLA) materials using atmospheric pressure plasma (APP) is described. PLA films plasma exposure time was 20, 60, 120 s. The surface morphology and wettability of the obtained PLA films were investigated by atomic force microscopy (AFM) and the sitting drop method. The atmospheric pressure plasma increased the roughness and surface energy of PLA film. The wettability of PLA has been improved with the application of an atmospheric plasma surface treatment. It was shown that it is possible to obtain PLA films with various surface relief and tunable wettability. Additionally, we demonstrated that the use of cold atmospheric pressure plasma for surface activation allows for the immobilization of bioactive compounds like hyaluronic acid (HA) on the surface of obtained films. It was shown that composite PLA-HA films have an increased long-term hydrophilicity of the films surface.

Monitoring renal function during biphosphonate treatment in patients with bone metastases - role of dynamic kidney scintigraphy

International Nuclear Information System (INIS)

Chavdarova, L.; Tzonevska, A.

2015-01-01

Full text: Biphosphonates (BP) are very effective in treatment of bone metastatic disease. Their renal excretion defines one of the major side effects - nephrotoxicity. Glomerular filtration rate (GFR) is a basic parameter for its early detection but clinical practice often uses only serum creatinine. Aim of our retrospective study is to assess the role of dynamic kidney scintigraphy (DKS) and the estimated during it GFR in BP-treated patients with bone metastatic disease. 61 patients (53 female, 8 male), aged 33-82, with biphosphonate-treated bone metastases from breast (n53), lung (n1) and prostate (n7) cancer were enrolled for the period 27.04.2012-14.04.2015. Overall 77 studies were made, in 13 patients more than one. GFR was assessed in 57 studies. Results were compared with serum creatinine. All patients with elevated creatinine showed low GFR and decreased renal function at DKS. With normal creatinine and decreased GFR: in 31 studies kidney function was reduced, in 14 function was normal but kidney scintigraphic appearance was disturbed- mostly as in diffuse parenchymal disease. In 5 studies GFR was normal and renal function decreased. In 3 studies both parameters were normal. Zoledronic acid was changed with denosumab in 2 patients because of worsened function and strongly reduced GFR, in one patient BP was stopped after DKS. In 3 patients the interval between BP was extended because of affected renal function. GFR is more sensitive than serum creatinine levels and changes in nephrographic curves. Dynamic kidney scintigraphy is a functional method directing clinical reaction to preserve renal function

Oil sands thickened froth treatment tailings exhibit acid rock drainage potential during evaporative drying.

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Kuznetsov, Petr; Kuznetsova, Alsu; Foght, Julia M; Siddique, Tariq

2015-02-01

Bitumen extraction from oil sands ores after surface mining produces different tailings waste streams: 'froth treatment tailings' are enriched in pyrite relative to other streams. Tailings treatment can include addition of organic polymers to produce thickened tailings (TT). TT may be further de-watered by deposition into geotechnical cells for evaporative drying to increase shear strength prior to reclamation. To examine the acid rock drainage (ARD) potential of TT, we performed predictive analyses and laboratory experiments on material from field trials of two types of thickened froth treatment tailings (TT1 and TT2). Acid-base accounting (ABA) of initial samples showed that both TT1 and TT2 initially had net acid-producing potential, with ABA values of -141 and -230 t CaCO₃ equiv. 1000 t(-1) of TT, respectively. In long-term kinetic experiments, duplicate ~2-kg samples of TT were incubated in shallow trays and intermittently irrigated under air flow for 459 days to simulate evaporative field drying. Leachates collected from both TT samples initially had pH~6.8 that began decreasing after ~50 days (TT2) or ~250 days (TT1), stabilizing at pH~2. Correspondingly, the redox potential of leachates increased from 100-200 mV to 500-580 mV and electrical conductivity increased from 2-5 dS m(-1) to 26 dS m(-1), indicating dissolution of minerals during ARD. The rapid onset and prolonged ARD observed with TT2 is attributed to its greater pyrite (13.4%) and lower carbonate (1.4%) contents versus the slower onset of ARD in TT1 (initially 6.0% pyrite and 2.5% carbonates). 16S rRNA gene pyrosequencing analysis revealed rapid shift in microbial community when conditions became strongly acidic (pH~2) favoring the enrichment of Acidithiobacillus and Sulfobacillus bacteria in TT. This is the first report showing ARD potential of TT and the results have significant implications for effective management of pyrite-enriched oil sands tailings streams/deposits. Copyright © 2014

Endoscopic treatment of vesicoureteral reflux with polyacrylate polyalcohol copolymer and dextranomer/hyaluronic acid in adults

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Akif Turk

2014-06-01

Full Text Available Purpose Aim of this study is to examine the effectiveness of dextranomer/hyaluronic acid copolymer and polyacrylate polyalcohol copolymer in endoscopic treatment of vesicoureteral reflux disease in adult patients with and without chronic renal failure. Materials and Methods Thirty two patients (12 female, 20 male with a total of 50 renal units were treated for vesicoureteral reflux. There were 26 (81% chronic renal failure patients. The success of treatment was evaluated by voiding cystouretrography at 3rd and 12th months after subureteric injection. The persistence of reflux was considered as failure. Patients were divided into two groups according to injected material. Age, sex, grade of reflux and treatment results were recorded and evaluated. Results Reflux was scored as grade 1 in seven (14%, grade 2 in 16 (32%, grade 3 in 21 (42% and grade 4 in six (12% renal units. There was not patient with grade 5 reflux. Fourteen renal units (28% were treated with dextranomer/hyaluronic acid copolymer (group 1 and 36 renal units (72% were treated with polyacrylate polyalcohol copolymer (group 2. The overall treatment success was achieved at 40 renal units (80%. The treatment was successful at 11 renal units (79% in group 1 and 29 renal units (81% in group 2 (p = 0.71. There was not statistically significant difference between two groups with patients with chronic renal failure in terms of treatment success (p = 1.00. Conclusions The effectiveness of two bulking agents was similar in treatment of vesicoureteral reflux disease in adult patients and patients with chronic renal failure.

Endoscopic treatment of vesicoureteral reflux with polyacrylate polyalcohol copolymer and dextranomer/hyaluronic acid in adults.

Science.gov (United States)

Turk, Akif; Selimoglu, Ahmet; Demir, Kadir; Celik, Osman; Saglam, Erkin; Tarhan, Fatih

2014-01-01

Aim of this study is to examine the effectiveness of dextranomer/hyaluronic acid copolymer and polyacrylate polyalcohol copolymer in endoscopic treatment of vesicoureteral reflux disease in adult patients with and without chronic renal failure. Thirty two patients (12 female, 20 male) with a total of 50 renal units were treated for vesicoureteral reflux. There were 26 (81%) chronic renal failure patients. The success of treatment was evaluated by voiding cystouretrography at 3rd and 12th months after subureteric injection. The persistence of reflux was considered as failure. Patients were divided into two groups according to injected material. Age, sex, grade of reflux and treatment results were recorded and evaluated. Reflux was scored as grade 1 in seven (14%), grade 2 in 16 (32%), grade 3 in 21 (42%) and grade 4 in six (12%) renal units. There was not patient with grade 5 reflux. Fourteen renal units (28%) were treated with dextranomer/hyaluronic acid copolymer (group 1) and 36 renal units (72%) were treated with polyacrylate polyalcohol copolymer (group 2). The overall treatment success was achieved at 40 renal units (80%). The treatment was successful at 11 renal units (79%) in group 1 and 29 renal units (81%) in group 2 (p = 0.71). There was not statistically significant difference between two groups with patients with chronic renal failure in terms of treatment success (p = 1.00). The effectiveness of two bulking agents was similar in treatment of vesicoureteral reflux disease in adult patients and patients with chronic renal failure.

Effect of tocopherol treatment on deterioration of edible oil quality (acid value, carbonyl value, free fatty acid and radical activity).

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Ogata, Fumihiko; Tanaka, Yuko; Kawasaki, Naohito

2014-01-01

In this study, waste edible oil was prepared by both heat and aeration treatment, and the increasing inhibitive effect of tocopherol treatment on the acid value (AV) and carbonyl value (CV) of the oil was investigated. The AV and CV of waste edible oil treated with tocopherol were 0.1-1.0% lower than those of the nontreated oil, indicating that tocopherol exerted a radical-scavenging activity. The concentration of tocopherol decreased with time, while that of the remaining 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals increased. These results suggest that the addition of tocopherol proved to be useful for preventing the deterioration of waste edible oil.

A study comparing chemical peeling using modified jessner′s solution and 15% trichloroacetic acid versus 15% trichloroacetic acid in the treatment of melasma

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Safoury Omar

2009-01-01

Full Text Available Background: Melasma is a symmetric progressive hyperpigmentation of the facial skin that occurs in all races but has a predilection for darker skin phenotypes. Depigmenting agents, laser and chemical peeling as classic Jessner′s solution, modified Jessner′s solution and trichloroacetic acid have been used alone and in combination in the treatment of melasma. Objectives: The aim of the study was to compare the therapeutic effect of combined 15% Trichloroacetic acid (TCA and modified Jessner′s solution with 15% TCA on melasma. Materials and Methods: Twenty married females with melasma (epidermal type, with a mean age of 38.25 years, were included in this study. All were of skin type III or IV. Fifteen percent TCA was applied to the whole face, with the exception of the left malar area to which combined TCA 15% and modified Jessner′s solution was applied. Results: Our results revealed statistically highly significant difference between MASI Score (Melasma Area and Severity Index between the right malar area and the left malar area. Conclusion: Modified Jessner′s solution proved to be useful as an adjuvant treatment with TCA in the treatment of melasma, improving the results and minimizing postinflammatory hyperpigmentation.

Temperature dependence and P/Ti ratio in phosphoric acid treatment of titanium dioxide and powder properties.

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Onoda, H; Matsukura, A

2015-02-01

Titanium dioxide has photocatalytic activity and is used as a white pigment for cosmetics. A certain degree of sebum on the skin is decomposed by the ultraviolet radiation in sunlight. In this work, titanium dioxide was shaken with phosphoric acid to synthesize a white pigment for cosmetics. Titanium dioxide was treated with 0.1 mol/L of phosphoric acid at various P/Ti molar ratios, and then shaken in hot water for 1 h. The chemical composition, powder properties, photocatalytic activity, colour phase, and smoothness of the obtained powder were studied. The obtained materials indicated XRD peaks of titanium dioxide, however the peaks diminished subsequent to phosphoric acid treatment. The samples included small particles with sub-micrometer size. The photocatalytic activity of the obtained powders decreased, decomposing less sebum on the skin. Samples prepared at high P/Ti ratio with high shaking temperature indicated low whiteness in in L*a*b* colour space. The shaking and heating temperature and P/Ti ratio had influence on the smoothness of the obtained materials. Phosphoric acid treatment of titanium dioxide is an effective method to inhibit photocatalytic activity for a white pigment. © 2014 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Amino acid content in red wines obtained from grapevine nitrogen foliar treatments: consumption during the alcoholic fermentation

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Javier Portu

2014-12-01

Full Text Available Nitrogen is an important element for grapevine and winemaking which affects the development of the plant and yeast, and therefore it is important for wine quality. The aim of this work was to study the influence of foliar application to vineyard of proline, phenylalanine and urea and two commercial nitrogen fertilizers, without and with amino acids in their formulation, on the wine amino acid content and their consumption during the alcoholic fermentation. The results showed that these treatments did not affect the amino acid composition in wines. The differences observed for certain amino acids were so small that the concentration of total amino acids was not significantly different among wines. Moreover, it was observed that the higher the content of amino acids in the medium, the greater their consumption during the alcoholic fermentation.

Effect of combination treatment of gamma irradiation and ascorbic acid on physicochemical and microbial quality of minimally processed eggplant (Solanum melongena L.)

International Nuclear Information System (INIS)

Hussain, Peerzada R.; Omeera, A; Suradkar, Prashant P.; Dar, Mohd A.

2014-01-01

Gamma irradiation alone and in combination with ascorbic acid was tested for preventing the surface browning and maintaining the quality attributes of minimally processed eggplant. Eggplant samples after preparation were subjected to treatment of gamma irradiation in the dose range of 0.25–1.0 kGy and to combination treatments of ascorbic acid dip at a concentration of 2.0% w/v and gamma irradiation (dose range 0.5–2.0 kGy) followed by storage at 3±1 °C, RH 80%. Studies revealed inverse correlation (r=−0.93) between the polyphenol oxidase (PPO) activity, browning index and the treatments of ascorbic acid and gamma irradiation. Combinatory treatment of 2.0% w/v ascorbic acid and 1.0 kGy gamma irradiation proved to be significantly (p≤0.05) effective in inhibiting the PPO activity, preventing the surface browning and maintaining the creamy white color and other quality attributes of minimally processed eggplant up to 6 days of refrigerated storage. Sensory evaluation revealed that control and 0.25 kGy irradiated samples were unacceptable only after 3 days of storage. Samples irradiated at 0.5 kGy and 0.75 kGy were unacceptable after 6 days of storage. Microbial analysis revealed that radiation processing of minimally processed eggplant at 1.0 kGy with and without ascorbic acid resulted in around 1 and 1.5 log reduction in yeast and mold count as well as bacterial count just after treatment and 6 days of storage therefore, enhances the microbial safety. - Highlights: • 2.0% ascorbic acid and 1.0 kGy inhibited PPO activity in minimally processed eggplant. • Above treatment maintained creamy white color and storage quality up to 6 days at 3±1 °C. • The treatment gave 1.5 log reductions in microbial counts, thus enhancing microbial safety. • The treatment can provide convenience to consumer and will reduce spoilage during storage

EVALUATION OF SUGARCANE BAGASSE ACID HYDROLYZATE TREATMENTS FOR XYLITOL PRODUCTION

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P.V. GURGEL

1998-09-01

Full Text Available Acid sugarcane bagasse hydrolyzate was submitted to pH shifts in order to remove toxic compounds from the medium. The hydrolyzate was treated with bases containing mono-, di- or tri-valent cations and H2SO4, and its performance as a fermentation medium was evaluated by the production of xylitol by Candida guilliermondii FTI 20037. The use of bases containing mono-valent cations was not an efficient method of detoxification, and the use of a tri-valent cation did not show any detectable improvement in detoxification. The treated hydrolyzate recovery (in volume is greatly affected by the utilized base. Treatment using Al(OH3 and NaOH showed the best hydrolyzate recovery (87.5%, while the others presented a recovery of about 45% of the original hydrolyzate volume. Considering the whole process, best results were achieved by treatment using Al(OH3 and NaOH which allowed 0.55 g of xylitol produced from each gram of xylose in the raw hydrolyzate.

Two novel metal–organic coordination polymers based on diphosphonate and oxalate: Synthesis, structures and properties

International Nuclear Information System (INIS)

Niu, Qing-Jun; Zheng, Yue-Qing; Zhou, Lin-Xia; Zhu, Hong-Lin

2015-01-01

Two 2-(1-imidazole)-1-hydroxyl-1,1'-ethylidenediphosphonato and oxalic acid bridged coordination polymers (H 2 en)[Co 3 (H 2 zdn) 2 (ox)(H 2 O) 2 ] (1) and Cd 2 (H 2 zdn)(ox) 0.5 (H 2 O) (2) (2-(1-imidazole)-1-hydroxyl-1,1'-ethylidenediphosphonic acid=H 5 zdn; oxalic acid=H 2 ox) were synthesized under hydrothermal conditions and characterized by the infrared (IR), thermogravimetric analyses (TGA), elemental analyses (EA) and X-ray diffraction (XRD). Compound 1 is bridged by phosphonate anions to 1D chain, and further linked by oxalate anions to 2D layer. Compound 2 is bridged by O–P–O units of H 5 zdn to the layer, and then pillared by oxalate anions to generate 3D frameworks. Compound 1 shows anti-ferromagnetic behaviors analyzed with the temperature-dependent zero-field ac magnetic susceptibilities, while compound 2 exhibits an influence on the luminescent property. - Graphical abstract: Linked by oxalate, two zoledronate-based metal–organic frameworks are synthesized, which exhibits the different frameworks. Magnetism and luminescent properties have been studied. The weak antiferromagnetic coupling is conducted in 1. - Highlights: • Compound 1 and 2 are first linked by oxalate anion based on zoledronic acid. • Compound 1 generates a classic “dia Diamond” (6 6 ) topology. • Compound 2 exhibits a (4 4 ·6 2 )(4 4 ·6 6 ) topology. • Magnetism and luminescent properties of 1 and 2 have been studied, respectively

Osteoprotegerin reduces the development of pain behaviour and joint pathology in a model of osteoarthritis.

Science.gov (United States)

Sagar, Devi Rani; Ashraf, Sadaf; Xu, Luting; Burston, James J; Menhinick, Matthew R; Poulter, Caroline L; Bennett, Andrew J; Walsh, David A; Chapman, Victoria

2014-08-01

Increased subchondral bone turnover may contribute to pain in osteoarthritis (OA). To investigate the analgesic potential of a modified version of osteoprotegerin (osteoprotegerin-Fc (OPG-Fc)) in the monosodium iodoacetate (MIA) model of OA pain. Male Sprague Dawley rats (140-260 g) were treated with either OPG-Fc (3 mg/kg, subcutaneously) or vehicle (phosphate-buffered saline) between days 1 and 27 (pre-emptive treatment) or days 21 and 27 (therapeutic treatment) after an intra-articular injection of MIA (1 mg/50 µl) or saline. A separate cohort of rats received the bisphosphonate zoledronate (100 µg/kg, subcutaneously) between days 1 and 25 post-MIA injection. Incapacitance testing and von Frey (1-15 g) hind paw withdrawal thresholds were used to assess pain behaviour. At the end of the study, rats were killed and the knee joints and spinal cord removed for analysis. Immunohistochemical studies using Iba-1 and GFAP quantified levels of activation of spinal microglia and astrocytes, respectively. Joint sections were stained with haematoxylin and eosin or Safranin-O fast green and scored for matrix proteoglycan and overall joint morphology. The numbers of tartrate-resistant acid phosphatase-positive osteoclasts were quantified. N=10 rats/group. Pre-emptive treatment with OPG-Fc significantly attenuated the development of MIA-induced changes in weightbearing, but not allodynia. OPG-Fc decreased osteoclast number, inhibited the formation of osteophytes and improved structural pathology within the joint similarly to the decrease seen after pretreatment with the bisphosphonate, zoledronate. Therapeutic treatment with OPG-Fc decreased pain behaviour, but did not improve pathology in rats with established joint damage. Our data suggest that early targeting of osteoclasts may reduce pain associated with OA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Novel retinoic acid receptor alpha agonists for treatment of kidney disease.

Directory of Open Access Journals (Sweden)

Yifei Zhong

Full Text Available Development of pharmacologic agents that protect podocytes from injury is a critical strategy for the treatment of kidney glomerular diseases. Retinoic acid reduces proteinuria and glomerulosclerosis in multiple animal models of kidney diseases. However, clinical studies are limited because of significant side effects of retinoic acid. Animal studies suggest that all trans retinoic acid (ATRA attenuates proteinuria by protecting podocytes from injury. The physiological actions of ATRA are mediated by binding to all three isoforms of the nuclear retinoic acid receptors (RARs: RARα, RARβ, and RARγ. We have previously shown that ATRA exerts its renal protective effects mainly through the agonism of RARα. Here, we designed and synthesized a novel boron-containing derivative of the RARα-specific agonist Am580. This new derivative, BD4, binds to RARα receptor specifically and is predicted to have less toxicity based on its structure. We confirmed experimentally that BD4 binds to RARα with a higher affinity and exhibits less cellular toxicity than Am580 and ATRA. BD4 induces the expression of podocyte differentiation markers (synaptopodin, nephrin, and WT-1 in cultured podocytes. Finally, we confirmed that BD4 reduces proteinuria and improves kidney injury in HIV-1 transgenic mice, a model for HIV-associated nephropathy (HIVAN. Mice treated with BD4 did not develop any obvious toxicity or side effect. Our data suggest that BD4 is a novel RARα agonist, which could be used as a potential therapy for patients with kidney disease such as HIVAN.

Drug-induced Fanconi syndrome associated with fumaric acid esters treatment for psoriasis: A case series

NARCIS (Netherlands)

D.M.W. Balak (Deepak); J.N.B. Bavinck (Jan Nico Bouwes); De Vries, A.P.J. (Aiko P. J.); Hartman, J. (Jenny); Martino Neumann, H.A. (Hendrik A.); R. Zietse (Bob); H.B. Thio (Bing)

2016-01-01

textabstractBackground: Fumaric acid esters (FAEs), an oral immunomodulating treatment for psoriasis and multiple sclerosis, have been anecdotally associated with proximal renal tubular dysfunction due to a drug-induced Fanconi syndrome. Few data are available on clinical outcomes of FAE-induced

Mesenchymal Stem Cells Promote the Osteogenesis in Collagen-Induced Arthritic Mice through the Inhibition of TNF-α

OpenAIRE

Liu, Chang; Zhang, Huayong; Tang, Xiaojun; Feng, Ruihai; Yao, Genhong; Chen, Weiwei; Li, Wenchao; Liang, Jun; Feng, Xuebing; Sun, Lingyun

2018-01-01

Objective. To investigate the effects of umbilical cord mesenchymal stem cell (UC-MSC) transplantation on joint damage and osteoporosis in collagen-induced arthritis (CIA) mice and to explore the mechanisms by which UC-MSCs modulate the osteogenic differentiation. Methods. CIA mice were divided into the following treated groups: UC-MSC transplantation group, antitumor necrosis factor- (TNF-) α group, and zoledronic acid (ZA) group. Microcomputed tomography (micro-CT) was used to analyze the b...

Studying the Behavior of Lactic Acid Bacterias (BAL Culture Bioyogur to Different Doses of Magnetic Treatment

Directory of Open Access Journals (Sweden)

Yarindra Mesa-Mariño

2016-07-01

Full Text Available Yogurt is beneficial in the prevention and restoration of intestinal diseases probiotic. It is obtained from fermentation of bacterial cultures as BIOyogur comprising Lactobacillus acidophilus and Streptococcus thermophilus. In the milk combined Santiago de Cuba, the low viability of these starter cultures for industrial production is 86 %, with a cell concentration of 5,89 log ufcmL-1, affecting fermentation and quality of soy yogurt. Knowing the stimulatingaction of electromagnetic fields (EMF 60 Hz on microorganisms of industrial interest, it is desired to decrease the fermentation time of the production process and improve product quality. Therefore treatment with electromagnetic field to starter cultures, which contributes to the improvement of fermentation time established industry standards and the final product quality, is proposed. For this, the effect of a 60 Hz EMC applying a multifactorial design with treatments 4, 6 and 8 mT at 5, 10 and 15 respectively min exposure was assessed; selecting factors as exposure time, the magnetic induction and prior inoculation. Obtaining as a variables response: growth lactic acid bacteria (LAB, pH and acidity. An increase of 10,38 log ufcmL-1 equal to a value of pH 3.80 and an acidity of 0,81 %, maintaining the quality parameters of the final product 6 mT and 5 min of the selected treatment.

Preferential Treatment: Interaction Between Amino Acids and Minerals

Science.gov (United States)

Crapster-Pregont, E. J.; Cleaves, H. J.; Hazen, R. M.

2008-12-01

Amino acids are the building blocks of proteins and are important for some models of the origin of life. Polymerization of amino acids from dilute solution is unlikely without a scaffold or catalyst. The surfaces of early Earth minerals are the most likely candidates for this role. The surface adsorption behavior of 12 amino acids (L-alanine, L-serine, L-aspartic acid, L-proline, L- phenylalanine, L-valine, L-arginine, d-amino valeric acid, glycine, L-lysine, L-isoleucine, and B-alanine) on 21 minerals (quartz, calcite, enstatite, illite, olivine, pyrrhotite, pyrite, alkali basalt, albite, analcime, chlorite, barite, hydroxyl apatite, hematite, magnetite, aluminum hydroxide, kaolin, silica gel, corundum, rutile, and montmorillonite) was determined via batch adsorption experiments. Absorption was determined for concentrations between 10-4M and 10-6M in the presence of 0.1M NaCl, and between pH values of 3 and 9 at 25 degrees C. The equilibrated solutions were centrifuged, filtered, derivatized using a fluorescent amino group tag (dansyl-chloride) and analyzed by HPLC. Adsorption was standardized using BET surface area measurements for each mineral to give the number of mols of each amino acid adsorbed per square meter for each mineral. The results indicate an enormous difference in the adsorption of amino acids between minerals, along with major differences in the adsorption of individual amino acids on the same mineral surface. There is also a change in the absorbance of amino acids as the pH changes. Many previous studies of amino acid concentration and catalysis by minerals have used clay minerals because of their high surface areas, however, this data suggests that the surfaces of minerals such as calcite, quartz and pyrite have even higher affinities for amino acids. The results suggest mineral surfaces that could be optimal locations for the polymerization of molecules linked to the origin of life.

Removal of Anabaena flos-aquae in water treatment process using Moringa oleifera and assessment of fatty acid profile of generated sludge.

Science.gov (United States)

Moreti, Livia O R; Coldebella, Priscila Ferri; Camacho, Franciele P; Carvalho Bongiovani, Milene; Pereira de Souza, Aloisio Henrique; Kirie Gohara, Aline; Matsushita, Makoto; Fernandes Silva, Marcela; Nishi, Letícia; Bergamasco, Rosângela

2016-01-01

This study aimed to evaluate the efficiency of the coagulation/flocculation/dissolved air flotation (C/F/DAF) process using the coagulant Moringa oleifera (MO) seed powder, and to analyse the profile of fatty acids present in the generated sludge after treatment. For the tests, deionized water artificially contaminated with cell cultures of Anabaena flos-aquae was used, with a cell density in the order of 10(4) cells mL(-1). C/F/DAF tests were conducted using 'Flotest' equipment. For fatty acid profile analyses, a gas chromatograph equipped with a flame ionization detector was used. It was seen that the optimal dosage (100 mg L(-1)) of MO used in the C/F/DAF process was efficient at removing nearly all A. flos-aquae cells (96.4%). The sludge obtained after treatment contained oleic acid (61.7%) and palmitic acid (10.8%). Thus, a water treatment process using C/F/DAF linked to integral MO powder seed was found to be efficient in removing cells of cyanobacteria, and produced a sludge rich in oleic acid that is a precursor favourable for obtaining quality biodiesel, thus becoming an alternative application for the recycling of such biomass.

Combination of Successive Alkalinity Producing System (SAPS) and Aeration for Passive Treatment of Highly Acidic Mine Drainage

Science.gov (United States)

Oh, C.; Ji, S.

2015-12-01

Passive treatment system has been widely used for remediation of mine drainage since its advantage of low installation and maintenance cost. The system, however, has also a disadvantage in assuring remediation and management efficiency if the drainage is highly acidic mine drainage. To remediate acid mine drainage (AMD) especially showing high acidity, passive treatment system which consists of successive alkalinity producing system (SAPS) and subsequent aeration pond was proposed and its mechanisms and efficiency was evaluated in this research. Target AMD was obtained from Waryong coal mine and showed typical characteristics of AMD having high metal concentration and low pH (acidity > 300 mg/L as CaCO3). Four experimental cases were conducted; untreated, treated with SAPS, treated with aeration, treated with SAPS and aeration to compare role and mechanism of each unit. Between organic matter and limestone layer which constitute SAPS, the former eliminated most of Fe(III) and Al in the AMD so that the latter was kept from being clogged by precipitates. Net acidity of the AMD rapidly decreased by supplement of alkalinity at the limestone layer. A primary function of SAPS, producing alkalinity constantly without clogging, was attained due to addition a portion of limestone particle into the organic matter layer. The discharge from SAPS had low ORP and DO values because of an anaerobic environment formed at the organic matter layer although its alkalinity was increased. This water quality was unfavorable for Fe(II) to be oxidized. Installation of aeration pond after SAPS, therefore, could be effective way of enhancing oxidation rate of Fe(II). Among the experimental cases, the combination of SAPS and aeration pond was only able to remediate the AMD. This concluded that to remediate highly acidic mine drainage with passive treatment system, three critical conditions were required; pre-precipitation of Fe(III) and Al at organic matter layer in SAPS, constant alkalinity

Clinical observation of hemocoagulase combined with aminomethylbenzoic acid in the treatment of basal ganglia hemorrhage

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Min SU

2014-07-01

Full Text Available Patients with cerebral hemorrhage in basal ganglia were treated with hemocoagulase combined with aminomethylbenzoic acid from May 2010 to April 2013 in our hospital, and hematoma volume and neurological impairment were compared with the control group before and after treatment. This study confirmed that hemocoagulase combined with aninomethylbenzoic acid is a safe and effective method for cerebral hemorrhage in basal ganglia. It can effectively prevent the hematoma enlargement and improve neurological function and prognosis. doi: 10.3969/j.issn.1672-6731.2014.07.014

Microencapsulated acids associated with essential oils and acid salts for piglets in the nursery phase

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Marco Aurelio Callegari

2016-08-01

Full Text Available The objective of this study was to evaluate the use of commercial blends of organic and inorganic acids combined with essential oils for piglets in the nursery phase. The formulations were administered as microcapsules or as acid salts. Ninety-six, Pen Ar Lan, barrow and female piglets, weaned at a body weight of 600 kg ± 12 kg and age of 23 days were subjected to four treatments. The animals were distributed in randomized blocks of three animals per pen and 8 replicates per treatment. The treatments consisted of four different diets: control (free of organic acids; acid and essential oil blends (fumaric acid 10,5%, malic acid 8.0%, essential oils; in microencapsulated form; microencapsulated acid blend (phosphoric acid 10%, citric acid 10%, malic acid 10%, fumaric acid 20%; in microencapsulated form; and acid salt blend (formic acid 40.5%, phosphoric acid 13.6%, propionic acid 4.9% and salts (23.2% calcium and 4.4% phosphorus available. The performance parameters, digestive transit time, weights of organs of the digestive tract, bacterial count of feces (Lactobacillus, E coli and Salmonella ssp and Clostridium, pH of the stomach and duodenal content did not differ between treatment groups (P > 005. All treatments containing organic acids exhibited positive effects on diarrhea control (P < 005. The cecal contents of volatile fatty acids (VFA were higher in piglets fed diets containing acids than in animals that received the control diet (P < 005, and blends containing essential oils improved the jejunum villus height compared with the control group. The use of diets containing acids improved diarrhea control and VFA production in the cecum, and specifically the diets containing microencapsulated acid blends required the lowest doses to be effective.

Investigation of virgin coals and coals subjected to a mild acid treatment

Energy Technology Data Exchange (ETDEWEB)

Clark, T.M.; Evans, B.J.; Wynter, C.; Pollak, H.; Taole, S.; Radcliffe, D. [University of Michigan, Ann Arbor, MI (United States). Dept. of Chemistry

1998-06-01

A quantitative determination of the relative marcasite/pyrite contents in virgin coals is possible by means of {sup 57}Fe Moessbauer spectroscopy. Complications arise however, when iron-containing silicates, carbonates, or other salts are present. The application of a mild chemical treatment involving hydrofluoric acid has been employed to remove these Fe-containing phases while leaving the iron-disulfide phases unaffected. Several South African coal samples with non-iron disulfide, Fe-containing phases ranging from 18 to 30 weight percent were subjected to a hydrofluoric acid leaching at room temperature. The loss of mineral matter with HF leaching correlates well with the mineral matter residue following low temperature ashing. The {sup 57}Fe Moessbauer spectra of the resulting coal samples indicate that only FeS{sub 2} phases are present and the absence of appreciable quantities of marcasite in the coals.

Two-stage combined treatment of acid mine drainage and municipal wastewater.

Science.gov (United States)

Deng, Dongyang; Lin, Lian-Shin

2013-01-01

This study examined the feasibility of the combined treatment of field-collected acid mine drainages (AMD, pH = 4.2 ± 0.9, iron = 112 ± 118 mg/L, sulfate = 1,846 ± 594 mg/L) and municipal wastewater (MWW, avg. chemical oxygen demand (COD) = 234-333 mg/L) using a two-stage process. The process consisted of batch mixing of the two wastes to condition the mixture solutions, followed by anaerobic biological treatment. The mixings performed under a range of AMD/MWW ratios resulted in phosphate removal of 9 to ∼100%, the mixture pH of 6.2-7.9, and COD/sulfate concentration ratio of 0.05-5.4. The biological treatment consistently removed COD and sulfate by >80% from the mixture solutions for COD/sulfate ratios of 0.6-5.4. Alkalinity was produced in the biological treatment causing increased pH and further removal of metals from the solutions. Scanning electron microscopy of produced sludge with energy dispersion analysis suggested chemical precipitation and associated adsorption and co-precipitation as the mechanisms for metal removal (Fe: >99%, Al: ∼100%, Mn: 75 to ∼100%, Ca: 52-81%, Mg: 13-76%, and Na: 56-76%). The study showed promising results for the treatment method and denoted the potential of developing innovative technologies for combined management of the two wastes in mining regions.

Binary Solvent Extraction of Tocols, γ-Oryzanol, and Ferulic Acid from Rice Bran Using Alkaline Treatment Combined with Ultrasonication.

Science.gov (United States)

Truong, Hoa Thi; Luu, Phuong Duc; Imamura, Kiyoshi; Matsubara, Takeo; Takahashi, Hideki; Takenaka, Norimichi; Boi, Luu Van; Maeda, Yasuaki

2017-06-21

Alkaline treatment (Alk) combined with ultrasound-assisted extraction (UAE) (Alk+UAE) was examined as a means of extracting tocols and γ-oryzanol from rice bran into an organic phase while simultaneously recovering ferulic acid into an aqueous phase. The tocols and γ-oryzanol/ferulic acid yields were determined using high-performance liquid chromatography with fluorescence and UV detection. The effects of extraction conditions were evaluated by varying the Alk treatment temperature and extraction duration. The maximum yields of tocols and γ-oryzanol were obtained at 25 °C over a time span of 30 min. When the temperature was increased to 80 °C, the yield of ferulic acid increased dramatically, whereas the recovery of γ-oryzanol slightly decreased. Employing the Alk+UAE procedure, the recovered concentrations of tocols, γ-oryzanol, and ferulic acid were in the ranges of 146-518, 1591-3629, and 352-970 μg/g, respectively. These results are in good agreement with those reported for rice bran samples from Thailand.

Process for the treatment of hydrocarbons containing acidic or phenolic substances

Energy Technology Data Exchange (ETDEWEB)

1949-03-15

A process for the treatment of hydrocarbon substances containing acidic or phenolic substances, such as the pyrogenation products of wood, lignite peat, coals, shales, and the like consists in passing the vapours of the substances to be treated over a layer of molten metal whereby a first pyrogenous decomposition of the said vapours in their gaseous phase is obtained. The decomposed gases then pass over a layer of a basic alkaline earth salt heated to a temperature sufficient to maintain the substances in a vaporous condition and the salt in a reactive state.

Separation of phenolic acids from monosaccharides by low-pressure nanofiltration integrated with laccase pre-treatments

DEFF Research Database (Denmark)

Luo, Jianquan; Zeuner, Birgitte; Morthensen, Sofie Thage

2015-01-01